Different diets are used for weight loss. A Paleolithic-type diet (PD) has beneficial metabolic effects, but two of the largest iodine sources, table salt and dairy products, are excluded. The objectives of this study were to compare 24-h urinary iodine concentration (24-UIC) in subjects on PD with 24-UIC in subjects on a diet according to the Nordic Nutrition Recommendations (NNR) and to study if PD results in a higher risk of developing iodine deficiency (ID), than NNR diet.

A 2-year prospective randomized trial in a tertiary referral center where healthy postmenopausal overweight or obese women were randomized to either PD (n=35) or NNR diet (n=35). Dietary iodine intake, 24-UIC, 24-h urinary iodine excretion (24-UIE), free thyroxin (FT4), free triiodothyronine (FT3) and thyrotropin (TSH) were measured at baseline, 6 and 24 months. Completeness of urine sampling was monitored by para-aminobenzoic acid and salt intake by urinary sodium.

At baseline, median 24-UIC (71.0 μg/l) and 24-UIE (134.0 μg/d) were similar in the PD and NNR groups. After 6 months, 24-UIC had decreased to 36.0 μg/l (P=0.001) and 24-UIE to 77.0 μg/d (P=0.001) in the PD group; in the NNR group, levels were unaltered. FT4, TSH and FT3 were similar in both groups, except for FT3 at 6 months being lower in PD than in NNR group.

A PD results in a higher risk of developing ID, than a diet according to the NNR. Therefore, we suggest iodine supplementation should be considered when on a PD.

Background: Low vitamin D status is associated with autoimmune thyroid disease. Oral vitamin D supplementation was found to reduce titers of thyroid antibodies in levothyroxine-treated women with postpartum thyroiditis and low vitamin D status. Methods: The study included 34 women with Hashimoto's thyroiditis and normal vitamin D status (serum 25-hydroxyvitamin D levels above 30 ng/mL) who had been treated for at least 6 months with levothyroxine. On the basis of patient preference, women were divided into 2 groups, receiving (n=18) or not receiving (n=16) oral vitamin D preparations (2000 IU daily). Serum levels of thyrotropin, free thyroxine, free triiodothyronine and 25-hydroxyvitamin D, as well as titers of thyroid peroxidase and thyroglobulin antibodies were measured at the beginning of the study and 6 months later. Results: There were no significant differences in baseline values between both study groups. 25-hydroxyvitamin D levels inversely correlated with titers of thyroid antibodies. No changes in hypothalamic-pituitary-thyroid axis activity and thyroid antibody titers were observed in vitamin-naïve patients. Vitamin D increased serum levels of 25-hydroxyvitamin D, as well as reduced titers of thyroid antibodies. This effect was more pronounced for thyroid peroxidase than for thyroglobulin antibodies and correlated with their baseline titers. Conclusions: Vitamin D preparations may reduce thyroid autoimmunity in levothyroxine-treated women with Hashimoto's thyroiditis and normal vitamin D status.

Low triiodothyronine (T3) state is associated with poor prognosis in critical acute and prolonged illness. However, the information on thyroid dysfunction and cancer is limited. The aim of our study was to evaluate the prognostic value of low T3 syndrome in chronic lymphocytic leukemia (CLL). Two hundred and fifty-eight patients with detailed thyroid hormone profile at CLL diagnosis were enrolled. Low T3 syndrome was defined by low free T3 (FT3) level accompanied by normal-to-low free tetraiodothyronine (FT4) and thyroid-stimulating hormone (TSH) levels. A propensity score-matched method was performed to balance the baseline characteristics. Multivariate Cox regression analyses screened the independent prognostic factors related to time-to-first-treatment (TTFT) and cancer-specific survival (CSS). Area under the curve (AUC) assessed the predictive accuracy of CLL-International Prognostic Index (IPI) together with low T3 syndrome. The results showed that 37 (14.34%) patients had low T3 syndrome, which was significantly associated with unfavorable TTFT and CSS in the propensity-matched cohort, and it was an independent prognostic indicator for both TTFT and CSS. Serum FT3 level was positively related to protein metabolism and anemia, and inversely related to inflammatory state. Patients with only low FT3 demonstrated better survival than those with synchronously low FT3 and FT4, while those with synchronously low FT3, FT4 and TSH had the worst clinical outcome. Low T3 syndrome together with CLL-IPI had larger AUCs compared with CLL-IPI alone in TTFT and CSS prediction. In conclusion, low T3 syndrome may be a good candidate for predicting prognosis in future clinical practice of CLL.

