Comparison of pathophysiology in subclinical hyperthyroidism with different etiologies.

Subclinical hyperthyroidism (SHyper) is defined as normal levels of free thyroxine (fT4) and free triiodothyronine (fT3) with suppressed levels of TSH. Previous studies have reported the individual pathophysiology of endogenous SHyper patients and athyreotic patients receiving TSH suppression therapy with levothyroxine; however, apparently no studies have compared the two conditions. Five-hundred-forty untreated endogenous SHyper patients and 1,024 patients receiving TSH suppression therapy who underwent total thyroidectomy for papillary thyroid carcinoma were sampled. Thyroid hormone profiles and peripheral indices related to thyrotoxicosis were investigated in endogenous SHyper patients, athyreotic patients receiving TSH suppression therapy, and healthy participants. Endogenous SHyper patients showed significantly higher thyroid hormone levels (fT4 [p < 0.001] and fT3 [p < 0.001]), and peripheral indices showed a significant tendency towards thyrotoxicosis (strong TSH suppression: alkaline phosphatase [ALP, p < 0.001], creatinine [Cre, p < 0.001], pulse rate [p < 0.05]; and mild TSH suppression: Cre [p < 0.05]) than healthy participants. In contrast, athyreotic patients receiving TSH suppression therapy showed a significant tendency towards thyrotoxicosis than healthy participants only when TSH was strongly suppressed (fT3 [p < 0.001] and Cre [p < 0.001]). Endogenous SHyper patients showed significantly higher fT3 levels (p < 0.001) than athyreotic patients receiving TSH suppression therapy; however, there was a significant tendency towards thyrotoxicosis only when TSH was strongly suppressed (ALP [p < 0.05] and pulse rate [p < 0.05]). The effects of endogenous SHyper and TSH suppression therapy on target organ function are different. Although the serum thyroid hormone profile is similar to that of the thyrotoxic state, athyreotic patients receiving TSH suppression therapy with mildly suppressed serum TSH levels are not thyrotoxic.

Effects of Chronic Suppression or Oversuppression of Thyroid-Stimulating Hormone on Psychological Symptoms and Sleep Quality in Patients with Differentiated Thyroid Cancer.

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.

Risk of perioperative thyroid storm in hyperthyroid patients: a systematic review.

BACKGROUND: Thyroid storm is a feared complication in patients with hyperthyroidism undergoing surgery. We assessed the risk of thyroid storm for different preoperative treatment options for patients with primary hyperthyroidism undergoing surgery. METHODS: Pubmed, EMBASE, and The Cochrane Library were searched systematically for all studies reporting on adult hyperthyroid patients undergoing elective surgery under general anaesthesia. Selected studies were categorised based on preoperative treatment: no treatment, antithyroid medication (thionamides), iodine, ß-blocking medication, or a combination thereof. Treatment effect, that is restoring euthyroidism, was extracted from the publications if available. Risk of bias was assessed using the Risk of Bias in Non-randomised Studies of Interventions (ROBINS-I) or the Cochrane Risk of Bias tool for randomised studies. RESULTS: The search yielded 7009 articles, of which 26 studies published between 1975 and 2020 were selected for critical appraisal. All studies had moderate to critical risk of bias, mainly attributable to risk of confounding, classification of intervention status, and definition of the outcome. All studies reported on thyroidectomy patients. We found no randomised studies comparing the risk of thyroid storm between treated and untreated patients. Cases of thyroid storm were reported in all treatment groups with incidences described ranging from 0% to 14%. CONCLUSION: Evidence assessing the risk of perioperative thyroid storm is of insufficient quality. Given the seriousness of this complication and the impossibility of identifying patients at increased risk, preoperative treatment of these patients remains warranted.

ENDOCRINE TUMOURS: Thyrotropin-secreting pituitary adenoma: a structured review of 535 adult cases.

