The present study was conducted to investigate how thyroid function in rats is affected by administration of 3 mg per kg per day of zinc and/or melatonin. The study was conducted with 40 Sprague-Dawley adult male rats equally divided into four groups: 1 (controls), 2 (zinc-only), 3 (melatonin-only) and 4 (zinc- and melatonin-supplemented). The supplementation was continued for 4 weeks after which the animals were sacrificed and plasma samples were obtained for determination of zinc, melatonin, free- and total triiodothyronine (T3), thyroxine (T4) and thyroid-stimulating hormone (TSH) levels. The free T3, T4 and TSH levels were lower in the melatonin group than in all other groups (P<0.01), while free- and total T3 levels were higher in the zinc group (P<0.01). The group that received zinc and melatonin combined had free thyroid hormone levels higher than the only melatonin group. These results show that melatonin has a thyroid function suppressing action, just the opposite to the actions of zinc. When zinc is administered along with melatonin, its thyroid function suppression is diminished.

OBJECTIVE

To evaluate thyroid structure and function in patients with enlargement of the vestibular aqueduct (EVA) and sensorineural hearing loss.

METHODS

Prospective cohort survey.

METHODS

National Institutes of Health Clinical Center, a federal biomedical research facility.

METHODS

The study population comprised 80 individuals, aged 1.5 to 59 years, ascertained on the basis of EVA and sensorineural hearing loss.

METHODS

Associations among the number of mutant alleles of SLC26A4; volume and texture of the thyroid; percentage of iodine 123 ((123)I) discharged at 120 minutes after administration of perchlorate in the perchlorate discharge test; and peripheral venous blood levels of thyrotropin, thyroxine, free thyroxine, triiodothyronine, thyroglobulin, antithyroid peroxidase and antithyroglobulin antibodies, and thyroid-binding globulin.

RESULTS

Thyroid volume is primarily genotype dependent in pediatric patients but age dependent in older patients. Individuals with 2 mutant SLC26A4 alleles discharged a significantly (P < or = .001) greater percentage of (123)I compared with those with no mutant alleles or 1 mutant allele. Thyroid function, as measured by serologic testing, is not associated with the number of mutant alleles.

CONCLUSIONS

Ultrasonography with measurement of gland volume is recommended for initial assessment and follow-up surveillance of the thyroid in patients with EVA. Perchlorate discharge testing is recommended for the diagnostic evaluation of patients with EVA along with goiter, nondiagnostic SLC26A4 genotypes (zero or 1 mutant allele), or both.

OBJECTIVE

This study was designed to test the hypothesis that normal thyroid function is associated with non-alcoholic fatty liver disease (NAFLD) in euthyroid general subjects.

METHODS

A total of 739 euthyroid subjects were enrolled in this cross-sectional study. Using ultrasound, a diagnosis of NAFLD was made in subjects without a history of excessive alcohol consumption or liver diseases. Fasting serum samples were collected for determining thyroid function [thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) levels] and other biochemical parameters.

RESULTS

Among the enrolled subjects, 196 (26.5%) satisfied the diagnostic criteria for NAFLD. Subjects with NAFLD had significantly higher TSH levels and lower FT4 levels than those without NAFLD (p < 0.01 for both). NAFLD prevalence increased gradually with increasing quartiles of TSH levels and decreasing quartiles of FT4 levels. After adjustment for gender and age, TSH levels were found to correlate positively with body mass index (BMI), waist circumference (WC), and LDL-cholesterol levels (p < 0.05 for all) and negatively with HDL-cholesterol levels (p < 0.01). FT4 levels correlated negatively with both BMI and WC (p < 0.05 for both). Multiple logistic regression analysis showed that TSH and FT4 levels were independent risk factors for NAFLD [odds ratio (OR): 2.21, 95% confidence interval (CI): 1.21-4.02, p = 0.01, for TSH levels; OR: 0.39, 95% CI: 0.17-0.87, p = 0.02, for FT4 levels].

CONCLUSIONS

Our findings suggest that serum FT4 and TSH levels, even those within the reference range, are associated with NAFLD in the general population, independent of known metabolic risk factors.

BACKGROUND

Whether hypothyroidism is related to nonalcoholic fatty liver disease (NAFLD) is unclear. Thyroid dysfunction is closely related with components of metabolic syndrome. Given the hepatic manifestation of metabolic syndrome, several studies have investigated the association between NAFLD and thyroid dysfunction and have demonstrated inconsistent results. Thus, we conducted a systematic review and meta-analysis to better characterize the association between NAFLD and thyroid dysfunction.

