Thyroid Hormone Secretion Research Articles

규칙적 운동 및 식이요법이 비만여성의 안정시대사량과 호르몬 변화에 미치는 영향

운동과 식이요법을 병행한 체중감량 프로그램에 참여한 여성 비만인의 체지방량, 안정시대사량, 그리고 갑상선 호르몬 차이를 비교할 목적으로 실험한 결과, 체지방량, 체지방율, 체표면적이 유의하게 감소되었고, 안정시대사량 예측치와 실측치 모두 유의하게 감소되었지만, 갑상선 호르몬의 변화는 나타나지 않았다. 안정시대사량과 신체요인들과의 상관분석 결과, 제지방 체충이 가장 밀접한 관계를 보였으며, 안정시대사량과 갑상선 호르몬들과의 관계에서는 TSH와 가장 밀접한 관계를 나타내었다. 결론적으로 8주간 체중감량 프로그램 참여로 체지방은 효과적으로 감소되었으나, 갑상선 호르몬 차이는 없었고 체중감소에 비해 제지방이 유지됨으로써 안정시대사량의 감소는 최소화되어, 에너지 대사작용에 긍정적인 영향을 준 것으로 사료된다. The purpose of this study was to examine resting metabolic rate (RMR) and thyroid hormonal (TSH, <TEX>$T_3$</TEX>, and <TEX>$T_4$</TEX>) changes following weight loss by diet with regular exercise in obese women. The subjects of the present study were 7 women who were above 30% body fat. The subjects arrived into the laboratory in the morning after 12 hour overnight fasting. All subjects measured RMR, % body fat, and fat free mass at weight loss program start time, after 4 weeks and after 8 weeks. All the RMR values were expressed as absolute value (kcal/day), absolute value/FFM (kcal/day/FFM), and absolute value/BSA (kcal/<TEX>$m^2$</TEX>/hr), and were calculated predicted RMR value minus actual RMR value. Also, correlation of blood thyroid hormonal (TSH, <TEX>$T_3$</TEX>, and <TEX>$T_4$</TEX>) secretion and RMR were analyzed. There were significant differences in weight, % body fat, and BSA following diet with exercise (p<0.05). Also, there was a difference between predicted RMR and actual RMR value following weight loss (p<0.05). We also examined the hormonal changes according to weight loss. After weight loss, the level of TSH and <TEX>$T_4$</TEX> were higher than before. But there were no significant differences. Also, the level of <TEX>$T_3$</TEX> was lower than rather before but there was no significant difference. Among the anthropometric factors, FFM was highly correlated (r=0.761) with actual RMR value before weight loss. Also, there was a correlation (r=0.771) with actual RMR value after weight loss. Therefore, actual RMR expressed as FFM increased in weight loss program by diet with exercise. There were no changes in the level of thyroid hormonal TSH and <TEX>$T_4$</TEX>.

Phosphodiesterase 8B Gene Variants Are Associated with Serum TSH Levels and Thyroid Function

Thyroid-stimulating hormone (TSH) controls thyroid growth and hormone secretion through binding to its G protein-coupled receptor (TSHR) and production of cyclic AMP (cAMP). Serum TSH is a sensitive indicator of thyroid function, and overt abnormalities in thyroid function lead to common endocrine disorders affecting approximately 10% of individuals over a life span. By genotyping 362,129 SNPs in 4,300 Sardinians, we identified a strong association (p = 1.3 x 10(-11)) between alleles of rs4704397 and circulating TSH levels; each additional copy of the minor A allele was associated with an increase of 0.13 muIU/ml in TSH. The single-nucleotide polymorphism (SNP) is located in intron 1 of PDE8B, encoding a high-affinity cAMP-specific phosphodiesterase. The association was replicated in 4,158 individuals, including additional Sardinians and two genetically distant cohorts from Tuscany and the Old Order Amish (overall p value = 1.9 x 10(-20)). In addition to association of TSH levels with SNPs in PDE8B, our genome scan provided evidence for association with PDE10A and several biologically interesting candidates in a focused analysis of 24 genes. In particular, we found evidence for association of TSH levels with SNPs in the THRB (rs1505287, p = 7.3 x 10(-5)), GNAQ (rs10512065, p = 2.0 x 10(-4)), TG (rs2252696, p = 2.2 x 10(-3)), POU1F1 (rs1976324, p = 3.9 x 10(-3)), PDE4D (rs27178, p = 8.3 x 10(-3)), and TSHR (rs4903957, p = 8.6 x 10(-3)) loci. Overall, the results suggest a primary effect of PDE8B variants on cAMP levels in the thyroid. This would affect production of T4 and T3 and feedback to alter TSH release by the pituitary. PDE8B may thus provide a candidate target for the treatment of thyroid dysfunction.

