adrenals Flashcards
causes cushings syndrome
- most common cause is exogenous glucocorticoids
- ACTH secreting pituitary adenoma
- corticotroph cell hyperplasia
- secretion of ectopic ACTH
- primary adrenal neoplasms
ACTH secreting pituitary adenoms
most common endongenous cause
cushings DISEASE
young adults
usually microadenoma
corticotroph cell hyperplasia
primary or secondary d/t excessive ACTH from hypothalmic CRH producing tumor
secretion of ectopic ACTH
SCC of lung
primary adrenal neoplasms
adenomas and carcinomas most common cause of ACTH independent endogenous cushings
secondary hyperadrenocoritcal function morphology
pituitary shows Crooke hyaline change
adrenal Cx atrophy
b/l if exogenous cushings
u/l if ACTH independent hypersecretion is u/l
diffuse hyperplasia of adrenals
ACTH dependent cushings
adrenal adenomas morphology
YELLOW WITH CAPSULE
adrenal carcinomas
NOT capsulated
symptoms of cushings
HTN and weight gain truncal obestiy, moon facies, buffalo hump hyperglycemia, glucosuria, polydipsia decreased mm and weakness skin is thin, striae osteoporosis at risk for infections, poor wound healing mental disturbances hirsuitism and menstrual abnormalities
Dx of cushings
Dexamethasone suppression test
primary hyperaldosteronism
HTN most common manifestation
causes of primary hyperaldosteronism
b/l hyperaldosteronism (IHA)
adrenocortical neoplasm
glucocorticoid-remediable hyperaldosteronism
b/l hyperaldosteronism (IHA)
most common cause of primary hyperaldosteronism
older, less severe THn then adrenal neoplasms
familial maybe mutation in KCNJ5 encoding a KCh
adrenocortical neoplasm
adenomas rare caracinomas Conn syndrome if multiple more likely to be carcinoma also have KCNJ5 mutations
glucocorticoid-remediable hyperaldosteronism
uncommon
familial
under control of ACTH so will respond to dexamethasone
aldosterone adenomas morphology
solitary, well circumscribed, small
L>R
30-40
BRIGHT YELLOW lipid laden Cx cells resembling fasciulata cells
uniform size and shape
spironolactone bodies after Tx with spirnolactone
b/l idiopathic hyperplasia morphology
diffuse focal hyperplasia of glomerulosa
often wedge shaped
hyperaldosterone symptoms
HTN
Na retention -> increased fluid volume and CO
hypokalemia
long term effects of hyperaldosteronism
CV compromise
strokes
MI
symptoms of hypokalemia
weakness
paresthesias
visual disturbances
tetany
Dx of hyperaldosteronism
elevated aldosterone: renin ratio
aldosterone suppression test
reticularis secretes
DHEA
androstenedione
adrenocortical neoplams
androgen-secreting adrenal carcinomas are more common then adenomas
often also associated with hypercortisolism
congenital adrenal hyperplasia
severe autosomal recessive inherited metabolic errors d/t enzyme deficiencies
21-hydroxylase deficiency
mutations in CYP21A2 most common salt-wasting syndrome virulizing non-classical virulism
salt-wasting syndrome
total lack of 21-hydroxylase
soon after birth hyponatremia and hyperkalemia -> acidosis -> CV collapse -> death
virulization recognized in females at birth
simple virulizing androgential syndrome w/o salt wasting
genital ambiguity
due to increased T
non-classical/ late onset adrenal virilism
most common pattern
d/t partial deficiency
asymptomatic or mild
primary acute adrenocortical insufficiency
crisis
rapid withdrawal of meds
massive hemorrhage
waterhouse-friderichsen syndrome
crisis
chronic adrenochrotical insufficiency precipitated and exasperated by stress
massive adrenal hemorrhage
newborns post difficult delivery
anticoaglulant therapy
DIC -> waterhouse-friderichsen
waterhouse-friderichsen syndrome
overwhelming bacterial infection -> hypotensive shock -> DIC -> adrenocortical insufficiency associated with hemorrhage
usually in kids
bacterial infections leading to waterhouse-friderichsen
