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In differentiated thyroid cancer (DTC), the standard treatment includes total thyroidectomy and lifetime levothyroxine (LT4) replacement. However, long-term exogenous LT4 has become controversial due to the adverse effects of oversuppression. The study included 191 patients (aged 18-76 years) with a prospective diagnosis of non-metastatic DTC and 79 healthy individuals. The patients with DTC were stratified into three groups according to their TSH levels: suppressed thyrotropin if TSH was below 0.1 μIU/ml, mildly suppressed thyrotropin if TSH was between 0.11 and 0.49 μIU/ml, and low-normal thyrotropin if THS was between 0.5 and 2 μIU/ml. The Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Anxiety Sensitivity Index (ASI), Short Symptom Inventory (SSI), and Pittsburgh Sleep Quality Index (PSQI) were administered to all participants. It was found that the BDI, BAI, SSI and PSQI scores were worse in patients with DTC (p=0.024, p=0.014, p=0.012, and p=0.001, respectively). According to theTSH levels, the mean ASI was found to be higher in the suppressed and mildly suppressed thyrotropin groups (19±14.4 vs. 10.6±11.1; 16.4±14.9 vs. 10.6±11.1, p=0.024, respectively), the mean SSI was found higher in the suppressed group (61.0±55.5 vs. 35.1±37.0, p=0.046), and the mean PSQI was higher in all three groups (7.94±3.97 vs. 5.35±4.13; 7.21±4.59 vs. 5.35±4.13; 7.13±4.62 vs. 5.35±4.13, p=0.006) when compared with the controls. No significant difference was found between the groups. A positive correlation was detected in the duration of LT4 use and BDI and SSI, and a weak, negative correlation was detected between TSH levels and ASI and PSQI. Based on our study, it was found that depression, anxiety disorders, and sleep problems were more prevalent in patients with DTC, being more prominent in the suppressed TSH group. These results were inversely correlated with TSH values and positively correlated with the duration of LT4 use. Unnecessary LT4 oversuppression should be avoided in patients with DTC., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Inhibition of hypoxia-inducible factor prolyl hydroxylase (HIF-PH) is a novel choice for the treatment of renal anemia, and an oral HIF-PH inhibitor roxadustat was approved for renal anemia. Roxadustat has high affinity to thyroid hormone receptor beta, which may affect thyroid hormone homeostasis., Case Presentation: We present here a patient undergoing hemodialysis with primary hypothyroidism receiving levothyroxine replacement, who showed decreased free thyroxine (FT4) and thyroid stimulating hormone (TSH) after starting roxadustat. Pituitary stimulation test revealed selective suppression of TSH secretion. Recovery of TSH and FT4 levels after stopping roxadustat suggested the suppression of TSH was reversible., Conclusions: Physicians should pay special attention to thyroid hormone abnormalities in treatment with roxadustat.

Introduction: Administration of testosterone or dehydroepiandrosterone to subjects with low levels of these hormones was found to reduce thyroid antibody titres. Male-pattern baldness is accompanied by mildly increased androgen levels. The present study was aimed at investigating whether early-onset androgenetic alopecia determines the impact of exogenous levothyroxine on thyroid autoimmunity and hypothalamic-pituitary-thyroid axis activity in young men with autoimmune hypothyroidism., Material and Methods: The study included 2 thyroid-antibody-matched groups of men with autoimmune hypothyroidism: subjects with early-onset androgenetic alopecia (group 1; n = 24) and subjects with no evidence of hair loss (group 2; n = 24). All patients were treated with exogenous levothyroxine. Circulating titres of thyroid peroxidase and thyroglobulin antibodies, as well as levels of thyrotropin, free thyroxine, free triiodothyronine, prolactin, total testosterone, calculated bioavailable testosterone, dehydroepiandrosterone-sulphate, and oestradiol were measured before levothyroxine treatment and 6 months later., Results: In both study groups, levothyroxine decreased thyroid antibody titres, reduced thyrotropin levels and increased free thyroid hormone levels. However, these effects were less pronounced in the men with early-onset male-pattern baldness than in the control men. The degree of reduction in antibody titres and thyrotropin levels correlated with baseline levels of total and calculated bioavailable testosterone, as well with baseline insulin sensitivity and treatment-induced improvement in insulin sensitivity. Concentrations of the remaining variables remained unchanged throughout the study period., Conclusions: The results of the current study suggest that the benefits of levothyroxine therapy in men with autoimmune hypothyroidism are less pronounced in individuals with early-onset androgenetic alopecia.

Thyroid stimulating hormone (TSH) suppression therapy after thyroid carcinoma surgery could lead to cognitive impairment. But, the possible mechanism of TSH suppression therapy impairs cognitive function is yet unknown. In this study, forty Wistar rats were randomized into the sham operation control (OC), total thyroidectomy (TD), thyroxine replacement therapy (TR), and TSH suppression therapy (TS) groups. We observed that compared to the OC group, escape latency on 1-4 days was significantly prolonged in the TD and TS groups, and the number of rats crossing the virtual platform was significantly reduced in the TD and TS groups. In the TD, TR, and TS groups, the residence time in the target quadrant was significantly decreased, while the activity distance in the target quadrant in the TD group was significantly decreased compared with OC group. In the TD and TS groups, the pyramidal cells in the hippocampal CA1 region showed a disordered arrangement. The cytoplasm was lightly stained, the cells were swollen and round, and spotty liquefaction necrosis could be observed. Compared to the OC group, hippocampal p-mTOR and p-p70s6k levels were significantly decreased in the TD group, while no significant changes were detected in the TR group. Hippocampal p-mTOR and p-p70s6k amounts in the TS group were significantly increased compared with OC group. These results indicated that TSH suppression therapy after total thyroidectomy in rats could impair cognitive function, which might be related to the activation of the mTOR signaling pathway and the damage and necrosis of hippocampal neurons.

Tyrosine kinase inhibitors are widely utilized in veterinary oncology for the treatment of mast cell and solid tumours. In man, these drugs are associated with thyroid dysfunction: however, to date only one study has investigated this in dogs. The aim of this study was to prospectively assess thyroid function in a group of dogs with cancer receiving toceranib. Thirty-four dogs were prospectively enrolled at two referral hospitals into two groups; those receiving toceranib with prednisolone and those receiving toceranib alone. Total thyroxine (TT4) and thyroid stimulating hormone (TSH) was monitored at regular time points during treatment. Follow-up data was available for 19 dogs. Overall, 12 incidences of elevated TSH occurred but none of these dogs had concurrent low TT4 concentrations. There was a significant difference in median TSH at week six compared with baseline. Hypothyroidism was not diagnosed in any patient during the study period. Patient drop-out was higher than anticipated which prevented the assessment of longer term toceranib administration on thyroid function. Toceranib therapy was not associated with hypothyroidism in this study but did result in elevations in TSH which confirms what has been previously reported. Toceranib should be considered to cause thyroid dysfunction in dogs and monitoring is advised., (© 2019 John Wiley & Sons Ltd.)

