Endocrine Abstracts

A 25-year-old Caucasian male was reviewed in adult endocrinology in Leeds, with a background of non-classical congenital adrenal hyperplasia (CAH) due to partial 21-hydroxylase deficiency. He initially presented at age 5 with behavioural difficulties and body odour, suggestive of early androgen exposure. Examination revealed normal prepubertal genitalia. Investigations showed elevated 17-hydroxyprogesterone (17 OHP; 10.0 nmol/l) and suboptimal cortisol response on synacthen testing, with peak 17 OHP of 258 nmol/l. Urine steroid profiling and genetic testing confirmed the diagnosis. Hydrocortisone was commenced (8–10 mg/m²/day). By age 11, he showed pubertal advancement (bone age 15.1 years; G4 P4; testes 15 mL). GnRH analogue therapy was offered but declined. By age 13, puberty was nearly complete (G5 P5; testes 20–25 mL) with final height on the 50 th centile. Hydrocortisone was tapered to 6.9 mg/m²/day based on 17 OHP levels. Adolescence was complicated by poor adherence, emotional difficulties, and CAMHS involvement. At 16, synacthen testing showed adequate adrenal reserve (cortisol 243 → 457 nmol/l), and maintenance steroid therapy was discontinued. Hydrocortisone was advised only during illness or stress. During this time, he developed obesity and disordered eating behaviours. At age 25, he re-presented with fatigue, delayed sleep phase, and significant weight gain (BMI 47.5). He had restarted paediatric-dose hydrocortisone via his GP but noted no improvement. Repeat SST confirmed adequate adrenal reserve (cortisol 425 → 713 nmol/l), and steroids were stopped. 17 OHP remained elevated (147 nmol/l), as did androstenedione (14.8 nmol/l). Testosterone was low (6.2 nmol/l; ref 8–30) with low SHBG (17) and preserved gonadotropins (LH 4.5, FSH 2.9), consistent with obesity-induced hypogonadotropic hypogonadism. Estradiol was normal; libido and erectile function were intact. Testicular ultrasound was arranged to exclude TARTs. He is now a university student in a stable relationship and is keen to attend Tier 3 weight management services. He has been referred for sleep studies to exclude OSA.

Discussion: Dynamic interplay between adrenal and gonadal axes in non-classical CAH: Although adrenal androgen excess persisted, testicular output was suppressed by obesity-related hypogonadism. In adulthood: • Adrenal androgens in partial CAH may only modestly boost testosterone. • If obesity suppresses HPT axis, testicular loss outweighs adrenal contribution. • The result is low testosterone despite a condition once associated with excess androgens. Testes provide ~90–95% of adult male testosterone; adrenal overproduction cannot compensate when HPT axis function is impaired.

Conclusion: This case underscores the importance of holistic, longitudinal care in endocrine conditions with paediatric onset. In non-classical CAH, persistent adrenal androgen production does not guarantee sufficient androgenisation in adulthood if testicular output is compromised. Clinicians must be vigilant for obesity-related secondary hypogonadism, and management should prioritise metabolic health alongside endocrine control.