Endo - FA Patho p 333 - 347 Flashcards
High-dose dexamethasone suppression test causes what in Cushings dx?
Free cortisol suppression
How many mg is administred during High-dose dexamethasone test?
8mg - high dose
3 causes for inc cortisol?
- Exogenous corticosteroids - Primary adrenal adenoma, hyperplasia, or carcinoma - ACTH-secreting pituitary adenoma, paraneoplastic ACTH
Difference between Cushing syndrome and disease?
ACTH-secreting pituitary adenoma - C. disease incr Cortisol from variety of conditions - C. syndrome
2 paths causing paraneoplastic secretion of ACTH?
small cell lung cancer, bronchial carcinoids
Is adrenal tumor an ACTH-independent or dependent Cushing syndrome?
ACTH independent Cushing syndrome
Is ectopic ACTH secretion an ACTH-independent or dependent Cushing syndrome?
ACTH dependent
CRH stimulation test helps diagnose which pathology?
Cushing disease (inc ACTH) vs ectopic ACTH secretion (no inc of ACTH)
What an alternative test used to dx adrenal insufficiency?
Metyrapone stimulation test
Metyrapone blocks which step of cortisol synthesis?, What is normal response to it
The last one - 11DOC (deoxycortisol) –> cortisol. Normal response is dec cortisol and compensatory inc in ACTH, 11DOC. If they dont INC, then its a primary/secondary ACTH insufficiency, not a cortisol issue
Pt presents w/ sudden onset of massive hemorrhage and shock. What is the adrenal path?
Primary Acute adrenal insufficiency or Waterhouse-Friderichsen syndrome
Competitive athlete on school break shows signs of adrenal insufficiency, which type is his pathology?
Tertiary - chronic exogenous steroid use precipitated by abrupt withdrawal
skin and mucosal hyperpigmentation is seen in which type of adrenal insuff.?
primary
Why can Cushing lead to coronary a disease?
Inc cortisol –> inc stimulation of a1R on arterioles –> hypertension –> CAD
Cause of truncal obesity and buffalo hump in Cushing?
Inc cortisol –> glucose in blood –> deposit in fat, leading to inc fat deposition on face, trunk, back
Most accurate test for Cushings?
Los dose dexamethasone suppression test
Different pathological features of adrenal cortex with ACTH independent and dep Cushing?
In ACTH independent - atrophy in ZF, ZR In ACTH dep (Bilat adrenal hyperplasia) - ZF and ZR are diffuse, nodular
TB can cause what kind of adrenal insuff?
Chronic—aka Addison disease. Due to adrenal atrophy or destruction by disease
— is a byproduct of ACTH production from —-.
MSH pro-opiomelanocortin
In which type of Adrenal insuff. is Aldosterone synthesis unaffected?
2ndary and tertiary
Primary adrenal insuff. is associated with which autoimmune syndromes?
Polyglandular syndromes
Septicemia in Waterhouse Friderichsen is usually caused by what pathogen?
Neisseria
Which adrenal insuff. spares the skin and mucosa? and why?
Tertiary and Secondary, because there is a decr in ACTH production –> less MSH by product
What is the MC tumor of the adrenal medulla in children?
Neuroblastoma
Classic histology presentation of Neuroblastoma:
Homer-Wright rosettes and small, round, blue/purple nuclei
2 path from neural crest?
Neuroblastoma Pheochromocytoma
Homovanillic acid (HVA) a breakdown product of?
Dopamine
Signs of primary adrenal insuff?
Hypotension (hyponatremic volume contraction), Hyper Kalemia, metabolic acidosis, skin and mucosal hyperpigmentation
—- is a breakdown product of norepinephrine.
vanillylmandelic acid (VMA)
“dancing eyes-dancing feet” are seen in?
Neuroblastoma, Subacute sclerosing panencephalitis. - opsoclonus & myoclonus
Name episodic hyperadrenergic symptomsof pheochromocytoma (5 P’s):
Pressure (incr BP) Pain (headache) Perspiration Palpitations (tachycardia) Pallor
T or F? Wilms tumor can cross the midline vs. Neuroblastoma which is smooth and unilateral.
F - opposite
Why is α-blockade administred in Pheochromocytoma before giving β-blockers prior to tumor resection?
to avoid a hypertensive crisis.
What % of Pheo’s calcify and why?
10% bc of inc in pTrp
Neuroblastoma has an overexpression of which oncogene?