OBJECTIVE

Zinc (Zn) is an essential element involved in many basic biochemical reactions in thyroid. The aims of present study is to evaluate the Zn status in biological samples and thyroid hormones levels in 60 goitrous male (GMPs) and 72 female patients (GFPs), before and after 6 months treatment with Zn supplementation and compared with non-goitrous subjects of both genders (M=106, F=120) of age range 16-30 years.

METHODS

The biological samples were analyzed for Zn concentration using flame atomic absorption spectrophotometer, following their microwave assisted acid digestion. Quality control for the methodology was established with certified samples and with those obtained by conventional wet acid digestion method on the same CRMs and real samples.

RESULTS

The results showed that the significantly lower mean values of Zn in serum, while high level urine samples of GMPs and GFPs were observed as compared to control subjects (p<0.005 and 0.007) respectively. The mean values of free triiodothyronine and thyroxin were found to be lower in goitrous patients of both genders than in the age matched healthy control (p<0.006 and 0.002) respectively, in contrast high mean values of thyroid stimulating hormone were detected in GMPs and GFPs (p<0.009).

CONCLUSIONS

It was observed that Zn status and serum thyroid hormone levels were improved in goitrous patients after six months treatment with Zn supplementation.

BACKGROUND

A relationship between exposure to sexual violence and thyroid hormone alterations has been observed among women with posttraumatic stress disorder (PTSD). Women with borderline personality disorder (BPD) report a high estimate of childhood trauma.

OBJECTIVE

The aim of the present study was to assess relationships between thyroid hormone measures and exposure to violence in childhood in women with BPD.

METHODS

A total of 92 clinically euthyroid women with BPD (53% with comorbid PTSD) diagnosis and at least two prior suicide attempts were assessed with the Karolinska Interpersonal Violence Scales (KIVS). The KIVS contains four subscales with concrete examples of exposure to violence and expressed violent behavior in childhood (aged 6-14 years) and during adult life (15 years or older). Baseline thyroid function was evaluated by measuring plasma free and bound triiodothyronine (FT3 and T3), thyroxine (FT4 and T4), and thyroid-stimulating hormone (TSH) with immunoassays. The FT3/FT4 ratio was used to estimate peripheral deiodination. Plasma cortisol was also assessed.

RESULTS

Sixty-seven percent of patients reported medium high or high level of exposure to interpersonal violence as a child. The FT3/FT4 ratio showed a significant negative correlation with exposure to violence as a child. Patients with PTSD had significantly higher plasma cortisol levels. An ad hoc analysis revealed that the correlation between KIVS exposure to interpersonal violence as a child and FT3/FT4 ratio was significant only in patients with comorbid PTSD. Altered thyroid activity, especially FT3/FT4, levels was associated with exposure to violence in childhood in women with BPD.

CONCLUSIONS

Severe childhood trauma-related stress may promote lasting altered thyroid levels and/or contribute to the development of psychopathology associated with BPD traits or PTSD.

To establish their role in monitoring patients receiving thyroxine replacement biochemical tests of thyroid function were performed in 148 hypothyroid patients studied prospectively. Measurements of serum concentrations of total thyroxine, analogue free thyroxine, total triiodothyronine, analogue free triiodothyronine, and thyroid stimulating hormone, made with a sensitive immunoradiometric assay, did not, except in patients with gross abnormalities, distinguish euthyroid patients from those who were receiving inadequate or excessive replacement. These measurements are therefore of little, if any, value in monitoring patients receiving thyroxine replacement. To stop doing thyroid function tests in these cases would result in considerable savings nationally in the cost of reagents in laboratories using commercial kits.

OBJECTIVE

To study whether the suppression of the thyrotropin (thyroid-stimulating hormone, TSH) response to thyrotropin-releasing hormone (TRH) correlates with severity of illness and death in patients with nonthyroidal critical illness.

METHODS

Prospective study.

METHODS

Intensive care unit (ICU) of a university hospital.

METHODS

Forty-one critically ill patients without thyroid disease with multiple organ failure who were admitted to the ICU.

