Increase In Thyroxine Levels Research Articles

Biochemical and developmental effects of thyroid and anti-thyroid drugs on different early life stages of Xenopus laevis

The effects of two drugs containing the synthetic thyroid hormone levothyroxine (LEV) and an anti-thyroid drug containing propylthiouracil (PTU) on the three early life stages of Xenopus laevis were evaluated with the Frog Embryo Teratogenesis Assay-Xenopus, Tadpole Toxicity Test, and Amphibian Metamorphosis Assay using biochemical and morphological markers. Tested drugs caused more effective growth retardation in stage 8 embryos than stage 46 tadpoles. Significant inhibition of biomarker enzymes has been identified in stage 46 tadpoles for both drugs. AMA test results showed that LEV-I caused progression in the developmental stage and an increase in thyroxine level in 7 days exposure and growth retardation in 21 days exposure in stage 51 tadpoles. On the other hand, increases in lactate dehydrogenase activity for both drugs in the AMA test may be due to impacted energy metabolism during sub-chronic exposure. These results also show that the sensitivity and responses of Xenopus laevis at different early developmental stages may be different when exposed to drugs.

Thyroid Disease II: Hypothyroidism in Pregnancy

Hypothyroidism affects between 2 and 12 per 1000 pregnancies. Symptoms in pregnancy are similar those encountered in the nonpregnant population, but may be attributed to the pregnancy itself. Thyroxine-binding globulin increases in pregnancy, leading to increased thyroxine levels in order to meet the metabolic needs of normal pregnancy. Routine screening is not recommended, and testing should be done using a targeted approach in women with symptoms or history of thyroid disease. Diagnosis is based upon the finding of an elevated serum TSH using population and trimester-specific ranges. Overt hypothyroidism, identified by high serum TSH and low free thyroxine, is associated with increased risk of pregnancy-related complications, and is treated with maternal thyroxine supplementation. Adequate iodine is necessary for fetal neurodevelopment, and women with iodine deficiency may present with a goiter, though it is important to distinguish it from other causes of thyroid enlargement, including malignancy. Postpartum thyroiditis is diagnosed infrequently, as only a small subset of women will demonstrate the classic biphasic presentation, Additionally, symptoms are often vague, nonspecific, and self-limited. Importantly, many women are at risk of eventually developing permanent hypothyroidism. This review contains 6 tables, and 48 references. Key words: euthyroid, goiter, overt hypothyroidism, postpartum thyroiditis, thyroixine binding globulin, thyroid peroxidase, thryroid nodules

Role of oxidative stress and altered thyroid hormones in unexplained infertility

To explore the link between altered thyroid profile and oxidative stress marker in females with unexplained infertility. The cross-sectional case-control study was carried out at the Islamabad Clinic Serving Infertile Couples, Islamabad, Pakistan, from June 2016 to August 2017, and comprised women aged 18-40 years regardless of ethnic background who were divided into two groups; those with unexplained infertility were the cases, while fertile women acted as the controls. Serum was analysed for triiodothyronine, thyroxine and thyroid stimulating hormone as well as for oxidative stress markers including manganese superoxide dismutase, glutathione reductase and adrenaline using enzymelinked immunosorbent assay. Data was analysed using SPSS 19. Of the 88 subjects, there were 44(50%) in each of the two groups. There was no significant difference in terms of thyroids markers except thyroxine and thyroid stimulating hormone (p<0.05). There were significant differences in terms of oxidative stress markers between the groups (p<0.05). A significant positive correlation of thyroid stimulating hormone was observed with manganese superoxide dismutase and adrenaline (p<0.05) with a weak non significant association of glutathione reductase (p>0.05). Increased thyroxine levels in females with unexplained infertility was associated with decrease in the serum levels of antioxidants.

