Reverse T3 Concentrations Research Articles

Iodine in the Therapy of Graves' Disease: A Century After Henry S. Plummer.

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Effects of Selenium and/or N-Acetyl-Cysteine Supplementation on Nonthyroidal Illness Syndrome in Hemodialysis Patients: A Factorial Randomized Controlled Trial

Introduction: Nonthyroidal illness syndrome (NTIS) is common in hemodialysis patients (HPs). However, limited clinical trials have been conducted in this field. Therefore, the aim of this study was to investigate the effect of Se and/or N-acetyl-cysteine (NAC) on NTIS parameters in HPs. Methods: In this factorial randomized controlled trial, 68 HPs were divided into four groups: group A received placebo of Se and NAC, group B received 600 μg per day of NAC and placebo of Se, group C received 200 μg of Se per day and placebo of NAC and group D received 200 μg of selenium and 600 μg of NAC per day for 12 weeks. Blood samples were taken at baseline and after 12 weeks to assess free tri-iodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH), and reverse T3 (rT3) concentrations. Results: Our finding demonstrated that rT3 levels were decreased in B, C, and D groups and increased nearly to baseline levels in the A group after 12 weeks, with a marked difference between the groups (p < 0.001) based on ANOVA. Although there were no significant differences in FT3 (p = 0.39), FT4 (p = 0.76), and TSH (p = 0.71) between the groups at the end of the trial. Conclusion: This trial showed that Se and/or NAC exert beneficial effects on rT3 levels in HPs. However, long-term clinical trials with a larger sample size using more appropriate biomarkers are recommended to evaluate the efficacy and safety of Se and/or NAC in HPs.

Evaluation of the effects of chronic occupational exposure to metallic mercury on the thyroid parenchyma and hormonal function.

Experiments in animals exposed to mercury (Hg) in different chemical states have shown thyroid parenchymal and hormone alterations. However, these experiments did not allow the establishment of dose-response curves or provide an understanding of whether these Hg effects on the thyroid parenchyma occur in humans. To evaluate the association between chronic occupational exposure to metallic Hg and alterations in thyroid hormones and gland parenchyma 14years after the last exposure. A cross-sectional study including 55 males exposed in the past to metallic Hg and 55 non-exposed males, paired by age, was conducted in the Hospital das Clínicas (Brazil) from 2016 to 2017. Serum concentrations of total and free triiodothyronine (TT3 and FT3), free thyroxine (FT4), thyrotropin (TSH), reverse T3 (RT3), selenium and antithyroid antibody titers were obtained. The Hg and iodine concentrations were measured in urine. The thyroid parenchyma was evaluated by B-mode ultrasonography with Doppler. The nodules with aspects suspicious for malignancy were submitted to aspiration puncture with a thin needle, and the cytology assessment was classified by the Bethesda system. The t test or Mann-Whitney test, Chi-square test and Spearman correlation were used to compare the exposed and non-exposed groups and examine the relationships between the variables. Univariate and multivariate logistic regression models were used to trace determinants of the risk of thyroid hormone alteration. Statistical significance was defined by p < 0.05. The urinary Hg average was significantly higher in the exposed group than in the non-exposed group (p < 0.01). The mean TSH serum concentration in the exposed group was higher, with a statistically significant difference between the groups (p = 0.03). Serum concentrations of TSH exceeded the normality limit (4.20µIU/ml) in 13 exposed individuals (27.3%) and 4 non-exposed individuals (7.3%), with a statistically significant association between the hormonal increase and exposure to Hg (p = 0.02). In the logistic regression model, exposure to Hg (yes or no) showed an odds ratio = 4.86 associated with an increase of TSH above the normal limit (p = 0.04). The serum concentrations of RT3 showed a statistically borderline difference between the groups (p = 0.06). There was no statistically significant difference between the mean TT3, FT3 and FT4 serum concentrations in the Hg-exposed group compared to the non-exposed group. The proportions of the echogenicity alterations were higher in the exposed group compared to the non-exposed group (27.3% versus 9.1%; p = 0.03). Papillary carcinomas were documented in three exposed individuals and one non-exposed individual. A follicular carcinoma was recorded in one non-exposed individual. Due to the higher serum TSH concentration and the prevalence of parenchymal alterations in the Hg-exposed group, even after cessation of exposure, it is recommended that the thyroid status of exposed workers be followed for a long period.

