What is the treatment for adrenal hyperplasia with elevated androstenedione levels?

Treatment for Adrenal Hyperplasia with Elevated Androstenedione Levels

Glucocorticoid replacement therapy is the primary treatment for adrenal hyperplasia with elevated androstenedione levels, with hydrocortisone 15-20 mg daily in divided doses being the standard approach. The management strategy depends on the specific type of adrenal hyperplasia and the clinical presentation.

Diagnostic Evaluation

Before initiating treatment, proper diagnosis is essential:

• Measure hormone levels:

  • Androstenedione
  • 17-hydroxyprogesterone (key diagnostic marker in 21-hydroxylase deficiency)
  • DHEA-S
  • Testosterone
  • ACTH
  • Cortisol
  • Aldosterone and renin activity (if hypertension or hypokalemia present)

• Determine type of adrenal hyperplasia:

  • Congenital adrenal hyperplasia (CAH) - most commonly due to 21-hydroxylase deficiency
  • Bilateral adrenal hyperplasia
  • Primary hyperaldosteronism with adrenal hyperplasia

Treatment Algorithm

1. For Congenital Adrenal Hyperplasia (21-hydroxylase deficiency)

• First-line treatment: Glucocorticoid replacement

  • Children: Hydrocortisone 10-15 mg/m²/day divided in 3 doses
  • Adults: Hydrocortisone 15-20 mg daily (10-15 mg in morning, 5 mg in afternoon)
  • Goal: Normalize androstenedione and other adrenal androgens while avoiding cushingoid features

• For salt-wasting forms: Add mineralocorticoid replacement

  • Fludrocortisone 0.05-0.1 mg once daily

• Monitoring parameters:

  • Androstenedione levels (aim for age and sex-appropriate normal range)
  • 17-hydroxyprogesterone (ideally within ±2 SD of normal range)
  • Growth velocity and bone age in children
  • Blood pressure and electrolytes

2. For Primary Hyperaldosteronism with Adrenal Hyperplasia

• For unilateral adenoma: Laparoscopic adrenalectomy 1

• For bilateral adrenal hyperplasia: Medical management 1

  • Spironolactone 25-100 mg daily, titrated to control blood pressure and hypokalemia 2
  • Eplerenone as an alternative if spironolactone side effects occur

• Screening indications for primary hyperaldosteronism 1:

  • Resistant hypertension
  • Hypokalemia (spontaneous or substantial if diuretic-induced)
  • Incidentally discovered adrenal mass
  • Family history of early-onset hypertension
  • Stroke at young age (<40 years)

3. For Severe Cases with Uncontrolled Hyperandrogenism

• Consider bilateral adrenalectomy in select cases where medical management fails 3
  • Best suited for patients with severe CAH with:
    • Increasing steroid requirements
    • Persistent hyperandrogenism despite optimal medical therapy
    • Complications from high-dose glucocorticoid therapy

Special Considerations

For Children and Adolescents

• Prioritize growth and development by avoiding overtreatment with glucocorticoids
• Monitor bone age regularly to assess for advanced skeletal maturation
• Adjust dosing based on growth velocity, pubertal development, and hormone levels
• Consider expressing hormone levels as standard deviation scores to better track treatment efficacy 4

For Women with Hyperandrogenism

• Monitor for hirsutism, menstrual irregularities, and fertility issues
• Consider additional anti-androgen therapy if needed
• Evaluate for PCOS, which may coexist with mild forms of adrenal hyperplasia 1

Common Pitfalls to Avoid

1. Overtreatment with glucocorticoids - can lead to iatrogenic Cushing syndrome, growth suppression in children, and metabolic complications

2. Undertreatment - results in persistent androgen excess, virilization, accelerated bone maturation, and short stature

3. Inconsistent monitoring - random hormone measurements have limited value; consider timed measurements relative to medication administration 5

4. Inadequate stress dosing education - patients need clear instructions on increasing glucocorticoid doses during illness or stress to prevent adrenal crisis

5. Focusing only on androstenedione levels - comprehensive monitoring should include clinical parameters and multiple hormone measurements

Follow-up Recommendations

• Regular clinical assessment every 3-6 months
• Hormone measurements (androstenedione, 17-hydroxyprogesterone) every 3-6 months
• Annual bone age assessment in children
• Adjustment of medication based on clinical and biochemical response

The treatment of adrenal hyperplasia requires careful balancing of hormone replacement to control androgen excess while avoiding the complications of glucocorticoid overtreatment.