Carney Complex With Endocrine Involvement Isolated to the Thyroid Gland

Abstract

\n Introduction: Carney complex is a rare autosomal dominant disorder characterized by pigmented lesions of skin and mucosae, endocrine neoplasms or overactivity, and myxomas of the heart, skin, and other organs. Most patients have at least two affected endocrine organs at time of diagnosis. We present a case of Carney complex with endocrine involvement limited to the thyroid gland. Case: A 48-year-old female was referred for evaluation of thyroid nodules incidentally discovered on imaging for submandibular salivary gland swelling. Ultrasound evaluation of the thyroid revealed numerous, bilateral nodules that were mostly cystic or spongiform, though some had irregular borders and microcalcifications. A brother with Carney complex had been diagnosed with papillary carcinoma, and the patient decided to undergo thyroidectomy. Fortunately, no thyroid carcinoma was found on postsurgical histopathology. Initial biochemical evaluation showed no evidence of hypercortisolemia (8 AM cortisol 1.7 mcg/dL on 1 mg dexamethasone suppression test; 24-h urine cortisol 26.1 mcg [reference: 4-50]), growth hormone excess (IGF-1 190 ng/mL [reference: 52-328]), or hyperprolactinemia (prolactin 10 ng/mL [reference: 2.74-26.72]). Imaging showed no pituitary or adrenal masses. The patient underwent total hysterectomy with bilateral salpingo-oophorectomy for endometrial cancer prior to referral. She was diagnosed with Carney complex at age 19 years, and her manifestations included atrial and ventricular myxomas, intraductal adenoma of the breast, multiple skin lesions (lentigines, blue nevi, and cutaneous myxomas), and myxomas of the external auditory canals. She is in a Carney complex kindred that includes her mother, two brothers, and a niece. Discussion: Carney complex is usually caused by inactivating mutations or large deletions in the protein kinase A type I alpha regulatory subunit (PRKAR1A) gene located on chromosome 17q22-24. Most mutations are inherited in an autosomal dominant manner, though approximately 30% of cases are due to de novo mutations. In a review of 365 cases, the median age at diagnosis was 20 years. Growth hormone adenomas or somatomammotroph hyperplasia occurs in approximately 75% of patients, and most have at least one additional endocrine abnormality including multinodular goiter, primary pigmented nodular adrenocortical hyperplasia, and testicular or ovarian masses. There is an approximately 10% chance of developing well differentiated thyroid carcinoma. Treatment for Carney complex is individualized depending on the patient’s presentation and includes excision or surgical removal of myxomas, neoplasms, and skin lesions, as well as regular evaluation for cardiac myxomas and endocrine overactivity. This case of Carney complex is unusual because the only endocrinopathy is multinodular goiter.