On examination, systolic blood pressure was 120 mm Hg and diastolic 61 mm Hg.A morning cortisol level was normal at 6 μg/dl (166 nmol/liter), with an ACTH of 11 pg/ml (2.4 pmol/liter). The patient’s symptoms continued to resolve and there was rapid weight loss.The patient was eventually diagnosed with ACTH-independent Cushing syndrome, underwent bilateral adrenalectomy, and was found to have micronodular adrenocortical hyperplasia.However, the clinical presentation of the patient, and her tissue and genetic analyses, differentiates this case from classic PPNAD, Carney complex, or Mc Cune-Albright syndrome. The mother’s pregnancy had been complicated by maternal hypertension. The placenta was grossly normal but the umbilical cord was small.Infantile micronodular disease has some features of PPNAD and may represent its early form; however, at least in the case of the patient reported here, micronodular hyperplasia was not caused by coding mutations of the CUSHING SYNDROME IN childhood is most often iatrogenic caused by excessive glucocorticoid hormone administration (1–3).
An infant reported by Sobel and Taft in 1959 (28) may also have had Cushing syndrome since early infancy (21, 28).Evaluation was undertaken within a week after the onset of symptoms.Plethora and obesity were noted on physical examination (Fig. The growth velocity over the last 10 months had been normal.Most patients with PPNAD also have Carney complex, an autosomal dominant multiple neoplasia syndrome, which consists of skin lentigines, myxomas, and other nonendocrine and endocrine tumors, and is also caused by mutations (25, 26).Patients with PPNAD may present with atypical forms of Cushing syndrome such as cyclical or episodic Cushing syndrome (29–32).After bilateral adrenalectomy, both glands showed micronodular adrenocortical hyperplasia, but histology was not consistent with typical PPNAD.DNA analysis of the coding sequences of the gene (associated with Mc Cune-Albright syndrome) showed no mutations.Micronodular adrenocortical hyperplasia and its better-known pigmented variant, primary pigmented nodular adrenocortical disease (PPNAD), are invariably bilateral (24).Familial and sporadic cases of PPNAD have been reported to be associated with germline inactivating mutations of the gene (25–27).These unusual patients can have remitting and relapsing symptoms on a cycle ranging from days to years, a phenomenon that remains largely unexplained (33).Although cyclical Cushing syndrome has been reported before in a number of pediatric patients with (34, 35) or without PPNAD (4), it has not been documented in the neonatal period in a patient with micronodular disease.