The late health effects associated with radioiodine ( 131 I) given as treatment for thyroid cancer are difficult to assess since the number of thyroid cancer patients treated at each centre is limited. The risk of second primary malignancies (SPMs) was evaluated in a European cohort of thyroid cancer patients. A common database was obtained by pooling the 2-year survivors of the three major Swedish, Italian, and French cohorts of papillary and follicular thyroid cancer patients. A time-dependent analysis using external comparison was performed. The study concerned 6841 thyroid cancer patients, diagnosed during the period 1934 -1995, at a mean age of 44 years. In all, 17% were treated with external radiotherapy and 62% received 131 I. In total, 576 patients were diagnosed with a SPM. Compared to the general population of each of the three countries, an overall significantly increased risk of SPM of 27% (95% CI: 15 -40) was seen in the European cohort. An increased risk of both solid tumours and leukaemias was found with increasing cumulative activity of 131 I administered, with an excess absolute risk of 14.4 solid cancers and of 0.8 leukaemias per GBq of 131 I and 10 5 person-years of follow-up. A relationship was found between 131 I administration and occurrence of bone and soft tissue, colorectal, and salivary gland cancers. These results strongly highlight the necessity to delineate the indications of 131 I treatment in thyroid cancer patients in order to restrict its use to patients in whom clinical benefits are expected.

The use of recombinant human thyrotropin and low-dose (1.1 GBq) postoperative radioiodine ablation may be sufficient for the management of low-risk thyroid cancer. (Funded by the French National Cancer Institute [INCa] and the French Ministry of Health; ClinicalTrials.gov number, NCT00435851; INCa number, RECF0447.).

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Background Rare cancers here defined as those with an annual incidence rate less than 6/100,000 in Europe, pose challenges for diagnosis, treatments, and clinical decision-making. Information on rare cancers is scant. We updated the estimates of the burden of rare cancers in Europe, their time trends in incidence and survival, and provide information on centralization of treatments in seven European countries. Methods We analysed data on more than two million rare cancer diagnoses, provided by 83 cancer registries, to estimate European incidence and survival in 2000-2007 and the corresponding time trends during 1995-2007. Incidence rates were calculated as the number of new cases divided by the corresponding total person years in the population. Five-year relative survival (RS) was calculated by the Ederer-2 method. Seven registries

The thyrotropin receptor (TSHR), a member of the large family of G protein-coupled receptors, controls both the function and growth of thyroid cells via stimulation of adenylyl cyclase. We report two different mutations in the TSHR gene of affected members of two large pedigrees with non-autoimmune autosomal dominant hyperthyroidism (toxic thyroid hyperplasia), that involve residues in the third (Val509Ala) and seventh (Cys672Tyr) transmembrane segments. When expressed by transfection in COS-7 cells, the mutated receptors display a higher constitutive activation of adenylyl cyclase than wild type. This new disease entity is the germline counterpart of hyperfunctioning thyroid adenomas, in which different somatic mutations with similar functional characteristics have been demonstrated.