What are the implications and treatment options for an adult patient with an elevated Dehydroepiandrosterone (DHEA) level?

Elevated DHEA Level of 800: Clinical Implications and Management

Immediate Clinical Assessment

A DHEA level of 800 mcg/dL is markedly elevated and requires urgent evaluation for an androgen-secreting adrenal tumor or other pathologic adrenal conditions. Normal DHEA-S levels in adults typically range from 35-430 mcg/dL in men and 35-430 mcg/dL in women, making this value approximately 2-fold above the upper limit of normal 1.

Critical Differential Diagnosis to Evaluate

• Adrenal tumor (adenoma or carcinoma): This is the most concerning etiology requiring immediate imaging 1
• Adrenal hyperplasia: Can present with elevated DHEA but typically less dramatic elevations 1
• Congenital adrenal hyperplasia (late-onset): Consider in younger patients with virilization 1
• Polycystic ovary syndrome (PCOS): In women of reproductive age, though DHEA elevations are typically more modest 2
• Exogenous DHEA supplementation: Must be excluded through careful medication history 3, 4

Diagnostic Workup Algorithm

Step 1: Confirm the Elevation and Assess Clinical Context

• Repeat DHEA-S measurement (the sulfated form is more stable and preferred for clinical assessment) along with morning cortisol and ACTH to assess overall adrenal function 1
• Obtain comprehensive androgen panel: Total testosterone, free testosterone, androstenedione, 17-hydroxyprogesterone 1
• Assess for signs of virilization: Hirsutism, voice deepening, clitoral enlargement in women; assess for feminization in men 3
• Check for Cushing's syndrome: 24-hour urine free cortisol or late-night salivary cortisol, as adrenal tumors can co-secrete multiple hormones 1

Step 2: Imaging Evaluation

• Adrenal CT scan without and with contrast is the first-line imaging modality to evaluate for adrenal masses 1
• Look for characteristics suggesting malignancy: size >4 cm, irregular borders, heterogeneous enhancement, delayed washout 1
• MRI may be considered if CT findings are equivocal or for better characterization of lipid content 1

Step 3: Determine Functional Status and Lateralization

• If an adrenal mass is identified with biochemical evidence of hormone excess, adrenal venous sampling may be necessary to determine unilateral versus bilateral secretion, particularly if surgical intervention is being considered 1
• Measure plasma aldosterone and renin to exclude concurrent primary aldosteronism, which can coexist with adrenal adenomas 1

Treatment Approach Based on Etiology

If Adrenal Adenoma is Identified

• Unilateral laparoscopic adrenalectomy is the treatment of choice for hormone-secreting adrenal adenomas, particularly those >4 cm or with imaging characteristics concerning for malignancy 1
• Smaller adenomas (<4 cm) with clear benign features may be observed with serial imaging and biochemical monitoring every 6-12 months 1

If Adrenal Carcinoma is Suspected

• Immediate referral to endocrine surgery and oncology is mandatory 1
• Adrenal carcinomas typically present with very high DHEA levels, rapid growth, and imaging features of malignancy 1
• Open adrenalectomy with en bloc resection is preferred over laparoscopic approach to minimize tumor spillage 1

If No Structural Abnormality is Found

• Reassess for exogenous DHEA supplementation: Many patients take over-the-counter DHEA without disclosing it, as it is marketed as a dietary supplement in the United States 3, 4
• Consider functional adrenal hyperplasia: May require suppression testing with dexamethasone to assess suppressibility 1
• Evaluate for late-onset congenital adrenal hyperplasia: Measure 17-hydroxyprogesterone, particularly if patient has signs of androgen excess 1

Monitoring for Complications of Androgen Excess

Cardiovascular and Metabolic Effects

• Monitor blood pressure and lipid profile: Elevated androgens can affect cardiovascular risk, though DHEA itself may have some cardioprotective effects at physiologic levels 2
• Assess glucose metabolism: Check fasting glucose and HbA1c, as androgen excess can affect insulin sensitivity 2

Reproductive and Sexual Health Effects

• In women: Assess for menstrual irregularities, infertility, hirsutism, and virilization 3
• In men: Paradoxically, very high DHEA can suppress gonadotropins and lead to testicular atrophy 2

Bone Health

• Baseline bone density assessment may be warranted, as androgen excess can affect bone metabolism 2

Critical Pitfalls to Avoid

• Never dismiss markedly elevated DHEA as "normal aging": While DHEA declines with age, levels of 800 mcg/dL are pathologic at any age 4, 2
• Do not attribute elevated DHEA solely to stress or illness: While acute illness can transiently affect adrenal hormone production, sustained elevations of this magnitude require structural evaluation 1
• Do not delay imaging in patients with very high DHEA levels: Adrenal carcinomas can be rapidly progressive and early detection improves outcomes 1
• Do not forget to ask about supplement use: DHEA is widely available over-the-counter and many patients do not consider it a "medication" worth mentioning 3, 4
• Do not assume benign etiology based on lack of symptoms: Some adrenal adenomas are biochemically active but clinically silent until they reach significant size 1

Follow-Up Strategy

• If adrenalectomy is performed: Monitor for adrenal insufficiency postoperatively, as the contralateral gland may be suppressed 1
• If observation is chosen: Repeat imaging in 6 months, then annually if stable, with concurrent biochemical reassessment 1
• If exogenous supplementation is identified: Discontinue DHEA and recheck levels in 4-6 weeks to confirm normalization 3