N-myc
What malignancy is associated with c-myc (as opposed to n-myc)
Burkitt’s lymphoma
What is a typical histology of Pheochomocytoma?
enlarged pleomorphic nuclei, typical of malignancy.
2 tumor markers for Neuroblastoma?
Bombesin and neuron specific enolase
Name one path that use Bombesin and neuron-specific enolase as tumor markers?
Lung cancer (bronchial carcinoid)
Homer Wright rosettes also seen in what other path?
Medulloblastoma
Urine and plasma findings is Pheochromocytoma?
catecholamines and metanephrines in urine and plasma.
Which thyroid disorder is associated with Inc CK?
Hypothyroidism - myopathy (Normal Ck in Hyper)
Which thyroid disorder is associated with thinning, fine hair?
hyperthyroidism
Thyroid disorder with inc #/sensitivity of B adr receptors?
Hyperthyroid
Causes of smooth/diffuse goiter?
Graves, Hashimoto, Iodine def, TSH secreting pit adenoma
Causes of nodular goiter?
Toxic multinodular goiter, Thyroid adenoma, Thyroid cancer, Thyroid cyst
HLA # associated with Hashimoto’s?
HLA - DR3; HLA-DR5
Which thyroid disorder is assoc w/ non Hodgkin Lymphoma?
Hashimoto
Most common cause of thyroid disgenesis?
Congential hypothyroid (Cretinism)
Neck and jaw pain is assoc with which thyroid disorder?
Subacute granulomatous thyroiditis - jaw pain, very tender thyroid
Which disease is assoc with a rock like painless goiter? Why rock-like? (patho)
Riedel thyroiditis - thyroid replaced with fibrous tissue w/ inflammatory infiltrate.
What is the Wolff Chaikoff effect?
Thyroid gland will downregulate in response to inc iodide
Graves disease has what type of Ig, HS?
HS-II, IgG
The release of cytokines in the retroorbital space leads to secretion of _____ by _____ cells? (Eventually resulting in exophthalmus in Graves)
Inc secretion of hydrophilic GAGs by fibroblasts
focal patches of hyperfunctioning follicular cells = which thyroid disease?
Toxic multinodular goiter
Tall follicular epithelial cells with scalloped colloid is seen in which thyroid disease?
Graves
Tx for Thyoid Storm?
Propranolol (Nadolol), Propylthiouracil, Corticosteroids, Potassium Iodide
Jod-Basedow phenomenon
If a patient that is previously iodine deficient and has partially autonomous thryroid tissue, is then made iodine replete —> thyrotoxicosis
Most common histology of thyroid adenoma?
follicular - with no capsular or vascular invasion
Why is thyroid cancer treatment associated with hypocalcemia?
Due to surgery leading to possible removal of parathyroid glands
Which two Thyroid cancers are associated with Ret mutation?
Papillary CA and MEN 2A & 2B (medullary CA)
Empty appearing nuclei with a central clearing and nuclear grooves - which Thyroid disease?
Papillary (Orphan Annie eyes)
Which thyroid cancer stains with Congo Red?
Medullary CA - sheets of cells in amyloid stroma
High PTH and low Ca is which Parathyroid disordeR?
2ndary Hyper PTH - vitamin D def, chronic renal failure
Low Ca and Low PTH?
Primary HypoPTH
High Ca and low PTH?
PTH indep hyper Calcemia - excess intake of Ca, cancer, hyper vitaminosis D
Which endocrine disorder is associated with carpal spasm when one takes blood pressure?
HypoPTH - Trousseau sign
Which endocrine disorder is assoc with shortened 4th/5th digits, and short stature?
Pseudohypoparathyroidism type 1A
Which parathyroid disease is associated with a defective Gs protein alpha subunit ?
Psuedohypoparathyroidism type 1A and Pseudopseudohypoparathyroidism
Which parathyroid disorder is associated with maternal imprinting? paternal imprinting?
Pseudohypoparathyroidism 1A - mother Pseudopseudohypoparathyroidism - father
Which endocrine disorder is associated with a defective Ca 2+ sensing receptor?
Familial hypocalciuric hypercalcemia
Which endocrine disorder is assoc with constipation, and flank pain?
Primary hyperparathyroidism
Inc cAMP in urine is seen with which endocrine disordeR?
Primary Hyperparathyroidism
The cystic bone lesions are filled with brown tissue made of what?
Osteoclasts and deposited hemosiderin from hemorrhages
Most common manifestations of a pituitary adenoma?
Prolactinoma - galactorrhea, amenorrhea
Hyperpigmentation, headaches, and bitemporal hemianopsia is associated with which endocrine disorder?
