Cyclical Cushing Syndrome Presenting in Infancy: An Early Form of Primary Pigmented Nodular Adrenocortical Disease, or a New Entity?

• Published in: The journal of clinical endocrinology and metabolism 2004-07, Vol.89 (7), p.3173-3182
• Main Authors: Gunther, Daniel F., Bourdeau, Isabelle, Matyakhina, Ludmila, Cassarino, David, Kleiner, David E., Griffin, Kurt, Courkoutsakis, Nickolas, Abu-Asab, Mones, Tsokos, Maria, Keil, Meg, Carney, J. Aidan, Stratakis, Constantine A.
• Format: Article
• Language: English
• Subjects: Adrenal Cortex Diseases - blood; Adrenal Cortex Diseases - diagnosis; Adrenal Cortex Diseases - pathology; Adrenal Cortex Diseases - surgery; Adrenal Glands - pathology; Adrenalectomy; Adrenals. Adrenal axis. Renin-angiotensin system (diseases); Biological and medical sciences; Cushing Syndrome - diagnosis; Diagnosis, Differential; DNA, Neoplasm - analysis; Endocrinopathies; Female; Follow-Up Studies; Fundamental and applied biological sciences. Psychology; Hormones - blood; Humans; Hydrocortisone - blood; Hyperplasia; Infant, Newborn; Medical sciences; Microscopy, Electron; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Periodicity; Tomography, X-Ray Computed; Vertebrates: endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2003-032247

Cushing syndrome is uncommon in childhood and rare in infancy. We report the case of a 3-yr-old child who presented with symptoms of Cushing syndrome beginning shortly after birth. Her hypercortisolemia was cyclical, causing relapsing and remitting symptoms, which eventually led to suspicions of possible Munchausen syndrome by proxy. Investigation at the National Institutes of Health excluded exogenous administration of glucocorticoids and indicated ACTH-independent Cushing syndrome. Paradoxical response to dexamethasone stimulation (Liddle’s test) suggested a diagnosis of primary pigmented nodular adrenocortical disease (PPNAD). 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 PRKAR1A gene (associated with PPNAD and Carney complex) and the GNAS gene (associated with McCune-Albright syndrome) showed no mutations. We conclude that hypercortisolemia in infancy may be caused by micronodular adrenocortical hyperplasia, which can be cyclical and confused with exogenous Cushing syndrome. A paradoxical rise of glucocorticoid excretion during Liddle’s test may delineate these patients. 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 PRKAR1A or GNAS genes or associated with typical histology or any other features of Carney complex or McCune-Albright syndrome and may represent a distinct entity.