Treatment of hypothyroidism with levothyroxine or a combination of levothyroxine plus L-triiodothyronine.

At present, the drug of choice for the treatment of hypothyroidism is levothyroxine sodium, even though the thyroid gland secretes both thyroxine and 3',3,5-triiodothyronine; the latter is the more active of the two at the cellular level because of its higher affinity for the nuclear thyroid hormone receptors. To date, combined levothyroxine plus liothyronine treatment for hypothyroidism has been evaluated in 15 clinical trials in humans. In two studies, combined therapy seemed to have beneficial effects on mood, quality of life, and psychometric performance of patients, compared with levothyroxine alone; in some of these studies, the patients preferred levothyroxine plus liothyronine combinations.

Deiodinase activities in thyroids and tissues of iodine-deficient female rats.

Severe iodine deficiency is characterized by goiter, preferential synthesis, and secretion of T(3) in thyroids, hypothyroxinemia in plasma and tissues, normal or low plasma T(3), and slightly increased plasma TSH. We studied changes in deiodinase activities and mRNA in several tissues of rats maintained on low-iodine diets (LIDs) or LIDs supplemented with iodine (LID+I). T(4) and T(3) concentrations decreased in plasma, tissues, and thyroids of LID rats, and T(4) decreased more than T(3) (50%).

Neurodevelopment of preterm infants born at 28 to 36 weeks of gestational age: the role of hypothyroxinemia and long-term outcome at 4 years.

Context: Hypothyroxinemia in premature neonates may affect long-term neurodevelopment.

Objective: This study aimed to examine the effects of hypothyroxinemia of the newborn preterm infants born at 28-36 weeks of gestational age (GA) on the neurodevelopment at 4 years of age.

Patients: Prospective observational cohort study conducted in Madrid, Spain.

Lack of action of exogenously administered T3 on the fetal rat brain despite expression of the monocarboxylate transporter 8.

Mutations of the monocarboxylate transporter 8 gene (MCT8, SLC16A2) cause the Allan-Herndon-Dudley syndrome, an X-linked syndrome of severe intellectual deficit and neurological impairment. Mct8 transports thyroid hormones (T4 and T3), and the Allan-Herndon-Dudley syndrome is likely caused by lack of T3 transport to neurons during critical periods of fetal brain development. To evaluate the role of Mct8 in thyroid hormone action in the fetal brain we administered T4 or T3 to thyroidectomized pregnant dams treated with methyl-mercapto-imidazol to produce maternal and fetal hypothyroidism.

Parameters of thyroid function throughout and after pregnancy in an iodine-deficient population.

Background: The thyroid hormone milieu is of crucial importance for the developing fetus. Pregnancy induces physiological changes in thyroid homeostasis that are influenced by the iodine status. However, longitudinal studies addressing thyroid function during pregnancy and after delivery are still lacking in mild-to-moderate iodine-deficient populations.

Thyroid hormone regulation of gene expression in the developing rat fetal cerebral cortex: prominent role of the Ca2+/calmodulin-dependent protein kinase IV pathway.

Thyroid hormones influence brain development through regulation of gene expression mediated by nuclear receptors. Nuclear receptor concentration increases rapidly in the human fetus during the second trimester, a period of high sensitivity of the brain to thyroid hormones. In the rat, the equivalent period is the last quarter of pregnancy.

Phase 1 trial of 4 thyroid hormone regimens for transient hypothyroxinemia in neonates of <28 weeks' gestation.

Background: Transiently low levels of thyroid hormones occur in approximately 50% of neonates born 24-28 weeks' gestation and are associated with higher rates of cerebral palsy and cognitive impairment. Raising hormone levels shows promise for improving neurodevelopmental outcome.

Objective: To identify whether any of 4 thyroid hormone supplementation regimens could raise T(4) and FT(4) without suppressing TSH (biochemical euthyroidism).

The DREAM protein is associated with thyroid enlargement and nodular development.

G protein-coupled receptors (GPCRs) are involved in the pathophysiology of a wide range of diseases and constitute an attractive therapeutic target. In the thyroid gland, TSH receptor (TSHR), a member of the GPCR family, is a major regulator of thyroid differentiation and function. Alterations in TSHR activity are often involved in the development of pathologies such as thyroid cancer and thyroid enlargement (goiter).

