SAT-LB48 Novel Genetic Variant of Carney Complex With Acromegaly

Objective: To describe an uncommon case of Carney complex with acromegaly secondary to pituitary microadenoma with a novel genetic variant. Background: Carney complex (CNC) is a rare autosomal dominant syndrome characterized by myxomas, pigmented skin and mucosal lesions, as well as multiple endocrine tumors. The etiology is an inactivating mutation of the regulatory subunit type 1A of the cAMP-dependent protein kinase (PRKAR1A). Recently, additional CNC pathologic variants in PRKACA and PRKACB have been identified.[1] Elevated growth hormone (GH) and IGF-1 levels are sometimes seen in patients with CNC, thought to be secondary to somatotroph hyperplasia. However, less than one fifth of patients with CNC have clinical acromegaly. [2] Case: Here we describe a 35-year-old female diagnosed with atrial myxoma after presenting with fatigue in her 20s. After her fatigue failed to resolve following surgical excision, further investigation revealed an ovarian tumor. The patient sought care in Mexico where she underwent radiation for presumed ovarian malignancy. Review of the ovarian lesion biopsy at a university hospital later revealed benign melanocyte proliferation. She subsequently developed amenorrhea and hirsutism which prompted referral to endocrinology. Evaluation revealed coarse facial features, large hands, elevated IGF-1, and positive GH suppression test leading to a diagnosis of acromegaly. Gene sequencing revealed a novel pathologic variant of PRKAR1A consistent with CNC. MRI brain was originally negative for pituitary lesions; however follow up imaging after our visit with the patient showed a hypoenhancing lesion concerning for a pituitary microadenoma. Neurosurgical evaluation is underway. Discussion: Acromegaly with a pituitary adenoma is uncommon in patients with CNC. However, clinicians should have high suspicion for the disease in patients with CNC and other endocrine neoplasia disorders. The diagnosis has many deleterious consequences if not treated early. Additionally, this case represents a novel pathologic variant of PRKAR1A that has not previously been identified in Carney complex. References: 1. Correa, R., P. Salpea, and C.A. Stratakis, Carney complex: an update. Eur J Endocrinol, 2015. 173(4): p. M85-97. 2. Pack, S.D., et al., Genetic and histologic studies of somatomammotropic pituitary tumors in patients with the “complex of spotty skin pigmentation, myxomas, endocrine overactivity and schwannomas” (Carney complex). J Clin Endocrinol Metab, 2000. 85(10): p. 3860-5.