METHODS

MEDLINE and Embase were searched through July 2016. The primary outcome was the association between NAFLD and subclinical, overt, and overall hypothyroidism. The secondary outcome was the difference in thyroid hormone levels (free triiodothyronine [FT3], free thyroxine [FT4], or thyroid-stimulating hormone [TSH]) between NAFLD patients and non-NAFLD controls. Pooled odds ratios (OR) and 95% CI were calculated using a random-effects model. All continuous data are summarized as the mean difference along with 95% CI.

RESULTS

Data were extracted from 14 studies involving 7,191 NAFLD patients and 30,003 controls. NAFLD was not associated with subclinical, overt, or overall hypothyroidism compared with non-NAFLD controls. Patients who had NAFLD did not show a significant difference in FT3, FT4, or TSH compared with non-NAFLD controls.

CONCLUSIONS

Our meta-analysis demonstrates no significant association between NAFLD and subclinical, overt, or overall hypothyroidism, and we also found no significant difference in thyroid hormone levels between participants with and without NAFLD.

OBJECTIVE

The association between thyroid function and non-alcoholic fatty liver disease (NAFLD) remained controversial. A large cross-sectional study aimed to explore the relationship in euthyroid population.

METHODS

A total of 1773 euthyroid subjects who underwent health check-up during one-year period were enrolled. NAFLD was diagnosed by ultrasound and fatty liver index (FLI). Fibrosis was estimated by BARD score. Thyroid function parameters, including thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), were recorded. Multivariate logistic regression analyses were performed to identify the independent risk factors. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated.

RESULTS

NAFLD was diagnosed by ultrasound in 638 (35.98%) subjects and by FLI ≥ 60 in 694 (39.14%) subjects. Regardless of ultrasound or FLI, the overall analysis demonstrated that TSH and FT3 levels were significantly higher in subjects with NAFLD than subjects without NAFLD, but FT4 level was not significantly different between them. This association remained in middle-age subjects, but not elderly subjects. In the multivariate logistic regression analysis, TSH (OR = 1.108, 95%CI = 1.056-1.398, P = 0.024) and FT3 (OR = 1.258, 95%CI = 1.123-1.409, P = 0.000) levels were independently associated with the risk of NAFLD diagnosed by ultrasound; and only FT3 level (OR = 1.252, 95%CI = 1.074 - 1.460, P = 0.004) was independently associated with the risk of NAFLD estimated by FLI ≥ 60. Additionally, FT3 level (OR = 1.178, 95%CI = 1.025 - 1.354, P = 0.021) was independently associated with the risk of fibrosis estimated by BARD score ≥ 2 in NAFLD subjects.

CONCLUSIONS

Among the euthyroid population, FT3 and TSH levels were positively associated with the risk of NAFLD.

BACKGROUND

Polybrominated diphenyl ethers (PBDEs) are flame-retardant chemicals that are added to many consumer products. Multiple animal studies have shown PBDEs to be thyroid hormone (TH) disruptors. Epidemiologic evidence of PBDE exposure associated with TH disruption has been inconclusive.

OBJECTIVE

We used repeated measures to estimate associations between serum PBDE concentrations and THs in a North American adult cohort.

METHODS

From 2010 to 2011, we collected ≤ 3 serum samples at approximately 6-month intervals from 52 healthy adult office workers from Boston, Massachusetts, for analysis of PBDE congeners and THs.

RESULTS

The geometric mean sum concentrations of the most prevalent PBDE congeners (BDE-28, BDE-47, BDE-99, BDE-100, and BDE-153) were 22 ng/g lipid in winter 2010, 23 ng/g lipid in summer 2010, and 19 ng/g lipid in winter 2011. BDE-47 was the predominant congener. Based on a multivariable mixed regression model, we estimated that on average, a 1-ng/g serum increase in BDE-47 was associated with a 2.6-μg/dL decrease in total thyroxine (T4) (95% CI: -4.7, -0.35). Total T4 was inversely associated with each PBDE congener. Serum concentrations of PBDEs were not strongly associated with total triiodothyronine (T3), free T4, or thyroid-stimulating hormone (TSH).

CONCLUSIONS

These results are consistent with those from animal studies showing that exposure to PBDEs is associated with a decrease in serum T4. Because the other TH concentrations did not appear to be associated with BDE exposures, our findings do not indicate effects on the pituitary-thyroid axis. Taken together, our findings suggest that PBDE exposure might decrease the binding of T4 to serum T4 binding proteins.