BACKGROUND AND AIMS: Thyrotropin-secreting pituitary adenomas (TSHomas) are a rare entity, occurring in one per million people. We performed a systematic review of 535 adult cases summarizing the clinical, biochemical, hormonal and radiological characteristics of TSHoma. Furthermore, we discussed the current guidelines for diagnosis and treatment. METHODS: A structured research was conducted using Pubmed and Web of Science with the following MeSH terms: 'thyrotropin secreting pituitary adenoma' OR 'TSHoma' OR 'thyrotropinoma.' RESULTS: Our analysis included 535 cases originating from 18 case series, 5 cohort studies and 91 case reports. The mean age at diagnosis was 46 years. At presentation, 75% had symptoms of hyperthyroidism, 55.5% presented with a goitre and 24.9% had visual field defects. The median TSH at diagnosis was 5.16 (3.20-7.43) mU/L with a mean FT4 of 41.5 ± 15.3 pmol/L. The majority (76.9%) of the TSHomas were macroadenoma. Plurihormonality was seen in 37.4% of the adenoma with a higher incidence in macroadenoma. Surgical resection of the adenoma was performed in 87.7% of patients of which 33.5% had residual pituitary adenoma. Post-operative treatment with a somatostatin analogue (SSA) led to a stable disease in 81.3% of the cases with residual tumour. We noticed a significant correlation between the diameter of the adenoma and residual pituitary adenoma (r = 0.490, P < 0.001). However, in patients preoperatively treated with an SSA, this correlation was absent. CONCLUSION: TSHomas are a rare cause of hyperthyroidism and are frequently misdiagnosed. Based on our structured analysis of case series, cohort studies and case reports, we conclude that the majority of TSHomas are macroadenoma being diagnosed in the fifth to sixth decade of life and presenting with symptoms of hyperthyroidism. Plurihormonalitiy is observed in one-third of TSHomas. Treatment consists of neurosurgical resection and SSA in case of surgical failure.

Current approach to surgical management of hyperthyroidism.

Hyperthyroidism is a set of disorders that involve excess synthesis and secretion of thyroid hormones by the thyroid gland, which leads to thyrotoxicosis. The most common forms of hyperthyroidism include diffuse toxic goiter (Graves' disease), toxic multinodular goiter (Plummer disease), and a solitary toxic adenoma. The most reliable screening measure of thyroid function is the thyroid-stimulating hormone (TSH) level. Options for treatment of hyperthyroidism include: antithyroid drugs, radioactive iodine therapy (the preferred treatment of hyperthyroidism among US thyroid specialists), or thyroidectomy. Massive thyroid enlargement with compressive symptoms, a suspicious nodule, Graves' orbitopathy, and patient preference are indications for surgical treatment of thyrotoxicosis. This paper reviews the current literature and controversies on the surgical approach to the management of hyperthyroidism.

MANAGEMENT OF ENDOCRINE DISEASE: Thyroid and female infertility: more questions than answers?!

Severe thyroid dysfunction may lead to menstrual disorders and infertility via direct and indirect interactions with the hypothalamo-pituitary-ovarian axis and the reproductive organs. However, the exact prevalence of infertility in women with thyroid disorders remains unknown. Fertility problems may persist even after restoring normal thyroid function, and then surgery and/or an assisted reproductive technology (ART) may be necessary to obtain a pregnancy. The initial step in an ART treatment is the ovarian stimulation, putting strain on the thyroid gland, potentially leading to (permanent) hypothyroidism in women with thyroid autoimmunity (TAI) or when already treated with thyroid hormones (LT4). Moreover, women with ovarian and unexplained causes of infertility have a higher prevalence of TAI. In women treated with LT4, a serum TSH level <2.5 mIU/L should be targeted before ART. In women with TSH levels >4.0 mIU/L, fertilisation rates, embryo quality and live birth rates may be impaired but also improved with LT4 therapy. In euthyroid women with TAI, LT4 should not be given systematically, but on a case-by-case basis if serum TSH is >2.5 mIU/L. For all of the above reasons, women of infertile couples should be screened routinely for the presence of thyroid disorders. In this review, we will focus on the gaps in the current knowledge, the remaining questions on the associations between thyroid (disorders) and (assisted) reproduction and make proposals for future investigations that may lead to a better understanding and contribute to novel treatment options in the long term.

The Role of Nuclear Medicine in the Clinical Management of Benign Thyroid Disorders, Part 1: Hyperthyroidism.

