ࡱ> gif@ AbjbjFF "l,,9|||||||4!4!4!4!L!\U)!!!!!!!!((((((($A*R,(|s$!!s$s$(||!!)%%%s$ |!|!(%s$(%% (||X(!! A 4!}$ $((%)0U),(,-$-X(||||-|X(|!v^"T%"D"}!!!((4!% 4!Adrenal Disease Hormones Aldosterone Major mineralocorticoid secreted by the zona glomerulosa(outer layer of the cortex) Stimulates the absorption of Na and K Protects against hypovolemia and hyperkalemia Hyperkalemia stimulates aldosterone secretion Cortisol- Secreted diurnally, Highest levels in the morning, lowest at night Major glucocorticoid secreted by the middle zona fasciculate and inner zona reticularis of the adrenal cortex Cortisol counters insulin effects Causes hyperglycemia by inhibiting insulin and increasing gluconeogenesis in the liver Dampens defense mechanisms helping to prevent overactivity Inhibits production and action of mediators of inflammation and immunity Ex. Interleukin IL-6, lymphokines, prostoglandins, histamine Androgens Produced in the adrenal cortex, mostly by the inner zona fasciculate Makes large amounts of DHEAS Most abundantly secreted steroid in the adrenals Testosterone and androstenedione are the major functional androgens secreted by the adrenal glands Secretion declines with age Hypercortisolism Cushings syndrome- Refer to manifestations of prolonged use of exogenous steroids and/or ACTH Can also be causes by excessive ACTH-independent autonomous secretion of cortisol by the adrenal cortex Cushings disease- Refers to a manifestation of hypercortisolism due to pituitary Hypersecretion of ACTH Generally caused by a small benign pituitary adenoma Doesnt cause a bronzing of the skin Can also be caused by non-pituitary neoplasms (small cell Ca Produces excessive amounts of ectopic ACTH Risk Factors Prolonged use of corticosteroids, Females>males, MEN, Pituitary tumor, adrenal mass, or neuroendocrine tumor Signs and symptoms Moon face and buffalo hump(central trunkal obesity with thin extremities) Hyperpigmentation (acanthosis nigracans), purple striae on skin Emotional lability (unstable), mood disorders, depression HTN, DM, fasting hyperglycemia Muscle wasting, osteoporosis, poor wound healing Hirsutism, amenorrhea, cataracts, glaucoma Thin easily bruised skin Diagnosis Elevated 24-hour urinary cortisol, serum cortisol and urinary free cortisol Dexamethasone suppression- given at 11pm with 8am cortisol level- lack of normal suppression Initial test given***************************** Best screening test for cushings disease Plasma ACTH- decreased levels suggest adrenal tumor, increased levels suggest pituitary or ectopic tumor Hyperglycemia (insulin resistance), glycosuria, diminished glucose tolerance Hyperlipidemia Neutrophilia, leukocytosis- suppression of normal mechanism of cortisol on the immune system MRI/CT to locate pituitary, adrenal or ectopic tumors Treatment Surgery is the treatment of choice for hypercortisolism****** Transphenoidal microsurgery or adrenalectomy IV rehydration/glucose-lowering agents for hyperglycemia Radiation/chemotherapy for persistent disease Control other conditions Must taper steroids due to negative feedback Addisons disease Caused by the destruction of the adrenal cortex causing inadequate cortisol secretion to meet the bodys stress requirements Characterized by chronic deficiency of cortisol, aldosterone, and adrenal androgens Will cause subtle or strikingly dark pigmentation as well as volume, potassium, and sodium depletion If secondary to pituitary or hypothalamic failure steroid production will persist and will not cause hyperkalemia No other signs and symptoms of adrenal destruction Causes Autoimmune adrenal destruction is the MCC of Addisons disease in the US Bilateral adrenal hemorrhage may occur during sepsis, heparin associated thrombocytopenia or anticoagulation, major surgery or trauma Presents 1 week after the event with pain, fever, and shock Signs and symptoms Weakness, easy fatigability, fever, amenorrhea Axillary/pubic hair loss and increased skin pigmentation Especially over knuckles, elbows, knees, posterior neck, palmar creases, nipples, areolas, skin in pressure areas, and nail beds Some patients have vitiligo AMS, depression, lethargy, malaise, myalgia, arthralgia Anorexia, abdominal pain, N/V/D, diarrhea, weight loss Temperature changes, tachycardia, hypotension, small heart Goiter, hypogonadism, hyperkalemia Diagnosis Plasma cortisol level- Values will be low ACTH serum