A novel IGSF1 mutation in a large Irish kindred highlights the need for familial screening in the IGSF1 deficiency syndrome.

SummaryObjectiveLoss‐of‐function mutations in IGSF1 result in X‐linked central congenital hypothyroidism (CeCH), occurring in isolation or associated with additional pituitary hormone deficits. Intrafamilial penetrance is highly variable and a minority of heterozygous females are also affected. We identified and characterized a novel IGSF1 mutation and investigated its associated phenotypes in a large Irish kindred.Design, Patients and MeasurementsA novel hemizygous IGSF1 mutation was identified by direct sequencing in two brothers with CeCH, and its functional consequences were characterized in vitro. Genotype‐phenotype correlations were investigated in the wider kindred.ResultsThe mutant IGSF1 protein (c.2318T > C, p.L773P) exhibited decreased plasma membrane expression in vitro due to impaired trafficking from the endoplasmic reticulum. Ten hemizygous males and 11 heterozygous females exhibited characteristic endocrine deficits. Ireland operates a TSH‐based CH screening programme, which does not detect CeCH; therefore, genetic ascertainment preceded biochemical diagnosis of moderate CH in five of seven boys as well as their 75‐year‐old grandfather. Clinical features potentially attributable to hypothyroidism were variable; normal free T3 (FT3) and low/low normal reverse T3 (rT3) concentrations suggested that preferential deiodination of FT4 to FT3 may help maintain tissue euthyroidism in some individuals. However, neonatal jaundice, delayed speech or growth, and obesity were observed in seven subjects in whom diagnosis was delayed.ConclusionsAs observed with other IGSF1 mutations, p.L773P results in variably penetrant IGSF1 deficiency syndrome. Our observations emphasize the need for multi‐generation genetic ascertainment in affected families, especially where TSH‐based CH screening programmes may fail to detect CeCH at birth.

Response to capture stress involves multiple corticosteroids and is associated with serum thyroid hormone concentrations in Guadalupe fur seals (Arctocephalus philippii townsendi)

AbstractGuadalupe fur seals are a threatened species with few breeding locations, which potentially makes them sensitive to environmental or anthropogenic stressors. We present the first study to quantify adrenal and thyroid function in this species in an effort to measure their stress response to capture. We analyzed a suite of corticosteroid hormones released over time during capture in both adult females (n = 10) and weanling pups (n = 26) during March 2016. Multiple corticosteroids were released during capture, and aldosterone was associated with the response to stress in adults only. These results suggest the regulation of aldosterone secretion in association with the HPA axis in otariids as reported in other marine mammals. Individuals varied markedly in the magnitude of their endocrine response to capture. A lower total integrated stress response to capture for both cortisol and corticosterone was associated with decreased concentrations of thyroid hormone T3 and elevated concentrations of reverse T3 (rT3), suggesting parallel downregulation of adrenal and thyroid endocrine axes in some individuals. A scaled body condition index was negatively associated with T3 and positively associated with rT3 in adults. Together these findings suggest utility in using endocrine responses to capture stress to evaluate individual and population health.

Variation in adrenal and thyroid hormones with life-history stage in juvenile northern elephant seals (Mirounga angustirostris)

The classical approach to quantifying the impact of stressors on wildlife is through characterization of hormones associated with the generalized stress response. However, interpretation of hormone data can be difficult due to the range of natural variation within a species and potential confounds of individual and life-history variables. Blood adrenal and thyroid hormones were measured in 144 chemically immobilized yearling northern elephant seals (Mirounga angustirostris) to characterize variation between sexes and across semiannual haul-outs. There was no relationship between hormone concentrations and time needed for collecting blood nor evidence of diel patterns, suggesting that collection of samples for baseline values can be accomplished without bias due to handling artifacts or time of day. Serum cortisol concentrations did not vary with gender or across haul-out fasts but increased dramatically during molting. Cortisol was correlated with aldosterone across all measured life-history stages. Thyroid hormone levels were lower in females and decreased with fasting in both sexes during the fall haul-out. Cortisol concentrations were inversely associated with total triiodothyronine (T3) and positively associated with reverse T3 concentrations across all measured life-history stages suggesting an important impact of cortisol on deiodinase enzymes and thyroid function. Epinephrine concentrations increased across fasts and norepinephrine concentrations were higher in males than in females. Significant variation in stress hormone concentrations with gender and life-history stage emphasizes the importance of contextual variables when interpreting serum hormone concentrations.