Functional State of the Thyroid Gland and Lipid Peroxidation and Antioxidant Protection System in Women of Reproductive Age with Chronic Form of Parenteral Viral Hepatitis

Background. Chronic viral hepatitis is a complex global problem and is still far from being solved. Many researchers point out influence of viral hepatitis on the reproductive system of women.Aim. To identify features of the functional state of pituitary-thyroid units of neuroendocrinal regulation, and to evaluate lipid peroxidation – antioxidant protection with determination of the oxidative stress coefficient in perimenopausal women with chronic form of hepatitis.Materials and methods. Study included 44 women with chronic viral hepatitis and 28 healthy women of the same age. Immunoabsorbent, spectrophotometric, fluorometric and statistical methods were used.Results. In patients with chronic viral hepatitis, we detected an increase in thyroxine levels – by 29.6% (р &lt; 0.001) and free triiodothyronine values – by 65.7% (р = 0.008) in comparison with the control group. In the group with chronic viral hepatitis, the TBA-reactive products level increased by 1.9 times (р = 0.006), and superoxide dismutase activity decreased by 1.3 times (р &lt; 0.001), total antioxidant activity – by 1.7 times (р &lt; 0.001) and α-tocopherol level – by 1.3 times (р = 0.005) in comparison with the control group.Conclusions. The obtained data demonstrate the features of the pituitary-thyroid system functioning and the lipid peroxidation – antioxidant protection system in patients with chronic hepatitis. The chronic form of hepatitis is characterized by metabolic disorders that require a more careful approach in diagnosis and management.

Non-Specific Porins of Yersinia pseudotuberculosis as Inductors of Experimental Hyperthyroidism in Mice.

In vivo experiments showed that antibodies to OmpC and OmpF porins of Yersinia pseudotuberculosis increased thyroxine (T4) level in the blood of experimental animals. The mice were immunized with different antigens: recombinant OmpF porin in a soluble monomeric form, trimers of OmpC and OmpF porins isolated from the outer membrane, or antibodies to them. The level of thyroxine in the blood of mice immunized with OmpF and OmpC porins increased by 5.47 and 22.3 times, respectively; after immunization with antibodies to these proteins, blood thyroxine increased by 9.28 and 14.29 times. Immunization with recombinant OmpF porin induced no reliable increase in thyroxine level. Hence, the serum to recombinant OmpF porin contains no antibodies specific to conformational antigenic determinants that are present in the protein trimer and, according to our previous findings from molecular docking studies, determine cross-reactions between OmpF porin of Y. pseudotuberculosis and thyroidstimulating hormone receptor.

Thyroid endocrine disruption in male zebrafish following exposure to binary mixture of bisphenol AF and sulfamethoxazole.

Thyroid endocrine disruption by bisphenol AF (BPAF) alone or in combination with sulfamethoxazole (SMX) exposure was evaluated in adult male zebrafish. Changes in thyroid gene transcription were examined using microarrays and were linked to effects on thyroxine hormone production and transcription of genes related to the hypothalamic-pituitary-thyroid axis. BPAF alone or in combination with SMX affected genes related to thyroid hormone production and receptor activity, thyroid gland development, and deiodinase activity. Increases in thyroxine levels, and gene transcription were more pronounced in the BPAF and SMX mixture group than in the BPAF group. Significant down-regulation of trh and tshβ genes in the brain suggested a negative feedback response resulting in increased thyroxine levels. The present study indicated that BPAF exposure alone alters transcription of genes associated with the thyroid endocrine system, and combination with SMX could increase the endocrine disrupting effect of BPAF.

Thyroid endocrine disruption of acetochlor on zebrafish (Danio rerio) larvae.

