Abstractsue-specific and dose-related changes in tissue T3 concentra-We have studied whether, or not, tissue-specific regulatory mechanisms provide normal 3,5,3'-triiodothyronine (T3) concentrations simultaneously in all tissues of a hypothyroid animal receiving thyroxine (T4), an assumption implicit in the replacement therapy of hypothyroid patients with T4 alone. 1. Abbreviations used in this paper: 5 'D-I, type I 5'-iodothyronine deiodinase; 5 'D-II, type II 5 '-iodothyronine deiodinase; SD-III, 5-deiodinase; BAT, brown adipose tissue (interscapular pads); BW, body weight; Cb, cerebellum; Cx, cerebral cortex; d.f., degrees of freedom; H, heart; K, kidney; L, liver; Lu, lung; Mu, skeletal muscle (musculus quadriceps femoris); P1, plasma; PTU, 2-N-propyl-6-thiouracil; R2, coefficient of determination; rT3, reverse 3,5 ',3 '-triiodothyronine; S, spleen; T3, 3,5,3 '-triiodothyronine; T3S, 3,5,3 '-triiodothyronine sulfate; T4, thyroxine; TSH, thyroid-stimulating hormone.tions.In conclusion, euthyroidism is not restored in plasma and all tissues of thyroidectomized rats on T4 alone. These results may well be pertinent to patients on T4 replacement therapy. (J. Clin. Invest. 1995Invest. . 96:2828Invest. -2838

Physiologic combinations of L-thyroxine plus liothyronine do not offer any objective advantage over l-thyroxine alone, yet patients prefer combination treatment.

Aims/Hypothesis. Increased serum inflammatory markers have been found in obesity and insulin-resistant states, and could play a causative role in insulin resistance, atherosclerosis and cardiovascular disease. The polycystic ovary syndrome represents a human model of insulin resistance because both lean and obese polycystic ovary syndrome patients are insulin-resistant compared with non-hyperandrogenic women. We evaluated whether obesity, insulin resistance, or both, are related to the increased concentrations of inflammatory markers in pre-menopausal women. Methods. We compared 35 patients with polycystic ovary syndrome and 28 healthy women, paired for BMI, prevalence of obesity and smoking. Measurements included serum inflammatory markers, BMI, waist-to-hip ratio, blood pressure, serum glucose, insulin, lipid and hormone concentrations, and insulin sensitivity index. Results. The insulin sensitivity index was reduced in polycystic ovary syndrome patients compared with controls. However, no differences were observed between both groups in C-reactive protein, interleukin 6, tumour necrosis factor-α, soluble type 2 tumour necrosis factor receptor, and soluble intercellular cell adhesion molecule-1. When considering patients and controls as a whole, C-reactive protein and interleukin 6, were increased in obese subjects compared with lean women. Inverse correlations existed between insulin sensitivity index and C-reactive protein, interleukin 6, tumour necrosis factor-α, soluble type 2 tumour necrosis factor receptor, and soluble intercellular cell adhesion molecule-1. Only the weak correlation with C-reactive protein persisted after controlling for BMI. Conclusion/interpretation Obesity, and not insulin resistance, is the major determinant of serum inflammatory cardiovascular risk markers in pre-menopausal women. [Diabetologia (2003)

We have recently shown that it is not possible to restore euthyroidism completely in all tissues of thyroidectomized rats infused with T4 alone. The present study was undertaken to determine whether this is achieved when T3 is added to the continuous sc infusion of T4. Thyroidectomized rats were infused with placebo or T4 (0.80 and 0.90 microgram/100 g BW.day), alone or in combination with T3 (0.10, 0.15, or 0.20 microgram/100 g BW.day). Placebo-infused intact rats served as euthyroid controls. Plasma and 12 tissues were obtained after 12 days of infusion. Plasma TSH and plasma and tissue T4 and T3 were determined by RIA. Iodothyronine deiodinase activities were assayed using cerebral cortex, pituitary, brown adipose tissue, liver, and lung. Circulating and tissue T4 levels were normal in all the groups infused with thyroid hormones. On the contrary, T3 in plasma and most tissues and plasma TSH only reached normal levels when T3 was added to the T4 infusion. The combination of 0.9 microgram T4 and 0.15 microgram T3/100 g BW.day resulted in normal T4 and T3 concentrations in plasma and all tissues as well as normal circulating TSH and normal or near-normal 5'-deiodinase activities. Combined replacement therapy with T4 and T3 (in proportions similar to those secreted by the normal rat thyroid) completely restored euthyroidism in thyroidectomized rats at much lower doses of T4 than those needed to normalize T3 in most tissues when T4 alone was used. If pertinent to man, these results might well justify a change in the current therapy for hypothyroidism.