Various Endocrine Glands of the Body Types of Hormones Proteins, peptides and amino acid derivatives...
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Various Endocrine Glands of the Body
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Types of Hormones
• Proteins, peptides and amino acid derivatives– Proteins are large molecules made of many
amino acids– Peptides are smaller molecules typically made
of a few amino acids– Amino acid derivatives are molecules derived
from a single amino acid
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Lipid Hormones
• Steroid hormones– Derived from cholesterol– All similar in structure, but small differences
confer different effects– Similarities responsible for some cross
reactivity
• Eicosanoids– Derived from arachadonic acid (fat)
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The hypothalamus
• Integrates information and many functions of the nervous system
• The hypothalamus controls the function of the pituitary gland in two ways
• It can secrete releasing hormones that act on the pituitary to stimulate secretion of stimulating hormones
• It can also stimulate the release of hormones from the posterior pituitary via nervous input
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The Pituitary
• Divided into two halves
• The anterior portion is comprised of epithelial cells that act primarily as a glandular structure
• The posterior portion has extensive innervation and responds to nervous sytem input from the hypothalamus
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The hypothalamus and the Pituitary
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Table. 10.3a
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Table. 10.3b
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Hormones of the Pituitary• Growth hormone
– Controls growth and glucose metabolism
– Mediated via the somatomedins
• ACTH– Acts on the adrenal gland to stimulate the release of
cortisol
• Gonadotropins– Leutinizing hormone- ovulation, secretion of sex
hormones
– Follicle stimulating hormone – development of follicles and sperm cells
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• Prolactin – stimulates breasts to develop milk
• Melanocyte stimulating hormone– Causes synthesis of melanin
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Hormones of the Posterior Pituitary
• Antidiuretic hormone (aka vasopressin)– Causes the retention of fluid in the urine– Combats dehydration
• Oxytocin– Causes lactation– Contractions during child birth
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The Thyroid Gland
• Secretes two hormones that regulate metabolic rate– Thyroxine (T4) – contains four iodine atoms– Triiodothyronine (T3) – contains three iiodine
atoms – Insufficient iodine impairs T3 and T4 synthesis
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The Parathyroid Gland
• Primarily responsible for calcium homeostasis
• Parathyroid hormone– Causes increased production of vitamin D and
increased absorption of calcium in the intestine– Also causes resorption of calcium from the
bones– Increased retention of calcium in the kidneys
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Regulation of the Thyroid Gland
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Clinical Indication
Thyroid Hormones:
Replacement or supplement in hypothyroidism of any cause• cretinism- mental & physical retardation in• children with chronic untreated hypothyroidism• nontoxic goiter in adults• myxedema in adults
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Thyroid HormonesHormones (proteins) secreted from the thyroidgland include:• Triiodothyronine (T3)• Thyroxine (T4)• and Thyrocalcitonin
TSH (Thyroid Stimulating Hormone)• Is secreted from the anterior pituitary gland in
response to changes in the blood levels of T3 and T4
• Triggers T3, T4 secretion from the thyroid gland
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T3, T4- concerned with muscle and nerve tissue growth
• stimulates protein synthesis• increases the intestinal absorption of glucose• increases glycogen synthesis• mobilizes fatty acids• decreases serum cholesterol• increases BMR (basal metabolic rate)
Thyroid Hormones
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Adverse Effects Related to Overdosing
Symptoms are dose and time dependent and characteristic of hyperthyroidism and increase in sympathetic tone:
• Mental confusion to psychotic behavior• Increased blood pressure• Increased heart rate • Diarrhea• Weight loss• Sweating• Menstrual irregularities• Tremors• Headache• Nervousness • Anginal episodes
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Cautions and Contraindications
Thyroid hormone therapy
• is contraindicated in patients with myocardial infarction
• is not recommended for weight reduction in the management of obesity
• should be used with caution in patients – With cardiovascular disease, diabetes, adrenal
insufficiency– Who are elderly
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Antithyroid Drugs
Clinical Indication
