Adrenal Cortico Hypo- and Hyperfunction Flashcards Preview

Endocrine Week 2 > Adrenal Cortico Hypo- and Hyperfunction > Flashcards

Flashcards in Adrenal Cortico Hypo- and Hyperfunction Deck (37):
1

What are the general (widespread) symptoms of Cushing syndrome?

Obesity due to hyperphagia and insulin resistance

HTN due to Na retention

2

What are the skin symptoms of Cushing syndrome?

plethora, striae and bruising due to skin thinning

hirsutism and acne due to androgen excess

3

What are the MSK symptoms of Cushing syndrome?

osteopenia due to increased bone resorption

weakness due to catabolic effects of cortisol on muscle

4

What are the gonadol symptoms of Cushing syndrome?

menstrual disorders and impotence, decreased libio due to inhibition of GnRH, LH and FSH

5

What are the pediatric symptoms of Cushing syndrome?

growth retardation due to GH inhibition

6

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

7

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

8

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)

9

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 

10

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

11

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

12

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

13

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)

14

How would Cushing's be treated?

remove either the pituitary or the adrenals

15

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

16

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

17

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

18

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)

19

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)

20

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

21

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

22

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

23

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 

24

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

25

What is familial hyperald type I?

glucocorticoid-remediable aldosteronism (GRA)

26

What is familial hyperald type III?

germline mutations in the KCNJ5 K+ channel

27

What are the clinical features of hyperaldosteronism?

HTN, hypokalemia, and metabolic alkalosis

mild hypernatremia, hypomagnesemia

muscle weakness and CV risks

28

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)

29

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

30

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

31

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

32

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

33

How is primary hyperald caused by a solitary ald-secreting adenoma treated?

adrenalectomy

34

How is primary hyperald caused by bilateral adrenal hyperplasia  treated?

use of a nonselective (spironolactone) or more selective (eplernone) aldosterone blocking agent

35

What causes 17,20 lyase deficiency?

mutation on 10q24.3

36

How does 17,20 lyase deficiency present?

sexual infantilism, HTN, and cortisol deficiency

37

What causes 17a-hydroxylase deficiency and how does it present?

CYP17 mutation causing ambiguous genitalia in males