RESULTS

The TSH response to TRH was tested within 24 hrs of ICU admission. Blood samples were obtained just before, and at 15, 30, 60, 90, and 120 mins after 500-micrograms injection of synthetic TRH. Triiodothyronine, free-triiodothyronine, thyroxine, free-thyroxine and TSH concentrations were measured in the samples obtained just before TRH injection. Acute Physiology and Chronic Health Evaluation (APACHE II) scores and Sepsis scores were calculated based on the data obtained within 24 hrs of ICU admission. Individual variables were compared between survivors and nonsurvivors. The APACHE II scores and Sepsis scores of nonsurvivors were significantly higher than those scores of survivors. The overall occurrence of suppressed TSH response to TRH was 88%. Peak TSH concentration of the TSH response was significantly lower in nonsurvivors than in survivors. Serial measurement of the TSH response showed that nonsurvivors experienced a decrease in peak TSH concentration from 1.55 +/- 0.78 to 0.55 +/- 0.30 microIU/mL; in survivors, it increased from 2.10 +/- 0.26 to 7.38 +/- 1.83 microIU/mL. Conversely, the basal TSH concentration did not change in either survivors or nonsurvivors. The "severity" of illness of nonsurvivors remained high; their mean APACHE II score varied from 20.0 +/- 1.9 to 22.1 +/- 1.3 and the mean Sepsis score varied from 20.0 +/- 4.3 to 25.4 +/- 4.0, while the same scores for survivors decreased significantly (p < .05): their APACHE II score decreased from 16.2 +/- 0.7 to 7.6 +/- 2.0 and the Sepsis score went from 14.0 +/- 1.9 to 6.0 +/- 1.6.

CONCLUSIONS

In critically ill patients with multiple organ failure, suppression of the TSH response to TRH frequently occurs and correlates with severity of illness and outcome. Our data indicate that measurement of the TSH response is helpful in evaluating the severity of illness and prognosis for critically ill patients.

OBJECTIVE

Type 2 deiodinase gene (DIO2) polymorphisms have been associated with changes in pituitary-thyroid axis homeostasis. The -258A/G (SNP rs12885300) polymorphism has been associated with increased enzymatic activity, but data are conflicting. To characterize the effects of -258A/G polymorphism on intrathyroidal thyroxine (T(4)) to triiodothyronine (T(3)) conversion and thyroid hormone (TH) secretion pattern, we studied the effects of acute, TRH-mediated, TSH stimulation of the thyroid gland.

METHODS

Retrospective analysis.

METHODS

The TH secretion in response to 500 μg i.v. TRH injection was studied in 45 healthy volunteers.

RESULTS

Twenty-six subjects (16 females and ten males, 32.8 ± 10.4 years) were homozygous for the ancestral (-258A/A) allele and 19 (11 females and eight males, 31.1 ± 10.9 years) were carriers of the (-258G/x) variant. While no differences in the peak TSH and T(3) levels were observed, carriers of the -258G/x allele showed a blunted rise in free T(4) (FT(4); P<0.01). The -258G/x92Thr/Thr haplotype, compared with the other groups, had lower TSH values at 60 min (P<0.03). No differences were observed between genotypes in baseline TH levels.

CONCLUSIONS

The -258G/x DIO2 polymorphism variant is associated with a decreased rate of acute TSH-stimulated FT(4) secretion with a normal T(3) release from the thyroid gland consistent with a shift in the reaction equilibrium toward the product. These data indicate that the -258G DIO2 polymorphism causes changes in the pattern of hormone secretion. These findings are a proof of concept that common polymorphisms in DIO2 can subtly affect the circulating levels of TH and might modulate the TH homeostasis.

