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Metformin-induced thyrotropin suppression is not associated with cardiac effects

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Abstract

OBJECTIVE

Metformin treatment may induce a decrease/suppression in serum TSH levels, mimicking sub-clinical hyperthyroidism (SHT). The aim of the present study was to retrospectively evaluate changes in several electrocardiographic indices in euthyroid subjects with diabetes who, after starting metformin treatment, developed a low serum TSH as compared to patients with SHT resulting from an underlying thyroid disease or TSH suppressive treatment with L-thyroxine.

DESIGN

Heart rate, P wave duration, P wave dispersion, QTmax, QTmin and QT-dispersion were assessed in 23 patients with diabetes treated with metformin before and after 6 months of TSH-suppression and in 31 control patients with SHT.

RESULTS

No significant changes in electrocardiographic parameters were observed from baseline to the TSH-suppression measurement. A significant difference in P wave duration (102.9 ±7.4 vs. 92.1 ±5.8 ms, p<0.001), P wave dispersion (13.1 ±3.4 vs. 7.1 ±3.5 ms, p<0.001), QTmax (399±18 vs. 388 ±16 ms, p = 0.024), QTmin (341 ±14 vs. 350±17 ms, p = 0.038) and QT dispersion (49.9 ±9.6 vs. 30.9 ±9.2 ms, p< 0.001) were observed between the control group with SHT and the group of diabetic patients with low serum levels of TSH.

CONCLUSIONS

Our results show that the TSH-suppressive effect observed in patients taking metformin is not associated with peripheral markers of thyroid hormone excess, at least at the cardiac level.

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References

  1. DeFronzo RA, Goodman AM, 1995 Efficacy of metformin in patients with non insulin-dependent diabetes mellitus. The Multicenter Metformin Study Group. N Eng J Med 333: 541.

    Article  CAS  Google Scholar 

  2. UK Prospective Diabetes Study (UKPDS) Group, 1998 Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 352: 854.

    Article  Google Scholar 

  3. Abdelghaffar S, Attia A, 2009 Metformin added to insulin therapy for type 1 diabetes mellitus in adolescents. Coch Data Sys Rev 21: CD006691.

    Google Scholar 

  4. Scheen AJ, 2005 Drug interactions of clinical importance with antihyperglycaemic agents: an update. Drug Saf 28: 601–631.

    Article  CAS  PubMed  Google Scholar 

  5. Stocker DJ, Vigersky RA, Stocker DJ, 2005 The effects of metformin and rosiglitazone on vitamin B12, folate and homocysteine in patients with poorly controlled type 2 diabetes. Abstract book of the 87th Annual Meeting of The Endocrine Society; Abstract P3: 604–693.

  6. Vigersky RA, Filmore-Nassar A, Glass AR, 2006 Thyreotropin suppression by metformin. J Clin Endocrinol Metab 91: 225–227.

    Article  CAS  PubMed  Google Scholar 

  7. Isidro ML, Penin MA, Nemina R, Cordida F, 2007 Metformin reduces thyrotropin levels in obese, diabetic women with primary hypothyroidism on thyroidism on thyroxine replacement therapy. Endocrine 32: 79–82.

    Article  CAS  PubMed  Google Scholar 

  8. Cappelli C, Rotondi M, Pirola I, et al, 2009 TSH-lowering effect of metformin in type 2 patients with diabetes. Diabetes Care 32: 1589–1590.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Morteza Taghavi S, Rokni H, Fatemi S, 2011 Metformin decreases thyrotropin in overweight women with polycystic ovarian syndrome and hypothyroidism. Diab Vasc Dis Res 8: 47–48.

    Article  CAS  PubMed  Google Scholar 

  10. Rotondi M, Cappelli C, Magri F, et al, 2011 Thyroidal effect of metformin treatment in patients with polycystic ovary syndrome. Clin Endocrinol 75: 378–381.

