Case Presentation: H.C. was admitted to the hospital at 7 weeks of age for failure to thrive. Patient is an ex 37 6/7 weeker, BW was 1.84 kg (0.02%, Z=-3.57), and was induced due to IUGR and oligohydramnios. H.C had an uneventful newborn nursery stay and normal newborn screen. On admission, weight was 2870 g, (<0.01%, Z= -3.96), length 42.5 cm (<0.01%, Z = -6.83), and head circumference 32cm (<0.01%, Z=-4.87). Physical exam was significant for moon facies, hyper-pigmented labia majora, slightly enlarged clitoral length, and mild hypotonia. No rashes or birthmarks. On review of systems, patient exhibited difficulty feeding with frequent emesis after feeds. No family history of genetic or endocrine disorders.Lab findings were significant for persistent leukocytosis, thrombocytosis, hyperkalemia, hypercalcemia, hypophosphatemia, hypoparathyroidism, elevated cortisol, and elevated DHEA. Constellation of findings were failure to thrive, Cushingoid features, nephrocalcinosis, ovarian cyst, ventricular hypertrophy on echocardiogram, heterogeneous bone density, and bilateral adrenal gland hypertrophy. Hypertension was protracted, with systolic blood pressures in 130s, and unresponsive to Amlodipine.
A dexamethasone suppression test indicated an ACTH independent hypercortisolemia. Differential was broad for genetic disorder versus cortisol secreting tumor. GNAS sequencing of peripheral blood for McCune Albright Syndrome, at 8 weeks of age, was negative. Focus shifted to treating hypercortisolism with Metyrapone and Ketoconazole. Patient continued to express hypercortisolism and hypertension with both medications, so a bilateral adrenalectomy was done at 12 weeks of age. Post-operative pathology confirmed a GNAS mutation consistent with McCune Albright Syndrome. H.C. was started on Hydrocortisone and Fludrocortisone, and weaned off Amlodipine three months after surgery. The first appearance of a café au lait macule occurred at three months of age. H.C is now 15 months, weight 7.7kg (3.3%, Z=-1.84), length 65.5cm (<0.01%, Z=-4.42), able to walk with assistance and babble.
Discussion: McCune Albright Syndrome (MAS) is rare and due to a mutation in the GNAS, resulting in a constant activation of Gsα-cAMP signaling pathway. Fibrous dysplasia is the most common presentation of MAS. Café-au-lait spots usually appear in the neonatal period and are midline with irregular boarders resembling “the coast of Maine”. Other manifestations are acromegaly, hyperthyroidism, and Cushing syndrome (the most rare). Genetic testing can often be falsely negative (due to the somatic mosaic nature of the disease). Treatment is symptom dependent; fibrous dysplasia; palliative, with surgery as needed for fractures. For precious puberty; tamoxifen or letrozole. For hyperthyroidism; thionamides, with surgery or radiation as a last resort. For acromegaly; long-acting somatostatin analogues are used or GH receptor antagonist (pegvisomant). For cushing syndrome; Metyrapone or Ketoconazole, with adrenalectomy for refractory patients.
Conclusions: MAS most commonly presents with fibrous dysplasia, precocious puberty, and café-au-lait macules. A primary presentation of cushing syndrome is a rare, however, it is a fatal manifestation of MAS. In this case report, cushingoid features were the primary set of symptoms that lead to further work-up, and eventual diagnosis.