Download PDF
Exp Clin Endocrinol Diabetes 2015; 123(09): 561-566
DOI: 10.1055/s-0035-1564073
Article
© Georg Thieme Verlag KG Stuttgart · New York

Different Effects of Metformin on the Hypothalamic-Pituitary-Thyroid Axis in Bromocriptine- and Cabergoline-treated Patients with Hashimoto’s Thyroiditis and Glucose Metabolism Abnormalities

R. Krysiak
1   Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Medyków, Katowice, Poland
,
J. Okrzesik
1   Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Medyków, Katowice, Poland
,
B. Okopien
1   Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Medyków, Katowice, Poland
› Author Affiliations
Further Information

Publication History

received 27 June 2015
first decision 27 June 2015

accepted 19 August 2015

Publication Date:
15 September 2015 (online)

Also available at
    Permissions and Reprints

Abstract

Metformin was found to reduce serum thyrotropin levels in patients with hypothyroidism. This effect was less pronounced if patients were additionally treated with bromocriptine. The study included 39 premenopausal women with autoimmune thyroiditis and thyrotropin levels exceeding 3.0 mU/L. All patients had been treated for at least 6 months with bromocriptine (5.0–7.5 mg daily) or cabergoline (0.5–1.0 mg weekly). Because of coexisting type 2 diabetes or impaired glucose tolerance, they were then given metformin (1.7–2.55 g daily). Glucose homeostasis markers, thyroid antibody titers, as well as serum levels of thyrotropin, total and free thyroid hormones and prolactin were determined before and after 6 months of metformin treatment. At baseline, cabergoline-treated patients were less insulin resistant as well as tended to have lower levels of prolactin than bromocriptine-treated patients. Although in both treatment groups, metformin decreased plasma levels of fasting and post-challenge plasma glucose and improved insulin receptor sensitivity, this effect was more prominent in patients receiving cabergoline. However, only in bromocriptine-treated patients, metformin decreased serum thyrotropin and this effect reached the level of significance in a subgroup of patients with subclinical hypothyroidism. Neither in cabergoline- nor in bromocriptine-treated patients, metformin affected thyroid hormone levels and thyroid antibody titers. Our results indicate that the effect of metformin on hypothalamic-pituitary-adrenal axis activity is partially determined by endogenous dopaminergic tone, thyrotrope activity and insulin sensitivity.

Key words

Hashimoto’s thyroiditis - dopamine agonists - metformin - hypothalamic-pituitary-thyroid axis
 