nisseria, pseudo, H. influenza, penumo, staph)
addisons
primary chronic adrenal insufficiency
90% d/t autoimmune, TB, AIDs, or mets
autoimmune adrenalitis
Abs to several steriodogenic enzymes
APS1
APS2
APS1
candiasis
ectodermal dystrophy
autoimmune endocrine disorders
AIRE mutations (central T cell tolerance is broken)
APS2
adrenal insufficiency
autoimmune thyroiditis or DMI
TB and other infections
usually have active TB infection in lungs and/or GU tract
histo and coccidiodes
AIDs
MAI
CMV
kaposi
METs
carcinomas of lungs and breast
usually b/l
symptoms of addisons
progressive weakness and easy fatigability
GI: anorexia, nausea, vomiting, weight loss, diarrhea
hyperpigmentation of skin
hyperkalemia, hyponatremia, volume depletion, hypotensive
secondary adrenocortical insufficency
Mets, infections, infarction, or radiation of pituitary
NO hyperpigmentation
normal or near normal aldosterone synthesis
familial syndromes with risk of adrenocortical neoplasms
LiFraumeni
Beckwith Widemann
LiFraumeni
TP53 mutation
Beckwith Widenmann
epigenetics macroglossia macrosomnia abdominal wall defects neonatal hypoglycemia Wilms tumor
Functional adenomas of adrenal
most commonly associated with hyperaldosteronism and cushings, virulizing are usually caracinomas
adrenocoritcal adenomas
YELLOW
usually incidentalomas
adrenocortial carcinomas
rare more likely to be functional large, not well circumscribed varigated necrosis, hemorrhage, cysts invade adrenal v -> IVC invade lymph
adrenal cysts
relatively uncommon
may cause abdominal and flank pain
adrenal myelolipomas
usually benign composed of fat and hematopoietic cells
usually found inceidentally
adrenal medulla cells
chromaffin- specialized neural crest cells
sustentacular cells- supporting
pheochromocytomas
neoplasms of chropmaffin cells secreting catecholamines and sometimes peptides
pheochromocytoma rule of 10s
10% are extra-adrenal (organs of Zuckerkandl and carotid body)
10% of sporadic are b/l
10% are malignant
10% are NOT associated with HTN
familial pheochromocytomas
younger
b/l
mutations
familial mutations of pheochromocytomas
enhance GF pathways: RET, NF1
increase HIF1alpha- mutated in VHL syndrome
morphology of pheochromocytomas
richly vascularized producing lobular pattern
potassium dichromate turns dark brown
Zellballen
only way to determine malignancy is mets
MEN general features
tumors at younger age tumors are in multiple endocrine organs tumors in single organ are multiple usually proceeded by asymptomatic stage of hyperplasia more aggressive and recur
MEN-1
aka Wermer syndrome -parathyroid primary hyperplasia -pancreas endocrine tumor -pituitary adenoma gastrinomas can also occur in duodenum germline mutationi n MEN1 -> menin
parathyroid primary hyperplasia in MEN-1
usually initial MEN manifestation, appears by 40-50
hyperplasia and adenomas
pancreas endocrine tumor in MEN-1
leading cause of M&M
aggressive with mets
usually functional (PPP, gastrin, insulin)
pituitary adenomas in MEN-1
usually ant
prolactinoma most common
also somatotrophin secreting
MEN-2A
sipple syndrome pheochromocytoma parathyroid hyperplasia medullary carcinoma of thyroid gain of fnx in RET
pheochromocytoma in MEN
b/l
extrarenal sites
parathyroid hyperplasia in MEN-2A
hypercalcemia and renal stones
medullary carcinoma of thyroid in MEN-2A
in almsot 100%
multifocal
C-cell hyperplasia in adjacent cells
calcitonin
MEN-2B
pheochromocytomas
medullary carcinomas
neuromas or ganglioneuromas
different RET mutation (point)
medullary carcinomas of MEN-2B
more aggressive then 2A
neuromas and ganglioneuromas of MEN-2B
skin, oral mucosa, eyes, respiratory tract, GI tract
marfanoid habitus
familial medullary thyroid CA
variant of MEN-2A
strong disposition to medullary thyroid CA
develop at older age and are more indolent then MEN-2A