Benign thyroid disorders, especially hyper- and hypothyroidism, are the most prevalent endocrine disorders. The most common etiologies of hyperthyroidism are autoimmune hyperthyroidism (Graves disease, GD), toxic multinodular goiter (TMNG), and toxic thyroid adenoma (TA). Less common etiologies include destructive thyroiditis (e.g., amiodarone-induced thyroid dysfunction) and factitious hyperthyroidism. GD is caused by autoantibodies against the thyroid-stimulating hormone (TSH) receptor. TMNG and TA are caused by a somatic activating gain-of-function mutation. Typical laboratory findings in patients with hyperthyroidism are low TSH, elevated free-thyroxine and free-triiodothyronine levels, and TSH-receptor autoantibodies in patients with GD. Ultrasound imaging is used to determine the size and vascularity of the thyroid gland and the location, size, number, and characteristics of thyroid nodules. Combined with lab tests, these features constitute the first-line diagnostic approach to distinguishing different forms of hyperthyroidism. Thyroid scintigraphy with either radioiodine or 99mTc-pertechnetate is useful to characterize different forms of hyperthyroidism and provides information for planning radioiodine therapy. There are specific scintigraphic patterns for GD, TMNG, TA, and destructive thyroiditis. Scintigraphy with 99mTc-sestamibi allows differentiation of type 1 from type 2 amiodarone-induced hyperthyroidism. The radioiodine uptake test provides information for planning radioiodine therapy of hyperthyroidism. Hyperthyroidism can be treated with oral antithyroid drugs, surgical thyroidectomy, or 131I-iodide. Radioiodine therapy is generally considered after failure of treatment with antithyroid drugs, or when surgery is contraindicated or refused by the patient. In patients with TA or TMNG, the goal of radioiodine therapy is to achieve euthyroid status. In GD, the goal of radioiodine therapy is to induce hypothyroidism, a status that is readily treatable with oral thyroid hormone replacement therapy. Dosimetric estimates based on the thyroid volume to be treated and on radioiodine uptake should guide selection of the 131I-activity to be administered. Early side effects of radioiodine therapy (typically mild pain in the thyroid) can be handled by nonsteroidal antiinflammatory drugs. Delayed side effects after radioiodine therapy for hyperthyroidism are hypothyroidism and a minimal risk of radiation-induced malignancies.

Exposure to the Chinese Great Famine in Early Life and Thyroid Function and Disorders in Adulthood: A Cross-Sectional Study.

Background: Malnutrition in early life may permanently change the structure and function of the body, which lead to a number of diseases in adulthood. The effect of famine exposure during the early life on thyroid function and disorders remains unclear. This study investigated the association between exposure to the Great Chinese Famine (1959-1961) in early life and thyroid function and disorders in adulthood. Methods: Nine thousand eight hundred eighty-one subjects with appropriate birth dates derived from the Thyroid disorders, Iodine status, and Diabetes Epidemiological survey were included. Thyroid function and disorders were defined by the test results of blood sample and ultrasonography of all participants. Associations between famine exposure in early life and thyroid function and disorders in adulthood were assessed with binary logistic regression and linear regression. Results: Participants exposed to the Great Chinese Famine during the fetal stage was associated with a higher thyrotropin (TSH) level in adulthood (ß = 0.024; p = 0.038), compared with the nonexposed participants. The association was significant among rural participants (ß = 0.039; p = 0.02) but not in urban participants (ß = 0.005; p = 0.77). Fetal-exposed group did not show a higher risk of thyroid disorders than the age-matched balanced control group, including overt hyperthyroidism, subclinical hyperthyroidism, overt hypothyroidism, subclinical hypothyroidism, autoimmune thyroiditis, and thyroid nodules (p > 0.05). Conclusions: Famine exposure during the fetal stage was associated with a higher TSH level in adulthood. The fetal stage could be the critical period for programming the pituitary-thyroid axis.

Serum Elabela Levels Are Elevated in Patients with Hyperthyroidism.

