What does an elevated Dehydroepiandrosterone (DHEA) level indicate in a patient?

Elevated DHEA: Clinical Significance and Evaluation

Elevated dehydroepiandrosterone (DHEA) levels may indicate adrenal androgen excess, which requires further evaluation to determine the underlying cause, with potential etiologies including polycystic ovary syndrome, adrenal hyperplasia, or rarely, adrenal tumors.

Understanding DHEA and Its Significance

DHEA is a steroidal hormone secreted by the zona reticularis of the adrenal cortex. It serves as an important precursor to sex hormones (estrogen and testosterone) and has a characteristic age-related pattern of secretion, declining approximately 2% per year with age 1. When elevated, DHEA and its sulfated form (DHEAS) can provide important diagnostic clues about underlying endocrine disorders.

Common Causes of Elevated DHEA/DHEAS

1. Polycystic Ovary Syndrome (PCOS)

• Most common cause of hyperandrogenism in women
• Approximately 50% of anovulatory women exhibit increased adrenal androgen secretion with elevated DHEAS 2
• Often presents with oligomenorrhea, hirsutism, and other signs of androgen excess
• Notably, 77% of women with elevated DHEAS may be non-hirsute 2

2. Non-Classical Congenital Adrenal Hyperplasia (NCCAH)

• Can present with hyperandrogenism and oligomenorrhea
• Diagnosed by elevated basal or ACTH-stimulated 17-hydroxyprogesterone levels
• May show significant decrease in serum testosterone and DHEAS with dexamethasone suppression test 3

3. Adrenal Tumors (Rare)

• Should be considered with very high DHEAS levels (>16.3 μmol/L or >6000 ng/mL)
• More likely with rapid onset of severe virilization
• However, the positive predictive value of high DHEAS for adrenal tumors is low 4

4. Primary Adrenal Insufficiency (PAI)

• Typically presents with low DHEA, but replacement therapy can cause elevated levels
• DHEA replacement (10-50 mg daily) is sometimes used in women with PAI who have persistent lack of libido or low energy 5

Diagnostic Approach

1. Assess clinical presentation:

   • Duration and progression of symptoms
   • Presence of virilization (hirsutism, deepening voice, clitoromegaly)
   • Associated symptoms (fatigue, weight changes, blood pressure issues)

2. Laboratory evaluation:

   • Confirm elevated DHEAS levels
   • Measure total and free testosterone
   • Check 17-hydroxyprogesterone (to rule out NCCAH)
   • Consider morning cortisol and ACTH levels
   • Evaluate for hyperprolactinemia in cases with recent oligomenorrhea 3

3. Imaging studies (if clinical suspicion warrants):

   • Adrenal CT scan if DHEAS >16.3 μmol/L (6000 ng/mL) or rapid onset of severe symptoms
   • Pelvic ultrasound to evaluate for polycystic ovaries

Clinical Pearls and Pitfalls

• Pitfall: Relying solely on DHEAS levels to diagnose adrenal tumors. Despite high specificity (98%), the positive predictive value is low due to the rarity of these tumors 4.

• Pearl: Consider the pattern and timing of symptom onset. Rapid progression of virilization suggests a possible androgen-secreting tumor, while gradual onset after menarche is more consistent with PCOS 3.

• Pitfall: Overlooking non-classical congenital adrenal hyperplasia, which can mimic PCOS but requires different management.

• Pearl: In patients with chronic fatigue syndrome, elevated DHEA levels have been correlated with higher disability scores, suggesting a potential role in stress-related disorders 6.

Management Considerations

Management depends on the underlying cause:

• PCOS: Lifestyle modifications, oral contraceptives, anti-androgens
• NCCAH: Low-dose glucocorticoids
• Adrenal tumors: Surgical removal
• Iatrogenic: Adjustment of DHEA supplementation if applicable

In all cases, addressing the underlying cause rather than simply normalizing DHEA levels should be the primary goal of treatment.