  • References

  • 1 American Diabetes Association . Standards of medical care in diabetes - 2015. Approaches to glycemic treatment. Diabetes Care 2015; 38 (Suppl. 01) S42-S48
    PubMedGoogle Scholar
  • 2 Vigersky RA, Filmore-Nassar A, Glass AR. Thyrotropin suppression by metformin. J Clin Endocrinol Metab 2006; 91: 225-227
    CrossrefPubMedGoogle Scholar
  • 3 Isidro ML, Penín MA, Nemiña R et al. Metformin reduces thyrotropin levels in obese, diabetic women with primary hypothyroidism on thyroxine replacement therapy. Endocrine 2007; 32: 79-82
    CrossrefPubMedGoogle Scholar
  • 4 Cappelli C, Rotondi M, Pirola I et al. TSH-lowering effect of metformin in type 2 diabetic patients: differences between euthyroid, untreated hypothyroid, and euthyroid on L-T4 therapy patients. Diabetes Care 2009; 32: 1589-1590
    CrossrefPubMedGoogle Scholar
  • 5 Morteza Taghavi S, Rokni H, Fatemi S. Metformin decreases thyrotropin in overweight women with polycystic ovarian syndrome and hypothyroidism. Diab Vasc Dis Res 2011; 8: 47-48
    CrossrefPubMedGoogle Scholar
  • 6 Rotondi M, Cappelli C, Magri F et al. Thyroidal effect of metformin treatment in patients with polycystic ovary syndrome. Clin Endocrinol (Oxf) 2011; 75: 378-381
    CrossrefPubMedGoogle Scholar
  • 7 Lupoli R, Di Minno A, Tortora A et al. Effects of treatment with metformin on TSH levels: a meta-analysis of literature studies. J Clin Endocrinol Metab 2014; 99: E143-E148
    CrossrefPubMedGoogle Scholar
  • 8 Fournier JP, Yin H, Yu OH et al. Metformin and low levels of thyroid-stimulating hormone in patients with type 2 diabetes mellitus. CMAJ 2014; 186: 1138-1145
    CrossrefPubMedGoogle Scholar
  • 9 Cappelli C, Rotondi M, Pirola I et al. Metformin-induced thyrotropin suppression is not associated with cardiac effects. Hormones (Athens) 2014; 13: 252-258
    PubMedGoogle Scholar
  • 10 Krysiak R, Okopien B. The effect of metformin on the hypothalamic-pituitary-thyroid axis in women with polycystic ovary syndrome and subclinical hypothyroidism. J Clin Pharmacol 2015; 55: 45-49
    CrossrefPubMedGoogle Scholar
  • 11 Krysiak R, Okopien B. Thyrotropin-lowering effect of metformin in a patient with resistance to thyroid hormone. Clin Endocrinol 2011; 75: 404-406
    CrossrefPubMedGoogle Scholar
  • 12 Oleandri SE, Maccario M, Rossetto R et al. Three-month treatment with metformin or dexfenfluramine does not modify the effects of diet on anthropometric and endocrine-metabolic parameters in abdominal obesity. J Endocrinol Invest 1999; 22: 134-140
    CrossrefPubMedGoogle Scholar
  • 13 Krysiak R, Szkrobka W, Okopien B. The effect of metformin on the hypothalamic-pituitary-thyroid axis in patients with type 2 diabetes and subclinical hyperthyroidism. Exp Clin Endocrinol Diabetes 2015; 123: 205-208
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 Krysiak R, Okrzesik J, Okopien B. The effect of short-term metformin treatment on plasma prolactin levels in bromocriptine-treated patients with hyperprolactinaemia and impaired glucose tolerance: a pilot study. Endocrine 2015; 49: 242-249
    CrossrefPubMedGoogle Scholar
  • 15 DeFronzo RA. Bromocriptine: a sympatholytic, D2-dopamine agonist for the treatment of type 2 diabetes. Diabetes Care 2011; 34: 789-794
    CrossrefPubMedGoogle Scholar
  • 16 Weiland CM, Hilaire ML. Bromocriptine mesylate (Cycloset) for type 2 diabetes mellitus. Am Fam Physician 2013; 87: 718-720
    PubMedGoogle Scholar
  • 17 Gaziano JM, Cincotta AH, Vinik A et al. Effect of bromocriptine-QR (a quick-release formulation of bromocriptine mesylate) on major adverse cardiovascular events in type 2 diabetes subjects. J Am Heart Assoc 2012; 1: e002279
    PubMedGoogle Scholar
  • 18 Krysiak R, Gdula-Dymek A, Okopien B. Monocyte-suppressing effect of high-dose metformin in fenofibrate-treated patients with impaired glucose tolerance. Pharmacol Rep 2013; 65: 1311-1316
    CrossrefPubMedGoogle Scholar
  • 19 Krysiak R, Okopien B. Lymphocyte-suppressing and systemic anti-inflammatory effects of high-dose metformin in simvastatin-treated patients with impaired fasting glucose. Atherosclerosis 2012; 225: 403-407
    CrossrefPubMedGoogle Scholar
  • 20 Krysiak R, Okopien B. The effect of levothyroxine and selenomethionine on lymphocyte and monocyte cytokine release in women with Hashimoto's thyroiditis. J Clin Endocrinol Metab 2011; 96: 2206-2215
    Google Scholar
  • 21 Pappa T, Alevizaki M. Metformin and thyroid: an update. Eur Thyroid J 2013; 2: 22-28
    PubMedGoogle Scholar
  • 22 Iván G, Szigeti-Csúcs N, Oláh M et al. Treatment of pituitary tumors: dopamine agonists. Endocrine 2005; 28: 101-110
    CrossrefPubMedGoogle Scholar
  • 23 Molitch ME. Management of medically refractory prolactinoma. J Neurooncol 2014; 117: 421-428
    CrossrefPubMedGoogle Scholar
  • 24 Kvernmo T, Härtter S, Burger E. A review of the receptor-binding and pharmacokinetic properties of dopamine agonists. Clin Ther 2006; 28: 1065-1078
    CrossrefPubMedGoogle Scholar
  • 25 Ortega-González C, Cardoza L, Coutiño B et al. Insulin sensitizing drugs increase the endogenous dopaminergic tone in obese insulin-resistant women with polycystic ovary syndrome. J Endocrinol 2005; 184: 233-239
    CrossrefPubMedGoogle Scholar
  • 26 Shin S, Hyun B, Lee A et al. Metformin suppresses MHC-restricted antigen presentation by inhibiting co-stimulatory factors and MHC molecules in APCs. Biomol Ther (Seoul) 2013; 21: 35-41
    CrossrefPubMedGoogle Scholar
  • 27 Kang KY, Kim YK, Yi H et al. Metformin downregulates Th17 cells differentiation and attenuates murine autoimmune arthritis. Int Immunopharmacol 2013; 16: 85-92
    CrossrefPubMedGoogle Scholar
  • 28 McDonnell ME, Ganley-Leal LM, Mehta A et al. B lymphocytes in human subcutaneous adipose crown-like structures. Obesity (Silver Spring) 2012; 20: 1372-1378
    CrossrefPubMedGoogle Scholar
  • 29 Krysiak R, Okopien B. Different effects of cabergoline and bromocriptine on metabolic and cardiovascular risk factors in patients with elevated prolactin levels. Basic Clin Pharmacol Toxicol. 2015; 116: 251-256
    CrossrefPubMedGoogle Scholar
  • 30 Chau-Van C, Gamba M, Salvi R et al. Metformin inhibits adenosine 5′-monophosphate-activated kinase activation and prevents increases in neuropeptide Y expression in cultured hypothalamic neurons. Endocrinology 2007; 148: 507-511
    CrossrefPubMedGoogle Scholar
  • 31 Alquier T, Kawashima J, Tsuji Y et al. Role of hypothalamic adenosine 5′-monophosphate-activated protein kinase in the impaired counterregulatory response induced by repetitive neuroglucopenia. Endocrinology 2007; 148: 1367-1375
    CrossrefPubMedGoogle Scholar
  • 32 Duntas LH, Orgiazzi J, Brabant G. The interface between thyroid and diabetes mellitus. Clin Endocrinol 2011; 75: 1-9
    CrossrefPubMedGoogle Scholar
  • 33 López M, Varela L, Vázquez MJ et al. Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance. Nat Med 2010; 16: 1001-1008
    CrossrefPubMedGoogle Scholar
  • 34 Szybinski Z. Polish Council for Control of Iodine Deficiency Disorders. Work of the Polish Council for Control of Iodine Deficiency Disorders, and the model of iodine prophylaxis in Poland. Endokrynol Pol 2012; 63: 156-160
    PubMedGoogle Scholar