What is Congenital Adrenal Hyperplasia (CAH) and its treatment?

From the Guidelines

Congenital adrenal hyperplasia (CAH) is a group of genetic disorders that require lifelong hormone replacement therapy to correct deficiencies and suppress excess hormone production, with the primary goal of minimizing morbidity, mortality, and improving quality of life. The most common form of CAH is 21-hydroxylase deficiency, accounting for about 95% of cases. Treatment for classic CAH includes daily oral glucocorticoids, such as hydrocortisone (10-15 mg/m²/day divided into 2-3 doses), with some adults using longer-acting options like prednisone (3-5 mg/day) or dexamethasone (0.25-0.5 mg/day) 1.

Key Treatment Considerations

• Mineralocorticoid replacement with fludrocortisone (0.05-0.2 mg/day) is needed for salt-wasting forms.
• Stress dosing is crucial during illness or surgery, typically tripling the usual glucocorticoid dose.
• For infants with ambiguous genitalia, surgical correction may be considered, with female gender assignment warranted for several reasons, including the potential for normal sexual function and fertility 1.

Monitoring and Adjustments

• Regular blood tests to measure 17-hydroxyprogesterone, androgen levels, and electrolytes help guide therapy adjustments.
• The goal is to provide adequate hormone replacement while minimizing side effects and allowing normal growth and development.
• Patients with CAH should wear a Medic Alert Bracelet and carry a steroid card to inform medical personnel on chronic CAH status, and education on how to increase steroid doses during concurrent illnesses or injury is important to prevent adrenal crisis 1.

From the FDA Drug Label

Endocrine disorders: Primary or secondary adrenocortical insufficiency (hydrocortisone or cortisone is the drug of choice; synthetic analogs may be used in conjunction with mineralocorticoids where applicable; in infancy, mineralocorticoid supplementation is of particular importance), congenital adrenal hyperplasia, hypercalcemia associated with cancer, nonsuppurative thyroiditis Fludrocortisone acetate tablets, 0.1 mg are indicated as partial replacement therapy for primary and secondary adrenocortical insufficiency in Addison’s disease and for the treatment of salt-losing adrenogenital syndrome.

Congenital Adrenal Hyperplasia (CAH) is a group of inherited disorders that affect the adrenal glands, leading to hormone imbalances.

• The treatment of CAH may involve the use of hydrocortisone 2 or other glucocorticoids to replace deficient hormones.
• Fludrocortisone 3 may be used as partial replacement therapy for primary and secondary adrenocortical insufficiency in Addison’s disease and for the treatment of salt-losing adrenogenital syndrome, which can be associated with CAH.
• The specific treatment approach may vary depending on the individual case and the severity of the condition.

From the Research

Definition and Causes of Congenital Adrenal Hyperplasia

• Congenital adrenal hyperplasia (CAH) is an autosomal-recessive disease causing cortisol deficiency, aldosterone deficiency, and hyperandrogenism 4.
• The most common enzyme defect associated with CAH is 21-hydroxylase deficiency (21-OHD), which accounts for 95% of cases 5, 6.
• CAH due to 21-OHD shows a wide range of clinical severity and is caused by mutations in the CYP21 gene encoding the steroid 21-hydroxylase enzyme 7.

Diagnosis of Congenital Adrenal Hyperplasia

• Diagnosis of 21-OHD is confirmed by steroid analysis in newborn screening or later on 4.
• Neonatal screening by hormonal methods identifies affected children before salt wasting crises develop, reducing mortality from this condition 7.
• Prenatal diagnosis by direct mutation detection permits prenatal treatment of affected females to minimize genital virilization 7.

Treatment of Congenital Adrenal Hyperplasia

• Standard medical treatment consists of oral glucocorticoid and mineralocorticoid administration in order to suppress adrenal androgens and to compensate for adrenal steroid deficiencies 4.
• Glucocorticoid therapy aiming to suppress adrenocorticotrophic hormone (ACTH)-mediated hyperandrogenemia and to replace glucocorticoid deficiency, if indicated, remains the first line of management in CAH with or without mineralocorticoid replacement therapy and salt supplementation 8.
• Treatment of CAH, especially in the adult patient, remains controversial given the lack of prospective randomized controlled trials comparing treatment regimens 6.
• Patients benefit from careful individualized therapy with avoidance of Cushingoid side effects and optimization of reproductive, sexual, and bone health 6.

Outcomes and Management of Congenital Adrenal Hyperplasia

• Important long-term health issues for adults with CAH affect both men and women, including final height, fertility, cardiometabolic risk, bone metabolism, neuro-cognitive development, and the quality-of-life 5.
• Patients with CAH should be regularly followed-up from childhood to adulthood by multidisciplinary teams who have knowledge of CAH 5.
• Optimal replacement therapy, close clinical and laboratory monitoring, early life-style interventions, early and regular fertility assessment, and continuous psychological management are needed to improve outcome 5.