The apelinergic system plays an important role in the modulation of the cardiovascular system via the apelin peptide and the apelin receptor (APJ receptor). Apelin and elabela, also known toddler, are peptide ligands for the apelin receptor. These two peptides show similar biological actions, such as vasodilatation, increased myocardial contractility, angiogenesis, and energy metabolism. However, the serum levels of elabela in patients with hyperthyroidism are not well known. The aim of this study was to investigate the changes in serum elabela levels in patients with hyperthyroidism and its association with hypertension. This cross-sectional study included 74 patients with newly diagnosed hyperthyroidism due to Graves' disease and 20 healthy individuals. Serum elabela levels were measured by enzyme-linked immunosorbent assay. The patients were divided into two groups: hyperthyroid patients without hypertension (n = 51) and those with hypertension (n = 23). Basal heart rate, serum glucose and high-sensitive C reactive protein were significantly higher in hyperthyroid patients with and those without hypertension than in healthy controls (p < 0.05 for each). Serum elabela levels were significantly elevated in hyperthyroid patients compared with healthy controls, with higher serum elabela levels found in hyperthyroid patients with hypertension than those without hypertension. Linear regression analysis showed that serum elabela levels were correlated with systolic blood pressure (p < 0.001). In conclusion, serum elabela levels were significantly increased in patients with hyperthyroidism, especially in hyperthyroid patients with hypertension. Elevation in serum elabela levels may contribute to alleviation of cardiovascular complications of hyperthyroidism and hypertension.

Platelet function in cats with hyperthyroidism.

OBJECTIVES: Cats with hyperthyroidism have been reported to develop thromboembolism, with and without echocardiographic abnormalities consistent with hyperthyroidism. The objective of this study was to compare platelet function in cats with hyperthyroidism with euthyroid age-matched cats. We hypothesized that cats with hyperthyroidism have shortened collagen and adenosine diphosphate (C-ADP) closure times as measured with the platelet function analyzer (PFA-100) in comparison with healthy, age-matched controls. METHODS: Sixteen hyperthyroid and nine euthyroid healthy cats >7 years of age were recruited from the hospital population. Platelet function, measured using the C-ADP closure times by the PFA-100, and platelet count were measured in healthy euthyroid cats and cats with hyperthyroidism. RESULTS: Mean ± SD closure times were not significantly different between control (66.3 ± 9.6 s) and hyperthyroid cats (65.9 ± 11.5 s; P = 0.75). The mean ± SD closure times of hyperthyroid cats that either were untreated or received methimazole for ⩽3 weeks (n = 6; mean 68.5 ± 15.4 s) was not different than that of cats treated for >3 weeks (n = 10; mean 64.3 ± 8.9 s; P = 0.57). The mean automated platelet count was higher in the hyperthyroid group than in the control group (P = 0.023). CONCLUSIONS AND RELEVANCE: Platelet function, as measured by closure time under high shear conditions using C-ADP as an agonist, was not affected by hyperthyroidism in this group of cats. Further research is needed to determine if a hypercoagulable state exists in hyperthyroid cats and the potential roles platelets and von Willebrand factor may have.

Resultados de la tiroidectomía total en el tratamiento del hipertiroidismo / Results of total thyroidectomy in the treatment of hyperthyroidism

INTRODUCCIÓN: En el tratamiento del hipertiroidismo se recurre a la cirugía en casos de bocio grande, fracaso del tratamiento médico o indicación social de tratamiento definitivo. OBJETIVO: Analizar los resultados en cuanto a función tiroidea del tratamiento del hipertiroidismo mediante tiroidectomía total (TT). MATERIAL Y MÉTODO: Estudio retrospectivo de 26 pacientes con hipertiroidismo, intervenidos en el Hospital de la Plana durante 2015-2018, con seguimiento de 36 meses. Tras estudio estadístico descriptivo e inferencial, se analizó la probabilidad de recidiva del hipertiroidismo mediante el método de Kaplan-Meier, y se utilizó el modelo de Cox para ajustar los efectos sobre la recidiva de las diferentes variables. RESULTADOS: El 73,1% tenían normofunción tiroidea; el 19,2%, hiperfunción, y en otro 7,7% existía hipofunción. El tiempo medio de supervivencia (normofunción) fue de 25,87 meses (IC: 17,52-34,21). En el estudio de supervivencia con el log-rank en función de la variable anatomía patológica y complicaciones, no hay diferencias estadísticamente significativas en la supervivencia de ambos grupos. DISCUSIÓN: Coincide con otros trabajos publicados. CONCLUSIÓN: La TT es un método efectivo de tratamiento para el hipertiroidismo, con baja incidencia de complicaciones. Sin embargo, no hemos encontrado ninguna variable que nos permita predecir el resultado.

