Endocrine Abstracts

Introduction: CNC (Carney complex) is a rare inherited autosomal dominant syndrome characterized by prominent pigmented lesions on the skin and mucosal surfaces, cardiac and noncardiac myxomatous tumors, and multiple endocrine neoplasms. About 70% of cases have a family history, while the remaining 30% occur sporadically as a result of de novo mutation. Two genetic loci linked to CNC have been found: the CNC1 gene on chromosome 17q22-24, which encodes the regulatory subunit (R1a) of protein kinase A (PRKAR1A) and is responsible for 2/3 of cases, and the CNC 2 gene is responsible for 1/3 of cases. The "CNC2" gene encoding the PKA (protein kinase A) catalytic subunit located at 2p16. Because clinical manifestations vary even within families, so-called "sporadic" cases require careful clinical evaluation by first-degree family members. Major, complementary and suggestive or possibly associated with CNC, but not diagnostic criteria for the disease are used for diagnosis. Endocrine neoplasms due to adrenal, pituitary gland tumors, or testicular tumors are the most common systemic manifestations of CNC.

Case: A 63-year-old female patient diagnosed with operated Merkel cell carcinoma was examined for primary hyperparathyroidism. The patient had hypercalcemia, hypophosphatemia and elevated parathormone since 2018, and the last corrected Ca-11.5 (8.8-10.6 mg/dl), P -2.4 (2.8-4.1 mg), PTH -146 (14-72 pg/ml), vitamin D-10.2 (30-100 ng/ml), 24-hour urinary calcium was 167.75 (100-300 mg). The bone mineral density was reduced. Ultrasound revealed parathyroid adenoma and multi-nodular goiter (MNG). Parathyroid scintigraphy revealed increased activity uptake. PRKAR1A gene mutation was positive in 2 daughters and 1 granddaughter of the patient, and her granddaughter had been operated for bilateral adrenal cushing. The patient had a nonfunctional pituitary microadenoma and bilateral adrenal nodular hyperplasia. The patient was operated for parathyroid adenoma and the pathology was compatible with adenoma. In the pathology of the nevus removed from the patient’s neck who had congenital nevi, was found melanocytic nevus. PRKAR1A gene mutation was negative. Other genetic analyzes associated with CNC could not be performed. Carney complex was considered in the patient because the patient had 1 major (bilateral adrenal nodular hyperplasia), 1 complementary (positive PRKAR1A gene mutation in first-degree relatives) and criteria suggestive of CNC (congenital nevi, MNG, family history of Cushing’s syndrome).

Conclusion: The highest risk of death in CNC is associated with heart disease, particularly cardiac myxomas and complications of cardiac surgery. Other causes of death include metastatic or intracranial psammomatous melanotic schwannoma, carcinoma, or metastatic tumors.