What are the evaluation and treatment options for a female patient with elevated Dehydroepiandrosterone (DHEA) levels, potentially associated with Polycystic Ovary Syndrome (PCOS) or adrenal gland disorders?

Elevated DHEA in Females: Evaluation and Management

When DHEA or DHEAS is elevated in a female patient, the primary concern is ruling out non-classical congenital adrenal hyperplasia (NCAH) and adrenal/ovarian tumors, followed by evaluation for PCOS as a common cause of modest elevations. 1

Diagnostic Thresholds and Initial Workup

Age-Specific DHEAS Cutoffs

• DHEAS >3800 ng/mL in women aged 20-29 years warrants investigation for NCAH 1
• DHEAS >2700 ng/mL in women aged 30-39 years warrants investigation for NCAH 1
• These thresholds are critical decision points, as values above them require exclusion of adrenal pathology before attributing elevation to PCOS 1

Concurrent Androgen Assessment

• Measure testosterone (day 3-6 of cycle): values >2.5 nmol/L suggest PCOS, valproate use, or NCAH with modest elevation 1
• Measure androstenedione: values >10.0 nmol/L mandate exclusion of adrenal or ovarian tumor 1
• Elevated DHEAS in PCOS is typically part of generalized hyperandrogenism, with concurrent elevations in testosterone and androstenedione 2

Differential Diagnosis Algorithm

Rule Out Adrenal/Ovarian Neoplasm FIRST

• Androstenedione >10.0 nmol/L requires immediate imaging to exclude tumor 1
• For confirmed adrenal neoplasms, surgical intervention is first-line treatment per National Comprehensive Cancer Network guidelines 3
• Laparoscopic adrenalectomy is recommended for benign tumors when feasible 3
• Open adrenalectomy is preferred for suspected malignancy (size >4-5 cm, irregular margins, heterogeneous appearance) 3

Evaluate for PCOS as Common Cause

• PCOS affects 4-6% of the general population and commonly causes modest DHEAS elevation 1
• Approximately 20-30% of PCOS women demonstrate excess adrenal androgen production 4
• Elevated DHEAS is more prevalent in non-classic PCOS phenotypes (B and C) compared to classic phenotype A 2

PCOS Diagnostic Workup

• LH/FSH ratio >2 supports PCOS diagnosis (measure days 3-6 of cycle, average of three samples 20 minutes apart) 1
• Mid-luteal progesterone <6 nmol/L indicates anovulation, common in PCOS 1
• Fasting glucose/insulin ratio >4 suggests reduced insulin sensitivity associated with PCOS 1
• Pelvic ultrasound (days 3-9): >10 peripheral cysts 2-8 mm diameter with stromal thickening confirms polycystic ovaries 1
• Two-hour insulin during OGTT is independently associated with higher DHEAS in non-obese PCOS patients 5

Clinical Context Matters

• In non-obese PCOS with elevated DHEAS, stimulated insulin (2-hour OGTT) is an independent predictor of DHEAS levels 5
• Women with PCOS and elevated DHEAS tend to be younger and have higher 2-hour insulin levels 5
• High DHEAS in PCOS is associated with acne but paradoxically with reduced risk of abdominal obesity 6

Treatment Approaches

For Adrenal Neoplasms

• Surgical resection is definitive treatment per National Comprehensive Cancer Network 3
• Medical management with ketoconazole (400-1200 mg/day) can inhibit adrenal steroidogenesis for functional DHEA excess 3
• Monitor liver function tests with ketoconazole therapy 3
• Watch for signs of adrenal insufficiency with high-dose steroid suppression 3

For PCOS-Related Elevation

• Treatment focuses on managing PCOS itself rather than isolated DHEAS elevation 1
• Address insulin resistance, menstrual irregularity, and hyperandrogenic symptoms based on clinical presentation 1
• Approximately 70% of PCOS women have elevated DHEAS, and ovarian suppression with GnRH agonists can reduce DHEAS in those with elevated baseline levels 7

Critical Pitfalls to Avoid

• Do NOT attribute elevated DHEAS to PCOS until adrenal/ovarian tumors are excluded, especially when androstenedione >10.0 nmol/L 1
• Do NOT confuse isolated polycystic ovaries (17-22% of general population) with PCOS requiring treatment 1
• Do NOT measure prolactin postictally in epilepsy patients, as it may be falsely elevated 1
• Remember that DHEAS values are age-dependent and decline by 40% from twenties to thirties 2
• In primary adrenal insufficiency, DHEA is LOW, not elevated—supplementation may be considered in that context 3, 8