Endo- adrenal/ MEN syndrome pathology Flashcards
autoimmune polyendocrine syndrome type 1 vs 2
type 1: (ME HAPPy) AIRE gene mutation -mucocutaneous candidiasis/ thrush (IL-17 /22 Abs) -ectodermal dystrophy (APECED) -hypogonadism -adrenalitis -parathyroiditis -pernicious anemia
type 2: (TAD)
- thyroiditis
- adrenalitis
- DM (T1DM)
features of 21-hydroxylase deficiency non- classic form
- simple virilizing syndrome (without salt wasting)
- only a partial lack in 21 hydroxyls enzyme (some aldosterone and cortisol present but still very high ACTH production)
- presents later in life with androgen excess leading to precocious (early) puberty in males or hirtuisism/virilization in females with acne at puberty
**MORE COMMON TYPE vs classic
Waterhouse Friderichsen syndrome is classically due to
sepsis and DIC in young children with Neisseria meningitidis infection
(is hemorrhagic necrosis of adrenal glands resulting in primary acute adrenocortical insufficiency)
how to dx a pheochromocytoma
urine and plasma metanephrines and catecholamines
MEN 2B
- pheochromocytoma
- medullary thyroid carcinoma
- mucosal neuromas
(marfanoid body type)
**germline gain of function mutation in RET photo-oncogene (specific point mutation)
define congenital adrenal hyperplasia (CAH)
-AR inherited error of metabolism causes defect in cortisol production/steriodogenesis (high ACTH from decreased negative feedback leads to bilateral hyperplasia)
-most common enzyme deficiency is 21-hydroxylase
where cortisol and aldosterone production is inhibited and androgen production is increased
features of 21-hydroxylase deficiency classic form
classic : “salt wasting syndrome”
- presents in neonates as hyponatremia (no aldosterone) and hyperkalemia, with life-threatening hypotension from salt wasting
- females also present with genital ambiguity/virilization
- -> clitoromegaly and fusion of labia
- *long term consequence of adrenomedullary dysplasia
bilateral cortical hyperplasia of adrenal glands would be expected in ACTH _____ cushing syndrome
ACTH dependent (usually from cushings disease of pituitary origin)
how does primary ACUTE adrenocortical insufficiency present ? what are potential causes?
- presents as weakness and shock (hypotension, hyponatremia, hypoglycemia, fever, ab pain, N/V)
- causes:
1. abrupt withdrawal of glucocorticoids/steroids (exogenous source removed without compensation) - long term corticosteroid/steroid use atrophies the adrenals therefore it is important to taper steroids every once in a while
- adrenal crisis (insufficient cortisol production- can be seen in chronic pts put under stress without adequate response to increase cortisol)
(or could be result of Cushing syndrome tx-removal of tumor/adrenals)
3.Waterhouse Friderichsen syndrome (massive adrenal hemorrhage and hemorrhagic necrosis of adrenal gland)
golden solid yellow small adenoma that can be very small (<2cm) and seen in young patients. when removed see spironolactone bodies from tx, associated with high incidence of ischemic heart disease
aldosterone-secreting adenoma
patients (children) with Men 2a/b dx get prophylactic ____ before 10yo
thyroidectomy due to >95% chance of getting medullary thyroid carcinoma
tumor of chromaffin cells in adrenal medulla
pheochromocytoma
how to dx for CAH
serum 17-hydroxyprogesterone (should be high)
can also do ACTH stimulation test
Heel stick during routine newborn screening includes testing for 17-hydroxyorogesterone
signs of adrenal crisis seen in relative adrenal insufiency
hypotension (shock)
hyponatremia
hyperkalemia
*tx with steroid supplementation
what to do if you find a “adrenal incidentaloma”
(incidentally identified adrenal nodules on imaging)
- proper management depends on many factors:
1. size - (>4cm means more likely malignant )
2. functional assays - (dexamethasone suppression test for hypercortisolism, or metanephrines for pheochromocytoma)
3. CT enhancement details
what is the common etiology of secondary hyperaldosteronism
- usually renal origin and RAAS defect that increases fxn
- diruretic use
- decreased renal perfusion from renal A. stenosis
- arterial hypovolemia
- pregnancy
- renin-secreting tumors
**SEE high renin and aldosterone (PRA and PAC) on labs
common association with autoimmune adrenalitis causes chronic insufficiency (addisons)
autoimmune polyendocrine syndrome (type 1 and 2)
an adrenal cortical tumor presenting with virilization (adrenogenital syndrome) is more likely benign or malignant?
malignant
* carcinomas are more common than adenomas in terms of primary adrenal neoplasms
what is the 10% rule of pheochromocytoma (5 things) ? 25% are ___?