Non-thyroidal illness in the ICU: a syndrome with different faces.

Critically ill patients typically present with low or low-normal plasma thyroxine, low plasma triiodothyronine (T3), increased plasma reverse T3 (rT3) concentrations, in the absence of a rise in thyrotropin (TSH). This constellation is referred to as nonthyroidal illness syndrome (NTI). Although it is long known that the severity of NTI is associated with risk of poor outcomes of critical illness, the causality in this association has not been well investigated. In this narrative review, the different faces of NTI during critical illness are highlighted. Acute alterations are dominated by changes in thyroid hormone binding, peripheral thyroid hormone uptake, and alterations in the expression and activity of the type-1 and type-3 deiodinases. It was recently shown that at least part of these acute changes are brought about by concomitant macronutrient restriction, and this part appears adaptive and beneficial. However, the face of the NTI in the prolonged phase of critical illness is different, when patients are fully fed but continue to depend on intensive medical care. In that prolonged phase of illness, hypothalamic thyrotropin releasing hormone (TRH) expression is suppressed and explains reduced TSH secretion and whereby reduced thyroidal hormone release. During prolonged critical illness, and in the presence of adequate nutrition, several tissue responses could be interpreted as compensatory to low thyroid hormone availability, such as increased expression of monocarboxylate transporters, upregulation of type-2 deiodinase activity, and increased sensitivity at the receptor level. Infusing hypothalamic releasing factors in these prolonged critically ill patients can reactivate the thyroid axis and induce an anabolic response. It is clear that the name "NTI" during critical illness refers to a syndrome with different faces. Tolerating the early "fasting response" to critical illness and its concomitant changes in thyroid hormone parameters appears to be wise and beneficial. This thus applies to the NTI present in the majority of the patients treated in intensive care units. However, the NTI that occurs in prolonged critically ill patients appears different with regard to both its causes and consequences. Future studies should specifically target this selected population of prolonged critically ill patients, and, after excluding iatrogic drug interferences, investigate the effect on outcome of treatment with hypothalamic releasing factors in adequately powered randomized controlled trials.

Thyroid hormone changes associated with prolonged food deprivation in adult male northern elephant seals (1101.6)

During food deprivation in mammals, thyroid hormone (TH) concentrations and deiodinase (DI) content is typically reduced to suppress metabolism. However, in metabolically active elephant seal pups the hypothalamic‐pituitary‐thyroid axis is up‐regulated during prolonged fasting. To better understand the mechanisms regulating the cellular function of TH in a fasting, yet metabolically active mammal, we measured plasma TH concentrations and mRNA expressions of DI type II (DI2) and TH receptor beta‐1 (THrβ‐1) in adult male northern elephant seals (n=8) over 8 weeks of fasting (early vs. late). We hypothesized that natural fasting in male seals decreases TH levels and DI expression. Fasting did not alter the concentrations of plasma reverse T3 and total T4. However, free T4 (0.25 ± 0.03 to 0.78 ± 0.08 ng/dL) and free T3 (0.61 ± 0.06 to 0.83 ± 0.08 pg/mL) increased between early to late fasting suggesting that there is an increased potential for TH‐mediated cellular effects. Conversely, total T3 decreased (63 ± 5 to 50 ± 4 ng/mL) suggesting that DI2 or DI3 may be contributing to the changes in TH metabolism. mRNA expressions of DI2 and THrβ‐1 decreased 87% ± 7 and 93% ± 2, respectively, between early to late fasting suggesting that there is a down‐regulation in cellular TH potential during fasting duration consistent with the effects of fasting in other mammals. When compared to the opposite effects observed in fasting pups, we conclude that elephant seals have evolved age‐dependent changes in fasting‐induced TH dynamics that may reflect differences in TH‐associated metabolic mechanisms.Grant Funding Source: Supported by NIH/NHLBI 442606‐RO‐29013

Two patients with atypical low triiodothyronine syndrome: primary deiodinase abnormalities?

