3. Pathology of Endocrine Systems (Adrenal).pdf

The Adrenal Glands -cortisol produce : - adrenaline - aldosterone - androgen  Glucocorticoid...

The Adrenal Glands -cortisol produce : - adrenaline - aldosterone - androgen  Glucocorticoid # § Two distinct parts: Andwea troid TGAM] 1. C o r t e x – p r o d u c e s 3 s t e r o i d h o r m o n e s : to increase glucose Glucocorticoid, Mineralocorticoid, androgen - level in the body ae :Cushing'sSur -- ey = = 2. Medulla : a part of sympathetic nervous system : [NA] Adrenalin,e Noradrenaline = § Cortex is more essential to life as compared to Medulla of which it only become pathologically importance in the occurrence of catecholamine – secreting tumors (eg: Pheochromocytoma Introduction § Hormones secreted by adrenal cortex are synthesized from cholesterol by sequence of enzymatic reaction. § The pathways of these enzymatic reaction is important in investigating congenital adrenal hyperplasia , a condition caused by a lack of one of these hormones.Cenzyme deficiency)  cortisol Hypothalamus > Anterior ATH Adrena > - Body a pituitary § The most important Glucocorticoid which is adrenocorticotropic hormone CORTISOL is secreted in response to ACTH which the secretion is stimulated by hypothalamic corticotropic-releasing CRH. hormone § Cortisol serves many biological functions and important in mediating body’s response to stress. § Among functions: (6) muscle Weakness 1. Increase protein catabolism cuase Glucocorticoid: - => 3 regulate 2. increase hepatic glycogen synthesis Cortisol 3. increase hepatic gluconeogenesis glucose & = (middle) zona 4. Inhibit ACTH secretion (negative feedback fasciculata - mechanism) catabolism -protein 5. Sensitize arterioles to action of adrenaline , [sap Punai Akon Sakit Gici = hence involved in hemostasis of blood pressure. sinconeogenesic glycosed synthesis LEACTH 6. Immunosuprresive , Immunosupressant sensitize = certerroles to action of adrenality  § Mineralocorticoid which is aldosterone is secreted in response to angiotensin II following activation of renin-angiotensin system by a decrease in renal blood flow, reduced ECF volume. Textracellular fluid Mineralocorticoi § Secretion of Aldosterone is also directly d: stimulated by - hyperkalemia. aldosterone↑ - Aldosterone ↑ K+ in blood , ↑ aldosterone zona glomerulosa § A l d o s t e ro n e f u n c t i o n i s t o s t i m u l a t e Contermost layer) (DT)sodium reabsorption at distal convoluted aldosterone tubules in the kidneys in exchange to ↓Stimulate ↓ potassium and hydrogen ions , thus play > release reabsorp Na - + + central role in ECF volume maintenance. k +H L regulate avolume  androgen § Adrenal cor tex produces andogens including of dehydroepiandrosterone (DHEA) and DHEA sulphate. Androgens § The clinical effects of excess androgens I can be a prominent feature of adrenal zona disorders in females. reticularis (innermost ↑ androgen > adrenal disorder layer) - in female  Adrenal Cortical Disorders Diseases of Adrenal Cortex Hypercorticol Hypersecretion of Hypocorticol Hyperaldosteronism adrenal androgens Function fuctioning and estrogens Cushing syndrome, Conn Disease, Feminization, Addison Cushing Disease Bartter Syndromes Virilization Diseases  Hypercortical Function - Chronic Hyper corticolism How ? ectopic ACTH production - Cushing syndrome - pituitary independent ~ outside ,rece chronic hypercortisolism by hyperfunction of adrenal cortex or due to ectopic ACTH production Cushing Disease pituitary dependent hypercortisolism (eg: pituitary adenoma) ~ overproduction of ACTH by pituitary - secondary hyperfunction treatment/procedure occur due to Cushing – like syndrome / iatrogenic disease. - use of exogenous corticosteroids -stip consume , hilang features Cashing Pseudo-Cushing syndrome patient with cushingoid feature and may have some biochemical finding of true Cushing’s disease. & Cushing tapi buleen) Macam This can occur in severe depression and alcoholics resolves rapidly on withdrawal of alcohol. -  Cushing’s Syndrome Clinical Presentation: 1. Glucocorticoid Effects: “cushingoid habitus”, bone demineralization, glucose intolerance, hyperglycemia, muscle weakness and wasting hypernatremia ↓ 2. Mineralocorticoid effects: Sodium retention, Hypertension, potassium wasting leading to hypokalemic alkalosis (in iatrogenic disease eg use of synthetic glucocorticoid, mineralocorticoid effects is absent) 3. Sex steroid