Endocrine Abstracts

Introduction

Carney Complex is a rare syndrome characterized by lentiginosis cutis and/or blue nevi, multiple endocrine neoplasia and non-endocrine tumors (cutaneous, mucosal, mammary or cardiac myxomata, bone osteochondromyxoma, psammomatous melanotic schwannoma, multiple ovarian cysts, multiple mammary ductal adenoma). Most cases are familiar, with autosomal dominant heredity and penetrance close to 100%. It is caused by a variety of mutations that activate the PKA (Protein Kinase A) pathway, inactivating mutations of the PRKAR1A gene being the most frequent. The endocrine manifestations may include PPNAD (primary pigmented nodular adrenocortical disease) Cushing syndrome, acromegaly (rarely gigantism), hyperthyroidism and LCCSCT (large cell calcifying Sertoli cell tumors). Most of the Carney Complex-associated neoplasms are benign, but in a few patients a particularly aggressive variant of follicular thyroid carcinoma has been described. Malignant tumors such as ovarian, pancreatic, gastric or hepatic carcinoma are also associated with the Carney Complex.

Methods

Review of the patient’s Clinical Record and of the relevant literature.

Clinical Case

A 56 year old man of black African descent was referred to the Endocrinology Clinic due to a cervical mass in the context of Carney Complex. No relatives of his have been diagnosed. Since his adolescence he had intense facial lentiginosis and scattered blue nevi. The diagnostic workup revealed bilateral nodular adrenocortical disease, small myxomata in both atria, with normal pituitary, adrenal and thyroid function and normal glucose tolerance. The atrial myxomata were resected without complications and the cardiac function is normal. The thyroid ultrasonography revealed multinodular goiter with dominant nodules measuring 3.5 cm (craniocaudal) in the left thyroid lobe adjacent to the isthmus, and 2.7 cm in the right lobe, with multiple cervical adenopathies. Ultrasound guided FNAC was performed, with both dominant nodules and 4/7 adenopathies positive for non-oncocytic follicular thyroid carcinoma (Bethesda IV, ATA stage IV-A, T2(m)N1bM0), Total thyroidectomy with radical cervical lymphadenectomy was performed, but plasma thyroglobulin was 97 ng/ml with negative antithyroglobulin antibodies. A rhTSH stimulated radioiodine scan was performed and the patient received 100 mCi of ¹³¹I but the response was poor and plasma thyroglobulin remained high (78 ng/ml). A PET-CT scan did not reveal abnormal activity beyond the cervical region. The patient has been referred to Oncology for kinase inhibitor therapy.

Conclusions

Although most of the tumors associated with Carney Complex are benign, the existence of malignant tumors of diverse origins must be ruled out. An aggressive variant of follicular thyroid carcinoma is a particularly ominous possibility.