A. Januszewicz et al., Incidence and clinical relevance of RET proto-oncogene germline mutations in pheochromocytoma patients, J HYPERTENS, 18(8), 2000, pp. 1019-1023
Citations number
24
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Background Autosomal dominant cancer syndrome multiple endocrine neoplasia
type 2 (MEN 2), may exist more often than expected in patients with pheochr
omocytoma. Germline mutations identified recently in MEN 2 can be revealed
by genetic screening,
Objective To evaluate the frequency of RET (rearranged during transfection)
mutations in patients with pheochromocytoma.
Design and methods We genetically screened germline mutations in the RET pr
oto-oncogene and clinically reevaluated patients with pheochromocytoma. A p
entagastrin test and other biochemical studies were performed in all patien
ts.
Setting Department of Internal Medicine and Hypertension, The Medical Unive
rsity of Warsaw, Warsaw, Poland and the Department of Nephrology and Hypert
ension, Albert Ludwigs University, Freiburg, Germany.
Participants Seventy seven unselected patients with pheochromocytoma (19 me
n, 58 women, mean age: 51.55 +/- 1.5 years; pheochromocytoma confirmed hist
opathologically) out of 162 diagnosed and treated in the years 1957-1998 in
the Department of Internal Medicine and Hypertension in Warsaw, Poland. Th
e other 85 patients did not respond to the written invitation.
Main outcome measures The finding of RET mutations and diagnosis of MEN 2 i
n patients with pheochromocytoma.
Results Genetic testing revealed germline mutations in the RET proto-oncoge
ne in six patients (7.8%). All carriers had mutation of exon 11, codon 634:
TGC to CGC. In four patients with this mutation, medullary thyroid carcino
ma (MIC) was diagnosed and in three cases, surgically treated.
Biochemical parameters: parathormone 31.88 +/- 2.87 pg/ mi, calcitonin: 0 m
in 0.23 +/- 0.14 ng/ml; 2 min 0.49 +/- 0.21 ng/ml; 5 min 0.48 +/- 0.21 ng/m
l, metoxycatecholamines: 601.62 +/- 42.71 mu g/24h, epinephrine: 1.94 +/- 0
.17 mu g/24h, norepinephrine 13.96 +/- 1.3 mu g/24h, carcinoembryonic antig
en (CEA) 9.94 +/- 4.3 ng/ml. Ambulatory blood pressure monitoring (ABPM): s
ystolic blood pressure (SBP): 116 +/- 1.9 mmHg, diastolic blood pressure (D
BP): 73.7 +/- 0.9 mmHg. Clinical, biochemical and imaging procedures did no
t reveal any recurrence of pheochromocytoma in the 77 patients studied.
Conclusions Patients with pheochromocytoma should be genetically screened f
or mutations of the RET proto-oncogene. These patients should undergo clini
cal screening for MEN 2. In addition, genetic studies can be useful for the
screening of the families of the carriers. J Hypertens 2000, 18:1019-1023
(C) Lippincott Williams & Wilkins.