Endocrine Abstracts

Background: Ectopic-ACTH syndrome (EAS) is an extremely rare cause of Cushing’s syndrome in young children. The intensity of ACTH secretion and hypercortisolaemia is greater in EAS than in Cushing’s disease. Control of hypercortisolaemia represents a key management step while awaiting localization of the ACTH source or in preparation to surgery. Etomidate inhibits cortisol synthesis and its rapid onset of action makes it an ideal medication in severe hypercortisolaemia.

Clinical case: A 6-year-old girl presented with hypertensive encephalopathy on a 6-months background history of excessive weight gain. On examination, she had moon facies, centripetal obesity and abdominal wall striae. Investigations showed markedly elevated serum cortisol (>2500 nmol/l) with loss of circadian rhythm and unsuppressed ACTH (95 ng/l). MRI-brain showed evidence of posterior reversible encephalopathy syndrome and normal appearances of pituitary gland. MRI of adrenal glands was normal. CT chest identified an enlarged partially calcified nodular thymus.

In view of life-threatening clinical presentation, hypercortisolaemia was managed with intravenous Etomidate (2.5–3.5 mg/h) infusion with close monitoring of serum cortisol. Hydrocortisone (1 mg/h) was added when serum cortisol <200 nmol/l. The thymic mass was surgically excised and histology showed a highly infiltrative neuroendocrine carcinoma with positive immunohistochemistry for ACTH. Post-resection, etomidate was stopped and hydrocortisone was weaned to maintenance doses (12 mg/m² per day). Serum ACTH levels decreased to <15 ng/l. PET-scan suggested residual disease and trough serum cortisol were still elevated. Hypercortisolaemia was managed with etomidate and hydrocortisone infusions prior to bilateral adrenalectomy. Currently she is on hydrocortisone and fludrocortisone replacement, and undergoing chemotherapy for residual disease.

Conclusions: Etomidate is a useful therapeutic agent for rapid control of hypercortisolaemic crisis. Close monitoring of serum cortisol and level of sedation is required while on etomidate infusion. Complete block and replace with hydrocortisone when serum cortisol <200 nmol/l is more convenient than achieving partial blockade by altering the etomidate infusion rate.