Transcript Slide 1
Adrenocortical hormones Hormones The adrenal cortex secretes 3 types of hormones: • Mineralocorticoids (mainly aldosterone) • Glucocorticoids (mainly cortisol = hydrocortisol) • Androgens Hormones - Regulation of secretion: Hypothalamus - CRF - Anterior Pituitary ACTH = Corticotropin Adrenal cortex Glucocorticoids Hormones Very important Long-term administration of exogenous GCs -ve feedback on ACTH & CRH Suppression of Adrenal cortices Too rapid withdrawal of GCs acute adrenal insufficiency may lead to death!!! Hence, GCs should be GRADUALLY withdrawn Hormones 1- Glucocorticoids Diurnal (circadian rhythm) • ACTH is secreted in irregular bursts through out the day • Plasma cortisol tends to rise and fall in response to these bursts • These bursts are most frequent in early morning and least frequent in the evening Hormones Actions of GCs: 1. Metabolism: CHO metabolism: maintains an adequate glucose supply within a normal range. Similar to growth hormone (GH), GC has anti-insulin activity utilization of glucose by peripheral tissues GC also gluconeogenesis hepatic glucose output Both hyperglycemia insulin secretion (hyperinsulinemia) Hormones Protein metabolism: pharmacological or therapeutic dose of GC has catabolic effect on protein. Fat metabolism: pharmacological or therapeutic dose of GC causes peculiar redistribution of fats thin extremities & central obesity (↑ fat deposition in abdominal area & in face & back of neck & shoulders moon-face & buffalo hump) Hormones 2. Electrolyte balance: hydrocortisone has a weak mineralocorticoid-like activity Na+& H2O reabsorption & K+ & H+ secretion. 3. CVS: blood Pressure. 4. CNS: behavioral changes. 5. GIT: PGs HCl & mucus formation predispose to peptic ulcer. 6. Skeletal muscles: GCs are essential for normal muscle work ( GC muscle weakness due to protein catabolism and electrolyte imbalance) 7. Anti-inflammatory effect 8. Immunosuppressive effect Hormones Clinical disorders Hypercorticism: Cushing`s syndrome Hypocorticism: Addison`s disease Hormones Cushing’s syndrome Clinical state of excess free GCs occurs due to: Therapeutic administration of ACTH or GCs for long periods Endocrine disorder (Pituitary ACTH dependent ACTH secretion), Known as cushing disease (Pituitary ACTH independent adrenal tumor) Tumor outside the normal pituitary-adrenal system, which produces ACTH (ectopic Cushing’s syndrome) (small cell lung cancer). Hormones The dexamethasone suppression test is designed to diagnose and differentiate among the various types of Cushing's syndrome Dexamethasone is given at night & plasma cortisol is measured next morning Cortisol Interpretation Not suppressed Adrenal CS Suppressed Pituitary CS Hormones Features of Cushing`s syndrome : Hyperglycemia . Thinning of skin. Myopathy & muscle weakness Uneven fat redistribution. • Buffalo hump. • Moon face. • abdominal fat. Hormones Features of Cushing`s syndrome….. contd. Hormones Features of Cushing`s syndrome…… contd. Hypertension. Poor wound healing. susceptibility to infection. in hair growth (increase androgens and inhibition of GNRH FSH and LH, estrogen). Osteoporosis (decrease Ca abs, increase Ca secretion, stimulate PTH to increse ). Euphoria, psychosis or depression. bone resorption, inhibition of GnRH Hormones Features of Cushing`s syndrome …… contd. Purple or red stria (the weight gain in Cushing's syndrome stretches the skin, which is thin and weakened, causing it to hemorrhage) Hormones ☺ Treatment of Cushing’s syndrome: - or stop exogenous GC gradually (risk vs benefit) - Surgical removal of the tumor - Using inhibitors of biosynthesis, e.g.: Aminoglutethimide Trilostane Metyrapone -Using GCs receptor antagonists , e.g.: Mifepristone Hormones Addison’s disease This clinical state occurs due to: 1ry adrenal insufficiency: Adrenal cortex dysfunction ( GCs ACTH) 2ry adrenal insufficiency: pituitary disorder ( ACTH GCs) 3ry adrenal insufficiency: hypothalamic disorder ( CRF ACTH GCs) Hormones Features of Addison`s disease : Weakness & fatigue. Hypotension. Anorexia & , weight loss. Hyperpigmentation (bronzing of skin) Why? Due to ↑ ACTH, which has structural similarity with MSH ↑ melanin production by melanocytes also MSH is a by product of ACTH synthesis from common precursor. Hormones ☺ Treatment of Addison’s disease: Replacement therapy with: • GCs as prednisolone & • Mineralocorticoids as fludrocortisone N.B. Immune mediated destruction of the adrenal glands often occurs in conjunction with other autoimmune endocrine diseases such as thyroiditis (hypothyroidism), diabetes mellitus or hypoparathyroidism or non endocrine disease as vitiligo (autoimmune polyendocrine syndrome ) Hormones Diagnosis: Physical examination Laboratory tests: Laboratory tests Serum cortisol (190-680 mmol/l) Serum ACTH (10-47 ng/l) Na+ K+ Fasting BGL (70-120 mg/dl) Cushing’s syndrome ↑ Addison’s disease ↓ ↑ or ↓ ↑ ↑ ↓ ↑ ↓ ↑ ↓ Hormones 2- Mineralocorticoids Actions: - ↑ Na+ & H2O reabsorption and ↑ K+ & H+ secretion. - Regulation of aldosterone secretion: ↓ plasma Na+ , ↑ K+ ↑ aldosterone. ↓ Na+ , ↓ BP ↑ renin ↑ Ang II ↑ aldosterone. ACTH also stimulates secretion but to a much smaller extent. Hormones Clinical disorders Hyperfunction: 1ry hyperaldosteronism (CONN`s disease) • Hypertension • Hypernatremia • Hypokalemia • Alkalosis ttt: Aldosterone antagonist e.g. Spironolactone Hypofunction: Hypoaldosteronism • Hypotension • Hyponatremia • Hyperkalemia • Acidosis ttt: RT with fludorocortisone Hormones Hyperfunction: 2ry hyperaldosteronism (hyperreninism, or hyperreninemic hyperaldosteronism) due to overactivity of the renin-angiotensin system. As in Juxtaglomerular cell tumor. Renal artery stenosis. Hyporeabsorption of sodium from kidney tubules Instructions •Students will be informed with their antibiotics (drug profile) on Monday. •Only presentations are required. •Presenting time = 10 min. •The presentations will be held on Sunday (30/11) and Tuesday (2/12), each group in their corresponding labs. Assessment Chrousos syndrome Thank You!