Enhancement of Vascular Endothelial Function by Recombinant Human Thyrotropin

The cardiovascular consequences of thyroid diseases are attributed to the altered secretion of thyroid hormones. The possibility that TSH also affects the cardiovascular system has been poorly explored. Endothelial cells and vascular smooth muscle cells possess TSH receptors. The study was designed to determine whether TSH exerts any effect on vascular homeostasis. Two different double-blind, controlled studies were performed, one in eight healthy volunteers and the other in six thyroidectomized patients. Recombinant human (rh) TSH (or saline) was infused intrabrachially (1 mU/min) to raise TSH to severe hypothyroidism levels (approximately 100 microU/ml). Endothelium-dependent and -independent vasodilation was tested by intraarterial infusion of acetylcholine and sodium nitroprusside, respectively, and forearm blood flow was measured by plethysmography. Endothelium-dependent vasodilation was potentiated by rhTSH (P < 0.05 for the treatment effect; general linear model). The dynamics of the response was also profoundly affected by rhTSH because the dose-response curve was much steeper than in controls (P < 0.02 for the interaction between TSH and acetylcholine). rhTSH had no effect on endothelium-independent vasodilation (P = NS for both treatment and interaction). During rhTSH infusion, free T(3) levels increased slowly from 2.3 +/- 0.2 to 3.6 +/- 0.2 pg/ml. In thyroidectomized patients, rhTSH potentiated endothelium-mediated vasodilation to an extent similar to that of healthy subjects (P = 0.05 for the treatment effect and P = 0.01 for the interaction), without affecting the response to nitroprusside. In these patients, thyroid hormones remained unchanged during rhTSH infusion. rhTSH exerts marked effects on the resistance vessels by enhancing endothelial-mediated vasodilation, independent of changes in thyroid hormone concentration.

Fasting-Induced Changes in the Hypothalamus–Pituitary–Thyroid Axis

Fasting induces profound changes in the hypothalamus-pituitary-thyroid (HPT) axis. The alterations observed in humans and rodents are similar in many ways, although they may be more pronounced and more acute in rodents. The molecular mechanisms underlying the resetting of HPT axis regulation in the framework of caloric deprivation are still incompletely understood. Fascinating studies in rats and mice have shown a dramatic downregulation of thyrotropin-releasing hormone (TRH) gene expression in hypophysiotropic paraventricular nucleus (PVN) neurons during fasting. Direct and indirect effects of decreased serum leptin, as well as effects of increased local triiodothyronine (T3) concentrations, in the hypothalamus during food deprivation contribute to the decreased activity of TRH neurons in the PVN. However, the relative contributions of these complex determinants remain to be defined in more detail. Pituitary thyroid-stimulating hormone (TSH) beta mRNA expression decreases during fasting, and this may be relatively independent of leptin and/or TRH, since leptin administration in this setting does not fully restore pituitary TSH expression, while it does restore TRH expression in the PVN. There may be a role for pituitary peptides, such as neuromedin B, in altered TSH gene expression during fasting. The observed decrease in serum thyroid hormone concentrations results to some extent from diminished thyroidal secretion of thyroid hormones, especially in rodents. Decreased thyroxine (T4) and T3 contribute to the downregulation of T3-responsive genes such as liver D1. The overall result of these complex HPT axis changes in various tissues during fasting is downregulation of the HPT axis, which is assumed to represent an energy-saving mechanism, instrumental in times of food shortage.

