Flashcards in Path: Adrenal & Pancreas Deck (47):
What causes most cases of Cushing syndrome?
iatrogenic (exogenous) - drugs force pituitary through negative feedback to reduce ACTH, ZF and ZR atrophy
too much cortisol, not necessarily too much ACTH
Other than pituitary adenoma, what can cause Cushing dz?
corticotroph hyperplasia w/o a mass - pituitary defect or hypothalamus releasing excess CRH
What would the adrenals look like in Cushing dz?
hyperplastic ZF and ZR, compressed ZG, unaffected medulla
maybe nodules, brown or yellow cortical thickening
larger, more vacuolated cells
What findings are present in both primary adrenocortical hyperplasia and neoplasia?
elevated cortisol with low ACTH
What are the characteristics of primary (bilateral) adrenal hyperplasia?
micronodular or macronodular
micronodular - familial, pigmented adrenal nodules, large cortical cells
What are the characteristics of adrenocortical neoplasia?
benign or malignant
almost always unilateral
encapsulated, yellow to black
What are the more common non-endocrine neoplasms that make ACTH?
SCC of lung
medullary thyroid carcinoma
pancreatic islet cell tumors
can release CRH, ACTH or mimics = paraneoplastic syndrome
What are some of the normal effects of glucocorticoids?
makes glucose, inhibits insulin action
liver gluconeogenesis and protein catabolism
anti-inflammation and stress protection
mineralocorticoid-like effects (due to shared receptor)
What are the clinical manifestations of hypercortisolism?
HTN (due to aldo-like effects)
weight gain, truncal obesity, moon facies, fat depo in neck and back
atrophy of fast twitch muscles
hyperglycemia - due to gluconeogenesis
osteoperosis and bone fractures
stria, easy bruising
immunosuppression (suppresses cytokines)
What are the effects of hyperaldosteronism?
causes Na retention and K excretion - pts volume overloaded and hypokalemic
renin and angiotensin down due to feedback on JG cells
What is Conn's syndrome?
aldo secreting adenoma in adrenal
do not usually suppress ACTH - no atrophy
look for new onset HTN
most common primary hyperaldo
What is the second cause of primary hyperaldo?
primary adrenocortical hyperplasia - ZG
mostly children and young adults
possible CYP11B2 gene overactivity
What causes secondary hyperaldo?
stimulation of RAAS, higher rates of aldo than primary
decreased blood flow to kidney
hypovolemia and edema from other dz
What are the signs and symptoms of hyperaldo?
What is adrenogenital syndrome?
adrenocortical hyperplasia from increased ACTH, may be mixed w Cushings
What can cause adrenogenital syndrome?
adrenocortical carcinoma - virilization more often
What is CAH?
mutated CYP21B (21-hydroxylase) enzyme
hypocortisolemia stimulates ACTH then bottle neck at defective enzyme and divert down androgen synthetic pathway
What types of adrenal insufficiency are there?
acute and chronic (Addisons) primary
What can cause acute primary adrenal insufficiency?
Waterhouse-Friderichsen syndrome: massive hemorrhage, children, sepsis by meningococcus (also pseudomonas, staph, strep), maybe endotoxins damage vessels
adults - hemorrhage, stress in setting of chronic
What can cause chronic primary adrenocortical insufficiency?
autoimmune - most common, Ab to 21-hydroxylase or ACTH receptor
inf - tb, fungi w granulomas
metastases - bronchogenic, breast
What are signs and symptoms of Addisons dz?
dark skin pigment - ACTH released w proopiomelanocortin
nausea, anorexia, weight loss
Na wasting, volume loss, hypotension
crisis b/c can't handle stress - coma or death
What causes secondary adrenocortical insufficiency and what are its signs and symptoms?
reduced pituitary ACTH output
same as primary but no skin pigment or loss of aldo
What are the basics of adrenal adenomas?
can secrete any of the hormones, mixes, or none (rare)
associated w Cushings - <500g, pink ovoid cells
cut surface is yellow
What are findings specific to adenomas causing Cushings?
remaining normal adrenal and contralateral atrophic due to feedback
What are findings specific to adenomas causing Conns?
unencapsulated, adrenals not atrophic, spironolactone bodies
What is important to remember about lesions in the adrenals?
histology alone does not help predict whether adenoma is functioning or not and which hormone it is secreting
What are the basics of adrenal carcinomas?
can secrete everything but aldo, mixed syndromes more common than adenomas
poor prognosis - metastasis to lung common
metastatic tumors more common than primary
What are pheochromocytomas?
adrenal medulla tumor
release catecholamines sporadically --> HTN, tachycardia, headaches, sweating, tremors
risk for MI, stroke, renal injury, death
What factors distinguish an adrenal carcinoma from an adenoma?
How is pheo diagnosed?
detecting elevated urinary catecholamines and their metabolites (vanillylmandelic acid, metanephrines)
What is the rule of 10?
followed by pheo
10% familial (MEN and neurofibromatosis)
10% extradrenal (carotid body, neural crest cells)
What does pheo look like histologically?
Zellballen - nests of cells encased by rich vascular network
What is the treatment for pheo?
give adrenergic blockers and resect
What contributes to the pathogenesis of type II diabetes?
FFA and TGs inhibit insulin signalling
adipokines promote insulin resistance
adipocytes have PPARgamma that promotes insulin sensitivity - maybe mutated
What could cause type I diabetes?
HLA-DR3 or DR4 are associated
maybe inf or environmental trigger
overload hypothesis - sedentary and overeating children make beta cells vulnerable
What are the 3 criteria for diagnosing diabetes?
any 1 of the following:
random glucose >200 w signs and symptoms
fasting glucose >125 >1 time
abnormal glucose tolerance test
What happens in both types of diabetes that cause the complications?
excess glucose binds and glycosylates proteins
Blood vessels-cross-linked glycosylated collagen entraps lipoprotein → atherosclerosis
Glycosylated capillary basement membrane entraps plasma proteins
Glycosylated plasma proteins affect endothelial permeability, coagulation, extracellular matrix production
Elevated blood glucose causes increased intracellular sorbitol → oxidative cell damage
What are diabetic complications in the kidneys?
BM and mesangial thickening
Kimmelsten-Weilson - hyaline nodular glomerulosclerosis
micro --> macroproteinuria and nephrotic syndrome
What is the role of diabetes in infections?
more prone to severe inf - malignant otitis media from pseudomonas, mucormycosis (mucor or rhizopus fungi in nose and brain)
What are pancreatic endocrine tumors?
functional more likely benign
arise in islets
What is Whipple's triad of symptoms?
hypoglycemic attacks with serum glucose <50
attacks characterized by stupor, confusion, loss of consciousness, slurred speech, coma
brought on by fasting/exercise, relieved by eating
What happens with an insulinoma?
episodic release of insulin and catecholamines
only small percentage secrete enough to be symptomatic
What are gastrinomas?
gastrin causes gastric ulcers (Zollinger-Ellison)
25% in MEN-1 pts
What is a glucagonoma?
from alpha cells
necrolytic migratory erythema - esp in areas w lots of friction
What are somatostatinomas?
from delta cells, most malignant
diabetes, gallstones, steatorrhea
What are MEN syndromes?
AD inherited disorders w hyperplasias, adenomas, and carcinomas in several endocrine organs
manifest at younger age
multifocal w/i individual organ
tumors preceded by asymptomatic hyperplasia