Pituitary Gland Pituitary Gland DiseasesDiseases

SMS 3023Dr. Mohanad R. Alwan

Endocrine Glands

• Controls many body functions– exerts control by releasing special chemical substances

into the blood called Hormones– Hormones affect other endocrine glands or body

systems

• Ductless glands

• Secrete hormones directly into bloodstream– Hormones are quickly distributed by bloodstream

throughout the body

Hormones• Chemicals produced by endocrine glands.

• Act on target organs elsewhere in body.

• Control/coordinate widespread processes:• Homeostasis.

• Reproduction.

• Growth & Development.

• Metabolism.

• Response to stress.• Overlaps with the Sympathetic Nervous System

Hormones

Hormones are classified as:ProteinsPolypeptides (amino acid derivatives)Lipids (fatty acid derivatives or steroids)

Hormones

Amount of hormone reaching target tissue directly correlates with concentration of hormone in blood.

Constant level hormones• Thyroid hormones

Variable level hormones• Epinephrine (adrenaline) release

Cyclic level hormones• Reproductive hormones

The Endocrine System Consists of several glands located in various parts of

the body Specific Glands

Hypothalamus Pituitary Thyroid Parathyroid Adrenal Kidneys Pancreatic Islets Ovaries Testes

Hypothalamus Produces several releasing and inhibiting factors

that stimulate or inhibit anterior pituitary’s secretion of hormones.

Produces hormones that are stored in and released from posterior pituitary.

Hypothalamus Also responsible for:

Regulation of water balanceEsophageal swallowingBody temperature regulation (shivering)Food/water intake (appetite)Sleep-wake cycleAutonomic functions

HypothalamicHypothalamic

Hypothalamic neural cells synthesize specific releasing and inhibiting hormones that are secreted directly into the portal vessels of the pituitary stalk.

Hypothalamic-pituitary portal plexus provides the major blood source for the anterior pituitary.

Hypothalamic releasing hormonesHypothalamic releasing hormones

Hypothalamic releasing hormone Effect on pituitary

Corticotropin releasing hormone (CRH)

Stimulates ACTH secretion

Thyrotropin releasing hormone (TRH)

Stimulates TSH and Prolactin secretion

Growth hormone releasing hormone (GHRH)

Stimulates GH secretion

Somatostatin Inhibits GH (and other hormone) secretion

Gonadotropin releasing hormone (GnRH) a.k.a LHRH

Stimulates LH and FSH secretion

Prolactin releasing hormone (PRH) Stimulates PRL secretion

Prolactin inhibiting hormone (dopamine)

Inhibits PRL secretion

Hypothalamic -Pituitary communicationHypothalamic -Pituitary communication

Pituitary Gland

Small gland located on stalk hanging from base of brain.

“The Master Gland” Primary function is to control other glands.Produces many hormones.Secretion is controlled by hypothalamus in base of brain.

Pituitary Gland• Weight 600 mg• Is located within the bony cavity (sella turcica)• Anatomically and functionally distinct anterior

and posterior lobes• Anterior Pituitary-adenohypophysis • Posterior pituitary-neurohypophysis

Histology of the PG

Anterior pituitary cells were originally classified as

• Acidophils cells• Basophils cells• Chromophope cells

Histology of PG Now with immunocytochemical and electron

microscopic techniques,classified cells by their secretary products

• Somatotrophs cells • a. GH secreting cells • Account about 50% of anterior P.G • Acidophilic stained

Histology of PG

• Lactotrophic • a. Prl secreting cells • b. acidophilic stained • c. 10-15% of anterior PG• Thyrotrophis • a. TSH secreting cells • b. basophilic cells • c. < 10% of anterior PG

Histology of PG

• Corticotrophs a. ACTH secretary cells b. basophilic cells c. 15-20% of anterior PG

• Gonadotrophs a. LH,FSH secretary cells b. basophilic staining c. 10-15% of anterior PG

Pituitary Development

• The pituitary originate from different source. • The anterior pituitary from Rathke´s pouch

(which is an embryonic invagination of the pharyngeal

epithelium).• The posterior pituitary from an outgrow of the

hypothalamus.

