THE ADRENAL GLAND GLUCOCORTICOIDS

Dr Eman El Eter

Adrenal Gland

Small triangular glands loosely attached to the kidneys

Divided into two morphologically and distinct regions

- Adrenal medulla- Adrenal cortex

Hormones of Adrenal gland

Cortex (Secretes steroid hormones) Glucocorticoids Mineralocorticoids Androgens

Medulla (Amino acid secretions) Catecholamines

Mechanism of action of steroid hormones

Glucocorticoids

Main glucocorticoids in humans Cortisol Corticosterone Cortisolcorticosterone produced in

humans in a ratio of 10190-95 bound to plasma proteinUnder control primarily by ACTH

Natural episodic secretion rhythms

After ACTH has been produced cortisol will be evident 15 to 30 minutes later

There are usually 7-15 episodes per day There is a major burst in the early

morning before awakening

Pattern of cortisol secretion

increased release with coffee consumption

increases with increased exercise time amp intensity

Steroid Hormones Transport

Steroid hormones when released from adrenal cortex into blood stream they bind to protein carriers

Cortisol binding globulin (CBG) (transcortin) Albumin Only unbound steroid hormones are biologically active (~2) To cross the target tissue membrane the hormone must dissociate from its carrier proteinImportance Binding to plasma proteins act as a reservoirs and

ensure a uniform distribution to all tissuesAldosteron has a lower half life than cortisol

Figure 2115

Regulation of Cortisol

release

Cortisol metabolism

Free cortisol is excreted into urine Metabolized in liver by reductases amp

conjugated to glucuronides and excreted via kidney

Regulation of cortisol releaseStimuli releasing cortisolbull physical trauma

bull infection

bull extreme heat and cold

bull exercise to the point of exhaustion

bull extreme mental anxiety

Physiological effects of cortisol Carbohydrate metabolismIncreases blood glucose levels by

(+) glucogenesis in the liver

Decreasing utilization of glucose by cells via direct inhibition of glucose transport into cells

Physiological effects of cortisol

Protein metabolism Reduces protein formation in all tissues Except

liver Extrahepatic protein stores reduced (catabolic) amino acids not transported into muscle cells darr

protein synthesis amp uarr amino acid blood levels These high blood amino acid levels are

transported more rapidly to hepatic cells for glucogenesis and protein synthesis in liver

Physiological effects of cortisol

Fat metabolism Lipolytic Mobilizes fatty acids amp glycerol from adipose

tissue lead touarr their blood concentrations makes more glycerol available for glucogenesis

Fat broken down amp less formed due to less glucose transported into fat cells

Redistribution of body fatuarr formation of fat in trunk areas amp facedarr fat (amp muscle) from extremities

Increases appetite

Physiological effects of cortisol

Anti-inflammatory

Stabilizes lysosomal membrane

Reduces degree of vasodilatation

Decreases permeability of capillaries

Decreases migration of white blood cells

Suppresses immune system

Physiological effects of cortisol

Effect on Blood Cells and Immunity Decrease production of eoisinophils and

lymphocytes Suppresses lymphoid tissue systemically therefore

decrease in T cell and antibody production decreasing immunity

Decrease immunity could be fatal in diseases such as tuberculosis

Decrease immunity effect of cortisol is useful during transplant operations in reducing organ rejection

Physiological effects of cortisol

Functions - circulation Maintains body fluid volumes amp vascular

integrity Cortisol has mineralcorticoid effect Not as

potent as aldosterone BP regulation amp cardiovascular function Sensitizes arterioles to action of

noradrenaline (Permissive effect) Decreased capillary permeability Maintains normal renal function

Physiological effects of cortisol

Functions - CNS responses

Negative feedback control on release of ACTH

Modulates perception amp emotion

Mineral metabolismAnti-vitamin D effect

GITIncreases HCl secretion

Physiological effects of cortisol

Developmental Functions Permissive regulation of fetal organ

maturation

Surfactant synthesis (phospholipid that maintains alveolar surface tension)

Inhibition of linear growth in children due to direct effects on bone amp connective tissue

Disorders of cortisol

Cortisol excessexogenous amp endogenous Exogenous Most cortisol excess is induced by steroid

therapy (prednisone) to manage disease 1048708 asthma 1048708 rheumatoid arthritis 1048708 lupus 1048708 other inflammatory diseases 1048708 immunosuppression after transplantation

Cortisol excessexogenous amp endogenous

Endogenous Due to excessive production of cortisol ACTH- independent

Primary adrenal defect (adenoma) ACTH-dependent

Overproduction of ACTH by pituitaryOverproduction of ACTH by ectopic ACTH-

producing tumor

Both exogenous amp endogenous hyperfunction show manifestations of Cushingrsquos

Cortisol excessIntermediary metabolism

Carbohydrate metabolismuarr blood glucose levelsdarr sensitivity to insulin

Protein metabolismuarr protein lossmuscle atrophythin skinbone matrix amp mass losses bone formation

darrlessCa2+ absorbed amp more excreted in urine osteoporosis

Cortisol excess

Intermediary metabolism

Fat metabolismredistribution of body fatuarrtrunk amp face fat deposition amp darr

extremities fat deposition

Cortisol excess

Circulation

Hypertension due to Na retention amp K excretion

Hypervolemia

Hypernatremia due to increased Na absorption

Hypokalemia due to increased K excretion

Cortisol excessinflammation amp immunity

Decreases inflammatory response Increased infection susceptibility Ab synthesis suppressed amp normal

immune responses to infecting pathogens suppressed

Decrease in fibrous tissue formation

Cortisol excess ndash effects on CNS

Initially euphoria but replaced with depression

Characteristics

Buffalo torso Redistribution of fat from lower parts of the

body to the thoracic and upper abdominal areas

Moon Face Edematous appearance of face Acne amp hirsutism( excess growth of facial

hair)

Effects on Carbohydrate Metabolism ldquoAdrenal diabetesrdquo

Hypersecretion of cortisol results in increase blood glucose levels up to 2 x normal (200mgdl)

Prolonged oversecretion of insulin ldquoburns outrdquo the beta cells of the pancreas resulting in life long diabetes mellitus

Effects on Protein Metabolism Decrease protein content in most parts of

the body resulting in muscle weakness In lymphoid tissue ndash decrease protein

synthesis results in suppression of the immune system

Lack of protein deposition in bones can result in osteoporosis

Collagen fibers in subcutaneous tissue tear forming striae

Cushing syndrome

ndash Hypersecretion of glucocorticoids by the adrenal

cortex characterized by weight gain in the trunk of the body but not arms and legs

Cushingrsquos Syndrome

striae

ldquomoon facerdquo

Cushingrsquos Disease

Proximal muscle wasting amp weakness

Osteoporosis Glucose intolerance HTN hypokalemia Thromboembolism Depression Psyc Infection Glaucoma

Treatment

Removal of adrenal tumor if this is the cause

Microsurgical removal of hypertrophied pituitary elements to reduce ACTH secretion

Partial or total adrenalectomy followed by administration of adrenal steroids to compensate insufficiencies that develop

• PowerPoint Presentation
• Slide 5
• Slide 11
• Slide 33

Adrenal Gland

Small triangular glands loosely attached to the kidneys

Divided into two morphologically and distinct regions

- Adrenal medulla- Adrenal cortex

Hormones of Adrenal gland

Cortex (Secretes steroid hormones) Glucocorticoids Mineralocorticoids Androgens

Medulla (Amino acid secretions) Catecholamines

Mechanism of action of steroid hormones

Glucocorticoids

Main glucocorticoids in humans Cortisol Corticosterone Cortisolcorticosterone produced in

humans in a ratio of 10190-95 bound to plasma proteinUnder control primarily by ACTH

Natural episodic secretion rhythms

After ACTH has been produced cortisol will be evident 15 to 30 minutes later

There are usually 7-15 episodes per day There is a major burst in the early

morning before awakening

Pattern of cortisol secretion

increased release with coffee consumption

increases with increased exercise time amp intensity

Steroid Hormones Transport

Steroid hormones when released from adrenal cortex into blood stream they bind to protein carriers

Cortisol binding globulin (CBG) (transcortin) Albumin Only unbound steroid hormones are biologically active (~2) To cross the target tissue membrane the hormone must dissociate from its carrier proteinImportance Binding to plasma proteins act as a reservoirs and

ensure a uniform distribution to all tissuesAldosteron has a lower half life than cortisol

Figure 2115

Regulation of Cortisol

release

Cortisol metabolism

Free cortisol is excreted into urine Metabolized in liver by reductases amp

conjugated to glucuronides and excreted via kidney

Regulation of cortisol releaseStimuli releasing cortisolbull physical trauma

bull infection

bull extreme heat and cold

bull exercise to the point of exhaustion

bull extreme mental anxiety

Physiological effects of cortisol Carbohydrate metabolismIncreases blood glucose levels by

(+) glucogenesis in the liver

Decreasing utilization of glucose by cells via direct inhibition of glucose transport into cells

Physiological effects of cortisol

Protein metabolism Reduces protein formation in all tissues Except

liver Extrahepatic protein stores reduced (catabolic) amino acids not transported into muscle cells darr

protein synthesis amp uarr amino acid blood levels These high blood amino acid levels are

transported more rapidly to hepatic cells for glucogenesis and protein synthesis in liver

Physiological effects of cortisol

Fat metabolism Lipolytic Mobilizes fatty acids amp glycerol from adipose

tissue lead touarr their blood concentrations makes more glycerol available for glucogenesis

Fat broken down amp less formed due to less glucose transported into fat cells

Redistribution of body fatuarr formation of fat in trunk areas amp facedarr fat (amp muscle) from extremities

Increases appetite

Physiological effects of cortisol

Anti-inflammatory

Stabilizes lysosomal membrane

Reduces degree of vasodilatation

Decreases permeability of capillaries

Decreases migration of white blood cells

Suppresses immune system

Physiological effects of cortisol

Effect on Blood Cells and Immunity Decrease production of eoisinophils and

lymphocytes Suppresses lymphoid tissue systemically therefore

decrease in T cell and antibody production decreasing immunity

Decrease immunity could be fatal in diseases such as tuberculosis

Decrease immunity effect of cortisol is useful during transplant operations in reducing organ rejection

Physiological effects of cortisol

Functions - circulation Maintains body fluid volumes amp vascular

integrity Cortisol has mineralcorticoid effect Not as

potent as aldosterone BP regulation amp cardiovascular function Sensitizes arterioles to action of

noradrenaline (Permissive effect) Decreased capillary permeability Maintains normal renal function

Physiological effects of cortisol

Functions - CNS responses

Negative feedback control on release of ACTH

Modulates perception amp emotion

Mineral metabolismAnti-vitamin D effect

GITIncreases HCl secretion

Physiological effects of cortisol

Developmental Functions Permissive regulation of fetal organ

maturation

Surfactant synthesis (phospholipid that maintains alveolar surface tension)

Inhibition of linear growth in children due to direct effects on bone amp connective tissue

Disorders of cortisol

Cortisol excessexogenous amp endogenous Exogenous Most cortisol excess is induced by steroid

therapy (prednisone) to manage disease 1048708 asthma 1048708 rheumatoid arthritis 1048708 lupus 1048708 other inflammatory diseases 1048708 immunosuppression after transplantation

Cortisol excessexogenous amp endogenous

Endogenous Due to excessive production of cortisol ACTH- independent

Primary adrenal defect (adenoma) ACTH-dependent

Overproduction of ACTH by pituitaryOverproduction of ACTH by ectopic ACTH-

producing tumor

Both exogenous amp endogenous hyperfunction show manifestations of Cushingrsquos

Cortisol excessIntermediary metabolism

Carbohydrate metabolismuarr blood glucose levelsdarr sensitivity to insulin

Protein metabolismuarr protein lossmuscle atrophythin skinbone matrix amp mass losses bone formation

darrlessCa2+ absorbed amp more excreted in urine osteoporosis

Cortisol excess

Intermediary metabolism

Fat metabolismredistribution of body fatuarrtrunk amp face fat deposition amp darr

extremities fat deposition

Cortisol excess

Circulation

Hypertension due to Na retention amp K excretion

Hypervolemia

Hypernatremia due to increased Na absorption

Hypokalemia due to increased K excretion

Cortisol excessinflammation amp immunity

Decreases inflammatory response Increased infection susceptibility Ab synthesis suppressed amp normal

immune responses to infecting pathogens suppressed

Decrease in fibrous tissue formation

Cortisol excess ndash effects on CNS

Initially euphoria but replaced with depression

Characteristics

Buffalo torso Redistribution of fat from lower parts of the

body to the thoracic and upper abdominal areas

Moon Face Edematous appearance of face Acne amp hirsutism( excess growth of facial

hair)

Effects on Carbohydrate Metabolism ldquoAdrenal diabetesrdquo

Hypersecretion of cortisol results in increase blood glucose levels up to 2 x normal (200mgdl)

Prolonged oversecretion of insulin ldquoburns outrdquo the beta cells of the pancreas resulting in life long diabetes mellitus

Effects on Protein Metabolism Decrease protein content in most parts of

the body resulting in muscle weakness In lymphoid tissue ndash decrease protein

synthesis results in suppression of the immune system

Lack of protein deposition in bones can result in osteoporosis

Collagen fibers in subcutaneous tissue tear forming striae

Cushing syndrome

ndash Hypersecretion of glucocorticoids by the adrenal

cortex characterized by weight gain in the trunk of the body but not arms and legs

Cushingrsquos Syndrome

striae

ldquomoon facerdquo

Cushingrsquos Disease

Proximal muscle wasting amp weakness

Osteoporosis Glucose intolerance HTN hypokalemia Thromboembolism Depression Psyc Infection Glaucoma

Treatment

Removal of adrenal tumor if this is the cause

Microsurgical removal of hypertrophied pituitary elements to reduce ACTH secretion

Partial or total adrenalectomy followed by administration of adrenal steroids to compensate insufficiencies that develop

• PowerPoint Presentation
• Slide 5
• Slide 11
• Slide 33

Hormones of Adrenal gland

Cortex (Secretes steroid hormones) Glucocorticoids Mineralocorticoids Androgens

Medulla (Amino acid secretions) Catecholamines

Mechanism of action of steroid hormones

Glucocorticoids

Main glucocorticoids in humans Cortisol Corticosterone Cortisolcorticosterone produced in

humans in a ratio of 10190-95 bound to plasma proteinUnder control primarily by ACTH

Natural episodic secretion rhythms

After ACTH has been produced cortisol will be evident 15 to 30 minutes later

There are usually 7-15 episodes per day There is a major burst in the early

morning before awakening

Pattern of cortisol secretion

increased release with coffee consumption

increases with increased exercise time amp intensity

Steroid Hormones Transport

Steroid hormones when released from adrenal cortex into blood stream they bind to protein carriers

Cortisol binding globulin (CBG) (transcortin) Albumin Only unbound steroid hormones are biologically active (~2) To cross the target tissue membrane the hormone must dissociate from its carrier proteinImportance Binding to plasma proteins act as a reservoirs and

ensure a uniform distribution to all tissuesAldosteron has a lower half life than cortisol

Figure 2115

Regulation of Cortisol

release

Cortisol metabolism

Free cortisol is excreted into urine Metabolized in liver by reductases amp

conjugated to glucuronides and excreted via kidney

Regulation of cortisol releaseStimuli releasing cortisolbull physical trauma

bull infection

bull extreme heat and cold

bull exercise to the point of exhaustion

bull extreme mental anxiety

Physiological effects of cortisol Carbohydrate metabolismIncreases blood glucose levels by

(+) glucogenesis in the liver

Decreasing utilization of glucose by cells via direct inhibition of glucose transport into cells