INTRODUCTION: Surgery is used in the management of hyperthyroidism in cases of large goiter, failure of medical treatment or social indication of definitive treatment. AIM: To analyze the results of the treatment of hyperthyroidism by total thyroidectomy (TT) regarding to thyroid function. MATERIAL AND METHODS: Retrospective study of 26 patients with hyperthyroidism, operated on the Hospital de la Plana during 2015-2018, with a follow-up of 36 months. After a descriptive and inferential statistical study, the probability of recurrence of hyperthyroidism was analyzed using the Kaplan-Meier method, and the Cox model was used to adjust the effects on recurrence of the different variables. RESULTS: 73.1% had thyroid normofunction; in 19.2% there was hyperfunction, and in another 7.7% there was hypofunction. The average survival time (normofunction) was 25,87 months (CI: 17,52-34,21). In the study of survival with the log-rank depending on the pathological results and complications, there are no statistically significant differences in the survival of both groups. DISCUSSION: This coincides with other published works. CONCLUSION: TT is an effective method of treatment for hyperthyroidism, with a low incidence of complications. However, we have not found any variable that allows us to predict the result.

Thyroid and Eye: Where They Meet in Clinical Practice.

OBJECTIVE: Thyroid Hormones (TH) are essential for normal growth, development and continued optimal function of most of the body organs including the eye. TH signaling plays a central role in the regulation of retinal development and maturation. Deficiency in TH during fetal and early postnatal development impairs growth of the eye and proliferation of all retinal cell types. The present article reviews the most important topics of the different derangements in thyroid function and structure and its relation with eye diseases. METHODS: A literature search strategy was conducted for all English-language literature. RESULTS: From a clinical practice viewpoint, it should be mentioned that both hypothyroidism and hyperthyroidism are accompanied by ocular diseases i.e. thyroid-associated ophthalmopathy, diabetic retinopathy and age-related macular degeneration. Although the orbit and globe are not common sites for metastatic thyroid cancers, orbital metastasis may be the primary clinical manifestation of thyroid carcinoma. Finally, some medications as amiodarone may be accompanied by both thyroid dysfunction and adverse ocular events. CONCLUSION: Thyroid disorders and eye diseases are interrelated through several mechanisms thus, awareness of this relation has a great impact on early diagnosis and treatment.

Thyroid dysfunction: how concentration of toxic and essential elements contribute to risk of hypothyroidism, hyperthyroidism, and thyroid cancer.

This study was conducted to evaluate the levels of trace metals Fe, Cr, Co, Cd, Cu, Ni, Hg, Zn, and Pb in healthy individuals and patients with thyroid disease (hyperthyroidism, hypothyroidism, and cancerous). The serum levels of 110 participants living in Birjand City, east of Iran, were collected and analyzed using ICP-MS (Agilent 7900). Results showed that the concentration levels of Cr, Co, Zn, Cd, and Pb were significantly higher at case-patients (p < 0.05), but the levels of Fe, Ni, and Hg were similar between healthy and patient subjects (p > 0.05). In patients with high or low thyroid activity, strong mutual correlations between Cr, Ni, and Fe were noticeable (p < 0.05). In hypothyroid patients, no significant correlation between Zn and Hg, Co, and Cd was found, but Zn was moderately and positively correlated with other trace metals. The moderate negative correlations between Cd-Cr (p = - 0.46) and Cd-Fe (p = - 0.43) were also observed. Logistic regression analysis showed that the effect of Cr, Co, Pb, Cu, Zn, and Cd was significant in developing hyperthyroidism and hypothyroidism; whereas, in patients with thyroid cancer, the effect of Cr, Cd, and Pb was found to be significant. In conclusion, our findings suggest that toxic metals such as Pb, Cd, and Cr can increase the risk of developing hypothyroidism and thyroid cancer, but more research is needed to evaluate the potential toxicity mechanisms of Pb, Cd, and Cr.

Age effect on thyroid hormone brain response in male mice.