A 69-year-old woman with a remote history of Graves' disease treated with radioactive iodine ablation, who was maintained on a stable dose of levothyroxine for 15 years, presented with abnormal and fluctuating thyroid function tests which were confusing. After extensive evaluation, no diagnosis could be made, and it became difficult to optimise the levothyroxine dose, until we became aware of the recently recognised biotin-induced lab interference. It was then noticed that her medication list included biotin 10 mg two times per day. After holding the biotin and repeating the thyroid function tests, the labs made more sense, and the patient was easily made euthyroid with appropriate dose adjustment. We also investigated our own laboratory, and identified the thyroid labs that are performed with biotin-containing assays and developed strategies to increase the awareness about this lab artefact in our clinics., Competing Interests: Competing interests: For SA Abbott Diagnostics (Consultant), since October 2019. Related to biotin interference with labs. This COI is recent and it started after we began writing the case up. The company approached SA given his prior published work on biotin.The other authors have no competing interests., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Graves' disease is associated with thyrotropin receptor (TSHR) antibodies of variable bioactivity. Recently, antibodies have been characterized that bind to the cleavage region of the TSHR ectodomain (C-TSHR-Ab), and their ability to induce thyroid cell apoptosis in vitro via excessive cell stress involving multiple organelles was demonstrated. Methods: To investigate the in vivo effects of C-TSHR-Ab, first a murine monoclonal antibody (mAb) directed against residues 337 to 356 of the TSHR cleavage region was developed, and then it was injected into mice. Results: These injections caused reduced serum total triiodothyronine and thyroxine and increased TSH levels compared to control mAb-injected mice. The C-TSHR-mAb induced histological evidence of endoplasmic reticulum stress, mitochondrial stress, and apoptosis in the thyroid glands. C-TSHR-mAb-mediated apoptosis was associated with cellular infiltrates consisting mostly of macrophages, dendritic cells, and neutrophils, while T- and B-lymphocytes were scarce. In addition, in the treated mouse thyroid tissue, hyper-citrullination of histone H3 was also found. This is known to occur via peptidylarginine deiminase 4 and plays an important role in the formation of neutrophil extracellular traps, which are likely to be partly responsible for thyroid infiltration, as seen in many autoimmune diseases. Examination of thyroid tissue from patients with Graves' disease also showed increased stress and some thyrocyte apoptosis compared to normal thyroid tissues. Conclusions: The fact that the C-TSHR-mAb induced accumulation of macrophages, neutrophils, and dendritic cells indicates that innate immunity plays a central role in shaping the adaptive immune response to the TSHR. In addition, this study provides further evidence that the hinge region of the TSHR ectodomain is intimately involved in the immune response in autoimmune thyroid disease.

Thyroid hormone suppression therapy is designed to lower serum thyrotropin (TSH) levels using doses of thyroid hormone in excess of what would normally be required to maintain a euthyroid state. The basis of this therapy is the knowledge that TSH is a growth factor for thyroid cancer, so that lower serum TSH levels might be associated with decreased disease activity. However, clinical studies have not documented improved outcomes with TSH suppression, except in patients with the most advanced disease. Furthermore, there are a number of negative outcomes related to aggressive thyroid hormone therapy, including osteoporosis, fracture, and cardiovascular disease. Therefore, a graded approach to TSH suppression is recommended by the American Thyroid Association, based on initial risk and ongoing risk assessment., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Although previous studies have investigated the influence of antiepileptic drugs (AEDs) on lipid profiles and thyroid hormone levels, there is little evidence regarding the effects of levetiracetam (LEV). Therefore, we conducted a prospective longitudinal study to evaluate the effects of LEV and carbamazepine (CBZ) treatment on lipid profile and thyroid hormone levels in patients newly diagnosed with epilepsy. Inclusion criteria were as follows: (a) age between 4 and 15 years, (b) diagnosis of epilepsy with at least two focal seizures within a year, and (c) newly treated with LEV or CBZ monotherapy. Serum lipid profile and thyroid hormone levels were measured before and after 1 and 6 months of AED initiation. Among the 21 included patients (LEV: 13 patients, CBZ: 8 patients), all but one patient in the LEV group continued AED monotherapy during the study period. Although triglyceride (TG) levels tended to be increased in the CBZ group (baseline: 58.3 ± 22.0 mg/dl, 1 month: 63.8 ± 21.6 mg/dl, 6 months: 92.3 ± 63.6 mg/dl, p = 0.22, analyses of variance (ANOVA)), there were no significant changes in total cholesterol (TC), TG levels, high-density lipoprotein cholesterol (HDL-C), or low-density lipoprotein cholesterol (LDL-C) in either group. Serum free thyroxine (fT4) levels were significantly decreased in the CBZ group (baseline: 1.15 ± 0.06 ng/dl, 1 month: 1.00 ± 0.16 ng/dl, 6 months: 0.98 ± 0.14 ng/dl, p = 0.03, ANOVA). In contrast, there were no significant changes in fT4 or thyroid-stimulating hormone (TSH) levels in the LEV group. The results of the present study suggest that LEV monotherapy does not affect lipid profile or thyroid function while CBZ monotherapy may cause thyroid dysfunction., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Both vitamin D preparations and high-dose statin therapy were found to reduce thyroid antibody titers., Objective: The purpose of this study was to assess whether vitamin D status determines the effect of statin therapy on thyroid autoimmunity., Methods: The study population consisted of 39 euthyroid women with Hashimoto's thyroiditis and moderate or moderately high cardiovascular risk divided into two groups: women with vitamin D deficiency or insufficiency (group A; n=19) and women with normal vitamin D status (group B, n=20). All patients received atorvastatin therapy (20-40 mg daily) for the following 6 months. Plasma lipids, circulating levels of thyrotropin, free thyroid hormones, prolactin and 25-hydroxyvitamin D, titers of thyroid peroxidase and thyroglobulin antibodies, as well as Jostel's, the SPINA-GT and the SPINA-GD indices were assessed at the beginning and at the end of the study., Results: The study completed all women. At baseline, with the exception of 25-hydroxyvitamin D, there were no significant differences between both study groups in plasma lipids, circulating hormone levels and titers of thyroid peroxidase and thyroglobulin antibodies. Despite improving plasma lipids in both study groups, atorvastatin reduced thyroid antibody titers only in women with normal vitamin D status. Moreover, in this group of patients, atorvastatin increased the SPINA-GT index. Circulating levels of the measured hormones, Jostel's thyrotropin index and the SPINA-GD index remained at a similar level throughout the study., Conclusions: The results of the study suggest that the effect of atorvastatin therapy on thyroid autoimmunity depends on vitamin D status., Competing Interests: No conflict of interest has been declared by the authors., (© Georg Thieme Verlag KG Stuttgart · New York.)

Myo-inositol (Myo-Ins) plays an important role in thyroid function and autoimmunity. Myo-Ins is the precursor for the synthesis of phosphoinositides, which takes part in the phosphatidylinositol (PtdIns) signal transduction pathway, and plays a decisive role in several cellular processes. In the thyroid cells, PtdIns is involved in the intracellular thyroid-stimulating hormone (TSH) signaling, via Phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3) (PIP-3). Moreover, the phosphatidyl inositol 3 kinases (PI3K) family of lipid kinases regulates diverse aspects of T, B, and Tregs lymphocyte behaviour. Different mouse models deficient for the molecules involved in the PIP3 pathway suggest that impairment of PIP3 signaling leads to dysregulation of immune responses and, sometimes, autoimmunity. Studies have shown that cytokines modulate Myo-Ins in thyroid cells. Moreover, clinical studies have shown that after treatment with Myo-inositol plus seleniomethionine (Myo-Ins + Se), TSH levels significantly declined in patients with subclinical hypothyroidism due to autoimmune thyroiditis. The treatment was accompanied by a decline of antithyroid autoantibodies. After treatment serum CXCL10 levels declined, confirming the immune-modulatory effect of Myo-Ins. Additional research is necessary in larger population to evaluate the effect on the quality of life, and to study the mechanism of the effect on chemokines.

