What does an isolated elevation of Dehydroepiandrosterone (DHEA) indicate?

Isolated Elevated DHEA: Clinical Significance and Evaluation

An isolated elevation of dehydroepiandrosterone (DHEA) most commonly indicates a functional adrenal issue rather than a pathological condition, but should be evaluated to rule out potential adrenal hyperplasia or rare adrenal tumors. 1, 2

Differential Diagnosis for Isolated DHEA Elevation

Physiological Causes

• Normal variation (especially in adolescents)
• Stress-induced elevation
• Laboratory error (consider repeating test)

Pathological Causes

• Functional adrenal hyperandrogenism 1
• Mild congenital adrenal hyperplasia (particularly 3β-hydroxysteroid dehydrogenase deficiency) 1
• Early presentation of Cushing's syndrome 3
• Rare adrenal androgen-secreting tumor (uncommon with isolated DHEA elevation) 2, 4

Diagnostic Approach

1. Confirm isolated elevation

   • Verify other adrenal hormones are normal (cortisol, testosterone, androstenedione)
   • Rule out laboratory error with repeat testing if clinically indicated

2. Clinical correlation

   • Assess for hyperandrogenic symptoms:
     • Hirsutism, acne, male-pattern baldness in women
     • Menstrual irregularities in women
     • Rapid virilization (suggests neoplasm) 4
   • Check for symptoms of Cushing's syndrome (central obesity, moon facies, striae)

3. Additional testing if clinically indicated:

   • Dexamethasone suppression test (functional hyperandrogenism typically suppresses) 1
   • ACTH stimulation test if adrenal insufficiency is suspected 3
   • First-line screening tests for Cushing's syndrome if clinically suspected:
     • Late-night salivary cortisol
     • 1mg overnight dexamethasone suppression test
     • 24-hour urinary free cortisol 3

Interpretation of Results

• Mild-moderate elevation with no symptoms: Likely functional/physiological and may not require intervention 1
• Significant elevation (DHEAS >600 mg/dl) with symptoms: Consider imaging to rule out adrenal tumor 2
• Elevation with suppression on dexamethasone: Suggests functional nature 1
• Elevation without suppression: Consider pathological cause requiring further workup

Clinical Significance

DHEA serves as a precursor hormone that can be converted to more potent androgens and estrogens in peripheral tissues 5, 6. While isolated elevation is often benign, it's important to note:

• DHEA levels naturally decline with age (approximately 2% per year after peak) 5
• In women, elevated DHEA may contribute to androgenic symptoms even with normal testosterone 6
• Isolated DHEA elevation is rarely associated with malignancy 4

Important Considerations

• The positive predictive value of elevated DHEAS for adrenal tumors is quite low (studies show no tumors found in patients with isolated DHEAS >16.3 μmol/L) 4
• Clinical presentation is crucial - rapid onset of virilization suggests neoplasm regardless of hormone levels 4
• False positive results can occur with various medications and conditions affecting hormone binding proteins 3, 2

Management

Management depends on the underlying cause and clinical presentation:

• Asymptomatic mild elevation: Observation and periodic monitoring
• Symptomatic elevation: Address specific symptoms and underlying cause
• Suspected pathology: Referral to endocrinology for specialized evaluation

Remember that isolated DHEA elevation without clinical symptoms rarely indicates serious pathology, but comprehensive evaluation is warranted to exclude uncommon but important diagnoses.