Carney complex with adrenocorticotropic hormone-independent Cushing syndrome with PRKAR1A gene variant: a case report

Primary pigmented nodular adrenal disease (PPNAD) is an autosomal dominant condition and a rare cause of Cushing syndrome, independent of pituitary origin, and is adrenocorticotropin (ACTH) independent. Carney complex PPNAD (cPPNAD) is associated with inactivating mutations of the regulatory subunit type 1A of the cAMP-dependent protein kinase (PRKAR1A) gene which is found in more than 70% of Carney complex cases. PRKAR1A is a tumor suppressor gene located in the 17q23-24 region of the human chromosome and plays an important role in regulating cellular metabolism, differentiation, and proliferation. Here we report a case of PPNAD in a 15 year old Indian female presenting with endogenous Cushing syndrome. She underwent bilateral adrenalectomy which on histological evaluation demonstrated pigmented nodular adrenocortical hyperplasia with small to normal sized adrenal glands showing varying number of cortical nodules. In view of the presence of characteristic lentigines, she underwent further evaluation for carney complex and was found to have harbor the PRKAR1A mutation. Subsequent evaluation of her sibling found him to be symptomatic and harbor a similar mutation in a heterozygous state. In young female patients presenting with Cushing’s syndrome, and skin pigmentation, evaluation for PRKAR1A mutation and presence of Carney complex should be considered pre-operatively. Unilateral adrenalectomy can be done in young women who may consider pregnancy in the future. Genetic counselling for the patients and the parents may be needed regarding the potential risks associated and educated about the endocrine and cardiac complications. Family members of these patients should undergo appropriate screening, endocrine evaluations, echocardiography, and genetic testing, for early detection and treatment of lesions.