Resting metabolic rate (RMR) was measured in 154 women and 48 men before the beginning of a weight reduction program. In both sexes there were significant univariate correlations between RMR and fat-free mass, body fat, weight, fat cell weight, and fat cell number (from total body water). Women also showed significant correlations between RMR and fat cell number (from total body potassium), free triiodothyronine index, and fasting and postglucose insulin levels. Multiple regression analysis showed that both fat-free mass and fat cell weight and number were significant predictors of RMR. The contribution of fat-free mass was three to five times greater per kg than that of body fat. There was no significant contribution of thyroid hormones or insulin to the prediction of RMR. Fat cell number and fat cell weight were significant predictors of RMR, whether determined from body water, body potassium, or a formula using both water and potassium. There was no significant difference in regression coefficients between men and women. Thus the difference in RMR between the sexes is probably caused by the higher proportion of fat-free mass in men. The effect of age was small and not statistically significant.

OBJECTIVE

We studied the clinical and hormonal profiles of patients with central hypothyroidism (CH), the adequacy of levothyroxine (L-T4) treatment and the influence of other pituitary hormone replacement therapies.

METHODS

We reviewed medical records of 108 adult patients with child-onset (CO; n=26) or adult-onset (AO; n=82) CH.

RESULTS

At diagnosis, the most frequently reported symptoms were fatigue and headaches in AO patients, and growth retardation in CO patients. Serum TSH was normal in a majority of CH patients, low in 8% and elevated in 8%. Serum free thyroxine (fT(4)) was usually reduced, but remained within the low normal range in 28% of the study population (mostly CO patients). Similarly, serum total T(4) (tT(4)), total triiodothyronine (tT(3)) and free T(3) (fT(3)) were found to be within the normal range in significant subsets of patients. Interestingly, the clinical and biochemical characteristics of CH patients with normal f/t T(4) levels were not different from those of the patients with low fT(4) values. The thyroid hormonal profile was not influenced by gender, etiology or by the number of hormone deficiencies. At last evaluation, the mean dose of L-T(4) was 1.6+/-0.5 microg/kg/day and was negatively correlated to current age (P<0.001) but positively correlated to the number of hormone deficiencies (P<0.05). Treatment suppressed TSH in 75% of the patients, induced normal fT(4) in 94%, but normal fT(3) in only 49% of them. Male GH-treated patients and estrogen-treated females needed a higher L-T(4) dose compared with non-treated patients.

CONCLUSIONS

fT(4) is clearly the best indicator of CH, but remains in the low normal range in a significant subset of patients, especially in those with CO disease. Adequacy of therapy is mostly reflected by the combination of upper normal fT(4) and low normal fT(3) levels. Pituitary hormone replacement therapy may require an adjustment of T(4) treatment, as female patients under estrogen treatment and male patients under GH treatment will need a higher T(4) dose in order to remain in the euthyroid range.

Thyrotoxicosis may be associated with a variety of abnormalities of liver function. The pathogenesis of hepatic dysfunction in thyrotoxicosis is unknown, but has been attributed to mitochondrial dysfunction. We studied the effect of altered thyroid function on the apoptotic index in rat liver. Extensive DNA fragmentation and significantly increased caspase-3 activity (P <.001) and caspase-9 activation (P <.005) were observed in hyperthyroid rat liver; cell death by apoptosis was confirmed. In hyperthyroid rat liver, 60% of mitochondria exhibited disruption of their outer membranes and a decrease in the number of cristae. These findings, along with significant translocation of cytochrome c and second mitochondria-derived activator of caspases to cytosol (P <.005), suggest activation of a mitochondrial-mediated pathway. However, no change in the expression levels of Bcl-2, Bax, and Bcl-x(L) were found in hyperthyroidism. For in vitro experiments, rat liver mitochondria were isolated and purified in sucrose density gradients and were treated with triiodothyronine (T3; 2-8 microM). T3 treatment resulted in an abrupt increase in mitochondrial permeability transition. Using a cell-free apoptosis system, the apoptogenic nature of proteins released from mitochondria was confirmed by observing changes in nuclear morphologic features and DNA fragmentation. Proteins released by 6 microM T3 contained significantly increased amounts of cytochrome c (P <.01) and induced apoptotic changes in 67% of nuclei. In conclusion, using in vivo and in vitro approaches, we provide evidence that excess T3 causes liver dysfunction by inducing apoptosis, as a result of activation of a mitochondria-dependent pathway. Thus, the results of this study provide an explanation for liver dysfunction associated with hyperthyroidism.