Painless thyroiditis occurring during post-menopausal period, following remission of Graves’ disease

Painless thyroiditis (also called “silent thyroiditis”) is a clinical entity that belongs to the spectrum of autoimmune thyroiditis (1). Patients usually experience an initial thyrotoxic phase, followed by a hypothyroid state and returning to a euthyroid state. This disorder often develops in patients with positive tests for anti-thyroid antibodies during the post-partum period (2). Thyrotoxicosis observed in painless thyroiditis differs from that in Graves’ disease. In the former, thyroid hormones leak into the circulation as a result of thyroid destruction, whereas in the latter anti-TSH receptor antibodies stimulate production and secretion of thyroid hormones. The therapeutic approaches for both disorders are completely different and thus differential diagnosis is important in clinical practice. Here, we describe a patient developing painless thyroiditis during menopausal pe

Sexual dimorphism in the acute effects of secondhand smoke on thyroid hormone secretion, inflammatory markers and vascular function

Experimental evidence for the physiological effects of secondhand smoke (SHS) is limited, although it affects millions of people globally and its prevalence is increasing, despite currently adopted antismoking measures. Also, scarce evidence suggests that the effects of SHS may be more pronounced in men. We conducted a randomized single-blind crossover study to investigate the sex-specific SHS effects in a controlled simulated bar/restaurant environment on gonadal and thyroid hormones, inflammatory cytokines, and vascular function. Twenty-eight (women = 14) nonsmoking adults underwent a 1-h exposure to moderate SHS and a 1-h control trial. Serum and urine cotinine, gonadal and thyroid hormones, inflammatory cytokines, heart rate, and arterial blood pressure were assessed before exposure and immediately after in both trials. Results showed that testosterone (P = 0.019) and progesterone (P < 0.001) in men and 17beta-estradiol (P = 0.001) and progesterone (P < 0.001) in women were significantly decreased after SHS. In men, SHS was accompanied by increased free thyroxine (P < 0.001), triiodothyronine (P = 0.020), and decreased the triiodothyronine-to-free thyroxine ratio (P = 0.033). In women, significant SHS-induced change was observed only in free thyroxine (P = 0.010), with considerable sex variation in free thyroxine and triiodothyronine and a decrease in luteinizing hormone (P = 0.026) and follicle-stimulating hormone (P < 0.001). After SHS, IL-1beta (P = 0.001) and systolic blood pressure (P = 0.040) were increased in men but not women. We concluded that a 1-h SHS exposure at bar/restaurant levels is accompanied by decrements in gonadal hormones in both sexes and marked increases in thyroid hormone secretion, IL-1beta production, and systolic blood pressure in men.

Thyrocyte-specific Gq/G11 deficiency impairs thyroid function and prevents goiter development

The function of the adult thyroid is regulated by thyroid-stimulating hormone (TSH), which acts through a G protein-coupled receptor. Overactivation of the TSH receptor results in hyperthyroidism and goiter. The Gs-mediated stimulation of adenylyl cyclase-dependent cAMP formation has been regarded as the principal intracellular signaling mechanism mediating the action of TSH. Here we show that the Gq/G11-mediated signaling pathway plays an unexpected and essential role in the regulation of thyroid function. Mice lacking the alpha subunits of Gq and G11 specifically in thyroid epithelial cells showed severely reduced iodine organification and thyroid hormone secretion in response to TSH, and many developed hypothyroidism within months after birth. In addition, thyrocyte-specific Galphaq/Galpha11-deficient mice lacked the normal proliferative thyroid response to TSH or goitrogenic diet, indicating an essential role of this pathway in the adaptive growth of the thyroid gland. Our data suggest that Gq/G11 and their downstream effectors are promising targets to interfere with increased thyroid function and growth.