Physiological effects of cortisol

Protein metabolism Reduces protein formation in all tissues Except

liver Extrahepatic protein stores reduced (catabolic) amino acids not transported into muscle cells darr

protein synthesis amp uarr amino acid blood levels These high blood amino acid levels are

transported more rapidly to hepatic cells for glucogenesis and protein synthesis in liver

Physiological effects of cortisol

Fat metabolism Lipolytic Mobilizes fatty acids amp glycerol from adipose

tissue lead touarr their blood concentrations makes more glycerol available for glucogenesis

Fat broken down amp less formed due to less glucose transported into fat cells

Redistribution of body fatuarr formation of fat in trunk areas amp facedarr fat (amp muscle) from extremities

Increases appetite

Physiological effects of cortisol

Anti-inflammatory

Stabilizes lysosomal membrane

Reduces degree of vasodilatation

Decreases permeability of capillaries

Decreases migration of white blood cells

Suppresses immune system

Physiological effects of cortisol

Effect on Blood Cells and Immunity Decrease production of eoisinophils and

lymphocytes Suppresses lymphoid tissue systemically therefore

decrease in T cell and antibody production decreasing immunity

Decrease immunity could be fatal in diseases such as tuberculosis

Decrease immunity effect of cortisol is useful during transplant operations in reducing organ rejection

Physiological effects of cortisol

Functions - circulation Maintains body fluid volumes amp vascular

integrity Cortisol has mineralcorticoid effect Not as

potent as aldosterone BP regulation amp cardiovascular function Sensitizes arterioles to action of

noradrenaline (Permissive effect) Decreased capillary permeability Maintains normal renal function

Physiological effects of cortisol

Functions - CNS responses

Negative feedback control on release of ACTH

Modulates perception amp emotion

Mineral metabolismAnti-vitamin D effect

GITIncreases HCl secretion

Physiological effects of cortisol

Developmental Functions Permissive regulation of fetal organ

maturation

Surfactant synthesis (phospholipid that maintains alveolar surface tension)

Inhibition of linear growth in children due to direct effects on bone amp connective tissue

Disorders of cortisol

Cortisol excessexogenous amp endogenous Exogenous Most cortisol excess is induced by steroid

therapy (prednisone) to manage disease 1048708 asthma 1048708 rheumatoid arthritis 1048708 lupus 1048708 other inflammatory diseases 1048708 immunosuppression after transplantation

Cortisol excessexogenous amp endogenous

Endogenous Due to excessive production of cortisol ACTH- independent

Primary adrenal defect (adenoma) ACTH-dependent

Overproduction of ACTH by pituitaryOverproduction of ACTH by ectopic ACTH-

producing tumor

Both exogenous amp endogenous hyperfunction show manifestations of Cushingrsquos

Cortisol excessIntermediary metabolism

Carbohydrate metabolismuarr blood glucose levelsdarr sensitivity to insulin

Protein metabolismuarr protein lossmuscle atrophythin skinbone matrix amp mass losses bone formation

darrlessCa2+ absorbed amp more excreted in urine osteoporosis

Cortisol excess

Intermediary metabolism

Fat metabolismredistribution of body fatuarrtrunk amp face fat deposition amp darr

extremities fat deposition

Cortisol excess

Circulation

Hypertension due to Na retention amp K excretion

Hypervolemia

Hypernatremia due to increased Na absorption

Hypokalemia due to increased K excretion

Cortisol excessinflammation amp immunity

Decreases inflammatory response Increased infection susceptibility Ab synthesis suppressed amp normal

immune responses to infecting pathogens suppressed

Decrease in fibrous tissue formation

Cortisol excess ndash effects on CNS

Initially euphoria but replaced with depression

Characteristics

Buffalo torso Redistribution of fat from lower parts of the

body to the thoracic and upper abdominal areas

Moon Face Edematous appearance of face Acne amp hirsutism( excess growth of facial

hair)

Effects on Carbohydrate Metabolism ldquoAdrenal diabetesrdquo

Hypersecretion of cortisol results in increase blood glucose levels up to 2 x normal (200mgdl)

Prolonged oversecretion of insulin ldquoburns outrdquo the beta cells of the pancreas resulting in life long diabetes mellitus

Effects on Protein Metabolism Decrease protein content in most parts of

the body resulting in muscle weakness In lymphoid tissue ndash decrease protein

synthesis results in suppression of the immune system

Lack of protein deposition in bones can result in osteoporosis

Collagen fibers in subcutaneous tissue tear forming striae

Cushing syndrome

ndash Hypersecretion of glucocorticoids by the adrenal

cortex characterized by weight gain in the trunk of the body but not arms and legs

Cushingrsquos Syndrome

striae

ldquomoon facerdquo

Cushingrsquos Disease

Proximal muscle wasting amp weakness

Osteoporosis Glucose intolerance HTN hypokalemia Thromboembolism Depression Psyc Infection Glaucoma

Treatment

Removal of adrenal tumor if this is the cause

Microsurgical removal of hypertrophied pituitary elements to reduce ACTH secretion

Partial or total adrenalectomy followed by administration of adrenal steroids to compensate insufficiencies that develop

• PowerPoint Presentation
• Slide 5
• Slide 11
• Slide 33

Mechanism of action of steroid hormones

Glucocorticoids

Main glucocorticoids in humans Cortisol Corticosterone Cortisolcorticosterone produced in

humans in a ratio of 10190-95 bound to plasma proteinUnder control primarily by ACTH

Natural episodic secretion rhythms

After ACTH has been produced cortisol will be evident 15 to 30 minutes later

There are usually 7-15 episodes per day There is a major burst in the early

morning before awakening

Pattern of cortisol secretion

increased release with coffee consumption

increases with increased exercise time amp intensity

Steroid Hormones Transport

Steroid hormones when released from adrenal cortex into blood stream they bind to protein carriers

Cortisol binding globulin (CBG) (transcortin) Albumin Only unbound steroid hormones are biologically active (~2) To cross the target tissue membrane the hormone must dissociate from its carrier proteinImportance Binding to plasma proteins act as a reservoirs and

ensure a uniform distribution to all tissuesAldosteron has a lower half life than cortisol

Figure 2115

Regulation of Cortisol

release

Cortisol metabolism

Free cortisol is excreted into urine Metabolized in liver by reductases amp

conjugated to glucuronides and excreted via kidney

Regulation of cortisol releaseStimuli releasing cortisolbull physical trauma

bull infection

bull extreme heat and cold

bull exercise to the point of exhaustion

bull extreme mental anxiety

Physiological effects of cortisol Carbohydrate metabolismIncreases blood glucose levels by

(+) glucogenesis in the liver

Decreasing utilization of glucose by cells via direct inhibition of glucose transport into cells

Physiological effects of cortisol

Protein metabolism Reduces protein formation in all tissues Except

liver Extrahepatic protein stores reduced (catabolic) amino acids not transported into muscle cells darr

protein synthesis amp uarr amino acid blood levels These high blood amino acid levels are

transported more rapidly to hepatic cells for glucogenesis and protein synthesis in liver

Physiological effects of cortisol

Fat metabolism Lipolytic Mobilizes fatty acids amp glycerol from adipose

tissue lead touarr their blood concentrations makes more glycerol available for glucogenesis

Fat broken down amp less formed due to less glucose transported into fat cells

Redistribution of body fatuarr formation of fat in trunk areas amp facedarr fat (amp muscle) from extremities

Increases appetite

Physiological effects of cortisol

Anti-inflammatory

Stabilizes lysosomal membrane

Reduces degree of vasodilatation

Decreases permeability of capillaries

Decreases migration of white blood cells

Suppresses immune system

Physiological effects of cortisol

Effect on Blood Cells and Immunity Decrease production of eoisinophils and

lymphocytes Suppresses lymphoid tissue systemically therefore

decrease in T cell and antibody production decreasing immunity

Decrease immunity could be fatal in diseases such as tuberculosis

Decrease immunity effect of cortisol is useful during transplant operations in reducing organ rejection

Physiological effects of cortisol

Functions - circulation Maintains body fluid volumes amp vascular

integrity Cortisol has mineralcorticoid effect Not as

potent as aldosterone BP regulation amp cardiovascular function Sensitizes arterioles to action of

noradrenaline (Permissive effect) Decreased capillary permeability Maintains normal renal function

Physiological effects of cortisol

Functions - CNS responses

Negative feedback control on release of ACTH

Modulates perception amp emotion

Mineral metabolismAnti-vitamin D effect

GITIncreases HCl secretion

Physiological effects of cortisol

Developmental Functions Permissive regulation of fetal organ

maturation

Surfactant synthesis (phospholipid that maintains alveolar surface tension)

Inhibition of linear growth in children due to direct effects on bone amp connective tissue

Disorders of cortisol

Cortisol excessexogenous amp endogenous Exogenous Most cortisol excess is induced by steroid

therapy (prednisone) to manage disease 1048708 asthma 1048708 rheumatoid arthritis 1048708 lupus 1048708 other inflammatory diseases 1048708 immunosuppression after transplantation

Cortisol excessexogenous amp endogenous

Endogenous Due to excessive production of cortisol ACTH- independent

Primary adrenal defect (adenoma) ACTH-dependent

Overproduction of ACTH by pituitaryOverproduction of ACTH by ectopic ACTH-

producing tumor

Both exogenous amp endogenous hyperfunction show manifestations of Cushingrsquos

Cortisol excessIntermediary metabolism

Carbohydrate metabolismuarr blood glucose levelsdarr sensitivity to insulin

Protein metabolismuarr protein lossmuscle atrophythin skinbone matrix amp mass losses bone formation

darrlessCa2+ absorbed amp more excreted in urine osteoporosis

Cortisol excess

Intermediary metabolism

Fat metabolismredistribution of body fatuarrtrunk amp face fat deposition amp darr

extremities fat deposition

Cortisol excess

Circulation

Hypertension due to Na retention amp K excretion

Hypervolemia

Hypernatremia due to increased Na absorption

Hypokalemia due to increased K excretion

Cortisol excessinflammation amp immunity

Decreases inflammatory response Increased infection susceptibility Ab synthesis suppressed amp normal

immune responses to infecting pathogens suppressed

Decrease in fibrous tissue formation

Cortisol excess ndash effects on CNS

Initially euphoria but replaced with depression

Characteristics

Buffalo torso Redistribution of fat from lower parts of the

body to the thoracic and upper abdominal areas

Moon Face Edematous appearance of face Acne amp hirsutism( excess growth of facial

hair)

Effects on Carbohydrate Metabolism ldquoAdrenal diabetesrdquo

Hypersecretion of cortisol results in increase blood glucose levels up to 2 x normal (200mgdl)

Prolonged oversecretion of insulin ldquoburns outrdquo the beta cells of the pancreas resulting in life long diabetes mellitus

Effects on Protein Metabolism Decrease protein content in most parts of

the body resulting in muscle weakness In lymphoid tissue ndash decrease protein

synthesis results in suppression of the immune system

Lack of protein deposition in bones can result in osteoporosis

Collagen fibers in subcutaneous tissue tear forming striae

Cushing syndrome

ndash Hypersecretion of glucocorticoids by the adrenal

cortex characterized by weight gain in the trunk of the body but not arms and legs

Cushingrsquos Syndrome

striae

ldquomoon facerdquo

Cushingrsquos Disease

Proximal muscle wasting amp weakness

Osteoporosis Glucose intolerance HTN hypokalemia Thromboembolism Depression Psyc Infection Glaucoma

Treatment

Removal of adrenal tumor if this is the cause

Microsurgical removal of hypertrophied pituitary elements to reduce ACTH secretion

Partial or total adrenalectomy followed by administration of adrenal steroids to compensate insufficiencies that develop

• PowerPoint Presentation
• Slide 5
• Slide 11
• Slide 33

Glucocorticoids

Main glucocorticoids in humans Cortisol Corticosterone Cortisolcorticosterone produced in

humans in a ratio of 10190-95 bound to plasma proteinUnder control primarily by ACTH

Natural episodic secretion rhythms

After ACTH has been produced cortisol will be evident 15 to 30 minutes later

There are usually 7-15 episodes per day There is a major burst in the early

morning before awakening

Pattern of cortisol secretion

increased release with coffee consumption

increases with increased exercise time amp intensity

Steroid Hormones Transport

Steroid hormones when released from adrenal cortex into blood stream they bind to protein carriers

Cortisol binding globulin (CBG) (transcortin) Albumin Only unbound steroid hormones are biologically active (~2) To cross the target tissue membrane the hormone must dissociate from its carrier proteinImportance Binding to plasma proteins act as a reservoirs and

ensure a uniform distribution to all tissuesAldosteron has a lower half life than cortisol

Figure 2115

Regulation of Cortisol

release

Cortisol metabolism

Free cortisol is excreted into urine Metabolized in liver by reductases amp

conjugated to glucuronides and excreted via kidney

Regulation of cortisol releaseStimuli releasing cortisolbull physical trauma

bull infection

bull extreme heat and cold

bull exercise to the point of exhaustion

bull extreme mental anxiety

Physiological effects of cortisol Carbohydrate metabolismIncreases blood glucose levels by

(+) glucogenesis in the liver

Decreasing utilization of glucose by cells via direct inhibition of glucose transport into cells

Physiological effects of cortisol

Protein metabolism Reduces protein formation in all tissues Except

liver Extrahepatic protein stores reduced (catabolic) amino acids not transported into muscle cells darr

protein synthesis amp uarr amino acid blood levels These high blood amino acid levels are

transported more rapidly to hepatic cells for glucogenesis and protein synthesis in liver

Physiological effects of cortisol

Fat metabolism Lipolytic Mobilizes fatty acids amp glycerol from adipose

tissue lead touarr their blood concentrations makes more glycerol available for glucogenesis

Fat broken down amp less formed due to less glucose transported into fat cells

Redistribution of body fatuarr formation of fat in trunk areas amp facedarr fat (amp muscle) from extremities

Increases appetite

Physiological effects of cortisol

Anti-inflammatory

Stabilizes lysosomal membrane

Reduces degree of vasodilatation

Decreases permeability of capillaries

Decreases migration of white blood cells

Suppresses immune system

Physiological effects of cortisol

Effect on Blood Cells and Immunity Decrease production of eoisinophils and

lymphocytes Suppresses lymphoid tissue systemically therefore

decrease in T cell and antibody production decreasing immunity

Decrease immunity could be fatal in diseases such as tuberculosis

Decrease immunity effect of cortisol is useful during transplant operations in reducing organ rejection

Physiological effects of cortisol

Functions - circulation Maintains body fluid volumes amp vascular

integrity Cortisol has mineralcorticoid effect Not as

potent as aldosterone BP regulation amp cardiovascular function Sensitizes arterioles to action of

noradrenaline (Permissive effect) Decreased capillary permeability Maintains normal renal function

Physiological effects of cortisol

Functions - CNS responses

Negative feedback control on release of ACTH

Modulates perception amp emotion

Mineral metabolismAnti-vitamin D effect

GITIncreases HCl secretion

Physiological effects of cortisol

Developmental Functions Permissive regulation of fetal organ

maturation

Surfactant synthesis (phospholipid that maintains alveolar surface tension)

Inhibition of linear growth in children due to direct effects on bone amp connective tissue

Disorders of cortisol

Cortisol excessexogenous amp endogenous Exogenous Most cortisol excess is induced by steroid

therapy (prednisone) to manage disease 1048708 asthma 1048708 rheumatoid arthritis 1048708 lupus 1048708 other inflammatory diseases 1048708 immunosuppression after transplantation