Treatment of hypersecretory conditions of
the thyroid in order to:
inactivate overactive tissue
inhibit production of T3 and T4
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Effects of Hypersecretion or Hyperthyroidism
May be caused by tumors on the thyroid (thyrotoxic
crisis), pituitary, or hypothalamus
or
Autoimmune disease (Grave’s Disease) – LATS (long-acting thyroid stimulating protein) not the
same as TSH but same responses occur
Symptoms are dose and time dependent and
characteristic of hyperthyroidism especially increased
sympathetic autonomic tone
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Antithyroid DrugsMechanism of action
Accumulate within the thyroid and destroy overactive tissue or inhibit the incorporation
of iodine for production of T3 and T4
• Radioactive Iodide (immediate onset)• Methimazone (requires time to see effect)• Propylthiouracil (requires time to see effect)
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Antithyroid Drugs Special Considerations & Contraindications• Cross the placenta and affect fetal thyroid
development• Abrupt discontinuation of iodide may cause thyroid
storm• Iodide should be discontinued if fever, rash, soreness
in gums & teeth occur• Iodide-containing drugs are contraindicated in patients
with pulmonary edema• Radioactive iodide is present in the saliva and urine 24
hours after dosing
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Calcium Homeostasis Parathyroid Hormones
Calcium ions
• Essential for neuromuscular and endocrine
function
• Serum levels strictly regulated by two polypeptide hormones– calcitonin (thyroid) – parathormone (parathyroid)
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Calcium HomeostasisParathormone
Stimulated when serum calcium levels are low Stimulates bone resorption to mobilize calciumIncreases intestinal and renal reabsorption of calcium
Calcitonin Stimulated when serum calcium levels are highInhibits bone resorption
No effect on the intestine or kidneyAntagonizes parathormone
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Calcium Disorders & Treatment• Hypocalcemia
Parathyroid damage during surgery
Treatment: calcium salts and vitamin D
• Hypercalcemia
Neoplasms, multiple myeloma, renal dysfunction
Treatment: diuretics to increase the renal clearance of calciumcalcitonin and bisphosphonates
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Degenerative Bone Disease & Treatment
• OsteoporosisDecreased bone massDecreased mineral depositionIncreased bone resorptionTreatment: Bisphosphonates, estrogen
• Paget’s DiseaseHyperactive bone metabolismFragile bone and microfracturesTreatment: Calcitonin, bisphosphonates
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Bisphosphonates
• Alendronate
• Etidronate
• Pamidronate
Poorly absorbed, not metabolized, excreted
in urine
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The Adrenal Glands
• Adrenal medulla responsible for the hormonal fight or flight response
• Adrenal medulla releases epinephrine (adrenaline) and small amounts of norepinephrine
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Fight or Flight Hormones
• Increases breakdown of glycogen to glucose in the liver
• Increase heart rate– Increases cardiac output to the tissues
• Increases blood pressure
• Increases metabolic rate in skeletal muscle, cardiac muscle and nervous tissue
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The Adrenal Cortex
• Produces gluccocorticoids – Cortisol
• Regulates blood glucose levels
• Causes amino acids to be converted to glucose in the liver
• Cortisol secreted in times of stress to maintain glucose and energy levels
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Clinical Indication
GlucocorticoidsReplacement therapy in adrenal insufficiency (Addison’s Disease)
Interrupt moderate to severe pain associated with conditions of inflammation
MineralocorticoidsReplacement therapy in adrenalectomy or adrenal tumors
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Glucocorticoids• Adrenal cortex secretes glucocorticoids• Typically referred to as steroids• Regulate the metabolism of carbohydrates and
proteins• Demand for cortisol rises during stress and
tissue repair (e.g. wound healing)• Produce and conserve glucose• Promote protein catabolism and gluconeogenesis• Some mineralocorticoid activity i.e., sodium
retention
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Corticosteroids Source of steroids-natural & synthetic
cortisone, hydrocortisone, prednisone, methylprenisolone, triamcinolone, betamethasone, dexamethasone
Vary in duration of action and potencyAntiinflammatory action
stabilize cell membranesprevent edema
Systemic use in patients with normal adrenal function arthritis, collagen disease, rheumatic disorders, respiratory disease, spinal cord injury
Topical use for skin irritation, rashes, itching
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Corticosteroids Adverse Effects Associated with high doses and chronic use• Exaggeration of steroid symptoms of Cushing’s