Gender Difference in the Effects of Organochlorines and Mercury Exposure on Thyroid Hormones Levels

ISEE-618 Objective: Organochlorines pollutants (OCs) and mercury (Hg) are widespread environmental pollutants, characterized by their accumulation in the food web chain. PCBs are known endocrine disruptors particularly with respect to thyroid function and/or action. Little data are available on thyrotoxic effects of OCs in adult men and women although recent studies have reported a striking excess of hypothyroidism and a higher prevalence of thyroid disorders in women in relation to OCs exposure. The objectives of the study are to examine THs levels in relation to blood concentrations of OCs and Hg for men and women. Materials and Methods: This cross-sectional study was carried out in 2 fishing communities in Quebec, Canada. An interviewer-administered questionnaire was used to assess species specific fish consumption and a self-administered questionnaire was used to collect sociodemographics, work and medical history. The group (N=213) consisted of 125 (59%) men and 88 (41%) women) with an average age of 49.2 ± 13.1 years old. Results: Overall, OCs concentrations were low and thyroid hormone secretion was within the normal range. For women, TT3 was negatively related to PCB-138, PCB-153, noncoplanar congeners, Arochlor 1260, dioxine-like congeners σ PCBs and DDE levels, but no relation was observed between TT4, TSH, and OCs. On the contrary, for men TT4 decreased in relation to dioxine-like congeners and σ PCBs concentrations and TSH increased significantly in relation to PCB-180, Arochlor 1260, σ PCBs, noncoplanar and dioxine-like congeners levels. However no relation was noted between TT4, TSH, and POCs. The only significant decrease of TT3 levels was in relation to σ POCs. In regard to Hg body burden, for men, a positive relationship was observed between blood total Hg and THs. Conclusions: These findings suggest that at even low levels of exposure, these persistent environmental contaminants can interfere with thyroid status and that there may be important gender differences.

Cyclic Adenosine 3′,5′-Monophosphate (cAMP)-Dependent Protein Kinases, But Not Exchange Proteins Directly Activated by cAMP (Epac), Mediate Thyrotropin/cAMP-Dependent Regulation of Thyroid Cells

TSH, mainly acting through cAMP, is the principal physiological regulator of thyroid gland function, differentiation expression, and cell proliferation. Both cAMP-dependent protein kinases [protein kinase A (PKA)] and the guanine-nucleotide-exchange factors for Rap proteins, exchange proteins directly activated by cAMP (Epac) 1 and Epac2, are known to mediate a broad range of effects of cAMP in various cell systems. In the present study, we found a high expression of Epac1 in dog thyrocytes, which was further increased in response to TSH stimulation. Epac1 was localized in the perinuclear region. Epac2 showed little or no expression. The TSH-induced activation of Rap1 was presumably mediated by Epac1 because it was mimicked by the Epac-selective cAMP analog (8-p-chloro-phenyl-thio-2'-O-methyl-cAMP) and not by PKA-selective cAMP analogs. Surprisingly, in view of the high Epac1 expression and its TSH responsiveness, all the cAMP-dependent functions of TSH in cultures or tissue incubations of dog thyroid, including acute stimulation of thyroid hormone secretion, H(2)O(2) generation, actin cytoskeleton reorganization, p70(S6K1) activity, delayed stimulation of differentiation expression, and mitogenesis, were induced only by PKA-selective cAMP analogs. The Epac activator 8-p-chloro-phenyl-thio-2'-O-methyl-cAMP, used alone or combined with PKA-selective cAMP analogs, had no measurable effect on any of these TSH targets. Therefore, PKA activation seems to mediate all the recognized cAMP-dependent effects of TSH and is thus presumably responsible for the pathological consequences of its deregulation. The role of Epac1 and TSH-stimulated Rap1 activation in thyrocytes is still elusive.