Cortisol excessexogenous amp endogenous

Endogenous Due to excessive production of cortisol ACTH- independent

Primary adrenal defect (adenoma) ACTH-dependent

Overproduction of ACTH by pituitaryOverproduction of ACTH by ectopic ACTH-

producing tumor

Both exogenous amp endogenous hyperfunction show manifestations of Cushingrsquos

Cortisol excessIntermediary metabolism

Carbohydrate metabolismuarr blood glucose levelsdarr sensitivity to insulin

Protein metabolismuarr protein lossmuscle atrophythin skinbone matrix amp mass losses bone formation

darrlessCa2+ absorbed amp more excreted in urine osteoporosis

Cortisol excess

Intermediary metabolism

Fat metabolismredistribution of body fatuarrtrunk amp face fat deposition amp darr

extremities fat deposition

Cortisol excess

Circulation

Hypertension due to Na retention amp K excretion

Hypervolemia

Hypernatremia due to increased Na absorption

Hypokalemia due to increased K excretion

Cortisol excessinflammation amp immunity

Decreases inflammatory response Increased infection susceptibility Ab synthesis suppressed amp normal

immune responses to infecting pathogens suppressed

Decrease in fibrous tissue formation

Cortisol excess ndash effects on CNS

Initially euphoria but replaced with depression

Characteristics

Buffalo torso Redistribution of fat from lower parts of the

body to the thoracic and upper abdominal areas

Moon Face Edematous appearance of face Acne amp hirsutism( excess growth of facial

hair)

Effects on Carbohydrate Metabolism ldquoAdrenal diabetesrdquo

Hypersecretion of cortisol results in increase blood glucose levels up to 2 x normal (200mgdl)

Prolonged oversecretion of insulin ldquoburns outrdquo the beta cells of the pancreas resulting in life long diabetes mellitus

Effects on Protein Metabolism Decrease protein content in most parts of

the body resulting in muscle weakness In lymphoid tissue ndash decrease protein

synthesis results in suppression of the immune system

Lack of protein deposition in bones can result in osteoporosis

Collagen fibers in subcutaneous tissue tear forming striae

Cushing syndrome

ndash Hypersecretion of glucocorticoids by the adrenal

cortex characterized by weight gain in the trunk of the body but not arms and legs

Cushingrsquos Syndrome

striae

ldquomoon facerdquo

Cushingrsquos Disease

Proximal muscle wasting amp weakness

Osteoporosis Glucose intolerance HTN hypokalemia Thromboembolism Depression Psyc Infection Glaucoma

Treatment

Removal of adrenal tumor if this is the cause

Microsurgical removal of hypertrophied pituitary elements to reduce ACTH secretion

Partial or total adrenalectomy followed by administration of adrenal steroids to compensate insufficiencies that develop

• PowerPoint Presentation
• Slide 5
• Slide 11
• Slide 33

Natural episodic secretion rhythms

After ACTH has been produced cortisol will be evident 15 to 30 minutes later

There are usually 7-15 episodes per day There is a major burst in the early

morning before awakening

Pattern of cortisol secretion

increased release with coffee consumption

increases with increased exercise time amp intensity

Steroid Hormones Transport

Steroid hormones when released from adrenal cortex into blood stream they bind to protein carriers

Cortisol binding globulin (CBG) (transcortin) Albumin Only unbound steroid hormones are biologically active (~2) To cross the target tissue membrane the hormone must dissociate from its carrier proteinImportance Binding to plasma proteins act as a reservoirs and

ensure a uniform distribution to all tissuesAldosteron has a lower half life than cortisol

Figure 2115

Regulation of Cortisol

release

Cortisol metabolism

Free cortisol is excreted into urine Metabolized in liver by reductases amp

conjugated to glucuronides and excreted via kidney

Regulation of cortisol releaseStimuli releasing cortisolbull physical trauma

bull infection

bull extreme heat and cold

bull exercise to the point of exhaustion

bull extreme mental anxiety

Physiological effects of cortisol Carbohydrate metabolismIncreases blood glucose levels by

(+) glucogenesis in the liver

Decreasing utilization of glucose by cells via direct inhibition of glucose transport into cells

Physiological effects of cortisol

Protein metabolism Reduces protein formation in all tissues Except

liver Extrahepatic protein stores reduced (catabolic) amino acids not transported into muscle cells darr

protein synthesis amp uarr amino acid blood levels These high blood amino acid levels are

transported more rapidly to hepatic cells for glucogenesis and protein synthesis in liver

Physiological effects of cortisol

Fat metabolism Lipolytic Mobilizes fatty acids amp glycerol from adipose

tissue lead touarr their blood concentrations makes more glycerol available for glucogenesis

Fat broken down amp less formed due to less glucose transported into fat cells

Redistribution of body fatuarr formation of fat in trunk areas amp facedarr fat (amp muscle) from extremities

Increases appetite

Physiological effects of cortisol

Anti-inflammatory

Stabilizes lysosomal membrane

Reduces degree of vasodilatation

Decreases permeability of capillaries

Decreases migration of white blood cells

Suppresses immune system

Physiological effects of cortisol

Effect on Blood Cells and Immunity Decrease production of eoisinophils and

lymphocytes Suppresses lymphoid tissue systemically therefore

decrease in T cell and antibody production decreasing immunity

Decrease immunity could be fatal in diseases such as tuberculosis

Decrease immunity effect of cortisol is useful during transplant operations in reducing organ rejection

Physiological effects of cortisol

Functions - circulation Maintains body fluid volumes amp vascular

integrity Cortisol has mineralcorticoid effect Not as

potent as aldosterone BP regulation amp cardiovascular function Sensitizes arterioles to action of

noradrenaline (Permissive effect) Decreased capillary permeability Maintains normal renal function

Physiological effects of cortisol

Functions - CNS responses

Negative feedback control on release of ACTH

Modulates perception amp emotion

Mineral metabolismAnti-vitamin D effect

GITIncreases HCl secretion

Physiological effects of cortisol

Developmental Functions Permissive regulation of fetal organ

maturation

Surfactant synthesis (phospholipid that maintains alveolar surface tension)

Inhibition of linear growth in children due to direct effects on bone amp connective tissue

Disorders of cortisol

Cortisol excessexogenous amp endogenous Exogenous Most cortisol excess is induced by steroid

therapy (prednisone) to manage disease 1048708 asthma 1048708 rheumatoid arthritis 1048708 lupus 1048708 other inflammatory diseases 1048708 immunosuppression after transplantation

Cortisol excessexogenous amp endogenous

Endogenous Due to excessive production of cortisol ACTH- independent

Primary adrenal defect (adenoma) ACTH-dependent

Overproduction of ACTH by pituitaryOverproduction of ACTH by ectopic ACTH-

producing tumor

Both exogenous amp endogenous hyperfunction show manifestations of Cushingrsquos

Cortisol excessIntermediary metabolism

Carbohydrate metabolismuarr blood glucose levelsdarr sensitivity to insulin

Protein metabolismuarr protein lossmuscle atrophythin skinbone matrix amp mass losses bone formation

darrlessCa2+ absorbed amp more excreted in urine osteoporosis

Cortisol excess

Intermediary metabolism

Fat metabolismredistribution of body fatuarrtrunk amp face fat deposition amp darr

extremities fat deposition

Cortisol excess

Circulation

Hypertension due to Na retention amp K excretion

Hypervolemia

Hypernatremia due to increased Na absorption

Hypokalemia due to increased K excretion

Cortisol excessinflammation amp immunity

Decreases inflammatory response Increased infection susceptibility Ab synthesis suppressed amp normal

immune responses to infecting pathogens suppressed

Decrease in fibrous tissue formation

Cortisol excess ndash effects on CNS

Initially euphoria but replaced with depression

Characteristics

Buffalo torso Redistribution of fat from lower parts of the

body to the thoracic and upper abdominal areas

Moon Face Edematous appearance of face Acne amp hirsutism( excess growth of facial

hair)

Effects on Carbohydrate Metabolism ldquoAdrenal diabetesrdquo

Hypersecretion of cortisol results in increase blood glucose levels up to 2 x normal (200mgdl)

Prolonged oversecretion of insulin ldquoburns outrdquo the beta cells of the pancreas resulting in life long diabetes mellitus

Effects on Protein Metabolism Decrease protein content in most parts of

the body resulting in muscle weakness In lymphoid tissue ndash decrease protein

synthesis results in suppression of the immune system

Lack of protein deposition in bones can result in osteoporosis

Collagen fibers in subcutaneous tissue tear forming striae

Cushing syndrome

ndash Hypersecretion of glucocorticoids by the adrenal

cortex characterized by weight gain in the trunk of the body but not arms and legs

Cushingrsquos Syndrome

striae

ldquomoon facerdquo

Cushingrsquos Disease

Proximal muscle wasting amp weakness

Osteoporosis Glucose intolerance HTN hypokalemia Thromboembolism Depression Psyc Infection Glaucoma

Treatment

Removal of adrenal tumor if this is the cause

Microsurgical removal of hypertrophied pituitary elements to reduce ACTH secretion

Partial or total adrenalectomy followed by administration of adrenal steroids to compensate insufficiencies that develop

• PowerPoint Presentation
• Slide 5
• Slide 11
• Slide 33

Pattern of cortisol secretion

increased release with coffee consumption

increases with increased exercise time amp intensity

Steroid Hormones Transport

Steroid hormones when released from adrenal cortex into blood stream they bind to protein carriers

Cortisol binding globulin (CBG) (transcortin) Albumin Only unbound steroid hormones are biologically active (~2) To cross the target tissue membrane the hormone must dissociate from its carrier proteinImportance Binding to plasma proteins act as a reservoirs and

ensure a uniform distribution to all tissuesAldosteron has a lower half life than cortisol

Figure 2115

Regulation of Cortisol

release

Cortisol metabolism

Free cortisol is excreted into urine Metabolized in liver by reductases amp

conjugated to glucuronides and excreted via kidney

Regulation of cortisol releaseStimuli releasing cortisolbull physical trauma

bull infection

bull extreme heat and cold

bull exercise to the point of exhaustion

bull extreme mental anxiety

Physiological effects of cortisol Carbohydrate metabolismIncreases blood glucose levels by

(+) glucogenesis in the liver

Decreasing utilization of glucose by cells via direct inhibition of glucose transport into cells

Physiological effects of cortisol

Protein metabolism Reduces protein formation in all tissues Except

liver Extrahepatic protein stores reduced (catabolic) amino acids not transported into muscle cells darr

protein synthesis amp uarr amino acid blood levels These high blood amino acid levels are

transported more rapidly to hepatic cells for glucogenesis and protein synthesis in liver

Physiological effects of cortisol

Fat metabolism Lipolytic Mobilizes fatty acids amp glycerol from adipose

tissue lead touarr their blood concentrations makes more glycerol available for glucogenesis

Fat broken down amp less formed due to less glucose transported into fat cells

Redistribution of body fatuarr formation of fat in trunk areas amp facedarr fat (amp muscle) from extremities

Increases appetite

Physiological effects of cortisol

Anti-inflammatory

Stabilizes lysosomal membrane

Reduces degree of vasodilatation

Decreases permeability of capillaries

Decreases migration of white blood cells

Suppresses immune system

Physiological effects of cortisol

Effect on Blood Cells and Immunity Decrease production of eoisinophils and

lymphocytes Suppresses lymphoid tissue systemically therefore

decrease in T cell and antibody production decreasing immunity

Decrease immunity could be fatal in diseases such as tuberculosis

Decrease immunity effect of cortisol is useful during transplant operations in reducing organ rejection

Physiological effects of cortisol

Functions - circulation Maintains body fluid volumes amp vascular

integrity Cortisol has mineralcorticoid effect Not as

potent as aldosterone BP regulation amp cardiovascular function Sensitizes arterioles to action of

noradrenaline (Permissive effect) Decreased capillary permeability Maintains normal renal function

Physiological effects of cortisol

Functions - CNS responses

Negative feedback control on release of ACTH

Modulates perception amp emotion

Mineral metabolismAnti-vitamin D effect

GITIncreases HCl secretion

Physiological effects of cortisol

Developmental Functions Permissive regulation of fetal organ

maturation

Surfactant synthesis (phospholipid that maintains alveolar surface tension)

Inhibition of linear growth in children due to direct effects on bone amp connective tissue

Disorders of cortisol

Cortisol excessexogenous amp endogenous Exogenous Most cortisol excess is induced by steroid

therapy (prednisone) to manage disease 1048708 asthma 1048708 rheumatoid arthritis 1048708 lupus 1048708 other inflammatory diseases 1048708 immunosuppression after transplantation

Cortisol excessexogenous amp endogenous

Endogenous Due to excessive production of cortisol ACTH- independent

Primary adrenal defect (adenoma) ACTH-dependent

Overproduction of ACTH by pituitaryOverproduction of ACTH by ectopic ACTH-

producing tumor

Both exogenous amp endogenous hyperfunction show manifestations of Cushingrsquos

Cortisol excessIntermediary metabolism

Carbohydrate metabolismuarr blood glucose levelsdarr sensitivity to insulin

Protein metabolismuarr protein lossmuscle atrophythin skinbone matrix amp mass losses bone formation

darrlessCa2+ absorbed amp more excreted in urine osteoporosis

Cortisol excess

Intermediary metabolism

Fat metabolismredistribution of body fatuarrtrunk amp face fat deposition amp darr

extremities fat deposition

Cortisol excess

Circulation

Hypertension due to Na retention amp K excretion

Hypervolemia

Hypernatremia due to increased Na absorption

Hypokalemia due to increased K excretion

Cortisol excessinflammation amp immunity

Decreases inflammatory response Increased infection susceptibility Ab synthesis suppressed amp normal

immune responses to infecting pathogens suppressed

Decrease in fibrous tissue formation

Cortisol excess ndash effects on CNS

Initially euphoria but replaced with depression

Characteristics

Buffalo torso Redistribution of fat from lower parts of the

body to the thoracic and upper abdominal areas

Moon Face Edematous appearance of face Acne amp hirsutism( excess growth of facial

hair)

Effects on Carbohydrate Metabolism ldquoAdrenal diabetesrdquo

Hypersecretion of cortisol results in increase blood glucose levels up to 2 x normal (200mgdl)

Prolonged oversecretion of insulin ldquoburns outrdquo the beta cells of the pancreas resulting in life long diabetes mellitus

Effects on Protein Metabolism Decrease protein content in most parts of

the body resulting in muscle weakness In lymphoid tissue ndash decrease protein

synthesis results in suppression of the immune system

Lack of protein deposition in bones can result in osteoporosis

Collagen fibers in subcutaneous tissue tear forming striae

Cushing syndrome

ndash Hypersecretion of glucocorticoids by the adrenal

cortex characterized by weight gain in the trunk of the body but not arms and legs

Cushingrsquos Syndrome

striae

ldquomoon facerdquo

Cushingrsquos Disease

Proximal muscle wasting amp weakness

Osteoporosis Glucose intolerance HTN hypokalemia Thromboembolism Depression Psyc Infection Glaucoma

Treatment

Removal of adrenal tumor if this is the cause

Microsurgical removal of hypertrophied pituitary elements to reduce ACTH secretion

Partial or total adrenalectomy followed by administration of adrenal steroids to compensate insufficiencies that develop

• PowerPoint Presentation
• Slide 5
• Slide 11
• Slide 33

Steroid Hormones Transport

Steroid hormones when released from adrenal cortex into blood stream they bind to protein carriers

Cortisol binding globulin (CBG) (transcortin) Albumin Only unbound steroid hormones are biologically active (~2) To cross the target tissue membrane the hormone must dissociate from its carrier proteinImportance Binding to plasma proteins act as a reservoirs and

ensure a uniform distribution to all tissuesAldosteron has a lower half life than cortisol

