Adrenal Cortico Hypo- and Hyperfunction Flashcards
What are the general (widespread) symptoms of Cushing syndrome?
Obesity due to hyperphagia and insulin resistance
HTN due to Na retention
What are the skin symptoms of Cushing syndrome?
plethora, striae and bruising due to skin thinning
hirsutism and acne due to androgen excess
What are the MSK symptoms of Cushing syndrome?
osteopenia due to increased bone resorption
weakness due to catabolic effects of cortisol on muscle
What are the gonadol symptoms of Cushing syndrome?
menstrual disorders and impotence, decreased libio due to inhibition of GnRH, LH and FSH
What are the pediatric symptoms of Cushing syndrome?
growth retardation due to GH inhibition
What are the metabolic symptoms of Cushing syndrome?
diabetes due to insulin resistance (20%)
polyuria (30%) due to suppression of AVP
kidney stones (50%) due to increased calcium, uric acid, and oxalate and decreased citrate
One of the first derangements that occurs in Cushing’s syndrome is _________.
failure to achieve a normal late-night circadian nadir. I.e. the cortisol does not come down around midnight like it should
How is Cushing’s diagnosed?
measure of the following:
24 hr urine free cortisol
late-night salivary cortisol
1-mg overnight dexamethasone suppression test (cortisol should be less than 1.8 (5) mcg/dL when measured in the morning)
There are high false-positive rates for the overnight DST in what pts.?
50% of women taking oral contraceptive pills because of increased cortisol binding globulin (CBG) levels
What is a standard two-day 2mg low dexamethasone suppression test?
consists of administering 0.5mg dexa every 6 hrs for 8 doses, and measurement of serum cortisol either 2 or 6 hrs after the last dose. The same criteria for normal suppression (less than 1.8 (5) mcg/dl) used for the 1mg dex test are used
Once Cushing Syndrome has been diagnosed, how can Cushing disease be determined as the cause?
First measure plasma ACTH and if its normal or elevated, its abnormal and you have ACTH-dependent Cushing syndrome
Then MRI the pituitary and if its abnormal, the Dx is made
Once Cushing Syndrome has been diagnosed, how can ectopic ACTH be determined as the cause?
First measure plasma ACTH and if its normal or elevated, its abnormal and you have ACTH-dependent Cushing syndrome
Then get a pituitary MRI and if normal do a bilateral petrosal sinus sampling for ACTH with CRH administration and if there is no pituitary gradient for ACTH, the diagnosis is ectopic ACTH but if there is, the cause is Cushing disease
Once Cushing Syndrome has been diagnosed, how can adrenal source be determined as the cause?
Measure plasma ACTH and it will be low (then get an adrenal CT)
How would Cushing’s be treated?
remove either the pituitary or the adrenals
What is one lab way to differentiate primary and secondary adrenal insufficiency?
In primary all three hormone lines (cortisol, aldosterone, and andogrens) will be effected while in secondary probably only the cortisol and androgens will be because aldosterone is under other control
How is adrenal insufficiency diagnosed?
ACTH stimulation test in which a basline sample for cortisol is drawn, a bolus injection of 250mcg ACTH is given, and cortisol is chest at 30 and 60 min.
Cut off for an adequate peak serum cortisol is 18mcg/dl
Describe congential adrenal hyperplasia
AR disorder caused by defects in the cholesterol hormon pathways that is usually discovered at birth and is characterized by a hyperplastic adrenal cortex
NOTE: Nonclassic CAH can manifest in adolescence or even adulthood
Defective ______ enzyme (hint: mediates conversion of 17-hydroxyprogesterone to 11-deoxycortisol) accounts for more than 95% of CAH cases
21-hydroxylase (mutation of the CYP21A2 gene)
In terms of androgen production, DHEA can be converted to androstenedione (so can 17-hydroxyprogesterone). What happens to androstenedione?
Oxidoreductase converts it to testosterone which is then extra-adrenally converted to dhydrotestosterone (DHT) via 5a-reductase (target of the ‘steride drugs)
High (3500+ng/dL) serum levels of what enzyme would be diagnostic of 21-hydroxylase deficiency? How does it present in girls as neonates? Males?