diseasemood changesinsomniaweight gain, obesityprotein catabolism, muscle weakness, wastingosteoporosisdecreased wound healingincreased infections
fat deposition, moon facies
• Steroid addiction personality changes- “steroid psychosis”
psychological dependency (falacy)
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Steroid Contraindications
• Patients with systemic fungal infections
• Local viral herpes infections
• Topical application to the eyes or orbital area
• Live virus vaccinations
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The Pancreas
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• The pancreas produces insulin and glucagon– The primary blood glucose regulatory
hormones
• Insulin produced in the beta cells of the islets of Langerhans
• Glucagon produced in the alpha cells
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Insulin
• The primary glucoregulatory hormone
• Elevated in response to increased blood glucose or amino acids
• Inhibited when blood glucose is low
• Diabetes results from perturbed insulin metabolism
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Diabetes
• Type 1- insulin dependent diabetes– The individual does not produce insulin
• Type II- non-insulin dependent diabetes mellitus (adult onset)– The individual does not respond appropriately
to insulin
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Clinical Indication
Maintain circulating glucose levels sufficient to promote intracellular glucose transport and provide a source of energy for cells
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Pancreatic Endocrine Function
The pancreas secrets two polypeptidehormones that regulate carbohydratemetabolism and blood glucose levels• Insulin
Promotes glucose movement into cells and carbohydrate storage
• GlucagonIncreases glucose in the blood by stimulatingglycogen breakdown
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Insulin & Glucagon SecretionInsulin is secreted by beta cells in response to elevated glucose levels
• Mobilizes glucose into skeletal, heart, fat cells
• Promotes storage of fat and protein
Glucagon is secreted by alpha cells in response to low glucose levels
• Stimulates glyocogenolysis (breakdown)
• Mobilizes glucose into the circulation
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• Defect in beta cell function
• Deficiency in insulin production and secretion
• Type I DM is insulin dependent (juvenile diabetes)genetic predisposition
• Type II DM relative insulin deficiency
(maturity-onset) aging, improper diet, obesity
Diabetes Mellitus (DM)
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Diabetes Mellitus Symptoms • Persistently high blood glucose levels• Spill over into high urine glucose (glycosuria)• Volume of water excreted (polyuria)• Dehydration and thirst • Excessive fluid intake (polydipsia)• Excessive food intake (polyphagia)• Fat breakdown produces ketosis• Neuropathy, retinal hemorrhage• Renal dysfunction• Atherosclerosis
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Treatment of Diabetes MellitusCorrect the metabolic imbalance with dietadjustment and administration of• Insulins• Oral sulfonylureas
acetohexamide, glipizide, glyburide, tolazamide, tolbutamide
• Glucose absorption inhibitorsacarbose, miglitol
• Antihyperglycemic drugsMetformin, troglitazone
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Treatment of Diabetes MellitusInsulin (Type I, II DM)
• Sources: animal or recombinant DNA
• Onset of action varies with each insulin type
• Provides single peak of glucose activity
• Requires multiple daily doses
• Injected 15 to 30 minutes before meals
• Juice or sugar can reverse hypoglycemia
• Salicylates, beta-blockers, MAOI potentiate
insulin-induced hypoglycemia
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Treatment of Diabetes MellitusOral sulfonylureas (oral hypoglycemics)• Type II DM only• Enter the beta cells and cause insulin release• Vary in onset and duration of action• Delay in onset related to absorption• Not a substitute for insulin• Prolonged action sustains hypoglycemia• Cause gastrointestinal irritation, nausea, diarrhea,
weakness, fatigue, dizziness,hypersensitivity reactions (rash), elevated serum liver enzymes, leukopenia, thrombocytopenia & anemia
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Contraindications & Drug Interactions with Oral Hypoglycemics
Contraindicated in patients:• With a known hypersensitivity• With complications of fever, ketoacidosis or coma• With liver or renal disease, peptic ulcers• Who are pregnant
Drug Interactions occur because of• Protein binding displacement• Liver enzyme inhibition• Inhibition of glucose metabolism
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Treatment of Diabetes Mellitus
Glucose Absorption Inhibitors• Do not reduce blood glucose levels• Do not release insulin• Interfere with dietary carbohydrate digestion• Delay a peak in glucose absorption after meals• Are ingested with meals• Do not impair liver enzymes• Cause flatulence, diarrhea, and abdominal pain• Contraindicated in patients with ketoacidosis, impaired
absorption, or hypersensitivity reaction
