Vol 6, No 4 (2002)
Original paper
Published online: 2002-10-18

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RET Proto-Oncogene Germline Mutation in Pheochromocytoma Patients - Incidence and Clinical Consequences

Mariola Pęczkowska, Andrzej Januszewicz, Gerlind Franke, Stefan Hoegerle, Cezary Szmigielski, Izabella Łoń, Magdalena Cieśla, Jadwiga Janas, Magdalena Januszewicz, Idalia Cybulska, Bożenna Wocial, Mariusz Łapiński, Witold Cieśla, Mieczysław Szostek, Włodzimierz Januszewicz, Hartmut P.H. Neumann
Nadciśnienie tętnicze 2002;6(4):279-284.


Background In patients with pheochromocytoma there may exist more often than expected the autosomal dominant cancer syndrome — multiple endocrine neoplasia type 2 (MEN 2). The susceptibility gene for MEN 2 is the RET proto-oncogene. Germline mutations can be identified by analysis of exons 10, 11, 13–16 of the RET gene.
The aim of the study was to evaluate the frequency of these mutations in patients with pheochromocytoma and to report on the conclusions which patients and physicians have drawn.
Material and methods We screened for germline mutations in the RET proto-oncogene and clinically evaluated 106 unselected patients with pheochromocytoma (mean age: 49 ± 14,1 years, 26 male, 80 female) histopathologically confirmed, diagnosed and treated in the years 1957–1998 in the Department of Internal Medicine and Hypertension, Warsaw School of Medicine and in the years 1980/81–2001 in the Department of Hypertension, Institute of Cardiology, Warsaw. Determination of calcitonin concentration (CT) was performed in basal conditions and after pentagastrin stimulation; parathormone level was also determined.
Results Genetic testing revealed germline mutations in the RET proto-oncogene in 8 patients (7,4%). Carriers had mutation of exon 11, codon 634: TGC to CGC (5 patients), exon 11, codon 634: TGC to GGC (1 patient), exon 11, codon 634: TGC to TGG (1 patient) and in exon 13, codon 791: TAT to TTT (1 patient). Hyperactivity of thyroid C-cells was found in 5 carriers, borderline values of basal and after pentagastrin CT were found in 2 carriers and in only one patient CT concentration was normal. In four patients with RET proto-oncogene mutations, MTC was confirmed histopathologically in fine-needle biopsy. In three of them total thyroidectomy was performed. Two patients refused to be surgically treated (one with positive result of biopsy); the next three RET proto-oncogene germline mutation carriers have been informed that prophylactic total thyroidectomy should be considered. In none of the carriers hyperparathyroidism was observed.
Conclusions Our study indicates that patients with pheochromocytoma should be genetically screened for mutations of the RET proto-oncogene. The carriers of these mutations should undergo thyroidectomy. In addition, genetic studies can be useful for the screening of the carriers families.

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