Background: Disturbances in thyroid function have been associated with use of psychotropic drugs, including antipsychotics. Still, the thyroid function in relation to commonly prescribed antipsychotic drugs and polypharmacy is not fully known. We investigated thyroid function associated with use of antipsychotics in patients with psychotic disorders compared with healthy controls., Methods: We included 1345 patients and 989 healthy controls from the Thematically Organized Psychosis (TOP) study, recruiting participants between 18 and 65 years of age in the Oslo-area. All patients underwent a thorough clinical investigation and assessment of medication data. Thyroid function was determined from plasma levels of free thyroxin (fT4) and thyroid-stimulating hormone (TSH). Multiple linear regression analyses were performed to evaluate the association between thyroid parameters and use of antipsychotics, and monotherapy users of olanzapine, quetiapine, aripiprazole or risperidone (N = 473) were investigated separately., Results: We found lower levels of fT4 (median 13.70 vs 14.00, p < 0.001) in patients compared to healthy controls, and a prevalence of 12.9% of previously undiagnosed deviant thyroid states in the patient group. Lower fT4 levels was associated with use of antipsychotics in general (p = 0.001), and quetiapine (p = 0.003) and olanzapine (p = 0.018) in particular, while the associations with TSH were non-significant. Using antipsychotics in combination with other psychotropic drugs, and with antidepressants in particular, was associated with lower fT4 level (p < 0.001) than use of antipsychotics alone., Conclusions: Our findings indicate an association between use of antipsychotics and lower fT4. Clinicians should be aware that patients using quetiapine, olanzapine or antipsychotics in psychotropic polypharmacy are especially at risk., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: TSH-suppression is a therapy for thyroid cancer management, but it may lead to adverse effects, which should be balanced with its benefits. Previous studies evaluating the consequences of TSH suppression on insulin sensitivity have only been done with indirect techniques, and results were controversial. Therefore, we aimed to assess insulin sensitivity in patients with thyroid cancer and suppressed thyroid-stimulating hormone (TSH) with the most appropriate direct method (hyperinsulinemic-euglycemic clamp) in order to get a more conclusive response about the topic., Methods: A group of 20 non-obese and non-diabetic thyroid cancer patients with suppressed TSH underwent a hyperinsulinemic-euglycemic clamp to evaluate insulin sensitivity. Their results were compared to the results of a sex and body mass index (BMI) -paired control group composed of 20 healthy volunteers., Results: Patients were all female, aged 36.8 ± 10.2 years-old, with mean TSH 0.1 ± 0.1 μIU/mL and mean BMI 26.2 ± 3.3 kg/m 2 . Insulin sensitivity, determined by the insulin-stimulated glucose uptake (M-value), was lower in the patients group (4.2 ± 1.6 mg/min*kg versus 5.8 ± 1.7, age-adjusted p-value = 0.0205)., Conclusion: This study shows for the first time that subclinical thyrotoxicosis in patients with thyroid cancer is associated with insulin resistance, as measured by hyperinsulinemic-euglycemic clamp technique. Such finding may be taken into consideration by clinicians when balancing risks and benefits of TSH-suppression therapy in thyroid cancer patients.

Objectives: Thyroid gland regulates the body's metabolic rate and plays an exquisitely important role in the human health. Fluoride exposure can affect thyroid function. Curcumin is a potent antioxidant that works through several mechanisms. The aim of the present study was to demonstrate the hormonal, histological, and ultrastructural changes occurred in the thyroid gland induced by exposure to sodium fluoride (NaF) and study the possible protective effect of curcumin on the NaF-induced effects., Methods: Thirty male albino rats were randomly divided into 3 equal groups (10 rats each): the control group, NaF group, and NaF+Curcumin (NaF+Cur) group. Thyroid-stimulating hormone (TSH), triiodothyronine (T3) and thyroxine (T4) levels were assayed and thyroid tissues processed for light and transmission electron microscopic study., Results: In NaF group, serum T3 and T4 levels were significantly decreased whereas TSH level was significantly increased compared to the control group. Thyroid tissues showed flattening of the epithelial lining with several follicular cell degenerations, hyperplasia, decreased colloid, disrupted basement membrane, cytoplasmic vacuolations, degenerated mitochondria, widening of rough endoplasmic reticulum cisternae, and vascular congestion compared to the control group. In the NaF+Cur group, serum TSH levels were significantly decreased in comparison with NaF group and no significant difference in comparison with the control group. Thyroid sections appeared apparently normal compared to the control group and NaF group., Conclusions: Sodium fluoride affected both the function and structure of the thyroid gland while curcumin was protective against these toxic effects.

The elevated fluoride from drinking water impacts on T 3 , T 4 and TSH hormones. The aim was study impacts of drinking water fluoride on T 3 , T 4 and TSH hormones inYGA (Yazd Greater Area). In this case- control study 198 cases and 213 controls were selected. Fluoride was determined by the SPADNS Colorimetric Method. T 3 , T 4 and TSH hormones tested in the Yazd central laboratory by RIA (Radio Immuno Assay) method. The average amount of TSH and T 3 hormones based on the levels of fluoride in two concentration levels 0-0.29 and 0.3-0.5 (mg/L) was statistically significant (P = 0.001 for controls and P = 0.001 for cases). In multivariate regression logistic analysis, independent variable associated with Hypothyroidism were: gender (odds ratio: 2.5, CI 95%: 1.6-3.9), family history of thyroid disease (odds ratio: 2.7, CI 95%: 1.6-4.6), exercise (odds ratio: 5.34, CI 95%: 3.2-9), Diabetes (odds ratio: 3.7, CI 95%: 1.7-8), Hypertension (odds ratio: 3.2, CI 95%: 1.3-8.2), water consumption (odds ratio: 4, CI 95%: 1.2-14). It was found that fluoride has impacts on TSH, T 3 hormones even in the standard concentration of less than 0.5 mg/L. Application of standard household water purification devices was recommended for hypothyroidism.

Background: In the management of differentiated thyroid carcinoma, surgery with or without postoperative radioiodine, and thyroid-stimulating hormone (TSH) suppression is the standard of care in most patients. Levothyroxine is recommended for long-term TSH suppression. For some patients, this may be difficult to tolerate due to adverse effects, such as impaired cognitive function., Methods: This article reviews the evidence for the role of combination treatment with triiodothyronine (T3) and levothyroxine (T4) in these patients., Results: The evidence for combination T3 and T4 treatment comes mainly from studies on hypothyroidism, and research into its use for TSH suppression is limited., Conclusion: Although the evidence base is not strong, there is a small group of patients who may benefit from combination T3 and T4 treatment due to difficulty tolerating thyroxine. Until further evidence is available, a case-by-case approach is recommended., (© 2017 Wiley Periodicals, Inc.)