Recombinant human growth hormone (GH) is routinely administered as daily subcutaneous injections to patients with GH deficiency (GHD). However, in the hypophysectomized rat, pulsatile and continuous infusion of GH has been shown to differ in terms of the magnitude of effect on longitudinal bone growth, serum insulin-like growth factor-I (IGF-I) concentrations, and hepatic metabolism. The aim of the present study was to compare the effects of daily injections and continuous infusion of GH in GHD adults on previously well-documented GH-dependent factors. Recombinant human GH (0.25 U/kg/wk) was administered to nine men with GHD for 14 days in two different ways, ie, as a daily subcutaneous injection at 8 PM and as a continuous subcutaneous infusion, with 1 month of washout between treatments. Blood samples and tests were performed in the morning after an overnight fast before the start of GH treatment (day 0) and on day 2 and day 14 of treatment. An oral glucose tolerance test (OGTT) was performed on day 0 and day 14. Daily injections and continuous infusion of GH exerted similar effects in terms of body weight and body composition. The two modes of administration resulted in similar daily urinary GH excretion and similar serum GH concentrations in the morning. GH binding protein (GHBP) concentrations did not change significantly during the various treatment periods. Serum IGF-I and IGF-I binding protein (IGFBP)-3 concentrations increased to a greater degree during continuous infusion of GH versus daily injections. Serum IGFBP-I concentrations decreased to a similar degree during the two modes of administration. Serum concentrations of free triiodothyronine and total triiodothyronine (T3) increased and free thyroxine (T4) decreased to a similar degree, independent of the mode of administration. However, total T4 concentrations were unchanged during both modes of treatment. Serum thyrotropin (TSH) concentrations decreased during continuous infusion, and there was a similar nonsignificant decrease during daily injections of GH. Fasting free fatty acid (FFA) levels increased during treatment with only daily injection of GH, but there was no significant effect from continuous infusion. Results of measurements of fasting concentrations of blood glucose and oral glucose tolerance (OGT) indicated a more impaired glucose tolerance after daily injections of GH versus continuous infusion. In conclusion, continuous infusion and daily injections of GH have similar effects on the variables described, but the magnitude of the effects differs.

1. We have investigated the relations between changes in plasma insulin and 3,5,3'-triiodothyronine (T3), and muscle growth and protein turnover in the rat in response to diets of varying protein concentrations. 2. Young rats were fed ad lib. on a control (180 g casein/kg) diet or low-protein diets containing 80, 45 and 0 g casein/kg in four separate experiments. Measurements were made of food intakes, muscle and body-weight growth rates, muscle protein turnover in vivo, plasma insulin, and plasma free and total T3. 3. The food intakes of the 80 and 45 g casein/kg diet groups were variable, with the 80 g casein/kg diet group consuming either the same or more than the controls, and the 45 g casein/kg diet group consuming less or more than the controls. Body-weight and skeletal-muscle growth rates varied with the protein but not energy intakes, which in turn reflected both dietary composition and the food intake, with the hyperphagic 80 g casein/kg diet group of rats growing almost normally and the 0 g casein/kg diet group losing body-weight and muscle mass. 4. Changes in rates of muscle growth were accompanied by parallel changes in rates of protein synthesis and degradation, as well as parallel changes in concentrations of plasma insulin and free T3, to the extent that all these variables were highly correlated with each other. 5. Partial correlation analysis was used to separate interactions between variables. This indicated that dietary energy had no identifiable influence on muscle growth. In contrast dietary protein appeared to stimulate muscle growth directly by increasing muscle RNA content and inhibiting proteolysis, as well as increasing insulin and free T3 levels. Insulin and free T3 stimulated each other as well as muscle protein turnover; insulin stimulating the RNA activity particularly at low insulin levels, free T3 stimulating the RNA content and both hormones stimulating proteolysis. 6. These apparent relations are shown to be consistent in the main part with previous studies of the mechanism of action of insulin and T3, but the possibility cannot be discounted that other anabolic hormones not measured in these studies are involved, particularly in the apparent direct influence of dietary protein on muscle.

BACKGROUND

Laboratory testing is an essential tool for diagnosis and management of thyroid diseases. However, the current status of standardization hampers the interchangeability of results. To improve this situation, the Working Group for Standardization of Thyroid Function Tests was established.

METHODS

Method comparisons were organized for measurement of human thyroid stimulating hormone (TSH), and free and total thyroid hormone in serum from apparently healthy donors. The aim was to assess the status of standardization and the quality of the performance of current routine assays. A second objective was to investigate the effect of mathematical recalibration of the results using their relationship to the overall mean (TSH) or the reference measurement procedure values (other thyroid hormones).

RESULTS

The need for standardization was shown to be highest for free thyroid hormone and total triiodothyronine measurements, while the majority of TSH and total thyroxine assays agreed within 10% of the reference. Most assays showed good performance. However, some could benefit from improved precision, consistency of calibration, or within- and between-run stability. Recalibration eliminated assay-specific bias. Thus, the residual spread was due to within-method effects. Not withstanding, sample-related effects remained.