levels- high normal, low Electrolytes- hyponatremia, hyperkalemia (absence of aldosterone), decreased glucose Elevated BUN due to dehydration Cosyntropin stimulation test- failure of cortisol elevation between 30-60 minutes after administration of Cosyntropin (synthetic ACTH) Metyrapone stimulation test- for patients with normal Cosyntropin tests but suspected pituitary-adrenal insufficiency; failure of cortisol and 11-deoxycortisol elevation after giving Metyrapone Anti-adrenal antibodies are found in the serum in about 50% of cases of autoimmune disease CBC- Anemia, low glucose levels, neutropenia CT and/or MRI to locate tumor Treatment Glucocorticoid replacement- IV hydrocortisone (Drug of choice) or Dexamethasone Mineralocorticoids replacement- check plasma rennin to diagnose effectiveness Volume expansion- Normal saline, dont restrict salt intake Treat underlying cause and any complications Addisonian (adrenal) Crisis Life threatening emergency that presents with Fever, shock, hyponatremia, hyperkalemia, hypoglycemia, weakness, abdominal pain, N/V/D, AMS, dehydration Can be caused by chronic adrenal insufficiency, acute adrenal hemorrhage, rapid steroid withdrawal, bilateral adrenalectomy, sudden destruction of the pituitary gland, after treatment of hypothyroidism Can also be caused from stressors like pregnancy, surgery, trauma, infection, prolonged fasting Labs Cortisol, ACTH, decreased glucose, decrease Na and K Dont wait for results to treat Treatment Hydrocortisone and saline immediately upon suspicion Hyperaldosteronism Primary Hyperaldosteronism with hypokalemia is a minor cause of HTN Milder Hyperaldosteronism is more commonly seen Primary hyperaldosteronism Can be due to unilateral adrenocortical aldosterone-producing adenoma (Conns syndrome, 73%) Or idiopathic bilateral cortical hyperplasia or carcinoma Secondary hyperaldosteronism Extra-adrenal stimulation and there is physiologic stimulation of the renin-angiotensin-aldosterone axis to maintain serum electrolyte concentrations or fluid volume Causes Renovascular hypertension, juxtaglomerular hyperplasia, renin-producing tumors, and defect in renal conservation of sodium or chloride Risk factors Genetics, gender, MEN Signs and symptoms Usually asymptomatic Mild to severe hypertension with-without edema Marked hypokalemia Can cause muscle weakness and cramping, headaches, palpitations, polydipsia, polyuria, nocturia Diagnosis Must discontinue all anti-HTN medications and must have a high Na intake Hypokalemia with inappropriate kaliuresis- metabolic alkalosis hydrogen switch 24-hour urine collection for aldosterone-elevated Renin- low plasma renin High plasma aldosterone to rennin ration- diagnose primary vs. secondary Cortisol- make sure there is normal glucocorticoid secretion Aldosterone suppression test- high salt diet or saline infusion- insuppressible urine/plasma levels Abdominal CT to locate tumor Treatment Unilateral adenoma (Conns syndrome)-unilateral adrenalectomy Bilateral hyperplasia- medical therapy only. Lifelong spironolactone. Low sodium diet and exercise, maintain ideal BW, avoid tobacco Anti-hypertensive agent-lifelong spironolactone (Aldactone) therapy HTN is reversible in 2/3 of patients but persists in the remainder Pheochromocytoma Usually lethal unless diagnosed and treated appropriately Excessive levels of catecholamines cause HTN Characterized by paroxysmal (sudden/acute) or sustained hypertension due to tumor located in either or both adrenals or anywhere along the sympathetic nervous chain. Pheochromocytomas secrete a wide range of other peptides that can sometimes cause Cushings syndrome (ACTH), erythrocytosis (erythropoietin), or Hypercalcemia (parathyroid-related peptide; PTHrP) Rule of Tens 10% not associated with HTN, 10% are extra-adrenal, 10% occur in children, 10% are familial, 10% involves both adrenal glands; bilateral glands, 10% have metastatic disease noted at diagnosis, 10% recur after surgical removal Signs and symptoms Paroxysmal episodes under displacement of abdominal contents pushing on tumor HTN- constantly elevated in 60% of patients Headache, chest and abdominal pain, palpitations, tachycardia Dyspnea, pallor, fever, flushing, heat intolerance, diaphoresis Hyperglycemia Constipation, tremor, weight loss, anxiety, and sense of impending doom Risk factors Genetic- MEN Von Hippel-Lindau syndrome- autosomal disorder