Endocrine late effects of cancer treatment — branching viva

Branch 1 — the brain-tumour survivor with growth failure

The candidate is expected to justify growth hormone deficiency over a normal variant from the growth velocity, the delayed bone age and the low IGF-1, and to explain that growth hormone deficiency is the earliest and most common endocrine late effect of cranial radiation because the somatotroph axis is the most radiosensitive, with a dose-dependent threshold near 18 Gy and near-universal occurrence at the 36 Gy cranial dose. The confirmation is the growth hormone stimulation test with a peak below the age-appropriate cutoff, and the imaging is the pituitary magnetic resonance imaging scan that must precede any recombinant growth hormone because growth hormone is a mitogen. [1] [2]

The examiner branches into the dose hierarchy: growth hormone deficiency at 18 Gy, gonadotropin disturbance at 24 to 30 Gy, TSH and ACTH deficiency above 30 to 40 Gy, and panhypopituitarism at the highest doses — so this survivor must be screened across the whole axis, not only for growth hormone deficiency. The replacement order is named and justified: hydrocortisone before levothyroxine before sex steroids, with recombinant growth hormone after the magnetic resonance imaging, because giving thyroxine before cortisol precipitates an adrenal crisis. [2] [6]

Branch 2 — the leukaemia survivor with rapid puberty

The candidate is expected to recognise paradoxical central precocious puberty after lower-dose cranial radiation. At doses between roughly 18 and 24 Gy the radiation disinhibits the hypothalamic gonadotropin-releasing-hormone pulse generator before the gonadotroph neurones are destroyed, so the same exposure that causes gonadotropin deficiency at higher doses causes precocious puberty at lower doses. The GnRH stimulation test confirms central activation, the accelerated bone age threatens final height, and a gonadotropin-releasing-hormone analogue halts the progression and preserves final height. [1] [2]

The examiner branches into the differential and the surveillance: the rapid progression must be distinguished from a normal-variant early puberty and from a peripheral cause, the response to the analogue is monitored by growth velocity and bone age, and the family is counselled that the therapy is time-limited and that ongoing surveillance of the other axes is lifelong because further late effects will accumulate. [1] [3]

Branch 3 — the transplant survivor with primary amenorrhoea

The candidate is expected to diagnose primary gonadal failure from the alkylating chemotherapy and total-body irradiation conditioning, confirmed by raised gonadotropins with a low oestradiol, and to distinguish it from central hypogonadism (low or inappropriately normal gonadotropins) that would follow high-dose cranial radiation. The Vatanen study documented the high rate of primary ovarian failure after allogeneic stem cell transplantation and its dependence on the conditioning regimen and the age at transplantation, underpinning the move toward fertility preservation counselling before conditioning begins. [3] [11]

The examiner branches into management and transition: sex-steroid replacement at the physiological age, early fertility counselling and referral to the reproductive medicine service, and the structured transition to adult survivorship care with a written handover and a named adult provider — because surveillance adherence falls and the metabolic, bone and cardiovascular late effects continue to accumulate across the lifespan. [6] [11]