What is the clinical long-term management of a patient with Congenital Adrenal Hyperplasia (CAH)?

Long-Term Management of Congenital Adrenal Hyperplasia (CAH)

Hormone Replacement Therapy

Patients with CAH require lifelong glucocorticoid replacement with hydrocortisone 15-25 mg daily or cortisone acetate 25-37.5 mg daily, divided into 2-3 doses with the first dose upon awakening and the last dose 4-6 hours before bedtime. 1

• Hydrocortisone is available in 20,10, and 2.5 mg tablets; cortisone acetate in 25 and 5 mg tablets 1
• The first dose should be taken upon awakening, with some patients benefiting from waking earlier to take the dose and returning to sleep to relieve morning nausea 2
• Mineralocorticoid replacement with fludrocortisone 50-200 µg daily is required for primary adrenal insufficiency 2
• Salt supplementation may be needed to compensate for increased renal sodium loss 1

Laboratory Monitoring Schedule

Annual laboratory monitoring should include morning serum cortisol and plasma ACTH, serum sodium and potassium, plasma glucose, HbA1c, complete blood count, vitamin B12 levels, thyroid function (TSH, FT4, TPO antibodies), and tissue transglutaminase antibodies with total IgA. 1

• Morning cortisol and ACTH measurements assess adequacy of replacement therapy 2
• A cortisol day curve (before and 2,4, and 6 hours following the morning dose) can be useful when suspecting under-replacement or rapid cortisol clearance 1
• Plasma renin activity (PRA) assessment helps evaluate mineralocorticoid replacement adequacy in patients with features of mineralocorticoid deficiency 1
• 17-hydroxyprogesterone should be measured to assess disease control in CAH patients 1
• DHEA-S monitoring in women with persistent symptoms despite optimized replacement may guide DHEA supplementation (10-50 mg daily) 3

Screening for Associated Conditions

Screen annually for autoimmune thyroid disease, type 1 diabetes, pernicious anemia, and celiac disease, as autoimmune polyglandular syndrome commonly develops in patients with autoimmune adrenal insufficiency. 1, 2

• Thyroid function monitoring every 12 months is critical, including subclinical thyroid disease which contributes to fatigue 1
• Women of reproductive age should be informed about the possibility of premature ovarian insufficiency, especially with positive side-chain cleavage enzyme autoantibodies 1
• In patients with episodic diarrhea, screen for celiac disease with tissue transglutaminase antibodies and total IgA 1

Clinical Assessment at Annual Visits

Annual physical examination should assess for signs of glucocorticoid under-replacement (lethargy, nausea, poor appetite, weight loss, increased pigmentation) or over-replacement (weight gain, truncal obesity, hypertension, glucose intolerance, decreased bone mineral density). 1, 4, 5

• Normal skin color indicates sufficient replacement therapy 1
• Postural hypotension reflects insufficient mineralocorticoid therapy or low salt intake 1
• Monitor for cardiometabolic complications including obesity, diabetes, and hypertension 4, 5
• Assess bone mineral density periodically to detect osteoporosis risk 6, 5

Fertility and Reproductive Health Monitoring

Female patients require monitoring for menstrual irregularities, hirsutism, and fertility concerns, with treatment goals focusing on preventing hyperandrogenism symptoms while preserving menstrual regularity and fertility. 4, 6

• Inadequate androgen suppression leads to menstrual irregularities and reduced fertility 4
• Male patients should be screened for testicular adrenal rest tumors with testicular ultrasound 6
• Prepregnancy counseling is essential for women with CAH to develop a management plan for labor and postpartum period 1

Patient Education Requirements

All patients must receive education on stress-dose glucocorticoid management during illness, injury, or surgery, wear a medical alert bracelet, carry a steroid emergency card, and have injectable hydrocortisone available for self-administration during adrenal crisis. 1, 2

• Patients should increase steroid doses 2-3 times maintenance during concurrent illnesses, vomiting, injuries, or other stressors 1, 2
• Training in intramuscular administration of hydrocortisone 100 mg during acute adrenal crisis is mandatory 1
• Endocrine consultation is required prior to surgery or procedures for stress-dose planning 2
• Patients must understand that delays in emergency glucocorticoid administration can be fatal 1

Imaging Studies

Adrenal CT imaging should be obtained at diagnosis to evaluate for structural abnormalities, hemorrhage, or tumors if 21-hydroxylase autoantibodies are negative. 2

• Repeat imaging is not routinely required unless new symptoms develop or there is concern for adrenal tumor formation 1
• In male patients with negative autoantibodies, very long-chain fatty acids should be measured to screen for adrenoleukodystrophy 1, 2

Transition to Adult Care

Adolescents with CAH require coordinated transition from pediatric to adult endocrinology care with a multidisciplinary team approach, as this period is particularly challenging due to changes in growth, sex hormone levels, and treatment adherence issues. 4, 6

• Treatment goals shift from optimizing growth and pubertal timing to preventing hyperandrogenism, preserving fertility, and monitoring long-term complications 4
• Psychosocial issues frequently affect adherence to glucocorticoid treatment during transition 6
• Regular follow-up every 6-12 months is essential to monitor for complications and adjust therapy 1, 6

Common Pitfalls to Avoid

• Never rely solely on electrolyte abnormalities for diagnosis or monitoring, as hyponatremia may be marginal and hyperkalemia occurs in only 50% of cases 2
• Do not delay treatment of suspected adrenal crisis for diagnostic testing—mortality is high if untreated 2
• Avoid exogenous steroid medications (prednisolone, dexamethasone, inhaled fluticasone) that can confound cortisol measurements and suppress the HPA axis 2
• When treating concurrent hypothyroidism, start corticosteroids several days before thyroid hormone replacement to prevent precipitating adrenal crisis 2