17-hydroxyprogesterone
Girls as neonates present with: ambiguous genitalia, clitoral enlargement, a common urethral-vaginal orifice, and may present with a salt-losing adrenal crisis at 1-2 weeks of age
NOTE: Internal female reproductive organs (uterus and ovaries) are normal
Males present with salt-losing adrenal crises or as toddlers with signs of early puberty but typically dont show signs of CHA< although phallic enlargement and scrotal hyperpigmentation is sometimes present
What causes nonclassical CAH?
Same pathophys invovled BUT enzymatic activity is only reduced (20-50%) but sufficient to maintain normal glucocorticoid and mineralcorticoid production, at the expense of excessive androgen production
Salt wasting is absent and affected females do not ambiguous genitalia
What symptoms might someone with nonclassical CAH present with?
premature pubarche
acne
accelerate bone age
hirsutism and menstrual irregularities in women
Although most men with the nonclassical form are though to have normal teticular function and fertility, some do present with testicular adrenal rests (benign tumors) and infertility
How is NCCAH diagnosed in women?
basal 17-hydroxyprogesterone greater than 200 ng/dl and confirmed with a high-dose ACTH stimulation test (gold standard).
In NCCAH, the response to ATCH is exaggerated, leading to a serum 17-hydroxyprogesterone value exceeding 1500ng/dl
What are some common causes of primary aldosteronism?
-bilateral idiopathic hyperaldosteronism (60-70%)
Unilateral aldosterone producing adenomas (30-40%)
familial hyperald types I, II, and III
pur aldosterone-producing adrenocortical carcinomas anc ectopic aldosterone-secreting tumors
What is familial hyperald type I?
glucocorticoid-remediable aldosteronism (GRA)
What is familial hyperald type III?
germline mutations in the KCNJ5 K+ channel
What are the clinical features of hyperaldosteronism?
HTN, hypokalemia, and metabolic alkalosis
mild hypernatremia, hypomagnesemia
muscle weakness and CV risks
How is primary hyperald diagnoed?
simultaneously measure morning ald and renin levels. In most pts. with hyperalp, the plasma ald level exceeds 15ng/dl, but the plasma renin activtiy is very low or undetectable
A ratio of plasma ald: plasma renin greater than 30 has a 90% sensitivity and specificity for diagnosis (but a ratio of 20-30 is also highly suggestive, especially when the plasma ald is greater than 15ng/dL)
What should you do if you give a PAC/PRA to a pt. with HTN and hypokalemia and PRA AND PAC are elevated and the ratio=~10?
investigate for causes of secondary hyperald such as:
renovascular HTN, diuretic overuse, renin-secreting tumor, malignant HTN, or coarctation of the aorta
What should you do if you give a PAC/PRA to a pt. with HTN and hypokalemia and PRA is down, PAC is elevated, the ratio=~20+, and PAC is over 15ng/dL?
suggests primary hyperald
What should you do if you give a PAC/PRA to a pt. with HTN and hypokalemia and PRA AND PAC are both decreased?
Investigate for:
Congenital adrenal hyperplasia
exogenous mineralcorticoid use
Cushing syndrome
11B-HSD deficiency
Liddle’s syndrome
After the biochemical diagnosis of primary hyperald is confirmed, what is done?
CT of the adrenal gland. It can show either a solitary adrenal adenoma or diffuse bilateral adrenal hyperplasia
How is primary hyperald caused by a solitary ald-secreting adenoma treated?
adrenalectomy
How is primary hyperald caused by bilateral adrenal hyperplasia treated?
use of a nonselective (spironolactone) or more selective (eplernone) aldosterone blocking agent
What causes 17,20 lyase deficiency?
mutation on 10q24.3
How does 17,20 lyase deficiency present?
sexual infantilism, HTN, and cortisol deficiency
What causes 17a-hydroxylase deficiency and how does it present?
CYP17 mutation causing ambiguous genitalia in males