OBJECTIVE

To establish the role of percutaneous ethanol injection (PEI) treatment in benign thyroid lesions by evaluating: (1) the long-term efficacy and side effects of the treatment, (2) the factors predictive of efficacy of PEI, and (3) the cost effectiveness of the procedure.

METHODS

Fifty-eight recurrent cystic nodules, 95 autonomously functioning nodules (AFTN), and 17 hyperfunctioning nodules causing thyrotoxicosis (toxic nodules) were treated by PEI from 1990 to 1996 in our center. Ultrasound (US) and color flow doppler (CFD) examinations were carried out before and after each treatment. In patients with AFTN, serum thyrotropin (TSH), free triiodothyronine (FT3), free thyroxine (FT4), thyroid peroxidase antibody (TPOAb) levels were tested before and after PEI. All patients were independently reexamined by two external reviewers after a minimum follow-up of 5 years (median, 6.9 years).

RESULTS

The median number of treatments was 2.0 (range, 1.0-4.0) for cystic nodules, 4 (range, 2.0-6.0) for AFTN, and 5 (range, 3.0-7.0) for toxic nodules. At the 5-year evaluation cystic nodules showed a volume reduction greater than 75% versus baseline in 86.2% of cases and an improvement of local symptoms in 91.4% of cases. AFTN presented serum TSH within normal limits in 60.0% of patients. Toxic nodules showed a detectable serum TSH and normal FT3 and FT4 values in 35.3% of cases. Two cases of transient dysphonia were observed. In cystic lesions no significant correlation was found between the baseline and the final volume (r2 = 0.17) and no significant predictor of treatment efficacy was found. However, unilocularity was associated with a lower number of treatments than multilocularity (median, 2.0 vs. 3.0). Independent predictors of clinical efficacy in both AFTN and toxic nodules were a baseline volume less than 5.0 mL and a fluid component greater than 30% (odds ratio [OR] = 6.1 and 3.3, respectively).

CONCLUSIONS

Most recurrent cystic lesions of the thyroid can be cured by PEI, which should become the first line of treatment. The majority of AFTN and toxic nodules with volume less than 5.0 mL presented a marked volume decrease and normal serum TSH levels when treated by PEI, which seems a valid alternative to clinical follow-up alone in patients refusing 131I. PEI is not indicated in large or toxic nodules, for which 131I is the treatment of choice.

BACKGROUND

There are many studies concerning thyroid function in obesity, and some of them describe higher TSH levels in obese subjects. Few studies evaluated long-term changes in thyroid function caused by weight loss after bariatric surgery. Our aims were to evaluate the prevalence of subclinical hypothyroidism (SH) in a morbidly obese population and to analyze the effect of weight loss induced by Roux-en-Y gastric bypass (RYGBP) on TSH and thyroid hormone (TH) levels.

METHODS

TSH, free thyroxine (fT4) and total triiodothyronine (T3) levels were analyzed before and 12 months after RYGBP in patients with grade III or grade II obesity with co-morbidities. Subjects taking TH and/or with positive antithyroid antibodies and/or with overt hypothyroidism were excluded.

RESULTS

72 subjects (62F/10M), with mean age 39.6+/-9.8 years and mean BMI 53.0+/-10.4 kg/m2 were studied. The prevalence of SH before RYGBP was 25% (n=18). There was a significant post-surgical decrease in BMI in the whole population, as well as in SH patients. In the SH group and normal TSH group, there was a decrease in TSH and T3, but not in fT4. TSH was not correlated with initial BMI or percent change in BMI. TSH concentrations reached normal values in all SH patients after RYGBP.

CONCLUSIONS

Our data confirm that severe obesity is associated with increased TSH. The decrease in TSH was independent of BMI, but occurred in all SH patients. A putative effect of weight reduction on the improvement of SH in all patients may be an additional benefit of bariatric surgery.

BACKGROUND

Celiac disease (CD) may be associated with other immunologic disorders in adults and children. Previous studies linking CD and autoimmune thyroid disease in children have included very few patients with limited biochemical and immunologic screening tests. The aim of this multicenter study was to establish the prevalence of autoimmune thyroid involvement in a large series of pediatric patients with CD.

