What is the treatment for an adult with 11 beta-hydroxylase deficiency?

Treatment of 11β-Hydroxylase Deficiency in Adults

Adults with 11β-hydroxylase deficiency require lifelong glucocorticoid replacement therapy to suppress ACTH-driven androgen excess and prevent adrenal crisis, with the addition of mineralocorticoid receptor antagonists (spironolactone or eplerenone) to control hypertension when present. 1, 2

Primary Treatment: Glucocorticoid Replacement

Glucocorticoid therapy is the cornerstone of treatment and serves multiple critical functions 1, 3:

• Hydrocortisone is the preferred glucocorticoid, typically dosed at 15-25 mg daily in 2-3 divided doses to mimic physiologic cortisol secretion 1
• Dexamethasone (0.25-0.5 mg at bedtime) can be used as an alternative, particularly for overnight ACTH suppression, though some patients may not achieve adequate 24-hour androgen control 4
• The goal is to suppress ACTH secretion, thereby reducing excessive androgen production (testosterone, androstenedione) and 11-deoxycorticosterone (DOC), which causes hypertension 1, 4

Critical Safety Consideration

Patients must never abruptly discontinue glucocorticoid therapy - even though they have functioning adrenal glands, chronic ACTH suppression creates a state of functional adrenal insufficiency 3. Interruption of therapy can precipitate acute adrenal crisis, which is life-threatening and requires emergency treatment with intravenous hydrocortisone 3. Importantly, DOC alone (the mineralocorticoid that accumulates in this condition) cannot prevent adrenal crisis manifestations 3.

Hypertension Management

Approximately 50% of patients develop hypertension, often emerging in childhood or adolescence but requiring lifelong monitoring 5:

• Mineralocorticoid receptor antagonists are first-line antihypertensive agents: spironolactone (25-100 mg daily) or eplerenone (25-100 mg daily) 1, 2
• These agents directly block the effects of excess DOC at the mineralocorticoid receptor 1, 2
• Eplerenone monotherapy has been shown effective in controlling hypertension in non-classical cases, achieving target blood pressure without glucocorticoids in selected patients who cannot tolerate them 2
• Dietary sodium restriction is essential as an adjunctive measure in all patients with mineralocorticoid excess 1
• Additional antihypertensives (calcium channel blockers, ACE inhibitors) may be needed if blood pressure remains uncontrolled despite MR antagonists 1

Monitoring Parameters

Regular biochemical and clinical monitoring is mandatory 5, 4:

• Serum 11-deoxycortisol levels - should normalize with adequate glucocorticoid suppression 5
• Testosterone and androstenedione - monitor for adequate androgen suppression, particularly in females with virilization 5, 4
• 17-hydroxyprogesterone - typically elevated but less dramatically than in 21-hydroxylase deficiency 5, 4
• Blood pressure monitoring - both clinic and 24-hour ambulatory measurements to assess hypertension control 2
• Electrolytes - monitor potassium when using MR antagonists 2
• Morning cortisol - to avoid over-suppression and ensure adequate replacement 4

Monitoring Pitfall

Evening androgen levels may remain elevated despite normal morning values when using once-daily dexamethasone, indicating inadequate 24-hour ACTH suppression 4. This requires either switching to divided-dose hydrocortisone or adjusting the glucocorticoid regimen 4.

Refractory Cases: Bilateral Adrenalectomy

Bilateral adrenalectomy is reserved for severe, medically refractory cases where glucocorticoid therapy fails to adequately suppress androgens or control virilization 6, 4:

• Consider in patients with persistent virilization despite maximal medical therapy (multiple glucocorticoid regimens, anti-androgens) 4
• Laparoscopic approach is preferred for reduced morbidity 4
• Post-adrenalectomy, patients require lifelong glucocorticoid AND mineralocorticoid replacement (hydrocortisone plus fludrocortisone) 6, 4
• Risk of Nelson syndrome (progressive ACTH-secreting pituitary adenoma) exists post-adrenalectomy, though this is more commonly described in Cushing's disease 6
• This should only be performed at experienced centers and represents definitive but aggressive management 6, 4

Adjunctive Therapies

For females with persistent virilization despite adequate ACTH suppression 4:

• Anti-androgens (cyproterone acetate, spironolactone) may provide additional benefit 4
• Estrogen supplementation for those with delayed puberty or amenorrhea 4

Stress Dosing

Patients require stress-dose glucocorticoids during illness, surgery, or major physiologic stress 3:

• Double or triple maintenance dose during minor illness 3
• Intravenous hydrocortisone (100 mg every 6-8 hours) for major surgery or severe illness 3
• All patients should carry emergency glucocorticoid supplies and medical alert identification 3