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564 Cards in this Set
- Front
- Back
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most common basis of hyperpituitism
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autonomous pituitary hypersection
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which population is hyperpituitarism most common?
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young adult males
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most common pituitary tumor
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prolactinoma
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pituitary tumor that stains chromophobic
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prolactinoma
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exaggerated skeletal muscle growth with nerve, joint and muscle problems
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giantisim due to excess GH before puberty
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insidious enlargement and coarsening of the face, hands and feet
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acromegaly due to excess GH after puberty
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what are the problems associated with excess GH?
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HTN, glucose intolerance (DM), osteoporosis, gonadal dysfunction, muscle weakness , arthritis, CHF
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elevated IGF-1, failure to suppress GH after glucose load
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excess GH
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pituitary tumor that stains acidophilic
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somatotropic ademina (GH excess)
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pituitary tumor that stains basophilic
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excess ACTH
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most frequent cause of hypopituitarism
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non-functioning adenoma
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decreased growth, fasting hypoglycemia, delayed puberty
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GH deficiency due to hypopituitarism
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no puberty, amenorrhea, delyaed long bone closure
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FSH/LH deficiency due to hypopituitarism
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lethargy, cold intolerance, constipation, bradycardia, delayed deep tendon reflex
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TSH deficiency due to hypopituitarism
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orthostatic hypotension, weakness, hypothermia, nausea, vomiting, dehydration, lethargy, pallor, coma, death,
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loss of ACTH due to hypopituitarism
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acute massive pituitary destruction
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pituitary apoplexy
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headache, diplopia, photophobia, visual blurring, vomiting, fever; marked wasting
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pituitary apoplexy
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hemorrhage into pituitary adenoma
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pituitary apoplexy
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any mass in the suprasellar conpartment that distrubes the normal inhibitory influence on the hypothalamus on prolactin secretion
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stalk effect - hyperprolactemia
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cyst lined by cuboidal epithelium sometimes with goblet cells that collect proteinous fluid and expand compromising the surround gland
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rathke's cleft cyst
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postpartum hypopituitarism
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sheehan's syndrome
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which lobe of the pituitary gland is more susceptible to pituitary apoplexy?
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anterior lobe - the posterior lobe is less susceptible due to arterial blood supply (unlike low pressure venous portal system)
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fatigue, anorexia, poor lactation, loss of pubic and axillary hair in post partum women
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sheehan's syndrome
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absence of a pituitary gland in an otherwise enlarged or normal sella
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empty sella syndrome
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primary empty sella symdrome caused by?
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defect in diaphragm which allows herniation of arachoid membrane into the sella causing pituitary atrophy when there is increased CSF pressure
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What causes secondary empty sella syndrome?
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a mass that compromises and atrophies the pituitary
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large tongue with deep furrows, deep voice, large hands and feet, corase facial features, impaired glucose tolerance
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acromegaly due to excess GH after puberty
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HTN, weight gain, moon face, truncal obesity, buffalo hump, hyperglycemia, amenorrhea, immune suppression
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cushing's syndrome
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primary cushing's lab findings
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low ACTH, high cortisol
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secondary cushing's lab findings
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high ACTH, high cortisol
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cushing's disease
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high cortisol due to pituitary adenoma secreting ACTH
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most common ectopic cause of cushing's
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small cell lung cancer
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dex test: decreased cortisol after low dex dose
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normal
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dex test: increased cortisol after low dose, decreased cortisol after high dose
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ACTH producing pituitary adenoma
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dex test: increased cortisol after low and high dose
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ectopic ACTH producing tumor and cortisol producing tumors
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increased CRH, ACTH and cortisol
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pseudocushing's - secondary to alcohol, stress, renal failure, anorexia, obesity or depression
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expansion of pituitary postadrenalectomy
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nelson's syndrome; caused by loss of feedback inhibition
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HTN, hypokalemia, metaoblic acidosis, low plasma renin, no edema
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conn's syndrome - primary hyperaldosteronism (aldosterone secreting tumor)
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high plasma renin and aldosterone
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secondary hyperaldosteronism due to renal artery stenosis, chronic renal failure, CHF, cirrhosis or nephritic syndrome - kidney preception of low ECF results in over secretion of renin
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excessive water retention with hyponatremia
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SIADH
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urine osmolarity > serum osmolarity
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SIADH
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hypotension, hyperkalemia with skin hyperpigmentation
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Addison's disease - primary aldosterone deficiency due to adrenal atophy or destruction
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adrenal atrophy, absence of mineralocorticoids, glucocorticoids and androgens
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Addison's disease - primary aldosterone and cortisol deficiency due to adrenal atophy or destruction
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decreased cortisol, androgens and ACTH
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secondary adrenal insufficiency - due to decreased ACTH production by pituitary, aldosterone levels are normal!
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actue adrenocortical insufficency due to adrenal hemorrhage associated with meningococcal septicemia
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Waterhouse Friderichsen syndrome
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most common tumor of the adrenal medulla in adults
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pheochromocytoma
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medullary tumor derived from chromaffin cells
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pheochromocytoma
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episodic hypertension due to over secretion of E, NE and dopamine
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pheochromocytoma
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urinary VMA and elevated plasma catecholamines
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pheochromocytoma
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episodic hypertension, headache, perspiration, palpitation and pallor
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pheochromocytoma
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like pheochromocytoma but associated with ANS and scaterred throughout body
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paraganglion cell tumor
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non-functioning paraganglion cell tumor
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tumors derived from the parasympathetic cahin
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functional paraganglionic cell tumor
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tumors derived from the abdominal aorticosympathetic paraganglion
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tumor of the basal layer of the epidermis
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merkel cell tumor
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rare skin carcinoma of the head and upper extremities
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merkel cell tumor
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merkel cell tumors show histologic features of what?
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small cell endocrine neoplasms
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what population is most likely to get merkel cell tumors
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elderly
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do merkel cell tumor eleaborate endocrine substance
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not usually
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most common tumor of the adrenal gland in children
|
neuroblastoma
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where can neuroblastomas occur?
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anywhere along the sympathetic chain
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HVA in the urine
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neuroblastoma
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small blue cell malignant tumor of the adrenal medulla
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neuroblastoma
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most common thryoid anamoly
|
thyroid duct cyst
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self limiting hypothyroidism that presents initially as hyperthyroidism
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subactue thyroiditis - de Quervain's
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lymphocytic subactue thyroiditis that is painless
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subactue thyroiditis - de Quervain's
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thyroiditis with granulomatous (giant cells) inflammation without plasma cell or germinal centers
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subactue thyroiditis - de Quervain's
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elevated ESR, jaw pain, neck pain ealry on
|
subactue thyroiditis - de Quervain's
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results from bacterial or fungal seeding of the thyroid gland
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acute infectious thyroiditis
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painful neck swelling that is usually self limiting, little effect on TH
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acute infectious thyroiditis
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thyroid replaced by fibrous tissue
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riedel's thyroiditis
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fixed, hard painless goiter and hypothyroidism
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riedel's thyroiditis
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thyroid fibrosis that can extend beyond the capsule
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riedel's thyroiditis
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thyroditis due to viral infection
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subactue thyroiditis - de Quervain's
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antigen mediated immune response against the thyroid
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subactue thyroiditis - de Quervain's
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gross appearnce of the thyroid: firm, white-yellow nodules that are more rubbery than normal brown thyroid substance
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subactue thyroiditis - de Quervain's
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hyperthyroidism without ophthamopahty
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subacte infectious thyroiditis
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enlargement of the thyroid
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goiter
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nontoxic goiter without thyroid hormone dysfunction
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simple goiter
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goiter associated with hyperthyroidism
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toxic goiter
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goiter due to iodine deficiency in endemic areas
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endemic goiter
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goiter in non-iodine deficient areas
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sporadic goiter
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irregular enlargement resulting in nodule formation in the thyroid
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nodular goiter
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late stage of a simple goiter
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nodular cooid goiter
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what is the TH state in most goiters
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euthyroid - can develop hypothyroidism
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hypermetabolic state due to increased TH
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thyrotoxicosis
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myxedema
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hypothyroidism
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cold intolerance, hypoactivity, weight gain, decreased appetite, fatigue, lethargy, constipation, weakness, decreased reflexes, dry cool skin, coarse brittle hair
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hypothyroidism
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increased TSH, decreased TH
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hypothyroidism
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which hormone is most sensitive to test for hypothyroidism
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TSH
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slowing of physical and mental activities
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myxedema
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accumulation of matrix substances - GAG and hyaluronic acid - in the skin, subcutaneous tissue and visceral sites results in edema
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myxedema
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hurthle cells
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hashimoto's thyroiditis
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increased TSH, decreased TH, non-tender lympohcytic infiltration of the thyroid with germinal centers
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hashimoto's thyroiditis
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autoantibodies to the TSH receptor that block its binding
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hashimoto's thyroiditis
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progressive depletion of thyroid epithelial cells replaced by mononuclear cells and fiborosis
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hashimoto's thyroiditis
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severe fetal hypothyroidism
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cretinism
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pot-bellied, pale, puffy faced child with protruding umbilicus, protuberant tongue and mental retardation
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cretinism
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heat intolerance, hyperactivity, weight loss, increased appetite, palpitations, arrhythmias, diarrhea, increased reflexes, warm moist skin, fine hair
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hyperthyroidism
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decreased TSH, increased TH
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primary hyperthyroidism
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increased basal metabolic rate and increased beta adreneric tone
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hyperthyroidism
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what is a common complication of grave's disease in older men?