CONCLUSIONS

These studies confirmed the feasibility of standardization based on method comparison with native sera, but highlighted the need to resolve issues, such as sample-related effects. In view of the fact that in this phase the project worked with samples from individuals with euthyroid status, the next method comparison shall place emphasis on challenging the performance of the assays with clinical samples and expanding the covered measurement range.

A pesticide factory in Cidade dos Meninos village, Duque de Caxias County, Rio de Janeiro, Brazil, ended its activity in 1961, leading to widespread contamination of the environment by several organochlorine pesticides. The aim of this study was to investigate the effects of chronic exposure to organochlorine pesticides on thyroid hormone levels in children residing in Cidade dos Meninos. In a population-based survey carried out between 2003 and 2004, serum concentration of 19 pesticides and levels of free thyroxine (T4), total triiodothyronine (T3) and thyroid-stimulating hormone (TSH) were determined in 193 children younger than 15 years old. Multivariate linear regression was conducted to examine thyroid hormone levels according to quintiles of organochlorine exposure, controlling for age, gender and serum lipid content. Free T4 and TSH levels were within reference values (0.7-1.8 ng/dl and 0.35-5.5 mU/l), whereas total T3 was above the reference range (80-180 ng/dl) in 28% of children. More than 60% of the children had detectable levels of most organochlorine pesticides. With the exception of heptachlor and methoxychlor, total T3 levels showed a significant increasing linear trend regardless of pesticide type to which children were exposed. Free T4 levels were positively and significantly associated only with exposure to p,p'-DDD, endosulfan 1, and dieldrin. No significant trend was found for TSH. Data showed that exposure of children to organochlorine pesticides produced a significant increase in serum total T3 concentrations. The clinical implications of such a total T3 elevation and subsequent development are uncertain and warrant the need for health monitoring of these children.

Caloric restriction (CR) decreases circulating triiodothyronine (T(3)) concentration. However, it is not known if this effect is due to body fat mass reductions or due to CR, per se. The purpose of this study was to test the hypothesis that plasma T(3) concentration decreases with CR-induced reductions in fat mass but not in response to similar decreases in fat mass that are induced by exercise. Sedentary, nonobese 50- to 60-year-old men and women with no clinical evidence of cardiovascular or metabolic disease and not taking thyroid medications were randomly assigned to 12 months of caloric restriction (n = 18) or exercise-induced weight loss (n = 17) or to a control group (n = 9). Body weight and composition and plasma concentrations of the thyroid hormones T(3), thyrotropin (TSH), thyroxine (T(4)), and free thyroxine (FT(4)) were measured at baseline and 12 months. Fat mass changed significantly in the CR (-6.3 +/- 1.0 kg) and exercise (-5.5 +/- 1.0 kg) groups but not in the control group (-0.6 +/- 1.4 kg). The changes were not significantly different between the CR and exercise groups. Plasma T(3) concentration decreased in the CR group (-9.8 +/- 2.0 ng/dL, p < 0.0001) but not in the exercise (-3.8 +/- 2.1 ng/dL, p = 0.07) or control (-1.3 +/- 2.8 ng/dL, p = 0.65) groups. TSH, T(4), and FT(4) did not change in any of the study groups. Twelve months of CR decreased circulating T(3) concentrations in middle-aged adults. This effect does not appear to be attributable to changes in body fat mass because a comparable decrease in T(3) concentration was not observed in response to an exercise-induced fat mass reduction.

This study was performed to ascertain whether a relationship exists between thyroid function and blood pressure in school-aged Chinese subjects without overt thyroid disease. A cross-sectional survey of 880 subjects (541 females and 339 males) aged 7-18 years in Bengbu, Anhui province was conducted. The investigation, which was based on a stratified random cluster sampling method, included a questionnaire and measurements of blood pressure, height, and body weight. Fasting blood samples were taken for measurements of thyroid-stimulating hormone (TSH), free 3,5,3'-triiodothyronine (FT(3)) and free thyroxine (FT(4)). Serum TSH and FT(3) were positively correlated with systolic and diastolic blood pressure Z scores (SBP-Z and DBP-Z) even after adjusting for body mass index (BMI) (P < 0.05) but no correlation was observed between FT(4) and SBP-Z or DBP-Z after comparable adjustments (P>> 0.05). SBP-Z and DBP-Z in subjects with subclinical hypothyroidism were significant higher than in euthyroid subjects (P < 0.05). Both SBP-Z and DBP-Z increased linearly with TSH concentration in boys after adjusting BMI (P < 0.05); however, a similar linear trend was not observed in girls. Our findings support the hypothesis that elevated TSH and FT(3) concentrations increase blood pressure in school-aged Chinese subjects without overt thyroid disease; this increase may be even more significant in boys.

