Weight Management with Congenital Adrenal Hyperplasia (CAH) in South Africa

CAH Subtypes: The Weight Management Landscape

How CAH Treatment Causes Weight Gain

Glucocorticoid Replacement: Necessary but Weight-Promoting

All classic CAH patients require lifelong glucocorticoid replacement (typically hydrocortisone in children; prednisolone or dexamethasone in adults). This is not optional — cortisol deficiency is life-threatening, and adrenal crises (acute cortisol deficiency triggered by illness, surgery, or stress) can be fatal within hours. However, glucocorticoid therapy has well-known metabolic effects:

• Central adiposity — glucocorticoids preferentially drive fat deposition to the trunk, abdomen, and viscera
• Insulin resistance — glucocorticoids impair insulin signalling, promoting hyperglycaemia and fat storage
• Increased appetite — glucocorticoids stimulate appetite, particularly for calorie-dense foods
• Muscle catabolism — high or supraphysiological doses break down muscle protein, reducing metabolic rate
• Fluid retention — particularly with older formulations like prednisolone at higher doses
• Bone density loss — long-term glucocorticoids reduce bone density; weight-bearing exercise is important

Androgen Excess and Body Composition

Excess adrenal androgens (primarily DHEA-S, androstenedione, and testosterone from adrenal androgen pathway) in inadequately controlled CAH cause:

• Increased muscle mass initially — but also accelerated bone maturation causing early epiphyseal fusion and short adult stature
• Visceral adiposity — paradoxically, androgen excess in females (46,XX) drives abdominal fat accumulation via insulin resistance mechanisms similar to PCOS
• Insulin resistance and compensatory hyperinsulinaemia — driving further fat deposition
• Polycystic-appearing ovaries and menstrual irregularity — with PCOS-like metabolic syndrome risk in 46,XX patients

Optimising Glucocorticoid Dosing to Minimise Weight Gain

The most important weight management intervention in CAH is optimal glucocorticoid dose calibration — neither over- nor under-dosing. Both extremes cause problems:

Glucocorticoid Choice and Timing

In adults, the choice of glucocorticoid and dosing schedule matters for weight:

• Hydrocortisone (cortisol) — shortest-acting, most physiological; multiple daily doses (3x/day) mimic the natural cortisol rhythm better; generally preferred in adults despite tablet number burden
• Modified-release hydrocortisone (Plenadren) — once-daily formulation designed to replicate the diurnal cortisol profile; may cause less weight gain. Not widely available in SA currently.
• Prednisolone — longer-acting, more potent; convenient once or twice daily but greater risk of Cushingoid features and weight gain at equivalent doses
• Dexamethasone — very long-acting, very potent; useful for suppressing androgens in NCAH but highest Cushingoid risk; avoid high doses and avoid taking at night

Diet Strategies for Weight Management in CAH

Anti-Inflammatory, Low-Glycaemic Approach

Given the glucocorticoid-driven insulin resistance and androgen-mediated metabolic syndrome risk, the dietary pattern that best supports weight management in CAH is similar to that recommended for PCOS:

• Low glycaemic index carbohydrates — brown rice, sweet potato, legumes, oats over white bread, white rice, pap, and sweets; reduces postprandial glucose and insulin spikes
• Adequate dietary fibre — 25–35 g/day from vegetables, fruits, legumes; improves insulin sensitivity and supports satiety
• High-quality lean protein at each meal — chicken, fish, eggs, legumes, amasi (fermented milk); supports muscle mass maintenance
• Healthy fats — avocado, olive oil, nuts, pilchards/sardines (omega-3 for insulin sensitivity); limit saturated fat
• Limit ultra-processed foods — high-sugar, high-sodium processed items worsen fluid retention, which is particularly relevant in SW-CAH patients on fludrocortisone

Salt and Sodium in Salt-Wasting CAH

Patients with salt-wasting CAH on fludrocortisone have specific sodium management needs. While the general population is advised to limit sodium, SW-CAH patients — especially infants and in hot weather — may need adequate salt intake. However, excessive sodium from ultra-processed foods contributes to hypertension and fluid retention. Work with your endocrinologist to establish appropriate sodium targets for your individual situation.

