ESPEYB17 8. Adrenals Important for Clinical Practice (5 abstracts)
8.3. Frequency and incidence of Carney complex manifestations: A prospective multicenter study with a three-year follow-up
Espiard S , Vantyghem MC , Assié G , Cardot-Bauters C , Raverot G , Brucker-Davis F , Archambeaud-Mouveroux F , Lefebvre H , Nunes ML , Tabarin A , Lienhardt A , Chabre O , Houang M , Bottineau M , Stroër S , Groussin L , Guignat L , Cabanes L , Feydy A , Bonnet F , North MO , Dupin N , Grabar S , Duboc D & Bertherat J
To read the full abstract: J Clin Endocrinol Metab. 2020; 105(3): dgaa002. PMID: 31912137.
Carney complex (CNC) is a rare multiple endocrine and nonendocrine neoplasia syndrome, described in 1985 by J. Aidan Carney (1). The diagnostic criteria include dermatologic manifestations (spotty skin pigmentation with typical periorificial distribution [known as lentigines], cutaneous myxomas), cardiac myxoma, primary pigmented nodular adrenal disease (PPNAD) causing adrenal Cushing, acromegaly due to growth hormone (GH)-producing pituitary adenoma, breast myxomatosis and breast ductal adenoma, large cell calcified Sertoli cell tumors (LCCSCT), thyroid carcinoma or multiple nodules, psammomatous melanotic schwannoma (PMS) and osteochondromyxoma (2). The diagnosis is based on the presence of 2 or more manifestations. In addition, other endocrine manifestations suggestive of CNC include hyperprolactinemia, elevated IGF-I concentrations or inadequate GH suppression following an oral glucose tolerance test, or paradoxical GH responses to thyrotropin releasing hormone (TRH) stimulation in the absence of clinical acromegaly, blue nevi, or a single thyroid nodule. Non-endocrine manifestations possibly associated with CNC have been described, such as cardiomyopathy, colonic polyps, bronchogenic cysts, hepatocellular adenoma and carcinoma, colonic or gastric carcinomas, retroperitoneal fibrous histiocytomas and pancreatic tumors (2, 3). Approximately 30% of cases are sporadic and the remaining 70% are dominantly inherited (2). The causal gene for CNC was identified in 2000 as the tumor suppressor gene PRKAR1A, located at 17q22-24 and encoding for the regulatory subunit type 1 alpha of the protein kinase A (4, 5). Affected patients harbor a germline heterozygous PRKAR1A alteration, more often a mutation rather than an intragenic deletion, with large deletions being rarely observed.
In the present multicenter national prospective study, the authors evaluated for the first time the frequency, incidence, and evolution of the different manifestations of the condition in patients with genetically confirmed CNC during a 3-year follow-up period. The cohort included 70 patients (50 female/20 male, mean age 35.4 ± 16.7 years, 81% carrying PRKAR1A mutation). The initial investigations allowed identification of several manifestations. At the end of the 3-year follow-up, the newly diagnosed manifestations of the disease were subclinical acromegaly in 6 patients, bilateral testicular calcifications in 1 patient, and cardiac myxomas in 2 patients. Recurrences of cardiac myxomas were diagnosed in 4 patients during the 3-year follow-up study period. Asymptomatic abnormalities of the corticotroph and somatotroph axis that did not meet the criteria of PPNAD and acromegaly were observed in 11.4% and 30% of the patients, respectively. Patients carrying the PRKAR1A c.709- 7del6 mutation had a mild phenotype.
This study underlines the importance of a systematic follow-up of patients with CNC, including biannual assessment for cardiac myxomas. By contrast, regular screening for the other manifestations after a first extensive workup could be spread out, leading to a lighter and more acceptable follow-up schedule for patients.
References:
1. Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go VL. The complex of myxomas, spotty pigmentation, and endocrine over- activity. Medicine (Baltimore). 1985; 64(4):270–283.
2. Stratakis CA, Kirschner LS, Carney JA. Clinical and molecular features of the Carney complex: diagnostic criteria and recommendations for patient evaluation. J Clin Endocrinol Metab. 2001; 86(9): 4041–4046.
3. Gaujoux S, Tissier F, Ragazzon B, et al. Pancreatic ductal and acinar cell neoplasms in Carney complex: a possible new association. J Clin Endocrinol Metab. 2011; 96(11): E1888–E1895.
4. Kirschner LS, Carney JA, Pack SD, et al. Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit in patients with the Carney complex. Nat Genet. 2000; 26(1): 89–92.
5. Casey M, Vaughan CJ, He J, et al. Mutations in the protein kinase A R1alpha regulatory subunit cause familial cardiac myxomas and Carney complex. J Clin Invest. 2000; 106(5): R31–R38.
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ESPE Yearbook of Paediatric Endocrinology
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