Laboratory Workup and Treatment
PCOS Laboratory Workup
For suspected PCOS, screen all women with TSH, prolactin, and 17-hydroxyprogesterone (17-OHP) to exclude mimicking conditions, then diagnose PCOS if two of three criteria are met: androgen excess, ovulatory dysfunction, or polycystic ovaries 1.
Essential Screening Tests
- TSH - excludes thyroid disease causing menstrual irregularity
- Prolactin - excludes hyperprolactinemia (can present with amenorrhea or hirsutism)
- 17-OHP - excludes non-classic congenital adrenal hyperplasia (found in 1.5-6.8% of patients with androgen excess) 1
When to Screen for Cushing's Syndrome
Screen for Cushing's syndrome in women with suspected PCOS who have proximal muscle weakness, violaceous striae, facial plethora, rounded facies, or rapidly progressive hyperandrogenic features 1. This is critical because half of reproductive-age women with Cushing's disease were initially misdiagnosed and treated solely for PCOS 2.
Cushing's Screening Tests in PCOS Context
- 1 mg overnight dexamethasone suppression test (DST) - most specific test, unaffected by PCOS presence. Use 138 nmol/L (5 μg/dL) as cutoff for optimal specificity 3
- Midnight salivary cortisol - equally reliable, not affected by PCOS 3
- 24-hour urinary free cortisol (UFC) - use with caution in PCOS as these patients may have mildly elevated levels without true Cushing's syndrome 3
A total testosterone <1.39 nmol/L (40 ng/dL) warrants full Cushing's workup, as this level has 95% sensitivity for distinguishing mild Cushing's from PCOS 4.
Cushing's Syndrome Treatment
Surgical resection of the primary lesion is first-line treatment for all forms of Cushing's syndrome unless surgery is contraindicated or unlikely to reduce glucocorticoid excess 5.
Treatment Algorithm by Etiology
Pituitary Cushing's Disease (Most Common)
- Transsphenoidal selective adenomectomy by experienced pituitary surgeon 5
- If surgery fails or recurs: second-line options include repeat surgery, medical therapy, bilateral adrenalectomy, or radiation therapy
Adrenal Cushing's
- Unilateral adrenalectomy by experienced adrenal surgeon for benign unilateral disease 5
- Laparoscopic approach preferred when feasible
Ectopic ACTH Secretion
- Localize and resect ectopic ACTH-secreting tumor with appropriate node dissection 5
Treatment Goals
The primary goal is normalizing cortisol levels or blocking cortisol action at receptors to eliminate signs/symptoms and reduce mortality 5. This is non-negotiable for overt Cushing's syndrome.
Essential Adjunctive Management
All patients require monitoring and treatment of cortisol-dependent comorbidities 5:
- Psychiatric disorders - depression, anxiety (very common)
- Metabolic complications - diabetes, hypertension, hypokalemia, dyslipidemia
- Bone health - osteoporosis screening and treatment
- Infection risk - offer influenza, pneumococcal, and Herpes zoster vaccinations 5
- Thromboembolism - assess risk factors and provide perioperative prophylaxis for surgery 5
Critical Pitfalls to Avoid
- Do NOT treat to normalize cortisol without established diagnosis - borderline biochemical HPA axis abnormalities without specific Cushing's signs should not be treated 5
- Do NOT delay surgery when indicated - prolonged hypercortisolism increases mortality and morbidity 2
- Do NOT rely solely on UFC in PCOS patients - can be falsely elevated; use DST or midnight cortisol instead 3
- Do NOT overlook rapidly progressive hyperandrogenism - may indicate androgen-secreting adrenocortical carcinoma requiring urgent evaluation 6