SummaryLow triiodothyronine (T3) concentrations in the presence of normal thyroxine (T4) and TSH levels, referred to as the low T3 syndrome (LT3S), are common. LT3S may be caused by starvation, various non-thyroidal illnesses (NTIs) and some medications. Reverse T3 (rT3) concentrations are elevated in the more severely ill, and they characteristically fail to respond to exogenous levothyroxine (l-T4) therapy. The biochemical abnormalities have been explained on the basis of altered peripheral deiodinase activities. Herein, we report on two patients with hypothyroid symptoms who on testing were found to have LT3S. They were atypical clinically in not having LT3S due to any of the usual causes, had no increased rT3 concentrations, and had a normal negative TSH feedback response to l-T4. One (patient 1) had previously been diagnosed with Hashimoto's autoimmune primary hypothyroidism and was on l-T4 therapy. Both had T4 concentrations in the reference range. TSH levels were elevated in patient 1 and in the reference range in patient 2. Starting or increasing l-T4 doses resulted in no clinical improvement and no increase in T3 levels in spite of a marked increase in T4 levels. It is suggested that in the absence of the usual causes, lack of elevated rT3 levels, response to treatment and intact negative TSH feedback these two patients differ from the usual secondary causes of decreases in deiodinase activity. It is speculated that they may represent primary alterations in deiodinase enzymes possibly due to genetic variations in the deiodinase-encoding genes.Learning points LT3S is commonly found secondary to starvation, NTIs and use of some medications.Low T3 levels are the result of alterations in the activity of deiodinase enzymes.LT3S without the usual causes may represent a primary disturbance in deiodinase activity.

Unusual Case of Hypothyroidism in an Infant With Hepatic Hemangioma

Unusual Case of Hypothyroidism in an Infant With Hepatic Hemangioma

Presumptive nonthyroidal illness syndrome in critically ill foals

Hypothalamic-pituitary-thyroid (HPT) axis dysfunction is associated with morbidity and mortality in critically ill people. To date, investigations of HPT axis in critically ill foals are limited. To document the occurrence of low thyroid hormone concentrations (presumptive nonthyroidal illness syndrome; NTIS) in critically ill newborn foals and investigate whether NTIS is associated with severity of disease and outcome. NTIS occurs frequently in foals with sepsis and is associated with sepsis score and outcome. Reverse T3 (rT3) concentrations will be increased in septic foals and highest in nonsurvivors. Thyroid hormones (total and free thyroxine [TT4 and fT4], total and free tri-iodothyronine [TT3 and fT3], reverse T3 [rT3]) were prospectively measured in healthy, sick nonseptic and septic foals. Clinical and laboratory information was retrieved from the medical records. Hormones were measured by validated radioimmunoassays. Concentrations of all thyroid hormones except rT3 (P = 0.69) were decreased in septic and sick nonseptic foals (P < 0.01). Reductions in hormone concentrations were associated with an increased sepsis score (P < 0.01). Nonsurviving septic foals had lower TT4, fT4, TT3 and fT3 concentrations than surviving septic foals (P < 0.01). rT3 concentrations were higher in nonsurviving septic prematurefoals than surviving septic premature foals (P < 0.05). NTIS (euthyroid sick syndrome) is frequently observed in critically ill and premature foals, and associated with severity of disease and mortality. More research is needed to better understand the mechanism of this finding and determine whether manipulation of the HPT axis or thyroid replacement therapy could be beneficial.

Influence of Isoflurane General Anesthesia or Anesthesia and Surgery on Thyroid Function Tests in Dogs

