Adrenal

Question 1

What are primary causes of adrenal insufficiency?

Answer 1

Addison’s disease

CAH

Question 2

What are secondary causes of adrenal insufficiency?

Answer 2

Exogenous steroid exposure (most common)
Sheehan’s syndrome
Pituitary tumor s/p resection

Question 3

How do you diagnose Addison’s disease?

Answer 3

• Morning serum cortisol concentration (< 3 mcg/dL)

- Short ACTH stimulation test (high vs low dose)

Question 4

What is Addison’s disease and what is the prevalence of concomitant autoimmune disease? POI?

Answer 4

Autoimmune process that destroys adrenal cortex

• 53% have another autoimmune disease
• 20% have pOI

Question 5

How do you diagnose CAH?

Answer 5

-17-OHP (8am in follicular phase) >800 ng/dL (neonates > 3500 ng/dL)
< 200 ng/dL excludes diagnosis (<100 in neonates)
200-800 ng/dL indeterminate (per UTD >200 is virtually diagnostic)
-If indeterminate, perform High-dose ACTH stimulation test:
Phlebotomy ~ 1 hour post 1 ug/m2 (or 250 mcg) ACTH; >1500 ng/dL = diagnostic

Question 6

Describe pattern of 17-OHP secretion?

Answer 6

17-OH P has diurnal pattern – peak in AM and nadir late in day

Question 7

How do you treat CAH initially?

Answer 7

-Classical: Glucocorticoids (hydrocortisone) + mineralocorticoids (fludrocortisone)
-Potential for GnRH agonist to avoid/delay precocious puberty
-Monitoring:
*17-OHP between 400 and 1200 ng/dL
Bone density, serum 17 OHP, androstendione, testosterone
*Plasma-renin levels for MC treatment

Question 8

How do you manage CAH long term in adults?

Answer 8

Transition to PM long-acting glucocorticoids (dex – most potent, prednisone – mid potent)

Question 9

How do you treat NCCAH

Answer 9

• Children: Glucocorticoids if premature puberty/accelerated growth (hydrocortisone 10-15 mg/m2)
• Women: OCPs for hirsutism/acne +/- anti-androgens

Question 10

Describe presentation of Sheehan’s syndrome?

Answer 10

Failed lactation, secondary amenorrhea, loss of sexual hair

Question 11

How does adrenal insufficiency present clinically?

Answer 11

Nausea/vomiting, weakness, hypoglycemia, hypotension

Question 12

How do you diagnose Cushing’s Syndrome?

Answer 12

(One of three tests)

1. 24-hour urine free cortisol excretion (measured twice)
2. Late night salivary cortisol level (measured twice)
3. 1mg (high dose) overnight dexamethasone suppression test (best test in patient with hirsutism)
   * Take dexamethasone between 11pm-12am, measure serum cortisol at 8am
   * False positive in women on OCPs (E2 leads to increased CBG) and obesity

Question 13

What are the different etiologies of Cushing’s Syndrome?

Answer 13

Iatrogenic
Cushing’s Disease
Ectopic ACTH syndrome
Adrenal tumors

Question 14

How do you determine if the cause of Cushing’s Syndrome is ACTH independent or dependent?

Answer 14

-Measure serum ACTH (normal circadian rhythm is lost so can be measured anytime)
<5 pg/mL (low) = ACTH independent (adrenal tumor) -> CT A/P
>20pg/mL (high) = ACTH dependent (ACTH adenoma, ectopic ACTH secretion)

Question 15

What is the most common cause of secondary Cushing’’s Syndrome?

Answer 15

Cushing’s Disease

Question 16

What is the most common cause of primary Cushing’’s Syndrome?

Answer 16

Iatrogenic

*only one without hyperandrogenism

Question 17

Describe the role of CRH stim test in identifying the cause of Cushing’s Syndrome?

Answer 17

• Pituitary (responds to CRH)

- Ectopic (does not response to CRH) ACTH secretion

Question 18

Describe the role of high dose dexamethasone suppression test in identifying the cause of Cushing’s Syndrome?

Answer 18

High dose dexamethasone suppresses pituitary ACTH (i.e. CRH bronchiole tumor)
High dose dexamethasone does not suppress ectopic ACTH (i.e. small cell lung tumor)

Question 19

Describe the role of petrosal venous sinus catheterization in identifying the cause of Cushing’s Syndrome?

Answer 19

Measure differential in ACTH concentration

Higher in the brain if pituitary tumor, lower in the brain if ectopic ACTH secreting tumor

Question 20

Describe treatment approach for Cushing’s syndrome?

Answer 20

Address underlying cause (transsphenoidal surgery, lung tumor resection, adrenalectomy)
If surgery contraindicated or persistent/recurrent following surgery:
Adrenal enzyme inhibitors = 1st line (i.e. ketoconazole -> metyrapone)
Inhibits the first step in cortisol biosynthesis (side-chain cleavage) and, to a lesser extent, the conversion of 11-deoxycortisol to cortisol
Even more potent inhibitor of C17-20 desmolase, decreasing androstenedione and testosterone production
Also inhibits ACTH secretion in vitro at therapeutic doses by impairing corticotroph adenylate cyclase activation
Adrenolytic agents (i.e. mitotane)
If pituitary tumor, consider cabergoline or somatostatin-analog

Question 21

Describe clinical presentation of iatrogenic Cushing’s Syndrome?

Answer 21

Glaucoma
Cataracts
Osteonecrosis
Pseudotumor cerebri
Pancreatitis
Panniculitis

Question 22

Describe clinical presentation shared by Cushing’s Syndrome?

Answer 22

Central obesity
Psychiatric
Poor wound healing
Osteoporosis
Glucose intolerance
HPA supp.

Question 23

Describe clinical presentation of endogenous Cushing’s Syndrome?

Answer 23

HTN
Hirsutism
Striae
Menstrual abn
Impotence