Figure 2115

Regulation of Cortisol

release

Cortisol metabolism

Free cortisol is excreted into urine Metabolized in liver by reductases amp

conjugated to glucuronides and excreted via kidney

Regulation of cortisol releaseStimuli releasing cortisolbull physical trauma

bull infection

bull extreme heat and cold

bull exercise to the point of exhaustion

bull extreme mental anxiety

Physiological effects of cortisol Carbohydrate metabolismIncreases blood glucose levels by

(+) glucogenesis in the liver

Decreasing utilization of glucose by cells via direct inhibition of glucose transport into cells

Physiological effects of cortisol

Protein metabolism Reduces protein formation in all tissues Except

liver Extrahepatic protein stores reduced (catabolic) amino acids not transported into muscle cells darr

protein synthesis amp uarr amino acid blood levels These high blood amino acid levels are

transported more rapidly to hepatic cells for glucogenesis and protein synthesis in liver

Physiological effects of cortisol

Fat metabolism Lipolytic Mobilizes fatty acids amp glycerol from adipose

tissue lead touarr their blood concentrations makes more glycerol available for glucogenesis

Fat broken down amp less formed due to less glucose transported into fat cells

Redistribution of body fatuarr formation of fat in trunk areas amp facedarr fat (amp muscle) from extremities

Increases appetite

Physiological effects of cortisol

Anti-inflammatory

Stabilizes lysosomal membrane

Reduces degree of vasodilatation

Decreases permeability of capillaries

Decreases migration of white blood cells

Suppresses immune system

Physiological effects of cortisol

Effect on Blood Cells and Immunity Decrease production of eoisinophils and

lymphocytes Suppresses lymphoid tissue systemically therefore

decrease in T cell and antibody production decreasing immunity

Decrease immunity could be fatal in diseases such as tuberculosis

Decrease immunity effect of cortisol is useful during transplant operations in reducing organ rejection

Physiological effects of cortisol

Functions - circulation Maintains body fluid volumes amp vascular

integrity Cortisol has mineralcorticoid effect Not as

potent as aldosterone BP regulation amp cardiovascular function Sensitizes arterioles to action of

noradrenaline (Permissive effect) Decreased capillary permeability Maintains normal renal function

Physiological effects of cortisol

Functions - CNS responses

Negative feedback control on release of ACTH

Modulates perception amp emotion

Mineral metabolismAnti-vitamin D effect

GITIncreases HCl secretion

Physiological effects of cortisol

Developmental Functions Permissive regulation of fetal organ

maturation

Surfactant synthesis (phospholipid that maintains alveolar surface tension)

Inhibition of linear growth in children due to direct effects on bone amp connective tissue

Disorders of cortisol

Cortisol excessexogenous amp endogenous Exogenous Most cortisol excess is induced by steroid

therapy (prednisone) to manage disease 1048708 asthma 1048708 rheumatoid arthritis 1048708 lupus 1048708 other inflammatory diseases 1048708 immunosuppression after transplantation

Cortisol excessexogenous amp endogenous

Endogenous Due to excessive production of cortisol ACTH- independent

Primary adrenal defect (adenoma) ACTH-dependent

Overproduction of ACTH by pituitaryOverproduction of ACTH by ectopic ACTH-

producing tumor

Both exogenous amp endogenous hyperfunction show manifestations of Cushingrsquos

Cortisol excessIntermediary metabolism

Carbohydrate metabolismuarr blood glucose levelsdarr sensitivity to insulin

Protein metabolismuarr protein lossmuscle atrophythin skinbone matrix amp mass losses bone formation

darrlessCa2+ absorbed amp more excreted in urine osteoporosis

Cortisol excess

Intermediary metabolism

Fat metabolismredistribution of body fatuarrtrunk amp face fat deposition amp darr

extremities fat deposition

Cortisol excess

Circulation

Hypertension due to Na retention amp K excretion

Hypervolemia

Hypernatremia due to increased Na absorption

Hypokalemia due to increased K excretion

Cortisol excessinflammation amp immunity

Decreases inflammatory response Increased infection susceptibility Ab synthesis suppressed amp normal

immune responses to infecting pathogens suppressed

Decrease in fibrous tissue formation

Cortisol excess ndash effects on CNS

Initially euphoria but replaced with depression

Characteristics

Buffalo torso Redistribution of fat from lower parts of the

body to the thoracic and upper abdominal areas

Moon Face Edematous appearance of face Acne amp hirsutism( excess growth of facial

hair)

Effects on Carbohydrate Metabolism ldquoAdrenal diabetesrdquo

Hypersecretion of cortisol results in increase blood glucose levels up to 2 x normal (200mgdl)

Prolonged oversecretion of insulin ldquoburns outrdquo the beta cells of the pancreas resulting in life long diabetes mellitus

Effects on Protein Metabolism Decrease protein content in most parts of

the body resulting in muscle weakness In lymphoid tissue ndash decrease protein

synthesis results in suppression of the immune system

Lack of protein deposition in bones can result in osteoporosis

Collagen fibers in subcutaneous tissue tear forming striae

Cushing syndrome

ndash Hypersecretion of glucocorticoids by the adrenal

cortex characterized by weight gain in the trunk of the body but not arms and legs

Cushingrsquos Syndrome

striae

ldquomoon facerdquo

Cushingrsquos Disease

Proximal muscle wasting amp weakness

Osteoporosis Glucose intolerance HTN hypokalemia Thromboembolism Depression Psyc Infection Glaucoma

Treatment

Removal of adrenal tumor if this is the cause

Microsurgical removal of hypertrophied pituitary elements to reduce ACTH secretion

Partial or total adrenalectomy followed by administration of adrenal steroids to compensate insufficiencies that develop

• PowerPoint Presentation
• Slide 5
• Slide 11
• Slide 33

Figure 2115

Regulation of Cortisol

release

Cortisol metabolism

Free cortisol is excreted into urine Metabolized in liver by reductases amp

conjugated to glucuronides and excreted via kidney

Regulation of cortisol releaseStimuli releasing cortisolbull physical trauma

bull infection

bull extreme heat and cold

bull exercise to the point of exhaustion

bull extreme mental anxiety

Physiological effects of cortisol Carbohydrate metabolismIncreases blood glucose levels by

(+) glucogenesis in the liver

Decreasing utilization of glucose by cells via direct inhibition of glucose transport into cells

Physiological effects of cortisol

Protein metabolism Reduces protein formation in all tissues Except

liver Extrahepatic protein stores reduced (catabolic) amino acids not transported into muscle cells darr

protein synthesis amp uarr amino acid blood levels These high blood amino acid levels are

transported more rapidly to hepatic cells for glucogenesis and protein synthesis in liver

Physiological effects of cortisol

Fat metabolism Lipolytic Mobilizes fatty acids amp glycerol from adipose

tissue lead touarr their blood concentrations makes more glycerol available for glucogenesis

Fat broken down amp less formed due to less glucose transported into fat cells

Redistribution of body fatuarr formation of fat in trunk areas amp facedarr fat (amp muscle) from extremities

Increases appetite

Physiological effects of cortisol

Anti-inflammatory

Stabilizes lysosomal membrane

Reduces degree of vasodilatation

Decreases permeability of capillaries

Decreases migration of white blood cells

Suppresses immune system

Physiological effects of cortisol

Effect on Blood Cells and Immunity Decrease production of eoisinophils and

lymphocytes Suppresses lymphoid tissue systemically therefore

decrease in T cell and antibody production decreasing immunity

Decrease immunity could be fatal in diseases such as tuberculosis

Decrease immunity effect of cortisol is useful during transplant operations in reducing organ rejection

Physiological effects of cortisol

Functions - circulation Maintains body fluid volumes amp vascular

integrity Cortisol has mineralcorticoid effect Not as

potent as aldosterone BP regulation amp cardiovascular function Sensitizes arterioles to action of

noradrenaline (Permissive effect) Decreased capillary permeability Maintains normal renal function

Physiological effects of cortisol

Functions - CNS responses

Negative feedback control on release of ACTH

Modulates perception amp emotion

Mineral metabolismAnti-vitamin D effect

GITIncreases HCl secretion

Physiological effects of cortisol

Developmental Functions Permissive regulation of fetal organ

maturation

Surfactant synthesis (phospholipid that maintains alveolar surface tension)

Inhibition of linear growth in children due to direct effects on bone amp connective tissue

Disorders of cortisol

Cortisol excessexogenous amp endogenous Exogenous Most cortisol excess is induced by steroid

therapy (prednisone) to manage disease 1048708 asthma 1048708 rheumatoid arthritis 1048708 lupus 1048708 other inflammatory diseases 1048708 immunosuppression after transplantation

Cortisol excessexogenous amp endogenous

Endogenous Due to excessive production of cortisol ACTH- independent

Primary adrenal defect (adenoma) ACTH-dependent

Overproduction of ACTH by pituitaryOverproduction of ACTH by ectopic ACTH-

producing tumor

Both exogenous amp endogenous hyperfunction show manifestations of Cushingrsquos

Cortisol excessIntermediary metabolism

Carbohydrate metabolismuarr blood glucose levelsdarr sensitivity to insulin

Protein metabolismuarr protein lossmuscle atrophythin skinbone matrix amp mass losses bone formation

darrlessCa2+ absorbed amp more excreted in urine osteoporosis

Cortisol excess

Intermediary metabolism

Fat metabolismredistribution of body fatuarrtrunk amp face fat deposition amp darr

extremities fat deposition

Cortisol excess

Circulation

Hypertension due to Na retention amp K excretion

Hypervolemia

Hypernatremia due to increased Na absorption

Hypokalemia due to increased K excretion

Cortisol excessinflammation amp immunity

Decreases inflammatory response Increased infection susceptibility Ab synthesis suppressed amp normal

immune responses to infecting pathogens suppressed

Decrease in fibrous tissue formation

Cortisol excess ndash effects on CNS

Initially euphoria but replaced with depression

Characteristics

Buffalo torso Redistribution of fat from lower parts of the

body to the thoracic and upper abdominal areas

Moon Face Edematous appearance of face Acne amp hirsutism( excess growth of facial

hair)

Effects on Carbohydrate Metabolism ldquoAdrenal diabetesrdquo

Hypersecretion of cortisol results in increase blood glucose levels up to 2 x normal (200mgdl)

Prolonged oversecretion of insulin ldquoburns outrdquo the beta cells of the pancreas resulting in life long diabetes mellitus

Effects on Protein Metabolism Decrease protein content in most parts of

the body resulting in muscle weakness In lymphoid tissue ndash decrease protein

synthesis results in suppression of the immune system

Lack of protein deposition in bones can result in osteoporosis

Collagen fibers in subcutaneous tissue tear forming striae

Cushing syndrome

ndash Hypersecretion of glucocorticoids by the adrenal

cortex characterized by weight gain in the trunk of the body but not arms and legs

Cushingrsquos Syndrome

striae

ldquomoon facerdquo

Cushingrsquos Disease

Proximal muscle wasting amp weakness

Osteoporosis Glucose intolerance HTN hypokalemia Thromboembolism Depression Psyc Infection Glaucoma

Treatment

Removal of adrenal tumor if this is the cause

Microsurgical removal of hypertrophied pituitary elements to reduce ACTH secretion

Partial or total adrenalectomy followed by administration of adrenal steroids to compensate insufficiencies that develop

• PowerPoint Presentation
• Slide 5
• Slide 11
• Slide 33

Cortisol metabolism

Free cortisol is excreted into urine Metabolized in liver by reductases amp

conjugated to glucuronides and excreted via kidney

Regulation of cortisol releaseStimuli releasing cortisolbull physical trauma

bull infection

bull extreme heat and cold

bull exercise to the point of exhaustion

bull extreme mental anxiety

Physiological effects of cortisol Carbohydrate metabolismIncreases blood glucose levels by

(+) glucogenesis in the liver

Decreasing utilization of glucose by cells via direct inhibition of glucose transport into cells

Physiological effects of cortisol

Protein metabolism Reduces protein formation in all tissues Except

liver Extrahepatic protein stores reduced (catabolic) amino acids not transported into muscle cells darr

protein synthesis amp uarr amino acid blood levels These high blood amino acid levels are

transported more rapidly to hepatic cells for glucogenesis and protein synthesis in liver

Physiological effects of cortisol

Fat metabolism Lipolytic Mobilizes fatty acids amp glycerol from adipose

tissue lead touarr their blood concentrations makes more glycerol available for glucogenesis

Fat broken down amp less formed due to less glucose transported into fat cells

Redistribution of body fatuarr formation of fat in trunk areas amp facedarr fat (amp muscle) from extremities

Increases appetite

Physiological effects of cortisol

Anti-inflammatory

Stabilizes lysosomal membrane

Reduces degree of vasodilatation

Decreases permeability of capillaries

Decreases migration of white blood cells

Suppresses immune system

Physiological effects of cortisol

Effect on Blood Cells and Immunity Decrease production of eoisinophils and

lymphocytes Suppresses lymphoid tissue systemically therefore

decrease in T cell and antibody production decreasing immunity

Decrease immunity could be fatal in diseases such as tuberculosis

Decrease immunity effect of cortisol is useful during transplant operations in reducing organ rejection

Physiological effects of cortisol

Functions - circulation Maintains body fluid volumes amp vascular

integrity Cortisol has mineralcorticoid effect Not as

potent as aldosterone BP regulation amp cardiovascular function Sensitizes arterioles to action of

noradrenaline (Permissive effect) Decreased capillary permeability Maintains normal renal function

Physiological effects of cortisol

Functions - CNS responses

Negative feedback control on release of ACTH

Modulates perception amp emotion

Mineral metabolismAnti-vitamin D effect

GITIncreases HCl secretion

Physiological effects of cortisol

Developmental Functions Permissive regulation of fetal organ

maturation

Surfactant synthesis (phospholipid that maintains alveolar surface tension)

Inhibition of linear growth in children due to direct effects on bone amp connective tissue

Disorders of cortisol

Cortisol excessexogenous amp endogenous Exogenous Most cortisol excess is induced by steroid

therapy (prednisone) to manage disease 1048708 asthma 1048708 rheumatoid arthritis 1048708 lupus 1048708 other inflammatory diseases 1048708 immunosuppression after transplantation

Cortisol excessexogenous amp endogenous

Endogenous Due to excessive production of cortisol ACTH- independent

Primary adrenal defect (adenoma) ACTH-dependent

Overproduction of ACTH by pituitaryOverproduction of ACTH by ectopic ACTH-

producing tumor

Both exogenous amp endogenous hyperfunction show manifestations of Cushingrsquos

Cortisol excessIntermediary metabolism

Carbohydrate metabolismuarr blood glucose levelsdarr sensitivity to insulin

Protein metabolismuarr protein lossmuscle atrophythin skinbone matrix amp mass losses bone formation

darrlessCa2+ absorbed amp more excreted in urine osteoporosis

Cortisol excess

Intermediary metabolism

Fat metabolismredistribution of body fatuarrtrunk amp face fat deposition amp darr

extremities fat deposition

Cortisol excess

Circulation

Hypertension due to Na retention amp K excretion

Hypervolemia

Hypernatremia due to increased Na absorption

Hypokalemia due to increased K excretion

Cortisol excessinflammation amp immunity

Decreases inflammatory response Increased infection susceptibility Ab synthesis suppressed amp normal

immune responses to infecting pathogens suppressed

Decrease in fibrous tissue formation

Cortisol excess ndash effects on CNS

Initially euphoria but replaced with depression

Characteristics

Buffalo torso Redistribution of fat from lower parts of the

body to the thoracic and upper abdominal areas

Moon Face Edematous appearance of face Acne amp hirsutism( excess growth of facial

hair)

Effects on Carbohydrate Metabolism ldquoAdrenal diabetesrdquo

Hypersecretion of cortisol results in increase blood glucose levels up to 2 x normal (200mgdl)