Anesthesia and surgery affect thyroid function tests in humans but have not been studied in dogs. Anesthesia and anesthesia with surgery will affect thyroid function tests in dogs. Fifteen euthyroid dogs. Prospective, controlled, interventional study. Dogs were assigned to one of 3 groups: control, general anesthesia, and general anesthesia plus abdominal exploratory surgery. Dogs in the anesthesia and surgery groups were premedicated with acepromazine and morphine, induced with propofol, and maintained on isoflurane. Samples for measurement of serum thyroxine (T4), free T4 (fT4) by equilibrium dialysis, triiodothyronine (T3), reverse T3 (rT3), and thyroid-stimulating hormone concentrations were collected from each dog immediately before premedication, at multiple times during anesthesia, surgery, 4, 8, 12, 24, 36, and 48 hours after anesthesia, once daily for an additional 5 days, and once 14 days after anesthesia. Sampling was performed at identical times in the control group. Serum T4 decreased significantly from baseline in the surgery and anesthesia groups compared with the control group at 0.33 (P= 0.043) and 1 hour (P= 0.018), and 2 (P= 0.031) and 4 hours (P= 0.037), respectively, then increased significantly in the surgery group compared with the control group at 24 hours (P= 0.005). Serum T3 decreased significantly from baseline in the anesthesia group compared with the control group at 1 hour (P= 0.034). Serum rT3 increased significantly from baseline in the surgery group compared with the control and anesthesia groups at 8 (P= 0.026) and 24 hours (P= 0.0001) and anesthesia group at 8, 12, 24, and 36 hours (P= 0.004, P= 0.016, P= 0.004, and P= 0.014, respectively). Serum fT4 increased significantly from baseline in the surgery group compared to the control at 24 hours (P= 0.006) and at day 7 (P= 0.037) and anesthesia group at 48 hours (P= 0.023). Surgery and anesthesia have a significant effect on thyroid function tests in dogs.

Effect of Long-Term Calorie Restriction with Adequate Protein and Micronutrients on Thyroid Hormones

Caloric restriction (CR) retards aging in mammals. It has been hypothesized that a reduction in T(3) hormone may increase life span by conserving energy and reducing free-radical production. The objective of the study was to assess the relationship between long-term CR with adequate protein and micronutrient intake on thyroid function in healthy lean weight-stable adult men and women. In this study, serum thyroid hormones were evaluated in 28 men and women (mean age, 52 +/- 12 yr) consuming a CR diet for 3-15 yr (6 +/- 3 yr), 28 age- and sex-matched sedentary (WD), and 28 body fat-matched exercising (EX) subjects who were eating Western diets. Serum total and free T(4), total and free T(3), reverse T(3), and TSH concentrations were the main outcome measures. Energy intake was lower in the CR group (1779 +/- 355 kcal/d) than the WD (2433 +/- 502 kcal/d) and EX (2811 +/- 711 kcal/d) groups (P < 0.001). Serum T(3) concentration was lower in the CR group than the WD and EX groups (73.6 +/- 22 vs. 91.0 +/- 13 vs. 94.3 +/- 17 ng/dl, respectively) (P < or = 0.001), whereas serum total and free T(4), reverse T(3), and TSH concentrations were similar among groups. Long-term CR with adequate protein and micronutrient intake in lean and weight-stable healthy humans is associated with a sustained reduction in serum T(3) concentration, similar to that found in CR rodents and monkeys. This effect is likely due to CR itself, rather than to a decrease in body fat mass, and could be involved in slowing the rate of aging.

Depression and thyroid axis function in coronary artery disease: Impact of cardiac impairment and gender

Increased rates of depression are reported in coronary artery disease (CAD). In heart disease, depression increases disability, reduces quality of life, and increases mortality. The study was undertaken to examine the relationship between depression and thyroid axis function in patients with CAD. In all, 73 patients with CAD, consecutively admitted to a cardiac rehabilitation hospital, were assessed for depression using the Hospital Anxiety and Depression scale (HADS). Blood was drawn for assessment of thyroid axis hormones and the N-amino terminal fragment of the pro-B-type natriuretic peptide (NT-pro BNP). The patients with CAD with depressive symptoms had a higher prevalence of cardiac failure (p = 0.04), higher NT-pro BNP concentrations (p = 0.02), and lower free triiodothyronine (T3) concentrations (p = 0.04) than patients with CAD but without depressive symptoms. They also showed a strong trend (p = 0.058) toward a higher incidence of the low T3 syndrome. Higher NT-pro BNP concentrations were related to lower total T3 concentrations (r = -0.294, p = 0.011) and to higher reverse T3 concentrations (r = 0.353, p = 0.002). In men, higher scores of depression were related to lower total T3 concentration (r = -0.289, p = 0.034) and to higher NT-pro BNP concentration (r = 0.380, p = 0.005). These findings suggest that symptoms of depression in patients with CAD are associated with changes in thyroid axis function and with cardiac impairment, especially in men.