Background: Delayed thyroid-stimulating hormone (TSH) recovery during treatment of Graves' disease is caused by long-term excessive thyroid hormone, which results in downregulation of pituitary thyrotrophs. However, it is unknown whether delayed TSH recovery exists after levothyroxine (LT4) dose reduction in patients with differentiated thyroid cancer (DTC) after long-term TSH suppression., Methods: We retrospectively reviewed 97 DTC patients with LT4 dose reduction after long-term TSH suppression. TSH levels at baseline (point 1), 6 months (point 2) and 12-18 months (point 3) after LT4 dose reduction were compared. A delayed TSH recovery group whose TSH levels changed to upper target TSH category (2015 revised ATA guidelines) from point 2 to point 3 was identified, and risk factors were analysed., Results: The median TSH level at point 3 was significantly higher than that of point 2 (0.17 vs 0.09 mIU/L; P<.001). The delayed TSH recovery group (44.3%) showed increased body weight (60.84 vs 62.73 kg; P=.01), while normal response group did not. Greater reduction (%) in the LT4 dose per weight [HR 1.10, 95% CI (1.00-1.22), P=.04] and higher BMI before thyroid surgery [1.19, 1.03-1.38, P=.01] predicted the occurrence of delayed TSH recovery, while higher dose of LT4 per weight after reduction showed preventive effect [HR 0.01, 95% CI (0.00-0.54); P=.02]., Conclusions: Delayed TSH recovery was common during LT4 dose reduction after long-term TSH suppression for DTC management. Six months may not be enough for TSH recovery and to evaluate thyroid hormone status by serum TSH., (© 2017 John Wiley & Sons Ltd.)

Differentiated thyroid cancer is the most common form of thyroid cancer and its prognosis is favourable in most cases. Suppression of thyroid stimulating hormone (TSH) by supra-physiological thyroid hormone replacement has been the mainstay of long-term management for over 60 years. However, evidence for a beneficial outcome of TSH suppression is conflicting and intervention must be balanced against adverse effects, particularly affecting the cardiovascular system and skeleton. Here we discuss the role of TSH suppression in the long-term management of differentiated thyroid cancer in the context of risk stratification for disease recurrence and the latest clinical guidelines., (Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background: Fine-needle aspiration biopsy (FNAB) cannot distinguish a follicular thyroid carcinoma (FTC) from a follicular adenoma in follicular lesions. We designed this study to determine whether the preoperative thyroglobulin (Tg) and change in serum Tg during thyroid-stimulating hormone (TSH) suppression can predict FTC in thyroid nodules with a cytological diagnosis of follicular lesion., Methods: Among 854 patients who underwent thyroid surgery, the 198 patients who presented with thyroid nodules with a cytological diagnosis of follicular lesion were analyzed. Predictive factors for malignancy were evaluated using multivariate logistic regression models. Subgroup analyses of patients with TSH suppression therapy by levothyroxine were also conducted., Results: Thirty-two patients (16%) had FTC, and 166 patients had confirmed benign nodules. The median preoperative serum Tg levels were significantly higher in patients with FTC compared to those with benign pathology (449 vs. 34 ng/mL, p < 0.001). The serum Tg (odds ratios (OR) 10.311, p < 0.001) and tumor volume (OR 4.500, p = 0.035) were found to be independent predictors for FTC in all patients with a cytological diagnosis of follicular lesion. Forty-eight patients received TSH suppression therapy. When we performed subgroup analyses on the patients with TSH suppression therapy, decrease less than 15% in serum Tg during TSH suppression was found to be an independent predictor of FTC (OR 13.918, p = 0.018)., Conclusion: Preoperative serum Tg and changes in serum Tg during TSH suppression independently predict FTC in thyroid nodules with a cytological diagnosis of follicular lesion.

Introduction: Glucocorticoids represent the therapy of choice for active and moderate-to-severe Graves' orbitopathy (GO). In some patients, rituximab, a monoclonal antibody against the cluster of differentiation (CD) 20 receptor of B-lymphocytes, can serve as a second-line or an alternative treatment. The effect of very low-dose of rituximab on the clinical activity of GO and corresponding clinical or laboratory changes is reported., Material and Methods: Changes of Clinical Activity Score (CAS) for GO, proptosis, levels of thyroid-stimulating hormone receptor antibodies, and depletion of CD19+ and CD20+ B-lymphocytes were determined in ten patients (two men and eight women) with active moderate-to-severe GO treated with a single 100-mg dose of rituximab. Correlations between differences of clinical and laboratory parameters were performed., Results: A significant decrease of CAS was found during subsequent examinations compared to the baseline values. A significant depletion of CD19+ and CD20+ B-lymphocytes was detected after rituximab administration. Differences between follow-up and baseline levels of CD20+ positively correlated with differences in CAS after six (p < 0.05) and 12 months (p < 0.01). Differences in CD19+ levels correlated with differences in CAS after 12 months (p < 0.05) of the treatment. Two patients developed dysthyroid optic neuropathy (DON) requiring orbital decompression. No other rituximab side effects were reported during the whole study duration., Conclusions: A single very low-dose of rituximab appears to be very well tolerated and effective enough to reduce clinical activity in active moderate-to-severe GO patients without impending DON.

Objective: To compare the effects of a unique fixed combination levothyroxine/liothyronine (LT4/LT3) therapy in patients with primary hypothyroidism., Subjects and Methods: This is a randomized, double-blind, crossover study. Adults with primary hypothyroidism (n = 32, age 42.6 ± 13.3, 30 females) on stable doses of LT4 for ≥ 6 months (125 or 150 μg/day) were randomized to continue LT4 treatment (G1) or to start LT4/LT3 therapy (75/15 μg/day; G2). After 8 weeks, participants switched treatments for 8 more weeks. Thyroid function, lipid profile, plasma glucose, body weight, electrocardiogram, vital signs, and quality of life (QoL) were evaluated at weeks 0, 8 and 16., Results: Free T4 levels were significantly lower while on LT4/LT3 (G1: 1.07 ± 0.29 vs. 1.65 ± 0.46; G2: 0.97 ± 0.26 vs. 1.63 ± 0.43 ng/dL; P < 0.001). TSH and T3 levels were not affected by type of therapy. More patients on LT4/LT3 had T3 levels above the upper limit (15% vs. 3%). The combination therapy led to an increase in heart rate, with no significant changes in electrocardiogram or arterial blood pressure. Lipid profile, body weight and QoL remained unchanged., Conclusions: The combination therapy yielded significantly lower free T4 levels, with no changes in TSH or T3 levels. More patients on LT4/T3 had elevated T3 levels, with no significant alterations in the evaluated outcomes. No clear clinical benefit of the studied formulation could be observed. Future trials need to evaluate different formulations and the impact of the combined therapy in select populations with genetic polymorphisms.