Prolonged oversecretion of insulin ldquoburns outrdquo the beta cells of the pancreas resulting in life long diabetes mellitus

Effects on Protein Metabolism Decrease protein content in most parts of

the body resulting in muscle weakness In lymphoid tissue ndash decrease protein

synthesis results in suppression of the immune system

Lack of protein deposition in bones can result in osteoporosis

Collagen fibers in subcutaneous tissue tear forming striae

Cushing syndrome

ndash Hypersecretion of glucocorticoids by the adrenal

cortex characterized by weight gain in the trunk of the body but not arms and legs

Cushingrsquos Syndrome

striae

ldquomoon facerdquo

Cushingrsquos Disease

Proximal muscle wasting amp weakness

Osteoporosis Glucose intolerance HTN hypokalemia Thromboembolism Depression Psyc Infection Glaucoma

Treatment

Removal of adrenal tumor if this is the cause

Microsurgical removal of hypertrophied pituitary elements to reduce ACTH secretion

Partial or total adrenalectomy followed by administration of adrenal steroids to compensate insufficiencies that develop

• PowerPoint Presentation
• Slide 5
• Slide 11
• Slide 33

Regulation of cortisol releaseStimuli releasing cortisolbull physical trauma

bull infection

bull extreme heat and cold

bull exercise to the point of exhaustion

bull extreme mental anxiety

Physiological effects of cortisol Carbohydrate metabolismIncreases blood glucose levels by

(+) glucogenesis in the liver

Decreasing utilization of glucose by cells via direct inhibition of glucose transport into cells

Physiological effects of cortisol

Protein metabolism Reduces protein formation in all tissues Except

liver Extrahepatic protein stores reduced (catabolic) amino acids not transported into muscle cells darr

protein synthesis amp uarr amino acid blood levels These high blood amino acid levels are

transported more rapidly to hepatic cells for glucogenesis and protein synthesis in liver

Physiological effects of cortisol

Fat metabolism Lipolytic Mobilizes fatty acids amp glycerol from adipose

tissue lead touarr their blood concentrations makes more glycerol available for glucogenesis

Fat broken down amp less formed due to less glucose transported into fat cells

Redistribution of body fatuarr formation of fat in trunk areas amp facedarr fat (amp muscle) from extremities

Increases appetite

Physiological effects of cortisol

Anti-inflammatory

Stabilizes lysosomal membrane

Reduces degree of vasodilatation

Decreases permeability of capillaries

Decreases migration of white blood cells

Suppresses immune system

Physiological effects of cortisol

Effect on Blood Cells and Immunity Decrease production of eoisinophils and

lymphocytes Suppresses lymphoid tissue systemically therefore

decrease in T cell and antibody production decreasing immunity

Decrease immunity could be fatal in diseases such as tuberculosis

Decrease immunity effect of cortisol is useful during transplant operations in reducing organ rejection

Physiological effects of cortisol

Functions - circulation Maintains body fluid volumes amp vascular

integrity Cortisol has mineralcorticoid effect Not as

potent as aldosterone BP regulation amp cardiovascular function Sensitizes arterioles to action of

noradrenaline (Permissive effect) Decreased capillary permeability Maintains normal renal function

Physiological effects of cortisol

Functions - CNS responses

Negative feedback control on release of ACTH

Modulates perception amp emotion

Mineral metabolismAnti-vitamin D effect

GITIncreases HCl secretion

Physiological effects of cortisol

Developmental Functions Permissive regulation of fetal organ

maturation

Surfactant synthesis (phospholipid that maintains alveolar surface tension)

Inhibition of linear growth in children due to direct effects on bone amp connective tissue

Disorders of cortisol

Cortisol excessexogenous amp endogenous Exogenous Most cortisol excess is induced by steroid

therapy (prednisone) to manage disease 1048708 asthma 1048708 rheumatoid arthritis 1048708 lupus 1048708 other inflammatory diseases 1048708 immunosuppression after transplantation

Cortisol excessexogenous amp endogenous

Endogenous Due to excessive production of cortisol ACTH- independent

Primary adrenal defect (adenoma) ACTH-dependent

Overproduction of ACTH by pituitaryOverproduction of ACTH by ectopic ACTH-

producing tumor

Both exogenous amp endogenous hyperfunction show manifestations of Cushingrsquos

Cortisol excessIntermediary metabolism

Carbohydrate metabolismuarr blood glucose levelsdarr sensitivity to insulin

Protein metabolismuarr protein lossmuscle atrophythin skinbone matrix amp mass losses bone formation

darrlessCa2+ absorbed amp more excreted in urine osteoporosis

Cortisol excess

Intermediary metabolism

Fat metabolismredistribution of body fatuarrtrunk amp face fat deposition amp darr

extremities fat deposition

Cortisol excess

Circulation

Hypertension due to Na retention amp K excretion

Hypervolemia

Hypernatremia due to increased Na absorption

Hypokalemia due to increased K excretion

Cortisol excessinflammation amp immunity

Decreases inflammatory response Increased infection susceptibility Ab synthesis suppressed amp normal

immune responses to infecting pathogens suppressed

Decrease in fibrous tissue formation

Cortisol excess ndash effects on CNS

Initially euphoria but replaced with depression

Characteristics

Buffalo torso Redistribution of fat from lower parts of the

body to the thoracic and upper abdominal areas

Moon Face Edematous appearance of face Acne amp hirsutism( excess growth of facial

hair)

Effects on Carbohydrate Metabolism ldquoAdrenal diabetesrdquo

Hypersecretion of cortisol results in increase blood glucose levels up to 2 x normal (200mgdl)

Prolonged oversecretion of insulin ldquoburns outrdquo the beta cells of the pancreas resulting in life long diabetes mellitus

Effects on Protein Metabolism Decrease protein content in most parts of

the body resulting in muscle weakness In lymphoid tissue ndash decrease protein

synthesis results in suppression of the immune system

Lack of protein deposition in bones can result in osteoporosis

Collagen fibers in subcutaneous tissue tear forming striae

Cushing syndrome

ndash Hypersecretion of glucocorticoids by the adrenal

cortex characterized by weight gain in the trunk of the body but not arms and legs

Cushingrsquos Syndrome

striae

ldquomoon facerdquo

Cushingrsquos Disease

Proximal muscle wasting amp weakness

Osteoporosis Glucose intolerance HTN hypokalemia Thromboembolism Depression Psyc Infection Glaucoma

Treatment

Removal of adrenal tumor if this is the cause

Microsurgical removal of hypertrophied pituitary elements to reduce ACTH secretion

Partial or total adrenalectomy followed by administration of adrenal steroids to compensate insufficiencies that develop

• PowerPoint Presentation
• Slide 5
• Slide 11
• Slide 33

Physiological effects of cortisol Carbohydrate metabolismIncreases blood glucose levels by

(+) glucogenesis in the liver

Decreasing utilization of glucose by cells via direct inhibition of glucose transport into cells

Physiological effects of cortisol

Protein metabolism Reduces protein formation in all tissues Except

liver Extrahepatic protein stores reduced (catabolic) amino acids not transported into muscle cells darr

protein synthesis amp uarr amino acid blood levels These high blood amino acid levels are

transported more rapidly to hepatic cells for glucogenesis and protein synthesis in liver

Physiological effects of cortisol

Fat metabolism Lipolytic Mobilizes fatty acids amp glycerol from adipose

tissue lead touarr their blood concentrations makes more glycerol available for glucogenesis

Fat broken down amp less formed due to less glucose transported into fat cells

Redistribution of body fatuarr formation of fat in trunk areas amp facedarr fat (amp muscle) from extremities

Increases appetite

Physiological effects of cortisol

Anti-inflammatory

Stabilizes lysosomal membrane

Reduces degree of vasodilatation

Decreases permeability of capillaries

Decreases migration of white blood cells

Suppresses immune system

Physiological effects of cortisol

Effect on Blood Cells and Immunity Decrease production of eoisinophils and

lymphocytes Suppresses lymphoid tissue systemically therefore

decrease in T cell and antibody production decreasing immunity

Decrease immunity could be fatal in diseases such as tuberculosis

Decrease immunity effect of cortisol is useful during transplant operations in reducing organ rejection

Physiological effects of cortisol

Functions - circulation Maintains body fluid volumes amp vascular

integrity Cortisol has mineralcorticoid effect Not as

potent as aldosterone BP regulation amp cardiovascular function Sensitizes arterioles to action of

noradrenaline (Permissive effect) Decreased capillary permeability Maintains normal renal function

Physiological effects of cortisol

Functions - CNS responses

Negative feedback control on release of ACTH

Modulates perception amp emotion

Mineral metabolismAnti-vitamin D effect

GITIncreases HCl secretion

Physiological effects of cortisol

Developmental Functions Permissive regulation of fetal organ

maturation

Surfactant synthesis (phospholipid that maintains alveolar surface tension)

Inhibition of linear growth in children due to direct effects on bone amp connective tissue

Disorders of cortisol

Cortisol excessexogenous amp endogenous Exogenous Most cortisol excess is induced by steroid

therapy (prednisone) to manage disease 1048708 asthma 1048708 rheumatoid arthritis 1048708 lupus 1048708 other inflammatory diseases 1048708 immunosuppression after transplantation

Cortisol excessexogenous amp endogenous

Endogenous Due to excessive production of cortisol ACTH- independent

Primary adrenal defect (adenoma) ACTH-dependent

Overproduction of ACTH by pituitaryOverproduction of ACTH by ectopic ACTH-

producing tumor

Both exogenous amp endogenous hyperfunction show manifestations of Cushingrsquos

Cortisol excessIntermediary metabolism

Carbohydrate metabolismuarr blood glucose levelsdarr sensitivity to insulin

Protein metabolismuarr protein lossmuscle atrophythin skinbone matrix amp mass losses bone formation

darrlessCa2+ absorbed amp more excreted in urine osteoporosis

Cortisol excess

Intermediary metabolism

Fat metabolismredistribution of body fatuarrtrunk amp face fat deposition amp darr

extremities fat deposition

Cortisol excess

Circulation

Hypertension due to Na retention amp K excretion

Hypervolemia

Hypernatremia due to increased Na absorption

Hypokalemia due to increased K excretion

Cortisol excessinflammation amp immunity

Decreases inflammatory response Increased infection susceptibility Ab synthesis suppressed amp normal

immune responses to infecting pathogens suppressed

Decrease in fibrous tissue formation

Cortisol excess ndash effects on CNS

Initially euphoria but replaced with depression

Characteristics

Buffalo torso Redistribution of fat from lower parts of the

body to the thoracic and upper abdominal areas

Moon Face Edematous appearance of face Acne amp hirsutism( excess growth of facial

hair)

Effects on Carbohydrate Metabolism ldquoAdrenal diabetesrdquo

Hypersecretion of cortisol results in increase blood glucose levels up to 2 x normal (200mgdl)

Prolonged oversecretion of insulin ldquoburns outrdquo the beta cells of the pancreas resulting in life long diabetes mellitus

Effects on Protein Metabolism Decrease protein content in most parts of

the body resulting in muscle weakness In lymphoid tissue ndash decrease protein

synthesis results in suppression of the immune system

Lack of protein deposition in bones can result in osteoporosis

Collagen fibers in subcutaneous tissue tear forming striae

Cushing syndrome

ndash Hypersecretion of glucocorticoids by the adrenal

cortex characterized by weight gain in the trunk of the body but not arms and legs

Cushingrsquos Syndrome

striae

ldquomoon facerdquo

Cushingrsquos Disease

Proximal muscle wasting amp weakness

Osteoporosis Glucose intolerance HTN hypokalemia Thromboembolism Depression Psyc Infection Glaucoma

Treatment

Removal of adrenal tumor if this is the cause

Microsurgical removal of hypertrophied pituitary elements to reduce ACTH secretion

Partial or total adrenalectomy followed by administration of adrenal steroids to compensate insufficiencies that develop

• PowerPoint Presentation
• Slide 5
• Slide 11
• Slide 33

Physiological effects of cortisol

Protein metabolism Reduces protein formation in all tissues Except

liver Extrahepatic protein stores reduced (catabolic) amino acids not transported into muscle cells darr

protein synthesis amp uarr amino acid blood levels These high blood amino acid levels are

transported more rapidly to hepatic cells for glucogenesis and protein synthesis in liver

Physiological effects of cortisol

Fat metabolism Lipolytic Mobilizes fatty acids amp glycerol from adipose

tissue lead touarr their blood concentrations makes more glycerol available for glucogenesis

Fat broken down amp less formed due to less glucose transported into fat cells

Redistribution of body fatuarr formation of fat in trunk areas amp facedarr fat (amp muscle) from extremities

Increases appetite

Physiological effects of cortisol

Anti-inflammatory

Stabilizes lysosomal membrane

Reduces degree of vasodilatation

Decreases permeability of capillaries

Decreases migration of white blood cells

Suppresses immune system

Physiological effects of cortisol

Effect on Blood Cells and Immunity Decrease production of eoisinophils and

lymphocytes Suppresses lymphoid tissue systemically therefore

decrease in T cell and antibody production decreasing immunity

Decrease immunity could be fatal in diseases such as tuberculosis

Decrease immunity effect of cortisol is useful during transplant operations in reducing organ rejection

Physiological effects of cortisol

Functions - circulation Maintains body fluid volumes amp vascular

integrity Cortisol has mineralcorticoid effect Not as

potent as aldosterone BP regulation amp cardiovascular function Sensitizes arterioles to action of

noradrenaline (Permissive effect) Decreased capillary permeability Maintains normal renal function

Physiological effects of cortisol

Functions - CNS responses

Negative feedback control on release of ACTH

Modulates perception amp emotion

Mineral metabolismAnti-vitamin D effect

GITIncreases HCl secretion

Physiological effects of cortisol

Developmental Functions Permissive regulation of fetal organ

maturation

Surfactant synthesis (phospholipid that maintains alveolar surface tension)

Inhibition of linear growth in children due to direct effects on bone amp connective tissue

Disorders of cortisol

Cortisol excessexogenous amp endogenous Exogenous Most cortisol excess is induced by steroid

therapy (prednisone) to manage disease 1048708 asthma 1048708 rheumatoid arthritis 1048708 lupus 1048708 other inflammatory diseases 1048708 immunosuppression after transplantation

Cortisol excessexogenous amp endogenous

Endogenous Due to excessive production of cortisol ACTH- independent

Primary adrenal defect (adenoma) ACTH-dependent

Overproduction of ACTH by pituitaryOverproduction of ACTH by ectopic ACTH-

producing tumor

Both exogenous amp endogenous hyperfunction show manifestations of Cushingrsquos

Cortisol excessIntermediary metabolism

Carbohydrate metabolismuarr blood glucose levelsdarr sensitivity to insulin

Protein metabolismuarr protein lossmuscle atrophythin skinbone matrix amp mass losses bone formation

darrlessCa2+ absorbed amp more excreted in urine osteoporosis

Cortisol excess

Intermediary metabolism

Fat metabolismredistribution of body fatuarrtrunk amp face fat deposition amp darr

extremities fat deposition

Cortisol excess

Circulation

Hypertension due to Na retention amp K excretion

Hypervolemia

Hypernatremia due to increased Na absorption

Hypokalemia due to increased K excretion

Cortisol excessinflammation amp immunity

Decreases inflammatory response Increased infection susceptibility Ab synthesis suppressed amp normal

immune responses to infecting pathogens suppressed

Decrease in fibrous tissue formation

Cortisol excess ndash effects on CNS

Initially euphoria but replaced with depression

Characteristics

Buffalo torso Redistribution of fat from lower parts of the

body to the thoracic and upper abdominal areas

Moon Face Edematous appearance of face Acne amp hirsutism( excess growth of facial

hair)