• Adrenocorticotropic hormone(ACTH)• Thyroid-stimulating hormone(TSH)• Growth hormone, Prolactin • Luteinizing hormone, • Follicle stimulating hormone• melanocyte–stimulating hormones

o Oxytocin,o Antidiuretic hormone

Pituitary Gland Two areas

Anterior PituitaryPosterior Pituitary

Structurally, functionally different

Pituitary Gland

Anterior Pituitary HormonesThyroid-Stimulating Hormone (TSH)

stimulates release of hormones from Thyroid thyroxine (T4) and triiodothyronine (T3): stimulate

metabolism of all cellscalcitonin: lowers the amount of calcium in the blood by

inhibiting breakdown of bone

released when stimulated by TSH abnormal conditions

hyperthyroidism: too much TSH releasehypothyroidism: too little TSH release

Pituitary Gland

Anterior PituitaryGrowth Hormone (GH)

stimulates growth of all organs and increases blood glucose concentration

decreases glucose usage increases consumption of fats as an energy source

Adreno-Corticotrophic Hormone (ACTH)stimulates the release of adrenal cortex hormones

Pituitary Gland

Anterior PituitaryFollicle Stimulating Hormone (FSH)

females - stimulates maturation of ova; release of estrogen

males - stimulates testes to grow; produce spermLuteinizing Hormone (LH)

females - stimulates ovulation; growth of corpus luteum

males - stimulates testes to secrete testosterone

Pituitary Gland

Anterior PituitaryProlactin

stimulates breast development during pregnancy; milk production after delivery

Melanocyte Stimulating Hormone (MSH)stimulates synthesis, dispersion of melanin pigment

in skin

Pituitary GlandPituitary Gland

Posterior PituitaryStores, releases two hormones produced in

hypothalamusAntidiuretic hormone (ADH)Oxytocin

Pituitary Gland

Posterior Pituitary Hormones: Antidiuretic hormone (ADH)

Stimulates water retention by kidneys reabsorb sodium and water

Abnormal conditionsUndersecretion: diabetes insipidus (“water diabetes”)Oversecretion: Syndrome of Inappropriate Antidiuretic

Hormone (SIADH)

OxytocinStimulates contraction of uterus at end of pregnancy

(Pitocin®); release of milk from breast

Pineal Gland Located within the Diencephalon Melatonin

Inhibits ovarian hormonesMay regulate the body’s internal clock

Anterior PituitaryAnterior Pituitary

Is often referred to as the “MASTER GLAND” because, it orchestrates the complex regulatory functions of multiple other endocrine glands.

Anterior Pituitary Anterior Pituitary InsufficiencyInsufficiency

EtiologyEtiology

Reduced pituitary function can result from inhereited disorders; more commonly,

it is acquired and reflects the mass effects of tumors or the consequences of inflamation or vascular damage.

Causes of hypopituitarismCauses of hypopituitarism

Tumours (tu’) Pituitary tumor Adenoma,craniopharyngioma Cerebral tumor

Hypothalamic disorders Tumor Functional disturbance-Eg -Anorexia nervosa Isolated GH and GnH

secretion due to impaired secretion of hypothalamic releasing hormones

Miscellaneous Sarcoidosis (inflammation of L.N) Histocytosis X (abnormal increase

in the number of immune cells ) Haemochromatosis

Vascular ds Necrosis (Sheehan’s synd) Infarction Severe hypotension Cranial arteritisTrauma

Infection Meningitis esp TB, syphilis

Iatrogenic Surgery Irradiation Prolonged rx with glucocorticoid

or thyroid hormones-isolated ACTH or TSH suppression

Developmental and Genetic Causes of Developmental and Genetic Causes of HypopituitarismHypopituitarism

Pituitary DisplasiaTissue-Specific Factor MutationsDevelopmental Hypotalamic Dysfunction:

Kallmann Syndrome (Hypogonadotropic hypogonadism)

Laurence-Moon-Bardet-Biedl Syndrome (involves many body systems)

Fröhlich Syndrome (childhood metabolicdisorder)

Prader-Willi Syndrome.

Acquired HypopituitarismAcquired Hypopituitarism

Trauma. Vascular Pituitary or hypothalamic neoplasms Inflammatory diseases. Infiltrative disorders such as sarcoidosis,

hemochromatosis.

ANTERIOR PITUITARY HYPOFUNCTION ANTERIOR PITUITARY HYPOFUNCTION (hypopituitarism)(hypopituitarism)

3 most common causes:3 most common causes: Non secretory adenoma of ant pituitaryNon secretory adenoma of ant pituitary Sheehan’s syndrome Sheehan’s syndrome ((postpartum pituitary

necrosis) Empty sella syndrome Empty sella syndrome ((pituitary gland become

shrinks or becomes flattened)

Partial hypopituitarism is more frequent than complete Partial hypopituitarism is more frequent than complete loss of pit functionsloss of pit functions

Sx/signs do not manifest until > 75% of ant lobe is Sx/signs do not manifest until > 75% of ant lobe is destroyeddestroyed

GH secretion is an early feature of pit failure-effects > GH secretion is an early feature of pit failure-effects > dramatic in children but less significant in adultsdramatic in children but less significant in adults

LH/ FSH are affected before ACTHLH/ FSH are affected before ACTH Hypothyroidism is an uncommon presenting feature of Hypothyroidism is an uncommon presenting feature of

pit failurepit failure

Clinical featuresClinical features

Hormone Features of deficiency

GH Children: growth retardationAdults: ↓muscle bulkTendency to hypoglycaemia.