A mathematical model of pituitary–thyroid interaction to provide an insight into the nature of the thyrotropin–thyroid hormone relationship

The mathematical model proposed focuses on the description of the behavior of the interaction between thyrotropin (i.e. thyroid-stimulating hormone (TSH)) and thyroid hormones with the objective of providing a better understanding of the behavior of TSH-T4 relationship in health and in disease. The normal pituitary–thyroid axis is tightly coupled and regulated with a servomechanism. In the physiological situation, any elevation of thyroid hormones will inhibit TSH secretion by the thyrotrophs of the pituitary, which in turn lead to an appropriate reduction in stimulation of the thyroid, accompanied by a decline of thyroid hormones towards normal. Similarly, a decline in thyroid hormones represents a potent input signal that when sensed by the pituitary thyrotrophs, will result in an increase of TSH output by the latter to accelerate the synthesis and secretion of thyroid hormones to drive the state towards normal equilibrium. Using this model, the profound sensitivity of thyrotrophs to feedback by thyroid hormones can be appreciated and understood better in the context of diseases of thyroid hormone excess and deficiency.

Molecular characterization and seasonal changes in gonadal expression of a thyrotropin receptor in the European sea bass

The thyroid stimulating hormone (TSH) is a glycoprotein synthesized and secreted from thyrotrophs of the anterior pituitary gland. It acts by binding to and activating its specific receptor, the TSHR, to induce the synthesis and secretion of thyroid hormones. Recent studies conducted in diverse fish species suggest a direct role of TSH on gonadal physiology. In this work, we describe the cloning of a cDNA encoding a TSHR which was isolated from the gonads of the European sea bass ( Dicentrarchus labrax). The mature protein displays typical features of the members of the glycoprotein hormone receptor family and shows the highest amino acid sequence identity with the TSHRs of other fish species. An insertion of approximately 50 amino acids, specific for the TSHR subfamily is also present in the carboxyl end of the extracellular domain of the sbsTSHR. By RT-PCR analysis, we demonstrate the extrathyroidal expression of sbsTSHR in numerous tissues of the sea bass. Also, two transcripts that differ in the length of their 3′ untranslated regions were found. They reflect the use of alternative polyadenylation cleavage sites. Seasonal changes in sbsTSHR mRNA levels in female and male sea bass during the first ovarian and testicular recrudescence suggest that in females the TSHR could participate in active vitellogenesis and in the regulation of gamete maturation and ovulation, whereas in males, the TSHR would be involved in the regulation of processes that occur during the early stages of the gonadal development and also of gamete maturation and spermiation. The results of this work indicate that a sbsTSHR has been cloned from the testis of the European sea bass and they provide the basis for future studies concerning the function of TSHR in this species.

Antithyroid Drugs Inhibit Thyroid Hormone Receptor-Mediated Transcription

Methimazole (MMI) and propylthiouracil (PTU) are widely used as antithyroid drugs (ATDs) for the treatment of Graves' disease. Both MMI and PTU reduce thyroid hormone levels by several mechanisms, including inhibition of thyroid hormone synthesis and secretion. In addition, PTU decreases 5'-deiodination of T(4) in peripheral tissues. ATDs may also interfere with T(3) binding to nuclear thyroid hormone receptors (TRs). However, the effect of ATDs on the transcriptional activities of T(3) mediated by TRs has not been studied. The present study was undertaken to determine whether ATDs have an effect on the gene transcription regulated by T(3) and TRs in vitro. Transient gene expression experiments and GH secretion assays were performed. To elucidate possible mechanisms of the antagonistic action of ATDs, the interaction between TR and nuclear cofactors was examined. In the transient gene expression experiments, both MMI and PTU significantly suppressed transcriptional activities mediated by the TR and T(3) in a dose-dependent manner. In mammalian two-hybrid assays, both drugs recruited one of the nuclear corepressors, nuclear receptor corepressor, to the TR in the absence of T(3). In addition, PTU dissociated nuclear coactivators, such as steroid receptor coactivator-1 and glucocorticoid receptor interacting protein-1, from the TR in the presence of T(3). Finally, MMI decreased the GH release that was stimulated by T(3). ATDs inhibit T(3) action by recruitment of transcriptional corepressors and/or dissociation of coactivators. This is the first report to show that ATDs can modulate T(3) action at the transcriptional level.

