Usera: Endocrine Pathology Flashcards
What are the three zones of the adrenal cortex, and what does each layer produce?
- zona glomerulosa: mineralocorticoids –> aldosterone
- zona fasciculata: glucocorticoids –> cortisol
- zona reticularis: sex hormones
The adrenal medulla is derived from (blank) and produces (blank)
neural crest; catecholamines (tyrosine –> DOPA –> dopamine –> NE –> epinephrine)
List three ways in which you can get acute adrenocortical insufficiency
- abrupt withdrawal of corticosteroids (most commonly)
- anticoagulation therapy
- Waterhouse-Friderichsen Syndrome
Bilateral adrenal hemorrhage
Associated with Neisseria Meningitidis septicemia
Endotoxic shock with DIC
Waterhouse-Friderichsen syndrome
What are 3 components of Waterhouse-Friderichsen syndrome?
bilateral hemorrhage necrosis of adrenal glands
associated with N. meningitidis septicemia
endotoxic shock with DIC
What are 5 ways in which you can get CHRONIC adrenocortical insufficiency?
- autoimmune destruction (80%)
- Infectious - TB (most common cause in developing world)
- mets from lung cancer (or RCC)
- adrenogenital syndrome
- AIDS
What are the findings in chronic adrenal insufficiency?
weakness (no cortisol –> breakdown of muscles)
hypotension (no mineralocorticoids)
hyperpigmentation (increased ACTH)
What are the lab findings in chronic adrenal insufficiency?
Sodium?
Potassium?
H+?
low sodium high potassium (principal cells are not exchanging Na+/K+) metabolic acidosis (H+ not being dumped along with K+)
What happens to fasting glucose levels in chronic adrenal insufficiency? Why?
fasting hypoglycemia, because you are lacking cortisol, which is gluconeogenic
What happens to ACTH levels in chronic adrenal insufficiency? What happens when you administer an ACTH stimulation test?
they increase, because you aren’t making cortisol; no response to ACTH stimulation test
Describe how the metyrapone test works for diagnosing adrenal insufficiency
Metyrapone inhibits 11-beta hydroxylase, and prevents cortisol synthesis. When administered, it should increase ACTH secretion and increase steroid precursors. If there is an increase in ACTH but NO increase in 11-deoxycortisol, this indicates adrenal insufficiency.
What enzymes are necessary to take pregnenolone to aldosterone (mineralocorticoids)?
21 & 11
21 hydroxylase
then 11 hydroxylase to make more complex mineralocorticoids
What enzymes are necessary to take pregnenolone to cortisol (glucocorticoids)?
17, 21, & 11
17 alpha-hydroxylase takes pregnenolone to 17-hydroxypregnenolone
then, you need 21 hydroxylase and 11 hydroxylase to form cortisol
What enzymes are necessary to take pregnenolone to the sex hormones?
17
17 alpha-hydroxylase takes pregnenolone to 17-hydroxypregnenolone
What are the three autosomal recessive disorders of adrenal biosynthetic enzymes that can lead to adrenal hyperplasia? Which is the most common?
21 hydroxylase deficiency **most common
11 hydroxylase deficiency
17 hydroxylase deficiency
Congenital adrenal hyperplasia occurs when there are disorders in adrenal biosynthesic enzymes. What effect do these disorders have?
increase ACTH, bc no negative feedback
accumulation of enzymes proximal to enzyme block
blockage in 21-hydroxylase or 11-hydroxylase increases 17-ketosteroids & testosterone
What should you do if you suspect adrenogenital syndrome (congenital adrenal hyperplasia?
chromosomal analysis
test serum 17-hydroxyprogesterone levels - increased in 21 and 11-hydroxylase deficiency
decreased in 17-hydroxylase deficiency
What can 21-hydroxylase deficiency cause in males & females? In neonates?
neonates: hyponatremia, hyperkalemia, hypovolemia, females with congenital ambiguity (clitoral enlargement)
rapid growth as children, but short stature as adults
nonclassic form presents later in life: precocious puberty in males & hirtuism or menstrual irregularities in females
Decrease in cortisol & sex hormones
Salt retainers because weak mineralocorticoids are increased (leading to HTN & mild hypokalemia)
Females: delayed menarche & secondary sexual characteristics
Males: pseudohermaphroditism
17 hydroxylase deficiency
**17 hydroxylase is necessary to take pregnenolone to both glucocorticoids & sex hormones
What will you see physically in 17-hydroxylase deficiency?
clitoris hypertrophy
poor development of labial structure
no palpable gonad
What things can cause cushing syndrome (adrenocortical hyperfunction)?
prolonged corticosteroid use
Cushing disease
hyperfunctional adrenal adenoma
ectopic ACTH production
Hyperaldosteronism - also due to a hyperfunctional adrenal adenoma
hyperaldosteronism
Signs & symptoms of cushing syndrome and why do you see them?