Objective: Investigate the differences in cardiopulmonary (CP) capacity and Quality of Life (QOL) between healthy elderly (≥ 65 years) with different TSH levels (< 1.0 and ≥ 1.0 μIU/mL) both within the normal range. Also, evaluate the effects of TSH elevation on CP test and QOL, by administering methimazole to subjects with initial lower-normal TSH, in order to elevate it to superior-normal limit., Materials and Methods: Initially, a cross-sectional study was performed to compare CP capacity at peak exercise and QOL (using WHOQOL-OLD questionnaire) between healthy seniors (age ≥ 65 years) with TSH < 1.0 μIU/mL vs. TSH ≥1.0 μIU/mL. In the second phase, participants with TSH < 1.0 μIU/mL were included in a non-controlled-prospective-interventional study to investigate the effect of TSH elevation, using methimazole, on QOL and CP capacity at peak exercise., Results: From 89 elderly evaluated, 75 had TSH ≥ 1 μIU/mL and 14 TSH < 1 μIU/mL. The two groups had similar basal clinical characteristics. No difference in WHOQOL-OLD scores was observed between groups and they did not differ in terms of CP function at peak exercise. QOL and CP variables were not correlated with TSH levels. Twelve of 14 participants with TSH < 1.0 μIU/mL entered in the prospective study. After one year, no significant differences in clinical caracteristics, QOL, and CP variables were detected in paired analysis before and after methimazole intervention., Conclusions: We found no differences in CP capacity and QOL between health elderly with different TSH levels within normal range and no impact after one year of methimazole treatment. More prospective-controlled-randomized studies are necessary to confirm or not the possible harm effect in normal low TSH.

Medications administered during the neonatal period may mask the diagnosis of congenital hypothyroidism. Herein, we report a case of undiagnosed congenital hypothyroidism while the infant was on treatment with dopamine. Given the inhibitory effect of dopamine on thyroid-stimulating hormone, a high index of suspicion for potential congenital hypothyroidism is needed in such neonates., (© The Author [2015]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: Selenium is present in the active site of proteins important for thyroid hormone synthesis and metabolism. The objective of this study is to investigate the effect of selenium supplementation in different doses on thyroid function, under conditions of suboptimal dietary selenium intake., Design: The Danish PREvention of Cancer by Intervention with SElenium pilot study (DK-PRECISE) is a randomized, double-blinded, placebo-controlled trial. A total of 491 males and females aged 60-74 years were randomized to 100 μg (n=124), 200 μg (n=122), or 300 μg (n=119) selenium-enriched yeast or matching yeast-based placebo tablets (n=126). A total of 361 participants, equally distributed across treatment groups, completed the 5-year intervention period., Methods: Plasma samples were analyzed for selenium and serum samples for TSH, free triiodothyronine (FT3), and free thyroxine (FT4) at baseline, and after 6 months, and 5 years of supplementation., Results: Plasma selenium concentrations increased significantly and dose-dependently in treatment groups receiving selenium (P<0.001). Serum TSH and FT4 concentrations decreased significantly and dose-dependently by 0.066 mIU/l (P=0.010) and 0.11 pmol/l (P=0.015), respectively, per 100 μg/day increase, with insignificant differences between 6 months and 5 years. No significant effects were found for FT3 and FT3:FT4 ratio., Conclusions: In euthyroid subjects, selenium supplementation minutely and dose-dependently affects thyroid function, when compared with placebo, by decreasing serum TSH and FT4 concentrations. Based on these findings, selenium supplementation is not warranted under conditions of marginal selenium deficiency. However, a role for selenium supplementation in the treatment of autoimmune thyroid diseases is still unresolved., (© 2015 European Society of Endocrinology.)

Background: Thyroid hormones (TH) are regulated by the hypothalamic-pituitary axis, which plays an important role in cell growth, differentiation, development and other aspects of metabolism. It is believed that an active hypothalamic-pituitary axis increases the susceptibility of thyroid dysfunction during systemic chemotherapy. In order to investigate the relation between thyroid function and chemotherapy the present study was designed to investigate TH in breast cancer patients receiving at least three cycles of chemotherapy. The levels of TH were measured at the baseline and before each cycle of chemotherapy., Materials and Methods: Blood samples for estimation of TH levels were collected from 80 (pre-menopausal-40; post-menopausal-40) breast cancer patients just before they were undergoing--1st, 2nd, 3rd and 4th cycle of chemotherapy. The serum was separated and T3, T4 and TSH levels were determined by chemiluminescence method., Results: T3 and T4 were found significantly decreased and TSH was found significantly increased after 1st (p<0.001), 2nd (p<0.0001) and 3rd cycle of chemotherapy (p<0.0001). The variation of T3 levels (decreased) and TSH levels (increased) was found more in post-menopausal (p<0.0001) women then in pre-menopausal women after 3rd cycle of chemotherapy as compared to baseline (p<0.001)., Conclusions: TH were remarkably altered after each cycle of chemotherapy leading to decline in thyroid function of breast cancer patients. Further, the results also indicated that post- menopausal women were more prone towards decline in thyroid function then pre-menopausal women. The present study proposes the monitoring of TH after each cycle of chemotherapy in breast cancer patients.

Objective: The aim of this study was to determine the extent of drug interactions affecting levothyroxine, using study drugs often co-administered to patients on long-term levothyroxine therapy., Design: A retrospective population analysis linking biochemistry and prescription data between 1 January 1993 and 31 December 2012 was used., Patients: The study population was Tayside residents prescribed levothyroxine on at least three occasions, within a six-month period, prior to the start of a study drug. Individuals acted as their own controls pre- and postinitiation of study drug. Overall, 10 999 patients (mean age 58 years, 82% female) being treated with thyroxine were included in the study., Measurements: Changes in TSH following initiation of study drug., Results: Iron, calcium, proton pump inhibitors and oestrogen all increased serum TSH concentration: an increase of 0·22 mU/l (P < 0.001), 0·27 mU/l (P < 0·001), 0·12 mU/l (P < 0·01), and 0·08 mU/l (P < 0·007), respectively. For these four study drugs, there was a clinically significant increase of over 5 mU/l in serum TSH, in 7·5%, 4·4%, 5·6% and 4·3% patients, respectively. There was a decrease of 0·17 mU/l (P-value 0.01) in the TSH concentration for those patients on statins. The TSH decreased by 5 mU/l in 3·7% of patients. There was no effect with H2 receptor antagonists or glucocorticoids., Conclusion: This large population-based study demonstrates significant interaction between levothyroxine and iron, calcium, proton pump inhibitors, statins and oestrogens. These drugs may reduce the effectiveness of levothyroxine, and patients' TSH concentrations should be carefully monitored., (© 2014 John Wiley & Sons Ltd.)

Reduced sensitivity to thyroid hormones (RSTH) is a rare disease that affects about 3,000 individuals, belonging to about 1,000 families. It results from reduced intracellular action of thyroid hormones (TH) genetically determined and manifests as persistent hyperthyroxinemia with non-suppressed thyroid-stimulating hormone (TSH). We describe a 67-years old, Caucasian woman, with past history of subtotal thyroidectomy due to diffuse goiter, who presents with a recurrence of goiter. Although she is clinically euthyroid, laboratory evaluation shows persistent hyperthyroxinemia with non-suppressed TSH. Response to thyrotropin releasing hormone (TRH) test was normal and TSH concentrations were not suppressed during oral administration of suprafisiologic doses of levothyroxine (L-T4). Peripheral blood DNA was extracted from the patient and a mutation was found localized in cluster one, at codon 346 of the ligand binding domain of the THRB gene. The patient's son underwent thyroid function testing (TFT) and genetic study, both negative, suggesting a sporadic mutation. RSTH should be considered in all hyperthyroxinemic patients who are clinically euthyroid. Mutations interfering with three major steps required for TH action on target tissues have been, so far, identified (TR-β, TR-α, MCT8, SPB2). Each mutation is associated with a distinctive syndrome. Goal of management is to maintain a normal serum TSH level and a eumetabolic state and offer appropriate genetic counselling and prenatal diagnosis. Inappropriate treatment of eumetabolic patients results in hypothyroidism and need for TH replacement.

