Syndromes of Acquired Resistance to Thyroid Hormones and Tissue Hypotheroidism: Reasons and Clinical-Therapeutic Challenge
Author: Losanov, Bojan St., Clinic of Internal Medicine, AcibademCity Clinic, Tokuda Hospital Sofia
Abstract: The biological activity of thyroid hormones (TН) at the tissue level is determined by two important processes: 1) the activity of T4-deiodinase systems converting Т4 to bioactive T3; 2) the transmembrane transport of TH in the target cells depending on the expression of the tissue-specific peripheral transporters (MCT8, MCT-10, OATP1C1). Decreased FT4 and FT3 transport has been demonstrated in a wide range of conditions -insulin resistance, diabetes, obesity, dyslipidemias, chronic and acute stress, severe infectious and autoimmune diseases, sepsis, heart failure, low calorie diets, starvation and depression, In most of these cases, the level of FT3 in the pituitary remains unaffected as different transmembrane transporters are involved which are independent of the caloric status and other factors. In such conditions the serum TSH may remain within the reference range despite the presence of tissue hypothyroidism with various clinical manifestations. Since FT3 transporters in peripheral tissues are more energy-independent than FT4 ones it is not surprising that substitution with levothyroxine in hypothyroidism patients in many cases appears inadequate whereas T3 is effective and in some cases life-saving (Sick syndrome). An important laboratory criterion for tissue hypothyroidism is serum “reverse T3” (T3 / rT3 ratio <0,2) as well as SHBG (low values). With oxidative stress and starvation deiodinases are essential. Their activity can be reduced due to depletion due to their binding to free radicals and/or selenium deficiency. Application of Selenium in such cases is justified.
Key words: Tissue hypothyroidism, Reverse Т3, FT3/rT3 ratio, MCT8, MCT10, Deiodinases, Transmembrane FT4/ FT3–transport, combined therapy (T4 + T3)
