Adrenal Flashcards
What are primary causes of adrenal insufficiency?
Addison’s disease
CAH
What are secondary causes of adrenal insufficiency?
Exogenous steroid exposure (most common)
Sheehan’s syndrome
Pituitary tumor s/p resection
How do you diagnose Addison’s disease?
- Morning serum cortisol concentration (< 3 mcg/dL)
- Short ACTH stimulation test (high vs low dose)
What is Addison’s disease and what is the prevalence of concomitant autoimmune disease? POI?
Autoimmune process that destroys adrenal cortex
- 53% have another autoimmune disease
- 20% have pOI
How do you diagnose CAH?
-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
Describe pattern of 17-OHP secretion?
17-OH P has diurnal pattern – peak in AM and nadir late in day
How do you treat CAH initially?
-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
How do you manage CAH long term in adults?
Transition to PM long-acting glucocorticoids (dex – most potent, prednisone – mid potent)
How do you treat NCCAH
- Children: Glucocorticoids if premature puberty/accelerated growth (hydrocortisone 10-15 mg/m2)
- Women: OCPs for hirsutism/acne +/- anti-androgens
Describe presentation of Sheehan’s syndrome?
Failed lactation, secondary amenorrhea, loss of sexual hair
How does adrenal insufficiency present clinically?
Nausea/vomiting, weakness, hypoglycemia, hypotension
How do you diagnose Cushing’s Syndrome?
(One of three tests)
- 24-hour urine free cortisol excretion (measured twice)
- Late night salivary cortisol level (measured twice)
- 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
What are the different etiologies of Cushing’s Syndrome?
Iatrogenic
Cushing’s Disease
Ectopic ACTH syndrome
Adrenal tumors
How do you determine if the cause of Cushing’s Syndrome is ACTH independent or dependent?
-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)
What is the most common cause of secondary Cushing’’s Syndrome?
Cushing’s Disease
What is the most common cause of primary Cushing’’s Syndrome?
Iatrogenic
*only one without hyperandrogenism
Describe the role of CRH stim test in identifying the cause of Cushing’s Syndrome?
- Pituitary (responds to CRH)
- Ectopic (does not response to CRH) ACTH secretion
Describe the role of high dose dexamethasone suppression test in identifying the cause of Cushing’s Syndrome?
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)
Describe the role of petrosal venous sinus catheterization in identifying the cause of Cushing’s Syndrome?
Measure differential in ACTH concentration
Higher in the brain if pituitary tumor, lower in the brain if ectopic ACTH secreting tumor
Describe treatment approach for Cushing’s syndrome?
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
Describe clinical presentation of iatrogenic Cushing’s Syndrome?
Glaucoma Cataracts Osteonecrosis Pseudotumor cerebri Pancreatitis Panniculitis
Describe clinical presentation shared by Cushing’s Syndrome?
Central obesity Psychiatric Poor wound healing Osteoporosis Glucose intolerance HPA supp.
Describe clinical presentation of endogenous Cushing’s Syndrome?
HTN Hirsutism Striae Menstrual abn Impotence
