ESPE Abstracts

Cafe au-lait skin macules, Cushing syndrome (CS), hyperthyroidism, liver and cardiac dysfunction have been described as presenting features of neonatal McCune Albright Syndrome (MAS). Despite being defined, neonatal diabetes mellitus due to hypercortisolism is a rare presenting feature. Outcome of patients presenting in neonatal period is usually unfavorable, tthough spontaneous resolution of hypercortisolism have been reported. Newborn girl was born at 38 weeks of gestation via C/S weighing 2340g following an uneventful pregnancy as second child of healthy, nonconsanguineous couple. On her first day, she was hospitalized due to respiratory distress, liver enzymes were elevated. Neonatal sepsis was suspected, intravenous antibiotic was started. On 7^th day, she was discharged. She was referred to our hospital due to weight loss and deterioration of well-being on 11^th day. Hypotonia, round facies, hypertrichosis on forehead and extremities, large hyperpigmented macules on trunk were observed. Elevated liver enzymes and persistent hyperglycemia were noted (blood glucose: 240 mg/dl, insulin: 18 mIU/ml, urinary ketone: negative). Subcutaneous intermediate acting insulin (0.5 U/kg/day) was started. On 20^th day, hypertension was evident, antihypertensives were started. Further endocrinologic evaluation revealed increased serum cortisol (225 mg/dl), suppressed ACTH (10 pg/ml). 24-hour urinary free cortisol was 25 times the upper limit, high dose dexamethasone did not suppress cortisol. Further endocrine evaluation was normal otherwise. Mutation of GNAS was not detected by sequence analysis in peripheral blood. Metyrapone was preferred as liver functions were impaired. On 25^th day, as soon as metyrapone (300 mg/m²/day) was initiated, insulin and antihypertensives were ceased and she was discharged. Despite gradual increase in metyrapone (1850 mg/m²/day), cortisol and liver enzymes remained elevated, adrenal androgens increased and virilization was observed. As persistent hypercortisolism led to growth retardation, developmental delay, severe osteoporosis and left ventricle hypertrophy, right total and left three quarters adrenalectomy was performed at nine months. Cortisol (8 mg/dl) and adrenal androgens decreased substantially, ACTH (<5 pg/ml) remained suppressed. Due to symptoms of steroid withdrawal and hypoglycemia, oral hydrocortisone was started. Adrenal tissue GNAS sequence analysis detected pathogenic heterozygous missense mutation (c.2530C>A (p.Arg844Ser)), bilateral nodular hyperplasia was noted. This case underlines the unique phenotype of MAS specific to neonatal period. Persistent hyperglycemia was caused by initial excessive cortisol, which may be a negative prognostic factor for response to medical treatment and spontaneous resolution, an indication of early adrenalectomy. Three quarters adrenalectomy is an effective treatment option for CS due to MAS.