期刊
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
卷 100, 期 2, 页码 E308-E318出版社
ENDOCRINE SOC
DOI: 10.1210/jc.2014-2473
关键词
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资金
- Voelcker Fund
- Alex's Lemonade Stand Foundation
- FAPESP
- National Counsel of Technological and Scientific Development (CNPQ) fellowship
- CNPq [201142/2014-7]
- Brazilian Federal Agency
- Evaluation of Graduate Education-CAPES National Senior Visiting Professor (PVNS program) at the Federal University of Sao Paulo School of Medicine, Clinical Endocrinology Division
- University of Sao Paulo School of Medicine, Sao Paulo, Brazil
- Cancer Prevention and Research Institute of Texas Individual Investigator Award [RP140473]
- Department of Defense (DOD) Investigator Initiated Research Award [DOD-PRMRP PR110571]
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [13/19810-2] Funding Source: FAPESP
Context: The phenotype of familial pheochromocytoma (PHEO) associated with germline TMEM127 mutations (TMEM127-related PHEO) has not been clearly defined. Objective: This study aimed to investigate the penetrance, full phenotypic spectrum and effectiveness of clinical/genetic screening in TMEM127-related PHEO. Design, Setting, and Participants: Clinical and genetic screening, and genetic counseling were offered to 151 individuals from a six-generation family carrying a TMEM127 germline mutation in a referral center. Intervention and Main Outcome Measures: TMEM127 genetic testing was offered to at-risk relatives and clinical surveillance for pheochromocytoma was performed in mutation-positive carriers. Results: Forty seven individuals carried the c.410-2A>C TMEM127 mutation. Clinical data were obtained from 34 TMEM127-mutation carriers followed up for 8.7 +/- 8.1 years (range, 1-20 y). Pheochromocytoma was diagnosed in 11 carriers (32%) at a median age of 43 years. In nine patients, symptoms started at 29 years (range, 10-55 y) and two cases were asymptomatic. Tumors were multicentric in five (45%) and bilateral in five (45%) patients. Six patients (54%) had at least one adrenomedullary nodule less than 10 mm. No paragangliomas, distant metastases, or other manifestations were detected. Cumulative penetrance of pheochromocytoma was 0% at 0-20 years, 3% at 21-30 years, 15% at 31-40 years, 24% at 41-50 years, and 32% at 51-65 years. The youngest case was diagnosed at 22 years and the earliest symptoms were reported at age 10. Conclusions: Tumor multicentricity, nodular adrenomedullary hyperplasia, and the occurrence of symptoms more than a decade earlier than the age at diagnosis are novel findings in TMEM127-related PHEO. The high penetrance of pheochromocytoma in this condition validates the benefits of genetic testing of at-risk relatives. We thus recommend that TMEM127 genetic testing should be offered to at-risk individuals at age 22 years and mutation carriers should undergo clinical surveillance annually.
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