During winter sleep the black bear has decreased levels of serum total and free thyroxine (T4) and triiodothyronine (T3) and a prolonged, delayed response of serum thyrotropin (TSH) (bioassay) to thyrotropin-releasing hormone (TRH). Four weeks after the end of winter sleep, levels of serum thyroid hormones increase, and TSH response to TRH is short and brisk. Serum T4 and T3 rise after TRH administration both during and after winter sleep; however, the maximum increment in serum T3 is greater during winter sleep when the TSH rise is also prolonged and exaggerated. These observations suggest that transient hypothyroidism of possible hypothalamic origin occurs in bears during winter sleep.

A biologically based dose-response model (BBDR) for the hypothalamic pituitary thyroid (HPT) axis was developed in the near-term pregnant mother and fetus. This model was calibrated to predict serum levels of iodide, total thyroxine (T4), free thyroxine (fT4), and total triiodothyronine (T3) in the mother and fetus for a range of dietary iodide intake. The model was extended to describe perchlorate, an environmental and food contaminant, that competes with the sodium iodide symporter protein for thyroidal uptake of iodide. Using this mode-of-action framework, simulations were performed to determine the daily ingestion rates of perchlorate that would be associated with hypothyroxinemia or onset of hypothyroidism for varying iodide intake. Model simulations suggested that a maternal iodide intake of 75 to 250 µg/day and an environmentally relevant exposure of perchlorate (~0.1 µg/kg/day) did not result in hypothyroxinemia or hypothyroidism. For a daily iodide-sufficient intake of 200 µg/day, the dose of perchlorate required to reduce maternal fT4 levels to a hypothyroxinemic state was estimated at 32.2 µg/kg/day. As iodide intake was lowered to 75 µg/day, the model simulated daily perchlorate dose required to cause hypothyroxinemia was reduced by eightfold. Similarly, the perchlorate intake rates associated with the onset of subclinical hypothyroidism ranged from 54.8 to 21.5 µg/kg/day for daily iodide intake of 250-75 µg/day. This BBDR-HPT axis model for pregnancy provides an example of a novel public health assessment tool that may be expanded to address other endocrine-active chemicals found in food and the environment.

Six of 50 (12%) patients with chronic hepatitis C who were treated with interferon developed thyroid disease or an autoimmune thyroid reaction while undergoing treatment. One patient developed silent thyroiditis, with an increase in serum triiodothyronine (T3), thyroxine (T4), free T3, free T4, and markedly suppressed thyroid-stimulating hormone (TSH) levels, accompanied by the appearance of both antithyroglobulin (TgAb) and antimicrosomal antibodies (McAb). One patient developed hypothyroidism in association with moderately elevated TSH levels and high titers of McAb. TSH, TgAb, and McAb levels returned to the initial values at least 4 months after the end of interferon treatment (9 months of follow up). Four patients whose TgAb and/or McAb levels were elevated during treatment with interferon had been diagnosed as having subclinical autoimmune thyroiditis; however, their thyroid function remained in the normal range. These results suggested that treatment with interferon can cause a transient autoimmune thyroid reaction and disease as a side effect.

It is well established that bone turnover increases and bone resorption exceeds bone formation in patients with hyperthyroidism. Recently, urinary pyridinoline and deoxypyridinoline have been employed as indicators of bone resorption. In this study, urinary pyridinoline and deoxypyridinoline levels in fourteen female patients with untreated hyperthyroidism were measured and compared with levels in 134 healthy females. Values of urinary pyridinoline and deoxypyridinoline were significantly higher than in age-matched controls. Moreover, values of serum free triiodothyronine correlated with urinary pyridinoline (r = 0.769, p < 0.01), and urinary deoxypyridinoline (r = 0.799, p < 0.001) in patients with hyperthyroidism.

OBJECTIVE

Operating far from its equilibrium resting point, the thyroid gland requires stimulation via feedback-controlled pituitary thyrotropin (TSH) secretion to maintain adequate hormone supply. We explored and defined variations in the expression of control mechanisms and physiological responses across the euthyroid reference range.