Nelson syndrome
Major causes of hyperparathyroidism?
Pit adenoma, hyperplasia
Which parameters increase with primary hyperparathyroidism?
calcium (se and urine), inc PTH, inc ALP, inc urinary cAMP
In Osteitis fibrosa cystica, what are the cystic bone spaces filled with?
filled with brown fibrous tissue - brown because of deposited hemosiderin from hemorrhage
Presentation of hyperparathyroidism?
weakness, constipation, abdominal/flank pain ( kidney stones, acute pancreatitis) depression
Most common cause of secondary hyperparathyroidism? What sets it apart from other causes?
chronic renal disease, will show hyperphosphatemia (other causes = hypophosphatemia)
Pituitary adenomas are most often associated with the increase of what hormone?
PRL - sx/ amenorrhea, galactorrhea, low libido, infertility
Treatment for prolactinoma
- Dopamine agonist - Bromocriptine, Cabergoline 2.Transsphenoidal resection
Which test is associated with acromegaly to Dx?
Inc serum IGF-1 ; failure to suppress serum GH following oral glucose tolerance test
What is increased in serum with acromegaly?
IGF-1
Which two drugs are used in acromegaly and mech of action?
Octreotide - somatostatin analogue (-) GH release Pegvisomant - ( GH-R inhibitor - “Put a peg in that viisible growth, man”)
Secondary Nephrogenic DBI is associated with which drugs?
Lithium, Demeclocycline (ADH antagonist)
Difference in lab values with Central v Nephrogenic DBI?
Central - dec ADH, increase in urine osmo with ADH analogue Nephrogenic - normal ADH , no change in urine osm with ADH analogue
3 drugs used to treat Nephrogenic DBI?
HCTZ, Indomethacin, Amiloride
4 major causes of SIADH?
Ectopic (Small cell lung cancer) CNS disorders/head trauma Pulm disease Drugs (“Lungs, and brain, and drugs, and cancer)
Which endocrine disorder is associated with large tongue ,odor, spaces between the teeth?
Acromegaly - tongue has deep furrows, have big sweat glands and are prone to odor, and have spaces between teeth Other poss q stem sx/ arthritis, gout, large toes/fingers/nose/head, impaired glucose tolerance, polyps, thick neck, coarse facial features, carpal tunnel, cardiomegaly
What is the carrier protein for ADH?
Neurophysin
Failing to correct sodium levels slowly in SIADH leads to what pathology?
Osmotic demyelination syndrome
Why do you not see edema, rales, or JVD in SIADH?
It’s a euvolemic condition, only Na is decreased in the body, urinating out a ton of Na, while retaining H2O
What is ischemic infarct of the pituitary associated with?
postpartum bleeding
Most common presentation of Sheehan syndrome?
failure to lactate (Opp of GH-oma) and loss of pubic hair Other sx/dec T4, 24hr cortisol,
Most common cause of death in Diabetes mellitus?
MI - when associated with large vessel atherosclerosis
Osmotic damage in DB associated with?
increased sorbitol in organs with aldose reductase or dec/no sorbitol DH
HLA associations of T1DB?
DR3 DR4
What type of deposits are seen in islet cells in T2DB?
amyloid polypeptide
leukocyte infiltration is seen in islets of which type of diabetes?
T1DB
Most common infection precipitating diabetic ketoacidosis? Most common infection as a result of it?
UTI, mucormycosis
Inc c peptide levels associated with which Dx?
Insulinoma
Most common malignancy in SI?
Carcinoid syndrome
Why are high levels of 5-HT not seen in carcinoid syndrome localized in GI?
Undergoes first pass metabolism
Which vitamin deficiency is associated with carcinoid syndrome?
niacin - pellagra
What marker is increased in the urine with carcinoid syndrome?
5-HIAA
Which side of the heart is affected in carcinoid syndrome (valves)?
R sided valvular disease
Increased gastrin secretion from a tumor can be localized in which two areas?
Pancreas and duodenum
A gastrin secreting tumor is associated with which endocrine neoplasia?
MEN I
proliferation and hyperplasia of parietal cells leading to increase mass of fundic glands is assoc with which dx?
Z-E syndrome
Why is Z-E syndrome associated with diarrhea?
Bc inc gastric acid will inhibit digestive enzmes, cant digest nutrients
Increased risk of colorectal polyps and cancer in which endocrine cancer?
Acromegaly
Mech of action of Pegvisomant? Is Tx for which disease?
