What are the treatment options for a high level of Dehydroepiandrosterone sulfate (DHEAS)?

Treatment Options for High DHEAS Levels

The treatment of high DHEAS levels should be directed at the underlying cause, with adrenocortical carcinoma (ACC) being a critical diagnosis to rule out when DHEAS levels are significantly elevated. 1

Diagnostic Approach to High DHEAS

Before initiating treatment, it's essential to determine the cause of elevated DHEAS:

1. Rule out adrenal tumors:

   • DHEAS levels >600 mg/dl strongly suggest an androgen-secreting adrenal cortical adenoma 2
   • Imaging studies (CT or MRI of abdomen) are indicated for patients with significantly elevated DHEAS 1
   • Adrenal incidentalomas with signs of virilization require serum testing for excess androgens 1

2. Consider other causes:

   • Polycystic ovary syndrome (PCOS) - accounts for 20-30% of elevated DHEAS cases 3
   • Congenital adrenal hyperplasia (classic or non-classic) 3
   • Steroid sulfatase deficiency (rare) 4
   • Transporter protein defects affecting DHEAS metabolism 4

Treatment Options Based on Etiology

1. Adrenocortical Carcinoma (ACC)

• Surgical resection is the primary treatment for unilateral adrenal masses suspected of being ACC
• Minimally invasive surgery should be performed when feasible 1
• Post-surgical follow-up with hormone level monitoring is essential

2. Benign Adrenal Adenoma

• Surgical resection for functional adenomas causing significant hormonal effects
• For mild autonomous cortisol secretion (MACS):
  • Surgery may be considered for younger patients with progressive metabolic comorbidities 1
  • Medical management of associated conditions (hypertension, diabetes) if surgery is not performed

3. PCOS-Related DHEAS Elevation

• Lifestyle modifications (weight loss in overweight patients)
• Oral contraceptives to suppress ovarian androgen production
• Metformin for insulin resistance which can contribute to adrenal androgen excess
• Anti-androgens (spironolactone, cyproterone acetate) for hirsutism and other androgenic symptoms

4. Congenital Adrenal Hyperplasia

• Glucocorticoid replacement therapy (hydrocortisone 10-30 mg daily in divided doses) 5
• Dosage should be carefully titrated to suppress excess adrenal androgen production without causing cushingoid side effects
• Regular monitoring of hormone levels to adjust dosage

5. Idiopathic DHEAS Elevation

• If levels are only mildly elevated and without clinical symptoms, observation may be appropriate
• Treatment of specific symptoms (e.g., anti-androgens for hirsutism)

Monitoring and Follow-up

• Regular monitoring of DHEAS levels to assess treatment efficacy
• For patients on glucocorticoid therapy, monitor for side effects including lipodystrophy, hypertension, cardiovascular disease, osteoporosis, and metabolic disorders 5
• For patients with adrenal tumors who undergo surgery, follow-up imaging and hormone testing is recommended

Important Considerations

• The positive predictive value of elevated DHEAS (>16.3 μmol/L or 6000 ng/ml) for adrenal tumors is relatively low 6
• However, very high DHEAS levels warrant thorough investigation to rule out malignancy
• Dexamethasone suppression testing can help differentiate between adrenal and other causes of high DHEAS 7
• Paradoxically, elevated DHEAS may be protective against cardiovascular risk in women, although its role in PCOS remains unclear 3

Pitfalls to Avoid

• Don't assume all elevated DHEAS cases require treatment; asymptomatic mild elevations may be observed
• Don't miss the diagnosis of adrenocortical carcinoma, which requires prompt surgical intervention
• Don't over-treat with glucocorticoids, as this can lead to iatrogenic Cushing's syndrome
• Don't forget to evaluate for other hormonal abnormalities, as DHEAS elevation often occurs with other endocrine disorders