Endocrine late effects of cancer treatment — formative SAQs

SAQ 1 (10 marks)

An 8-year-old boy was treated for a medulloblastoma at age 5 with surgical resection, craniospinal radiation (36 Gy to the craniospinal axis with a posterior fossa boost) and adjuvant chemotherapy. Eighteen months later his growth velocity has fallen to 3 cm/year, his height has crossed two centile lines downward, and his bone age is delayed by two years. His IGF-1 is low for age. [1] [3]

a) State the most likely endocrine diagnosis, justify it from the growth and biochemical findings, and name the exposure and dose threshold responsible. (3 marks) [1] [2]

b) Outline the next investigations, including the confirmatory test, the full pituitary axis panel, and the imaging that must precede any growth hormone therapy. (4 marks) [2] [6]

c) Describe the definitive management: the drug, the route and timing, and the single most important prerequisite before starting it. Then outline the broader surveillance plan for this survivor. (3 marks) [1] [2]

Answer

a) Growth hormone deficiency after cranial irradiation. The growth velocity of 3 cm/year is subnormal for age, the height is crossing centiles downward, the bone age is delayed, and the IGF-1 is low — the auxological and biochemical signature of growth hormone deficiency, which is the earliest and most common endocrine late effect of cranial radiation, with a dose-dependent threshold near 18 Gy and near-universal occurrence at the 36 Gy cranial dose this survivor received. [1] [2]

b) A growth hormone stimulation test (clonidine or arginine; glucagon) with a peak growth hormone below the age-appropriate cutoff confirming deficiency; a full pituitary axis panel — morning cortisol with a dynamic test (low-dose cosyntropin or insulin tolerance) for ACTH deficiency, TSH and free thyroxine for central hypothyroidism, gonadotropins and sex steroids — because the dose hierarchy means the other axes are also at risk; and a pituitary magnetic resonance imaging scan to exclude tumour recurrence, which must be obtained before any recombinant growth hormone is started because growth hormone is a mitogen. [2] [6]

c) Recombinant human growth hormone, subcutaneous once daily at bedtime, titrated to the IGF-1 in the age-appropriate range. The single most important prerequisite is a stable magnetic resonance imaging scan excluding tumour recurrence — never give growth hormone into an unimaged sella. The broader surveillance plan adds an annual morning cortisol, TSH and free thyroxine, gonadotropins at the expected age of puberty, a metabolic panel and bone density scan, and lifelong follow-up in the long-term follow-up programme. [1] [2]