Internal Medicine exam questions; 3 rd dep. 3 rd year, 2 nd semester 08/09 Exam Questions - 3rd Year, 2nd Semester Academic Year 2008/2009 Tests of the anterior pituitary function. Hypopituitarism. Syndromes of anterior pituitary hyperfunction. Disorders of the posterior pituitary. Diabetes mellitus. Hypoglycemic disorders. Pancreatic islet Diseases of the hypothalamus. cell tumors. Evaluation of the adrenal function. Adrenocortical hypofunction. Cushing's syndrome. Mineralocorticoid excess states. The adrenogenital syndromes. The disorders of the adrenal medulla. Tests of thyroid function and thyroid regulation. Hyperthyreoidism. Hypothyroidism. Thyroiditis. Sporadic and endemic goiter. Benign and malignant tumors of the Hyperparathyroidism. thyroid. Hypoparathyroidism. Diseases of the breast. The carcinoid syndrome. The disorders of lipid metabolism. Principles of alimentation and hyperalimentation. Protein-calory undernutrition. Anorexia nervosa and bulimia nervosa. Obesity. Disorders of purine metabolism. Gout. Alcoholism. Amenorrhea. Hypogonadism in males. Hirsutism. Acid-base disorders. Volume disorders. Osmolality disorders. Vitamine deficiencies and hypervitaminoses. Budapest, 17. January, 2009. Dr. Katalin Keltai English Tutor ECH 1 Tests of the anterior pituitary function -Basal pituitary hormones: ACTH; TSH; LH, FSH; GH; PRL -Target gland hormones: cortisol (circadian); thyroxine, T3; testosterone or estradiol; IGF-1 Stimulation tests -stimulation of the hypothalamus: -INS hypoglycemia test stimulates ACTH, GH, PRL synthesis. Contraindicated in patients >65yrs, pt.’s with CHD, uncontrolled HTN or epilepsy -clonidine/arginine: stim. release of GH -clomiphene: test LH, FSH. It inhibits the action of estrogen on the hypothalamus by binding to estrogen Rs for a long time prevents normal R recycling, in hypothalamic R no loss of FB FSH & LH -metoclopramide: test PRL. It binds to DA D2-Rs antagonistically inhibits DA PRL. Contraindicated in pheochromocytoma -stimulation of the ant. pit. with hypophysiotropic hormones: CRH; TRH; GnRH, GHRH; TRH (theoretical, rarely of practical clinical significance) -stimulation of the target gland with tropic hormones: -Short Synacthen test (short ACTH stim. test): to assess adrenal axis: do plasma cortisol before and 30 min after tetracosactide (=Synacthen) 250 g IM. Addison’s is excluded if 2nd cortisol >550 nmol/L -hCG test: LH, FSH Other dynamic tests: -INS tolerance test (ITT): in specialist centers, to assess adrenal and GH axes. Contraindications: epilepsy, heart disease, adrenal failure. Done in the morning by injecting IV INS to induce hypoglycemia, causing stress to ACTH and GH secretion. Glc must fall below 2.2 mM, normal is GH >20 mU/L and peak cortisol >550 nmol/L -when ITT is contraindicated: arginine + GHRH test; glucagon stimulation test -glucose tolerance test (OGTT): with GH measurement; done if acromegaly is suspected; test is done at 09.00 with fasting from midnight. GH and glc samples taken at 0, 30, 60, 90, 120, 150 min. Normally GH secretion is inhibited by a rice in glc, and GH should be undetectable – in acromegaly there is failure to suppress GH release (false positive results are seen in puberty, pregnancy, hepatic and renal disease, anorexia nervosa, and DM) -dexamethasone suppression test: screening test to diagnose and differentiate among types of Cushing’s and other hypercortisol states. Give dexamethasone 1mg PO at midnight; check serum cortisol before, and at 8AM. In normal pt.’s this high dose of steroid ECH 2 causes neg. FB ACTH and cortisol secretion to <50 nmol/L; in Cushing’ syndrome, there is a failure to suppress cortisol secretion ACTH Cortisol Interpretation Undetectable/ Not suppressed Adrenal Cushing’s sy. is likely / Not suppressed Ectopic ACTH prod. is likely Pituitary Cushing’s d. should be / Suppressed considered (do MRI) Hypopituitarism -diminished secretion of ant. pituitary hormones (loss or absence of >75% of anterior pituitary parenchyma -affected in the following order: GH, gonadotropins (FSH, LH), PRL, TSH, ACTH -panhypopituitarism is usually caused by irradiation, surgery or pituitary tumor -hypopituitarism accompanied by posterior pituitary dysfunction (diabetes insipidus) is almost always of hypothalamic origin Causes are from 3 levels: -Hypothalamus: Kallman’s sy. (gonadotropin releasing hormone def., often with anosmia and color blindness secondary hypogonadism), tumor, inflammation, infection (meningitis, TB), ischemia -Pituitary stalk: trauma, surgery, mass lesion (craniopharyngioma – from Rathke’s pouch, commonest childhood cranial tumor), meningioma, carotid artery aneurysm -Pituitary: tumor, irradiation, inflammation, infiltration (hemochromatosis, amyloidosis, metastatic cancer), ischemia (apoplexy, Sheehan sy. – postpartum pituitary necrosis) Features: -GH lack: central obesity; atherosclerosis; dry wrinkly skin; dec. strength, balance, CO; osteoporosis; dec. glc; growth failure (pituitary dwarfism) in children -gonadotropin lack: ♀: oligomenorrhea/amenorrhea, osteoporosis, breast atrophy, dyspareunia, dec. fertility and libido. ♂: erectile dysfunction, dec. libido and muscle bulk, hypogonadism -thyroid lack: tiredness, lethargy, depression, cold intolerance, weight gain, constipation, menorrhagia, hoarse voice, poor cognition/dementia, myalgia -corticotropin lack: nonspecific symptoms: fatigue, weakness, anorexia etc. -prolactin lack: rare – failure of lactation -pallor from loss of stimulatory effects of MSH on melanocytes -If the cause is pituitary tumor mass effect, or hormone secretion with dec. secretion of other hormones (eg. prolactinoma, acromegaly, Cushing’s) ECH 3 Tests: -Basal: LH & FSH or Testosterone or estradiol TSH or T4 Prolactin May be due to loss of DA from hypoth. IGF-1 cortisol Na+ - dilution Hb (normochromic, normocytic) -Dynamic tests: -Short Synacthen test: ACTH stim. test, to assess the adrenal axis -ITT: assess adrenal and GH axes; IV INS hypoglycemia ( cortisol and GH secretion) -Arginine + GH releasing hormone test -Glucagon stim. test -MRI to look for lesion Treatment: -hormone replacement, treatment of underlying cause -Hydrocortisone for secondary adrenal failure -Thyroxine for hypothyroid - For symptoms of hypogonadism and to prevent osteoporosis: ♀estrogen (estradiol implants, patches, pills) ♂ testosterone enanthate (IM, gels, tablets) -Gonadotropin therapy to induce fertility (-Somatropin for GH def.) !Hypopituitary coma: usually develops gradually in a person with known hypopituitarism (rarely due to infarction of pituitary tumor – pituitary apoplexy) -symptoms: headache, meningism (DDx: subarachnoid hemorrhage) -pt present with headache, ophthalmoplegia, consciousness, hypotension, hypothermia, hypoglycemia -tests: T4, cortisol, TSH, ACTH, glc. Pituitary fossa CT/MRI -Rx: hydrocortisone sodium succinate + T3 (after hydrocortisone); surgery if the cause is pituitary apoplexy Syndromes of anterior pituitary hyperfunction ECH 4 -adenohypophysis; originates from invagination of oral ectoderm (Rathke’s pouch); peptide hormones; pars distalis, tuberalis, intermedia; ACTH, TSH, FSH, LH, GH, PRL, -endorphin -10% of intracranial neoplasms (almost always benign adenomas); peak incidence from 30s to 50s -chromophobe: 70%, PRL (ACTH, GH); local pressure effect in 30% -acidophil: 15%, GH, PRL; local pressure effect in 10% -basophil: 15%, ACTH; local pressure effect rare -local pressure effects: headache, bilateral temporal hemianopsia, CN palsies, disturbance of hypothalamic centers of T, sleep, and appetite, CSF rhinorrhea (erosion through floor of sella) -investigations: MRI, assessment of visual fields, screening tests (PRL, IGF-1, ACTH, cortisol, TFTs, LH/FSH, testosterone in males, short Synachten test, OGTT (acromegaly), water deprivation test (DI) -water deprivation test: to see if the kidneys persist in producing dilute urine despite dehydration -treatment: surgery (trans-sphenoidal, trans-frontal), post-op radiotherapy if complete removal has not been possible -pituitary apoplexy: acute hemorrhage into an adenoma rapid enlargement of the lesion, depression of consciousness; may cause sudden death (Rx: steroids) -functional (hormone excess, clinical manifestation of hyperproduction) vs. silent (immunohistochemical demonstration of hormone production at tissue level only; without clinical manifestation of hormone excess) -approx. 40% of somatotropic adenomas and a minority of corticotropic adenomas bear GNAS1 mutations (chr. 20q13; mutation in -subunit of Gs GTPase activity, constitutive activation of Gs, persistent activation of cAMP, unchecked cellular proliferation) -cellular monomorphism, absence of reticulin network Prolactinoma with hyperprolactinemia -most common pituitary tumor (30%) -PRL >5000 mU/L is likely to be due to a prolactinoma (N=♂<450 mU/L, ♀<600 mU/L (<900 pmol/L)) -chromophobic staining -hyperprolactinemia can be caused by hypothalamic lesions or by medications (methyldopa, reserpine) that interfere with dopamine (prolactin-inhibitory factor) secretion. Can be associated with estrogen therapy -DDx: pregnancy, high-dose estrogen therapy, renal failure, hypothyroidism (TRH), stalk effect (mass in suprasellar compartment disturb normal inhibitory influence of hypothalamus on prolactin secretion) -loss of libido, infertility, amenorrhea, galactorrhea in women -loss of libido, infertility, impotence, sometimes galactorrhea in men ECH 5 -management: dopamine agonists (bromocriptine, cabergoline) Somatotropic adenoma with hypersecretion of GH -2nd