What is the diagnosis and treatment approach for patients with elevated Dehydroepiandrosterone (DHEA) levels?

Diagnosis and Treatment of Elevated DHEA Levels

Elevated DHEA/DHEAS levels should be evaluated for potential underlying causes including polycystic ovary syndrome (PCOS), adrenal tumors, or other adrenal disorders, with treatment directed at the underlying cause rather than the DHEA elevation itself. 1

Diagnostic Approach

Initial Evaluation

• Assess for clinical manifestations:
  • Hirsutism, acne, virilization, or accelerated growth in children
  • Menstrual irregularities in women
  • Signs of other endocrine disorders

Laboratory Testing

1. Confirm elevated DHEA/DHEAS levels

   • Morning serum DHEA and DHEAS measurements
   • Consider age-appropriate reference ranges (DHEAS levels naturally decline with age) 2

2. Additional hormone evaluation:

   • Morning serum cortisol and ACTH
   • Total and free testosterone
   • Androstenedione
   • Plasma renin activity and aldosterone (if adrenal dysfunction suspected)
   • Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in women 1, 3

Imaging Studies

• Adrenal imaging (CT scan or MRI) when:

  • DHEAS levels >16.3 μmol/L (6000 ng/mL)
  • Rapid onset of symptoms
  • Signs of virilization
  • Clinical suspicion of adrenal tumor 1, 3

• Pelvic ultrasound in women to evaluate for PCOS or ovarian pathology 4

Common Causes of Elevated DHEA/DHEAS

1. Polycystic Ovary Syndrome (PCOS)

• Most common cause in women of reproductive age
• Approximately 33% of PCOS patients have elevated DHEAS
• Higher prevalence in non-classic (B or C) phenotypes of PCOS 4
• Associated with higher overall androgen production

2. Adrenal Tumors

• Rare but serious cause of elevated DHEA/DHEAS
• Often associated with very high DHEAS levels and rapid progression of symptoms
• May present with virilization and accelerated growth in children 3
• Early diagnosis and surgical excision improve prognosis

3. Other Causes

• Congenital adrenal hyperplasia
• Cushing's syndrome
• Stress-related elevations
• Medication effects

Treatment Approach

Treatment Based on Underlying Cause

1. For PCOS:

   • Weight loss if overweight/obese
   • Oral contraceptives to suppress ovarian androgen production
   • Anti-androgen therapy (e.g., spironolactone) for hirsutism/acne
   • Metformin for insulin resistance 4

2. For Adrenal Tumors:

   • Surgical excision is the primary treatment
   • Complete removal improves prognosis and normalizes hormone levels 3

3. For Congenital Adrenal Hyperplasia:

   • Glucocorticoid replacement therapy
   • Dose adjusted to normalize androgen levels 1

4. For Age-Related DHEA Decline:

   • DHEA supplementation is not routinely recommended
   • May be considered in specific cases of adrenal insufficiency at doses of 25-50 mg daily 1, 5

Monitoring and Follow-up

• Regular monitoring of DHEA/DHEAS levels to assess treatment response
• Follow-up imaging for patients with adrenal pathology
• Monitor for clinical improvement of hyperandrogenic symptoms
• Annual screening for metabolic complications in PCOS patients

Important Caveats

• Isolated elevation of DHEAS without clinical symptoms may not require treatment
• The positive predictive value of elevated testosterone (>8.67 nmol/L) for androgen-secreting neoplasms is only 9%, while the negative predictive value is 100% 6
• DHEAS levels >16.3 μmol/L (6000 ng/mL) have high specificity (98%) but low positive predictive value for adrenal tumors 6
• DHEAS levels are strongly influenced by age, with values declining approximately 40% from the twenties to thirties 4, 2
• Measurement of DHEAS is advantageous as levels remain stable throughout the day due to its long half-life 2

Clinical Pearls

• In children with persistent acne and elevated DHEA/DHEAS, evaluate for signs of virilization and accelerated growth which may indicate an adrenocortical tumor 3
• The combination of clinical features and laboratory findings is more valuable than isolated hormone measurements
• DHEA supplementation in elderly individuals with low levels may have immunoenhancing properties but is not standard practice 5
• Rapid onset or progression of hyperandrogenic symptoms should prompt immediate evaluation for an androgen-secreting tumor