Hypopituitarism and pituitary lesions — formative SAQs

SAQ 1 — The hypoglycaemic newborn (20 marks, ~15 minutes)

A term male newborn is admitted on day four with recurrent hypoglycaemia, prolonged jaundice and poor feeding. On examination he has a small phallus and both testes are undescended. A critical sample taken during a documented blood glucose of 1.8 mmol per litre is pending. Congenital hypopituitarism is suspected. [1]

Questions

1. State the biochemical tests you would ensure were taken on the critical sample and the two hormone deficiencies that together explain the hypoglycaemia. (5 marks) [1]
2. Outline your immediate management before the results return, and state the single most dangerous deficiency to miss. (5 marks) [9]
3. When replacement is started for combined deficiency, state the correct order of glucocorticoid and thyroxine and explain why. (5 marks) [10]
4. List two associated central nervous system findings that would support a congenital cause. (5 marks) [1]

Model answer (must-hit)

1. The critical sample should include paired glucose, cortisol, growth hormone, insulin, free thyroxine and thyroid-stimulating hormone drawn at the time of the hypoglycaemia. The hypoglycaemia is explained by combined growth hormone and cortisol (adrenocorticotrophin) deficiency, both of which are counter-regulatory hormones. [1]
2. Give an intravenous glucose bolus followed by a maintenance infusion, and administer stress-dose intravenous hydrocortisone without waiting for the results. The most dangerous deficiency to miss is central adrenal insufficiency (cortisol deficiency), which can be rapidly fatal. [9]
3. Glucocorticoid must be started before levothyroxine. Thyroxine raises the metabolic rate and accelerates cortisol clearance, so starting it first in a child with unrecognised cortisol deficiency can precipitate an adrenal crisis. [10]
4. Optic nerve hypoplasia and an absent septum pellucidum (septo-optic dysplasia), or a midline cleft lip and palate with a single central incisor, support a congenital midline cause. [1]

SAQ 2 — Short stature with a visual field defect (20 marks, ~15 minutes)

A 9-year-old boy is referred with short stature. His height has fallen from the fiftieth to below the third percentile over three years, with a low height velocity. His mother reports recent morning headaches, and on testing he has a bitemporal visual field defect. [5]

Questions

1. State the single most important imaging investigation and the lesion you most expect to find. (4 marks) [5]
2. State the usual order in which anterior pituitary hormones are lost. (4 marks) [1]
3. Explain why a random growth hormone level cannot diagnose growth hormone deficiency and name the confirmatory test. (6 marks) [7]
4. State how central hypothyroidism is distinguished biochemically from primary hypothyroidism. (6 marks) [1]

Model answer (must-hit)

1. Magnetic resonance imaging of the hypothalamus and pituitary with contrast. The combination of growth failure, headache and a bitemporal field defect from chiasmal compression makes a craniopharyngioma the most likely lesion. [5]
2. Growth hormone is usually lost first, then the gonadotrophins (luteinising hormone and follicle-stimulating hormone), then thyroid-stimulating hormone, and finally adrenocorticotrophin, so cortisol deficiency is last but most dangerous. [1]
3. Growth hormone secretion is pulsatile, so a random level drawn between pulses reads low in normal children and cannot diagnose deficiency. Deficiency is confirmed by a growth hormone stimulation test (insulin tolerance, glucagon, arginine or clonidine) showing a subnormal peak, together with a low IGF-1 and clinical growth failure. [7]
4. In central hypothyroidism the free thyroxine is low while the thyroid-stimulating hormone is low or inappropriately normal, because the failing pituitary cannot drive it up. In primary hypothyroidism the free thyroxine is low but the thyroid-stimulating hormone is high. Measuring the free thyroxine, not the thyroid-stimulating hormone alone, is essential. [1]