What is the management and treatment approach for a patient with elevated Dehydroepiandrosterone (DHEA) levels?

Management of Elevated DHEA Levels

The most critical first step is urgent adrenal imaging with CT scan to rule out an androgen-secreting adrenal tumor, particularly if DHEA elevation is accompanied by any virilization symptoms, as malignancy must be excluded before considering other etiologies. 1

Immediate Diagnostic Priorities

Rule Out Malignancy First

• Obtain adrenal CT imaging urgently if DHEA/DHEAS is markedly elevated, especially in patients over 40 years old or with rapid symptom progression 1
• Suspect adrenocortical carcinoma if the tumor is >4-5 cm, has irregular margins, is lipid-poor, doesn't wash out on contrast-enhanced CT, or secretes multiple hormones 2, 1
• Approximately 60% of androgen-secreting adrenal tumors present with virilization and/or evidence of steroid hormone excess 1
• Peak incidence occurs in the fourth to fifth decades with a female-to-male ratio of 1.5:1 1

Clinical Assessment for Hyperandrogenism

Evaluate specifically for:

• Virilization signs: hirsutism, deepening voice, clitoromegaly, androgenetic alopecia, acne, menstrual irregularities 1
• Cushing syndrome features: centripetal obesity, purple striae, buffalo hump, proximal muscle weakness, hypertension, psychiatric disturbances 1
• Rapidity of symptom onset: rapidly progressive virilization strongly suggests malignancy 1

Comprehensive Hormone Panel

Obtain the following laboratory tests:

• Morning ACTH and cortisol to distinguish adrenal from pituitary sources 1
• Complete androgen panel: free and total testosterone, DHEAS, androstenedione 1
• Gonadotropins: LH and FSH 1
• Electrolytes to assess for concurrent aldosterone excess 1
• Additional steroids if malignancy suspected: 17β-estradiol, 17-OH progesterone, 11-deoxycorticosterone, progesterone 2

Management Algorithm Based on Findings

If Tumor Identified on Imaging

For suspected malignant tumors (>4-5 cm, irregular margins, heterogeneous):

• Perform open adrenalectomy rather than laparoscopic approach, as these tumors are prone to rupture 2, 1
• Obtain imaging of chest, abdomen, and pelvis to evaluate for metastases and local invasion 2

For benign-appearing adrenal adenomas:

• Perform laparoscopic adrenalectomy when feasible 1
• Postoperative corticosteroid supplementation is required until recovery of the hypothalamus-pituitary-adrenal axis 2

If No Tumor Found

For functional androgen excess without structural lesion:

• Ketoconazole 400-1200 mg/day can inhibit adrenal steroidogenesis and reduce DHEA production 2, 1
• Monitor DHEA/DHEAS levels and liver function tests regularly during ketoconazole therapy 1
• Consider mitotane as an alternative adrenostatic agent, though ketoconazole is preferred due to better tolerability 2

For DHEA deficiency in women with adrenal insufficiency:

• DHEA replacement is controversial but can be considered in women with persistent low libido and/or low energy despite optimized glucocorticoid and mineralocorticoid replacement 2
• Trial dose: 25 mg daily (range 10-50 mg), guided by morning DHEAS, androstenedione, and testosterone levels maintained in normal range 2
• Offer a 6-month trial and continue only if clinically effective 2
• Use with caution as long-term effects are not well established 2

Critical Pitfalls to Avoid

• Never delay imaging in the presence of rapidly progressive virilization, as this pattern strongly suggests malignancy 1
• Do not assume polycystic ovary syndrome without excluding neoplasm, as the positive predictive value of elevated androgens for tumors is low (9%) but missing a malignancy has catastrophic consequences 3
• Avoid laparoscopic approach for suspected malignant tumors >4-5 cm, as tumor rupture worsens prognosis 2, 1
• Do not use DHEA supplementation in women with elevated endogenous DHEA levels, as this context involves androgen excess, not deficiency 2

Special Considerations

In congenital adrenal hyperplasia:

• DHEAS responds sluggishly to treatment changes and is elevated (>100 μg/dL) only in significantly undertreated patients 4
• Not all CAH patients present with elevated DHEAS, so it can only be used as a control index in those with documented baseline elevation 4

Endocrinology consultation is appropriate for all cases of significantly elevated DHEA to guide workup, interpret complex hormone patterns, and manage treatment 2