ABSTRACT
Medullary Thyroid Carcinoma [MTC] occurs in either sporadic or hereditary forms. The susceptibility gene for hereditary MTC is the RET proto-oncogene. The aim of this study was to evaluate the prevalence of common germline RET mutations in exons 10 and 11 among Iranian MTC patients. 57 non-related MTC patients were examined in this survey [F: M=1.2:1.0, 40.0 +/- 11.5 years]. Genomic DNA was extracted from their peripheral blood samples and exons 10 and 11 of the RET proto-oncogene were amplified using polymerase chain reaction [PCR]. The PCR products were then digested by specific restriction enzymes and the Restriction Fragment Length Polymorphism [RFLP] patterns were analyzed for common RET mutations in exons 10 and 11. Only the MEN2A patient displayed a C634W mutation in exon 11. Three of the six first-degree relatives of the MEN2A evaluated patient had the same mutation. Among apparently sporadic MTC patients [53 cases], one patient showed a C620R mutation in exon 10 and two other patients displayed C634Y mutations in exon 11 of the RET proto-oncogene. Neither were the only MEN2B patient nor the two FMTC patients found to carry germline mutations in exons 10 and 11 of the RET proto-oncogene. It seems that the prevalence of germline RET mutations in exons 10 or 11 is prominent [5.7%] among Iranian, apparently sporadic, MTC patients. We conclude that a routine germline mutation analysis of the RET proto-oncogene should be advised for apparently sporadic MTC patients. Hereditary forms of MTC require a more extended investigation for RET mutations
ABSTRACT
Determination of thyrotropin, total and free thyroxine and triiodothyronine are widely used as diagnostic methods for thyroid function evaluation. There have been numerous reports of interferences in thyroid hormone immunoassays. Herein, a prominent positive interference is reported for a radioimmunoassay kit of total triiodothyronine. In this study, a total of 3471 patients, referred by endocrinologists, were examined by serum level measurement of thyroid stimulating hormone [TSH], total thyroxine [T4] and triiodothyronine [T[3]]. T[3] analysis was made through a competitive solid-phase radio labeled [I[125]] immunoassay by T[3] Izotop kit [Izotop Co. Budapest, Hungary]. The presence of T[3] assay interference was considered probable if the hormone profile was inconsistent with the clinical picture and/or the obtained value for T[3] was extremely deviated from normal levels, i.e. it was above 780 ng/dL. For such patients, the possibility of T[3] assay interference was investigated through re-measuring T[3] level by another RIA kit [Immunotech kit, Marseille, France]. Among 3471 patients studied, 40 cases [36 women, 4 men], with a mean +/- D age of 38.8 +/- 15.0 years, had T3 serum levels inconsistent with their clinical pictures and/or above 780 ng/dL. The mean serum levels of T4 and TSH in this group were 9.0 +/- 2.0 micro g/dL and 1.79 +/- 1.47 micro U/mL, respectively. In all these 40 cases, T[3] level was in the normal range according to T[3]-Immunotech kit [with a mean +/- SD of 132.k1 +/- 31.0 ng/dL], in accordance with their clinical pictures. Results clearly indicate the presence of positive interference[s] in some of T[3] assays made with Izotop T[3]-RIA kits. The probable explanations for the observed positive interference are discussed