Effects on Carbohydrate Metabolism ldquoAdrenal diabetesrdquo

Hypersecretion of cortisol results in increase blood glucose levels up to 2 x normal (200mgdl)

Prolonged oversecretion of insulin ldquoburns outrdquo the beta cells of the pancreas resulting in life long diabetes mellitus

Effects on Protein Metabolism Decrease protein content in most parts of

the body resulting in muscle weakness In lymphoid tissue ndash decrease protein

synthesis results in suppression of the immune system

Lack of protein deposition in bones can result in osteoporosis

Collagen fibers in subcutaneous tissue tear forming striae

Cushing syndrome

ndash Hypersecretion of glucocorticoids by the adrenal

cortex characterized by weight gain in the trunk of the body but not arms and legs

Cushingrsquos Syndrome

striae

ldquomoon facerdquo

Cushingrsquos Disease

Proximal muscle wasting amp weakness

Osteoporosis Glucose intolerance HTN hypokalemia Thromboembolism Depression Psyc Infection Glaucoma

Treatment

Removal of adrenal tumor if this is the cause

Microsurgical removal of hypertrophied pituitary elements to reduce ACTH secretion

Partial or total adrenalectomy followed by administration of adrenal steroids to compensate insufficiencies that develop

• PowerPoint Presentation
• Slide 5
• Slide 11
• Slide 33

Physiological effects of cortisol

Fat metabolism Lipolytic Mobilizes fatty acids amp glycerol from adipose

tissue lead touarr their blood concentrations makes more glycerol available for glucogenesis

Fat broken down amp less formed due to less glucose transported into fat cells

Redistribution of body fatuarr formation of fat in trunk areas amp facedarr fat (amp muscle) from extremities

Increases appetite

Physiological effects of cortisol

Anti-inflammatory

Stabilizes lysosomal membrane

Reduces degree of vasodilatation

Decreases permeability of capillaries

Decreases migration of white blood cells

Suppresses immune system

Physiological effects of cortisol

Effect on Blood Cells and Immunity Decrease production of eoisinophils and

lymphocytes Suppresses lymphoid tissue systemically therefore

decrease in T cell and antibody production decreasing immunity

Decrease immunity could be fatal in diseases such as tuberculosis

Decrease immunity effect of cortisol is useful during transplant operations in reducing organ rejection

Physiological effects of cortisol

Functions - circulation Maintains body fluid volumes amp vascular

integrity Cortisol has mineralcorticoid effect Not as

potent as aldosterone BP regulation amp cardiovascular function Sensitizes arterioles to action of

noradrenaline (Permissive effect) Decreased capillary permeability Maintains normal renal function

Physiological effects of cortisol

Functions - CNS responses

Negative feedback control on release of ACTH

Modulates perception amp emotion

Mineral metabolismAnti-vitamin D effect

GITIncreases HCl secretion

Physiological effects of cortisol

Developmental Functions Permissive regulation of fetal organ

maturation

Surfactant synthesis (phospholipid that maintains alveolar surface tension)

Inhibition of linear growth in children due to direct effects on bone amp connective tissue

Disorders of cortisol

Cortisol excessexogenous amp endogenous Exogenous Most cortisol excess is induced by steroid

therapy (prednisone) to manage disease 1048708 asthma 1048708 rheumatoid arthritis 1048708 lupus 1048708 other inflammatory diseases 1048708 immunosuppression after transplantation

Cortisol excessexogenous amp endogenous

Endogenous Due to excessive production of cortisol ACTH- independent

Primary adrenal defect (adenoma) ACTH-dependent

Overproduction of ACTH by pituitaryOverproduction of ACTH by ectopic ACTH-

producing tumor

Both exogenous amp endogenous hyperfunction show manifestations of Cushingrsquos

Cortisol excessIntermediary metabolism

Carbohydrate metabolismuarr blood glucose levelsdarr sensitivity to insulin

Protein metabolismuarr protein lossmuscle atrophythin skinbone matrix amp mass losses bone formation

darrlessCa2+ absorbed amp more excreted in urine osteoporosis

Cortisol excess

Intermediary metabolism

Fat metabolismredistribution of body fatuarrtrunk amp face fat deposition amp darr

extremities fat deposition

Cortisol excess

Circulation

Hypertension due to Na retention amp K excretion

Hypervolemia

Hypernatremia due to increased Na absorption

Hypokalemia due to increased K excretion

Cortisol excessinflammation amp immunity

Decreases inflammatory response Increased infection susceptibility Ab synthesis suppressed amp normal

immune responses to infecting pathogens suppressed

Decrease in fibrous tissue formation

Cortisol excess ndash effects on CNS

Initially euphoria but replaced with depression

Characteristics

Buffalo torso Redistribution of fat from lower parts of the

body to the thoracic and upper abdominal areas

Moon Face Edematous appearance of face Acne amp hirsutism( excess growth of facial

hair)

Effects on Carbohydrate Metabolism ldquoAdrenal diabetesrdquo

Hypersecretion of cortisol results in increase blood glucose levels up to 2 x normal (200mgdl)

Prolonged oversecretion of insulin ldquoburns outrdquo the beta cells of the pancreas resulting in life long diabetes mellitus

Effects on Protein Metabolism Decrease protein content in most parts of

the body resulting in muscle weakness In lymphoid tissue ndash decrease protein

synthesis results in suppression of the immune system

Lack of protein deposition in bones can result in osteoporosis

Collagen fibers in subcutaneous tissue tear forming striae

Cushing syndrome

ndash Hypersecretion of glucocorticoids by the adrenal

cortex characterized by weight gain in the trunk of the body but not arms and legs

Cushingrsquos Syndrome

striae

ldquomoon facerdquo

Cushingrsquos Disease

Proximal muscle wasting amp weakness

Osteoporosis Glucose intolerance HTN hypokalemia Thromboembolism Depression Psyc Infection Glaucoma

Treatment

Removal of adrenal tumor if this is the cause

Microsurgical removal of hypertrophied pituitary elements to reduce ACTH secretion

Partial or total adrenalectomy followed by administration of adrenal steroids to compensate insufficiencies that develop

• PowerPoint Presentation
• Slide 5
• Slide 11
• Slide 33

Physiological effects of cortisol

Anti-inflammatory

Stabilizes lysosomal membrane

Reduces degree of vasodilatation

Decreases permeability of capillaries

Decreases migration of white blood cells

Suppresses immune system

Physiological effects of cortisol

Effect on Blood Cells and Immunity Decrease production of eoisinophils and

lymphocytes Suppresses lymphoid tissue systemically therefore

decrease in T cell and antibody production decreasing immunity

Decrease immunity could be fatal in diseases such as tuberculosis

Decrease immunity effect of cortisol is useful during transplant operations in reducing organ rejection

Physiological effects of cortisol

Functions - circulation Maintains body fluid volumes amp vascular

integrity Cortisol has mineralcorticoid effect Not as

potent as aldosterone BP regulation amp cardiovascular function Sensitizes arterioles to action of

noradrenaline (Permissive effect) Decreased capillary permeability Maintains normal renal function

Physiological effects of cortisol

Functions - CNS responses

Negative feedback control on release of ACTH

Modulates perception amp emotion

Mineral metabolismAnti-vitamin D effect

GITIncreases HCl secretion

Physiological effects of cortisol

Developmental Functions Permissive regulation of fetal organ

maturation

Surfactant synthesis (phospholipid that maintains alveolar surface tension)

Inhibition of linear growth in children due to direct effects on bone amp connective tissue

Disorders of cortisol

Cortisol excessexogenous amp endogenous Exogenous Most cortisol excess is induced by steroid

therapy (prednisone) to manage disease 1048708 asthma 1048708 rheumatoid arthritis 1048708 lupus 1048708 other inflammatory diseases 1048708 immunosuppression after transplantation

Cortisol excessexogenous amp endogenous

Endogenous Due to excessive production of cortisol ACTH- independent

Primary adrenal defect (adenoma) ACTH-dependent

Overproduction of ACTH by pituitaryOverproduction of ACTH by ectopic ACTH-

producing tumor

Both exogenous amp endogenous hyperfunction show manifestations of Cushingrsquos

Cortisol excessIntermediary metabolism

Carbohydrate metabolismuarr blood glucose levelsdarr sensitivity to insulin

Protein metabolismuarr protein lossmuscle atrophythin skinbone matrix amp mass losses bone formation

darrlessCa2+ absorbed amp more excreted in urine osteoporosis

Cortisol excess

Intermediary metabolism

Fat metabolismredistribution of body fatuarrtrunk amp face fat deposition amp darr

extremities fat deposition

Cortisol excess

Circulation

Hypertension due to Na retention amp K excretion

Hypervolemia

Hypernatremia due to increased Na absorption

Hypokalemia due to increased K excretion

Cortisol excessinflammation amp immunity

Decreases inflammatory response Increased infection susceptibility Ab synthesis suppressed amp normal

immune responses to infecting pathogens suppressed

Decrease in fibrous tissue formation

Cortisol excess ndash effects on CNS

Initially euphoria but replaced with depression

Characteristics

Buffalo torso Redistribution of fat from lower parts of the

body to the thoracic and upper abdominal areas

Moon Face Edematous appearance of face Acne amp hirsutism( excess growth of facial

hair)

Effects on Carbohydrate Metabolism ldquoAdrenal diabetesrdquo

Hypersecretion of cortisol results in increase blood glucose levels up to 2 x normal (200mgdl)

Prolonged oversecretion of insulin ldquoburns outrdquo the beta cells of the pancreas resulting in life long diabetes mellitus

Effects on Protein Metabolism Decrease protein content in most parts of

the body resulting in muscle weakness In lymphoid tissue ndash decrease protein

synthesis results in suppression of the immune system

Lack of protein deposition in bones can result in osteoporosis

Collagen fibers in subcutaneous tissue tear forming striae

Cushing syndrome

ndash Hypersecretion of glucocorticoids by the adrenal

cortex characterized by weight gain in the trunk of the body but not arms and legs

Cushingrsquos Syndrome

striae

ldquomoon facerdquo

Cushingrsquos Disease

Proximal muscle wasting amp weakness

Osteoporosis Glucose intolerance HTN hypokalemia Thromboembolism Depression Psyc Infection Glaucoma

Treatment

Removal of adrenal tumor if this is the cause

Microsurgical removal of hypertrophied pituitary elements to reduce ACTH secretion

Partial or total adrenalectomy followed by administration of adrenal steroids to compensate insufficiencies that develop

• PowerPoint Presentation
• Slide 5
• Slide 11
• Slide 33

Physiological effects of cortisol

Effect on Blood Cells and Immunity Decrease production of eoisinophils and

lymphocytes Suppresses lymphoid tissue systemically therefore

decrease in T cell and antibody production decreasing immunity

Decrease immunity could be fatal in diseases such as tuberculosis

Decrease immunity effect of cortisol is useful during transplant operations in reducing organ rejection

Physiological effects of cortisol

Functions - circulation Maintains body fluid volumes amp vascular

integrity Cortisol has mineralcorticoid effect Not as

potent as aldosterone BP regulation amp cardiovascular function Sensitizes arterioles to action of

noradrenaline (Permissive effect) Decreased capillary permeability Maintains normal renal function

Physiological effects of cortisol

Functions - CNS responses

Negative feedback control on release of ACTH

Modulates perception amp emotion

Mineral metabolismAnti-vitamin D effect

GITIncreases HCl secretion

Physiological effects of cortisol

Developmental Functions Permissive regulation of fetal organ

maturation

Surfactant synthesis (phospholipid that maintains alveolar surface tension)

Inhibition of linear growth in children due to direct effects on bone amp connective tissue

Disorders of cortisol

Cortisol excessexogenous amp endogenous Exogenous Most cortisol excess is induced by steroid

therapy (prednisone) to manage disease 1048708 asthma 1048708 rheumatoid arthritis 1048708 lupus 1048708 other inflammatory diseases 1048708 immunosuppression after transplantation

Cortisol excessexogenous amp endogenous

Endogenous Due to excessive production of cortisol ACTH- independent

Primary adrenal defect (adenoma) ACTH-dependent

Overproduction of ACTH by pituitaryOverproduction of ACTH by ectopic ACTH-

producing tumor

Both exogenous amp endogenous hyperfunction show manifestations of Cushingrsquos

Cortisol excessIntermediary metabolism

Carbohydrate metabolismuarr blood glucose levelsdarr sensitivity to insulin

Protein metabolismuarr protein lossmuscle atrophythin skinbone matrix amp mass losses bone formation

darrlessCa2+ absorbed amp more excreted in urine osteoporosis

Cortisol excess

Intermediary metabolism

Fat metabolismredistribution of body fatuarrtrunk amp face fat deposition amp darr

extremities fat deposition

Cortisol excess

Circulation

Hypertension due to Na retention amp K excretion

Hypervolemia

Hypernatremia due to increased Na absorption

Hypokalemia due to increased K excretion

Cortisol excessinflammation amp immunity

Decreases inflammatory response Increased infection susceptibility Ab synthesis suppressed amp normal

immune responses to infecting pathogens suppressed

Decrease in fibrous tissue formation

Cortisol excess ndash effects on CNS

Initially euphoria but replaced with depression

Characteristics

Buffalo torso Redistribution of fat from lower parts of the

body to the thoracic and upper abdominal areas

Moon Face Edematous appearance of face Acne amp hirsutism( excess growth of facial

hair)

Effects on Carbohydrate Metabolism ldquoAdrenal diabetesrdquo

Hypersecretion of cortisol results in increase blood glucose levels up to 2 x normal (200mgdl)

Prolonged oversecretion of insulin ldquoburns outrdquo the beta cells of the pancreas resulting in life long diabetes mellitus

Effects on Protein Metabolism Decrease protein content in most parts of

the body resulting in muscle weakness In lymphoid tissue ndash decrease protein

synthesis results in suppression of the immune system

Lack of protein deposition in bones can result in osteoporosis

Collagen fibers in subcutaneous tissue tear forming striae

Cushing syndrome

ndash Hypersecretion of glucocorticoids by the adrenal

cortex characterized by weight gain in the trunk of the body but not arms and legs

Cushingrsquos Syndrome

striae

ldquomoon facerdquo

Cushingrsquos Disease

Proximal muscle wasting amp weakness

Osteoporosis Glucose intolerance HTN hypokalemia Thromboembolism Depression Psyc Infection Glaucoma

Treatment

Removal of adrenal tumor if this is the cause

Microsurgical removal of hypertrophied pituitary elements to reduce ACTH secretion

Partial or total adrenalectomy followed by administration of adrenal steroids to compensate insufficiencies that develop

• PowerPoint Presentation
• Slide 5
• Slide 11
• Slide 33

Physiological effects of cortisol

Functions - circulation Maintains body fluid volumes amp vascular

integrity Cortisol has mineralcorticoid effect Not as

potent as aldosterone BP regulation amp cardiovascular function Sensitizes arterioles to action of

noradrenaline (Permissive effect) Decreased capillary permeability Maintains normal renal function

Physiological effects of cortisol

Functions - CNS responses

Negative feedback control on release of ACTH

Modulates perception amp emotion

Mineral metabolismAnti-vitamin D effect

GITIncreases HCl secretion

Physiological effects of cortisol

Developmental Functions Permissive regulation of fetal organ

maturation

Surfactant synthesis (phospholipid that maintains alveolar surface tension)

Inhibition of linear growth in children due to direct effects on bone amp connective tissue

Disorders of cortisol

Cortisol excessexogenous amp endogenous Exogenous Most cortisol excess is induced by steroid

therapy (prednisone) to manage disease 1048708 asthma 1048708 rheumatoid arthritis 1048708 lupus 1048708 other inflammatory diseases 1048708 immunosuppression after transplantation

