••• Chapter 58^ Hyperandrogenism^581
❍ Why is osteoporosis common in Cushing syndrome?
Because there is decreased bone formation and increased bone resorption due to decreased intestinal calcium
absorption and decreased renal calcium absorption, approximately 20% have vertebral compression fractures.
❍ What are the ophthalmologic findings and why are they concerning?
Increased intraocular pressure in approximately 25% of patients, which is reversible; however, it can worsen
preexisting glaucoma. Therefore, patients with glaucoma should not receive high-dose glucocorticoid treatment as
they can have sudden irreversible deterioration of vision. In addition, posterior subcapsular cataracts can be caused
by chronic hypercortisolism.
❍ What are three screening tests for Cushing syndrome?
(1) Overnight dexamethasone suppression test (1 mg between 11pm-midnight followed by 8 am cortisol-
<1.8 μg/dL is nml).
(2) Urinary-free cortisol > 250 μg/24 hours or three times above the upper limit of normal.
(3) Late-night salivary cortisol level.
If the tests are equivocal, then a midnight serum cortisol and/or dexamethasone-CRH test may clarify the
diagnosis.
In addition, plasma ACTH concentration will help determine if the diagnosis is ACTH dependent or not.
❍ What things can falsely elevate salivary cortisol levels?
Licorice, chewing tobacco, and smoking.
❍ What common medication can cause false-positive dexamethasone suppression test?
Oral contraceptives (OCPs). Estrogen can increase cortisol-binding globulin concentration and since serum assays
measure total cortisol, OCPs can cause false-positive results.
❍ What is the treatment for Cushing disease?
Surgery or pituitary irradiation.
❍ What are the three distinct zones of the adrenal cortex and the corresponding steroids they produce?
The outer zona glomerulosa (mineralocorticoids), the middle zona fasciculata (glucocorticoids), and the inner zona
reticularis (sex steroids).
❍ Who should be screened for adult onset CAH?
Those having early onset of hirsutism, high androgen levels, strong family history of hirsutism, those of high risk
ethnic groups (Hispanic, Mediterranean, Slavic, or Ashkenazi Jewish heritage), and those with hypertension.
❍ What enzyme converts 17-hydroxyprogesterone to 11-deoxycortisol and when deficient accounts for >90%
of cases of CAH?
21-hydroxylase (CYP21A2).
❍ What does 21-hydroxylase deficiency pathophysiologically cause?
Decreased cortisol synthesis resulting in increased ACTH (corticotropin), causing adrenal stimulation leading to
increased androgen production.