Effect of recombinant bovine tumor necrosis factor‐α on hormone release in lactating cows

ABSTRACTTumor necrosis factor (TNF)‐α is a powerful macrophage cytokine released during infection, circulating in the blood to produce diverse effects in the organism. We examined the effect of recombinant bovine TNF‐α (rbTNF‐α) administration on hormone release in dairy cows during early lactation. Twelve non‐pregnant Holstein cows were treated subcutaneously with rbTNF‐α (2.5 µg/kg) or saline twice (at 11.00 and 23.00 hours). At 11.00 hours the next day, the cows were given growth hormone‐releasing hormone (GHRH, 0.25 µg/kg), thyrotrophin‐releasing hormone (TRH, 1.0 µg/kg), thyroid‐stimulating hormone (TSH, 10 µg/kg) or adrenocorticotropic hormone (500 µg/head) via the jugular vein. In the growth hormone‐releasing hormone challenge, the plasma growth hormone concentration was lower in the rbTNF‐α group than in the control (saline) group. The growth hormone and TSH responses to TRH were also smaller in the rbTNF‐α group than in the control. The plasma prolactin response to TRH was not affected by the rbTNF‐α treatment. In the TSH challenge, the rbTNF‐α‐treated cows had lower responses, as measured by plasma triiodothyronine and thyroxine, than the control cows. The rbTNF‐α treatment produced an increase in the basal plasma cortisol level, but the cortisol response to adrenocorticotropic hormone was the same level in both groups. The plasma concentrations of TNF‐α and interleukin‐1β in the cows were elevated by the rbTNF‐α treatment. The milk yield was reduced by the rbTNF‐α administration during 4 days. These data demonstrate that TNF‐α alters the secretion of pituitary and thyroid hormones in lactating cows. This effect may contribute to the suppression of the lactogenic function of the mammary gland observed in cases of coliform mastitis with high circulating TNF‐α levels.

TSH-Dependent Expression of the LDL Receptor–Associated Protein (RAP) in Thyroid Epithelial Cells

The low density lipoprotein (LDL) receptor-associated protein (RAP) is an endoplasmic reticulum (ER)-resident molecular chaperone for several LDL receptor family members and it also binds to thyroglobulin (Tg), the thyroid hormone precursor. Disruption of the RAP gene in thyrocytes results in impaired Tg secretion. To gain further insights into the function of RAP in the thyroid, we investigated whether its expression in thyrocytes is regulated by thyroid-stimulating hormone (TSH), a feature common to all proteins involved in thyroid hormone secretion. We found by immunofluorescence that in FRTL-5 cells cultured in the presence of TSH, RAP is expressed intracellularly. The levels of expression increased after exposure to TSH, beginning at 48 hours, in a concentration-dependent manner as observed by immunofluorescence and Western blotting. Expression of RAP was also increased by TSH in primary cultures of human thyrocytes as observed by Western blotting. In hypothyroid mice with high serum TSH, RAP was markedly increased compared with euthyroid mice as observed by immunohistochemistry and Western blotting. Based on these findings, we concluded that RAP is expressed by thyrocytes in a TSH-dependent manner, both in cultured thyroid cells and in vivo.

A Brief Exposure to Moderate Passive Smoke Increases Metabolism and Thyroid Hormone Secretion

Active smoking influences normal metabolic status and thyroid function. The objective was to assess experimentally the effects of 1 h of moderate passive smoking in a controlled simulated bar/restaurant environment on the metabolism and thyroid hormone levels in healthy nonsmokers. Eighteen (nine females, nine males) healthy individuals (mean +/- sd: age, 25.3 +/- 3.1 yr; height, 174.0 +/- 10.1 cm; weight, 65.2 +/- 13.7 kg) participated in the study. In repeated-measures randomized blocks, participants visited the laboratory on 2 consecutive days. In the experimental condition, they were exposed to 1 h of moderate passive smoking at a carbon monoxide concentration of 23 +/- 1 ppm in an environmental chamber, whereas in the control condition participants remained in the same chamber for 1 h breathing normal atmospheric air. In both conditions, cotinine serum and urine levels, resting energy expenditure (REE), as well as concentration of T3, free T4, and TSH were assessed before participants entered the chamber and immediately after their exit. Heart rate and blood pressure were tested in 10-min intervals during all REE assessments. The mean +/- sd difference of serum and urine cotinine levels (-0.27 +/- 3.94 vs. 14.01 +/- 6.54 and 0.05 +/- 2.07 vs. 7.23 +/- 3.75, respectively), REE (6.73 +/- 98.06 vs. 80.58 +/- 120.91) as well as T3 and free T4 (0.05 +/- 0.11 vs. 0.13 +/- 0.12 and 0.02 +/- 0.15 vs. 0.22 +/- 0.20) were increased in the experimental compared with the control condition at baseline and follow-up (P < 0.05). No statistically significant variation was observed in the mean difference of the remaining parameters (P > 0.05). Serum and urine cotinine values were linearly associated with REE (P < 0.05). One hour of passive smoking at bar/restaurant levels is accompanied by significant increases in metabolism and thyroid hormone levels.