effects: hirsutism, acne, amenorrhea, gynecomastia male : femmine feature (gynecomastia] female : male feature (hirsutism]  CL MANI INICAL FE OF C STATION US DISE HING ASE!! Truncal Obesity – accumulation adipose tissue Glucose intolerance – cortisol induced insulin resistance Muscle wasting – protein catabolism osteoporosis – loss protein matrix Affect GH on bone – bone disease Loss collagen – vasular rupture – bleeding problem Increased ACTH – hyperpigmentation ↓ teistimulating melanocy hormone active MSH more - ↓ ↑ Melanin production ↓ hyperpigmentation  Cushing Syndrome : Biochemical Investigations 1. Urinary Free cortisol 2. Serum cortisol especially for investigation of diurnal secretion pattern of cortisol 3. Serum ACTH : often very high with ectopic secretion and is low in primary hypercorticolism. 4. Dexamethasone Suppression Tests Overnight DST Low dose DST High dose DST  00 : : 57 mon tynen: naktenuoua pre Overnight Dexamethasone Suppression Test - works like ACTH Dexamethasone: cortisol analogue that should suppress ACTH in normal person and reduce cortisol. Procedure Dexamethasone (1 mg) is given orally at 11pm. A single blood specimen is collected for serum cortisol between 8am – 9am the following morning. Interpretation Normal individuals suppress serum cortisol to 140 nmol/l and rises by at least 200 nmol/l after stimulation – adrenal hypofunction is unlikely.  no rise – primary hypoadrenalism  Rise by less than 200 nmol/l in short acting / rises daily for long acting– secondary hypoadrenalism  Mineralocorticoid (Aldosterone) Regulation: ALDOSTERONE (predominant mineralocorticoid) is secreted by cells in the zona glomerulosa in response to ANGIOTENSIN (mainly); and by ACTH (not significant) Clinical effects: Retains sodium and water accompanied by potassium depletion leads to excess intravascular volume HYPERTENSION  HYPERALDOSTERONISM Primary hyperaldosteronism condition may be defined as autonomous hypersecretion of aldosterone by the adrenal gland. Secondary hyperaldosteronism may be defined as an increase in aldosterone secretion secondary to an increase in renin. Hypoaldosteronism is a rare but potential cause of unexpected hyperkalemia in the presence of only moderately impaired renal function, usually occurring in old patients.  Hyperaldosteronism Excess aldosterone secretion Primary : abnormal adrenal cortex Conn disease due to adrenal adenoma / carcinoma. Secondary : extra-adrenal stimulus (renin-angiotensin, ACTH, elevated pottasium). Bartter syndrome : renin – secreting tumors by kidney Hypovolemia, dehydration  ESTATION CLINICAL MANIF Sodium and Water retention Hypertension Hypokalemia Hipernatremia Hypervolemia  Blood pressure ↑ BP  Elevated  Serum & urinary electrolytes EVALUATION serum Sodium H, Serum pottasium L , urinari Pottasium H  Serum & urinary aldosterone Increased  Aldosterone suppression test : Measure Aldosterone and Renin level. Interpretation: secondary a. Both Renin and Aldosterone High = Seconday Hyperaldosteronism b. Aldosterone High, Renin Normal / Low= Primary Hyperaldosteronism  Imaging techniques : to localize causes  Tests for Hyperaldosteronism 1. Basal level of plasma aldosterone 2. Urinary Aldosterone 3. Captopril Suppression Test Angiotensin- converting enzyme inhibitor decrease the renin-stimulated aldosterone production in secondary aldosteronism no response in primary aldosteronism (Conn’s disease) 4. Aldosterone Suppression test (Isotonic Saline infusion) Normal response  suppress aldosterone release by decreasing renin Primary aldosteronism  lack of aldosterone suppression  Hypersecretion of adrenal androgens and estrogens  Effects depend on 1. Hormone secreted 2. Gender 3. Age  Estrogen : Feminization 1. Male : gynecomastia, testicular atrophy, reduced libido 2. Female : early development of sex characteristics  Hypersecretion of adrenal androgens and estrogens  Androgen : Virilization 1. Female : hirsutism, deepening voice, amenorrhea, breast atrophy, acne Treatment 1. Surgical removal of androgen – secreting tumors  Pheochromocytomas Cadreral modula tumor)  Tumors of adrenal medula ~ renalize adrenaline  Secrete excess catecholamines  Cause persistent hypertension ↑ BP  Headaches – affected cerebral blood flow  Many others metabolic symptoms Evaluation & Treatments  Increased cathecolamine in serum & urine 3 clinical manifestation  Imaging - to locate tumor  Treatment – surgical tumor removal