Prolactin Failure of lactation

Gonadotrophins Children: delayed pubertyFemale: oligomenorrhoea, infertility,atrophy of breast & genitaliaMale:Impotence,azoospermia,testicular atrophyBoth sexes: LO libido,LO body hair

ACTH Weight loss, hypotension, hypoglycaemia, decrease skin pigmentation

TSH Weight gain, cold intolerence,fatique

Vasopressin Thirst, polyuria

Posterior Pituitary Posterior Pituitary hypofunctionhypofunction

CausesCauses ADH production ADH production cranial diabetes cranial diabetes

insipidus insipidus (DI)(DI)

Causes of cranial DICauses of cranial DI Tumours-craniopharyngioma, secondary tumours Tumours-craniopharyngioma, secondary tumours

(metastatic CA), pituitary tumours with suprasella (metastatic CA), pituitary tumours with suprasella extension.extension.

Granulomatous disease.Granulomatous disease. Meningitis, abscess and encephalitis.Meningitis, abscess and encephalitis. Vascular disorders.Vascular disorders. Trauma.Trauma. Surgery.Surgery. Idiopathic.Idiopathic.

Posterior Pituitary Posterior Pituitary hypofunctionhypofunction

EffectsEffects

Polyuria-uncontrolled renal water Polyuria-uncontrolled renal water excretion, tendency to dehydrationexcretion, tendency to dehydration

Polydipsia-excessive thirst, dehydration Polydipsia-excessive thirst, dehydration stimulate thirst centre resulting in stimulate thirst centre resulting in increase water intakeincrease water intake

Key featuresKey features

Hypotension Decreased pulse pressure Tachycardia Increased Hbg,hct and BUN Increased UOP Poor skin turgor Irritablilty Decreased coginition Hyperthermia Lethargy leading to coma

PITUITARY HYPERFUNCTIONPITUITARY HYPERFUNCTION(HYPERPITUITARISM)(HYPERPITUITARISM)

CausesCauses

Pituitary adenoma Pituitary adenoma Carcinoma (rare)Carcinoma (rare) Hypothalamic disorder-excess stimulation of the Hypothalamic disorder-excess stimulation of the

pituitary (rare)pituitary (rare)

Order of frequency with which hormone secretion Order of frequency with which hormone secretion occurs in pituitary tumour is prolactin (relatively occurs in pituitary tumour is prolactin (relatively common) common) GH GH ACTH ACTH gonadotrophin gonadotrophin TSH TSH

HyperpituitarismHyperpituitarism - - excessive production of adenohypophexcessive production of adenohypophyyssealeal hormones

PITUITARY HYPERFUNCTIONPITUITARY HYPERFUNCTION(HYPERPITUITARISM)(HYPERPITUITARISM)

Prolactin excess Hyperprolactinaemia

GH excess Acromegaly/ gigantism

ACTH excess Cushing’s disease

TSH excess (rare) Secondary hyperthyroidism

Gonadotrophin excess

menstrual disorders and infertillity

Consequences:Consequences:

a)a) Excessive Secretion ofExcessive Secretion of prolactinprolactin secretion secretion of GnRH of GnRH gonadotrophinsgonadotrophins

In men: impotency, decreased libidoIn men: impotency, decreased libido

In women: amenorrhea, galactorrheaIn women: amenorrhea, galactorrhea

b) Excessive Secretion ofb) Excessive Secretion of somatotrophinesomatotrophine (growth (growth hormonehormone))

acromegaly (in adults)acromegaly (in adults)

gigantism (in adolescents whose epiphysealgigantism (in adolescents whose epiphyseal

plates have not yet closed)plates have not yet closed)

b)-continuing b)-continuing PathomechanismsPathomechanisms involved involved::-The usual GH baseline secretion pattern is lost (as are sleep –The usual GH baseline secretion pattern is lost (as are sleep – related GHrelated GH peaks)peaks)

- GH secretion is slightly elevated GH secretion is slightly elevated somatomedin somatomedin stimulation of growth stimulation of growth (in adolescent)(in adolescent)

