Treatment of Non-Congenital Adrenal Hyperplasia
For non-congenital (late-onset) adrenal hyperplasia, treatment should only be initiated when patients are symptomatic with androgen excess manifestations, not merely to normalize hormone levels. 1
When to Treat vs. Observe
Treatment is NOT required for asymptomatic patients with biochemically confirmed non-classic CAH. The decision to treat must be symptom-directed rather than laboratory-driven 1, 2:
- In children: Treat only if experiencing abnormal linear growth velocity, accelerated skeletal maturation, or premature puberty 1
- In adolescent/adult women: Treat for irregular menstrual cycles, progressive hirsutism, severe acne, or infertility 1
- In men: Treatment is rarely necessary as most are asymptomatic 2
Medical Management Approach
Glucocorticoid Therapy
Hydrocortisone is the preferred glucocorticoid for hormone replacement at 15-25 mg daily in split doses for adults 3, 4. Alternative agents include:
- Prednisone: FDA-approved for congenital adrenal hyperplasia, typically dosed lower than hydrocortisone equivalents 4
- Dexamethasone: FDA-approved for congenital adrenal hyperplasia but has longer half-life and higher potency, increasing risk of iatrogenic Cushing's syndrome 5
The primary pitfall is over-treatment leading to iatrogenic Cushing's syndrome, which causes worse morbidity than undertreated hyperandrogenism 2. Doses should be titrated to control symptoms while avoiding cushingoid features, not to normalize androgen levels completely 1.
Mineralocorticoid Replacement
Most patients with primary adrenal insufficiency require fludrocortisone 50-200 μg as a single daily dose 6, 3. However, non-classic CAH typically does NOT involve aldosterone deficiency, so mineralocorticoid replacement is usually unnecessary 2.
Monitor for:
- Salt cravings or lightheadedness suggesting under-replacement 6
- Peripheral edema or hypertension suggesting over-replacement 6
- Avoid concurrent diuretics, NSAIDs, or liquorice which interact with fludrocortisone 6
Alternative and Adjunctive Therapies
For Women with Persistent Symptoms
When glucocorticoids alone are insufficient or poorly tolerated, consider:
- Spironolactone or eplerenone: Mineralocorticoid antagonists that block androgen receptors, useful for hirsutism and acne 3
- Oral contraceptives: Suppress ovarian androgen production and increase sex hormone-binding globulin 1
- Anti-androgen medications: Finasteride or flutamide for refractory hirsutism 1
Novel Approaches Under Investigation
Modified-release hydrocortisone preparations and continuous subcutaneous hydrocortisone pumps aim to better mimic physiologic cortisol secretion patterns 7, 8. Additionally, non-glucocorticoid strategies including CRH receptor antagonists and androgenic enzyme inhibitors are being studied but remain investigational 7.
Monitoring Protocol
Annual follow-up is mandatory for all treated patients 3:
- Clinical assessment: Weight, blood pressure, signs of glucocorticoid excess or androgen breakthrough 3
- Laboratory monitoring: Serum electrolytes, morning 17-hydroxyprogesterone, testosterone, androstenedione 6, 1
- Bone density: Every 3-5 years if on chronic glucocorticoid therapy 3
- Screen for autoimmune disorders: Particularly hypothyroidism 3
Critical Safety Measures
All patients on glucocorticoid replacement must:
- Wear medical alert identification and carry a steroid emergency card 3
- Receive education on stress-dose adjustments (double or triple dose during illness, injury, or surgery) 6
- Have access to emergency injectable hydrocortisone 100 mg for adrenal crisis 6, 3
During surgery or severe illness, administer IV/IM hydrocortisone 100 mg immediately, then 100 mg every 6-8 hours until recovery 6, 3.
Special Populations
Pregnancy
Glucocorticoid requirements increase during pregnancy, typically requiring an additional 2.5-10 mg hydrocortisone daily in the third trimester 6. Fludrocortisone dose may also need adjustment due to progesterone's anti-mineralocorticoid effects 6. During delivery, give 100 mg IV hydrocortisone bolus, repeated every 6 hours as needed 6.
Bilateral Adrenal Hyperplasia
If imaging reveals bilateral adrenal hyperplasia causing hormone excess, medical management with spironolactone or eplerenone is preferred over bilateral adrenalectomy 3, 9. Bilateral adrenalectomy creates permanent adrenal insufficiency requiring lifelong replacement and carries significant morbidity risk 9.