with hemangiomas of the retina, cerebellum, brainstem, and spinal cord; pancreatic cysts; renal cysts, adenomas and carcinomas Diagnosis Elevated 24-hour urine levels of catecholamines, metanephrine, and vanillylmandelic acid Direct assays of catecholamines in the blood and urine after an attack Decreased TSH, Increased T3 and T4- can be normal Hyperglycemia, leukocytosis, elevated ESR Clonidine suppression/glucagons stimulation test-Pharmacological provocative and suppressive tests that evaluate the rise and fall in blood pressure are usually not required or recommended Adrenal imaging with CT scan or MRI Treatment Pre-operative administration of combined alpha- and beta- blockade Treatment of choice- surgical resection of tumor(s) Acute hypertensive crises treated with IV nitroprusside Complications Hypertensive encephalopathy, retinopathy, CVA, MI, tachyarrythmias, orthostatic hypotension, pulmonary edema, renal infarction, DM, hypoglycemia, HTN crisis Multiple Endocrine Neoplasia (MEN) Groups of autosomal dominant disorders with sporadic forms where distinct syndromes occur MEN I (Wermers Syndrome) Parathyroid- hyper Pancreatic Pituitary MEN II-A (Sipple Syndrome) Parathyroid- hyper Adrenal- Pheochromocytoma Thyroid- Medullary carcinoma MEN II-B Mucosal and GI tumors Adrenal- pheochromocytoma Thyroid- medullary carcinoma Parathyroid Disease Effects Increases osteoclastic activity of bone Increases renal tubular reabsorption of calcium in the glomerular filtrate Inhibits the net absorption of phosphate and bicarbonate by the renal tubule Stimulates the synthesis of 1,25 dihydroxycholecalciferol by the kidney Calcium level should be corrected for serum albumin Serum Ca= serum Ca mg/dl + (0.8 x [4.0 Albumin g/dl]) Hyperparathyroidism Primary hyperparathyroidism Direct hyperfunction of the parathyroid glands due to either glandular hyperplasia or adenoma resulting in unregulated increase of PTH production and release, causing increase in serum calcium Secondary hyperparathyroidism Caused by chronic renal disease or vitamin D deficient states which causes hyperplasia of glands and associated increase in activity. Chronic renal failure causes decreased renal production of 1,25 (OH)2D3 and hyperphosphatemia initially produce a decrease in ionized calcium parathyroid glands may enlarge Signs and symptoms- Bones, stones, abdominal groans, muscle moans, psychic overtones Frequently asymptomatic, detected by screening Nephrolithiasis, reduced glomerular filtration rate Thirst, polydipsia, polyuria, muscle weakness, hypotonia- Hypercalcemia induced nephrogenic DI Abdominal pain, pancreatitis, constipation, vomiting, anorexia, weight loss Bone pain- Increase fractures, osteoporosis (vertebrae, distal radius, mid-shaft of femur) Fatigue, mental changes, apathy, depression, coma HTN, short QT interval (tachycardia) Calcium may precipitate in corneas (band keratopathy) or soft tissue (calciphylaxis) Risk factors Women 4:1 Age > 50 History of radiation therapy Diagnosis EKG- shortened QT interval Elevated serum PTH Elevated serum and urine calcium Elevated urinary phosphate with low serum phosphate levels Elevated alkaline phosphatase- May be normal Elevated serum chloride levels; decreased serum CO2, hyperchloremic metabolic acidosis Neck ultrasonography, CT scan or MRI imaging for parathyroid tumor/hyperplasia Percutaneous needle biopsy aspiration for cytology Treatment Surgical removal Large fluid intake-prevent renal stones Lasix- In well hydrated individuals who are hypercalcemic Complications Osteoporosis, osteomalacia, renal damage, UTI, hypertension, hypoparathyroidism, recurrent laryngeal nerve damage, bleeding, infection Hypoparathyroidism Most commonly seen following thyroidectomy or neck radiation therapy, when it is usually transient but may be permanent It may follow surgical removal of adenoma for primary hyperparathyroidism due to suppression of remaining parathyrois and accelerated remineralization of the skeleton (hungry bone syndrome) May also result from damage from heavy metals such as copper or iron, granulomas, autoimmunity, tumors, or infection. May also result from magnesium deficiency that prevents secretion Pseudohypothyroidism Group of diseases characterized by hypocalcemia due to renal resistance to PTH caused by mutations involving the PTH receptor. 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