Horm Metab Res 2011; 43(1): 22-25
DOI: 10.1055/s-0030-1265226
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

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

M. L. Sponziello1 , [*] , R. Bruno2 , [*] , C. Durante1 , M. D’Agostino3 , R. Corradino3 , P. Giannasio2 , E. Ciociola1 , E. Ferretti1 , M. Maranghi1 , A. Verrienti1 , G. De Toma1 , S. Filetti1 , D. Russo3
  • 1Dipartimento di Scienze Cliniche, Dipartimento di Medicina Sperimentale e Patologia and Dipartimento di Chirurgia, Università di Roma Sapienza, Roma, Italy
  • 2Ospedale di Tinchi-Pisticci, Matera, Italy
  • 3Dipartimento di Scienze Farmacobiologiche, Università di Catanzaro “Magna Graecia”, Catanzaro, Italy
Further Information

Publication History

received 07.07.2010

accepted 01.09.2010

Publication Date:
30 September 2010 (online)


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.


1 These authors contributed equally to the manuscript.


S. Filetti, MD 

Dipartimento di Scienze


Università di Roma Sapienza

Viale del Policlinico 155

00161 Rome


Phone: +39/06/4997 8304

Fax: +39/06/4463 783

Email: sebastiano.filetti@uniroma1.it

D. Russo, MD 

Dipartimento di Scienze


Campus Universitario


Viale Europa

88100 Catanzaro


Phone: +39/0961/3694 123

Fax: +39/0961/3694 237

Email: d.russo@unicz.it