Thyroid Hormone Synthesis and Secretion in Humans after 80 Milligrams of Iodine for 15 Days and Subsequent Withdrawal

In animals, acute iodine administration results in acute intrathyroidal inhibition of iodinations followed by escape of the inhibition if the excessive iodine intake continues. In humans, the intrathyroidal nonhormonal and hormonal iodine concentration after exposure to large doses of iodine for a relatively long period of time is not known. To determine whether, in human thyroid, administration of large doses of iodine for a relatively long time results in alterations of intrathyroidal hormonal (HI) T4 and T3 and total iodine (TI) content, as well as whether changes in serum concentration of thyroid hormones and TSH would occur after iodine administration or discontinuation. In 33 euthyroid patients with single thyroid nodule or hyperparathyroidism, Lugol solution (80 mg iodine) was administered for 15 d before operation. Groups of six to eight patients underwent operation 0, 5, 10, and 15 d after iodine withdrawal. TI, HI in a sample of thyroid tissue, and serum concentration of T4, T3, and TSH were measured. In 21 normal euthyroid subjects who did not undergo operation, a similar protocol was used and serial blood measurements were taken. Intrathyroidal TI, HI, and serum thyroid hormone and TSH measurements were the main outcome measure. Intrathyroidal HI content and serum T4 and T3 were unchanged during and after iodine discontinuation. TI was increased during iodine administration and returned to control values 5 d after discontinuation of iodine. The ratio of HI/TI was decreased and returned to control values 15 d after the iodine was discontinued. Serum TSH was increased during iodine administration and returned to control values 10 d after iodine withdrawal. In humans, administration of iodine for a relatively long period of time was accompanied by increased intrathyroidal TI, but no changes in HI or demonstrable increases of serum T4 and T3 were observed. It is hypothesized that the maintenance of normal intrathyroidal HI is the result of the combined inhibitory effect of iodine on thyroid hormone synthesis and on the release of T4 and T3 from the thyroid.

Evaluation of ammonium perchlorate in the endocrine disruptor screening and testing program's male pubertal protocol: Ability to detect effects on thyroid endpoints

The U.S. EPA Endocrine Disruptor Screening Program (EDSP) Tier 1 male pubertal protocol was designed as a screen to detect endocrine-disrupting chemicals which may alter reproductive development or thyroid function. One purpose of this in vivo screening protocol is to detect thyrotoxicants via a number of different mechanisms of action, such as thyroid hormone synthesis or clearance. Here we evaluate the ability of this EDSP male pubertal protocol to detect the known thyrotoxicant ammonium perchlorate as an endocrine disruptor. Ammonium perchlorate is a primary ingredient in rocket fuel, fertilizers, paints, and lubricants. Over the past 50 years, potassium perchlorate has been used to treat hyperthyroidism in humans. Perchlorate alters thyroid hormone secretion by competitively inhibiting iodide uptake by the thyroid gland. In this study, ammonium perchlorate was administered at 62.5, 125, 250, and 500 mg/kg to male Wistar rats based on a pilot study of oral dosing. Doses of 125–500 mg/kg perchlorate decreased T4 in a dose-dependent manner. TSH was significantly increased in a dose-responsive manner at the same doses, while T3 was unchanged at any dose. Thyroid histology was significantly altered at all doses, even at the 62.5 mg/kg, with a clear dose-dependent decrease in colloid area and increase in follicular cell height. No effects on preputial separation, a marker of pubertal progression, or reproductive tract development were observed at any dose. These results demonstrate that the male pubertal protocol is useful for detecting thyrotoxicants which target the thyroid axis by this mechanism (altered uptake of iodide). This study also found that perchlorate exposure during this period did not alter any of the reproductive developmental endpoints.