The herbicide acetochlor is widely used and detected in the environment and biota, and has been suspected to disrupt the thyroid endocrine system, but underlying mechanisms have not yet been clarified. In the present study, zebrafish larvae (7 days post-fertilization) were exposed to a series concentration of acetochlor (0, 1, 3, 10, 30, 100 and 300 µg l(-1) ) within a 14-day window until 21 days post-fertilization. Thyroid hormones and mRNA expression profiles of genes involved in the hypothalamic-pituitary-thyroid (HPT) axis were analyzed. Exposure to the positive control, 3,5,3'-triiodothyronine (T3 ), altered the mRNA expression, suggesting that the HPT axis in the critical window of zebrafish responded to chemical exposure and could be used to evaluate the effects of chemicals on the thyroid endocrine system. The mRNA expressions of genes involved in thyroid hormone synthesis (tshβ, slc5a5 and tpo) were upregulated significantly with acetochlor treatment, which might be responsible for the increased thyroxine concentrations. The downregulation of genes related to thyroid hormone metabolism (dio1 and ugt1ab) and transport (ttr) in zebrafish larvae exposed to acetochlor might further explain the increased thyroxine levels and decreased T3 levels. The mRNA expression of the thyroid hormone receptor (trα) was also upregulated upon acetochlor exposure. Results suggested that acetochlor altered mRNA expression of the HPT axis-related genes and changed the whole body thyroid hormone levels in zebrafish larvae. It demonstrated that acetochlor could cause endocrine disruption of the thyroid system by simulating the biological activity of T3 . Copyright © 2015 John Wiley & Sons, Ltd.

Short-term exposure of arsenite disrupted thyroid endocrine system and altered gene transcription in the HPT axis in zebrafish

Arsenic (As) pollution in aquatic environment may adversely impact fish health by disrupting their thyroid hormone homeostasis. In this study, we explored the effect of short-term exposure of arsenite (AsIII) on thyroid endocrine system in zebrafish. We measured As concentrations, As speciation, and thyroid hormone thyroxine levels in whole zebrafish, oxidative stress (H2O2) and damage (MDA) in the liver, and gene transcription in hypothalamic–pituitary–thyroid (HPT) axis in the brain and liver tissues of zebrafish after exposing to different AsIII concentrations for 48 h. Result indicated that exposure to AsIII increased inorganic As in zebrafish to 0.46–0.72 mg kg−1, induced oxidative stress with H2O2 being increased by 1.4–2.5 times and caused oxidative damage with MDA being augmented by 1.6 times. AsIII exposure increased thyroxine levels by 1.3–1.4 times and modulated gene transcription in HPT axis. Our study showed AsIII caused oxidative damage, affected thyroid endocrine system and altered gene transcription in HPT axis in zebrafish.

Effect of exogenous thyroxine supplementation on heamato-biochemical status in calves

ABSTRACT The lipid and HDL cholesterol levels are higher in the buffalo calves than that in the cow calves of the same age. This is due to lesser utilization of lipid substrates during the first week of post-natal life by the buffalo calves in comparison to that by the cow calves. Hyperlipidemia in the calves might be the result of hypothyroidism in neonatal calves. Poor utilization of lipids might be the triggering element for hypothermia in these neonatal buffalo calves. Exogenous supplementation of thyroxine will help in the maintenance of BMR of calves due to its calorigenic effects by uncoupling of oxidative phosphorylation process. Therefore, elevated body temperature will lead to sustenance of calves during initial two months of age. The total erythrocyte count (TEC) recorded was higher and it decreased significantly (P<0.05) in thyroxine supplemented buffalo calves and cow calves. In early age, the total leukocytes count (TLC) of thyroxine supplemented buffalo calves and cow calves decreased in comparison to control group. The biochemical parameters such as serum glucose and serum triglycerides increased significantly (P<0.05) whereas, serum protein and cholesterol level was decreased in thyroxine supplemented buffalo calves and cow calves as compared to buffalo calves and cow calves, respectively. The HDL cholesterol did not differ significantly in treatment groups as compared to control group. Mobilisation of lipids and HDL cholesterol of buffalo calves has produced heat to maintain homeostasis in buffalo calves. The increased thyroxine level in thyroxine supplemented buffalo calves helped to maintain their body temperature and increased basal metabolic rate, thus helped in the reduction of calf mortality. Keywords: thyroxine, buffalo calves, cow calves, lipid, basal metabolic rate

Effect of Exogenous Thyroxine Supplementation to Reduce the Incidence of Hypothermia in Dairy Calves

Higher serum lipids concentration in blood is the major cause of hypothermia due to lesser utilization of lipids by the buffalo calves for generation of body heat (thermogenesis). A study of effect of exogenous thyroxine supplementation on hormonal status in murrah buffalo and crossbreed cow calves has been evaluated. The study was conducted on 12 healthy buffalo calves and 12 cow calves at Livestock Farm (calf unit), Adhartal, N.D.V.S.U., Jabalpur, Madhya Pradesh. Oral supplementation of thyroxine (0.167 mg/kg body weight), in powder form mixed along with 5 gram jaggery on 15 day interval starting from age of 16-days, 31-days and 46-days. The findings lead to these conclusions that thyroxine supplementation was found mobilisation of lipids and high density lipoprotein cholesterol for heat production to maintain homeostasis. The increased thyroxine level in buffalo calves helped to maintain their body temperature and increased basal metabolic rate, thus helped in their survival and reduced mortality.

Subtle changes in thyroid indices during a placebo-controlled study of an extract of Withania somnifera in persons with bipolar disorder.

Laboratory indices of thyroid function (TSH, Free T4, and T3) were measured in a randomized clinical trial in which Ashwagandha (ASW) was used to improve cognitive function in patients with bipolar disorder. This was done in light of a case-report of ASW-associated thyrotoxicosis, and data from mice administered ASW that showed significant increases in thyroxine levels. Ten (of the original 60) patients showed abnormal results in one of the thyroid measures either at the beginning or end of the 8-week study. One ASW- treated patient had subclinical hypothyroidism (TSH - 5.7 mIU/L) at baseline that normalized, and all three ASW treated patients experienced T4 increases from baseline (7%, 12%, and 24%). Six of 7 placebo-assigned patients showed decreases in T4 from baseline (4% to 23%), and one patient's TSH moved from the normal to subclinical hypothyroid range (6.96 mIU/L). As thyroid indices were done for safety, and not the primary goal of the original study, only 16.7% had abnormal thyroid indices, and as there was no sub-stratification for treatment assignment by thyroid status, unequal numbers of subjects received ASW (n = 3) or placebo (n = 7). In spite of these limitations, the subtle laboratory changes noted in thyroid indices in an 8-week study suggest that ASW may increase thyroxine levels, and therefore vigilance regarding hyperthyroidism may be warranted. Nonetheless, the thyroid enhancing properties of ASW may also represent a clinical opportunity for the treatment of subclinical hypothyroidism, and these results suggest the need for further study of the effects of ASW on thyroid indices, especially in those with bipolar and unipolar mood disorders.

Serum leptin, thyroxine and thyroid-stimulating hormone levels interact to affect cognitive function among US adults: evidence from a large representative survey

Neuroanatomical connections point to possible interactions between areas influencing energy homeostasis and those influencing cognition. We assessed whether serum leptin, thyroxine, and thyroid stimulating hormone (TSH) levels are associated with and interact to influence cognitive performance among US adults. Data from the National Health and Nutrition Examination Survey III (1988–1994) were used. Measures included a battery of neuropsychological tests and serum leptin, thyroxine, and TSH levels (20–59-year-old: n = 1114–2665; 60–90-year-old: n = 1365–5519). Among those 20–59-year-old, the middle tertile of leptin (vs. first tertile) was inversely related to the number of errors on the symbol digits substitution test. Increased thyroxine level was associated with a poorer performance on the serial digits test in the 20–59-year-old, but a better performance on the math test in 60–90-year-old group. TSH was associated with poor performance on various tests in the 20–59-year-old, but better performance in the 60–90-year-old group. Significant antagonistic interactions were found in both age groups between thyroxine, TSH, and leptin for a number of tests, including between leptin and thyroxine in the 60–90-year-old group in their association with word recall-correct score. We found significant associations of our main exposures with cognitive function among US adults, going in opposite directions between age groups in the cases of thyroid hormonal levels, as well as some interactive effects between exposures. It is important to conduct prospective cohort studies to provide further insight into potential interventions that would assess interactive effects of various hormonal replacement regimens.