Background: The peptide hormone kisspeptin is essential for human reproduction, acting on the hypothalamus to stimulate gonadotrophin-releasing hormone (GnRH) secretion. Kisspeptin is currently being evaluated as a novel therapeutic for women with infertility. However, some animal studies suggest that kisspeptin may also stimulate growth hormone (GH), prolactin and thyroid-stimulating hormone (TSH) secretion, with implications for its safety; no previous study has investigated whether kisspeptin stimulates these pituitary hormones in humans., Aim: To determine whether kisspeptin-54 modulates GH, prolactin and TSH secretion in healthy women., Design and Participants: Prospective, single-blinded, placebo-controlled, one-way crossover study. Five healthy women received 7 days of twice-daily subcutaneous bolus vehicle (month 1) or 6·4 nmol/kg kisspeptin-54 (month 2)., Measurements: Serum samples were analysed post hoc for GH, prolactin and TSH., Results: Mean serum GH, PRL and TSH did not change during the first 4 h following kisspeptin-54 injection when compared with vehicle. The mean frequency or amplitude of GH pulses (which influence GH function) did not change acutely following kisspeptin-54 injection when compared with vehicle. No chronic changes in serum GH, PRL or TSH were observed over the 7-day period of twice-daily kisspeptin-54 injections when compared with vehicle., Conclusion: While we cannot exclude any effect of kisspeptin-54 on GH, prolactin or TSH secretion, we observed no significant changes in these hormones at a dose of kisspeptin-54 administration known to stimulate gonadotrophin secretion in a small study of healthy women. These data have important implications for the potential of kisspeptin to treat patients with infertility., (© 2014 John Wiley & Sons Ltd.)

Thyroid hormone biosynthetic defects are rare causes of congenital hypothyroidism. Although, initial presentations are usually diffuse goiter and hypothyroidism, subsequently they may develop thyroid nodules and or thyroid cancer. We describe a case of hypothyroidism due to dyshormonogenesis whose one of the previously solid nodules degenerates into a large cyst. A 22-year-old male was referred to our clinic for evaluation of enlarging thyroid nodule. Hypothyroidism was diagnosed in infancy, however due to poor compliance to treatment TSH values were elevated most of the times. When he was fifteen the first nodule was detected which was a solid cold nodule. Fine needle aspiration was in favor of benign follicular nodule. Seven years later we found a large multi nodular thyroid with a predominant large cyst corresponding to the previously detected solid nodule. 21cc straw colored fluid was aspirated. Cytology was reported as benign cystic nodule. The patient underwent thyroidectomy and pathology confirmed a benign thyroid cyst. Although underreported thyroid dyshormonogenesis may progress to cystic degeneration. Taking into account the risk of malignancy and eventually cyst formation, we recommend more frequent evaluation in the face of nodule formation in these patients.

Context: Some data suggest that metformin affects the thyroid profile in patients with type 2 diabetes, but contrasting results are reported in different settings., Objective: The aim of this meta-analysis was to assess the effect of metformin treatment on TSH in subjects with or without thyroid dysfunction., Data Sources: We performed a systematic search of articles evaluating changes in TSH levels in patients receiving metformin., Study Selection: Studies evaluating TSH levels before and after metformin treatment were included., Data Extraction: Clinical data, demographic variables, and TSH levels before and after treatment with metformin were extracted. Data were analyzed according to the underlying thyroid disease., Data Synthesis: A total of 7 datasets (206 patients) were included in the final analysis. After metformin treatment, a slight but significant reduction in TSH levels was found in 4 datasets on 119 patients with overt hypothyroidism receiving l-T4 replacement (mean difference, 1.08; 95% confidence interval [CI], 0.50, 1.65; P=.0003). Similarly, in 2 datasets reporting on a total of 33 patients with subclinical hypothyroidism not receiving treatment with l-T4, a significant reduction in TSH levels was reported (mean difference, 1.59; 95% CI, 1.32, 1.87; P<.00001) after treatment with metformin. In 1 dataset, including 54 euthyroid patients not receiving l-T4, no changes in TSH levels were reported after treatment with metformin (mean difference, 0.18; 95% CI, -0.20, 0.56; P=.35)., Conclusions: Metformin induces a reduction in TSH levels both in overt and in subclinical hypothyroidism. In contrast, no change in TSH levels is found in euthyroid patients.

The aim of this study was to see how a mixture of cadmium (Cd) and decabrominated diphenyl ether (BDE209) affect thyroid function, namely thyroid-stimulating hormone (TSH), thyroxin (T4), free thyroxin (FT4), triiodothyronin (T3), and free triiodothyronin (FT3) in Wistar rats (eight per group) receiving either a single substance or their combination by gavage for 28 days. Three groups were receiving Cd alone in the doses of 2.5 mg kg-1, 7.5 mg kg-1, or 15 mg kg-1 b. w. a day, three groups were receiving BDE209 in the doses of 1000 mg kg-1, 2000 mg kg-1, or 4000 mg kg-1 b. w. a day, while nine groups were receiving different mixtures of Cd and BDE209 in these doses (3x3 design). The results have indicated that the Cd+BDE209 mixtures more potently disrupt thyroid hormone homeostasis than would be expected from these chemicals alone.

Background: Recently, we reported that the thyroglobulin (Tg) doubling time (DT) was the most potent prognostic factor in patients with papillary thyroid carcinoma (PTC) who underwent total thyroidectomy. Interestingly 16.2% of the study patients had a decrease in Tg levels over time, giving negative values in Tg-DT. These patients had an excellent outcome. However, most of the patients did not receive ablation with radioactive iodine. Therefore, whether the Tg in these patients was derived from persistent disease or residual thyroid tissue could not be concluded. To resolve this question, we measured serum Tg levels in patients with medullary thyroid carcinoma (MTC) who underwent total thyroidectomy using similar surgical techniques for the treatment of PTC., Methods: Twenty-seven consecutive patients with MTC who underwent total thyroidectomy were selected. Of them, five patients with antibodies to Tg were excluded from the study. In the remaining 22 patients, serum Tg levels were measured before and after surgery. None of the patients received radioactive iodine ablation. They were prescribed levothyroxine as a replacement for the lost thyroid function., Results: Serum Tg levels were detectable preoperatively, while postoperative serum Tg levels were lower than the detectable level, 0.5 ng/mL, in all 22 patients., Conclusions: The results indicate that most of the patients with detectable Tg levels and negative Tg-DT values after total thyroidectomy for PTC in our previous study had persistent disease, and that their serum Tg was not from residual thyroid tissue, suggesting that up to 50% of patients with persistent PTC have a decrease in serum Tg levels in response to thyroid-stimulating hormone-suppressive therapy.