BACKGROUND

Makey CM, McClean MD, Braverman LE, Pearce EN, He XM, Sjödin A, Weinberg JM, Webster TF. 2016. Polybrominated diphenyl ether exposure and thyroid function tests in North American adults. Environ Health Perspect 124:420-425; http://dx.doi.org/10.1289/ehp.1509755.

Sixteen cases of transient infantile hyperthyrotrophinaemia were followed up for two to seven years. Concentrations of serum triiodothyronine, thyroxine, and free thyroxine were maintained within the normal range in all cases. All but one child, who had a hearing disturbance, showed normal mental development with normal physical and skeletal maturation. Eleven children had normal concentrations of serum thyroid stimulating hormone and no signs or symptoms of thyroid dysfunction; in three children, diffuse small goitres developed and two further children showed relapse with slightly raised concentrations of thyroid stimulating hormone. It is concluded that 'transient infantile hyperthyrotrophinaemia' is a syndrome, which differs from typical transient neonatal hypothyroidism, and that careful follow up is necessary because some children show signs of mild pituitary-thyroid dysfunction in later childhood.

BACKGROUND

The purpose of this study is to evaluate the possible predictors of thyroid disorders after neck radiotherapy, with a focus on radiation dose-volume factors.

METHODS

Thyroid function was measured in 100 patients who had received radiotherapy to the neck, including the thyroid. All radiation-induced thyroid dysfunctions were determined with an endpoint of abnormal thyroid stimulating hormone (TSH), free triiodothyronine (fT3) and thyroxine (fT4) and thyroid peroxidase antibodies and (TPA). The total volume of the thyroid, mean radiation dose to the thyroid (Dmean) and thyroid volume percentage that received radiation doses of 10-50 Gy (V10-V50) were calculated in all patients. The evaluated risk factors for thyroid dysfunction included dose-volume parameters, sex, age, previous surgery, chemotherapy and comorbidity.

RESULTS

There were 52 patients with hypothyroidism and V30 (p = 0.03), thyroid volume (p = 0.01) and Dmean (p = 0.03) appeared to be correlated with hypothyroidism in univariate analysis. However, there was not association found in multivariate analysis for these factors.

CONCLUSIONS

Thyroid disorders after radiation therapy to the neck still represent a clinically underestimated problem. V30 may be a useful tool for evaluating the risk of hypothyroidism when determining an individual patient's treatment.

Prolonged breast-feeding in humans is associated with increased low-density lipoprotein cholesterol and higher death rates from ischaemic heart disease in adult life. The reasons for this link are unclear. A possible explanation is that thyroid hormones present in breast milk and absorbed by the suckling infant could, by the process of hormonal imprinting, permanently down-regulate the set point of thyroid homeostasis. Thyroid hormones influence cholesterol metabolism, and could explain the link between infant feeding and the regulation of cholesterol levels in the adult. We therefore investigated whether infant feeding was related to adult thyroid function in 303 women aged 60-71 years who were born in the county of Hertfordshire, UK, where birthweight, the weight at 1 year and the method of infant feeding had been recorded routinely. Free thyroxine (FT4) concentrations but not free triiodothyronine (FT3) or thyrotrophin (TSH) were increased in the women who, as infants, had been breast-fed beyond 1 year of age (p < 0.01). In women who were bottle-fed, with or without breast-feeding, serum TSH rose and FT4 fell with increasing birthweight (p = 0.01 and p = 0.04, respectively). Although the metabolic significance of these findings is unclear, they suggest that the set point of thyroid function in the adult is determined by fetal growth and infant feeding.

BACKGROUND

This study was designed to assess both central and peripheral aspects of thyroid function in combat-related posttraumatic stress disorder (PTSD), with the particular purpose of finding a mechanistic explanation for an imbalance between serum levels of free thyroxine (T4) and total T4 previously observed in pilot work.

METHODS

A total of 96 male combat veterans with PTSD diagnosed by DSM-III-R (72 from the West Haven, Conn, Veterans Affairs Medical Center and 24 from the Menlo Park, Calif, Veterans Affairs Medical Center) were compared with 24 male control subjects. One or more serum samples were analyzed by radioimmunoassays for levels of total T4, free T4, total triiodothyronine (T3), free T3, T4-binding globulin, and thyrotropin.

RESULTS

The pilot observation of moderately elevated total T4 levels with no elevation in free T4 levels in patients with PTSD was confirmed, suggesting the hypotheses that (1) there may be an increased peripheral conversion of free T4 by deiodination to T3 or (2) there may be an increased binding of T4 secondary to elevated T4-binding globulin levels. Our findings support both hypotheses. The PTSD groups all showed a marked and sustained elevation in levels of both total T3 and free T3, as well as elevated T3/T4 ratios, supporting the increased T3 conversion hypothesis. The PTSD groups also showed a marked and sustained increase in T4-binding globulin levels, supporting the increased binding hypothesis. Thyrotropin levels did not differ between PTSD and control groups.

CONCLUSIONS

These findings demonstrate an unusual pattern of thyroid alterations, featuring substantial elevations in total T3, free T3, and T4-binding globulin levels, in combat-related PTSD that differs from established endocrinopathies, such as classic hyperthyroidism, T3 thyrotoxicosis, or chronic T4-binding globulin elevation.

Laboratory assessment of thyroid function is now often initiated with a low pre-test probability, by clinicians who may not have a detailed knowledge of current methodology or testing strategies. Skilled laboratory staff can significantly enhance the choice of appropriate tests and the accuracy of clinical response; such involvement requires both appropriate training and relevant information from the clinician. Measurement of the serum thyroid stimulating hormone (TSH) concentration with an assay of adequate sensitivity is now the cornerstone of thyroid function testing; for untreated populations at risk of primary thyroid dysfunction, a normal TSH concentration rules out an abnormality with a high degree of certainty. However, in several important situations, most notably pituitary abnormalities and early treatment of thyroid dysfunction, serum TSH can give a misleading indication of thyroid status. An abnormal TSH concentration alone is never an adequate basis for initiation of treatment, which should be based on the typical relationship between trophic and target gland hormones, based on serum TSH and an estimate of serum free thyroxine (T4). Six basic assumptions, some clinical, some laboratory-based, need to be considered, together with the relevant limiting conditions, for reliable use of this relationship. Current methods of free T4 estimation remain imperfect, especially during critical illness. Diagnostic approach differs significantly between initial diagnosis and follow-up of treated thyroid dysfunction. In some situations, serum triiodothyronine (T3) is also required, but serum T3 lacks sensitivity for diagnosis of hypothyroidism, and has poor specificity during non-thyroidal illness. Where assay results are anomalous, most atypical findings can be resolved by attention to the clinical context, without further investigation.

It is well known that clinical hypothyroidism (CH) can induce cognitive deficits, and the decision to start treatment for CH with thyroxine is usually straightforward. However, the relationship of cognition dysfunction with subclinical hypothyroidism (SCH) is inconsistent, and the decision concerning the need to treat SCH is controversial. In the present study, we induced a SCH rat model by hemi-thyroid electrocauterisation; then employed a serial of behavioural tests, including a beam balance, open field task and Morris water maze (MWM), to investigate the behaviour performance of SCH rats; and finally explored the protein expression of phosphorylated extracellular signal-regulated kinase (ERK)1/2 in the hippocampus by western blotting. The results demonstrated that hemi-thyroid electrocauterised rats had an elevated plasma thyrotrophin-stimulating hormone (TSH) level, with normal free thyroxine (fT4) and triiodothyronine (T3) concentrations, which defines SCH in humans. If rat SCH is diagnosed according to measurements of both plasma TSH higher than 97.5 percentile for the sham group and fT4 in the range 2.5-97.5 percentile for the sham group, the success rate of SCH modelling was 66.6%. SCH decreased exploratory behaviour but did not affect motor function in rats, showing a negative correlation of exploratory behaviour with plasma TSH concentration. Moreover, SCH rats displayed an impairment of learning and memory ability in the MWM task, with a longer escape latency in the acquisition phase and a shorter duration in the target quadrant in the test phase compared to that of sham rats. The mechanism for this might be related to the increased plasma TSH concentration, the decreased hippocampal T3 level and the enhanced expression of phosphorylated ERK1/2 in the hippocampus. The results of the present study, together with the results obtained in other studies, suggest that treatment is necessary for SCH.

The role of thyroid hormones in diet-induced weight loss and subsequent weight regain is largely unknown.

To examine the associations between thyroid hormones and changes in body weight and resting metabolic rate (RMR) in a diet-induced weight loss setting.