METHODS

We analyzed the relational equilibria between thyroid parameters defining thyroid production and thyroid conversion in a group of 271 thyroid-healthy subjects and 86 untreated patients with thyroid autoimmune disease.

RESULTS

In the euthyroid controls, the FT3-FT4 (free triiodothyronine-free thyroxine) ratio was strongly associated with the FT4-TSH ratio (tau = -0.22, p < 0.001, even after correcting for spurious correlation), linking T4 to T3 conversion with TSH-standardized T4 production. Using a homeostatic model, we estimated both global deiodinase activity and maximum thyroid capacity. Both parameters were nonlinearly and inversely associated, trending in opposite directions across the euthyroid reference range. Within the panel of controls, the subgroup with a relatively lower thyroid capacity (<2.5 pmol/s) displayed lower FT4 levels, but maintained FT3 at the same concentrations as patients with higher functional and anatomical capacity. The relationships were preserved when extended to the subclinical range in the diseased sample.

CONCLUSIONS

The euthyroid panel does not follow a homogeneous pattern to produce random variation among thyroid hormones and TSH, but forms a heterogeneous group that progressively displays distinctly different levels of homeostatic control across the euthyroid range. This suggests a concept of relational stability with implications for definition of euthyroidism and disease classification.

Changes in thyroid hormone metabolism in the low-3,5,3'-triiodothyronine (T3) syndrome cannot be fully explained in all conditions by a decrease in 5'-deiodinase activity. Recent observations showed that in rat hepatocytes iodothyronines are taken up by an active transport mechanism. To investigate whether regulation, i.e., inhibition of active transmembraneous transport for iodothyronines in humans may contribute to the generation of the low-T3 syndrome, tracer thyroxine (T4) and T3 kinetic studies were performed in 10 obese subjects before and after 7 days on a 240 kcal diet. Kinetics analyses were performed according to a three-pool model of distribution and metabolism for both T4 and T3. For T4 kinetics, during caloric deprivation serum total T4 and plasma pool did not change and production rate and metabolic clearance rate (MCR) were significantly lower. Despite a significantly higher serum free T4, the mass transfer rate to the rapidly equilibrating pool (REP) and the slowly equilibrating pool (SEP) diminished significantly, leading to smaller tissue pools. For T3 kinetics, both serum total T3, free T3, plasma pool, and production rate diminished significantly, while MCR remained unchanged. Mass transfer rates to the REP and the SEP were lowered by approximately 50%, leading to smaller tissue pools. These changes cannot be fully explained by a similar decrease of serum free T3 (only 25%), indicating a diminished transport efficiency for T3. In conclusion, during caloric restriction, transport of T4 and T3 into tissues is diminished, and this phenomenon is much more pronounced for T4 than for T3.(ABSTRACT TRUNCATED AT 250 WORDS)

OBJECTIVE

Elevated thyroid-stimulating hormone (TSH) concentrations in association with normal/slightly elevated free triiodothyronine (fT(3)) and/or free thyroxine (fT(4)) have been consistently found in obese children. To examine relationships between adiposity, insulin sensitivity, and TSH, fT(3) and fT(4).

METHODS

240 overweight/obese prepubertal children were studied. Fasting TSH, fT(3), fT(4), glucose, insulin, C-peptide, lipids, leptin and adiponectin were evaluated. Insulin sensitivity and resistance were estimated [quantitative insulin check index (QUICKI), insulin sensitivity index (ISI), and hepatic insulin resistance index]. Body fat was measured by dual-energy X-ray absorptiometry. The central obesity index was calculated as the ratio of fat tissue in the trunk region to fat tissue in the leg region.

RESULTS

The multiple regression analysis with age, gender and measures of fatness as covariates showed that QUICKI was the only significant negative predictor of TSH and central obesity index the strongest positive predictor of fT(3), in association with either age or hepatic insulin resistance index, and that the only positive determinant of fT(4) was hepatic insulin resistance index.

CONCLUSIONS

Reduced insulin sensitivity is associated with augmented TSH and fT(4), while progressive central fat accumulation is strictly related to a parallel increase in fT(3) levels, independently from total body fat. Further studies are needed to understand mechanisms linking thyroid function to insulin sensitivity and body composition in obese children.