Background: McCune Albright syndrome (MAS) is defined by the classic triad of precocious puberty, fibrous dysplasia of bone and café au lait skin pigmentation. However, the clinical spectrum is often more variable due to mosaic distribution of the postzygotic GNAS-mutation. Hypercortisolism occurs in a minority (5%) of patients. It is most frequently caused by nodular adrenal hyperplasia and can be life-threatening. Decisions on whether clinical management should be conservative or should involve active intervention are challenging.
Case presentation: We report a male neonate (birth weight 2 560 g; −2.5 S.D.) with café au lait skin pigmentation as described in MAS and neonatal cholestatic liver disease of unknown origin. At the age of 4 months he developed a Cushingoid appearance, failure to thrive (height 54.4 cm −3.2 S.D. and weight for height 3800 g −1.0 S.D.) and hypertension. Blood and saliva GNAS mutational analysis were both negative, but a mutation could be identified in tissue obtained during previous liver biopsy. Diagnostic work-up showed elevated evening saliva cortisol levels (22 nmol/l; ref1-6 nmol/l), normal urinary 24 h free cortisol excretion and variable serum cortisol levels. Cortisol levels were unsuppressed after a high-dose dexamethason suppression test. MRI showed unilateral enlargement of the adrenal gland. Therefore metyrapone treatment was initiated at the age of 6 months. A questionable clinical response and raising concerns towards the effect on cerebral white matter led to the decision to stop treatment after six months. Subsequently, growth and biochemistry were regularly assessed. At the age of 1.5 years the clinical condition of the toddler gradually improved. Currently, at age 2.5 years, failure to thrive has resolved and height growth is improving (−2 S.D. target height −0.8 S.D.). Cholestasic liver disease persists without deterioration. There are no signs of other hormonal involvement and clinical features of hypercortisolism have ameliorated.
Conclusion: Conservative treatment of neonatal Cushing syndrome in MAS allows partial or complete recovery of Cushing syndrome, although close monitoring is required.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology