Growth hormone deficiency and excess — formative SAQs

SAQ 1 (10 marks)

A 6-year-old boy is referred because he is the shortest in his class. His height is on the 0.4th centile, more than two standard deviations below the mid-parental target, his growth velocity over the past year has been 4 cm/year (subnormal for age), 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 and justify it from the growth-chart and biochemical findings. (2 marks) [1] [3]

b) Outline the next investigations, including the stimulation test, its agent and its cutoff, and the imaging. (4 marks) [5] [1]

c) Describe the definitive therapy: drug, route, starting dose, and the monitoring that makes it safe. (4 marks) [1] [2]

Answer

a) Growth hormone deficiency (isolated, pending exclusion of multiple pituitary hormone deficiency). The height is below the third centile and distant from the mid-parental range, the growth velocity is subnormal for age, the bone age is delayed, and the IGF-1 is low — the biochemical and auxological signature of an endocrine growth failure rather than a constitutional variant. [1] [2]

b) Two growth hormone stimulation tests (clonidine and arginine, or glucagon), with a peak growth hormone below 6.7 to 10 ng/mL consistent with deficiency; pituitary magnetic resonance imaging to define the anatomy and exclude a structural lesion; and a full pituitary axis panel (TSH, free T4, cortisol, prolactin, gonadotrophins) to detect accompanying deficiencies. The cutoff was lowered from 10 to 6.7 ng/mL with modern immunoassays to improve specificity. [5] [1]

c) Recombinant human growth hormone, subcutaneous once daily at bedtime, starting at 0.045 to 0.050 mg/kg/day and titrated to keep the IGF-1 in the upper half of the age- and sex-normal range. Monitor growth velocity, IGF-1, adherence and injection sites at each visit, and screen for adverse effects — headache and papilloedema (benign intracranial hypertension), slipped capital femoral epiphysis, scoliosis, glucose intolerance — with annual thyroid function. [1] [2]

SAQ 2 (10 marks)

A 9-year-old girl presents with rapid growth and increasing shoe size. Her growth velocity is above the 97th centile for age, her IGF-1 is markedly elevated, and her growth hormone does not suppress below 1 ng/mL after a 75-gram oral glucose load. An MRI shows a pituitary macroadenoma abutting the optic chiasm. [10] [12]

a) State the diagnosis and the two pathophysiological determinants of whether she has gigantism rather than acromegaly. (2 marks) [10]

b) Outline the immediate priorities before definitive treatment, including hormone replacement and visual assessment. (3 marks) [10]

c) Describe the stepwise definitive management, naming the surgical approach and the two medical agents used when surgery does not achieve biochemical control, and the role of genetic testing. (5 marks) [10] [11]

Answer

a) Pituitary gigantism from a growth hormone-secreting macroadenoma. The determinants are the autonomy of the somatotropinoma (sustained, non-suppressible growth hormone secretion) and the open state of her growth plates (she is prepubertal, so excess drives linear growth rather than acral overgrowth). [10]

b) Protect the chiasm with urgent ophthalmology and neurosurgery involvement; replace any deficient pituitary hormones, prioritising cortisol (hydrocortisone) and thyroid; and assess and control the metabolic consequences — glucose intolerance, hypertension and any cardiac dysfunction. Formal visual field testing documents the baseline chiasmal compression. [10]

c) Endoscopic transsphenoidal resection is first-line. When surgery cannot achieve biochemical control — common with large, invasive or AIP-mutant tumours — a somatostatin analogue (lanreotide autogel or octreotide) suppresses growth hormone secretion, and the growth hormone receptor antagonist pegvisomant blocks growth hormone action and normalises IGF-1; pegvisomant has a defined role in the AIP-mutant resistant tumours. Radiotherapy is reserved for residual or recurrent disease. Genetic testing for AIP, GPR101 duplication (X-linked acrogigantism), MEN1 and GNAS guides family surveillance and the choice of medical therapy. [10]