Endocrine Abstracts

A 16-year-old boy was referred to our endocrine unit. He had been diagnosed with constitutional short stature (height <10^th centile) aged 11, having not grown well for two years. At that time there were no features to suggest Cushing's syndrome (CS), though he was overweight (BMI 22kg/m², >90^th centile) and bone age was delayed by 2 years. A trial of growth hormone (GH) therapy did not increase growth velocity. By age 15, he was developing a florid appearance. Urinary free cortisol was raised (755nmol/day) but serum cortisol fully suppressed (<30nmol/L) following 1mg dexamethasone suppression. Pituitary MRI showed no convincing abnormality.
At 16 he was short (1.42m, <3rd centile), with a plethoric face. He had no other features of CS and was well virilised. Endocrine testing again did not confirm CS but multiple overnight cortisol/creatinine ratios were raised (>25nmol/mmol). Basal ACTH was 23ng/l and petrosal sinus sampling demonstrated a large gradient (30:1) of ACTH into the right petrosal sinus. Repeat MRI could not demonstrate any abnormality and he underwent a right hemihypophysectomy. Post-operative cortisol remained elevated (840nmol/l). Following repeat surgery a month later, he had undetectable serum cortisol on day 5.
At 17, he appeared to have completed puberty (Tanner stage 4-5) and had not grown in 9 months. Repeat bone age suggested some growth potential. His height remained 1.42m (MPH 1.72m), weight 60.4kg (BMI 30kg/m²) and he was restarted on GH. Six months later he has grown 6cm and lost 9kg in weight (BMI 23kg/m²) and is well on thyroxine, hydrocortisone and growth hormone replacement.
This case illustrates the challenges of diagnosing and treating CS in adolescence, where the only clinical feature may be growth failure (resistant to growth hormone) and, as in adults, endocrine testing and neuroradiology may be equivocal. In addition, growth potential in late adolescence may remain, and a trial of growth hormone following curative surgery in this young man brought significant benefits.