PURPOSE: Thyroid hormones (TH) are important for brain development and central nervous system (CNS) function. Disturbances of thyroid function occur with higher prevalence in the ageing population and may negatively impact brain function. METHODS: We investigated the age impact on behavior in young adult and old male mice (5 vs. 20 months) with chronic hypo- or hyper-thyroidism as well as in sham-treated controls. Expression of TH transporters and TH responsive genes was studied in CNS and pituitary by in situ hybridization and qRT-PCR, whereas TH serum concentrations were determined by immunoassay. RESULTS: Serum TH levels were lower in old compared with young hyperthyroid mice, suggesting a milder hyperthyroid phenotype in the aged group. Likewise, elevated plus maze activity was reduced in old hyperthyroid animals. Under hypothyroid conditions, thyroxine serum concentrations did not differ in young and old mice. Both groups showed a comparable decline in activity and elevated anxiety levels. However, an attenuated increase in hypothalamic thyrotropin releasing hormone and pituitary thyroid stimulating hormone transcript expression was found in old hypothyroid mice. Brain expression of monocarboxylate transporter 8 and organic anion transporting polypeptide 1c1 was not affected by age or TH status. CONCLUSIONS: In summary, ageing attenuates neurological phenotypes in hyperthyroid but not hypothyroid mice, which fits with age effects on TH serum levels in the animals. In contrast no changes in TH transporter expression were found in aged mouse brains with hyper- or hypo-thyroid state.

An underestimated comorbidity of COPD: Thyroid dysfunction.

Chronic obstructive pulmonary disease (COPD) has many systemic effects influencing morbidity and mortality of the disease. Thyroid diseases which are more common in COPD patients than who do not have COPD are underestimated despite important clinical consequences. Similar to general population, thyroid dysfunctions are more common in females than males among COPD patients. Both hypothyroidism and hyperthyroidism may be associated to COPD. As well as systemic inflammation hypoxia, age, glucocorticoid use and smoking are some of the effective factors on developing thyroid dysfunction in COPD patients. In this article thyroid dysfunctions that are underrecognized comorbidities of COPD patients, their mechanisms of action and clinical outcomes were reviewed.

Age-dependent evaluation of long-term depression responses in hyperthyroid rats: Possible roles of oxidative intracellular redox status.

BACKGROUND: According to the free radical theory, a gradual accumulation of the free radicals normally produced in the body underlies the changes associated with aging. Thyroid hormones (THs) are related to oxidative stress not only due to their stimulation of metabolism but also due to their effects on antioxidant mechanisms. Thyroid dysfunction increases with age; thus, changes in TH levels in elderly individuals could be a factor affecting the development of neurodegenerative diseases. However, the relationship is not always clear, based on current evidence regarding synaptic plasticity. METHODS: Hippocampal long-term depression (LTD) and oxidative status in the hippocampus were evaluated at two different ages (2-3 and 12-14 months) in male rats. Rats were administered 0.2 mg/kg/day of l-thyroxine for 21 days starting at postnatal day 40 to induce hyperthyroidism. LTD was induced in the dentate gyrus using low frequency stimulation of the perforant pathway. Spectrophotometry was performed to measure catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA) levels, glutathione peroxidase (GPx) activity, and total nitrite/nitrate (tNOx) and nitric oxide synthase (NOS) levels. RESULTS: A reliable LTD was elicited in young rats with hyperthyroidism, while the same protocol could induce a small magnitude of synaptic LTD in the absence of spike-LTD in control rats. In aged rats, controls did not express LTD, but a significant LTP of spike was induced in the absence of synaptic LTD in hyperthyroid rats. While CAT levels were significantly decreased, MDA levels were increased in the aged groups compared to the corresponding young groups. Young rats with euthyroidism had significantly lower GPx activity than each of the hyperthyroid groups. There was no significant difference in SOD levels among the groups. Compared with aged rats, young rats exhibited a hyperthyroidism-induced decrease in NOS levels. Nevertheless, neither the main effects of age and thyroxine administration nor the interaction between these factors reached significance for tNOx. CONCLUSION: These results indicate that hyperthyroidism-related changes in synaptic plasticity are modulated by aging. This modulation may explain the increased cognitive impairment in this disease at older ages, which probably depends on alterations in NOS levels.