Data analysis was conducted among 569 overweight and obese participants aged 30-70 years with normal thyroid function participating in the 2-year Prevention of Obesity Using Novel Dietary Strategies (POUNDS) LOST randomized clinical trial. Changes in body weight and RMR were assessed during the 2-year intervention. Thyroid hormones (free triiodothyronine (T3), free thyroxine (T4), total T3, total T4 and thyroid-stimulating hormone (TSH)), anthropometric measurements and biochemical parameters were assessed at baseline, 6 months and 24 months.

Participants lost an average of 6.6 kg of body weight during the first 6 months and subsequently regained an average of 2.7 kg of body weight over the remaining period from 6 to 24 months. Baseline free T3 and total T3 were positively associated, whereas free T4 was inversely associated, with baseline body weight, body mass index and RMR. Total T4 and TSH were not associated with these parameters. Higher baseline free T3 and free T4 levels were significantly associated with a greater weight loss during the first 6 months (P<0.05) after multivariate adjustments including dietary intervention groups and baseline body weight. Comparing extreme tertiles, the multivariate-adjusted weight loss±s.e. was -3.87±0.9 vs -5.39±0.9 kg for free T3 (Ptrend=0.02) and -4.09±0.9 vs -5.88±0.9 kg for free T4 (Ptrend=0.004). The thyroid hormones did not predict weight regain in 6-24 months. A similar pattern of associations was also observed between baseline thyroid hormones and changes in RMR. In addition, changes in free T3 and total T3 levels were positively associated with changes in body weight, RMR, body fat mass, blood pressure, glucose, insulin, triglycerides and leptin at 6 months and 24 months (all P<0.05).

In this diet-induced weight loss setting, higher baseline free T3 and free T4 predicted more weight loss, but not weight regain among overweight and obese adults with normal thyroid function. These findings reveal a novel role of thyroid hormones in body weight regulation and may help identify individuals more responsive to weight loss diets.

The influence of prolonged psychological stress on hormonal secretion was investigated in 84 East Germany refugees suffering from psychiatric disorders within 6 weeks of their arrival in West Berlin shortly before or after the fall of the Berlin Wall. Before leaving the German Democratic Republic, these patients had already experienced prolonged stress, which continued after migration. In most cases, the diagnosis was anxious-depressive syndrome with vegetative complaints and symptoms of increased arousal. Their formal DSM-III-R diagnoses (American Psychiatric Association, 1987) included adjustment disorders, depressive disorders, and anxiety disorders (the latter including posttraumatic stress disorder). Serum levels of thyroid stimulating hormone (TSH) and thyroid hormones (thyroxine, free thyroxine, triiodothyronine, and reverse triiodothyronine) were measured and compared with those of 20 healthy control subjects. TSH and all thyroid hormone concentrations were significantly reduced in the patient group. Fifty-two of the patients (62%) were in the hypothyroid range but did not show any clinical signs of hypothyroidism. These disturbances in hormonal secretion were not correlated to any psychiatric diagnosis or to the severity of acute or chronic stress. The marked abnormalities in the hypothalamic-pituitary-thyroid axis seen in these refugees differ from those reported in depression and would seem to reflect severe chronic stress rather than specific psychiatric disorders. The underlying neurochemical mechanisms remain to be investigated.

The aim of our study was to determine the prevalence of thyroid dysfunction and autoimmune abnormalities in rheumatoid arthritis (RA) and to further investigate the possible association between D-penicillamine and autoimmune thyroiditis. For this purpose, one hundred and one unselected consecutive patients with RA and 70 age and sex matched controls were studied prospectively. Evaluation included a complete history and physical examination with special attention to symptoms suggestive of thyroid pathology, routine laboratory and serologic immune profile, plus determination of serum levels of thyroxine (T4), triiodothyronine (T3), thyroid stimulating hormone (TSH), antibodies to thyroid peroxidase (AbTPO) and TSH receptor antibodies (TRAB). Serum thyroxine binding globulin (TBG) was measured in all subjects with high thyroid hormone levels, whereas free T3 and T4 concentrations were determined in all individuals with abnormal T3, T4, TSH or TBG. Six patients with hyperhyroidism, 3 with hypothyroidism and 1 with the euthyroid hyperthyroxinemia (EH) syndrome were found, whereas four of the controls had hyperthyroidism. Thirteen patients and 6 controls had high AbTPO levels whereas no one had high TRAB. No association was detected between thyroid abnormalities and any serologic RA finding. Furthermore, no correlation between thyroid dysfunction and elevated AbTPO's was found. A relatively high prevalence of thyroid dysfunction (9,9%) and subclinical autoimmune thyroiditis (12,9%), the latter indicated by elevated AbTPO's, was found in our RA patients. These figures were higher than those in the control group (5,7% and 8,6% respectively), but the difference did not reach statistical significance. Of further interest may be our finding that, despite anecdotal reports blaming D-penicillamine for cases of autoimmune thyroiditis, the incidence of the latter was similar among recipients and nonrecipients of the drug. Similarly, TRAB were not detected in any patient treated with D-penicillamine.