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a fib
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autoantibodies to TSH receptor that stimulate the receptor
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graves disease
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ophthalmopathy, peritibial myxedema, hyperthyroidism
|
graves disease
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when does graves disease usually present
|
in times of stress
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what is a serious copmlication of hyperthyroidism
|
stress-induced catecholamine surge that leads to death by arrhythmias
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TSI
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thyroid stimulating immunoglobulin - found in graves disease
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what is a long term complication of graves disease
|
glaucoma
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thyrotoxicosis due to iodine restoration in a iodine deprived patient
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Jod-Basedow phenomenon - toxic multinodular goiter
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|
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what population is thyroid cancer more frequently seen
|
female
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what is the most common thyroid cancer
|
papillary carcinoma
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ground glass nuclei (Orphan Annie eye), psammoma bodies, nuclear groves
|
papillary carcinoma
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thyroid carcinoma associated with inversion of chromosome 10 or translocation between 10 and 17
|
papillary carcinoma
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childhood radiation increases risk of what?
|
papillary carcinoma
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which thyroid cancer has uniform follicles with cells surrounding a lumen
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follicular carcinoma
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which thyroid cancer is associated with mutations in the RAS gene
|
follicular carcinoma
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histology: too many cells, scalloped colloid, papillar progections into the lumen
|
graves disease
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which thyroid cancer is associated with mutations in the RET gene
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medullary carcinoma
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which thyroid cancer is derived from follicular cells
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papillary and follicular carcinoma
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which thyroid cancer is derived from parafollicular "C" cells?
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medullary carcinoma
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which population is papillary carcinoma more often seen?
|
young adult females
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which population is follicular carinoma more often seen in?
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middle aged females
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thyroid histology: round to spindle shaped cells usually containing neurosecretory granules arranged in nests surrounded by deposition of amyloid
|
medullary carcinoma
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which thyroid carcinoma presents with a nontender neck mass that is very slow growing and non-functional
|
papillary carcinoma
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which thyroid carcinoma presents with a firm irregular nodular mass that grows slowly
|
follicular carcinoma
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which thyroid carcinoma presents with painless large solitary mass and may present with diarrhea
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medullary carcinoma
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what do medullary carcinomas secrete
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calcitonin - can secrete other (ACTH, prostaglandins)
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what is medullary carcinoma associated with?
|
MEN type 2 and pheochromocytoma
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which population is sporadic medullary carcinoma most likely seen in?
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middle aged adults
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which population is genetic medullary carcinoma most likely seen in?
|
adolescents with MEN type 2 or pheochromocytoma
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which population is undifferentiated thyroid carcinoma most likely seen in?
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older patients
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what is the progression to undifferentiated thyroid carcinoma associated with?
|
inactivation of p53
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what is thyroid lymphoma associated with?
|
hashimoto's thyroiditis
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what population is primary hyperparathyroidism usually seen in?
|
women older than 50
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hypercalcemia, hypercaciuria, hypophosphatemia, increased PTH, increased alkaline phosphatase, increased cAMP in urine
|
primary hyperparathyroidism
|
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what is osteitis fibrosa cystica?
|
cystic bone spaces filled with brown fibrous tissue - painful
|
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what is osteitis fibrosa cystica associated with?
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primary hyperparathyroidism
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what is the triad associated with primary hyperparathyroidism?
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stones, bones and groans
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hypocalcemia, hyperphosphatemia, increased alkaline phosphatase, increased PTH
|
secondary hyperparathyroidism
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when is secondary hyperparathyroidism most often seen
|
in chronic renal disease
|
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decreased gut calcium absorption and increased phosphorus
|
secondary hyperparathyroidism
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hypocalcemia, decreaed PTH, tetany
|
hypoparathyroidism
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|
tapping of facial nerve causes contraction of facial muscles
|
chvostek's sign - hypoparathyroidism
|
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|
occlusion of brachial artery with BP cuff gives carpal spasm
|
trousseau's sign - hypoparathyroidism
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|
|
autosomal dominant disorder where kidney is unresponsive to PTH
|
pseudohypoparathyroidism
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hypocalcemia, shortened 4th and 5th digits, short stature
|
pseudohypoparathyroidism
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hypocalcemia, normal PTH
|
pseudohypoparathyrodism
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what is pseudohypoparathyroidism associated with
|
albright heredity osteodystrophy
|
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tumors of enterochromaffin cells
|
carcinoid syndrome
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recurrent diarrhea, cutaneous flushing, asthmatic wheezing, right sided valvular disease, increased serotonin in the urine
|
carcinoid syndrome
|
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which carcinoid tumor would produce high levels of serotonin in the blood?
|
metastatic small bowel tumors (not seen if tumor is limited ot the GI due to high first pass effect on serotonin)
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increased serotonin in the urine
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carcinoid syndrome
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gastric secreting tumor of the pancreas or duodenum
|
Zollinger Ellison syndrome
|
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recurrent ulcers
|
gastrinomas
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ulcers in the jejunem
|
Zollinger Ellison syndrome
|
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what is associated with gastrinomas
|
MEN type 1
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what is the most common islet cell tumor
|
insulinomas
|
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which tumor is derived from beta cells of islets
|
insulinomas
|
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islet cell histology: giant islets with nests and cords or normal appearing beta cells
|
insulinomas
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watery diarrhea, hypokalemia, achlorhydria
|
VIPomas
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|
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what are VIPomas associated with?
|
neuroblastoma, ganglioneuroblastoma, ganglioneuromas, pheochromocytoma
|
|
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what is the most common tumor of the appendix?
|
carcinoid tumors
|
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|
Wermer's syndrome
|
MEN 1
|
|
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parathyroid tumors, pituitary tumors, pancreatic endocrine tumors
|
MEN 1
|
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MEN associated with chromosome 11
|
MEN 1
|
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Sipple's syndrome
|
MEN 2A
|
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medullary thyroid carcinoma, pheochromocytoma, parathyroid tumor
|
MEN 2A
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medullary thyroid carcinoma, pheochromocytoma, oral/intestinal ganglioneuromatosis
|
MEN 2B
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Which MEN is associated with mutations to the RET gene
|
MEN type 2
|
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what results in congenital adrenal hyperplasia
|
inherited metabolic defects that block the produciton of cortisol, eliminating negative feedback = increased ACTH
|
|
|
shunts steroid pathway from cortisol to androgens
|
partial 21 hydroxylase deficiency
|
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females present as virilization of infants or if less severe infertibility problems after puberty
|
partial 21 hydroxylase deficiency
|
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males present with precocious puberty
|
partial 21 hydroxylase deficiency
|
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what defect results in virilization
|
partial 21 hydroxylase deficiency
|
|
|
shunts steroid pathway from cortisol to androgens and interferes with aldosterone production
|
21 hydroxylase deficiency
|
|
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virilizing and salt losing
|
21 hydroxylase deficiency
|
|
|
hyponatremia, hyperkalemia and increased androgens
|
21 hydroxylase deficiency
|
|
|
shunts steroid pathway away from cortisol to androgens and causes a buildup of aldosterone precursor
|
11 hydroxylase deficiency
|
|
|
increased androgens, hypokalemia, hypernatremia, hypertension
|
11 hydroxylase deficiency
|
|
|
classic polyuria, polydipsia and polyphagia
|
Type 1 diabetes mellitus
|
|
|
what occurs due to insulin deficeincy/glucagon excess
|
decreased glucose uptake, increaed protein catabolism, increased lipolysis
|
|
|
what happens to GH and epinephrine in DM?
|
their secretion is unopposed - exacerbating the hyperglycemia
|
|
|
destruction of beta cells
|
Type 1 diabetes mellitus
|
|
|
increased insulin resistance
|
Type 2 diabetes mellitus
|
|
|
amyloid deposits within beta cells
|
Type 2 diabetes mellitus
|
|
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what is an important complication of Type 1 DM?
