Radiosensitivity-related postirradiation hypothyroidism in Graves' disease patients

Abstract

Purpose: The cumulative incidence of hypothyroidism, in ¹³¹I-treated patients with hyperthyroidism caused by Graves' disease, has been gradually increasing each year. Meanwhile, the role of the genes that control radiation sensitivity (GCRS) involved in ¹³¹I therapy is yet to be defined. The main purpose of the present study is to find GCRS that could indicate hypothyroidism in Graves' disease patients treated with ¹³¹I.

Methods: Thyroid tissue was collected from 59 patients who were diagnosed with Graves' disease. GCRS (including Bcl-2, NF-κB, Survivin, Ku-70, Tob1, EGFR, Egr-1, TP-53, BRCA-1, and ATM) mRNA levels were analyzed with qRT-PCR before radioiodine therapy. Patients were followed up and then grouped by end-point outcomes. The association of the variation of target genes with susceptibility to hypothyroidism was analyzed.

Results: Altogether 44 patients were enrolled, including 11 men and 33 women with an average age of 44.79 ± 12.94 years. Based on their clinical outcomes after at least 2-year follow-up, 59% (26/44) patients were evaluated as hypothyroid, while the remaining 41% (18/44) patients were non-hypothyroid, including 18% (8/44) with persistent hyperthyroidism. The hypothyroid group showed significantly lower Ku-70 mRNA expression levels than the non-hypothyroid group (p = 0.022), whereas no significance was detected regarding other target genes (p > 0.1). Multivariate analysis showed that Ku-70 was significantly correlated with hypothyroidism after ¹³¹I treatment (p = 0.033).

Conclusions: The opposing changes in mRNA expression levels of Ku-70 in patients with hypothyroidism indicate its potential as a prognostic marker for hypothyroidism induced by ¹³¹I treatment.

Keywords: 131I therapy; Hyperthyroidism; Hypothyroidism; Ku-70; Radiosensitivity.