In order to evaluate the function of the hypothalamic-pituitary-thyroid (HPT)-axis in unipolar depression, the authors measured basal 0800h plasma levels of free thyroxine (FT4), free triiodothyronine (FT3), and thyroid stimulating hormone (TSH) by means of the new, ultrasensitive assays (TSH-IRMA) in 69 healthy controls, 62 minor, 101 simple major, and 57 melancholic depressed subjects. Basal HPT-axis hormone levels of almost all (96.8%) unipolar depressed patients fell within the normal, euthyroid range. None of the major depressed subjects showed subclinical hypothyroidism. It was found that 8.8% of the melancholic subjects exhibited some degree of subclinical hyperthyroidism. Basal TSH-IRMA values were significantly lower in melancholic patients than in healthy controls, minor and simple major depressed patients, and in major vs. minor depressed subjects. FT4 circulating levels were significantly higher in melancholic patients than in all other subjects. Basal TSH-IRMA and FT4 levels were significantly correlated with severity of illness. In depression, there was a significant and negative correlation between basal TSH-IRMA values and FT4 concentrations. No significant gender- or age-related differences in TSH-IRMA or thyroid hormones were detected in depression. It is argued that--in depression research--the assays of basal TSH-IRMA should replace thyrotropin releasing hormone tests.

The aim of this study was to investigate the relationship between suicidal behavior and hypothalamic-pituitary thyroid (HPT) axis activity in depressed patients. The serum levels of thyrotropin (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were evaluated before and after 0800 and 2300 h thyrotropin-releasing hormone (TRH) challenges, on the same day, in 95 medication-free DSM-IV euthyroid major depressed inpatients and 44 healthy hospitalized controls. Compared to controls: (1) patients with a positive suicide history (PSH; n=53) showed lower basal FT4 (at 0800 h: p<0.005; at 2300 h: p<0.03), but normal FT3 levels, while patients with a negative suicide history (NSH; n=42) showed normal FT4 and FT3 levels; (2) TSH responses to TRH (DeltaTSH) were blunted in NSHs (at 0800 h: p<0.03; at 2300 h: p<0.00001), but not in PSHs; (3) both NSHs and PSHs showed lower DeltaDeltaTSH values (differences between 2300 h-DeltaTSH and 0800 h-DeltaTSH) (p<0.000001 and p<0.003, respectively). Compared to NSHs, basal FT4 levels were reduced in PSHs (at 0800 h: p<0.002; at 2300h: p<0.006). HPT parameters were not significantly different between recent suicide attempters (n=32) and past suicide attempters (n=21). However, compared to controls, recent suicide attempters showed lower 2300 h-DeltaTSH (p<0.04) and DeltaDeltaTSH (p<0.002) values, and lower basal FT4 values (at 0800 h: p<0.006; at 2300 h: p<0.02). Our results, obtained in a large sample of depressed inpatients, indicate that various degrees of HPT axis dysregulation are associated with the history of suicide.

BACKGROUND

Radiation-induced thyroid disorders have been reported in radiotherapy of head and neck cancers. This study evaluated the radiation-induced damages to thyroid gland in patients with nasopharyngeal carcinoma (NPC).

METHODS

Forty-five patients with NPC treated by radiotherapy underwent baseline thyroid hormones (free triiodothyronine, free thyroxine [fT4], and thyrotropin [TSH]) examination and CT scan before radiotherapy. The volume of the thyroid gland was calculated by delineating the structure in the corresponding CT slices using the radiotherapy treatment planning system. The thyroid doses were estimated using the treatment planning system. Subsequent CT scans were conducted at 6, 12, and 18 months after radiotherapy, whereas the hormone levels were assessed at 3, 6, 12, and 18 months after radiotherapy. Trend lines of the volume and hormone level changes against time were plotted. The relationship between the dose and the change of thyroid volume and hormone levels were evaluated using the Pearson correlation test.