Iodine balance, iatrogenic excess, and thyroid dysfunction in premature newborns.

Iodine is a trace element that is essential for the synthesis of thyroid hormones. The thyroid hormones, thyroxine and 3,5,3'-triiodothyronine, are necessary for adequate growth and development throughout fetal and extrauterine life. The iodine intake of newborns is entirely dependent on the iodine content of breast milk and the formula preparations used to feed them.

Iodine status of pregnant women and their progeny in the Minho Region of Portugal.

Background: Iodine sufficiency is particularly necessary throughout pregnancy, given its recognized impact on psychomotor performance of the offspring. There are no recent reports about iodine status or supplementation in Portugal, a country that the International Council for Control of Iodine Deficiency Disorders considered, in 2004, to have probably reached iodine sufficiency. The objective of this study was to evaluate in the Minho region of Portugal the iodine status of women throughout pregnancy and after delivery, and of their offspring.

Inadequate iodine nutrition of pregnant women from Extremadura (Spain).

Objective: To evaluate the iodine nutrition of the pregnant women of the Spanish Autonomous Community Extremadura. There are approximately 10,000 births per year in Extremadura, which historically contains areas with endemic goiter (Las Hurdes).

Design: Population study in which a representative sample of pregnant women of the general population was analyzed, along with another sample of pregnant women from traditionally goitrogenic areas.

Thyroid hormone action in the adult brain: gene expression profiling of the effects of single and multiple doses of triiodo-L-thyronine in the rat striatum.

Thyroid hormones have profound effects on mood and behavior, but the molecular basis of thyroid hormone action in the adult brain is relatively unknown. In particular, few thyroid hormone-dependent genes have been identified in the adult brain despite extensive work carried out on the developing brain. In this work we performed global analysis of gene expression in the adult rat striatum in search for genomic changes taking place after administration of T(3) to hypothyroid rats.

Iodine deficiency and brain development in the first half of pregnancy.

An inadequate supply of iodine during gestation results in damage to the foetal brain that is irreversible by mid-gestation unless timely interventions can correct the accompanying maternal hypothyroxinemia. Even mild to moderate maternal hypothyroxinemia may result in suboptimal neurodevelopment. This review mainly focuses on iodine and thyroid hormone economy up to mid-gestation, a period during which the mother is the only source for the developing brain of the foetus.

Serum thyroid hormone levels may not accurately reflect thyroid tissue levels and cardiac function in mild hypothyroidism.

The link between thyroid dysfunction and cardiovascular diseases has been recognized for more than 100 years. Although overt hypothyroidism leads to impaired cardiac function and possibly heart failure, the cardiovascular consequences of borderline low thyroid function are not clear. Establishment of a suitable animal model would be helpful.

Effects of excessive long-term exercise on cardiac function and myocyte remodeling in hypertensive heart failure rats.

The long-term effects of exercise on cardiac function and myocyte remodeling in hypertension/progression of heart failure are poorly understood. We investigated whether exercise can attenuate pathological remodeling under hypertensive conditions. Fifteen female Spontaneously Hypertensive Heart Failure rats and 10 control rats were housed with running wheels beginning at 6 months of age.

Making the gradient: thyroid hormone regulates cone opsin expression in the developing mouse retina.

Most mammals have two types of cone photoreceptors, which contain either medium wavelength (M) or short wavelength (S) opsin. The number and spatial organization of cone types varies dramatically among species, presumably to fine-tune the retina for different visual environments. In the mouse, S- and M-opsin are expressed in an opposing dorsal-ventral gradient.

Cardiac-specific elevations in thyroid hormone enhance contractility and prevent pressure overload-induced cardiac dysfunction.

Thyroid hormone (TH) is critical for cardiac development and heart function. In heart disease, TH metabolism is abnormal, and many biochemical and functional alterations mirror hypothyroidism. Although TH therapy has been advocated for treating heart disease, a clear benefit of TH has yet to be established, possibly because of peripheral actions of TH.

Generation and characterization of dickkopf3 mutant mice.

dickkopf (dkk) genes encode a small family of secreted Wnt antagonists, except for dkk3, which is divergent and whose function is poorly understood. Here, we describe the generation and characterization of dkk3 mutant mice. dkk3-deficient mice are viable and fertile.