Cortisol excessexogenous amp endogenous

Endogenous Due to excessive production of cortisol ACTH- independent

Primary adrenal defect (adenoma) ACTH-dependent

Overproduction of ACTH by pituitaryOverproduction of ACTH by ectopic ACTH-

producing tumor

Both exogenous amp endogenous hyperfunction show manifestations of Cushingrsquos

Cortisol excessIntermediary metabolism

Carbohydrate metabolismuarr blood glucose levelsdarr sensitivity to insulin

Protein metabolismuarr protein lossmuscle atrophythin skinbone matrix amp mass losses bone formation

darrlessCa2+ absorbed amp more excreted in urine osteoporosis

Cortisol excess

Intermediary metabolism

Fat metabolismredistribution of body fatuarrtrunk amp face fat deposition amp darr

extremities fat deposition

Cortisol excess

Circulation

Hypertension due to Na retention amp K excretion

Hypervolemia

Hypernatremia due to increased Na absorption

Hypokalemia due to increased K excretion

Cortisol excessinflammation amp immunity

Decreases inflammatory response Increased infection susceptibility Ab synthesis suppressed amp normal

immune responses to infecting pathogens suppressed

Decrease in fibrous tissue formation

Cortisol excess ndash effects on CNS

Initially euphoria but replaced with depression

Characteristics

Buffalo torso Redistribution of fat from lower parts of the

body to the thoracic and upper abdominal areas

Moon Face Edematous appearance of face Acne amp hirsutism( excess growth of facial

hair)

Effects on Carbohydrate Metabolism ldquoAdrenal diabetesrdquo

Hypersecretion of cortisol results in increase blood glucose levels up to 2 x normal (200mgdl)

Prolonged oversecretion of insulin ldquoburns outrdquo the beta cells of the pancreas resulting in life long diabetes mellitus

Effects on Protein Metabolism Decrease protein content in most parts of

the body resulting in muscle weakness In lymphoid tissue ndash decrease protein

synthesis results in suppression of the immune system

Lack of protein deposition in bones can result in osteoporosis

Collagen fibers in subcutaneous tissue tear forming striae

Cushing syndrome

ndash Hypersecretion of glucocorticoids by the adrenal

cortex characterized by weight gain in the trunk of the body but not arms and legs

Cushingrsquos Syndrome

striae

ldquomoon facerdquo

Cushingrsquos Disease

Proximal muscle wasting amp weakness

Osteoporosis Glucose intolerance HTN hypokalemia Thromboembolism Depression Psyc Infection Glaucoma

Treatment

Removal of adrenal tumor if this is the cause

Microsurgical removal of hypertrophied pituitary elements to reduce ACTH secretion

Partial or total adrenalectomy followed by administration of adrenal steroids to compensate insufficiencies that develop

• PowerPoint Presentation
• Slide 5
• Slide 11
• Slide 33

Physiological effects of cortisol

Functions - CNS responses

Negative feedback control on release of ACTH

Modulates perception amp emotion

Mineral metabolismAnti-vitamin D effect

GITIncreases HCl secretion

Physiological effects of cortisol

Developmental Functions Permissive regulation of fetal organ

maturation

Surfactant synthesis (phospholipid that maintains alveolar surface tension)

Inhibition of linear growth in children due to direct effects on bone amp connective tissue

Disorders of cortisol

Cortisol excessexogenous amp endogenous Exogenous Most cortisol excess is induced by steroid

therapy (prednisone) to manage disease 1048708 asthma 1048708 rheumatoid arthritis 1048708 lupus 1048708 other inflammatory diseases 1048708 immunosuppression after transplantation

Cortisol excessexogenous amp endogenous

Endogenous Due to excessive production of cortisol ACTH- independent

Primary adrenal defect (adenoma) ACTH-dependent

Overproduction of ACTH by pituitaryOverproduction of ACTH by ectopic ACTH-

producing tumor

Both exogenous amp endogenous hyperfunction show manifestations of Cushingrsquos

Cortisol excessIntermediary metabolism

Carbohydrate metabolismuarr blood glucose levelsdarr sensitivity to insulin

Protein metabolismuarr protein lossmuscle atrophythin skinbone matrix amp mass losses bone formation

darrlessCa2+ absorbed amp more excreted in urine osteoporosis

Cortisol excess

Intermediary metabolism

Fat metabolismredistribution of body fatuarrtrunk amp face fat deposition amp darr

extremities fat deposition

Cortisol excess

Circulation

Hypertension due to Na retention amp K excretion

Hypervolemia

Hypernatremia due to increased Na absorption

Hypokalemia due to increased K excretion

Cortisol excessinflammation amp immunity

Decreases inflammatory response Increased infection susceptibility Ab synthesis suppressed amp normal

immune responses to infecting pathogens suppressed

Decrease in fibrous tissue formation

Cortisol excess ndash effects on CNS

Initially euphoria but replaced with depression

Characteristics

Buffalo torso Redistribution of fat from lower parts of the

body to the thoracic and upper abdominal areas

Moon Face Edematous appearance of face Acne amp hirsutism( excess growth of facial

hair)

Effects on Carbohydrate Metabolism ldquoAdrenal diabetesrdquo

Hypersecretion of cortisol results in increase blood glucose levels up to 2 x normal (200mgdl)

Prolonged oversecretion of insulin ldquoburns outrdquo the beta cells of the pancreas resulting in life long diabetes mellitus

Effects on Protein Metabolism Decrease protein content in most parts of

the body resulting in muscle weakness In lymphoid tissue ndash decrease protein

synthesis results in suppression of the immune system

Lack of protein deposition in bones can result in osteoporosis

Collagen fibers in subcutaneous tissue tear forming striae

Cushing syndrome

ndash Hypersecretion of glucocorticoids by the adrenal

cortex characterized by weight gain in the trunk of the body but not arms and legs

Cushingrsquos Syndrome

striae

ldquomoon facerdquo

Cushingrsquos Disease

Proximal muscle wasting amp weakness

Osteoporosis Glucose intolerance HTN hypokalemia Thromboembolism Depression Psyc Infection Glaucoma

Treatment

Removal of adrenal tumor if this is the cause

Microsurgical removal of hypertrophied pituitary elements to reduce ACTH secretion

Partial or total adrenalectomy followed by administration of adrenal steroids to compensate insufficiencies that develop

• PowerPoint Presentation
• Slide 5
• Slide 11
• Slide 33

Physiological effects of cortisol

Developmental Functions Permissive regulation of fetal organ

maturation

Surfactant synthesis (phospholipid that maintains alveolar surface tension)

Inhibition of linear growth in children due to direct effects on bone amp connective tissue

Disorders of cortisol

Cortisol excessexogenous amp endogenous Exogenous Most cortisol excess is induced by steroid

therapy (prednisone) to manage disease 1048708 asthma 1048708 rheumatoid arthritis 1048708 lupus 1048708 other inflammatory diseases 1048708 immunosuppression after transplantation

Cortisol excessexogenous amp endogenous

Endogenous Due to excessive production of cortisol ACTH- independent

Primary adrenal defect (adenoma) ACTH-dependent

Overproduction of ACTH by pituitaryOverproduction of ACTH by ectopic ACTH-

producing tumor

Both exogenous amp endogenous hyperfunction show manifestations of Cushingrsquos

Cortisol excessIntermediary metabolism

Carbohydrate metabolismuarr blood glucose levelsdarr sensitivity to insulin

Protein metabolismuarr protein lossmuscle atrophythin skinbone matrix amp mass losses bone formation

darrlessCa2+ absorbed amp more excreted in urine osteoporosis

Cortisol excess

Intermediary metabolism

Fat metabolismredistribution of body fatuarrtrunk amp face fat deposition amp darr

extremities fat deposition

Cortisol excess

Circulation

Hypertension due to Na retention amp K excretion

Hypervolemia

Hypernatremia due to increased Na absorption

Hypokalemia due to increased K excretion

Cortisol excessinflammation amp immunity

Decreases inflammatory response Increased infection susceptibility Ab synthesis suppressed amp normal

immune responses to infecting pathogens suppressed

Decrease in fibrous tissue formation

Cortisol excess ndash effects on CNS

Initially euphoria but replaced with depression

Characteristics

Buffalo torso Redistribution of fat from lower parts of the

body to the thoracic and upper abdominal areas

Moon Face Edematous appearance of face Acne amp hirsutism( excess growth of facial

hair)

Effects on Carbohydrate Metabolism ldquoAdrenal diabetesrdquo

Hypersecretion of cortisol results in increase blood glucose levels up to 2 x normal (200mgdl)

Prolonged oversecretion of insulin ldquoburns outrdquo the beta cells of the pancreas resulting in life long diabetes mellitus

Effects on Protein Metabolism Decrease protein content in most parts of

the body resulting in muscle weakness In lymphoid tissue ndash decrease protein

synthesis results in suppression of the immune system

Lack of protein deposition in bones can result in osteoporosis

Collagen fibers in subcutaneous tissue tear forming striae

Cushing syndrome

ndash Hypersecretion of glucocorticoids by the adrenal

cortex characterized by weight gain in the trunk of the body but not arms and legs

Cushingrsquos Syndrome

striae

ldquomoon facerdquo

Cushingrsquos Disease

Proximal muscle wasting amp weakness

Osteoporosis Glucose intolerance HTN hypokalemia Thromboembolism Depression Psyc Infection Glaucoma

Treatment

Removal of adrenal tumor if this is the cause

Microsurgical removal of hypertrophied pituitary elements to reduce ACTH secretion

Partial or total adrenalectomy followed by administration of adrenal steroids to compensate insufficiencies that develop

• PowerPoint Presentation
• Slide 5
• Slide 11
• Slide 33

Disorders of cortisol

Cortisol excessexogenous amp endogenous Exogenous Most cortisol excess is induced by steroid

therapy (prednisone) to manage disease 1048708 asthma 1048708 rheumatoid arthritis 1048708 lupus 1048708 other inflammatory diseases 1048708 immunosuppression after transplantation

Cortisol excessexogenous amp endogenous

Endogenous Due to excessive production of cortisol ACTH- independent

Primary adrenal defect (adenoma) ACTH-dependent

Overproduction of ACTH by pituitaryOverproduction of ACTH by ectopic ACTH-

producing tumor

Both exogenous amp endogenous hyperfunction show manifestations of Cushingrsquos

Cortisol excessIntermediary metabolism

Carbohydrate metabolismuarr blood glucose levelsdarr sensitivity to insulin

Protein metabolismuarr protein lossmuscle atrophythin skinbone matrix amp mass losses bone formation

darrlessCa2+ absorbed amp more excreted in urine osteoporosis

Cortisol excess

Intermediary metabolism

Fat metabolismredistribution of body fatuarrtrunk amp face fat deposition amp darr

extremities fat deposition

Cortisol excess

Circulation

Hypertension due to Na retention amp K excretion

Hypervolemia

Hypernatremia due to increased Na absorption

Hypokalemia due to increased K excretion

Cortisol excessinflammation amp immunity

Decreases inflammatory response Increased infection susceptibility Ab synthesis suppressed amp normal

immune responses to infecting pathogens suppressed

Decrease in fibrous tissue formation

Cortisol excess ndash effects on CNS

Initially euphoria but replaced with depression

Characteristics

Buffalo torso Redistribution of fat from lower parts of the

body to the thoracic and upper abdominal areas

Moon Face Edematous appearance of face Acne amp hirsutism( excess growth of facial

hair)

Effects on Carbohydrate Metabolism ldquoAdrenal diabetesrdquo

Hypersecretion of cortisol results in increase blood glucose levels up to 2 x normal (200mgdl)

Prolonged oversecretion of insulin ldquoburns outrdquo the beta cells of the pancreas resulting in life long diabetes mellitus

Effects on Protein Metabolism Decrease protein content in most parts of

the body resulting in muscle weakness In lymphoid tissue ndash decrease protein

synthesis results in suppression of the immune system

Lack of protein deposition in bones can result in osteoporosis

Collagen fibers in subcutaneous tissue tear forming striae

Cushing syndrome

ndash Hypersecretion of glucocorticoids by the adrenal

cortex characterized by weight gain in the trunk of the body but not arms and legs

Cushingrsquos Syndrome

striae

ldquomoon facerdquo

Cushingrsquos Disease

Proximal muscle wasting amp weakness

Osteoporosis Glucose intolerance HTN hypokalemia Thromboembolism Depression Psyc Infection Glaucoma

Treatment

Removal of adrenal tumor if this is the cause

Microsurgical removal of hypertrophied pituitary elements to reduce ACTH secretion

Partial or total adrenalectomy followed by administration of adrenal steroids to compensate insufficiencies that develop

• PowerPoint Presentation
• Slide 5
• Slide 11
• Slide 33

Cortisol excessexogenous amp endogenous

Endogenous Due to excessive production of cortisol ACTH- independent

Primary adrenal defect (adenoma) ACTH-dependent

Overproduction of ACTH by pituitaryOverproduction of ACTH by ectopic ACTH-

producing tumor

Both exogenous amp endogenous hyperfunction show manifestations of Cushingrsquos

Cortisol excessIntermediary metabolism

Carbohydrate metabolismuarr blood glucose levelsdarr sensitivity to insulin

Protein metabolismuarr protein lossmuscle atrophythin skinbone matrix amp mass losses bone formation

darrlessCa2+ absorbed amp more excreted in urine osteoporosis

Cortisol excess

Intermediary metabolism

Fat metabolismredistribution of body fatuarrtrunk amp face fat deposition amp darr

extremities fat deposition

Cortisol excess

Circulation

Hypertension due to Na retention amp K excretion

Hypervolemia

Hypernatremia due to increased Na absorption

Hypokalemia due to increased K excretion

Cortisol excessinflammation amp immunity

Decreases inflammatory response Increased infection susceptibility Ab synthesis suppressed amp normal

immune responses to infecting pathogens suppressed

Decrease in fibrous tissue formation

Cortisol excess ndash effects on CNS

Initially euphoria but replaced with depression

Characteristics

Buffalo torso Redistribution of fat from lower parts of the

body to the thoracic and upper abdominal areas

Moon Face Edematous appearance of face Acne amp hirsutism( excess growth of facial

hair)

Effects on Carbohydrate Metabolism ldquoAdrenal diabetesrdquo

Hypersecretion of cortisol results in increase blood glucose levels up to 2 x normal (200mgdl)

Prolonged oversecretion of insulin ldquoburns outrdquo the beta cells of the pancreas resulting in life long diabetes mellitus

Effects on Protein Metabolism Decrease protein content in most parts of

the body resulting in muscle weakness In lymphoid tissue ndash decrease protein

synthesis results in suppression of the immune system

Lack of protein deposition in bones can result in osteoporosis

Collagen fibers in subcutaneous tissue tear forming striae

Cushing syndrome

ndash Hypersecretion of glucocorticoids by the adrenal

cortex characterized by weight gain in the trunk of the body but not arms and legs

Cushingrsquos Syndrome

striae

ldquomoon facerdquo

Cushingrsquos Disease

Proximal muscle wasting amp weakness

Osteoporosis Glucose intolerance HTN hypokalemia Thromboembolism Depression Psyc Infection Glaucoma

Treatment

Removal of adrenal tumor if this is the cause

Microsurgical removal of hypertrophied pituitary elements to reduce ACTH secretion

Partial or total adrenalectomy followed by administration of adrenal steroids to compensate insufficiencies that develop