RESULTS

An average of 20% thyroid volume reduction in the first 6 months and a further 8% shrinkage at 12 months after radiotherapy were observed. The volume reduction was dependent on the mean thyroid doses at 6, 12, and 18 months after radiotherapy (r = -0.399, -0.472, and -0.417, respectively). Serum free triiodothyronine and fT4 levels showed mild changes of <2.5% at 6 months, started to drop by 8.8% and 11.3%, respectively, at 12 months, and became stable at 18 months. The mean serum TSH level increased mildly at 6 months after radiotherapy and more steeply after 18 months. At 18 months after radiotherapy, 12 patients had primary hypothyroidism with an elevated serum TSH, in which 4 of them also presented with low serum fT4. There was a significant difference (p = 0.014) in the mean thyroid doses between patients with hypothyroidism and normal thyroid function.

CONCLUSIONS

Radiotherapy for patients with NPC caused radiation-induced changes of the thyroid gland. The shrinkage of the gland was greatest in the first 6 months after radiotherapy, whereas the serum fT4 and TSH levels changed at 12 months. Radiation-induced changes were dependent on the mean dose to the gland. Therefore, measures to reduce the thyroid dose in radiotherapy should be considered.

BACKGROUND

Weight loss leads to reduced resting energy expenditure (REE) independent of fat-free mass (FFM) and fat mass (FM) loss, but the effect of changes in FFM composition is unclear.

OBJECTIVE

We hypothesized that a decrease in REE adjusted for FFM with weight loss would be partly explained by a disproportionate loss in the high metabolic activity component of FFM.

METHODS

Forty-five overweight and obese women [body mass index (in kg/m(2)): 28.7-46.8] aged 22-46 y followed a low-calorie diet for 12.7 +/- 2.2 wk. Body composition was measured by magnetic resonance imaging, dual-energy X-ray absorptiometry, and a 4-compartment model. REE measured by indirect calorimetry (REEm) was compared with REE calculated from detailed body-composition analysis (REEc) by using specific organ metabolic rates (ie, organ REE/mass).

RESULTS

Weight loss was 9.5 +/- 3.4 kg (8.0 +/- 2.9 kg FM and 1.5 +/- 3.1 kg FFM). Decreases in REE (-8%), free triiodothyronine concentrations (-8%), muscle (-3%), heart (-5%), liver (-4%), and kidney mass (-6%) were observed (all P < 0.05). Relative loss in organ mass was significantly higher (P < 0.01) than was the change in low metabolically active FFM components (muscle, bone, and residual mass). After weight loss, REEm - REEc decreased from 0.24 +/- 0.58 to 0.01 +/- 0.44 MJ/d (P = 0.01) and correlated with the decrease in free triiodothyronine concentrations (r = 0.33, P < 0.05). Women with high adaptive thermogenesis (defined as REEm - REEc < -0.17 MJ/d) had less weight loss and conserved FFM, liver, and kidney mass.

CONCLUSIONS

After weight loss, almost 50% of the decrease in REEm was explained by losses in FFM and FM. The variability in REEm explained by body composition increased to 60% by also considering the weight of individual organs.

BACKGROUND

While overt thyroid disease is a well known risk factor for infertility, the potential consequences of mild thyroid dysfunction or thyroid autoimmunity remain unknown. Experimental studies suggest a considerable role for thyroid hormone in the physiological mechanisms of ovarian reserve, but translation of such findings to human studies remains rare. A potential role for thyroid function in female reproduction could be especially relevant when the cause of infertility remains unknown, such as in women with diminished ovarian reserve (DOR) or unexplained infertility. The aims of this study were to investigate the association of thyroid function and autoimmunity with markers of ovarian reserve day 3 follicle-stimulating hormone (FSH) concentrations and antral follicle count (AFC), and to investigate whether thyroid function or autoimmunity may have different effects in women with DOR or unexplained infertility.

METHODS

Thyrotropin, free thyroxine, thyroxine, free triiodothyronine (fT3), triiodothyronine, thyroid peroxidase antibodies (TPOAbs), and thyroglobulin antibodies (TgAbs), as well as AFC and the day 3 FSH concentration, were measured among women seeking fertility treatment at the Massachusetts General Hospital Fertility Center. Multiple linear or mixed regression models were used to study the association of thyroid function or autoimmunity with AFC or day 3 FSH.