METHODS

Five hundred seventy-three consecutive pediatric patients were enrolled from clinics in Torino, Bologna, Foggia, Rome (two clinics), Naples, and Bari. Three hundred forty-three patients with CD were studied, 230 girls and 113 boys (median age, 8.5 years). Two hundred fifty-six of the patients with CD (median age, 9 years) had been following a gluten-free diet for 3 months to 16 years; 87 patients were untreated (median age, 6.2 years). The diagnosis of CD was made using the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) criteria. A control group of 230 subjects (median age, 8.3 years) was enrolled. Serum free triiodothyronine, free thyroxine, and thyroid-stimulating hormone (TSH), antithyroperoxidase, antithyroglobulin, anti-TSH receptor antibodies, and thyroid echographic pattern were considered.

RESULTS

Autoimmune thyroid disease was found in 90 of 343 (26.2%) patients with CD (62 on a gluten-free diet) and in 20 (10%) of the control subjects (P = 0.001). Fifty-four (15.7%) patients with CD and autoimmune markers had normal thyroid function (euthyroidism) as did 12 (6.0%) of the control subjects; hypothyroidism was observed in 28 (8.1%) patients with CD and in 7 (3.5%) of the control subjects. Hyperthyroidism was diagnosed in four patients with CD and in none of the control subjects with autoimmune markers. An abnormal echographic pattern was seen in 37 patients with CD (16.8%) and only in 1 (1.6%) of the control subjects (P = 0.002).

CONCLUSIONS

The high frequency of autoimmune thyroid disease found among patients with CD, even those on a gluten-free diet, may justify a thyroid status assessment at diagnosis and at follow-up evaluation of children with CD.

Thyroid status was examined in children from two villages in central China where the iodine concentrations in drinking water were 462.5 and 54 micrograms/l. Goitres were present in 65% (n = 120) and 15.4% (n = 51), respectively. All children in both groups were clinically euthyroid and neurologically normal. Growth measurements and intellectual performance were similar in the two groups. Children from the high-iodine village had a lower mean serum triiodothyronine and higher serum free thyroxine and serum thyroid-stimulating hormone concentrations than the children from the control village. 2 cases of overt hypothyroidism were detected in the high-iodine village.

Total and free serum concentrations of thyroxine and triiodothyronine were measured in 122 subjects with hypothyroidism who were clinically well while receiving conventional replacement treatment with thyroxine. In a third of patients concentrations of total and free thyroxine were raised, often considerably; nevertheless concentrations of total and free triiodothyronine were usually normal. Though significant correlations were obtained between total triiodothyronine concentrations and total thyroxine concentrations (p less than 0.001) and between the triiodothyronine concentrations and free thyroxine concentrations (p less than 0.001) the slope of the line of the regression equation describing these correlations was small, hence large increases in both total and free thyroxine concentrations were accompanied by only modest increases in total and free triiodothyronine concentrations. The presence of total or free thyroxine concentrations above normal in patients taking thyroxine therefore are not necessarily of clinical consequence. In the assessment of adequacy of replacement treatment with thyroxine the most logical combination of in vitro thyroid function test results may be a normal thyrotrophin concentration and normal free triiodothyronine concentration.

Fifteen patients receiving standard thyroxine replacement therapy (100-200 micrograms daily) for primary hypothyroidism and who had persistently raised free thyroxine concentrations in their serum were investigated to see whether the dose being given was too high. In addition to the usual thyroid hormone assays systolic time intervals (which indicate left ventricular contractility) were calculated as accurate reflectors of tissue thyroid activity. All patients showed the expected increased free and total thyroxine concentrations; but mean total and free concentrations of triiodothyronine were normal, while reverse triiodothyronine values were raised. Mean systolic time intervals were significantly reduced as compared with normal and fell within the thyrotoxic range. Seven patients subsequently had their doses of thyroxine reduced by 50 micrograms daily and were reinvestigated one month later. All showed significant falls in circulating thyroxine and triiodothyronine concentrations and an increase in mean systolic time intervals to the normal range. In patients receiving thyroxine replacement therapy for primary hypothyroidism a raised serum thyroxine concentration may indicate tissue thyrotoxicosis and should prompt a reduction of the thyroxine dose.

BACKGROUND

Thyroid hormones (TH) may influence glucose metabolism. Hyperthyroid subjects have higher insulin secretion rates when compared with euthyroid individuals.

OBJECTIVE

To evaluate the association between TH concentrations and insulin secretion in euthyroid, healthy Pima Indian adults (n=55, 29+/-7 years, females/males 36/19) with normal glucose tolerance (NGT) admitted to a Clinical Research Unit.