• PowerPoint Presentation
• Slide 5
• Slide 11
• Slide 33

Cortisol excessIntermediary metabolism

Carbohydrate metabolismuarr blood glucose levelsdarr sensitivity to insulin

Protein metabolismuarr protein lossmuscle atrophythin skinbone matrix amp mass losses bone formation

darrlessCa2+ absorbed amp more excreted in urine osteoporosis

Cortisol excess

Intermediary metabolism

Fat metabolismredistribution of body fatuarrtrunk amp face fat deposition amp darr

extremities fat deposition

Cortisol excess

Circulation

Hypertension due to Na retention amp K excretion

Hypervolemia

Hypernatremia due to increased Na absorption

Hypokalemia due to increased K excretion

Cortisol excessinflammation amp immunity

Decreases inflammatory response Increased infection susceptibility Ab synthesis suppressed amp normal

immune responses to infecting pathogens suppressed

Decrease in fibrous tissue formation

Cortisol excess ndash effects on CNS

Initially euphoria but replaced with depression

Characteristics

Buffalo torso Redistribution of fat from lower parts of the

body to the thoracic and upper abdominal areas

Moon Face Edematous appearance of face Acne amp hirsutism( excess growth of facial

hair)

Effects on Carbohydrate Metabolism ldquoAdrenal diabetesrdquo

Hypersecretion of cortisol results in increase blood glucose levels up to 2 x normal (200mgdl)

Prolonged oversecretion of insulin ldquoburns outrdquo the beta cells of the pancreas resulting in life long diabetes mellitus

Effects on Protein Metabolism Decrease protein content in most parts of

the body resulting in muscle weakness In lymphoid tissue ndash decrease protein

synthesis results in suppression of the immune system

Lack of protein deposition in bones can result in osteoporosis

Collagen fibers in subcutaneous tissue tear forming striae

Cushing syndrome

ndash Hypersecretion of glucocorticoids by the adrenal

cortex characterized by weight gain in the trunk of the body but not arms and legs

Cushingrsquos Syndrome

striae

ldquomoon facerdquo

Cushingrsquos Disease

Proximal muscle wasting amp weakness

Osteoporosis Glucose intolerance HTN hypokalemia Thromboembolism Depression Psyc Infection Glaucoma

Treatment

Removal of adrenal tumor if this is the cause

Microsurgical removal of hypertrophied pituitary elements to reduce ACTH secretion

Partial or total adrenalectomy followed by administration of adrenal steroids to compensate insufficiencies that develop

• PowerPoint Presentation
• Slide 5
• Slide 11
• Slide 33

Cortisol excess

Intermediary metabolism

Fat metabolismredistribution of body fatuarrtrunk amp face fat deposition amp darr

extremities fat deposition

Cortisol excess

Circulation

Hypertension due to Na retention amp K excretion

Hypervolemia

Hypernatremia due to increased Na absorption

Hypokalemia due to increased K excretion

Cortisol excessinflammation amp immunity

Decreases inflammatory response Increased infection susceptibility Ab synthesis suppressed amp normal

immune responses to infecting pathogens suppressed

Decrease in fibrous tissue formation

Cortisol excess ndash effects on CNS

Initially euphoria but replaced with depression

Characteristics

Buffalo torso Redistribution of fat from lower parts of the

body to the thoracic and upper abdominal areas

Moon Face Edematous appearance of face Acne amp hirsutism( excess growth of facial

hair)

Effects on Carbohydrate Metabolism ldquoAdrenal diabetesrdquo

Hypersecretion of cortisol results in increase blood glucose levels up to 2 x normal (200mgdl)

Prolonged oversecretion of insulin ldquoburns outrdquo the beta cells of the pancreas resulting in life long diabetes mellitus

Effects on Protein Metabolism Decrease protein content in most parts of

the body resulting in muscle weakness In lymphoid tissue ndash decrease protein

synthesis results in suppression of the immune system

Lack of protein deposition in bones can result in osteoporosis

Collagen fibers in subcutaneous tissue tear forming striae

Cushing syndrome

ndash Hypersecretion of glucocorticoids by the adrenal

cortex characterized by weight gain in the trunk of the body but not arms and legs

Cushingrsquos Syndrome

striae

ldquomoon facerdquo

Cushingrsquos Disease

Proximal muscle wasting amp weakness

Osteoporosis Glucose intolerance HTN hypokalemia Thromboembolism Depression Psyc Infection Glaucoma

Treatment

Removal of adrenal tumor if this is the cause

Microsurgical removal of hypertrophied pituitary elements to reduce ACTH secretion

Partial or total adrenalectomy followed by administration of adrenal steroids to compensate insufficiencies that develop

• PowerPoint Presentation
• Slide 5
• Slide 11
• Slide 33

Cortisol excess

Circulation

Hypertension due to Na retention amp K excretion

Hypervolemia

Hypernatremia due to increased Na absorption

Hypokalemia due to increased K excretion

Cortisol excessinflammation amp immunity

Decreases inflammatory response Increased infection susceptibility Ab synthesis suppressed amp normal

immune responses to infecting pathogens suppressed

Decrease in fibrous tissue formation

Cortisol excess ndash effects on CNS

Initially euphoria but replaced with depression

Characteristics

Buffalo torso Redistribution of fat from lower parts of the

body to the thoracic and upper abdominal areas

Moon Face Edematous appearance of face Acne amp hirsutism( excess growth of facial

hair)

Effects on Carbohydrate Metabolism ldquoAdrenal diabetesrdquo

Hypersecretion of cortisol results in increase blood glucose levels up to 2 x normal (200mgdl)

Prolonged oversecretion of insulin ldquoburns outrdquo the beta cells of the pancreas resulting in life long diabetes mellitus

Effects on Protein Metabolism Decrease protein content in most parts of

the body resulting in muscle weakness In lymphoid tissue ndash decrease protein

synthesis results in suppression of the immune system

Lack of protein deposition in bones can result in osteoporosis

Collagen fibers in subcutaneous tissue tear forming striae

Cushing syndrome

ndash Hypersecretion of glucocorticoids by the adrenal

cortex characterized by weight gain in the trunk of the body but not arms and legs

Cushingrsquos Syndrome

striae

ldquomoon facerdquo

Cushingrsquos Disease

Proximal muscle wasting amp weakness

Osteoporosis Glucose intolerance HTN hypokalemia Thromboembolism Depression Psyc Infection Glaucoma

Treatment

Removal of adrenal tumor if this is the cause

Microsurgical removal of hypertrophied pituitary elements to reduce ACTH secretion

Partial or total adrenalectomy followed by administration of adrenal steroids to compensate insufficiencies that develop

• PowerPoint Presentation
• Slide 5
• Slide 11
• Slide 33

Cortisol excessinflammation amp immunity

Decreases inflammatory response Increased infection susceptibility Ab synthesis suppressed amp normal

immune responses to infecting pathogens suppressed

Decrease in fibrous tissue formation

Cortisol excess ndash effects on CNS

Initially euphoria but replaced with depression

Characteristics

Buffalo torso Redistribution of fat from lower parts of the

body to the thoracic and upper abdominal areas

Moon Face Edematous appearance of face Acne amp hirsutism( excess growth of facial

hair)

Effects on Carbohydrate Metabolism ldquoAdrenal diabetesrdquo

Hypersecretion of cortisol results in increase blood glucose levels up to 2 x normal (200mgdl)

Prolonged oversecretion of insulin ldquoburns outrdquo the beta cells of the pancreas resulting in life long diabetes mellitus

Effects on Protein Metabolism Decrease protein content in most parts of

the body resulting in muscle weakness In lymphoid tissue ndash decrease protein

synthesis results in suppression of the immune system

Lack of protein deposition in bones can result in osteoporosis

Collagen fibers in subcutaneous tissue tear forming striae

Cushing syndrome

ndash Hypersecretion of glucocorticoids by the adrenal

cortex characterized by weight gain in the trunk of the body but not arms and legs

Cushingrsquos Syndrome

striae

ldquomoon facerdquo

Cushingrsquos Disease

Proximal muscle wasting amp weakness

Osteoporosis Glucose intolerance HTN hypokalemia Thromboembolism Depression Psyc Infection Glaucoma

Treatment

Removal of adrenal tumor if this is the cause

Microsurgical removal of hypertrophied pituitary elements to reduce ACTH secretion

Partial or total adrenalectomy followed by administration of adrenal steroids to compensate insufficiencies that develop

• PowerPoint Presentation
• Slide 5
• Slide 11
• Slide 33

Cortisol excess ndash effects on CNS

Initially euphoria but replaced with depression

Characteristics

Buffalo torso Redistribution of fat from lower parts of the

body to the thoracic and upper abdominal areas

Moon Face Edematous appearance of face Acne amp hirsutism( excess growth of facial

hair)

Effects on Carbohydrate Metabolism ldquoAdrenal diabetesrdquo

Hypersecretion of cortisol results in increase blood glucose levels up to 2 x normal (200mgdl)

Prolonged oversecretion of insulin ldquoburns outrdquo the beta cells of the pancreas resulting in life long diabetes mellitus

Effects on Protein Metabolism Decrease protein content in most parts of

the body resulting in muscle weakness In lymphoid tissue ndash decrease protein

synthesis results in suppression of the immune system

Lack of protein deposition in bones can result in osteoporosis

Collagen fibers in subcutaneous tissue tear forming striae

Cushing syndrome

ndash Hypersecretion of glucocorticoids by the adrenal

cortex characterized by weight gain in the trunk of the body but not arms and legs

Cushingrsquos Syndrome

striae

ldquomoon facerdquo

Cushingrsquos Disease

Proximal muscle wasting amp weakness

Osteoporosis Glucose intolerance HTN hypokalemia Thromboembolism Depression Psyc Infection Glaucoma

Treatment

Removal of adrenal tumor if this is the cause

Microsurgical removal of hypertrophied pituitary elements to reduce ACTH secretion

Partial or total adrenalectomy followed by administration of adrenal steroids to compensate insufficiencies that develop

• PowerPoint Presentation
• Slide 5
• Slide 11
• Slide 33

Characteristics

Buffalo torso Redistribution of fat from lower parts of the

body to the thoracic and upper abdominal areas

Moon Face Edematous appearance of face Acne amp hirsutism( excess growth of facial

hair)

Effects on Carbohydrate Metabolism ldquoAdrenal diabetesrdquo

Hypersecretion of cortisol results in increase blood glucose levels up to 2 x normal (200mgdl)

Prolonged oversecretion of insulin ldquoburns outrdquo the beta cells of the pancreas resulting in life long diabetes mellitus

Effects on Protein Metabolism Decrease protein content in most parts of

the body resulting in muscle weakness In lymphoid tissue ndash decrease protein

synthesis results in suppression of the immune system

Lack of protein deposition in bones can result in osteoporosis

Collagen fibers in subcutaneous tissue tear forming striae

Cushing syndrome

ndash Hypersecretion of glucocorticoids by the adrenal

cortex characterized by weight gain in the trunk of the body but not arms and legs

Cushingrsquos Syndrome

striae

ldquomoon facerdquo

Cushingrsquos Disease

Proximal muscle wasting amp weakness

Osteoporosis Glucose intolerance HTN hypokalemia Thromboembolism Depression Psyc Infection Glaucoma

Treatment

Removal of adrenal tumor if this is the cause

Microsurgical removal of hypertrophied pituitary elements to reduce ACTH secretion

Partial or total adrenalectomy followed by administration of adrenal steroids to compensate insufficiencies that develop

• PowerPoint Presentation
• Slide 5
• Slide 11
• Slide 33

Effects on Carbohydrate Metabolism ldquoAdrenal diabetesrdquo

Hypersecretion of cortisol results in increase blood glucose levels up to 2 x normal (200mgdl)

Prolonged oversecretion of insulin ldquoburns outrdquo the beta cells of the pancreas resulting in life long diabetes mellitus

Effects on Protein Metabolism Decrease protein content in most parts of

the body resulting in muscle weakness In lymphoid tissue ndash decrease protein

synthesis results in suppression of the immune system

Lack of protein deposition in bones can result in osteoporosis

Collagen fibers in subcutaneous tissue tear forming striae

Cushing syndrome

ndash Hypersecretion of glucocorticoids by the adrenal

cortex characterized by weight gain in the trunk of the body but not arms and legs

Cushingrsquos Syndrome

striae

ldquomoon facerdquo

Cushingrsquos Disease

Proximal muscle wasting amp weakness

Osteoporosis Glucose intolerance HTN hypokalemia Thromboembolism Depression Psyc Infection Glaucoma

Treatment

Removal of adrenal tumor if this is the cause

Microsurgical removal of hypertrophied pituitary elements to reduce ACTH secretion

Partial or total adrenalectomy followed by administration of adrenal steroids to compensate insufficiencies that develop

• PowerPoint Presentation
• Slide 5
• Slide 11
• Slide 33

Effects on Protein Metabolism Decrease protein content in most parts of

the body resulting in muscle weakness In lymphoid tissue ndash decrease protein

synthesis results in suppression of the immune system

Lack of protein deposition in bones can result in osteoporosis

Collagen fibers in subcutaneous tissue tear forming striae

Cushing syndrome

ndash Hypersecretion of glucocorticoids by the adrenal

cortex characterized by weight gain in the trunk of the body but not arms and legs

Cushingrsquos Syndrome

striae

ldquomoon facerdquo

Cushingrsquos Disease

Proximal muscle wasting amp weakness

Osteoporosis Glucose intolerance HTN hypokalemia Thromboembolism Depression Psyc Infection Glaucoma

Treatment

Removal of adrenal tumor if this is the cause

Microsurgical removal of hypertrophied pituitary elements to reduce ACTH secretion

Partial or total adrenalectomy followed by administration of adrenal steroids to compensate insufficiencies that develop

• PowerPoint Presentation
• Slide 5
• Slide 11
• Slide 33

Cushing syndrome

ndash Hypersecretion of glucocorticoids by the adrenal

cortex characterized by weight gain in the trunk of the body but not arms and legs

Cushingrsquos Syndrome

striae

ldquomoon facerdquo

Cushingrsquos Disease

Proximal muscle wasting amp weakness

Osteoporosis Glucose intolerance HTN hypokalemia Thromboembolism Depression Psyc Infection Glaucoma

Treatment

Removal of adrenal tumor if this is the cause

Microsurgical removal of hypertrophied pituitary elements to reduce ACTH secretion

Partial or total adrenalectomy followed by administration of adrenal steroids to compensate insufficiencies that develop

• PowerPoint Presentation
• Slide 5
• Slide 11
• Slide 33

Cushingrsquos Syndrome

striae

ldquomoon facerdquo

Cushingrsquos Disease

Proximal muscle wasting amp weakness

Osteoporosis Glucose intolerance HTN hypokalemia Thromboembolism Depression Psyc Infection Glaucoma

Treatment

Removal of adrenal tumor if this is the cause

Microsurgical removal of hypertrophied pituitary elements to reduce ACTH secretion

Partial or total adrenalectomy followed by administration of adrenal steroids to compensate insufficiencies that develop

• PowerPoint Presentation
• Slide 5
• Slide 11
• Slide 33

Cushingrsquos Disease

Proximal muscle wasting amp weakness

Osteoporosis Glucose intolerance HTN hypokalemia Thromboembolism Depression Psyc Infection Glaucoma

Treatment

Removal of adrenal tumor if this is the cause

Microsurgical removal of hypertrophied pituitary elements to reduce ACTH secretion

Partial or total adrenalectomy followed by administration of adrenal steroids to compensate insufficiencies that develop

• PowerPoint Presentation
• Slide 5
• Slide 11
• Slide 33

Treatment

Removal of adrenal tumor if this is the cause

Microsurgical removal of hypertrophied pituitary elements to reduce ACTH secretion

Partial or total adrenalectomy followed by administration of adrenal steroids to compensate insufficiencies that develop

• PowerPoint Presentation
• Slide 5
• Slide 11
• Slide 33