|
ketoacidosis
|
|
|
water deprivation test - urine doesn't concentrate
|
diabetes insipidus - lack of ADH or response to ADH
|
|
|
What complication of diabetes is associated with AGEs?
|
nephropathy and atherosclerosis
|
|
|
what complication of diabetes is associated with activation of protein kinase C
|
retinopathy
|
|
|
what complication of diabetes is associated with intracellular hyperglycemia and distrubances with polyol pathways?
|
neuropathy
|
|
|
what is the result of chronic derangment of lipid metabolism in diabetes patients?
|
hypertrigylceremia
|
|
|
what is the most common cause of cushing's syndrome
|
administration of exogenous glucocorticoids
|
|
|
HTN and hypokalemia
|
hyperaldosteronism
|
|
|
what is the most common congenital adrenal hyperplasia?
|
21 hydroxylase deficiency
|
|
|
tumor cells concentrically arranged around a central space filled with neuropil
|
neuroblastoma
|
|
|
rathke's pouch
|
anterior lobe of the pituitary
|
|
|
small cellular nests that remain along the line of embryologic ascent of the anterior pituitary
|
craniopharyngiomas
|
|
|
benign but locally destructive remnants of rathke's pouch
|
craniopharyngiomas
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craniopharyngiomas are related to what endocrine structure?
|
anterior pituitary
|
|
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which cells of the anterior pituitary are acidophils
|
somatotrophs and lactotrophs
|
|
|
which cells of the anterior pituitary stain basophilic?
|
corticotrophs and thyrotrophs
|
|
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what is the staining of gonadotrophs of the anterior pituitary?
|
basophilic and chromophobes
|
|
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what are the bulk of chromophobe cells in the anterior pituitary?
|
non-secretory cells (most likely temporarily degraulated cells)
|
|
|
which hypothalamic nuclei have their axons in the posterior pituitary?
|
paraventricular and supraoptic nuclei
|
|
|
where are posterior pituitary hormones formed?
|
in the hypothalamus - paraventricular and supraoptic nuclei
|
|
|
where are posterior pituitary hormones stored?
|
they are stored in the posterior lobe but made in the hypothalamus
|
|
|
how are anterior pituitary, except prolactin, controlled?
|
they are controlled via the hypothalamus releasing factors
|
|
|
how is prolactin secretion control?
|
it is inhibited by normal hypothalamic dopamine release
|
|
|
other than inhibition of dopamine what other hormones can trigger prolactin secretion?
|
TRH or high levels of estrogen
|
|
|
how is secretion of pituitary hormones reduced?
|
by negative feedback on both the thalamus and pituitary by the hormone product of the target organs that were stimulated by pituitary hormones
|
|
|
what regulates release of ADH?
|
increased serum osmolality and decreased blood volume
|
|
|
what is the most common cause of autonomous pituitary hypersection?
|
functional, benign monoclonal neoplasm (pituitary adenoma)
|
|
|
if two hormones are secreted by a pituitary adenoma what are they most likely to be?
|
GH and prolactin
|
|
|
what population do adenomas tend to occur in?
|
young adult males
|
|
|
what is the gross appearance of most pituitary adenomas?
|
vary in size but are usually small, soft and red-brown to yellow-tan in appearance
|
|
|
are most overtly malignant pituitary adenomas functional or nonfunctional?
|
non-functional
|
|
|
extensive spontaneous necrosis or sudden hemorrhage of the pituitary due to a pituitary adenoma?
|
pituitary apoplexy
|
|
|
define hyperprolactinemia
|
consistently elevated serum prolactin (greater than 20 ng/ml) in the absense of pregnancy or postpartum lactation
|
|
|
what causes amenorrhea in hyperprolactinemia?
|
high prolactin will suppress pituitary gonadotropin release which often results in anovulation = secondary amenorrhea
|
|
|
what will hyperprolactinemia do in men?
|
may produce infertility or inpotence due to prolactins suppression of pituitary gonadotropin release
|
|
|
how can prolactinomas present in males?
|
if the hormone effects are asymptomatic, the tumor will be discovered due to mass effects - headache, visual field defects ect.
|
|
|
how are prolactinomas treated?
|
dopamine agonists - bromocryptine; usually medical treatment is sufficient and no surgery is needed
|
|
|
what is the second most common functional disorder of the pituitary?
|
acromegaly due to excess GH after puberty
|
|
|
what are the metabolic problems associated with excess GH?
|
HTN, glucose intolerance, osteoporosis
|
|
|
what is the treatment for GH secreting pituitary adenomas?
|
surgery and or radiation
|
|
|
what is the most common hypothalamic induced isolated anterior pituitary hormone deficit?
|
GH deficiency
|
|
|
what is the cause of most hypopituitarism?
|
extensive destruction of the anterior pituitary lobe tissue (75% destroyed before symptoms appear)
|
|
|
what does extensive destruction of the anterior pituitary result in?
|
panhypopituitarism - Simmond's disease
|
|
|
what are the symptoms of hypopituitarism?
|
symptoms are related to deficiencies of GH, gonadotropins, TSH and then ACTH - symptoms present temporally
|
|
|
what is the cause of pituitary dwarfism?
|
GH deficiency before puberty
|
|
|
short stature but with normal proportions
|
pituitary dwarfism
|
|
|
what occurs with pituitary dwarfism?
|
delayed sexual maturity
|
|
|
what are the symptoms of GH deficiency after puberty?
|
usually asymptomatic
|
|
|
what may cause delayed puberty in children?
|
gonadotropin deficiency
|
|
|
what are the symptoms of gonadotropin deficiency in adult women?
|
amenorrhea, loss of secondary sex characteristics and atrophy of the ovaries and external genitalia
|
|
|
what are the symptoms of gonadotropin deficiency in adult males?
|
aspermia, loss of secondary sex characteristics and testicular atrophy
|
|
|
what is the most common cause of extensive destruction of the pituitary (hypopituitarism)
|
events that arise from the sella itself
|
|
|
what can happen with suprasellar tumors?
|
they can impinge upon and destroy the anterior and or posterior pituitary usually resutling in hypopituitarism and or diabetes insipidus
|
|
|
what population is craniopharyngioma seen in?
|
it is a benign slow growth tumor than can be locally destructive seen in children and young adults
|
|
|
what tumor histiologicaly resembles embryonic tooth enamel formation with squamous and columnar epithelium set in loose fibrous tissue?
|
craniopharyngiomas
|
|
|
what tomur resembles ameloblastoma?
|
craniopharyngiomas - ameloblastoma = embryonic tooth enamel
|
|
|
what is a diagnostic clue of craniopharynginomas?
|
calcification - useful radiologic sign
|
|
|
what are germinomas?
|
tumors that arise from the pineal gland from germ cells that were embryologic 'left overs'
|
|
|
what tumor arise from the pineal gland from germ cells that were embryonic 'left overs'
|
germinomas
|
|
|
what is the most frequent cause of hypopituitarism?
|
non-functioning adenoma
|
|
|
how do non-funcitoning pituitary adenomas cause hypopituitarism?
|
as the neoplasm enlarges there is compression of the remainder of the gland resulting in a gradual loss of function
|
|
|
are non-functioning adenomas large or small when discovered?
|
large - since clinical symptoms are due to mass effects
|
|
|
describe the histology of non-functioning pituitary adenomas
|
cells are generally sparsely granulated (chromophobe adenoma) and may be derived from undifferentiated precursor cells
|
|
|
what tumors are usually made of sparsely granulated cells that may be derived from undifferentiated precursor cells?
|
non-functioning chromophobe pituitary adenomas
|
|
|
what pituitary tumor contains cells with clear cytoplasm?
|
null cell adenoma - a non-functioning pituitary adenoma
|
|
|
what pituitary tumor contains cells packed with mitochondria?
|
oncocytoma - a non-functioning pituitary adenoma
|
|
|
how may functioning adenomas cause hypopituitarism?
|
functioning adenomas may undergo secretory exhaustion, ischemic necrosis, hemorrhage or infarction leading to hypopituitarism
|
|
|
infarction of the anterior lobe secondary to hypotension or shock?
|
sheehan's syndrome
|
|
|
what pituitary problem is classically caused by obstetric hemorrhage and hypotension?
|
sheehan's syndrome
|
|
|
postpartum pituitary necrosis
|
sheehan's syndrome
|
|
|
what may be the first sign of sheehan's syndrome?
|
inability to lactate or failure to resume menses
|
|
|
in addition to failure to lactate and failure to resume menses what other symptoms are associated with postpartium pituitary necrosis?
|
lack of energy and loss of muscle strength
|
|
|
what are the symptoms of abnormal oxytocin levels?
|
none clinically
|
|
|
what does ADH promote?