10% extra-adrenal (paraganglioma) 10% bilateral 10% in kids 10% malignant (only dx when metastasis spread seen) 10% not associated with HTN
25% are familial!!! (associated with Men 2A,2B - RET mutations, VHL, and NF type 1)
what is APECED
autosommal polyendocrinopathy candidiasis, ectodermal dystrophy
-aka APST1 (type 1 )
( candidiasis infection of the skin, nails, and moist mucous membranes-mouth)
(parathyroidiits –> hypoparathyroidism)
(adrenalitis –> adrenal insufficiency
general features of MEN syndromes
- get tumors at younger ages
- tumors more likely bilateral/multiple
- preceding hyperplasia is often seen
- tumors tend to be aggressive and recurrent
anti-HTN med that is an aldosterone antagonist
spironolactone
how does a patient with a pheochromocytoma present
(due to episodic release of catecholamines)
- profound chronic or paroxysmal (episodic) HTN
- HA
- palpitations
- tachycardia
- sweating
-classic triad: HA, palpitations, diaphoresis
features of adrenal medulla myelolipoma
benign tumor of fat and bone marrow
(megakaryocytic, erythroid precursors, myeloid cells in all stages, and adipose tissue)
-gross: yellow with red solid tumor
-can present with hemorrhage (benign but can bleed and it can be dangerous)
features of adrenal carcinomas not seen in adenomas
both: incidental on radiography, and can be functional
carcinomas only: compression/invasion of adjacent structures (ex: kidneys) and virilization
adrenal medulla is comprised of ___? and derived from ? and responsible for secretion of??
comprised of chromatin cells derived from neural crest
-responsible for catecholamine secretion (epinephrine and norepinephrine) —**SNS effect and under SNS control
acute and chronic complications of a pheochromocytoma
acute: related to catecholamine surges
chronic: cardiomyopathy
layers of the adrenal cortex from out to in
- capsule
- zona glomerulosa
- zona fasiculata
- zona reticularis
- medulla (inner)
tx for CAH 21 H-deficiency
glucocorticoids (replenishes cortisol and provides negative feedback for ACTH suppression–> no further androgen overproduction)
mineralcorticods (replenishes aldosterone)
what is Conns syndrome ? what does it cause? MCC?
- primary hyperaldosteronism
- MCC: idiopathic (unknown) (second is adenoma)
- HTN (refractory HTN, adrenal mass and HTN, HTN at young age and hard to tx, severe HTN >160/100)
- hypokalemia
- hypomagnesemia
MEN 1
*3 P’s
-parathyroid adenoma/hyperplasia (hyperparathyroidism)
-pancreatic endocrine tumor
-pituatary adenomas (lactotroph, somatotroph)
(Duodenal gastrinomas can also be seen)
*germline mutation in MEN1 tumor suppressor gene (Menin loss of function mutation)
most important feature of adrenal carcinoma is how it act and its prognosis
size!
(larger than adenoma , wt > 200gm)
-because both can look really similar undermicrscope and sx therefore size is important in distinction of benign vs metastasis .. large = mass effect of compression and virilization
how does primary CHRONIC adrenocortical insufficiency (Addison’s Disease) present ? potential causes?
- long duration of malaise, fatigue
- anoerxia, weight loss
- joint pain
- hyperpigmentation of skin (due to melanocyte stimulating hormone from increased ACTH)
causes:
1. MCC in west: autoimmune destruction/adrenalitis
2. MCC worldwide: TB
3. metastatic adrenal carcinoma (esp from lung)
* autoimmune adrenalitis is commonly a component of autoimmune polyendorcrine syndromes
MEN 2A
- pheochromocytoma
- medullary thyroid carcinoma
- parathyroid hyperplasia/ adenomas (hyperparathyroidism)
*germline gain of function mutation in RET photo-oncogene
testing for adrenocortical insufficiency
- random cortisol (if low go to step 2 )
2. ACTH stimulation test (if does increase cortisol = primary insufficiency)
what use to be one of the most common causes of Addisons Disease (still is in underdeveloped countries)
TB
*would see calcified adrenals on X-ray
___ is comprised of photoreceptor neural tissue and is responsible for melatonin secretion
pineal glad
how does familial medullary thyroid carcinoma differ from MEN 2a/b
both have RET got mutations, however important to dintinguish the two because familial type has better prognosis and will not develop other tumors vs MEN2a/b which will need to screen for others