METHODS

TSH, free thyroxine (FT4), 3,5,3'-L-tri-iodothyronine (FT3), and fasting plasma insulin (FPI) concentrations were measured in fasting plasma samples, percentage of body fat (%BF) by dual energy x-ray absorptiometry (DXA), acute insulin response (AIR), and incremental area under the curve (AUC) of insulin in response to a 25 g intravenous glucose tolerance test (IVGTT) and 75 g oral glucose tolerance test (OGTT) respectively and insulin action (M) during an euglycemic clamp.

RESULTS

FT3 concentrations were associated with FPI, AIR, and insulin AUC both before (r=0.33, P=0.01; r=0.29, P=0.03; and r=0.35, P=0.008 respectively) and after adjustment for age, sex, %BF, glucose (fasting concentrations or glucose AUC), and M (beta=0.09, P=0.01; beta=0.16, P=0.03; and beta=0.24, P=0.0007 respectively). No associations were found for TSH or FT4.

CONCLUSIONS

FT3 was associated with several measurements of insulin secretion in euthyroid individuals with NGT. T3 concentrations may play a role in the regulation of insulin secretion.

Glycated albumin (GA) is used alongside glycated hemoglobin (HbA(1C)) as an indicator of glycemic control. Although serum GA levels are affected mainly by plasma glucose, they are also influenced by serum albumin metabolism. Thyroid hormone is known to promote albumin catabolism, and it is thus thought to affect serum GA levels. In the present study, the effects of thyroid hormone on serum GA measurements were investigated in patients with thyroid dysfunction. Six patients with untreated hypothyroidism and 17 patients with untreated thyrotoxicosis were investigated. Patients who had anemia or diabetes were excluded. A total of 25 non-diabetic, euthyroid individuals were enrolled as controls. HbA(1C), serum GA, thyroid-stimulating hormone (TSH), free triiodothyronine (T(3)), and free thyroxine (T(4)) levels were measured in all these subjects, and their relationships were examined. Although no intergroup differences were observed for HbA(1C), serum GA was significantly higher among patients with hypothyroidism than controls, and significantly lower among patients with thyrotoxicosis. Serum GA had a significant positive correlation with serum TSH and significant inverse correlations with free T(3) and free T(4). Thyroid hormone levels are inversely associated with serum GA levels. Cautions are necessary when evaluating serum GA levels in patients with thyroid dysfunction.

The adequate functioning of the maternal thyroid gland plays an important role to ensure that the offspring develop normally. Thus, maternal hypo- and hyperthyroidism are used from the gestation day 1 to lactation day 21, in general, to recognize the alleged association of offspring abnormalities associated with the different thyroid status. In maternal rats during pregnancy and lactation, hypothyroidism in one group was performed by antithyroid drug, methimazole (MMI) that was added in drinking water at concentration 0.02% and hyperthyroidism in the other group was induced by exogenous thyroxine (T4) (from 50 microg to 200 microg/kg body weight) intragastric administration beside adding 0.002% T4 to the drinking water. The hypothyroid and hyperthyroid states in mothers during pregnancy and lactation periods were confirmed by measuring total thyroxine (TT4) and triiodothyronine (TT3) at gestational day 10 and 10 days post-partum, respectively; the effect was more pronounced at the later period than the first. In offspring of control maternal rats, the free thyroxine (FT4), free triiodothyronine (FT3), thyrotropin (TSH) and growth hormone (GH) concentrations were pronouncedly increased as the age progressed from 1 to 3 weeks. In hypothyroid group, a marked decrease in serum FT3, FT4 and GH levels was observed while there was a significant increase in TSH level with age progress as compared with the corresponding control. The reverse pattern to latter state was recorded in hyperthyroid group. The thyroid gland of offspring of hypothyroid group, exhibited some histopathological changes as luminal obliteration of follicles, hyperplasia, fibroblastic proliferation and some degenerative changes throughout the experimental period. The offspring of hyperthyroid rats showed larger and less thyroid follicles with flattened cell lining epithelium, decreased thyroid gland size and some degenerative changes along the experimental period. On the other hand, the biochemical data revealed that in control offspring, the levels of iodothyronine 5'-monodeiodinase (5'-DI), monoamines, gamma-aminobutyric acid (GABA), acetylcholinesterase (AchE), ATPase-enzymes (Na(+),K(+)-ATPase, Ca(2+)-ATPase and Mg(2+)-ATPase) follow a synchronized course of development in all investigated brain regions (cerebrum, cerebellum and medulla oblongata). In addition, the depression in 5'-DI activity, monoamines levels with age progress in all investigated regions, was more pronounced in hypothyroid offspring, while they were increased significantly in hyperthyroid ones in comparison with their respective controls. Conversely, the reverse pattern was recorded in level of the inhibitory transmitter, GABA while there was a disturbance in AchE and ATPases activities in both treated groups along the experimental period in all studied regions. In conclusion, the hypothyroid status during pregnancy and lactation produced inhibitory effects on monoamines, AchE and ATPases and excitatory actions on GABA in different brain regions of the offspring while the hyperthyroid state induced a reverse effect. Thus, the maternal hypothyroidism and hyperthyroidism may cause a number of biochemical disturbances in different brain regions of their offspring and may lead to a pathophysiological state. These alterations were age dependent.