|
together with thirst (water ingestion) ADH regulates water balance to maintain steady-state solute concentrations within tissues
|
|
|
what causes renal tentionof water with hypervolemia, hemodilution and inability to dilute urine?
|
excess secretion of ADH - SIADH
|
|
|
what is the usual cause of SIADH?
|
ectopic production of ADH by various neoplasms (classicaly small cell undifferentiated carcinoma of the lung)
|
|
|
other than small cell carcinomas of the lung, what other conditions can cause SIADH?
|
meningitis, pneumonia and head trauma
|
|
|
what causes excessive renal sodium excretion in absense of hypotension, hypovolemia or edema forming states?
|
SIADH
|
|
|
what is the cause of diabetes insipidus?
|
posterior pituitary tissue destruction (metastatic neoplasm, surgical removal), disruption of the hypothalamic-hypophyseal axis (trauma, inflammation) or idiopathic causes
|
|
|
what is nephrogenic diabetes insipidus?
|
sufficient ADH but end organ upresponsiveness (kidney) to the hormone
|
|
|
what are the most common symptoms of mass effect of the pituitary?
|
visual impariemtn (bitemporal hemianopsia) due to expansion beyond the sella and impingment on the optic chiasm or compression of the oculomotor nerves
|
|
|
what symptoms occur if an expanding pituitary mass compresses the floor of the 3rd ventricle?
|
increased cranial pressure producing headaches, nausea, and vomiting
|
|
|
what may precede the development of clinical sign of pituitary mass effects?
|
radiographic evidenc eof an enlarging sella
|
|
|
what do TH do?
|
regulate cellular oxygen consumption, metabolism of protein, carbs and lipids and renders tissues more sensitive to the effects of catecholamines
|
|
|
how is TH stored?
|
complexed to thyroglobulin, stored in the follicles as colloid
|
|
|
what is the action of TSH on the thyroid?
|
stimulates production of TH
|
|
|
what happens to colloid under periods of activity?
|
thyroglobulin is taken up from the colloid by follicular cells and undergoes proteolysis to release thyroxine and small amouts of T3 into perifollicular capillaries
|
|
|
how do TH circulate in the blood?
|
primarily bound to throxine binding globulin (TBG)
|
|
|
can normal levels of free thyroid hormone be seen even if total thyroid hormone is elevated?
|
yes - if TBG is elevated total TH can be elevated but the proportion of free hormone is still in normal ranges. The opposite is also true
|
|
|
what conditions can lead to elevated TBG?
|
pregnancy, estrogen therapy and a genetically determined increase in TBG - will cause elevated total TH
|
|
|
what diseases cause TBG to be decreased?
|
liver disease, nephrotic syndrome, androgen treatment or a genetic defect in TBG synthesis - will cause elevated total TH but normal free levels will be seen
|
|
|
how much of TBG is normally saturated?
|
one third, this is maintained dispite abnormal levels of TBG to keep pts euthyroid
|
|
|
what is the origination of the thyroid?
|
the thyroid originates as a tubular evagination from the foramen cecum at the root of the tongue and grows caudally anterior to the trachea
|
|
|
which portion of the embryonic thyroid regresses?
|
the proximal protion regresses while the distal portion forms the thyroid
|
|
|
what happens if there is improper decsent of the thyroid?
|
aberrent location - substernal or sublingual; most are midline but can be in lateral in the anterior triangle of the neck
|
|
|
failure of the proximal portion to degenerate
|
thryoglossal duct cyst
|
|
|
what is a thyroglossal duct cyst?
|
failure of the proximal portion of the embryonic thyroid to dengereate - may not be apparent until adulthood
|
|
|
what midline neck structure contians mucinious fluid and is lined by squamous cuboidal epithelium overying a lymphocytic infiltrate containing scattered thyroid follicles
|
thyroglossal duct cyst
|
|
|
what are complications of thyroglossal duct cysts?
|
abscess formation and or draining sinus tracts
|
|
|
what measure measurement is too sensitive for hyperthyroidism?
|
RIA of T3
|
|
|
what measurements are helpful to diagnose hyperthyroidism?
|
TSH and free T4
|
|
|
what are the 3 major causes of hyperthyroidism?
|
graves disease, toxic multinodular goiter and toxic adenoma
|
|
|
what is the most sensitive indicator of primary hypothyroidism?
|
serum TSH
|
|
|
insidious onset of tiredness, apathy and lethargy
|
myxedema
|
|
|
mucopolysacchardie deposited in CT throughout the body giving subcutaneous tissue a doughy consistency
|
myxedema
|
|
|
periorbital soft tissue puffiness, enlarged tongue, flabby dilated heart
|
myxedema
|
|
|
what is seen in the BP of patients with myxedema?
|
narrowed pulse pressure
|
|
|
what causes the narrowed pulse pressure seen with myxedema?
|
increased peripheral vascular resistance and decreased cardiac output
|
|
|
what effects on serum lipids is seen in myxedema?
|
hyperlipidemia
|
|
|
what causes cold intolerance in myxedema?
|
decreased perfusion of the skin due to low cardiac output
|
|
|
retarded brain development, spasticity and deaf-mutism
|
neurologic cretinism
|
|
|
what causes neurologic cretinism?
|
deficiency of TH early in fetal life
|
|
|
feeding difficulty, somnolence, hoarse low pitched cry and failure to thrive
|
cretinism caused by deficiency of TH late in pregnancy or learly infancy
|
|
|
what happens if cretinism is left untreated?
|
impaired skeletal growth, dry skin and protuberant abdomen
|
|
|
what are the later manifestations of cretinism?
|
wide set eyes, broad flat nose, enlarged tonge, periorbital puffiness
|
|
|
what mass effects are seen with thyroid goiters?
|
dysphagia, inspiratory stridor, hoarseness, dyspnea
|
|
|
painful swelling of the thyroid gland that is caused by bacterial or fungal seeding
|
acute infectious thyroiditis
|
|
|
what is the natural course of acute infectious thyroiditis?
|
usually self limiting with no sequelae except focal scarring
|
|
|
immune attack on the thyroid typically following a previous viral infection
|
subactue granulomatous thyroiditis (de Quervain's)
|
|
|
which population most frequently presents with de Quervain's thyroiditis?
|
young adult females
|
|
|
what is the clinical presentation of de Quervain's thyroidits?
|
acute febrile flu like systemic illness that may have sudden painful and diffuse irregular enlargement of the thyroid
|
|
|
what is seen in the early stage of de Quervain's thyroiditis?
|
transient thyrotoxicosis
|
|
|
what is seen in the later stage of de Quervain's thyroiditis?
|
hypothyroidism which gradually resolves over several months
|
|
|
what may occur in the thyroid gland early in de Quervain's thyroiditis?
|
microabscesses
|
|
|
what eventually occurs in the thyroid in de Quervain's thyroiditis?
|
follicular destruction with granulomatous 'foreign body' inflammatory reaction to pools of colloid
|
|
|
what is the end result of de Quervian's thyroiditis?
|
focal scarring of the thyroid that is usually not clinically significant
|
|
|
what causes subacute lymphocytic thyroidits?
|
unknown etiology
|
|
|
how does subacute lymphocytic thyroidits present?
|
painless mild to moderate enlargement of the thyroid and or transient hyperthyroidism which is usually self limiting
|
|
|
what is the histology of subacute lymphocytic thyroiditis?
|
lymphocytic stromal infiltrate WITHOUT plasma cells or germinal centers, may have mild fibrosis
|
|
|
what causes lymphocytic stromal infiltrate of the thyroid gland WITHOUT plasma cells or germinal centers and may have mild fibrosis?
|
subactue lymphocytic thyroidits
|
|
|
Riedel's thyroiditis is seen in what population?
|
middle aged females
|
|
|
aggressive fibrosis of the thyroid parenchyma and adjacent structures
|
riedel's thyroiditis
|
|
|
what presents as hard, non-tender fixed nodule of irregular outline in the neck?
|
riedel's thyroiditis
|
|
|
what clinical presentation can riedel's thyroiditis have other than the enlarged neck mass
|
mass effects - stridor, dysphagia, hoarseness, dyspnea
|
|
|
what do patients with riedel's thyroiditis often have - hyperthyroidism or hypothyroidism?
|
hypothyroidism - up to 50% of patients
|
|
|
what population does hashimotos usually present in?
|
middle aged women
|
|
|
gradual enlargement of the thyroid that is painless and associated with insidious onset of hypothyroidism
|
hashimoto's thyroiditis
|
|
|
can patients with hashimoto's thyroiditis have hyperthyroidism?
|
yes - they can go through transient thyrotoxicosis
|
|
|
what is a predisposing factor for hashimoto's thyroiditis?
|
other collage vascular disorder - associated with HLA-DR5
|
|
|
what may allow autoantibodies to form in hashimoto's thyroiditis?