Weight gain & round face –> hyperglycemia –> secondary hyperinsulinism –> fat deposition in face, nape, and trunk
Hirsutism –> due to increased androgens
Abdominal stria –> weakened collagen & rupture of blood vessels
Diastolic hypertension –> increased mineralocorticoids
Muscle weakness –> breakdown of muscle for gluconeogenesis
What will happen to the following lab values in cushing syndrome?
urine cortisol?
blood sugar?
H+ acid/base status?
increased urine free cortisol
hyperglycemia
hypokalemic metabolic alkalosis
What causes Conn’s syndrome?
aldosterone secreting adrenal adenoma (in zona glomerulosa)
Clinical findings of Conn’s syndrome?
diastolic hypertension
muscle weakness
Lab findings in Conn’s syndrome?
hypernatremia
hypokalmia
alkalosis
decreased plasma renin
Catecholamine secreting tumor of the adrenal medulla chromaffin cells (epi & NE)
pheochromocytoma
What is the rule of 10’s for pheochromocytoma?
10% are bilateral
10% are malignant (90% benign)
10% located outside of the renal medulla (ex: bladder wall)
Signs & symptoms of pheochromocytoma?
episodic or sustained hypertension headache palpitations tachycardia sweating anxiety chest pain constipation
**increased catecholamines
How do you diagnose Cushing syndrome?
dexamethasone suppression test
- *low dose of dexamethasone should suppress ACTH in normal individuals
- *high dose of dexamethasome can suppress cortisol in cushing DISEASE, but not other forms
- *ACTH coming from pituitary ACTH secreting cells can be suppressed, but not from ectopic sites or adrenal adenomas
This form of pheochromocytoma is extramedullar & only produces norepinephrine, because it lacks phenylethamine-N-methyltransferase
paraganglioma
What 3 diseases are associated with pheochromocytomas?
neurofibromatosis type I
MEN 2A and 2B
von Hippel-Lindau disease
What is the best confirmatory test for diagnosing pheochromocytoma? What test has the best sensitivity?
plasma serum free metanephrines - best confirmatory test
increased 24-hour urine metanephrines - best sensitivity
**you can also test 24-hour urine VMA
What will you find in the urine of patients with pheochromocytoma?
increased urine metanephrine and normetanephrine
both of these products are broken down into vanillylmandelic acid, so you will get an increase in urine VMA too
What other lab findings will you have in pheochromocytoma?
no suppression with clonidine
hyperglycemia
neutrophilia
Why does removal of a pheochromocytoma require pre-op stabilization with an alpha-inhibitor & beta-blocker
because during surgical excision, catecholamines may leak into the bloodstream
**PBZ is an irreversible alpha blocker to prevent hypertensive crisis
Malignant neoplasm of post-ganglionic sympathetic neurons
Small round blue cell tumor
Common in children less than 5 years old
N-MYC amplication in 20-30% of cases, marker of aggressive behavior
70% are metastatic at diagnosis
Prognosis good if less than 1 year old or hyperdiploid
Prognosis bad if greater than 1 year or 1p deletion
Large palpable abdominal mass
Neuroblastoma
Who gets neuroblastomas?
common in children less than 5yo
What genetic abnormality is associated with neuroblastomas are is a marker of aggressive behavior?
N-MYC
What makes the prognosis better for neuroblastoma? What makes it worse?
good: less than 1yo, hyperdiploid
bad: older than 1yo, 1p deletion
70% of neuroblastomas will have (blank) at diagnosis
metastasized
What does neuroblastoma look like histologically?
small round blue cell tumor
How will neuroblastoma present physically?
large, palpable abdominal mass
How can you diagnose neuroblastoma?
increased urine VMA and HVA
large palpable abdominal mass
small round blue cell tumor on histology
What is the overall survival like for neuroblastoma?
40%
