Cushing syndrome in children

The single observation that organises everything in paediatric Cushing syndrome is the growth chart decoupling. Cortisol is catabolic and it suppresses the growth-hormone axis, so a child bathed in cortisol gains weight while height falls away. A fat child who keeps growing is almost never Cushing; a fat child who has stopped growing is Cushing until you prove otherwise. [1] [9]

This page covers the recognition and management of Cushing syndrome in children: the growth-arrest presentation, the ACTH-dependent versus ACTH-independent split, the three-test confirmatory work-up, the localising steps including inferior petrosal sinus sampling, transsphenoidal surgery for pituitary disease, adrenalectomy for adrenal disease, and the perioperative glucocorticoid replacement that prevents the adrenal crisis of a suddenly cured child. It links to the adrenal insufficiency leaf for stress-dose detail rather than repeating it. [3] [10]

Overview & Definition

Cushing syndrome means any state of chronic endogenous cortisol excess, whatever the source. The name Cushing disease is reserved for the specific cause — a pituitary corticotroph adenoma that secretes adrenocorticotrophic hormone (ACTH) and drives both adrenal glands to overproduce cortisol. Everything else is Cushing syndrome: adrenal tumours, bilateral adrenal hyperplasia, ectopic ACTH, and the exogenous steroids that cause the commonest form of all. [5]

What makes the paediatric disease distinctive is that children are still growing, and growth is exquisitely sensitive to cortisol. The adult face of Cushing is central obesity, a moon face, striae and hypertension, and those all appear in children too — but the first and most reliable sign is that the child falls off their height centile. Growth arrest is reported in roughly four out of five children with endogenous Cushing, and it is the feature that distinguishes the disease from simple obesity, where height tracks upward with weight. [1] [2]

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1. [1]Magiakou MA; Mastorakos G; Oldfield EH; et al Cushing's syndrome in children and adolescents. Presentation, diagnosis, and therapy. N Engl J Med, 1994.PMID 8052272
2. [2]Magiakou MA; Chrousos GP Cushing's syndrome in children and adolescents: current diagnostic and therapeutic strategies. J Endocrinol Invest, 2002.PMID 11929092
3. [3]Nieman LK; Biller BM; Findling JW; et al The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab, 2008.PMID 18334580
4. [4]Nieman LK; Biller BM; Findling JW; et al Treatment of Cushing's Syndrome: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab, 2015.PMID 26222757
5. [5]Lacroix A; Feelders RA; Stratakis CA; Nieman LK Cushing's syndrome. Lancet, 2015.PMID 26004339
6. [6]Kanter AS; Diallo AO; Jane JA Jr; et al Single-center experience with pediatric Cushing's disease. J Neurosurg, 2005.PMID 16302612
7. [7]Magiakou MA; Smyrnaki P; Chrousos GP Hypertension in Cushing's syndrome. Best Pract Res Clin Endocrinol Metab, 2006.PMID 16980206
8. [8]Stratakis CA; Mastorakos G; Magiakou MA; et al Thyroid function in children with Cushing's disease before and after transsphenoidal surgery. J Pediatr, 1997.PMID 9427898
9. [9]Ferrigno R; Hasenmajer V; Caiulo S; et al Paediatric Cushing's disease: Epidemiology, pathogenesis, clinical management and outcome. Rev Endocr Metab Disord, 2021.PMID 33515368
10. [10]Korbonits M; Blair JC; Boguslawska A; et al Consensus guideline for the diagnosis and management of pituitary adenomas in childhood and adolescence: Part 2, specific diseases. Nat Rev Endocrinol, 2024.PMID 38336898