Subclinical hypothyroidism and metabolic syndrome: reasons for drug intervention

Abstract

The high prevalence of metabolic syndrome (MS) and subclinical hypothyroidism (SHypo) creates danger of integral cardio-metabolic risk (CMR). A concept is being developed to increase thyroid-stimulating hormone (TSH) levels as a component of MS with the key role of insulin resistance (IR). To identify groups of active intervention, the definitions of SHypo with age and gender characteristics are analyzed. The results of randomized clinical trials showed a higher incidence of prediabetes and type 2 diabetes mellitus (T2DM) in SHypo, as well as positive associations of autoimmune thyroiditis (AIT) with components of MS, especially in postmenopausal women. The association of SHypo with a systemic inflammatory response is analyzed, which can determine an increase in cardio-metabolic risk. At the same time, most of the thyroid dysfunction and the components of MS are associated with insulin resistance.
 The feasibility of SHypo treating with levothyroxine is discussed: the threshold parameters of thyroid-stimulating hormone (TSH) are not determined for initiating treatment; in old age, due to a decrease in the need for thyroid hormones, an increase in the upper reference range of TSH is discussed; there is no evidence of a decrease in cardiovascular risk and mortality. In parallel, data have been accumulated on a decrease in TSH levels in overt and subclinical hypothyroidism in patients with MS and T2DM with metformin therapy. The gender effect of metformin on the activity of the hypothalamus-pituitary-thyroid axis was suggested, its new antihyperglycemic mechanism of action, including the activation of the AMP protein kinase (adenosine monophosphate (AMP) -activated protein kinase) in the pituitary gland, was revealed.
 It is possible that metformin is a promising therapeutic agent not only for patients with type 2 diabetes and thyroid disease, but also for MS and obesity. The multifaceted capabilities of metformin, including the correction of peripheral and central insulin resistance and a decrease in TSH levels in patients with SHypo, emphasizes an integrated approach to the prevention of CMR. The prolonged release form of metformin has several advantages: better tolerance, greater efficiency in the correction of IR, lipid and carbohydrate metabolism, additional indication - treatment of prediabetes, the possibility of prescribing for creatinine clearance up to 30 ml/min.