|
deficiency of antigen specific suppressor T cells
|
|
|
what disease may be caused by deficiency of antigen specific suppressor T cells?
|
hashimoto's thyroiditis
|
|
|
what is the result of the deficiency of antigen specific suppressor T cells in hashimoto's thyroiditis?
|
cytotoxic killer T cells are free to attack follicular cell antigens while helper T cells assist in the B cell production of autoantibodies (microsomal, thryogobulin and TSH receptor)
|
|
|
what types of autoantibodies are seen in Hashimoto's thyroidits?
|
microsomal thyroglobulin and TSH receptor autoantibodies (may be TSH blocking Ab)
|
|
|
what are the two forms of TSH receptor autoantibodies?
|
thyroid growth Ig (TGI) and thyroid stimulating Ig (TSI)
|
|
|
what type of TSH receptor antibodies are commonly seen in hashimoto's thyroiditis?
|
TGI mostly or TGI and TSI with TSI blocking antibody
|
|
|
growth of the thyroid gland without hyperfunction
|
hashimoto's thyroiditis
|
|
|
what is the gross appearance of the thyroid in hashimoto's?
|
symmetrically enlarged, firm and rubbery
|
|
|
what is the histologic appearance of the thyroid in hashimoto's?
|
destruction of the follicles and extensive infiltration of the stroma by lymphocytes, immunoblasts, plasma cells and marcophages often with prominent germinal centers
|
|
|
what causes Hurthle cell appearnce?
|
cytoplasm of residual non-functional follicular cells that are packed with mitochondria giving an eosinophilic granular appearance to the cell
|
|
|
what HLA is grave's disease associated with?
|
HLA-DR3
|
|
|
what stimulates the production of TSI and TGI in grave's disease?
|
TGI and TSI are produced as a result of an antigen specific T suppressor cell deficiency
|
|
|
what is the result of the deficiency of antigen specific suppressor T cells in grave's disease?
|
enlarged hyperfunctioning gland
|
|
|
what is the effect of thyrotoxicosis on graves?
|
it can aggravate the underlying pathology by further depressing T suppressor cell activity
|
|
|
in addition to autoantibodies directed at the thyroid what other autoantibodies are produced?
|
autoantibodies that react with or at least cross react eye muscle antigens
|
|
|
what is the result of cross reaction of autoantibodies in graves to the eye muscles?
|
subsequent lymphocytic infiltration of and mucopolysacchardie deposition in the extraocular eye muscles and retrorbital fatty tissue
|
|
|
what results from lymphocytic infiltration of and mucopolysaccharide deposition in the extraocular eye muslces and retroorbital fatty tissue?
|
these changes cause proptosis and ocular changes
|
|
|
what causes pruritic pretibial myxedema seen in graves disease?
|
lymphocytic infiltration of and mucopolysaccharide deposition in the dermis and subcutaneous tissues (analogous to changes that cause proptosis)
|
|
|
what is an adverse effect of graves on the eye?
|
blindness despite successful treatment of the thyrotoxicosis - although most eye problems regress spontaneously
|
|
|
what does the thyroid look like grossely in grave's disease?
|
moderate diffuse enlargement of the thyroid with the parenchyma having a soft meaty appearance
|
|
|
what is the histologic appearance of the thyroid in graves?
|
increased numbers of tall columnar follicular epithelial cells creating papillary infoldings into the follicle lumen which is almost devoid of colloid materal
|
|
|
increased numbers of tall columnar follicular epithelial cells creating papillary infoldings into the follicle lumen which is almost devoid of colloid materal
|
graves disease
|
|
|
what occurs in the stroma of the thyroid in graves
|
heavy stromal lymphocytic infiltrate and increased stromal vascularity - may form lymphoid follicles
|
|
|
what is the aciotn of thiourea dn mercaptoimidazole?
|
they block the coupling of MIT and DIT to form T3 and T4; the serum TH decreases but the TSH is increased exaggerting the hyperplasia of the follicular cells and scant colloid
|
|
|
do thiourea and mercaptoimidazole decrease the hyperplasia of the thyroid gland?
|
no- they decrease TH but INCREASE TSH so that the hyperplasia of the follicular epithelial cells is exaggerated and the colloid remains scant
|
|
|
what is the action of high dose iodines?
|
inhibiton of proteolysis of thyroglobulin so that colloid increases within the follicles and flattens the follicular epithelium
|
|
|
what extrathyroid tissues may show morphological changes in graves?
|
heart, skeletal muscles, liver and lymphoid organs
|
|
|
gradual painless enlargement of the thyroid due to compensatory hyperplasia secondary to a defect in production or inability to secrete function TH
|
diffuse non-toxic goiter (simple or colloid)
|
|
|
in patients with goiters what is their TH status at the time of diagnosis of the goiter?
|
most are euthyroid
|
|
|
in what populations are sporatic goiters found?
|
typically in adolescent or young adult women
|
|
|
what is the presumed cause of diffuse nontoxic goiters?
|
TSH stimulation of the gland - although not all patients have high TSH levels
|
|
|
if increased TSH is not the cause of the diffuse nontoxic goiter what probably is?
|
the patient was marginally euthyroid to begin with and there was an increased demand for TH like in pregnancy; or they could be caused by introduction of goitrogens (foods or drugs)
|
|
|
what are the more rare causes of nontoxic diffuse goiters?
|
uncommon herditary defects in hormone syntehsis or transport, excess production of TBG or possible unknown - immulogic mechanism
|
|
|
describe the development of nontoxic diffuse goiters
|
initial hyperplastic stage (meaty appearance) followed by a colloid involution (gelatinous appearnce)
|
|
|
describe the hyperplastic stage of nontoxic diffuse goiter development
|
it is the initial stage where TSH stimulation causes increased follicular cell activity reflected by increased cell mass and tall columnar epithelial cells lining colloid depleted follicles = moderate diffuse enlargement of the gland; looks meaty when cut
|
|
|
what is the end result of the hyperplastic stage of nontoxic diffuse goiter development?
|
moderate diffuse enlargement of the gland which has a meaty appearance on cut surface
|
|
|
describe the colloid involution in the development of nontoxic diffuse goiters
|
as euthyroid state is reach colloid (generally thyroglobulin deficient) accumulates unevenly in follicles flattening the epithelium and enlarging the gland even further; the accumulation of colloid gives it a gelatinous appearance on cut surface
|
|
|
during the colloid involution stage of nontoxic diffuse goiter development what is the composition of the colloid?
|
it is generally thyroglobulin deficient
|
|
|
what is the end result of the colloid involution stage of nontoxic diffuse goiter development?
|
enlargment of the gland even further with accumulation of colloid that gives it a gelatinous appearance on cut surface
|
|
|
what is the end result of a long standing diffuse nontoxic goiter?
|
multinodular goiter (adenomatous goiter)
|
|
|
what can result form multinodular goiters?
|
they can cause tremendous thryomegaly - up to 1500 gm)
|
|
|
what population are multinodular goiters most often seen?
|
in older women - since they are derived from simple goiters which occur more in younger women
|
|
|
what is the thyroid state of a patient with a multinodular goiter?
|
most often euthyroid - if they are funcitonal termed toxic multinodular goiter
|
|
|
are multinodular goiters symmetrical?
|
the entire gland contains multiple nodules but the nodularity may be more prominent within one lobe so that it looks asymmetrical
|
|
|
what does scarring do to multinodular goiters?
|
irregular scarring creates nodules of varying size which in turn contain follicles of varying size and colloid content
|
|
|
what clinical symptoms are seen with multinodular goiters?
|
mass effects - stridor, dysphagia, superior vena cava syndrome; and or hyperthyroidism - les severe than in graves and not associated with eye or skin problems!
|
|
|
what can cause acute painful inlargement in multinodular goiters?
|
sudden hemorrhage
|
|
|
what is the most common type of benign neoplasm that causes solitary thyroid nodules?
|
adenomas; although lipomas and hemangiomas can occur
|
|
|
how do thyroid adenomas usually present?
|
small to moderate sized discrete nodules
|
|
|
what is a risk factor for thyroid adenomas?
|
increasing age
|
|
|
are thyroid adenomas funcitonal?
|
rarely
|
|
|
what occurs when benign neoplasms of the thyroid udnergo cystic degeneration?
|
they degenerate with replacement of solid tissue by cell debris and a thin brown fluid representing old hemorrhage
|
|
|
what are the 4 criteria for classification of a adenoma?
|
1. complete fibrous encapsulation of the nodule, 2. compression of adjacent thyroid parenchyma, 3. different histologic appearance of neoplastic and non-neoplastic tissue and 4. lack of multinodularity in the remainder of the gland
|
|
|
do thyroid ademonas have malignant potential?