Arterial stiffness in hyperthyroid patients is deteriorated due to thyroid hormones

ABSTRACT Objective The aim of this study is to evaluate and compare arterial stiffness, which is an independent risk indicator for cardiovascular diseases (CVDs), between patients with overt hyperthyroidism, subclinical hyperthyroidism, euthyroidism by antithyroid therapy and healthy volunteers with pulse wave analysis (PWA). Subjects and methods A total of 102 volunteers were included in the study (30 in the overt hyperthyroid group, 28 in the subclinical hyperthyroid group and 14 with euthyroidism by antithyroid therapy and 30 healthy). The arterial stiffness measurements of the participants in the study were performed with the Mobil-O-Graph PWA device (I.E.M. GmBH, Stolberg, Germany), which makes cuff based oscillometric measurement from the brachial artery. Results Systolic blood pressure, pulse rate, central systolic blood pressure, cardiac output, heart rate-corrected augmentation index (Aix@75) and pulse wave velocity (PWV) measurements were significantly higher in the hyperthyroid group than in the control group. The heart rate and PWV in the subclinical hyperthyroid group were significantly higher than the control group. In the euthyroid group, systolic blood pressure, central systolic blood pressure, cardiac output, cardiac index and PWV were found significantly higher than the control group. There was also a negative correlation between Aix@75 and thyroid-stimulating hormone (TSH), and a positive correlation between Aix@75 and free thyroid hormones. Conclusion In our study, we observed that the arterial stiffness was adversely affected by an overt or subclinical increase in thyroid hormones and this correlated with thyroid hormone levels. We recommend that PWV measurement, which is a simple method for detecting CVD risk, can be used in these patients.

Subclinical Thyroid Dysfunction was not Associated with Cardiac Arrhythmias in a Cross-Sectional Analysis of the ELSA-Brasil Study / Disfunção Tireoidiana Subclínica não foi Associada com Arritmias Cardíacas em Análise Transversal do Estudo ELSA-Brasil

Abstract Background: The association of subclinical thyroid dysfunction (STD) with cardiac arrhythmias remains controversial, particularly in the non-elderly population. Objective: To investigate whether STD was associated with cardiac arrhythmias in a cohort of middle-aged and older adults. Methods: Baseline data of the Longitudinal Study of Adult Health, ELSA-Brasil (35-74 years) were collected from 2008 to 2010. After exclusion of clinical hypothyroidism and hyperthyroidism, participants were categorized as euthyroidism (TSH = 0.4-4.0 µU/mL), subclinical hypothyroidism (TSH > 4.0 µU/mL; FT4 = 0.8-1.9 ng/dL), and subclinical hyperthyroidism (TSH < 0.4 µU/mL; FT4 = 0.8-1.9 ng/dL). The prevalence rates of tachycardia (HR > 100) and bradycardia (HR < 60), atrial fibrillation/flutter, conduction disorders, extrasystoles, low QRS voltage, prolonged QT intervals, and persistent supraventricular rhythms were compared between groups after adjusting for age, sex, comorbidities, lifestyle, body mass index and medications. Results: The HR data of 13,341 participants (52% female; median age, 51 years) and the electrocardiogram readings of 11,795 were analyzed; 698 participants (5.23%) were classified as subclinical hypothyroidism, 193 (1.45%) as subclinical hyperthyroidism, and 12,450 (93.32%) as euthyroidism. The prevalence of rhythm and conduction disorders was similar, as were HR medians, even in the subgroups with TSH < 0.01 UI/mL or > 10.0 UI/mL or in older adults. Conduction disorders were less prevalent in older adults with subclinical hypothyroidism (adjusted OR = 0.44; 95% CI 0.24 to 0.80). Conclusion: In this large, multicenter and cross-sectional study, STD was not associated with cardiac arrhythmias, but a longitudinal assessment is necessary.

