MON-498 - Carney Complex Unmasked: A Spectrum of Endocrine Presentations

Introduction: Carney complex (CNC) is a rare autosomal dominant genetic cancer syndrome. Individuals with CNC are more likely to develop myxomas, abnormal skin pigmentation, endocrine tumors, schwannomas, ovarian and breast tumors. Most cases of CNC are associated with an inactivating mutation in the PRKAR1A gene. This mutation disrupts regulation of type 1a of protein kinase A (PKA), a critical enzyme in control of cell proliferation. Diagnosis of CNC is typically made in the second decade of life, following a significant delay despite early signs. Average life expectancy for individuals with CNC is 50 years old.
Case Presentations:
Case 1: A 30-year-old female with family history of early breast cancer in paternal aunt and grandmother, and prostate cancer in father underwent breast cancer risk assessment. A 70-gene multicancer panel identified a heterozygous pathogenic variant in PRKAR1A, concerning for CNC. Neither parent had the mutant gene. She reported hirsutism and previous removal of blue nevi. Exam revealed several lentigines on lips. An echocardiogram disclosed an irregular 2.1 x 1.5 cm echodensity in the left atrium, histopathologically confirmed to be an atrial myxoma. Biochemical evaluation indicated normal pituitary function. Serum AM cortisol was mildly elevated to 22.3 (4.8-19.5 ug/dL), with normal urine and saliva cortisol. Patient is scheduled to complete low dose dexamethasone test and if abnormal, will obtain adrenal imaging.
Case 2: A 57-year-old male with history of recurrent cardiac myxomas, infertility, and asthma was referred for evaluation of incidental 1.8cm complex adrenal lesion. On exam, he had multiple nevi, frontal bossing, slight tongue enlargement, hand enlargement, and deep voice. Hormonal evaluation revealed primary hypogonadism, mild autonomous cortisol secretion (MACS), and repeatedly elevated IGF-1. Random growth hormone (GH) and GH releasing hormone were normal, however GH during oral glucose tolerance test paradoxically increased. Pituitary MRI identified no gross abnormality. Echo showed 2.8 x 4.5 cm right ventricle lesion. Testicular ultrasound identified multiple micro- and macrocalcifications. Family members underwent genetic testing which was negative.

Discussion:
CNC has heterogeneous clinical presentations. Even without family history, evaluation of a patient presenting with endocrine tumors or Cushing disease should include assessment for abnormal skin pigmentation and consideration of prior tumors. Patients with history of cardiac myxomas or primary pigmented nodular adrenocortical disease should especially be considered given the rarity of these isolated disorders in the general population. Early identification of CNC is important as appropriate surveillance improves prognosis and can lead to normal life expectancy.

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