GH-R antagonist, Acromegaly
Which endocrine disorder is associated with saddle nose, prominent forehead, and small genitalia?
Laron syndrome
Which drugs are associated with Nephrogenic DBI?
Lithium, Demeclocycline
Tx for Nephrogenic DBI?
HCTZ, Indomethacin, Amiloride
Tx for SIADH?
- Fluid restriction
- Salt tablets
- IV hypertonic
- saline diuretics
- Rx/ Conivaptan Tolvaptan Demeclocycline
Failure to lactate, absent menstruation, cold intolerance
Sheehan syndrome
unopposed secretion of GH and Epi can cause what endocrine disorder?
DB
Why is there retinopathy/nephro/neuropathy with DB?
Due to nonenzymatic glycosylation in small vessels
Osmotic damage in DB due to?
sorbital accumulation in organs with aldose reductase or dec/absent sorbitol DH
What level of fasting plasma glucose is Dx for DB?
>126 mg/dL
What level for the 2 hr oral glucose tolerance test is Dx for DB?
> 200 mg/dL
Why can you potentially see vomiting with insulin def?
inc lipolysis –> inc ketogenesis, ketonemia –> vomiting
What type of metabolic issue with insulin def?
anion gap metabolic acidosis
HLA # for T1DB?
HLA DR3 DR4
Autoimmune destruction of Beta cells due to?
glutamic acid decarboxylase Ab
Sx of DB ketoacidosis?
Delirium, Kussmaul respirations, Abdom pain, n/v, dehydration, fruity breath odor
Infectious complication of DB ketoacidosis?
Rhizopus - mucormycosis
What is seen with elderly T2Db?
hyperglycemia induced dehydraion and inc serum osmo (Hyperosm hyperglycema non ketotic syndrome)
Glucose level in hyperosmolar hyperglycemic state?
>600 mg/dL
Serum Osmo level in hyperosmolar hyperglycemic state?
>320mOsm/kg
Pt with migratory erythema, hypergylcemia, DVT, weight loss, depression?
Glucagonoma
Whipple triad? in what Disease?
Low blood glucose Sx of hypoglycemia - lethargy, syncope, diplopia resolution of Sx with normalizing of glucose levels Seen in Insulinoma
10% of Insulinoma is associated with what, along with ZE syndrome?
MEN I
Pt with DB or glucose intolerance, steatorrhea, gallstones ?
Somatostatinoma
Cell type of carcinoid tumor?
neuroendocrine cells
Why are sx of Carcinoid not seen if tumor is in GI?
5-HT goes through first pass metabolism
Cardiac issue with carcinoid syndrome?
R side valvular disease - TR, Pulm stenosis
Lab test in carcinoid
5-HIAA Hydroxyindoleacetic acid
Dermatitis, diarrhea, and dementia seen in which endocrine disorder?
Carcinoid syndrome –> niacin Def
Definitive Dx of ZE syndrome?
Gastrin levels stay elevated after admin of secretin (would dec Normally)
Which thyroid disorder is associated with Inc CK?
Hypothyroidism - myopathy (Normal Ck in Hyper)
Which thyroid disorder is associated with thinning, fine hair?
hyperthyroidism
Thyroid disorder with inc #/sensitivity of B adr receptors?
Hyperthyroid
Hyperpigmentation, headaches, and bitemporal hemianopsia is associated with which endocrine disorder?
Nelson syndrome
3Ps for MEN1?
Parathyroid tumors Pituitary tumors (prolactin or GH) Pancreatic endocrine tumors (Zollinger Ellison syndrome, insulinomas, VIPomas, glucagonomas)
what gene is associated with MEN1?
MEN1 gene (menin, tumor suppressor) on chromosome 11
what MEN is associated with RET gene
MEN2A and MEN2B
What does RET gene code for?
Receptor Tyrosine kinase
symptoms of VIPomas?
WDHA Watery Diarrhea, Hypokalemia, and Achlorhydria
what path is associated with dermatitis (necrolytic migratory erythema), diabetes, DVT, and depression?
glucagonoma (also associated with MEN1)
2Ps of MEN 2A?
Parathyroid hyperplasia Pheochromocytoma
1P of MEN 2B?
Pheochromocytoma
what MEN is associated with medullary thyroid carcinoma?
MEN2A, 2B
which MEN is associated with mucosal neuromas (oral/intestinal ganglioneuromatosis)
MEN 2B
which multiple endocrine neoplasia is associated with marfanoid habitus?
MEN2B
