What are the treatment options for elevated Dehydroepiandrosterone (DHEA) levels?

Treatment of Elevated DHEA Levels

Surgical intervention with laparoscopic adrenalectomy is the first-line treatment for confirmed adrenal neoplasms causing elevated DHEA, while medical management with ketoconazole (400-1200 mg/day) serves as an alternative for functional DHEA excess when surgery is not feasible. 1, 2

Immediate Diagnostic Priorities Before Treatment

The critical first step is determining whether elevated DHEA represents a potentially malignant adrenal tumor requiring urgent intervention:

• Rule out androgen-secreting adrenal tumors urgently, particularly when virilization symptoms are present, as approximately 60% of androgen-secreting adrenocortical tumors demonstrate evidence of adrenal steroid hormone excess 2
• Obtain adrenal CT imaging immediately if rapidly progressive virilization is present, as delay can be catastrophic when malignancy is the underlying cause 2
• Suspect malignancy when tumors exceed 4-5 cm, demonstrate irregular margins, appear lipid-poor on imaging, show poor contrast washout, or secrete multiple hormones 3, 2
• Confirm androgen excess by testing serum DHEA-S, testosterone, 17β-estradiol, 17-OH progesterone, androstenedione, 17-OH pregnenolone, 11-deoxycorticosterone, progesterone, and estradiol when ACC is suspected or virilization is present 3

Surgical Management

For benign adrenal tumors causing elevated DHEA, laparoscopic adrenalectomy is the preferred surgical approach when technically feasible 1, 2:

• Minimally invasive surgery should be performed for confirmed benign lesions 3
• Open adrenalectomy is indicated for suspected malignant tumors, particularly those >4-5 cm with irregular margins or heterogeneous appearance on imaging 1, 2
• Patients with unilateral cortisol-secreting adrenal masses and clinically apparent Cushing's syndrome should undergo unilateral adrenalectomy of the affected gland 3

Medical Management Options

When surgery is not immediately feasible or for functional DHEA excess without a discrete tumor:

• Ketoconazole 400-1200 mg/day inhibits adrenal steroidogenesis and reduces DHEA production 1, 2
• Monitor liver function tests regularly in all patients receiving ketoconazole due to hepatotoxicity risk 1, 2
• Check DHEA/DHEAS levels periodically to assess treatment efficacy 1, 2
• Watch for signs of adrenal insufficiency with high-dose steroid suppression therapy, as excessive suppression can occur 1, 2

Critical Pitfalls to Avoid

• Never delay imaging when virilization symptoms are rapidly progressive, as this pattern strongly suggests malignancy requiring urgent intervention 2
• Do not confuse elevated DHEA with primary adrenal insufficiency, where DHEA levels are typically low rather than elevated 1, 2, 4
• Avoid relying solely on testosterone >8.7 nmol/L (250 ng/dl) or DHEAS >16.3 μmol/L (6000 ng/ml) as screening thresholds for neoplasms, as these have poor positive predictive value (only 9% for testosterone) despite high sensitivity, and clinical evaluation with imaging is more appropriate 5

Special Clinical Context

In primary adrenal insufficiency, DHEA levels are characteristically low, not elevated, and supplementation may be considered in that distinct clinical scenario 1, 4. This represents the opposite pathophysiology from elevated DHEA and requires entirely different management.