Nodular lesions and thyroid cancer in Graves' disease

Thyroid nodules in patients with Graves' disease (GD) are common and much controversy surrounds the incidence of coexistent thyroid cancer. In order to more accurately estimate this frequency we studied retrospectively 103 patients operated for GD in the University Clinic St Luc in Brussels, Belgium between 1990 and 2000. The patients were classified as Group I - with a solitary palpable nodule (n = 5; 4,9%); Group II - with multiple palpable nodules (n = 13; 12,6%); Group III - with a large diffuse goiter without clinical evidence of thyroid nodules (n = 85). Group III was subdivised in: Group IIIa - with nodule(s) evidenced by imaging techniques - radionuclide imaging and/or ultrasonography (n = 18; 17,5%) and Group IIIb - with diffuse goiter (n = 67; 65%). Our study shows that 35% (36/103) of a cohort of 103 subjects with GD had thyroid nodules. Eight patients (8/103 - 7,8%) had differentiated papillary cancer, all but one tumour were microcarcinomas. Malignancies were significantly more frequent when nodules were found on clinical examination (p = 0,03). We also observed more thyroid cancers in the total group of patients with nodules than in those with non-nodular diffuse goiter (p = 0,02). Our results suggest that thyroid nodules are frequent in GD and that differentiated cancers have high prevalence in GD patients with nodular lesions. Although in most cases there is no aggressive histological pattern, caution is needed in the follow-up

Impact of IL-10 and IL-12B single nucleotide polymorphisms on circulating cytokine level in development of Hashimoto's thyroiditis

Hashimoto's thyroiditis (HT) is an organ-specific, mainly Th1 autoimmune disorder. New evidence has accumulated for involvement of Treg-produced cytokines. Interleukin (IL)-12 and IL-10 are immunoregulatory cytokines with antagonistic effect on Th differentiation. This study was designed to investigate the correlation of circulating IL-10 and IL-12p40 with their genotypes in 124 HT patients in different stages of disease. The IL-10 and IL-12p40 circulating level in the serum of HT patients and healthy controls was determined by enzyme-linked immunosorbent assay. Genotyping for the 3’UTR A/C IL12B polymorphism was performed using restriction fragment length polymorphism–polymerase chain reaction and genotyping for −1082 A/G by amplification refractory mutation system (ARMS)-PCR. The results showed significantly enhanced IL-12p40 serum quantity both in euthyroid and hypothyroid stages compared to controls and insignificantly decreased level after levothyroxine treatment. Regarding the 3’UTR A/C IL12B polymorphism, a significantly higher frequency of the AA genotype was observed in HT patients than in healthy individuals. The serum IL-10 level was significantly increased in hypothyroid HT patients compared to controls and euthyroid patients. Stratification based on the −1082 A/G polymorphism revealed a significantly enhanced level of circulating IL-10 in hypothyroid patients with a GG genotype compared to AA and AG genotypes. There were also significant differences between the circulating IL-10 quantity in hypo- and euthyroid patients with GG genotypes. In conclusion, the IL-12p40 and IL-10 serum level in HT patients was dependent on the genotype and HT stages, suggesting that enhanced IL-10 serum level in combination with enhanced IL-12p40 is associated with hypothyroidism in HT development