- - CConnective tissue onnective tissue proliferationproliferation

- - BBony proliferation ony proliferation characteristic appearance of acromegaly characteristic appearance of acromegaly

- - PPhosphate reabsorbtion in renal tubules hosphate reabsorbtion in renal tubules hyperphosphatemia hyperphosphatemia

- - IImpairement of carbohydrate tolerancempairement of carbohydrate tolerance

- - M Metabolic rateetabolic rate

- HHyperglycemia - yperglycemia - it is a result of GH inhibition of peripheral glucose uptake it is a result of GH inhibition of peripheral glucose uptake

and increase hepatic glucose production and increase hepatic glucose production compensatory hyperinsulinism compensatory hyperinsulinism insulin resistance insulin resistance diabetes mellitus diabetes mellitus

C. C. In adultIn adultss::

D. D. Excessive Secretion of corticotrophinExcessive Secretion of corticotrophin ( (ACTH) ACTH) central form of central form of

Cushing syndrome (Cushing disease)Cushing syndrome (Cushing disease)

Causes:Causes: micro- or macroadenomas of adenohypophmicro- or macroadenomas of adenohypophyysis, hypothalamic sis, hypothalamic

disordersdisorders

Pathophysiology:Pathophysiology:CChronic hypercortisolismhronic hypercortisolism is the main disturbance is the main disturbance of of ACTH ACTH

Symptoms and signs:Symptoms and signs: weight gain:weight gain: - - accumulation of adipose tissue in the trunk, facial, and accumulation of adipose tissue in the trunk, facial, and cervical areas (truncal obesity, moon face, buffalo hump) cervical areas (truncal obesity, moon face, buffalo hump)

- - weight gain from Na and water retentionweight gain from Na and water retention

glucose intoleranceglucose intolerance DM type 2 DM type 2

polyuria:polyuria: osmotic polyuria due to glycosuria osmotic polyuria due to glycosuria

E. E. Protein WastingProtein Wasting: : due to catabolic effects of cortisol on peripheral tissue due to catabolic effects of cortisol on peripheral tissue

(muscle wasting (muscle wasting muscle atrophy and weakness muscle atrophy and weakness thin lower thin lower

extremitiesextremities))

in bone:in bone: - loss of protein matrix - loss of protein matrix osteoporosis osteoporosis - - blood calcium concentration blood calcium concentration renal stones renal stones

in skin:in skin: - loss of collagen loss of collagen thin, weakened integumentary thin, weakened integumentary tissues tissues purple striae; rupture of small vesels purple striae; rupture of small vesels

- thin, atrophic skin is easily damaged, leading to skin breaks thin, atrophic skin is easily damaged, leading to skin breaks and ulcerationand ulceration

F. F. Hyperpigmentation:Hyperpigmentation: due to very high levels of ACTHdue to very high levels of ACTH - - manifestation in: manifestation in: mucous membranes,mucous membranes, hair, andhair, and skinskin

Hypertension:Hypertension: results from permissive effect of cortisol on the actions of results from permissive effect of cortisol on the actions of

the catecholamines (KA) the catecholamines (KA) vascular sensitivity to KA vascular sensitivity to KA vasoconstriction vasoconstriction hypertension hypertension

Suppression of the immune systemSuppression of the immune system susceptibility to infections susceptibility to infections

alteration of mental statusalteration of mental status - - from irritability and depression from irritability and depression up to schizophreniaup to schizophrenia

symptoms and signs of symptoms and signs of adrenal androgenadrenal androgenss level level in women:in women:

- - hair growth (especially facial hair) hair growth (especially facial hair)- acne- acne- oligoamenorrhea- oligoamenorrhea

- changes of the vois- changes of the vois

Hyperglycemia, glycosuria, hypokalemia, metabolic alkalosis Hyperglycemia, glycosuria, hypokalemia, metabolic alkalosis

Excessive Secretion Of Thyreotrophin and GonadotrophinsExcessive Secretion Of Thyreotrophin and Gonadotrophins is is rarerare

Measurement of anterior pituitary Measurement of anterior pituitary hormoneshormones

Measured in serum by immunoassay Dynamic tests/ functional tests are important

tools in pituitary functions and other endocrine organs.

Basic principle of dynamic tests: Hypofunction - stimulation tests Hyperfunction-suppression tests

Magnetic resonance imaging (MRI)

TreatmentTreatment

Hormone replacement therapy, including glucocorticoids, thyroid hormone, sex steroids, growth hormone and vasopressin, is usually free of complications.

Glucocorticoid replacement require careful dose adjustments during stressful events.

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