Treatment for 11 Beta-Hydroxylase Deficiency
Primary Treatment Approach
Glucocorticoid replacement therapy is the cornerstone of treatment for 11β-hydroxylase deficiency, with the goal of suppressing ACTH-driven overproduction of mineralocorticoid precursors (11-deoxycorticosterone) and adrenal androgens while avoiding iatrogenic Cushing syndrome. 1, 2
Glucocorticoid Therapy
Standard Regimen
- Hydrocortisone is the preferred glucocorticoid in children and adolescents due to its short half-life allowing better dose titration and reduced growth suppression risk 1, 3
- Typical dosing: 10-15 mg/m²/day divided into 2-3 doses, with the largest dose given in the morning to mimic physiological cortisol secretion 1
- Dexamethasone (0.25-0.5 mg at bedtime) may be used in adolescents and adults to suppress early morning ACTH surge, though growth suppression risk limits pediatric use 4, 3
Monitoring Parameters
- Measure 11-deoxycortisol and 11-deoxycorticosterone levels as primary markers of disease control, along with adrenal androgens (testosterone, androstenedione, DHEAS) 1, 2
- Blood pressure monitoring is essential, as hypertension from mineralocorticoid excess is a hallmark feature 1, 2
- Monitor growth velocity, bone age, and pubertal progression in children to detect both under-treatment (accelerated bone age) and over-treatment (growth suppression) 1
Management of Hypertension
Mineralocorticoid Receptor Antagonists
- Add spironolactone (1-3 mg/kg/day) or eplerenone (25-100 mg daily) if hypertension persists despite adequate glucocorticoid replacement 5, 2
- Recent evidence demonstrates eplerenone monotherapy can effectively control hypertension in non-classical 11β-hydroxylase deficiency when glucocorticoids are not tolerated 5
- Monitor serum potassium closely, as these patients typically present with hypokalemia from mineralocorticoid excess 6, 2
Additional Antihypertensives
- Calcium channel blockers or ACE inhibitors may be added for refractory hypertension 2
- Sodium restriction is essential in all patients to reduce mineralocorticoid receptor activation 2
Surgical Management
Bilateral Adrenalectomy
- Reserve bilateral adrenalectomy only for severe, medically refractory cases where glucocorticoid therapy fails to control virilization or life-threatening hypertension 4
- This approach eliminates the source of excess androgens and mineralocorticoids but commits the patient to lifelong glucocorticoid and mineralocorticoid replacement 4
- Laparoscopic approach is preferred when surgery is indicated 4
Special Considerations
Virilization Management
- In females with ambiguous genitalia, surgical correction should be performed by experienced pediatric urologists, typically after 6-12 months of medical therapy to optimize tissue quality 1
- Antiandrogens (cyproterone acetate) may be considered as adjunctive therapy in severe virilization, though glucocorticoid optimization should be attempted first 4
Growth and Puberty
- Monitor bone age every 6-12 months to detect accelerated skeletal maturation from androgen excess 1
- If premature epiphyseal fusion occurs despite treatment, final adult height may be compromised 1
- Consider GnRH analogs in cases of gonadotropin-independent precocious puberty to preserve height potential 1
Critical Pitfalls to Avoid
- Do not use excessive glucocorticoid doses attempting to completely normalize all biochemical parameters, as this causes iatrogenic Cushing syndrome and growth suppression 1, 3
- Do not assume 21-hydroxylase deficiency based solely on elevated 17-hydroxyprogesterone—measure 11-deoxycortisol to distinguish 11β-hydroxylase deficiency, which shows markedly elevated levels 4
- Do not overlook hypokalemia, which requires correction before initiating treatment and ongoing monitoring 6
- Evening androgen levels may remain elevated despite morning suppression, indicating inadequate 24-hour control and need for regimen adjustment 4