Serum-free, hormonally defined media have been developed for optimal growth of a rat hepatoma cell line. The cells' hormonal requirements for growth are dramatically altered both qualitatively and quantitatively by whether they were plated onto tissue culture plastic or collagenous substrata. On collagenous substrata, the cells required insulin, glucagon, growth hormone, prolactin, and linoleic acid (bound to BSA), and zinc, copper, and selenium. For growth on tissue culture plastic, the cells required the above factors at higher concentrations plus several additional factors: transferrin, hydrocortisone, and triiodothyronine. To ascertain the relative influence of hormones versus substratum on the growth and differentiation of rat hepatoma cells, various parameters of growth and of liver-specific and housekeeping functions were compared in cells grown in serum-free, hormonally supplemented, or serum-supplemented medium and on either tissue culture plastic or type I collagen gels. The substratum was found to be the primary determinant of attachment and survival of the cells. Even in serum-free media, the cells showed attachment and survival efficiencies of 40-50% at low seeding densities and even higher efficiencies at high seeding densities when the cells were plated onto collagenous substrata. However, optimal attachment and survival efficiencies of the cells on collagenous substrata still required either serum or hormonal supplements. On tissue culture plastic, there was no survival of the cells at any seeding density without either serum or hormonal supplements added to the medium. A defined medium designed for cells plated on tissue culture plastic, containing increased levels of hormones plus additional factors over those in the defined medium designed for cells on collagenous substrata, was found to permit attachment and survival of the cells plated into serum-free medium and onto tissue culture plastic. Growth of the cells was influenced by both substrata and hormones. When plated onto collagen gel substrata as compared with tissue culture plastic, the cells required fewer hormones and growth factors in the serum-free, hormone-supplemented media to achieve optimal growth rates. Growth rates of the cells at low and high seeding densities were equivalent in the hormonally and serum-supplemented media as long as comparisons were made on the same substratum and the hormonally supplemented medium used was the one designed for that substratum. For a given medium, either serum or hormonally supplemented, the saturation densities were highest for tissue culture plastic as compared with collagen gels.(ABSTRACT TRUNCATED AT 400 WORDS)

Recent studies have shown that hepatic mRNAS14 responds rapidly to thyroid hormone administration. Moreover, this mRNA is known to increase in mass with the administration of a high carbohydrate fat-free diet. Therefore, it appears to share many of the same properties of the known hepatic lipogenic enzymes. Because the lipogenic enzymes display a synergistic interaction between thyroid hormones and carbohydrates, we investigated the kinetics of response of mRNAS14 to carbohydrate feeding, as well as its interaction with triiodothyronine (T3). We found that mRNAS14 responds rapidly to the dietary administration of sucrose in euthyroid rats, with a 2-fold increase within 30 min, and a 25-fold increase by 4 h. On the other hand, when given to hypothyroid rats, sucrose ultimately lead to only a 2-3-fold increase in the level of mRNAS14, attaining a level less than that found in starved euthyroid rats. The diminished response of mRNAS14 to sucrose in hypothyroidism could not be enhanced by insulin administration. However, administration of replacement doses of T3 (400 ng/100 g of body weight) immediately restored the rapid response to sucrose feeding. The response of sucrose and T3 was synergistic. Dose-response studies with T3 indicated that the rapid interaction between T3 and sucrose was limited by the occupancy of the T3 nuclear receptor. A similar synergistic response to T3 and glucose was noted in primary hepatocyte cultures, thus indicating that the synergism between these two stimuli is not due to changes in extrahepatic hormones or metabolites. Our data are most consistent with the hypothesis that the T3-nuclear receptor complex multiplies a signal generated by carbohydrate metabolism to induce hepatic mRNAS14. The interaction does not appear to require the preliminary induction of carbohydrate-metabolizing enzymes and their mRNAs.

