Effect of metformin on thyroid stimulating hormone and thyroid volume in patients with prediabetes

[Nelson Vergel]

Effect of metformin on thyroid stimulating hormone and thyroid volume in patients with prediabetes: A randomized placebo-controlled clinical trial.

Journal of Research in Medical Sciences. Nov2014, Vol. 19 Issue 11, p1019-1026. 8p.



Abstract:

Background: The people with prediabetes have insulin resistance (IR). IR may affect thyroid function, size and nodules. We investigated the effects of metformin on the thyroid gland in prediabetic people. Materials and Methods: In a randomized, double-blind placebo-control clinical trial, 89 people with prediabetes, aged 18-65 years were studied for 3 months. They were divided into two, metformin (n = 43) and placebo (n = 46) treated groups. Serum thyroid stimulating hormone (TSH) was measured and thyroid nodules and volume was studied by ultrasonography. The data were compared between and within groups, before and after the study. Results: Mean of the baseline characteristics in metformin and placebo-treated groups had no statistically significant difference. At the end of the study, serum TSH was not significantly different between the two groups. However, if the TSH range was divided into two low normal (0.3-2.5 μU/ml) and high-normal (2.6-5.5 μU/ml) ranges, significant decrease was observed in metformin-treated group with a high-normal basal serum TSH (P = 0.01). Thyroid volume did not change in metformin-treated group. However, in placebo-treated group, the thyroid was enlarged (P = 0.03). In 53.9% of participants, thyroid nodule was observed. There was just a decrease in the volume of small solid (not mixed) nodules from median of 0.07 ml to 0.04 ml in metformin-treated group (P = 0.01). Conclusion: In prediabetic people, metformin decreases serum TSH, only, in those people with TSH >2.5 μU/ml and reduces the size of small solid thyroid nodules. It also prevents an increase in the thyroid volume.

 

[Nelson Vergel]

Is it true that Metformin has a negative effect on the thyroid?

The study of Fournier et al. (1) a transverse observation study where data from 65626 patients who received metformin between 1988 and 2012 were collected, were divided into two cohorts of which one was composed of 5689 hypothyroids and 59937 eutroids. The aim was to see the correlation between metformin use and low TSH levels; the analysis showed that in hypothyroidism the risk of low levels of TSH increased by 55% compared with euthyroid drugs; Ok, all this can suffice to affirm a pathologic causal link between metformin and lower TSH levels? NO sure no!

In literature, the evidence on this correlation tells a somewhat different story if only to be analyzed, in Karimifar et al. (2) andomized double-blind placebo controlled (far different from observational retrospective analysis) were analyzed The effects of metformin on the thyroid for 3 months in 89 pre-diabetic subjects divided into two groups, in which the values ​​of TSH were measured, but also the glandular volume (in addition to the anthropometric measurements). The metformin group protocol included a scaling dose of 500mg to 1500mg based on subjective tolerance but no less than 500mg. The results of the study were that metformin did not significantly affect TSH alteration, But dividing the group into two subgroups based on baseline TSH values ​​(ie 0.3-2.5 μU / ml and 2.6-5.5 μU / ml) it was seen that a significant reduction in TSH occurred in the group showing higher basal values ; No significant difference between the first and the subsequent on the average nodular volume in both groups, but isolating the solid nodules was seen to have decreased their volume in the metformin group. As for insulin resistance, it obviously showed a significant reduction in the metformin group compared to baseline values. But isolating the solid nodules was seen to have decreased their volume in the metformin group. As for insulin resistance, it obviously showed a significant reduction in the metformin group compared to baseline values. But isolating the solid nodules was seen to have decreased their volume in the metformin group. As for insulin resistance, it obviously showed a significant reduction in the metformin group compared to baseline values.

Now the causal correlation between metformin and low TSH levels does not seem as reliable as it may have seemed from a surface analysis.

A retrospective analysis prior to Fournier et al. Conducted by an Italian team (Cappeli et al. (3) 2012) a sample of 393 Euthyroid Diabetic subjects was divided into 3 groups, the group taking only metformin (203 subjects) showed a significant reduction in TSH only in the subgroup With baseline values ​​of between 2.51 mIU / 4.5 mIU / m and not in that with ≥ 2.5 mIU values ​​/ the important thing is that fT4 levels have not changed at the end of treatment in all 3 groups .

By itself, the reduction in TSH does not mean anything but contextualization.

In a previous work by Cappell et al. (4) the metformin group formed by diabetic patients with mild hypothyroidism (mean values ​​of 4.5mIU / l TSH) had reported a reduction in TSH at 2,93mIU / l after 1 year Without ever going down to levels lower than normal; Both here and in the other groups, the values ​​of fT4 and other parameters were not changed as a result of TSH reduction.

In short, what we can extrapolate is that metformin has shown to reduce TSH only in hypothyroidism who showed baseline TSH values ​​in the medium to high ranges and not in those in the mid-low range, furthermore the values ​​of fT4 and others Thyroid parameters have not changed; No significant change occurred in euthyroid subjects.

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