    Article  CAS  Google Scholar 

  11. Pappa T, Alevizaki M, 2013 Metformin and thyroid: an update. Eur Thyroid J 2: 22–28.

    PubMed  PubMed Central  CAS  Google Scholar 

  12. Portella RB, Pedrosa RC, Coeli CM, Buescu A, Vaisman M, 2007 Altered cardiovascular vagal responses in nonelderly female patients with subclinical hyperthyroidism and no apparent cardiovascular disease. Clin Endocrinol 67: 290–294.

    Article  CAS  Google Scholar 

  13. Petretta M, Bonaduce D, Spinelli L, et al, 2001 Cardiovascular haemodynamics and cardiac autonomic control in patients with subclinical and overt hyperthyroidism. Eur J Endocrinol 145: 691–696.

    Article  CAS  PubMed  Google Scholar 

  14. Collet TH, Gussekloo J, Bauer DC, et al, 2012 Thyroid Studies Collaboration. Subclinical hyperthyroidism and the risk of coronary heart disease and mortality. Arch Intern Med 172: 799–809.

    Article  CAS  PubMed  Google Scholar 

  15. Kikuya M, Hozawa A, Ohokubo T, et al, 2000 Prognostic significance of blood pressure and heart rate variabilities: the Ohasama study. Hypertension 36: 901–906.

    Article  CAS  PubMed  Google Scholar 

  16. Shah S, Kambur T, Chan C, et al, 2013 Relation of short-term heart rate variability to incident heart failure (from the multi-Ethnic study of atherosclerosis). Am J Cardiol 112: 533–540.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Galetta F, Franzoni F, Fallahi P, et al, 2009 Changes in autonomic regulation and ventricular repolarization induced by subclinical hyperthyroidism. Biomed Pharmacoter 64: 546–549.

    Article  CAS  Google Scholar 

  18. Owecki M, Michalak A, Nikisch E, Sowiński J, 2006 Prolonged ventricular repolarization measured by corrected QT interval (QTc) in subclinical hyperthyroidism. Horm Metab Res 38: 44–47.

    Article  CAS  PubMed  Google Scholar 

  19. Smit JW, Eustatia-Rutten CF, Corssmit EP, et al, 2005 Reversible diastolic dysfunction after long-term exogenous subclinical hyperthyroidism: a randomized, placebo-controlled study. J Clin Endocrinol Metab 90: 6041–6047.

    Article  CAS  PubMed  Google Scholar 

  20. Diez JJ, Iglesias P, 2013 Relationship between serum thyrotropin concentrations and metformin therapy in euthyroid patients with type 2 diabetes. Clin Endocrinol 78: 505–511.

    Article  CAS  Google Scholar 

  21. Cappelli C, Rotondi M, Pirola I, et al, 2012 Thyreotropin levels in patients with diabetes on metformin treatment. Eur J Endocrinol 167: 261–265.

    Article  PubMed  CAS  Google Scholar 

  22. Alevizaki M, 2013 Metformin and thyroid: some questions still remain. Clin Endocrinol 78: 503–504.

    Article  CAS  Google Scholar 

  23. Biondi B, Cooper DS, 2012 The clinical significance of subclinical thyroid dysfunction. Endocr Rev 29: 76–131.

    Article  CAS  Google Scholar 

  24. Parle JV, Maisonneuve P, Sheppard MC, Boyle P, Franklyn JA, 2001 Prediction of all-cause and cardiovascular mortality in elderly people from one low serum thyrotropin result: a 10-year cohort study. Lancet 358: 861–865.

    Article  CAS  PubMed  Google Scholar 

  25. Iervasi G, Molinaro S, Landi P, et al, 2007 Association between increased mortality and mild thyroid dysfunction in cardiac patients. Arch Intern Med 167: 1526–1532.

    Article  PubMed  Google Scholar 

  26. Sawin CT, Geller A, Wolf PA, 1994 Low serum thyrotropin concentrations as a risk factor for atrial fibrillation in older persons. N Eng J Med 331: 1249–1252.

