Endocrine Abstracts

Introduction: Carney complex (CNC) is a rare multiple neoplasia syndrome characterized by pigmented lesions of the skin and mucosa in association with various endocrine and non-endocrine tumors. The disease can be inherited in an autosomal-dominant fashion or occur sporadically due to novel mutations in the PRKAR1A gene. Primary pigmented nodular adrenocortical disease (PPNAD) is a common endocrine manifestation of CNC.

Case description: A 20-year-old woman with bilateral avascular necrosis of the femoral heads was referred for suspected Cushing’s syndrome. She reported a 34 kg weight gain, significant stretch marks, rounding of the face, and worsening anxiety over the past year. Physical examination revealed facial plethora, dorsal fat pad, truncal obesity, and multiple striae. In addition, she had several hyperpigmented macules on her lips. Biochemical investigation showed 24 hour urine free cortisol of 22 μg/24 h (reference range 3.5–45 μg/24 h) and non-suppressible serum cortisol levels of 9.5 μg/dl (262 nmol/l) and 13.0 μg/dl (359 nmol/l) following 1 and 8 mg overnight dexamethasone administration respectively. Adrenocorticotrophic hormone (ACTH) was undetectable at <5.0 pg/ml (reference range 10–60 pg/ml), suggestive of ACTH independent Cushing’s syndrome. Non-contrast CT imaging of the abdomen failed to identify an adrenal mass and was read as normal. On closer examination, however, there appeared to possible bilateral adrenal micronodular disease present. She subsequently underwent bilateral laparoscopic adrenalectomy, and pathology confirmed PPNAD. Genetic testing revealed a novel frameshift pathogenic variation in the PRKAR1A gene, consistent with a Carney complex diagnosis. Screening echocardiogram and thyroid ultrasound did not reveal cardiac myxoma or thyroid disease. Femoral head necrotic lesions resolved without the need for orthopedic intervention.

Discussion: We present a case of Cushing’s syndrome revealing CNC due to a novel inactivating PRKAR1 mutation. PPNAD, in association with CNC, should be considered in the differential for ACTH independent Cushing’s syndrome, especially when adrenal imaging appears normal.