Effect of Se on selenoprotein activity and thyroid hormone metabolism in beef and dairy cows and calves.

Although Se is essential for antioxidant and thyroid hormone function, factors influencing its requirement are not well understood. A survey and two experiments were conducted to determine the influence of cattle breed and age on selenoprotein activity and the effect of maternal Se supplementation on cow and calf selenoprotein activity and neonatal thyroid hormone production. In our survey, four cowherds of different ages representing three breeds were bled to determine the influence of breed and age on erythrocyte glutathione peroxidase activity (RBC GPX-1). All females were nonlactating, pregnant, and consumed total mixed diets (Holstein) or grazed pasture (Angus and Hereford). In our survey of beef breeds, yearlings had greater average RBC GPX-1 activity than mature cows. In Exp. 1, neonatal Holstein heifers (n = 8) were bled daily from 0 to 6 d of age to determine thyroid hormone profile. An injection of Se and vitamin E (BO-SE) was given after the initial bleeding. Thyroxine (T4) and triiodothyronine (T3) concentrations were greatest on d 0 and decreased (P < 0.05) continuously until d 5 postpartum (156.13 to 65.88 and 6.69 to 1.95 nmol/L, d 0 to 5 for T4 and T3, respectively). Reverse T3 concentrations were 3.1 nmol/L on d 0 and decreased (P < 0.05) to 0.52 nmol/ L by d 5. In Exp. 2, multiparous Hereford cows were drenched weekly with either a placebo containing 10 mL of double-deionized H2O (n = 14) or 20 mg of Se as sodium selenite (n = 13). After 2 mo of treatment, Se-drenched cows had greater (P < 0.01) plasma concentrations than control cows (84.92 vs. 67.08 ng/mL), and at parturition, they had plasma Se concentrations twofold greater than (P < 0.05) control cows (95.51 vs. 47.14 ng Se/mL). After 4 mo, cows receiving Se had greater (P < 0.05) RBC GPX-1 activity than controls; this trend continued until parturition. Colostrum Se concentration was twofold greater (P < 0.05) in Se-drenched cows than control cows (169.97 vs. 87.00 ng/mL). Calves born to cows drenched with Se had greater (P < 0.05) plasma Se concentration, RBC GPX-1, and plasma glutathione peroxidase activity on d 0 compared with calves born to control cows. By d 7, no differences in plasma glutathione peroxidase activity in calves were observed. Maternal Se supplementation did not influence calf thyroid hormone concentrations. Selenium provided by salt and forages is not adequate for cattle in Se-deficient states.

Effects of propylthiouracil and bromocryptine on serum concentrations of thyrotrophin and thyroid hormones in normal female horses.

There exists a need for better diagnostic tests to characterise thyroid disease in horses. Currently available diagnostic tests fail to differentiate between thyroid gland disorders and thyroid abnormalities resulting from pituitary or hypothalamic problems. To evaluate the effects of treatment with propylthiouracil (PTU) and bromocryptine (BROM) on serum concentrations of triiodothyronine (T3), thyroxine (T4), reverse T3 (rT3) and equine thyroid-stimulating hormone (e-TSH, thyrotrophin) in mature horses. Healthy mature horses were treated using either PTU or BROM for 28 days. The effect of treatment on the thyroid axis was assessed by measuring T3, T4, rT3 and e-TSH before and at +14 and +28 days. The effect of PTU and BROM on the response of T3, T4, rT3 and e-TSH to thyrotrophin-release hormone (TRH) administration was also assessed before and at +14 and +28 days of treatment. Treatment with PTU led to a significant reduction in serum concentrations of T3, T4 and rT3 on Day 28 and increase of e-TSH on Day 28 (P < 0.05). Treatment with BROM did not cause any measurable effect on serum concentrations of T3, T4, rT3 or e-TSH. The percentage increment by which serum concentration of T4, T3 and e-TSH increased following stimulation with TRH was decreased by treatment with PTU for 28 days (P < 0.05) but were not affected by treatment with BROM for 28 days. These results suggest that 1) treatment with PTU may be used in horses as a model of primary hypothyroidism; 2) the use of BROM as a model of secondary hypothyroidism in horses is not supported; and 3) e-TSH assay deserves further investigation for the clinical diagnosis of thyroid axis dysfunction in horses. Propylthiouracil effectively causes primary hypothyroidism. There is substantial variability between horses with respect to their sensitivity to this substance when administered orally. Further studies pertaining to the characterisation of equine thyroid disorders are warranted and the use of both PTU for the experimental induction of primary hypothyroidism and e-TSH for the diagnostic characterisation of thyroid disorders in horses should be considered.