Objective: To investigate the effect of selenium on the TGAb, TMAb, FT3, FT4 and TSH level of rats with excessive intake of iodine., Methods: Wistar rats were divided into three groups by random:normal control, high iodine group and high iodine plus selenium group. Rats in the high iodine plus selenium group were lavaged with sodium selenite for 10 weeks. The levels of serum TGAb, TMAb, FT3, FT4 and TSH were tested at different time of the experiment., Results: There were no significant change on levels of FT3, FT4 and TSH (P > 0.05). The levels of TGAb and TMAb in the high iodine group were increased slowly (P < 0.05), but no significant change was observed in the high iodine plus selenium group., Conclusion: Excessive intake of iodine might induce goiter, and selenium might have antagonistic effect on it.

Objective: It has been shown that coenzyme Q(10) (CoQ(10)) supplementation in men with idiopathic oligoasthenoteratozoospermia (OAT) results in improved semen parameters. In present study, we evaluated the effects of coenzyme CoQ(10) supplementation on semen parameters and pregnancy rates in infertile men with idiopathic OAT., Patients and Methods: Two hundred and eighty-seven infertile men with idiopathic OAT were recruited in this study. These patients were treated with CoQ(10) 300 mg orally twice daily for 12 months. Two semen analyses and determination of resting levels of sex hormones were done in all participants. Patients were followed up for another 12 months after CoQ(10) discontinuation., Results: Mean sperm concentration, sperm progressive motility, and sperm with normal morphology improved significantly after 12-month CoQ(10) therapy by 113.7, 104.8, and 78.9%, respectively (all Ps < 0.05). The overall pregnancy rate was 34.1% within a mean of 8.4 ± 4.7 months., Conclusions: CoQ(10) supplementation improves semen quality with beneficial effect on pregnancy rate.

Objective: Compliance to levothyroxine treatment in hypothyroidism is compromised by daily schedule, and a weekly dose may be an alternative., Subjects and Methods: This was a randomized, crossover study. Fourteen females were assigned to daily or weekly doses of LT4. After six weeks, they switched regimens. Thyroid parameters were measured at baseline, and after 42 and 84 days. Echocardiogram and hyperthyroidism symptoms were evaluated before and four hours after LT4 intake., Results: In the weekly dose treatment, fT4 levels were higher after taking LT4, and lower seven days after the last dose; by the 6(th) week there was a small decrease in T3 levels. TSH remained unchanged and there were no hyperthyroidism symptoms or echocardiographic manifestations., Conclusion: Weekly dose leads to transient increases in fT4, without hyperthyroidism or cardiac symptoms. That approach seems to be a safe alternative for the treatment of hypothyroidism.

Background: Brominated flame retardants (BFRs) have been in widespread use in a vast array of consumer products since the 1970s. The metabolites of some BFRs show a structural similarity to thyroid hormones and experimental animal studies have confirmed that they may interfere with thyroid hormone homeostasis. A major concern has been whether intrauterine exposure to BFRs may disturb thyroid homeostasis since the fetal brain is particularly susceptible to alterations in thyroid hormones. However, few reports on newborns have been published to date., Objectives: To evaluate the association between BFRs and neonatal thyroid-stimulating hormone (TSH)., Methods: We studied six polybrominated diphenyl ethers (PBDEs) measured in milk samples from 239 women who were part of the "Norwegian Human Milk Study" (HUMIS), 2003-2006. Hexabromocyclododecane (HBCD) and BDE-209 were measured in a subset of the women (193 and 46 milk samples, respectively). The milk was sampled at a median of 33 days after delivery. TSH was measured in babies three days after delivery as part of the routine national screening program for early detection of congenital hypothyroidism. Additional information was obtained through the Medical Birth Registry and questionnaires to the mothers., Results: The PBDE concentrations in human milk in Norway were comparable to concentrations reported from other European countries and Asia, but not the US and Canada where levels are approximately one order of higher magnitude. We observed no statistically significant associations between BDE-47, 99, 153, 154, 209 and HBCD in human milk and TSH in models adjusted for possible confounders and other environmental toxicants including polychlorinated biphenyls (PCBs)., Conclusions: We did not observe an association between TSH and exposure to HBCD and PBDEs within the exposure levels observed., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Saisentong, as a thiadiazole fungicide, is widely used in China. The structure of saisentong shows a closer relationship to N, N-methylene-bis (2-amino-1, 3, 4-thiadiazole) (Bis-A-TDA), which is a teratogen. A few studies have shown that some of the thiadiazole fungicides act as endocrine disruptors via disturbance in thyroid hormone homeostasis. Little is known about the effect of pubertal exposure to saisentong on the development in pubertal female rats. Based on the protocol of the 20-Day Pubertal Female Assay, we attempt to estimate the possible effect of exposure to saisentong on thyroid hormone and hepatic enzyme activity in female rats. Postnatal days (PND) 22 old SD rats were administered with saisentong daily by oral gavage at doses of 0, 5, 10 or 15mg/kg/day for 20 days. After treatment, the rats were sacrificed for blood collection; the reproductive organs, liver, pituitary, adrenal and thyroid gland were harvested. The results indicated that saisentong administration increased thyroid weight and thyroid stimulating hormone (TSH) concentrations, and induced hepatic uridine diphosphate glucuronyl transferase (UDPGT) activities in the highest-dose group, although not statistically significant. The high dose caused a decrease in weight at vaginal opening (VO), but the age at VO was unaffected by saisentong in all treatment groups. No histological changes were observed in uterus and ovaries. These data and changes demonstrate that saisentong is a potential thyroid disrupter in female rat following exposure during development, but does not affect the development of pubertal female rats., (Copyright 2009 Elsevier GmbH. All rights reserved.)

Context: Patients treated with levothyroxine typically ingest it in a fasting state to prevent food impairing its absorption. The serum thyrotropin concentration is the therapeutic index of levothyroxine action., Objective: The study objective was to determine the effect of the timing of levothyroxine administration in relationship to food on serum thyrotropin levels., Design: Participants were randomized to one of six sequences, each consisting of three 8-wk regimens in a three-period crossover design. These regimens were in a fasting state, at bedtime, and with breakfast. The concentrations of TSH, free T(4), and total T(3) during each of the three timing regimens were documented. The primary outcome was the difference between serum TSH concentrations under fasting conditions compared with concentrations during the other 8-wk regimens., Setting: The study was conducted in an academic medical center., Participants: Study participants were receiving levothyroxine for treatment of hypothyroidism or thyroid cancer., Results: Sixty-five patients completed the study. The mean thyrotropin concentration was 1.06 +/- 1.23 mIU/liter when levothyroxine was administered in the fasting state. When levothyroxine was taken with breakfast, the serum thyrotropin concentration was significantly higher (2.93 +/- 3.29 mIU/liter). When levothyroxine was taken at bedtime, the serum TSH concentration was also significantly higher (2.19 +/- 2.66 mIU/liter)., Conclusion: Nonfasting regimens of levothyroxine administration are associated with higher and more variable serum TSH concentrations. If a specific serum TSH goal is desired, thereby avoiding iatrogenic subclinical thyroid disease, then fasting ingestion of levothyroxine ensures that TSH concentrations remain within the narrowest target range.

