Growth Factor Receptors Gene Expression and Akt Phosphorylation in Benign Human Thyroid Nodules are Unaffected by Chronic Thyrotropin Suppression

Abstract

Levothyroxine (L-T4)-based suppression of thyrotropin (TSH) secretion is widely used to prevent the growth of benign thyroid nodules, although the effectiveness of this approach has been demonstrated only in a subset of patients. In this study, we analyzed the in vivo effects of L-T4-mediated TSH suppression on elements of insulin/IGF-1-dependent growth-regulating pathways in tissues from patients with benign thyroid nodules. Nodular and non-nodular tissue specimens were collected from 63 patients undergoing thyroidectomy. 32 had received preoperative TSH suppressive therapy with TSH levels consistently below 0.5 mU/l (L-T4 group). TSH suppression had not been used in the other 31, and their TSH levels were normal (0.8-4 mU/l (control group). Quantitative RT-PCR was used to measure mRNA levels for TSH receptor, IGF1, IGF-1 receptor, insulin receptor, insulin receptor substrate 1 in nodular and non-nodular tissues from the 2 groups. Akt and phosphorylated Akt protein levels were detected by Western blot. Mean levels of mRNA for all genes tested were similar in the 2 groups, in both nodular and non-nodular tissues. The 2 groups were also similar in terms of phosphorylated Akt protein levels (measured by densitometric scan in 10 randomly selected nodules from each group). This is the first demonstration based on the study of human thyroid tissues that TSH suppression does not affect the expression of components of the insulin/IGF-1-dependent signaling pathways regulating thyrocyte growth. This may explain the lack of effectiveness of TSH-suppressive therapy in a substantial percentage of benign thyroid nodules.

Sodium/iodide symporter is expressed in the majority of seminomas and embryonal testicular carcinomas

“…Levels of NIS mRNA were determined with real-time quantitative RT-PCR, as described previously (Sponziello et al 2010). Briefly, total RNA was extracted from cells treated with various compounds at various incubation times using the TRIzol method, according to the manufacturer's instructions.…”

“…The experiments were repeated at least three times. Reactions, results determination, and expression and normalization were performed as previously reported (Sponziello et al 2010). …”

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Surgery for recurrent goiter: complication rate and role of the thyroid-stimulating hormone-suppressive therapy after the first operation

“…Finally, we are well conscious that probably more studies involving a higher number of patients are necessary before concluding about the lack of efficacy of a suppressive therapy based on levothyroxine, also trying to evaluate different growth factors other than TSH [20,[22][23][24], but certainly, a deeper debate about the relationship between costs and efficacy of such a therapy seems to be necessary. In particular, the role of iodized salt supplementation also ought to be discussed because, in some studies, it seems that iodized salt administration could increase the efficacy of TSH suppression through levothyroxine [25].…”