|
little if any
|
|
|
what is a thyroid adenoma that is histologically distinct from the follicular adenomas that are comprised of cells having a granular eosinophilic cytoplasm similar to changes in the follicular epithelium in hashimoto's thyroiditis?
|
Hurthle cell adenomas
|
|
|
what is the most common BENIGN thyroid adenoma?
|
follicular since most arise from follicular cells
|
|
|
if a solitary thyroid nodule is found in a male is it more or less likely to be malignant?
|
more likely - althought the total incidience of solitary thryoid nodules are higher in women
|
|
|
what is a predisposing factor for malignant neoplasia of the thyroid?
|
previous radiation exposure - especially in young females
|
|
|
do goiters, adenomas, hashimoto's thyroiditis or graves disease increase the risk of malignant neoplasia of the thyroid?
|
no
|
|
|
do thyroid malignancies produce TH?
|
rarely
|
|
|
what do thyroid malignancies produce?
|
TBG - can be used to monitor for recurrence or metastases
|
|
|
what is the most common malignant thyroid neoplasm?
|
papillary adenocarcinoma
|
|
|
when do papillary adenocarcinomas usually present?
|
in young adult females but can arise at any age
|
|
|
how do papillary adenocarcinomas present?
|
as a non-tender neck mass which is very slow growing and may have been present for years
|
|
|
are most papillary adenocarcinomas functional?
|
No, generally they are not
|
|
|
can papillary adenocarcinomas show follicular elements?
|
yes - many do, a few may even be devoid of any papillary structure BUT possess characteristic nuclear changes that indicate it will behave as a papillary adenocarcinoma
|
|
|
what are the characteristic nuclear changes seen in papillary adenocarcinoma?
|
ground glass or optically clear 'Orphan Annie eye' changes
|
|
|
what should you do if you see a follicular thyroid carcinoma with ground glass or optically clear nuclei?
|
treat it as a papillary adenocarcinoma - it will behave like one
|
|
|
what should you do if you see a thyroid lesion with any element of papillary architecture?
|
consider all lesions with any papillary archeticture malignant
|
|
|
what does the diagnosis of papillary adenocarcinoma imply?
|
papillary adenocarcinomas can be multifocal (maybe intraglandular metastasis) thus in treatment you must remove the WHOLE gland, not just a lobectomy
|
|
|
how do papillary adenocarcinomas spread?
|
via lymphatics to regional lymph nodes - up to 20% of patients have cervical lymph metastases at presentation
|
|
|
when do follicular thyroid carcinomas present?
|
middle aged females
|
|
|
how do follicular thyroid carcinomas present?
|
firm irregular nodular mass which grows relatively slowly
|
|
|
what is typically seen in follicular thyroid carcinoma histology?
|
central fibrosis and areas of necrosis, hemorrhage and cyst formation
|
|
|
how do follicular thyroid carcinomas spread?
|
follicular carcinomas invade vessels and spread heatogenously to distant organs
|
|
|
what is the aggressive thyroid malignancy of older populations?
|
undifferentiated carcinoma
|
|
|
what thyroid carcinoma is a rapidly grwoing anaplastic tumor with progressive local invasion and widespreading mestastases?
|
undifferentiated carcinoma
|
|
|
what thyroid carcinoma has histology that can be anaplastic spindle cells to multinucleated giat cells?
|
undifferentiated carcinoma
|
|
|
where can undifferentiated thyroid carcinomas arise from?
|
can be de-differentiation of pre-existing low grade carcinomas
|
|
|
what thyroid carcinoma arises from parafollicular C cells?
|
medullary carcinoma
|
|
|
what thyroid carcinoma arises from cells of neural crest origin?
|
medullary carcinoma
|
|
|
what thyroid carcinoma contains cells that are round to spindle shaped and contain enuroscretory granules arranged in nests surround by a fibrovascular stroma that has amyloid in it?
|
medullary carcinoma
|
|
|
which thyroid carcinoma contains amyloid in its stroma
|
medullary carcinoma
|
|
|
what makes up the amyloid seen in medulla carcinomas?
|
altered calcitonin molecules
|
|
|
what are the strongest predictors of outcome form medullary carcinomas?
|
stage and completeness of excision
|
|
|
when do sporadic forms of medullary carcinoma present?
|
middle aged adults
|
|
|
how do sporadec forms of medullary carcinoma present?
|
painless relatively large solitary mass
|
|
|
how often do sporadic forms of medullary carcinoma mestastasize?
|
in more than half they have metastasized to lymph, lung liver or bone at the time of diagnosis - prognosis is poor
|
|
|
when are genetic forms of medullary carcinoma usually diagnosed?
|
in adolescents as part of MENs or in association with pheochromocytoma and other endocrine tumors
|
|
|
what is the cause of genetic forms of medullary carcinoma?
|
mutations in the RET proto-oncogene on chromosome 10
|
|
|
how is the genetic form of medullary carcinoma different than the sporadic in terms of size and location
|
genetic forms tend to be multicentric, bilateral and smaller than sporadic forms
|
|
|
where are the parathyroid glands derived from
|
from the pharyngeal pouches
|
|
|
what is the major secretory cell of the parathyroid?
|
chief cells - which is also the precursor of the clear (wasserhelle) cells and oxyphils
|
|
|
what are clear cells of the parathyroid?
|
cells that contain abudant cytoplasmic glycogen
|
|
|
what are oxyphil cells of the parathyroid?
|
cells that have increased numbers of cytoplasmic mitochondria
|
|
|
what happens to PTH after secretion?
|
it is cleaved to an active N terminal polypeptide with a short half life and a non-funcitonal C terminal polypeptide with a longer half life that is more easily measured
|
|
|
what is the action of PTH
|
maintians serum calcium levels by stimulating renal activation of vitamin D, increasing renal resorption of calcium and increasing secretion of potassium; and increases bone reabsorption
|
|
|
what is vitamin D synthesis dependent on?
|
UV light activity on the skin, hydroxylation by the liver and activation by the kidney
|
|
|
what is the action of vitamin D on intestinal mucosa
|
increases calcium absorption
|
|
|
what can happen if hyperparathyroidism is left untreated?
|
nephrocalcinosis and renal stones, bone demineralization (osteomalacia), osteitis fibrosa cystica; and psychiatric disturbances, neurologic abnormalities and muscle weakness; peptic ulcers, pancreatitis and abdominal pains
|
|
|
what adverse effects can occur due to hyperparathyroidism?
|
HTN, chondrocalcinosis and metastatic calcification of soft tissues
|
|
|
what is the most frequent cause of hyperparathyroidism?
|
adenoma usually monoclonally of chief cells
|
|
|
what is the gross appearance of parathyroid adenomas?
|
encapsulated, soft, yellow-tan nodule
|
|
|
are parathyroid adenomas usually functional or non functional?
|
almost always functional
|
|
|
are parathyroid adenomas usually solitary or multifocal?
|
usually solitary
|
|
|
which glands are more likley involved in parathyroid adenomas?
|
inferior glands
|
|
|
which population are parathyroid adenomas more common in?
|
slightly more common in females
|
|
|
which glands are usually affected in primary hyperplasia of the parathyroid gland?
|
all four glands are affects but not necessarily equally - superior glands tend to be affected more
|
|
|
what is the most common cell type found in primary hyperplasia of the parathyroid?
|
chief cell proliferation with occiasional clusters of oxyphils that tend to crowd out the native fat cells
|
|
|
do the less common clear cell hyperplasias of the parathyroid tend to be smaller or larger than their chief cell cousins?
|
larger
|
|
|
what do you do if there is a single gland that is hard to distinguish between hyperplasia or adenoma?
|
you need to biopsy another gland - if there is hyperplasia treat as hyperplasia. Important because exision of a solitary adenoma is curative whereas excision of a solitary hyperplasia without looking at the other glands will continue to have increased PTH because they other glands will be hyperplastic
|
|
|
what are the growth characteristics and invasiveness of carcinomas of the parathyroid?
|
generally they are slow growing and eventually regionally invasive
|
|
|
describe the histology of carcinomas of the parathyroid
|
they show cytologic atypia with increased mitosis and may demonstrate capsular or vascular invasion; best criteria for malignancy is metastasis - but distant metastasis is uncommon with this neoplasia
|
|
|
compensatory hyperplasia of the parathyroid gland in response to chronic hypocalcemia and hyperphosphatemia
|
secondary hyperparathyroidism
|
|
|
is the hyperplasia seen in secondary hyperparathyroidism reversible?
|
yes - if the underlying cause is correct within a reasonable period
|
|
|
are the glands larger or smaller in secondary hyperparathyroidism vs hyperplasia in primary hyperparathyroidism?