    Article  CAS  Google Scholar 

  27. Cappola AR, Fried LP, Arnold AM, et al, 2006 Thyroid status, cardiovascular risk, and mortality in older adults. JAMA, 295: 1033–1041.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Auer J, Scheibner P, Mische T, Langsteger W, Eber O, Eber B, 2001 Subclinical hyperthyroidism as a risk factor for atrial fibrillation. Am Heart J 142: 838–842.

    Article  CAS  PubMed  Google Scholar 

  29. Cooper DS, Biondi B, 2012. Subclinical thyroid disease. Lancet 379: 1142–1154.

    Article  PubMed  Google Scholar 

  30. Gen R, Akbay E, Camsari A, Ozean T, 2010 P-wave dispersion in endogenous and exogenous subclinical hyperthyroidism. J Endocrinol Invest 33: 88–91.

    Article  CAS  PubMed  Google Scholar 

  31. Vadiveloo T, Donnan PT, Cochrane L, Leese GP, 2011 The thyroid epidemiology, audit, and research study (TEARS) morbidity in patients with endogenous subclinical hyperthyroidism. J Clin Endocrinol Metab 96: 1344–1351.

    Article  CAS  PubMed  Google Scholar 

  32. Ceresini G, Lauretani F, Maggio M, et al, 2009 Thyroid function abnormalities and cognitive impairment in elderly people: results of the Invecchiare in Chianti study. J AM Geriatr Soc 57: 89–93.

    Article  PubMed  Google Scholar 

  33. Collet TH, Gussekloo J, Bauer DC, et al, 2012 Subclinical hyperthyroidism and the risk of coronary heart disease and mortality. Arch Intern Med 172: 799–809.

    Article  CAS  PubMed  Google Scholar 

  34. Sgarbi JA, Matsumurs LK, Kasamatsu, et al, 2010 Subclinical thyroid dysfunctions are independent risk factors for mortality in a 7.5-year follow-up: the Japanese-Brazilian thyroid study. Eur J Endocrinol 162: 569–577.

    Article  CAS  PubMed  Google Scholar 

  35. Duntas LH, Orgiazzi J, Brabant G, 2011 The interface between thyroid and diabetes mellitus. Clin Endocrinol 75: 1–9.

    Article  CAS  Google Scholar 

  36. Lim CT, Kola B, Korbonits M, 2010 AMPK as amediator of hormonal signalling. J Mol Endocrinol 44: 87–97.

    Article  CAS  PubMed  Google Scholar 

  37. Lòpez M, Varela L, Vàzquez MJ, et al, 2010 Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance. Nat Med 16: 1001–1008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Medical and Surgical Sciences, Endocrine and Metabolic Unit, University of Brescia c/o 1, Medicina Spedali Civili di Brescia, Piazzale Spedali Civili n°1, 25100, Brescia, Italy

    Carlo Cappelli MD, Ilenia Pirola, Ana Maria Formenti, Massimo Salvetti & Maurizio Castellano

  2. Unit of Internal Medicine and Endocrinology, Fondazione Salvatore Maugeri Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Superiore Prevenzione e Sicurezza Lavoro Laboratory for Endocrine Disruptors, University of Pavia, Pavia, Italy

    Mario Rotondi, Pasquale De Cata & Luca Chiovato

  3. Diabetic Unit, Spedali Civili di Brescia, Brescia, Italy

    Barbara Agosti

Authors
  1. Carlo Cappelli MD
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  2. Mario Rotondi
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  3. Ilenia Pirola
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  4. Barbara Agosti
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  5. Ana Maria Formenti
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  9. Maurizio Castellano
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Correspondence to Carlo Cappelli MD.

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Cappelli, C., Rotondi, M., Pirola, I. et al. Metformin-induced thyrotropin suppression is not associated with cardiac effects. Hormones 13, 252–258 (2014). https://doi.org/10.1007/BF03401339

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  • DOI: https://doi.org/10.1007/BF03401339

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