Abstract
Background
Non-suppressive or partially suppressive L-T4 treatment demonstrated to be effective in reducing the volume of the nodules. However, studies with long follow-up are lacking and significant controversy exists regarding the efficacy of non-suppressive L-T4 treatment in benign nodular goiter.
Aim
The goal of this study was to determine the evolution of thyroid nodules in subjects treated with a non-suppressive levothyroxine (L-T4) dose, compared to untreated subjects.
Design and patients
We followed for a period of 1–9 years the thyroid nodule size in 356 female patients in the age range 19–45 at study entry, of which 201 untreated (Group 0) and 165 treated with a non-suppressive L-T4 dose (Group L-T4).
Measurements
We determined the volume of thyroid nodules by ultrasonography.
Results
The initial mean nodule volume in Group 0 and Group L-T4 was 3.91 ± 6.87 and 4.01 ± 7.35 mL, respectively. Nodule volume increase was inversely correlated to the initial volume. The final volume was slightly higher in untreated than in L-T4 treated subjects (5.37 ± 8.49 and 4.39 ± 6.72 mL). In both groups, the mean of annual fold increase of nodule volume was inversely correlated with the follow-up duration (P < 0.0046), indicating a slower growth as time advances. In the subjects treated with L-T4, the mean annual increase of nodule volume was significantly minor compared to untreated subjects. Concomitant nodules in ten multinodular goiters exhibited totally independent evolution, demonstrating that intranodular factors are more important for the nodule behavior than extra nodular factors.
Conclusions
Our study demonstrates that the growth of benign thyroid nodules is inversely correlated to their size, benign nodules naturally growth slowly as time advances, and that a chronic treatment with L-T4 at a non-TSH-suppressive dose significantly reduces their growth.
Similar content being viewed by others
References
Tunbridge WM, Evered DC, Hall R et al (1977) The spectrum of thyroid disease in a community: the Whickham survey. Clin Endocrinol (Oxf) 7:481–493
Tonacchera M, Pinchera A, Vitti P (2010) Assessment of nodular goitre. Best Pract Res Clin Endocrinol Metab 24:51–61
Ezzat S, Sarti DA, Cain DR, Braunstein GD (1994) Thyroid incidentalomas. Prevalence by palpation and ultrasonography. Arch Intern Med 154:1838–1840
Astwood EB, Cassidy CE, Aurbach GD (1960) Treatment of goiter and thyroid nodules with thyroid. JAMA 174:459–464
Shimaoka K, Sokal JE (1974) Suppressive therapy of nontoxic goiter. Am J Med 57:576–583
La Rosa GL, Lupo L, Giuffrida D et al (1995) Levothyroxine and potassium iodide are both effective in treating benign solitary solid cold nodules of the thyroid. Ann Intern Med 122:1–8
Lima N, Knobel M, Cavaliere H et al (1997) Levothyroxine suppressive therapy is partially effective in treating patients with benign, solid thyroid nodules and multinodular goiters. Thyroid 7:691–697
Zelmanovitz F, Genro S, Gross JL (1998) Suppressive therapy with levothyroxine for solitary thyroid nodules: a double-blind controlled clinical study and cumulative meta-analyses. J Clin Endocrinol Metab 83:3881–3885
Gharib H, James EM, Charboneau JW et al (1987) Suppressive therapy with levothyroxine for solitary thyroid nodules. A double-blind controlled clinical study. N Engl J Med 317:70–75
Cheung PS, Lee JM, Boey JH (1989) Thyroxine suppressive therapy of benign solitary thyroid nodules: a prospective randomized study. World J Surg 13:818–821
Reverter JL, Lucas A, Salinas I et al (1992) Suppressive therapy with levothyroxine for solitary thyroid nodules. Clin Endocrinol (Oxf) 36:25–28
Larijani B, Pajouhi M, Bastanhagh MH et al (1999) Evaluation of suppressive therapy for cold thyroid nodules with levothyroxine: double-blind placebo-controlled clinical trial. Endocr Pract 5:251–256
Kuma K, Matsuzuka F, Yokozawa T, Miyauchi A, Sugawara M (1994) Fate of untreated benign thyroid nodules: results of long-term follow-up. World J Surg 18:495–498
Papini E, Petrucci L, Guglielmi R et al (1998) Long-term changes in nodular goiter: a 5-year prospective randomized trial of levothyroxine suppressive therapy for benign cold thyroid nodules. J Clin Endocrinol Metab 83:780–783
Uzzan B, Campos J, Cucherat M et al (1996) Effects on bone mass of long term treatment with thyroid hormones: a meta-analysis. J Clin Endocrinol Metab 81:4278–4289
Koc M, Ersoz HO, Akpinar I et al (2002) Effect of low- and high-dose levothyroxine on thyroid nodule volume: a crossover placebo-controlled trial. Clin Endocrinol (Oxf) 57:621–628
Grussendorf M, Reiners C, Paschke R, Wegscheider K (2012) Reduction of thyroid nodule volume by levothyroxine and iodine alone and in combination: a randomized, placebo-controlled trial. J Clin Endocrinol Metab 96:2786–2795
Fine-needle aspiration cytology (FNAC). Guidelines for the management of thyroid cancer. 2nd edition. Royal College of Physicians, London: Perros: 9-10
Vanderpump MP, Tunbridge WM, French JM et al (1995) The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey. Clin Endocrinol (Oxf) 43:55–68
Kuma K, Matsuzuka F, Kobayashi A et al (1992) Outcome of long standing solitary thyroid nodules. World J Surg 16:583–587
Knudsen N, Bulow I, Laurberg P et al (2002) Low goitre prevalence among users of oral contraceptives in a population sample of 3712 women. Clin Endocrinol (Oxf) 57:71–76
Knudsen N, Bulow I, Laurberg P et al (2001) Alcohol consumption is associated with reduced prevalence of goitre and solitary thyroid nodules. Clin Endocrinol (Oxf) 55:41–46
Kristensen HL, Vadstrup S, Knudsen N, Siersbaek-Nielsen K (1995) Development of hyperthyroidism in nodular goiter and thyroid malignancies in an area of relatively low iodine intake. J Endocrinol Invest 18:41–43
Hegedus L, Rasmussen N, Ravn V et al (1988) Independent effects of liver disease and chronic alcoholism on thyroid function and size: the possibility of a toxic effect of alcohol on the thyroid gland. Metabolism 37:229–233
Knudsen N, Bulow I, Laurberg P et al (2002) Parity is associated with increased thyroid volume solely among smokers in an area with moderate to mild iodine deficiency. Eur J Endocrinol 146:39–43
Sapio MR, Guerra A, Marotta V et al (2011) High growth rate of benign thyroid nodules bearing RET/PTC rearrangements. J Clin Endocrinol Metab 96:E916–E919
Marotta V, Guerra A, Sapio MR et al (2010) Growing thyroid nodules with benign histology and RET rearrangement. Endocr J 57:1081–1087
Marotta V, Guerra A, Sapio MR et al (2010) Are RET/PTC rearrangements in benign thyroid nodules of biological significance? Thyroid 20:1191–1192
Conflict of interest
None.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Puzziello, A., Carrano, M., Angrisani, E. et al. Evolution of benign thyroid nodules under levothyroxine non-suppressive therapy. J Endocrinol Invest 37, 1181–1186 (2014). https://doi.org/10.1007/s40618-014-0128-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40618-014-0128-z