Clinical thyroidology volume 23 issue 6

METFORMIN SHRINKS THYROID NODULES
IN PATIENTS WITH INSULIN RESISTANCE
Editor-in Chief
Jerome M. Hershman, MD
VA Greater Los Angeles Healthcare System Rezzonico J, Rezzonico M, Pusiol E, Pistoia F, Niepomniszcze H. Metformin
treatment for small benign thyroid nodules in patients with
insulin resistance . Metab Syndr Relate Disord 2011;9:69-75. Epub
Telephone: 310-268-3852 Fax: 310-268-4879 Associate Editors:
BACKGROUND
In a prior study, these authors found that individuals with hyperinsulinemia had an increased thyroid volume as well as an increased number of thyroid Telephone: 617-638-8530 Fax: 617-638-7221 Eighty women who were thyroid peroxidase antibody–negative and living Professor of Clinical Medicine and OB/GYN in an iodine-sufficient area and who had insulin resistance (IR) and solid, benign, hyperplastic thyroid nodules were prospectively evaluated for nodule shrinkage using metformin, levothyroxine, or a combination of the two. Fourteen women did not complete follow-up, leaving 66 women with 75 thyroid nodules. IR was evaluated by homeostasis model assessment (HOMA; fasting serum insulin in microunits per milliliter multiplied by plasma glucose Telephone: 716-862-6530 Fax: 716-862-6526 in millimoles per liter divided by 22.5); a HOMA index of >2.5 indicated IR. Nodule volume determined using ultrasound was calculated with the elliptical President
shape volume formula. Women who qualified were randomly assigned to four treatment groups and followed for 6 months: group 1 (n = 14; 19 nodules) Secretary/Chief Operating Officer
Richard T. Kloos, MD
was treated with metformin alone; group 2 (n = 18; 21 nodules) was treated Treasurer
with metformin and levothyroxine; group 3 (n = 19; 20 nodules) was treated with levothyroxine alone; and group 4 (n = 15; 15 nodules) were controls. President-Elect
James A. Fagin, MD
The metformin dose was 1000 mg twice daily; the dose of levothyroxine was Secretary-Elect
adjusted to keep the serum thyrotropin (TSH) level at 0.11 to 0.99 mU/L. Patients were treated for 6 months and then reevaluated using ultrasound.
Past-President
Terry F. Davies, MD
Executive Director
The characteristics of the patients in the groups were similar at baseline (mean age, 43; mean weight, 80 kg; mean body-mass index [the weight in kilograms divided by the square of the height in meters], 31; mean HOMA score, 3.3; mean TSH, 2.55; median nodule volume, 298 mm3). Patients treated with levothyroxine had a significant decrease in TSH (mean, 0.59 mU/L). Designed By
Patients taking metformin had a significant decrease in their HOMA scores into the normal range. All patients on active treatment (groups 1 to 3) had Clinical Thyroidology
Copyright 2011
American Thyroid Association, Inc. Printed in the USA. All rights reserved.
METFORMIN SHRINKS THYROID NODULES
IN PATIENTS WITH INSULIN RESISTANCE
a significant reduction in thyroid volume, with no alone or those with no treatment. Similar nodule significant difference in the posttreatment thyroid shrinkage with metformin was seen with small (<1 volume between these three groups. Nodule size was markedly and significantly reduced in both groups treated with metformin (from 364 to 75 mm3 in CONCLUSIONS
group 1 and from 336 to 126 mm3 in group 2; 74% In patients with small hyperplastic thyroid nodules, of nodules were reduced with metformin alone, 95% metformin produced a significant decrease in were reduced with metformin plus levothyroxine nodule size, and the combination of metformin plus treatment), whereas nodule size was unchanged in levothyroxine showed the best reduction in nodule the other treatment groups. Patients treated with volume, whereas levothyroxine alone reduced nodule metformin alone had a significantly greater reduction in nodule size than those treated with levothyroxine COMMENTARY
2009 American Thyroid Association management guidelines for thyroid nodules do not recommend This small, relatively brief study reveals a marked levothyroxine suppressive therapy for patients with reduction in thyroid nodule volume in 74% of these benign nodules who live in iodine-sufficient areas insulin-resistant subjects who were being treated (3). In this study, metformin treatment appears with metformin. The overall reduction in thyroid to offer a tantalizing reduction in thyroid nodule volume was less impressive, perhaps because volume, with efficacy seen in a striking percentage of only small lesions were included in this study, treated patients. As insulin-resistant patients often hence making up a relatively small percentage of have multiple associated risk factors for surgery, this total thyroid volume. Combination therapy with would be an important group for further study of metformin plus levothyroxine was associated with a non-operative therapies, especially for larger nodules reduction in nodule size in 95% of lesions. In contrast, in which cosmesis may be an issue. As the authors suppressive therapy with levothyroxine alone did not point out, we need more studies done with metformin result in nodule shrinkage, perhaps because the TSH suppression was briefer and TSH was not suppressed to grossly hyperthyroid levels as has been done in — Jane Weinreb, MD
prior successful trials (1,2). Past studies evaluating Division of Endocrinology, Diabetes and Metabolism shrinkage of thyroid nodules with levothyroxine suppression have had mixed results, and the References
2. Papini E, Petrucci L, Guglielmi R, et al. Long-term 1. Wémeau J, Caron P, Schvartz C, et al. Effects of changes in nodular goiter: a 5-year prospective thyroid-stimulating hormone suppression with randomized trial of levothyroxine suppressive levothyroxine in reducing the volume of solitary therapy for benign cold thyroid nodules. J Clin thyroid nodules and improving extranodular no palpable changes: a randomized, double- 3. Cooper DS, Doherty GM, Haugen BR, et al. Revised blind, placebo-controlled trial by the French Thyroid Research Group. J Clin Endocrinol Metab guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid

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