Objective: Activation of ghrelin receptors stimulates GH secretion and appetite, increasing lean body mass and body weight. However, clinical use of ghrelin is limited because it has a short half-life and must be administered parenterally. Anamorelin is a novel, orally active, non-peptidic ghrelin mimetic and growth hormone secretagogue. Our objective was to evaluate its hormonal effects in healthy subjects., Design: A double-blind, randomized, placebo-controlled study evaluated the short-term effects of anamorelin on GH, insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), prolactin, ACTH, LH, FSH, TSH, cortisol, insulin and glucose. Normal healthy volunteers (n=32) recruited from the general population were administered escalating doses of anamorelin (25, 50, and 75 mg daily) vs. placebo., Results: Anamorelin significantly increased GH levels at all doses (p

Background: A variety of stimuli cause a rapid increase in polyamine synthesis by increasing an enzyme ornithine decarboxylase required for the biosynthetic pathway of protein synthesis. Difluoromethyl ornithine is a selective inhibitor of this enzyme and hence arrests cell replication strikingly. Its effects on thyroid gland are studied with respect to change in animal's weight and levels of Triiodothyronine, Thyroxine and Thyroid stimulating hormone. The study was conducted to evaluate the inhibitory effects of Di-fluoromethyl ornithine (DFMO) administration on polyamine metabolism of thyroid gland in rats., Methods: The study was conducted on rats weighing 248 to 320 grams, divided into control and DFMO treated group. A dose of 50 mg/rat was administered subcutaneously to the treated group for 5 consecutive days and placebo (normal saline) injections to control group. On sixth day, blood was collected by cardiac puncture and serum was separated. Serum T3, T4 and TSH were analyzed with the help of radioimmunoassay in both groups., Results: In treated group there was a fall in T3, T4 concentration with significant rise in TSH concentration as compared to control group., Conclusion: DFMO (Difluoro methyl ornithine) decreases cellular proliferation of thyroid gland as is assessed by decrease in thyroid hormone levels. The hypothalamo pituitary thyroid axis however remains intact as is shown by a feedback rise in TSH concentration. DFMO can thus be employed for anti-neoplastic clinical trials on account of interference with activity of ODC (Ornithine Decarboxylase) fundamental for polyamine biosynthesis.

Reported evidence regarding relationships between polychlorinated biphenyls (PCBs) and thyroid homeostasis in adults has been considered contradictory. The objective of this systematic review is to determine a possible association between PCB exposure and the circulating thyroid hormones and thyrotropin (TSH) levels in adults, by analyzing the quality of published studies. A systematic review of epidemiological papers was conducted using PubMed. An evaluation of the quality of 22 studies was performed, and the papers were classified into two tiers: Tier I for studies with higher quality scores (eight) and Tier II for studies with lower quality scores (14). It appears that PCBs can interfere with thyroid hormone homeostasis; however epidemiological evidence is not entirely clear. For triiodothyronine (T3) and thyroxine (T4), Tier I studies showed either an inverse (four cases for T3; five cases for T4) or no significant association (two cases for T3; five cases for T4) with PCBs. In the case of free thyroxine and TSH, the Tier I papers observed no clear association with PCB levels. Rigorous study design, assessment of potential confounding factors, and fuller reporting of methods and results in future studies will facilitate understanding of whether PCB exposure is associated with changes in thyroid function.

In contrast to chronic or subacute thyroiditis, Graves' disease rarely complicates IFN-alpha therapy for chronic viral C hepatitis. We report the case of a 51-year-old man in whom IFN-alpha treatment was followed by recurrence of Graves' disease 10 years after thyroidectomy was performed and the patient was declared cured. Despite severe thyrotoxicosis, combined IFN-alpha and ribavirin therapy was continued and radioiodine treatment was considered for Graves' disease.

Exposure to polychlorobiphenyl (PCB) mixtures at an early stage of development has been reported to affect endocrine glands; however, little is known about the precise toxicological properties of individual PCB. The present study was undertaken to determine whether prenatal exposure to 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153), a di-ortho-substituted non-coplanar congener, affects postnatal development in rat offspring. Pregnant Sprague-Dawley rats (Crj: CD (SD) IGS) were given PCB 153 (0, 16, or 64 mg/kg/day) orally from gestational day (GD) 10 through GD 16, and developmental parameters in the male and female offspring were examined. We found no dose-dependent changes in body weight, body length (nose-anus length), tail length, or the weights of kidneys, testes, ovaries and uterus in offspring at 1 or 3 weeks of age. Liver weights were increased in the PCB 153-treated groups, although we observed a significant difference only in males. Anogenital distance was unaffected in the PCB 153-treated groups. We observed a significant dose-dependent decrease in the plasma concentrations of thyroxine and tri-iodothyronine, whereas those of thyroid-stimulating hormone were not significantly changed. In addition, there were no dose-dependent changes in plasma concentrations of growth hormone and insulin-like growth factor-I in any dose group. These findings suggest that prenatal exposure to PCB 153 (GD 10-16, 16-64 mg/kg/day) may alter the thyroid status in rat offspring to some extent without affecting somatic growth or its related hormonal parameters.

A lower thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) in depressed women has been associated with violent suicide attempts, suicidal intent, higher lethality and suicide risk. The cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) levels are related to suicidal behaviour. We studied the HPT axis function in twelve male suicide attempters and eight healthy volunteers submitted to lumbar puncture and to TRH test. Suicidal behaviour and depression severity were assessed. There was no association between deltamaxTSH and violent suicidality or subsequent suicide. The deltamaxTSH correlated with CSF HVA in suicide attempters. The plasma T3 showed a negative correlation with the Beck Suicide Intent Scale and the Montgomery Asberg Depression rating scale. Dopaminergic regulatory mechanisms on the thyroid hormone activity may be altered in male suicide attempters.

In this study, the authors' objective was to determine whether serum concentrations of polychlorinated biphenyls (PCBs), hexachlorobenzene, p,p'-dichlorodiphenyl trichloroethane (DDT), o,p'-DDT, and p,p'-dichlorodiphenyl dichloroethylene (DDE) are associated with thyroid function during pregnancy. These compounds, as well as thyroid-stimulating hormone, total thyroxine, and free thyroxine, were measured in serum samples collected between October 1999 and October 2000 from 334 pregnant women living in the Salinas Valley, California. Data were analyzed by multivariate linear regression. After adjustment for covariates, seven of the 19 PCB congeners detected in more than 75% of participants and the sum of those congeners were negatively associated with free thyroxine concentrations. PCBs 44, 52, and 183 remained significant after the exclusion of two outliers. Hexachlorobenzene concentrations were negatively associated with both free thyroxine and total thyroxine. PCB and hexachlorobenzene concentrations were strongly correlated, which hampered the authors' ability to identify their independent associations with thyroid function. None of the exposures under study were associated with thyroid-stimulating hormone. Results suggest that exposure to PCBs and/or hexachlorobenzene at background levels may affect thyroid function during pregnancy. These findings are of particular significance, since thyroid hormones of maternal origin may play an essential role in fetal neurodevelopment.