What is the initial workup for a patient with elevated Dehydroepiandrosterone sulfate (DHEAS) levels?

Initial Workup for Elevated DHEAS Levels

The initial workup for a patient with elevated DHEAS levels should include a comprehensive hormonal evaluation focusing on adrenal function, with specific attention to ruling out adrenal tumors and other causes of adrenal hyperandrogenism. 1

Clinical Assessment

History and Physical Examination

• Symptoms to evaluate:

  • Hirsutism, acne, virilization
  • Weight gain, central obesity
  • Menstrual irregularities (in females)
  • Hypertension, muscle weakness
  • Rapid onset of symptoms (suggests neoplasm)
  • Family history of endocrine disorders

• Physical findings to document:

  • Pattern and extent of hirsutism
  • Signs of hypercortisolism (central obesity, striae, facial plethora)
  • Signs of virilization (clitoromegaly, male pattern baldness, deepening voice)
  • Blood pressure
  • Evidence of insulin resistance

Laboratory Evaluation

First-line Tests

1. Complete hormonal workup:

   • Total testosterone and free testosterone
   • DHEAS (already elevated)
   • 17-OH-progesterone
   • Androstenedione
   • Morning cortisol
   • 1 mg overnight dexamethasone suppression test (DST) 1

2. Additional tests based on clinical suspicion:

   • Aldosterone/renin ratio (if hypertensive or hypokalemic)
   • Plasma free metanephrines (to rule out pheochromocytoma)
   • 24-hour urinary free cortisol (if suspecting Cushing's syndrome)

Interpretation Guidelines

• DHEAS >600 μg/dL strongly suggests adrenal adenoma 2
• Total testosterone >8.7 nmol/L (250 ng/dL) warrants investigation for androgen-secreting neoplasm, though positive predictive value is only about 9% 3
• Cortisol >138 nmol/L after 1mg DST indicates cortisol hypersecretion 1

Imaging Studies

• Adrenal CT scan is the first-line imaging study for patients with significantly elevated DHEAS 1

  • Look for adrenal masses >1 cm
  • Assess for features suggesting malignancy (irregular margins, heterogeneity, size >4 cm)

• Consider additional imaging if initial CT is inconclusive:

  • MRI abdomen (alternative to CT)
  • If malignancy is suspected: chest CT to evaluate for metastases

Special Considerations

For Women with Reproductive Symptoms

• Transvaginal ultrasound to evaluate for polycystic ovaries or ovarian tumors
• Consider pelvic MRI if ovarian pathology is suspected but ultrasound is inconclusive

For Patients with Signs of Cushing's Syndrome

• ACTH level to differentiate ACTH-dependent from ACTH-independent causes
• Midnight salivary cortisol
• Confirm autonomous cortisol secretion with additional testing 1

Common Pitfalls and Caveats

1. Not all elevated DHEAS indicates pathology:

   • DHEAS levels naturally decline with age; reference ranges should be age-adjusted
   • Only 2.3% of patients with hyperandrogenism have androgen-secreting tumors 3
   • False positives are common; only ~9% of patients with testosterone >250 ng/dL actually have neoplasms 3

2. Consider medication effects:

   • Chronic narcotic use can lower DHEAS levels 4
   • Exogenous steroid use can suppress adrenal function

3. Don't miss adrenal insufficiency:

   • While elevated DHEAS typically suggests excess adrenal androgen production, remember that low DHEAS can indicate adrenal insufficiency 4
   • If clinical picture suggests possible adrenal insufficiency, include ACTH stimulation test

Follow-up Recommendations

• If initial workup is negative but DHEAS remains significantly elevated:

  • Consider referral to endocrinology
  • Periodic monitoring (every 6-12 months) with repeat DHEAS and testosterone measurements
  • Follow-up imaging if clinical symptoms worsen or hormone levels increase significantly

• If adrenal mass is identified:

  • Follow management algorithm for adrenal incidentalomas 1
  • Consider adrenalectomy for functional tumors or those with features concerning for malignancy