Cushing syndrome in children — formative SAQs

SAQ 1 — The adolescent who stopped growing (20 marks, ~15 minutes)

A 13-year-old girl presents with an eight-month history of weight gain, a round face, purple abdominal striae and fatigue. Her mother reports worsening mood and falling school marks. On the growth chart her weight has risen from the 75th to beyond the 95th centile, while her height has crossed down from the 50th to the 10th centile. Her blood pressure is 142/90. [1]

Questions

1. Give the most likely diagnosis and the single bedside feature that distinguishes it from simple obesity. (4 marks) [1]
2. Outline the confirmatory biochemical work-up, naming the three first-line tests and the principle that you use at least two. (5 marks) [3]
3. Once cortisol excess is confirmed, describe the localising step and the role of inferior petrosal sinus sampling. (5 marks) [5]
4. State the first-line definitive treatment and the perioperative medication that is mandatory to prevent adrenal crisis after cure. (6 marks) [6]

Model answer (must-hit)

1. This is Cushing syndrome (most likely pituitary Cushing disease). The discriminator from simple obesity is growth arrest — height crossing centiles downward while weight rises. In simple exogenous obesity the child is tall or growing normally, often with an advanced bone age, because over-nutrition drives growth; cortisol suppresses the growth-hormone axis. [1]
2. Confirm with at least two of three first-line tests: a late-night (midnight) salivary or serum cortisol (loss of the diurnal rhythm is the earliest and most sensitive change), a 24-hour urinary free cortisol, and an overnight dexamethasone suppression test (dexamethasone 15 µg per kilogram capped at 1 mg; an 8 am cortisol not suppressed below 1.8 µg per decilitre supports Cushing). Two tests are used because no single test is perfect and the disease is cyclic. [3]
3. Measure plasma ACTH. A high or inappropriately normal ACTH means ACTH-dependent disease (pituitary or, rarely, ectopic); a suppressed low ACTH means ACTH-independent adrenal disease. For ACTH-dependent disease, image the pituitary with dynamic gadolinium MRI. When the MRI is negative or non-lateralising, bilateral inferior petrosal sinus sampling confirms a pituitary source and helps lateralise the adenoma — a central-to-peripheral ACTH ratio above two at baseline, or above three after corticotrophin-releasing hormone, confirms pituitary Cushing disease. [5]
4. First-line treatment for pituitary Cushing disease is transsphenoidal selective adenomectomy by an experienced surgeon, with remission in roughly seventy to ninety percent of paediatric cases. The mandatory perioperative medication is stress-dose glucocorticoid, because the cured child's suppressed pituitary-adrenal axis cannot generate cortisol and tips into adrenal insufficiency within hours to days. Replace glucocorticoid until the axis recovers, often six to eighteen months. [6]

SAQ 2 — The Cushingoid child on inhaled steroids (20 marks, ~15 minutes)

An eight-year-old boy with severe asthma is brought in with a moon face, central obesity and purple striae over a six-month period. His height velocity has slowed. He takes high-dose inhaled fluticasone and has used oral prednisolone courses. His plasma ACTH is suppressed and the morning cortisol is low. [4]

Questions

1. Give the most likely diagnosis and the mechanism that explains the suppressed ACTH. (4 marks) [4]
2. Explain why you must not stop his steroids abruptly, and outline the safe approach. (5 marks) [4]
3. Contrast his ACTH result with that of a child who has pituitary Cushing disease, and explain the difference mechanistically. (5 marks) [5]
4. Describe the safety-net and education you would give the family during the taper. (6 marks) [4]

Model answer (must-hit)

1. This is iatrogenic (exogenous) Cushing syndrome from systemic absorption of inhaled and oral glucocorticoids, the single most common cause of a Cushingoid child. The exogenous steroid suppresses the hypothalamic-pituitary-adrenal axis through negative feedback, so the pituitary ACTH and endogenous cortisol both fall to low levels. [4]
2. Abrupt cessation would precipitate adrenal crisis, because the child's own axis is suppressed and cannot generate cortisol. The safe approach is to identify the source and taper it slowly under joint management with the prescribing respiratory team, with oral glucocorticoid cover maintained and adjusted, and intercurrent-illness cover provided throughout the wean. [4]
3. In iatrogenic Cushing the ACTH is suppressed (low or undetectable) because the exogenous steroid feeds back on the pituitary and hypothalamus. In pituitary Cushing disease the ACTH is high or inappropriately normal because a corticotroph adenoma secretes ACTH autonomously, ignoring the cortisol feedback; the high ACTH then drives bilateral adrenal hyperplasia and cortisol excess. The ACTH level is therefore the fork that separates the two mechanisms. [5]
4. Educate the family that the child is adrenally insufficient during and after the taper: give a written stress-dose plan (two to three times the replacement dose for illness), a parent-held intramuscular hydrocortisone emergency injection for vomiting or collapse, a MedicAlert identifier, and a school care plan. Counsel that fatigue and the need for replacement are expected during weaning, not a relapse. [4]