|
usually smaller
|
|
|
what causes tertiary hyperparathyroidism?
|
persistance of the underlying cause of secondary hyperparathyroidism causing irreversible changes in the gland which leads to autonomaticity of the gland
|
|
|
what are the lab values of tertiary hyperparathyroidism?
|
hypercalcemia in the face of high PTH
|
|
|
low PTH, hypocalcemia, hyperphosphatemia
|
hypoparathyroidism
|
|
|
can you have elevated PTH levels in hypoparathyroidism?
|
yes - if the PTH is non-functional or if there is end organ unresponsiveness PTH can be normal or elevated
|
|
|
what is the most common cause of hypoparathyroidism?
|
inadvertent removal of the parathyroid glands during thyroidectomy or radical neck dissection
|
|
|
weakness, paresthesias, muscle cramps/tetany, cataracts, headache, abdonimal pain
|
hypoparathyroidism
|
|
|
what disease results in end organ unresponsiveness to PTH?
|
psuedohypoparathyroidism
|
|
|
do parathyroid tumors usually cause mass effects
|
no, even they largests ones just aren't big enough
|
|
|
where is the adrenal cortex derived from?
|
mesodermal cells of the urogenital ridge
|
|
|
what is the gross appearance of the adrenal cortex?
|
yellow-brown due to lipochrome pigments and the lipid precursors (primarily chosterol and cholesterol esters) of the steroid hormones
|
|
|
what is the outer layer of the adrenal cortex?
|
zona glomerulosa
|
|
|
what is the histology of the zona glomerulosa?
|
clusters of cuboidal cells with dark nuclei and scanty cytoplasm contianing few lipid droplets
|
|
|
what hormone does the zona glomerulosa produce?
|
mineralocorticoids (aldosterone)
|
|
|
what is the action of mineralocorticoids?
|
it acts on the kidney to promote secretion of potassium and retention of sodium and water
|
|
|
how is mineralocorticoid secretion regulated?
|
primarily by serum potassium levels and the renin-angiotensin system = under normal conditions they do not respond direclty to ACTH!
|
|
|
what is the middle layer of the adrenal cortex?
|
zona fasiculata
|
|
|
what is the histology of the zona fasiculata?
|
columns of cells with dark nuclei and finely vacuolated clear cytoplasm containing lipid precurors of the steroid hormones
|
|
|
what is the inner layer of the adrenal cortex?
|
zona reticularis
|
|
|
what is the histology of the zona reticularis?
|
irregular clusters of darkly staining 'compact' cells with cytoplasmic lipochrome pigment but NO vacuoles
|
|
|
what do the zona reticularis and zona fasiculata produce?
|
they work in tandem to produce glucocorticoids and androgenic steroids
|
|
|
what happens to the zona fasiculata during times of increased production?
|
the zona fasciculata decreases in thickness due to cytoplasmic lipid depletion while the zona reticularis increases in thickness due to increased production. Thus - the zona fasiculata stores the precursors to be made into steroids in the zona reticularis
|
|
|
what is the action of glucocorticoids?
|
increase appetitie and promote fat deposition in the face, neck and trunk; increases protein breakdown and nitrogen excretion; increases gluconeogenesis in the liver but inhibits glucose uptake in the muscles; impairs inflammatory responses by inhibiting leukocyte marginationa nd pavementing and by inhibiting phagocytes, lyses T cells and increases the ECF volume by interferring with water transport into cells
|
|
|
what is the function of the androgenic steroids
|
promote masculinization and inhibit feminization
|
|
|
how are the zona fasiculata and zona reticularis controlled?
|
by ACTH secretion from the pituitary which is undercontrol of CRH secretion from the hypothalamus
|
|
|
what is the most common cause of cortical hyperplasia?
|
pituitary hypersecretion of ACTH = thus affects bilaterally and adrenals may show multiple hyperplastic nodules in the cortex
|
|
|
are most adrenal cortical adenomas functional or nonfunctional?
|
most are non-functional
|
|
|
what is the gross appearance of adrenal cortial adenomas?
|
expanding yellow-orange nodules of varying size
|
|
|
what types of cells are found in adrenal cortical adenomas?
|
usually lipid laden cells resembling those of the zona fasiculata admixed with a few cells resembling those of the zone reticularis
|
|
|
are adrenal cortical carcinomas aggressive?
|
yes, they are extremely malignant - although rare
|
|
|
are adrenal cortical carcinomas usually functional or nonfunctional?
|
most are functional - despite this they are usually large and infiltrative when first discovered
|
|
|
how do adrenal cortical carcinomas spread?
|
they invade veins and lymphatics and can disseminate widely
|
|
|
when does cushing's usually present
|
in middle aged females
|
|
|
what does the diagnosis of cushing's require
|
elevated cortisol levels
|
|
|
low serum ACTH, high cortisol, bilateral nodular hyperplasia of the adrenal cortex. What is the cause?
|
primary cushings - mediated by something other than ACTH stimulation
|
|
|
high cortisol, low ACTH, one adrenal cortex is atrophied. What is the cause?
|
primary cushings due to a cortisol secreting cortical neoplasia
|
|
|
what will happen to the adrenals in secondary cushings?
|
bilateral diffuse or nodular adrenal coritcal hyperplasia with the zona reticularis and to a lesser extent the zona fasiculata is expanded
|
|
|
high cortisol, low ACTH bilateral adrenal cortex atrophy. What is the cause?
|
Cushings syndrome caused by iatrogenic cortisol
|
|
|
which layers are most atrophied due to iatrogenic cushing syndrome?
|
mostly the zona fasiculata and zona reticularis
|
|
|
are neoplasms that secrete androgens more likely to be carcinomas or adenomas?
|
carcinomas
|
|
|
hypernatremia, hypertension, hypokalemia, hypokalemic alkalosis and increased urine potassium
|
excess mineralocorticoids
|
|
|
what is the consequence of hypokalemia?
|
cardiac arrhythmias
|
|
|
what is the most common cause of Conn's syndrome?
|
aldosterone secreting cortical adenoma
|
|
|
what causes Conn's syndrome in childhood?
|
idiopathic bilateral adreanl hyperplasia
|
|
|
inisidious onset of weakness, fatigue, anorexia, weight loss, nausea and vomiting, hypotension and hyperpigmentation
|
addison's disease
|
|
|
what eventually happens to serum chemistry in addison's disease?
|
increase in serum potassium - decrease in serum sodium, bicarbonate, chloride and glucose
|
|
|
what happens to cortisol levels in addison's disease?
|
decreased serum and urine cortisol
|
|
|
what must be demonstrated to diagnose addison's disease?
|
lack of adrenal response to ACTH stimulation must be demonstrated
|
|
|
what are the two causes of primary adrenal insufficiency?
|
idiopathic atrophy and destructive/infiltrative processes
|
|
|
what is the mechanism behind idiopathic atrophic seen in addison's disease?
|
probably autoimmune in origin, can occur as isolated disease or as part of a spontaneously or inherited clinical syndrome
|
|
|
What is the cause of Type 1 addison's disease related syndrome
|
Type 1 may be a defect in T suppressor cell function. Causes addison's disease, hypoparathyroidism, mucocutaneous candidias or other autoimmune diseases
|
|
|
what diseases can be cause by Type 1 addision's disease related syndrome
|
addison's disease, hypoparathyroidism, mucocutaneous candidias or other autoimmune disorders
|
|
|
what is type 2 addisons related disease syndrome (Schmidt's syndrome)
|
it is associated with HLA-A1 and HLA-B8 haplotypes; causes - addison's disease, autoimmune thyroid disease and or insulin dependent diabetes
|
|
|
what is the gross appearance of the adrenal glands in idiopathic addison's disease?
|
the glands are small with a thin, atrophic cortex draped around a relatively normal appearing medulla
|
|
|
what is the histology of idiopathy atrophy of the adrenal glands?
|
atrophic and degereated cortical cells, foci of fibrous scarring and variable lymphocytic infiltrate
|
|
|
what do many patients with idiopathic atrophy of the adrenal glands have?
|
autoantibodies to adrenal antigens
|
|
|
what are the destructive processes that can cause addison's disease?
|
infection - TB and histoplasmosis; metastatic tumors - frequently from lung stomach and breast; amyloidosis, hemosiderosis
|
|
|
what is the gross and microscopic appearance of the adrenal glands with destructive/infiltrative processes?
|
the glands are usually enlarged but micoscopically show extensive cortical destruction
|
|
|
what is the cause of secondary adrenocortical insufficiency?
|
decreased ACTH secretion from the pituitary due to any cause
|
|
|
what is different between secondary and primary adrenocortical insufficiency?