RESULTS

In the total study population (436 women, 530 AFC measurements), there was no association of thyroid function or TPOAb positivity with AFC. However, TgAb positivity was associated with a higher AFC (mean difference = 3.4 [95% confidence interval (CI) 1.8-5.1], p < 0.001). In women with DOR or unexplained infertility, lower fT3 and TPOAb positivity were associated with a lower AFC (fT3: continuous nonlinear association, p = 0.009; TPOAb positivity: -2.3 follicles [confidence interval -3.8 to -0.5], p = 0.01), while TgAb positivity was not associated with AFC. Neither thyroid function nor thyroid antibody positivity was associated with the day 3 FSH concentration.

CONCLUSIONS

This study found that lower fT3 and TPOAb positivity are associated with a lower AFC in women with DOR or unexplained infertility. Future studies are required to replicate these findings and further elucidate the role of TgAbs and underlying mechanisms through which thyroid function and autoimmunity is associated with ovarian reserve.

Thyroid hormones (THs) are primarily responsible for the regulation of energy balance and metabolism, suggesting that TH levels may contribute to the development of type 2 diabetes mellitus (T2DM). However, few studies have investigated the relationship between TH and T2DM in a general population. The aim of this study was to evaluate whether serum TH levels within the reference range are related to T2DM.

A cross-sectional study (n = 15,296) was performed in Tianjin, China. Serum free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) levels were measured by chemiluminescence immunoassay, and T2DM was defined according to the American Diabetes Association criteria. Multiple logistic regression models were used to assess the sex-specific relationships between FT3, FT4, FT3/FT4 ratios, and TSH quintiles and T2DM.

The prevalence of T2DM was 16.2% in males and 7.7% in females. In males, the multivariable-adjusted odds ratios (95% confidence interval) of T2DM for increasing quintiles of FT3, FT4, and FT3/FT4 ratios were 1.00, 0.75(0.63 to 0.89), 0.70(0.58 to 0.84), 0.63(0.52 to 0.76), 0.56(0.46 to 0.68; P for trend < 0.0001); 1.00, 1.05(0.87 to 1.27), 1.16(0.96 to 1.40), 1.09(0.90 to 1.31), 1.29(1.07 to 1.56; P for trend = 0.01); and 1.00, 0.69(0.58 to 0.83), 0.72(0.60 to 0.86), 0.59(0.48 to 0.71), and 0.55(0.46 to 0.66; P for trend < 0.0001), respectively. Similar results also were observed in females. In contrast, a strong negative correlation between TSH and T2DM was observed in males, but not in females.

This study demonstrated that decreased FT3, FT3/FT4 ratios, and increased FT4 levels are independently related to a higher prevalence of T2DM in both males and females, and TSH is inversely related to T2DM in males only.

Measurements of blood glucose and plasma free fatty acids (FFA), thyroxine (T4), free thyroxine (FT4), triiodothyronine (T3), and thyroid-stimulating hormone (TSH) were made on samples taken from fed and fasted human subjects while at rest and immediately after 20 min moderate exercise. Six subjects were studied on successive weeks before (LA1), during (HA1, HA2, HA3), and after (LA2) a 3-wk sojourn at high altitude (3,650 m). The subjects and location were the same as those used for the energy expenditure measurements described in the preceding paper (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 45:345--349, 1978). The most marked effect of altitude was to potentiate the rise in FFA due to exercise. This effect was most noticeable in fed subjects during HA1 and HA2. Changes in the plasma levels of the thyroid hormones correlated with the FFA changes and, once again, exercise at altitude caused the greatest increase in circulating levels. Possible causes of the parallel changes in FFA and thyroid hormone levels and their relationship to changes in energy metabolism are discussed.

Thyroid function was investigated in a group of 21 patients with severe senile dementia of the Alzheimer type (SDAT) and in a group of 17 age and sex matched normal controls. Free thyroid hormone levels (triiodothyronine (T3) and thyroxine (T4) were measured, as were also the thyrotrophin (TSH), prolactin (PRL) and growth hormone (GH) responses to thyrotrophin releasing hormone (TRH)). When compared to controls, patients demonstrated a significantly lower free T3 value (but not free T4), a blunted TSH response to TRH, slightly elevated basal PRL and GH values and a small GH response to TRH. However, all differences were small in biological terms and were within the laboratory's normal range. This emphasizes the relative normality of neuroendocrine function, particularly thyroid status, in SDAT.