Exercise in CAH

Benefits of Exercise

Exercise is one of the most effective interventions for counteracting the metabolic effects of glucocorticoid therapy:

• Resistance training (weights, bodyweight exercises) — preserves and builds muscle mass, counteracting glucocorticoid-induced muscle catabolism; significantly improves insulin sensitivity
• Aerobic exercise — walking, cycling, swimming, dancing — burns visceral fat, improves cardiovascular risk profile, reduces blood glucose
• Weight-bearing exercise — running, walking, strength training — essential for counteracting glucocorticoid-induced bone density loss
• Target minimum 150 minutes moderate aerobic activity plus 2–3 resistance sessions per week

Exercise Safety in CAH

• Always carry a medical alert bracelet or card identifying CAH and the need for emergency hydrocortisone
• Carry an emergency hydrocortisone injection kit (IM hydrocortisone 100 mg) for crisis management — available on prescription in SA
• Moderate-intensity exercise requires no dose adjustment in most patients
• Build exercise intensity gradually — especially if deconditioned from previous poor hormonal control

CAH in Females (46,XX): The PCOS Overlap

Adult females with CAH — both classic and non-classic — frequently present with features indistinguishable from PCOS:

• Polycystic-appearing ovaries on ultrasound
• Oligomenorrhoea or amenorrhoea
• Hirsutism, acne
• Central obesity and insulin resistance
• Reduced fertility

The key distinguishing test is an early morning (8 am) or ACTH-stimulated 17-OHP level. Women with NCAH are frequently misdiagnosed with PCOS for years. Correct diagnosis matters for treatment: NCAH responds to low-dose glucocorticoid supplementation (often dexamethasone 0.25 mg at night to suppress nocturnal ACTH), which is different from standard PCOS treatment. Weight loss responds better once the underlying androgen excess is adequately treated.

CAH in Males (46,XY)

CAH males face specific issues affecting weight and body composition:

• Testicular adrenal rest tumours (TARTs) — ectopic adrenal tissue in the testes, common in poorly controlled CAH males; can cause subfertility and testicular discomfort; improving CAH control reduces TARTs
• Short stature — excess androgens in childhood accelerate bone maturation; adult height often below genetic potential
• Increased central adiposity — particularly with over-treatment (Cushingoid pattern)
• Reduced bone density — from both the disease and glucocorticoid treatment

Monitoring in CAH

New Treatments Changing the Weight Equation

Several newer therapies are changing CAH management and have important weight implications:

• Crinecerfont (Neurocrine Biosciences) — a CRF1 receptor antagonist that suppresses ACTH directly at the pituitary, allowing glucocorticoid doses to be meaningfully reduced while maintaining androgen control. Clinical trial data shows significant weight reduction as glucocorticoid doses decrease. Not yet available in SA but likely to transform practice globally within the next few years.
• Tildacerfont — similar CRF1 receptor antagonist mechanism; in late-stage clinical trials
• Continuous subcutaneous hydrocortisone infusion — mimics the natural cortisol diurnal rhythm more precisely than oral tablets; may reduce glucocorticoid burden and improve metabolic outcomes; available at very limited specialist centres internationally

CAH Support in South Africa

• Steve Biko Academic Hospital, Pretoria — adult and paediatric endocrinology; major public sector CAH management centre
• Red Cross War Memorial Children's Hospital, Cape Town — leading paediatric endocrinology unit in SA
• Inkosi Albert Luthuli Central Hospital, Durban — paediatric and adult endocrinology
• Rare Diseases South Africa (RDSA): rarediseases.co.za
• CARES Foundation (international): caresfoundation.org — excellent CAH-specific resources including diet guides and patient community
• Endocrine Society of South Africa (ESSA): endocrine.org.za

Key Takeaways

• CAH causes cortisol deficiency, and often aldosterone deficiency, with androgen excess — all three hormonal imbalances affect body composition
• Lifelong glucocorticoid replacement is non-negotiable and life-saving, but promotes central adiposity and insulin resistance as side effects
• Optimal dose calibration — neither over- nor under-treating — is the single most important weight management intervention in CAH
• A low-glycaemic, high-fibre diet with adequate lean protein counteracts glucocorticoid-driven insulin resistance
• Resistance and aerobic exercise both counteract glucocorticoid-induced muscle loss and fat deposition — strongly recommended
• Never reduce glucocorticoid doses without specialist supervision — adrenal crisis is life-threatening
• Non-classic CAH (NCAH) frequently masquerades as PCOS — if standard PCOS treatment is not working, ask about 17-OHP testing