BACKGROUND

Adaptive alterations in maternal physiology cause changes in thyroid hormone levels throughout pregnancy, and precise biochemical evaluation is thus highly dependent on gestation-specific reference intervals and expected intra-individual variation.

OBJECTIVE

The aim of the study was the assessment of the intra-individual variation as well as the longitudinal course of thyroid hormones during normal pregnancy and factors that influence the normal reference range for thyroid function. For this purpose, a longitudinal statistical model was applied.

METHODS

In a cohort of 132 pregnant women, serial blood samples were obtained and ultrasound scans were performed throughout pregnancy.

METHODS

Serum levels of TSH, free and total thyroxine (T(4)), free and total triiodothyronine (T(3)) as well as autoantibodies against thyroid peroxidase and thyroglobulin were measured in 979 serum samples.

RESULTS

Intra-individual variations of thyroid hormone concentrations were smaller than inter-individual variations (individuality index range: 0.38-0.71). Maternal height was positively associated with free T(4) (FT(4)) (b=0.003; P=0.031) and pre-pregnancy body mass index with T(3) and free T(3) (b=0.017; <0.001 and b=0.007; P<0.001). Smoking was positively associated with T(4) and FT(4), but it was modulated by gestational age. Gestation-specific reference intervals for thyroid function variables from autoantibody-negative participants are presented.

CONCLUSIONS

In accordance with the data from nonpregnant adults, intra-individual variations of thyroid hormones were smaller than inter-individual variations also during pregnancy. In the evaluation of thyroid function in pregnancy, the individual longitudinal course of thyroid hormones rather than absolute values should be considered. We present a longitudinal model for the prediction of maternal thyroid function tests in pregnant women.

OBJECTIVE

The thyroid hormone system may be downregulated temporarily in patients who are severely ill. This "euthyroid sick syndrome" may be an adaptive response to conserve energy. However, thyroid hormone also has beneficial effects on the cardiovascular system, such as improving cardiac function, reducing systemic vascular resistance, and lowering serum cholesterol levels. We investigated whether thyroid hormone levels obtained at the time of myocardial infarction are associated with subsequent mortality.

METHODS

Serum levels of thyroid hormones (triiodothyronine [T3], reverse T3, free thyroxine [T4], and thyroid-stimulating hormone) were measured in 331 consecutive patients with acute myocardial infarction (mean age [+/- SD], 68 +/- 12 years), from samples obtained at the time of admission.

RESULTS

Fifty-three patients (16%) died within 1 year. Ten percent (16 of 165) of patients with reverse T3 levels (an inactive metabolite) >0.41 nmol/L (the median value) died within the first week after myocardial infarction, compared with none of the 166 patients with lower levels (P <0.0004). After 1 year, the corresponding figures were 24% (40 of 165) versus 7.8% (13 of 166; P <0.0001). Reverse T3 levels >0.41 nmol/L were associated with an increased risk of 1-year mortality (hazard ratio = 3.0; 95% confidence interval: 1.4 to 6.3; P = 0.005), independent of age, previous myocardial infarction, prior angina, heart failure, serum creatinine level, and peak serum creatine kinase-MB fraction levels.

CONCLUSIONS

Determination of reverse T3 levels may be a valuable and simple aid to improve identification of patients with myocardial infarction who are at high risk of subsequent mortality.

BACKGROUND

Physical activity influences energy metabolism in human subjects by increasing activity-induced energy expenditure and resting metabolic rate for several hours after exercise. Effects of exercise on circulating thyroid hormone values remain controversial. We have investigated the effect of acute aerobic exercise on thyroid hormone values.

METHODS

The effect of different intensity levels of acute aerobic exercise on thyroid hormones was investigated in 60 male well-trained athletes by performing bicycle ergometer at 45% (low intensity), 70% (moderate intensity), and 90% (high intensity). These intensities were selected according to their maximum heart rate (MHR). At each intensity level, heart rate, blood lactic acid, serum total thyroxine (T4), free thyroxine (fT4), total triiodothyronine (T3), free triiodothyronine (fT3) and thyroid stimulating hormone (TSH) values were measured.