Hypothalamic-pituitary-thyroid axis and sympathetic nervous system involvement in hyperthermia induced by 3,4-methylenedioxymethamphetamine (Ecstasy).

An acute and potentially life-threatening complication associated with the recreational use of the 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) is hyperthermia. In the present study, Sprague-Dawley rats treated with MDMA (40 mg/kg s.c.) responded with a significant increase (maximal at 1 h) in rectal and skeletal muscle temperatures that lasted for at least 3 h post-treatment. Hypophysectomized (HYPO) and thyroparathyroidectomized (TX) animals treated with MDMA (40 mg/kg s.c.) did not become hyperthermic and in fact displayed a significant hypothermia. The HYPO and TX animals were also resistant to the serotonergic neurotoxic effects of MDMA assessed by serotonin measurements 4 to 7 days later in the striatum and hippocampus. MDMA (40 mg/kg s.c.) induced a significant increase in thyroxine levels 1 h post-treatment. Thyroid hormone replacement in TX animals returned the hyperthermic response seen after MDMA. Prazosin, an alpha(1)-antagonist (0.2 mg/kg i.p.), administered 30 min before MDMA significantly attenuated the MDMA-induced increase in rectal temperature, but had no effect on skeletal muscle temperature. Cyanopindolol, a beta(3)-antagonist (4 mg/kg s.c.), administered 30 min before MDMA (40 mg/kg s.c.) significantly attenuated the increase in skeletal muscle temperature, but had no effect on the rise in rectal temperature. The combination of prazosin and cyanopindolol resulted in an abolishment of MDMA-induced hyperthermia. The mechanisms of thermogenesis induced by MDMA seem to result from an interaction between the hypothalamic-pituitary-thyroid axis and the sympathetic nervous system, wherein mechanisms leading to core and skeletal muscle hyperthermia after MDMA exposure seem to be differentially regulated by alpha(1)- and beta(3)-adrenergic receptors.

Effect of low dose mono- ortho 2,3′,4,4′,5 pentachlorobiphenyl on thyroid hormone status and EROD activity in rat offspring: consequences for risk assessment

Toxic equivalency factor (TEF) has been proposed to estimate the risk of polychlorinated biphenyl (PCB) congeners. However, ortho chlorine substitution in the two phenyl rings gives each PCB its own pattern of toxicity which is different from the mechanism of action of 2,3,7,8-tetrachlorodibenzo- p-dioxin. The present study evaluated the effect of prenatal and postnatal exposure to a low dose of the mono- ortho pentachlorobiphenyl PCB 118 on thyroid hormone concentrations and EROD activity in rats. Moreover, the tissue distribution of PCB 118 following one oral dose was evaluated. Sprague–Dawley rats were treated by gavage on GD 6 with 375 μg of PCB 118/kg b.w. Decreases in thyroxine and TSH levels were observed in dams at the end of lactation. Perinatal exposure to a low dose of PCB 118 permanently disrupted the hypothalamo-pituitary-thyroid (HPT) axis leading to a significant increase in thyroxine levels in offspring, as a ‘thyroid resistance syndrome’. It is noteworthy that no changes in hepatic EROD activity were detected in dams at the end of lactation, even in the presence of high amounts of PCB in liver. Based on hepatic EROD activity (as a biomarker for aryl hydrocarbon receptor (AhR) induction), the mechanism of thyroid homeostasis disruption seems to be AhR-independent. Additionally, the ‘thyroid resistance syndrome’ observed in our study indicates the need for further detailed investigations on the HPT axis. We conclude that not only TEF, but also AhR-independent responses should be taken into account for risk assessment of mono- ortho PCB congeners.