Resumo Fundamento: A associação de disfunção tireoidiana subclínica (DST) com arritmias cardíacas permanece controversa, particularmente na população não idosa. Objetivo: Investigar se a DST está associada a arritmias cardíacas em uma coorte de adultos de meia-idade e idosos. Métodos: Dados da linha de base do Estudo Longitudinal de Saúde do Adulto, ELSA-Brasil (35-74 anos) foram coletados de 2008 a 2010. Após exclusão de hipo e hipertireoidismo clínicos, os participantes foram categorizados como eutireoidismo (TSH = 0,4 a 4,0 µU/mL), hipotireoidismo subclínico (TSH > 4,0 µU/mL; T4L = 0,8-1,9 ng/dL) e hipertireoidismo subclínico (TSH <0,4 µU/mL; T4L = 0,8 a 1,9 ng/dL). As prevalências de taquicardia (Frequência cardíaca [FC] > 100) e bradicardia (FC < 60), fibrilação atrial/flutter, distúrbios de condução, extrassístoles, baixa voltagem do QRS, intervalos QT prolongados e ritmo supraventricular persistente foram comparadas entre os grupos após ajuste por idade, sexo, comorbidades, estilo de vida, índice de massa corporal e uso de medicamentos. Resultados: Foram analisados os dados da FC de 13.341 participantes (52% do sexo feminino; idade média de 51 anos) e das leituras de 11.795 ECG; 698 participantes (5,23%) foram classificados como hipotireoidismo subclínico, 193 (1,45%) como hipertireoidismo subclínico e 12.450 (93,32%) como eutireoidismo. A prevalência de distúrbios de ritmo e condução foi semelhante, assim como as médias de FC, mesmo nos subgrupos com TSH < 0,01 UI/mL ou > 10,0 UI/mL ou em idosos. Distúrbios de condução foram menos prevalentes em idosos com hipotireoidismo subclínico (OR ajustado = 0,44; IC95% 0,24-0,80). Conclusão: Neste grande estudo multicêntrico e transversal, a DST não foi associada a arritmias cardíacas, mas uma avaliação longitudinal é necessária.

Disruption of the Pituitary Circadian Clock Induced by Hypothyroidism and Hyperthyroidism: Consequences on Daily Pituitary Hormone Expression Profiles.

BACKGROUND: The secretion of pituitary hormones oscillates throughout the 24-hour period, indicating that circadian clock-mediated mechanisms regulate this process in the gland. Additionally, pituitary hormone synthesis has been shown to be altered in hypo- and hyperthyroidism. Although thyroid hormones can modulate the other peripheral clocks, the interaction between thyroid hormone levels and circadian clock gene expression in the anterior pituitary has yet to be elucidated. METHODS: Male Wistar rats were divided into three groups: control, hypothyroid, and hyperthyroid. Following the experimental procedures, animals were euthanized every three hours over the course of a 24-hour period. The anterior pituitary glands were excised and processed for mRNA expression analysis by quantitative reverse transcriptase polymerase chain reaction. One- and two-way analysis of variance as well as cosinor analysis were used to evaluate the time-of-day-dependent differential expression for each gene in each experimental group and their interactions. RESULTS: Hyperthyroidism increased the mRNA expression of core clock genes and thyrotrophic embryonic factor (Tef), as well as the mesor and amplitude of brain and muscle Arnt-like protein-1 (Bmal1) and the mesor of nuclear receptor subfamily 1 (Nr1d1) group D member 1, when compared to euthyroid animals. Hypothyroidism disrupted the circadian expression pattern of Bmal1 and period circadian regulator 2 (Per2) and decreased the mesor of Nr1d1 and Tef. Furthermore, it was observed that the pituitary content of Dio2 mRNA was unaltered in hyperthyroidism but substantially elevated in hypothyroidism during the light phase. The upregulated expression was associated with an increased mesor and amplitude, along with an advanced acrophase. The gene expression of all the pituitary hormones was found to be altered in hypo- and hyperthyroidism. Moreover, prolactin (Prl) and luteinizing hormone beta subunit (Lhb) displayed circadian expression patterns in the control group, which were disrupted in both the hypo- and hyperthyroid states. CONCLUSION: Taken together, the data demonstrate that hypo- and hyperthyroidism alter circadian clock gene expression in the anterior pituitary. This suggests that triiodothyronine plays an important role in the regulation of pituitary gland homeostasis, which could ultimately influence the rhythmic synthesis and/or secretion of all the anterior pituitary hormones.