Nonthyroidal illness syndrome in off-pump coronary artery bypass grafting

BackgroundCardiopulmonary bypass (CPB) is an established cause of nonthyroidal illness syndrome (NTIS). Off-pump coronary artery bypass (OPCAB) has been reported to be less invasive than coronary artery bypass grafting (CABG) with CPB. We prospectively evaluated thyroid metabolism in OPCAB patients. MethodsWe analyzed free thyroid hormones (FT3 and FT4), thyroid-stimulating hormone (TSH), and reverse T3 (rT3) in 20 consecutive patients undergoing CABG surgery. Nine patients underwent CABG with CPB, and 11 underwent OPCAB. Blood samples were taken on admission, on the day of surgery (7:30 am), after sternotomy, at the end of the operation, and at 2, 6, 12, 24, 36, 48, 72, 96, 120, and 144 hours postoperatively. The concentrations of FT3, FT4, and TSH were determined on each sample. Reverse T3 concentration was measured in 10 patients up to 48 hours and at 144 hours postoperatively. ResultsBaseline, operative, and postoperative variables were similar in the two groups. FT3 concentration dropped significantly (p < 0.0001), reaching its lowest value 12 hours postoperatively. There were no significant differences between CPB and OPCAB patients. FT4 varied significantly in both groups (p < 0.0001), but remained in the normal range. TSH variation was not significant. rT3 concentration rose significantly (p = 0.0002) in both groups, peaking 24 hours after surgery. ConclusionsOPCAB induces a NTIS similar to that observed after CPB, probably due to the inhibition of T4 conversion to T3. This finding suggests that NTIS is a nonspecific response to stress. CPB should not be considered as the sole trigger of NTIS in cardiac surgical patients.

Effects of low mercury vapour exposure on the thyroid function in chloralkali workers.

Forty-seven chloralkali workers exposed to mercury vapour for an average of 13.3 years were compared with 47 referents matched for age in a cross-sectional study of thyroid function. The mean urinary mercury concentration in the exposed workers was low compared with other studies of chloralkali workers: 5.9 nmol mmol-1 creatinine (range 1.1-16.8) vs 1.3 nmol mmol-1 creatinine (range 0.2-5.0) in the reference group. The median serum concentration of reverse triiodothyronine (rT3) was statistically significantly higher in the exposed subjects compared with the referents (268 pmol l (-1) and range 161-422 vs 240 pmol l(-1) and range 129-352; P = 0.009). The difference between the exposed subjects and the referents was most pronounced in the highest exposed sub-groups. The free thyroxine (T4)/free T3 ratio was also higher in the highest exposed subgroups compared with the referents. The median serum concentration of tumour necrosis factor alpha (TNF-alpha) was lower in the exposed subjects (7.3 pg ml(-1) and range 4.4-69.7 vs 8.0 pg ml(-1) and range 6.0-34.6; P = 0.004). Exposed subjects with the lowest urinary iodine (<67.8 nmol mmol(-1) Cr) had higher serum concentrations of reverse T 3 and a higher free T4/free T3 ratio than the other subjects, suggesting that a low concentration of iodine in urine may be a risk factor for increased serum concentrations of reverse T3 and the free T4/free T3 ratio in subjects exposed occupationally to mercury vapour. The study could indicate a slight effect of low mercury vapour exposure on the function of the enzyme type I iodothyronine deiodinase, possibly modified by comparatively low urinary iodine concentrations.

Use of propranolol and potassium iodate in the presurgical management of hyperthyroid cats.