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Treatment of Diabetes MellitusAntihyperglycemic Drugs• Do not reduce blood glucose levels or release insulin
• Keep glucose blood level from rising too fast• Decrease liver glucose production and intestinal glucose
absorption• Promote smoother distribution of glucose to tissues• Causes diarrhea, nausea, vomiting and flatulence• May cause lactic acidosis leading to respiratory and
cardiovascular distress• Contraindicated in patients with metabolic acidosis, renal
disease or abnormal creatinine clearance
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The Testes and the Ovaries
• The testes produce testosterone
• The ovaries produce estrogen and progesterone
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Clinical Indication
Female hormonesReplacement therapy in hypogonadism and menopause, or fertility enhancement, and adjunctive therapy for cancer
Prevent ovulation or implantation in the uterus
Alleviate menstrual disorders in nonmenopausal women
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Female Sex HormonesEstrogens and Progestogens
LH and FSH secreted from the anterior pituitary gland induce conditions for the secretion of estrogen and progesterone
Estrogens secreted from developing cells in the ovaries stimulate• uterine lining and mammary glands• motility within the fallopian tubes• endometrium for implantation of a fertilized egg
Progesterone secreted from the corpus luteum• completes development uterine lining for implantation• stimulates mammary ducts for lactation
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Pharmacological ActionsContraceptionEstrogen and progestogen combinations mimic the natural secretory cycle so that• FSH and LH secretions are suppressed• ovulation is blocked • cervical mucus is thickened decreasing the possibility of implantation
Hormone Replacement Therapy (HRT)Estrogens interact with receptors to reduce • hot flashes, sweating, muscle & joint aches that occur during menopause• bone resorption and turnover that decreases bone mineral density in osteoporosis• coronary artery disease by decreasing blood pressure, LDL- lipoproteins and insulin
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Estrogen and ProgestogensAdverse Effects
• Nausea• Vomiting• Headache• Dizziness• Irritability• Depression• Fluid retention• Breast tenderness• Weight gain• Thrombophlebitis (pain in legs, groin)• Double-vision
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Female Sex HormonesContraindicationsUse in pregnant women or those with a history of
ThrombophlebitisLiver diseaseBreast tumorsEstrogen-dependent cancersUndiagnosed vaginal bleeding
Special considerationsUse in women with a history of
DiabetesHigh blood pressureSeizure disorders
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Male Sex Hormones - Androgens
Clinical IndicationIn menReplacement therapy in hypogonadism, delayed puberty, and impotence due to androgen deficiency
In womenAdjunctive therapy for inoperable breast cancer and postpartum breast engorgement
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Androgens Pharmacologic Action
Anabolic action - Stimulate protein synthesisClinical benefit- Increase body weight and appetite
Nontherapeutic use- Increase muscle mass and enhance athletic performance
Erythropoiesis-Stimulate production of RBCs Clinical benefit- Reverse refractory anemia
Inhibit tumor growthClinical benefit- reduce pain & swelling in women with fibrocystic breast disease
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Adverse Effects
Men may develop Women may develop• Decreased sperm count Hirsutism• Increased breast tissue Menstrual irregularities• Sustained erection Acne• Tumors Deepening voice• Addiction syndrome
Men and women• Jaundice• Nausea• Vomiting• Diarrhea • Retention of sodium and water
Result from chronic high dose use
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Androgens Special Considerations and Contraindications
ContraindicationsMen breast or prostate cancerPregnant women- virilization of fetus
Special considerationsBlood glucose levels may fluctuate in diabetic patientsBruising and localized hemorrhages may increase in patients also receiving anticoagulants
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ImpotenceInability to achieve or maintain an erection
Causes include• Nerve or spinal cord damage• Diminished blood flow to penis• Medication-induced reduction in nerve excitability
during sexual performance
TreatmentSildenafil (oral phosphodiesterase PDE inhibitor)Inhibits an enzyme (PDE) in muscle metabolismThat increases blood flow and rigidity in the penis
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Sildenafil Adverse Effects
• Headache
• Flushing
• Nasal congestion
• Diarrhea
• Rash
• Upset stomach
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Sildenafil Contraindications
• Patients taking nitrates may develop live-threatening hypotension and cardiovascular collapse
• Patients predisposed to sustained erection (e.g., sickle cell anemia, leukemia)