Animal models of thyroid-associated ophthalmopathy.

Thyroid-associated ophthalmopathy (TAO) is an autoimmune condition most frequently associated with Graves' disease (GD). The thyrotropin receptor (TSHR) is an important target of the autoimmune response in both disorders. The last 5 years have seen some progress in the development of animal models, induced with TSHR preparations and reproducing some or all of the features of GD and TAO with variable incidence. The most promising approaches have used: (1) treatment of AKR/N mice with cells transfected with the homologous major histocompatibility complex class II molecule to the recipients and the full-length human or murine TSHR. Approximately 20% of mice develop thyroid-stimulating antibodies (TSAB) and increased thyroxine levels but no thyroiditis; (2) transfer of TSHR primed T cells to naive syngeneic recipients. Approximately 65% of BALBc mice develop thyroiditis and orbital changes similar to TAO; (3) genetic immunization of NMRI outbred mice with the full-length human TSHR. Approximately 20% of mice develop TSAB, hyperthyroidism, and orbital changes.

Animal models of Graves' disease.

Graves' disease (GD) is an autoimmune condition in which goitre and hyperthyroidism are induced by thyroid stimulating antibodies (TSAB) which mimic the action of thyrotrophin (TSH). The target of the autoimmune response is the thyrotrophin receptor (TSHR) and, since its cloning, a number of differing approaches have been adopted in an attempt to develop an animal model of GD. Methods in which synthetic peptides or fragments of the receptor produced in bacteria or insect cells have been injected into animals together with immunological adjuvants have had only limited success in inducing some of the signs and symptoms of GD. Genetic immunisation resulted in thyroiditis in the majority, but TSAB formation in only a minority, of treated inbred mice. Transfer of receptor in vitro primed T cells to syngeneic naive recipients, with priming either using a bacterial fusion protein or genetic immunisation, induced destructive thyroiditis in non-obese diabetic (NOD) mice but lymphocytic thyroiditis in BALBc mice. Furthermore, the orbits of 17/22 of the BALBc animals, but not the NOD animals, with thyroiditis had orbital changes similar to those seen in thyroid eye disease. TSAB and elevated thyroxine levels were induced in AKR/N mice injected with fibroblasts expressing the full length human TSHR and murine major histocompatibility complex (MHC) class II homologous to the recipient mice. No thyroiditis was induced but preliminary results from a different group using the same protocol suggest that receptor autoantibodies and thyroid dysfunction could be transferred using T cells primed in vitro with the receptor and MHC-II expressing cells. The majority of the studies described above have studied inbred mouse strains. In a novel departure, the NMR outbred strain has been treated by genetic immunisation with very promising results, including the induction of increased thyroxine levels in 4/30 female mice, accompanied by TSAB in addition to thyroiditis, and with signs of hyperactivity and orbital pathology. This review discusses the various protocols together with the information regarding the pathogenesis of GD which each has contributed, and concludes with an evaluation of how close we are to mimicking this polygenic, multifactorial disease.

Breast-feeding exposure of infants to environmental contaminants--a public health risk assessment viewpoint: chlorinated dibenzodioxins and chlorinated dibenzofurans.

Exposure of children to chlorinated dibenzodioxins and chlorinated dibenzofurans via breast-feeding has been well-documented in industrialized countries. Recent studies indicate a possible link between development of subtle health effects in children and their exposure to dioxin-like chemicals from maternal milk. Some examples of the effects are lower vitamin K levels, increased thyroxine levels, and mild changes in liver enzymes. The projected daily intakes of chlorinated dibenzodioxins and chlorinated dibenzofurans are compared with minimal risk levels for intermediate duration oral exposure (15-365 days) derived for these chemicals. Public health recommendations for future actions related to infant intake of chlorinated dibenzodioxin- and chlorinated dibenzofuran-contaminated breast milk are also addressed.