Thyroid Storm

Objectives—Following completion of this CE offering, the participant will be able to (1) describe the systemic action of thyroid hormone, (2) describe a negative feedback loop in relation to the control and regulation of the secretion of thyroid hormone, (3) list the potential symptoms that are associated with thyroid storm, and (4) discuss the implications of thyroid storm on the perianesthetic patient. Kim A. Noble, MSN, RN, CPAN, is an Assistant Professor at Temple University, Philadelphia, PA

Recovery of age‐dependent immunological deterioration in old mice by thyroxine treatment

On the basis that multiple interactions exist between thyroid hormones and immune system, and ageing is accompanied by changes in thyroid hormone secretion, it seems possible that thyroid hormones may be involved in the age-related immune dysfunction. The present study was conducted to evaluate in vivo and in vitro effects of thyroxine (T(4)) treatment on both cell-mediated and humoral immune responses of aged mice. In a trial to improve age-associated immune dysfunction, T(4) (0.2, 1.0 and 5.0 microg) was subcutaneously supplemented to BALB/c mice (over 18 months old) for 30 consecutive days. The present results showed that exogenous treatment of aged mice with T(4) was associated with a marked increase in serum T(4) level, and the total number of peripheral blood leukocytes as well as the total cellularity of thymus, spleen, peripheral lymph nodes (PLNs), mesenteric lymph nodes (MLNs) and bone marrow (BM). T(4) treatment also caused a significant increase in the total and differential numbers of peritoneal exudate cells (PECs), while it caused a slight increase in macrophages' phagocytic activity of PEC. Moreover, T(4) treatment elicited a statistically significant increase in both plaque-forming cell and rosette-forming cell responses. In vitro results showed that the addition of T(4) at concentrations of 0.001, 0.005 and 0.025 microg/well substantially potentiated the ability of splenocytes from aged mice to proliferate in the presence of concanavalin-A mitogen. Histological examination of thymuses from T(4)-treated aged mice revealed that the cortex was preferentially enlarged and repopulated with immature thymocytes. The present study postulates that thyroid hormones may be involved in the observed decrease in the immune responsiveness during ageing, and that T(4) treatment to aged mice is able to restore the age-related decline of the immune efficiency.

The Immune System as a Regulator of Thyroid Hormone Activity

It has been known for decades that the neuroendocrine system can both directly and indirectly influence the developmental and functional activity of the immune system. In contrast, far less is known about the extent to which the immune system collaborates in the regulation of endocrine activity. This is particularly true for immune-endocrine interactions of the hypothalamus-pituitary-thyroid axis. Although thyroid-stimulating hormone (TSH) can be produced by many types of extra-pituitary cells--including T cells, B cells, splenic dendritic cells, bone marrow hematopoietic cells, intestinal epithelial cells, and lymphocytes--the functional significance of those TSH pathways remains elusive and historically has been largely ignored from a research perspective. There is now, however, evidence linking cells of the immune system to the regulation of thyroid hormone activity in normal physiological conditions as well as during times of immunological stress. Although the mechanisms behind this are poorly understood, they appear to reflect a process of local intrathyroidal synthesis of TSH mediated by a population of bone marrow cells that traffic to the thyroid. This hitherto undescribed cell population has the potential to microregulate thyroid hormone secretion leading to critical alterations in metabolic activity independent of pituitary TSH output, and it has expansive implications for understanding mechanisms by which the immune system may act to modulate neuroendocrine function during times of host stress. In this article, the basic underpinnings of the hematopoietic-thyroid connection are described, and a model is presented in which the immune system participates in the regulation of thyroid hormone activity during acute infection.