RESULTS

The results of this study show that exercise performed at the anaerobic threshold (70% of maximum heart rate, lactate level 4.59 +/- 1.75 mmol/l) caused the most prominent changes in the amount of any hormone values. While the rate of T4, fT4, and TSH continued to rise at 90% of maximum heart rate, the rate of T3 and fT3 started to fall.

CONCLUSIONS

Maximal aerobic exercise greatly affects the level of circulating thyroid hormones.

BACKGROUND

The association of sarcoidosis (S) and thyroid autoimmunity has been reported by several studies in a wide range of variability. The aim of our study was to evaluate the prevalence of clinical and subclinical thyroid disorders in patients with S vs gender-matched and age-matched control subjects.

METHODS

Thyroid hormones and antithyroid antibodies, thyroid ultrasonography and fine-needle aspiration were performed in 111 patients with S who had been consecutively referred to the Respiratory Pathophysiology Section of the University of Pisa, and the results were compared to 333 gender-matched and age-matched control subjects from the same geographic area.

RESULTS

The odds ratio for subclinical hypothyroidism for female patients with S vs control subjects was 2.7 (95% confidence interval [CI], 1.3 to 5.9); for anti-thyroid peroxidase antibody titer (AbTPO) positivity, 2.2 (95% CI, 1.2 to 3.9); and for thyroid autoimmunity, 1.9 (95% CI, 1.1 to 3.2). The mean values of thyroid-stimulating hormone and AbTPO were higher in female S patients than in control subjects (p < 0.01). A significantly higher prevalence of clinical hypothyroidism (four patients) and Graves disease (three patients) was observed in female S patients than in control subjects (none; p = 0.005 and 0.0026, respectively). Two cases of papillary thyroid cancer were detected in S patients. No significant difference between S patients and control subjects was detected for free triiodothyronine and thyroxine, antithyroglobulin autoantibodies, thyroid volume and nodularity, and subclinical hyperthyroidism.

CONCLUSIONS

Thyroid function, AbTPO antibodies, and ultrasonography should be tested as part of the clinical profile in female S patients. Subjects who are at high risk (female subjects, those with positive AbTPOs, and those with hypoechoic and small thyroid) should have thyroid function follow-up and appropriate treatment in due course.

BACKGROUND

Perfluoroalkyl substances (PFASs) are synthetic compounds that are widely used in industry and are often detectable in humans. In pregnant rats and their pups, PFASs can interfere with thyroid hormone homeostasis. In humans, maternal thyroid hormones supply the fetus throughout pregnancy, and thyroid hormones play a critical role in fetal growth and neurodevelopment.

OBJECTIVE

We investigated the association between maternal PFAS exposure and thyroid hormone status in pregnant women and neonates.

METHODS

In a study of environmental exposure and health in Taiwan, we measured serum concentrations of nine PFASs and four thyroid hormones for 285 pregnant women in their third trimester, and also measured cord serum thyroid hormones for 116 neonates. Associations between maternal PFASs and maternal and cord thyroid hormones were examined in multiple linear regression models.

RESULTS

Perfluorohexanesulfonic acid concentrations were positively associated with maternal thyroid-stimulating hormone (TSH) levels. Pregnant women with higher levels of perfluorononanoic acid (PFNA), perfluoroundecanoic acid (PFUnDA), and perfluorododecanoic acid (PFDoDA) had lower free thyroxine (T4) and total T4 levels. For example, we estimated that maternal free T4 levels decreased 0.019 ng/dL (95% CI: -0.028, -0.009) with each nanogram per milliliter increase in maternal PFNA. Finally, maternal PFNA, PFUnDA, and PFDoDA levels were associated with lower cord total triiodothyronine (T3) and total T4 levels, and maternal perfluorodecanoic acid (PFDeA) was associated with lower cord total T3.

CONCLUSIONS

Our results suggest that exposure to some PFASs during pregnancy may interfere with thyroid hormone homeostasis in pregnant women and fetuses.

BACKGROUND

Reference intervals are indispensable in evaluating laboratory test results; however, appropriately partitioned pediatric reference values are not readily available. The Canadian Laboratory Initiative for Pediatric Reference Intervals (CALIPER) program is aimed at establishing the influence of age, sex, ethnicity, and body mass index on biochemical markers and developing a comprehensive database of pediatric reference intervals using an a posteriori approach.