Groundwater pesticides: Interactive effects of low concentrations of carbamates aldicarb and methomyl and the triazine metribuzin on thyroxine and somatotropin levels in white rats

Using full-factorial design experiments for three variables at two levels each and center replicates, we examined the effects of common agricultural carbamate insecticides, aldicarb and methomyl, and a triazine herbicide, metribuzin, on hormone levels in Sprague-Dawley rats. Fifty-four female rats were sampled at 2 and 6 wk during a 6-wk exposure to individual chemicals or to combinations of them. Some main effects and interaction effects were significant. For example, rats treated with the herbicide (metribuzin) were hyperthyroid. The interactions of all three chemicals also significantly increased thyroxine levels. One year later, we repeated these experiments for 16 wk using 54 male rats; the results were very similar. Metribuzin alone significantly increased thyroxine throughout the second study (at 7, 13, and 16 wk). Somatotropin levels were significantly altered after 13 wk of exposure. The same concentrations and mixtures of these three pesticides have now been shown to be implicated in learning impairment and other neurological functions, immune parameter changes, and endocrine changes. These findings support the concept of the interconnectedness of the nervous, endocrine, and immune systems and raise the likelihood of impacts on all three systems if one is shown to be affected. Development, growth, and reproduction all depend on the proper function of these three systems. These results strongly suggest the need to reassess currently allowed "safe" levels of chemicals based on adult dosages that are accepted in ground-water and in our food supplies.

Modulation by dimethyl sulphoxide of the toxicity induced by cis-diamminedichloroplatinum in cultured thyrocytes

Cis-diamminedichloroplatinum II (cisplatin) is an effective and widely used antitumour drug which induces many side-effects. We investigated the potency of dimethyl sulphoxide (DMSO) as an antidote to cisplatin-induced damage to cultured human thyrocytes. The effects of DMSO were studied on human thyroid cells cultured in monolayers and in follicles. Addition of 2% DMSO suppressed the cisplatin-induced decrease in intracellular lactate dehydrogenase, α-hydroxybutyryldehydrogenase and creatine kinase activities and in neutral red uptake. DMSO also partially or totally abolished the inhibition of cyclic AMP (cAMP), thyroglobulin (Tg) and triiodothyronine (T 3) production observed with 7.5, 15 or 30 μ m-cisplatin. In the presence of 75 μ m-cisplatin, cAMP, Tg and T 3 secretion was always totally inhibited. The increase in thyroxine levels observed with cisplatin administration did not occur in the presence of DMSO. These data indicate that 2% DMSO interacted with cisplatin and therefore prevented the cytotoxic and inhibitory effects of cisplatin on cultured thyroid cells.

Evidence for a slow tissue adaptation to circulating thyroxine in patients with chronic L-thyroxine treatment.

We measured serum procollagen-III-peptide in 67 women with long-term L-thyroxine treatment and compared the results with age-matched controls. The strong correlation between serum free thyroxine and procollagen-III-peptide concentrations previously found after 6 months of L-thyroxine treatment was not found after long-term treatment. There were slightly higher procollagen-III-peptide concentration values in those chronically treated patients who had high free thyroxine levels but this increase was less marked than in patients previously studied after short-term treatment. An increase in procollagen-III-peptide concentration reflects an increased biosynthesis of collagen III, which is present in connective tissues throughout the body, and our findings may be explained by slow tissue adaptation to increased levels of thyroxine. We conclude that the increased thyroxine levels found in L-thyroxine-treated patients are of less clinical importance than thought previously. We also conclude that peripheral markers of thyroid hormone peripheral effects such as procollagen-III-peptide may be of less use than thought previously due to this slow tissue adaptation to changes in thyroxine concentration.