A prospective study was carried out using a combination of propranolol and potassium iodate to assess whether there were beneficial effects in preparing hyperthyroid cats for surgical thyroidectomy. Group A (n = 11) received propranolol from days 1 to 10, followed by propranolol and potassium iodate from days 11 to 20; group B (n = 10) received the reverse regimen. Blood samples were taken daily for subsequent determination of serum total L-thyroxine (TT4), L-triiodothyronine (TT3) and reverse T3 (rT3) concentrations. The signs of hyperthyroidism improved in all cats over the treatment period. At surgery, 36 per cent of the cats in group A had reference range serum TT4 concentrations, while 89 per cent with initially elevated TT3 concentrations had reference range concentrations. In group B, 10 per cent of the cats had reference range TT4 concentrations, while 75 per cent with initially elevated TT3 concentrations had reference range concentrations. The drug regimen used in group A was better tolerated and more effective and offers an alternative before thyroidectomy in cats that cannot tolerate carbimazole.

Role of cytokines in the pathogenesis of the euthyroid sick syndrome.

Nonthyroidal illness (NTI) is associated with complex changes in thyroid function tests and thyroid regulation known as the euthyroid sick syndrome (ESS) (1). The most common abnormality is a reduction in serum total triiodothyronine (TT3) and, to a lesser extent, free T3 (FT3) concentrations (2). Kinetic studies showed that the daily production rate (PR) of T3 is decreased, while its clearance is unchanged in NTI (3). The reduction in serum TT3 concentration is usually accompanied by an increase in serum reverse T3 (rT3) concentration (1), although the latter is normal in patients with chronic renal failure (4), AIDS (5), or traumatic brain injury (6). PR of rT3 is unchanged, but its clearance is reduced (3). These changes in serum TT3 and rT3 concentrations are related to inhibition of the activity of type I 5-deiodinase (5-DI), the enzyme catalyzing deiodination of thyroxine (T4) to T3 and of rT3 to 3,3 -diiodothyronine (7). Serum thyrotropin (TSH) concentration is usually normal, although suppressed values may be found in a minority of patients (1). In addition, a decrease in the nocturnal surge of TSH has been consistently reported in patients with NTI (8–12). Abnormalities of TSH glycosylation causing its decreased biological activity were also described (13). The decrease in serum TSH secretion is in some instances related to the use of dopamine and glucocorticoids in critically ill patients (14). The pathogenesis of changes in serum thyroid hormone and TSH concentrations leading to ESS is not completely understood. Reduced T3 generation in peripheral tissue may be related not only to a decreased 5-DI activity, but also to decreased T4 transport into tissues (15). Substances, such as 3-carboxy-4-methyl-5propyl-2-furanpropanoic acid (CMPF) and indoxylsulfate, which are increased in chronic renal failure, and bilirubin and free fatty acids (FFA), which are increased in other NTI, were reported to decrease T4 uptake in rat liver tissue (16, 17). Interestingly, CMPF and indoxyl-sulfate did not affect TSH secretion in cultured rat anterior pituitary cells (18). Recently, particular attention was focused on the role of cytokines in the pathogenesis of ESS. Cytokines are multifunctional molecules with different biological effects and target cells, which can exert autocrine (on the same cells that secrete them) and paracrine (on adjacent cells), but also endocrine (on distant cells) actions (19). They are usually produced in response to inflammation, infections and cellular injury, and their physiological role remains to be clarified (19). In general, cytokines act through binding to specific cellsurface receptors that were demonstrated also in thyrocytes (20, 21). In addition, thyrocytes synthesize and release cytokines, which might be involved in autocrine or paracrine regulation of thyroid function (22–32). The importance of cytokines in thyroid pathophysiology was recently underscored (Fig. 1). They participate in the pathogenesis of thyroid autoimmune disease by contributing to the growth and differentiation of B and T cells, by inducing expression of HLA class II antigens and adhesion molecules, by recruiting and activating immune cells and by modulating the course of the disease (33). Interleukin-6 (IL-6) and possibly other cytokines are useful markers of thyroid-destructive processes (34). Cytokines have a role in the pathogenesis of Graves’ ophthalmopathy, since they induce orbital fibroblast proliferation and glycosaminoglycan production, and expression of HLA class II antigens, adhesion molecules and heat shock proteins in orbital fibroblasts (35). Numerous studies in vitro and in vivo (both in animals and humans) were carried out in recent years on the effects of cytokines on thyroid function. Since the number of published papers on this issue is very large, in this review we analyzed the most crucial studies to discuss the role of cytokines in the pathogenesis of ESS.