Altered Thyroid Hormone Levels Research Articles

Altered myocardial mechanics in diabetic rats.

Diabetes mellitus is associated frequently with congestive heart failure in humans, even in the absence of associated coronary disease or hypertension. Nevertheless, the effects of the diabetic state on myocardial mechanics have not been studied. Accordingly, diabetes was induced in female Wistar rats by injection of streptozotocin (60 mg/kg). Left ventricular papillary muscles were studied 5, 10, and 30 weeks later and compared with controls. Relaxation was delayed significantly and velocity of shortening was depressed at all loads. However, the passive and active force-length curves, as well as the series elastic properties, were not altered. The changes in cardiac performance were found over a range of muscle lengths, stimulus frequencies, and bath concentrations of calcium, glucose, and norepinephrine. The duration of diabetes had no major effect on the mechanical changes observed. The possible influences of drug-induced cardiac toxicity, malnutrition, and altered thyroid hormone levels have been considered; the latter two factors could not be excluded completely from having some influence on the mechanical properties of diabetic cardiac muscle. Evidence is cited showing abnormalities in calcium uptake by sarcoplasmic reticulum and depressed actomyosin ATPase activity. Thus a cardiomyopathic state has been produced in the rat consequent to the induction of experimental diabetes mellitus. Various mechanisms for this entity have been suggested.

Altered thyroid hormone levels in bacterial sepsis: The role of nutritional adequacy

Depressed triiodothyronine and elevated reverse triiodothyronine levels are commonly seen in patients with acute and chronic illness and in patients receiving markedly hypocaloric diets. To investigate the role of nutritional adequacy in causing the altered thyroid hormone levels found in severe illness, we studied patients with bacterial sepsis who were receiving a variety of nutritional regimens. Thirteen patients received only 5% dextrose in water (600–1000 kcal/day), 7 of whom were in shock. Seven patients received total parenteral nutrition (2500–3500 kcal/day). Analysis of thyroid hormone levels in these groups and in controls shows that a large component of the alteration in thyroid hormone levels found in patients with severe illness is due to the caloric deprivation associated with such severe illness.

Modulation of prolactin release by altered levels of thyroid hormones

In an attempt to delineate the effect of thyroid hormones on prolactin release, serum concentrations of prolactin in response to synthetic thyrotropin-releasing hormone (TRH) administration in subjects with normal and altered levels of thyroid hormones were determined by a heterologous radioimmunoassay for human prolactin. In 16 male and 19 female control subjects, an intravenous administration of TRH elicited a definite elevation in prolactin levels having a peak at 15 min after injection. This response of prolactin was markedly attenuated in all of the ten untreated hyperthyroid patients but was restored in eight subjects after the treatment. In contrast, TRH-mediated prolactin release was enhanced in most cases of primary hypothyroidism. Replacement of thyroid hormones in these patients resulted in a decrease in prolactin response to TRH. Treatment of six euthyroid subjects with triiodothyronine, on the other hand, unequivocally suppressed the release of prolactin. These results suggest that thyroid hormones per se are responsible for the blunted response of prolactin secretion to TRH administration.

The Thyroid and Auto-Immunity

Autoimmune thyroid diseases (Hashimoto thyroiditis, Graves' disease, postpartum thyroiditis, atrophic thyroiditis and drug induced thyroiditis) are prevalent disorders worldwide, especially in women (related to the millieu of sex steroids and X chromosome effects on the thyroid and the immune system). Disruption of thyroid self tolerance, usually induced by an infection, generates abnormal thyroid--immune interactions, implicating an array of cytokines and their receptors. Thyrocytes achieve antigen presenting cell properties which stimulate effector immune cells (Th1, Th2, Th17), in the context of defective immunomodulatory T regulatory cells, resulting in thyroid lymphocytic infiltration and activation of B cells, with production of antibodies against thyroid antigens, thyroid destruction or stimulation, depending on the Th1-Th2 balance. During pregnancy there is a Th2 predominance sustained by the increased glucocorticoid, estrogen and progesteron levels, which allows tolerance versus the histoincompatible fetoplacental unit. In the postpartum period, the return shift Th2 to Th1 favors the occurrence of postpartum thyroiditis. Altered thyroid hormone levels can influence the immune system, and, on the other side, some immune cells secrete TSH, which exerts endocrine and paracrine, cytokine-like effects. Understanding the complex pathogenesis of autoimmune thyroid disorders is crucial for prevention and management.