|
in secondary there is no hyperpigmentation of the skin and the zona glomerulosa is normal and no signs of hypoaldosteronism
|
|
|
what must be demonstrated to diagnose secondary adrenocortical insufficiency?
|
the capacity of the adrenals to respond ot exogenous ACTH
|
|
|
an addison's patient who experiences sudden stress which leads to hypotension, shock and vascular collapse
|
addisonian crisis
|
|
|
what are the 3 types of acute adrenocortical insufficiency?
|
addisonian crisis, iatrogenic abrupt withdrawal and hemorrhage
|
|
|
what usually causes hemorrhage that results in acute adrenocortical insufficiency?
|
usually the result of trauma - especially in newborns!
|
|
|
what are the causes of hemorrhage that results in acute adrenocortical insufficiency?
|
truama, anticoagulant thearpy, DIC, bacteremia (Waterhouse-Friderichsen syndrome)
|
|
|
what cause of acute adrenocortical insufficiency would be seen with a fever and petechia and purpura?
|
Hemorrhage caused by Waterhouse-Friderichsen syndrome (bacteremia)
|
|
|
what are neuroendocrine cells?
|
diffuse endocrine system cells
|
|
|
what are APUD (amine precursor uptake and decarboxylation) cells?
|
diffuse endocrine system cells
|
|
|
how are neuroendocrine cells stimulated to become neoplastic?
|
some cells are secondarily programmed by neural crest and or that non-endocrine tissues that are undergoing neoplastic transformation develop the capability to express polypeptide hormones by gene rearrangment or 'derepression' of a pre-existant gene
|
|
|
what are the metabolites of catecholamines that may appear in the urine when a catecholamine expressing tumor is present?
|
metanephrine, normetanephine, vanillylmandelic acid (VMA) and homovanillic acid (HVA)
|
|
|
where do neuroblastomas most often arise?
|
adrenal medulla or posterior mediastinum
|
|
|
what is the gross appearance of neuroblastomas?
|
bulky soft tumors with areas of hemorrhage and necrosis; MAY have calcification = radiological clue
|
|
|
Homer-Wright roseetes
|
neuroblastoma
|
|
|
Which age groups sees neuroblastomas that have metastasized?
|
those discovered after the age of 2 - propensity to metastazied to bone marrow and liver. Before 2 they are usually localized
|
|
|
histology: small round cells with scant cytoplasm and hyperchromatic nuclei which tend to grow in a disorganized manner
|
neuroblastoma
|
|
|
what can occur in neuroblastomas in children less than 2?
|
they can mature into ganglioneuroblastomas or ganglioneruomas or rarely spontaneously regress (even with metastases but excluding those with bone marrow metastases)
|
|
|
how do neuroblastomas present?
|
symptoms associated with rapid tumor growth or the effects of metastases - weight loss, abdominal mass, maliase
|
|
|
what do most neuroblastomas secrete?
|
NE
|
|
|
is hypertension seen in neuroblastomas?
|
rarely even though they secrete NE
|
|
|
which endocrine tumor is a surgically correctable cause of HTN?
|
pheochromocytoma
|
|
|
what is the progressive sequence of pheochromocytomas?
|
diffuse hyperplasia - nodular hyperplasia - neoplasm
|
|
|
what is the rule of 10's for pheochromocytomas?
|
10% extra-adrenal, 10% bilateral, 10% malignant, 10% inherited as MEN
|
|
|
what is the most likley extra adrenal location of pheochromocytomas?
|
below the diaphragm in the periarotic ganglia or the organ of Zuckerkandl (bifurcation of the aorta)
|
|
|
what is the gross appearance of most pheochromocytomas?
|
most are roudna nd well demarcated from the surrounding adrenal tissue
|
|
|
what is the histology of pheochromocytomas?
|
tumor cells may be highly pleomorphic but generally have abundant cytoplasm containing granules of stored catecholamines and are arranged in trabecular or alveolar patterns with rich vascularity and thin fibrous stroma
|
|
|
what patterns are cells of pheochromocytomas arranged in?
|
trabecular or alveolar patterns with rich vascularity and thin fibrous stroma
|
|
|
what happens if you poke a pheochromocytoma?
|
it can have acute release of catecholamines - attacks of HTN, diaphoresis, anxiety, nausea and vomiting, abdominal pain, tremors or worse MI or CVA
|
|
|
urinary catecholamines: metanephrine and VMA elevated
|
pheochromocytoma
|
|
|
what are the locations of parasympathetic SNS?
|
carotid body, glomus jugulare, aortic body
|
|
|
parasympathetic or aorticosympathetic: carotid body tumors
|
parasympathetic
|
|
|
parasympathetic or aorticosympathetic: glomus jugulare tumors
|
parasympathetic
|
|
|
parasympathetic or aorticosympathetic: aortic body tumors
|
parasympathetic
|
|
|
parasympathetic or aorticosympathetic: retroperitoneal paragangliomas
|
aorticosympathetic
|
|
|
parasympathetic or aorticosympathetic: extradrenal pheochromocytomas
|
aorticosympathetic
|
|
|
which tumors are more likely to be functional: parasympathetic or aorticosympathetic?
|
aorticosympathetic
|
|
|
are paraganglion cell tumors generally benign or malignant?
|
benign, but some can reculr locally; rarely they metastasize widely
|
|
|
do merkel cell tumors metastasize usually?
|
they can disseminate widely and are fatal 15-20% of cases
|
|
|
where can enterochromaffin cell tumor be found?
|
most frequently in respiratory or GI tracts. Can be in esophagus, stomach, biliary tract, pancreas, ovaries and urinary tract
|
|
|
what is the histology of enterchromaffin cell tumors?
|
nests, strands or sheets of small monotonous cuboidal cells which penetrate the submucosa and tend to invade the deeper tissues
|
|
|
what are the symptoms of enterchromaffin cells?
|
may be asymptomatic; symptoms related to local invasion or obstruction (due to desmoplastic tissue response to the neoplasm), or due to elaboration of secretory products
|
|
|
what is the metastases potential of the enterochromaffin cell tumors?
|
it is related to site or origin, depth of penetration and size of the tumor
|
|
|
enterochromaffin cell tumors originiating in the appendix: benign or malignant?
|
benign
|
|
|
enterochromaffin cell tumors originiating in the rectum: benign or malignant?
|
benign
|
|
|
enterochromaffin cell tumors originiating in the small bowel: benign or malignant?
|
malignant with metastases to regional lymph nodes or the liver at the time of diagnosis
|
|
|
enterochromaffin cell tumors originiating in the stomach: benign or malignant?
|
malignant with metastases to regional lymph nodes or the liver at the time of diagnosis
|
|
|
metastatic liver involvement from intestinal carcinoids or from extraintestinal carcinoids
|
carcinoid syndrome
|
|
|
vasomotor disturbances, intestinal hypermobility, bronchocontriction, cardiac involvement, hepatomegaly
|
carcinoid syndrome
|
|
|
what mediates the symptoms of carcinoid syndrome?
|
tumore secretion of serotonin, histamine and kinins
|
|
|
what is the prognosis for carcinoid syndrome
|
usually fatal
|
|
|
what cells secrete VIP?
|
D1 cells in the pancreas
|
|
|
are insulinomas solitary or mutliple?
|
usually solitary
|
|
|
round, firm, encapsulated nodules composed of nests and cords of normal appearing beta cells
|
insulinomas
|
|
|
are insulinomas benign or malignant?
|
benign - only 10% are malignant
|
|
|
are the malignant insulinomas more or less hormonally active?
|
more
|
|
|
hypoglycemic episodes that can cause stupor or loss of consciousness that are temporally related to periods of high glucose utalization (fasting, exercise)
|
insulinomas
|
|
|
where is the most common location for gastrin secreting tumors outside of the pancreas?
|
duodenum
|
|
|
gastric acid hypersecretion
|
gastrinomas
|
|
|
hyperplasia of gastric parietal cells
|
gastrinomas
|
|
|
in addition to ulcers what occurs with gastinomas?
|
fluid and electrolyte disturbances secondary to diarrhea and malabsorption
|
|
|
are gastrinomas benign or malignant?
|
50% are malignant - most at the time of diagnosis
|
|
|
what is MEN1 frequently associated with?
|
Zollinger Ellison syndrome
|
|
|
where do the mucocutaneous neuromas of MEN2B usually occur?
|
around the lips
|
|
|
which is more aggressive MEN2A or MEN2B?
|
MEN 2B
|
|
|
Which chromosome is MEN type 2 linked to?
|
chromosome 10
|
|
|
what two sites can be involved in MEN type 1 but aren't as commonly involved?
|
thyroid and adrenal cortex
|
|
|
what correlates with serum prolatin levels in prolatinomas?
|
prolactin levels correlate with the size of the tumor
|