METHODS

A total of 1482 samples were collected from ethnically diverse healthy children ages 2 days to 18 years and analyzed on the Abbott ARCHITECT i2000. Following the CLSI C28-A3 guidelines, age- and sex-specific partitioning was determined for each analyte. Nonparametric and robust methods were used to establish the 2.5th and 97.5th percentiles for the reference intervals as well as the 90% CIs.

RESULTS

New pediatric reference intervals were generated for 14 biomarkers, including α-fetoprotein, cobalamin (vitamin B12), folate, homocysteine, ferritin, cortisol, troponin I, 25(OH)-vitamin D [25(OH)D], intact parathyroid hormone (iPTH), thyroid-stimulating hormone, total thyroxine (TT4), total triiodothyronine (TT3), free thyroxine (FT4), and free triiodothyronine. The influence of ethnicity on reference values was also examined, and statistically significant differences were found between ethnic groups for FT4, TT3, TT4, cobalamin, ferritin, iPTH, and 25(OH)D.

CONCLUSIONS

This study establishes comprehensive pediatric reference intervals for several common endocrine and immunochemical biomarkers obtained in a large cohort of healthy children. The new database will be of global benefit, ensuring appropriate interpretation of pediatric disease biomarkers, but will need further validation for specific immunoassay platforms and in local populations as recommended by the CLSI.

Thyroid hormone levels are a major determinant of energy balance and are thought to modify body composition by their effects on metabolism of lipids, carbohydrate and protein. The present study evaluates changes of body composition and basal energy expenditure (BEE) in thyroidectomized patients studied during short-term profound hypothyroidism while off all thyroid hormone before diagnostic whole-body (131)I-imaging and while on thyrotropin-suppressive thyroxine therapy. Basal energy expenditure was assessed by indirect calorimetry, and four-point body impedance analysis was used to estimate body composition. Patients were compared with healthy controls matched with respect to sex, age, height and weight. Compared to healthy controls the percentages of body water and body cell mass were significantly lower while the percentage of fat was significantly higher in patients during short-term hypothyroidism. Weight did not change significantly when patients were put on thyroxine treatment, but body fat (-0.95 +/- 2.25 kg, p < 0.01) decreased while body water (+0.94 +/- 1.31 kg, p < 0.01) and body cell mass (+0.9 +/- 2.5 kg, p < 0.05) increased. With thyroxine replacement, body composition was not significantly different between patients and controls. Compared to healthy controls, BEE was significantly lower in patients without thyroxine replacement (5265 +/- 766 kJ/24h vs 6362 +/- 992 kJ/24h; p < 0.001). With thyroxine treatment, BEE increased (6492 +/- 967 kJ/24h) but was not significantly different from the controls (p>> 0.05). Neither body composition nor BEE was significantly different in a subgroup of thyroxine-treated patients with free triiodothyronine or thyroxine values above the normal range. In conclusion, both body composition and energy expenditure showed significant changes when patients were deprived of thyroid hormone. However, no evidence of excess metabolic effects of thyroid hormone during thyrotropin-suppressive thyroxine therapy was found.

BACKGROUND

The aim of this study was to investigate the effect of hypothyroidism on lipid peroxidation and the antioxidant profile, as well as to evaluate the interaction between thyroid hormones and biomarkers of oxidative stress in patients with overt hypothyroidism. We also evaluated the influence of cholesterol concentrations on biomarkers of oxidative stress in these same patients.

METHODS

Total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT), and vitamin E were measured in 20 subjects with overt hypothyroidism (OH) and 20 controls.

RESULTS

TC, LDL cholesterol, triglycerides, TBARS, SOD, CAT, and vitamin E were significantly higher in the OH group. Significant correlation was observed for TSH and SOD, CAT, vitamin E and TBARS. Correlation was observed for triiodothyronine (T3) and SOD, CAT, vitamin E and TBARS. Significant correlation was also observed for free thyroxine and vitamin E and TBARS. However, correlation between T3 and CAT remained significant after controlling for TC concentrations.

CONCLUSIONS

Overt hypothyroidism is associated with an increase in oxidative stress, and hypercholesterolemia has a stronger influence on development of oxidative stress in hypothyroid conditions compared with thyroid hormones.

We describe brain lesions in a patient with a monocarboxylate transporter 8 mutation. Imaging showed a high T2 lesion in the left putamen at age 3 and a right putamen lesion at age 6. Cerebrospinal fluid free thyroxine concentrations were low, with normal 3,3',5-triiodothyronine concentrations.