What is the management approach for a patient with mildly elevated DHEAS and total testosterone levels?

Management of Mildly Elevated DHEAS and Total Testosterone

Patients with mildly elevated DHEAS and borderline total testosterone (45 ng/dL) should undergo comprehensive endocrine evaluation including repeat hormone testing, pituitary imaging, and appropriate specialist referral to rule out underlying neoplasms and determine appropriate treatment.

Diagnostic Evaluation

Initial Assessment

• Confirm hormone abnormalities with repeat morning testing:
  • Total and free testosterone
  • DHEAS
  • LH and FSH
  • Sex hormone-binding globulin (SHBG) 1

Rule Out Serious Pathology

• For testosterone levels:

  • Values >250 ng/dL (8.7 nmol/L) warrant investigation for androgen-secreting neoplasms, though positive predictive value is only 9% 2
  • Evaluate for rapid onset of symptoms, virilization signs (clitoromegaly, male pattern baldness, voice deepening)

• For elevated DHEAS:

  • Values >6000 ng/ml (16.3 μmol/L) should prompt evaluation for adrenal pathology 2
  • DHEAS >600 mg/dl suggests possible androgen-secreting adrenal cortical adenoma 3

Imaging Studies

• Brain MRI with pituitary/sellar cuts (with and without contrast) if testosterone is elevated with normal LH and high FSH to identify pituitary adenoma 1
• Consider adrenal CT scan for significantly elevated DHEAS 2
• Transvaginal ultrasound to evaluate ovaries for polycystic changes or tumors

Treatment Approach

For Women

1. First-line therapy:

   • Combined oral contraceptives (COCs) to suppress ovarian androgen production, increase SHBG, reduce free testosterone, regulate menstrual cycles, and improve clinical symptoms 1

2. Second-line options:

   • Antiandrogens (spironolactone, finasteride) to block androgen receptors 1
   • Metformin for patients with insulin resistance 1

3. For adrenal androgen excess:

   • Low-dose glucocorticoid therapy may be considered for elevated DHEAS of adrenal origin 4
   • Dexamethasone suppression testing can predict response to chronic glucocorticoid therapy 4

4. DHEA replacement consideration:

   • For women with persistent symptoms despite optimized treatment, a 6-month trial of DHEA replacement (10-50 mg daily, often 25 mg) may be considered 5
   • Monitor DHEAS, androstenedione, and testosterone levels during treatment 5
   • Continue only if clinically effective, as long-term effects are not well established 5

For Men

1. Evaluate for testosterone deficiency:

   • If total testosterone <150 ng/dL with low/normal LH, pituitary MRI is indicated 5
   • Assess for symptoms of hypogonadism

2. Pre-treatment evaluation:

   • Measure hemoglobin/hematocrit (withhold therapy if Hct >50%) 5
   • Assess cardiovascular risk factors 5
   • Measure PSA in men over 40 years 5
   • Evaluate fertility status and reproductive health 5

3. Treatment options:

   • Lifestyle modifications (weight loss, physical activity, smoking cessation) as first-line approach 1
   • Testosterone replacement therapy (if indicated) with goal of mid-normal range (450-600 ng/dL) 1

Monitoring and Follow-up

• Regular follow-up with hormone measurements every 3-6 months initially, then annually 1
• Monitor clinical symptoms and response to therapy
• For women on spironolactone, monitor potassium levels if other risk factors for hyperkalemia exist 1
• For men on testosterone therapy, monitor hematocrit (intervention needed if >54%) 5

Special Considerations

• Fertility concerns: Testosterone therapy suppresses gonadotropins and spermatogenesis 5, 1
• Pregnancy: Hormone replacement needs adjustment during pregnancy 5
• Medication interactions: Avoid medications that interact with hormone therapy (e.g., diuretics with fludrocortisone) 5

Pitfalls to Avoid

1. Assuming mild elevations always indicate serious pathology - most cases represent functional disorders rather than tumors 2
2. Failing to repeat hormone measurements - single measurements can be misleading
3. Overlooking SHBG levels - low SHBG (common with obesity, metabolic syndrome) can affect interpretation of total testosterone 3
4. Missing non-classical congenital adrenal hyperplasia as a cause of mildly elevated androgens
5. Initiating treatment without adequate diagnostic evaluation