ESPE Abstracts

Carney Complex (CNC) is a rare genetic disorder characterized by multiple endocrine and nonendocrine neoplastic manifestations across various organ systems, primarily driven by mutations in the PRKAR1A gene. The most common clinical effects are on the adrenocortical axis. This study seeks to dissect the clinical heterogeneity observed in CNC patients with PRKAR1A mutations, emphasizing the adrenocortical axis and its impacts on patient outcomes.

Case 1: A 12-year-old female patient presents with ACTH-independent cyclic cushing syndrome and primary pigmented nodular adrenocortical Disease (PPNAD). In her family history, her mother had a history of psammomatous melanotic schwannomas and breast ductal adenoma. After being monitored without complications for approximately five years, the patient experienced increased attacks of cyclic Cushing syndrome and developed complications such as short stature, depression, and obesity. Consequently, adrenalectomy was planned for the case.

Case 2: A 9-year-old male patient, diagnosed clinically with CNC following the coexistence of histologically proven intranasal osteochondromyxoma and large cell calcifying Sertoli cell testis tumor. He had hypocortisolism due to ACTH deficiency, which was associated with a partial empty sella. Further clinical developments during follow-up included central precocious puberty and a growth hormone-secreting pituitary adenoma.

Case 3: A 12-year-old female patient presents with adrenal insufficiency due to ACTH deficiency, which was associated with a pituitary adenoma. She had cardiac myxoma. In her family history, her mother, who had passed away, had Carney syndrome-associated Cushing syndrome, myxoma, central nervous system tumors, and a PRKAR1A mutation. During the follow-up period, Cushing syndrome developed under hydrocortisone treatment. Despite discontinuing hydrocortisone treatment, hypercortisolism symptoms persisted. Diffuse adrenal enlargement was detected on adrenal magnetic resonance imaging. Based on the clinical and laboratory data, she was diagnosed with ACTH-independent cushing syndrome. Bilateral adrenalectomy was performed. All cases demonstrated unique clinical features and complex management challenges, emphasizing the lack of a clear genotype-phenotype correlation in CNC. Adrenocortical involvement was prevalent, with differing patterns of cortisol dysregulation observed.

Conclusion: Our findings illustrate the broad clinical spectrum and the complexities in diagnosing and managing CNC, particularly in pediatric populations. The absence of a consistent genotype-phenotype correlation necessitates a highly individualized approach to treatment and monitoring. The study calls for more extensive research into the underlying molecular mechanisms that contribute to this variability, potentially guiding more targeted therapies.

Key words: ACTH deficiency, ACTH-independent cyclic Cushing syndrome, Carney complex, Diffuse Primary Pigmented Nodular Adrenocortical Disease (PPNAD), PRKAR1A