Background: Neonatal Cushing syndrome is a rare and severe condition, mostly associated with the McCune-Albright (MCA) syndrome. Management options include medical treatment (with ketoconazole or metyrapone resulting in 11-beta-hydroxylase blockade) and radical treatment with bilateral adrenalectomy. Spontaneous regression in late infancy has been reported.
Objective and hypotheses: To report on the outcome of a 14 month-old girl with severe neonatal Cushing syndrome on long-term treatment with metyrapone.
Results: The patient was born with severe growth restriction (-4DS for height and weight) and initially presented with neonatal hyperglycaemia requiring insulin treatment during 1 month. At the age of 2 months she was referred for severe Cushing syndrome with growth arrest, clinical Cushingoid features, elevated circadian cortisol > 1000 nmol/l not suppressible by dexamethasone and undetectable ACTH levels. She showed severe complications including hypertension requiring three medications, hypotonia and immune depression resulting in Pneumocystis infection. Medical treatment with metyrapone, administered by nasogastric tubing was initiated at the dose of 80 mg every 6 h. The evolution of hormonal markers by UPLC-MSMS are reported on the table. At the patients most recent visit, at the age of 14 months, hypercorticism was controlled with catch-up growth, disappearance of Cushingoid features, normal blood pressure and no clinical hyperandrogenism. Adrenal imaging showed bilaterally enlarged adrenals. She had no other features of the MCA syndrome. A search for activating mutation of the GNAS gene in PBMC DNA was negative and sequencing of several genes involved in adrenal function (MC2R, ARMC5, PRKAR1A) was normal.
|S compound (nmol/l)||0.13||206||201||107||81||56|
Conclusion: Long-term treatment of severe neonatal Cushing syndrome with metyrapone is efficient, well tolerated and can avoid bilateral adrenalectomy in transient cases. Mass spectrometry (UPLC-MSMS) for monitoring steroid changes is needed. This ultra specific method avoids overestimation of actual levels related to crossreactions between close molecules of steroids.
10 Sep 2016 - 12 Sep 2016