Hyperthyroid Stage Research Articles

Changes in electrical parameters of the heart in an experimental model of malignant tumor growth during of hyperthyroidism

Experimental and clinical studies demonstrate the possibility of modulating the development of malignant tumors in thyroid imbalance, in particular hyperthyroidism, which negatively affects the electrophysiology of the heart. In an experimental model of tumor growth during of hyperthyroidism, activation of the tumor was shown.Aim: To study electrophysiological parameters of the mouse heart at the initial stages of transplantable tumor growth during of hyperthyroidism.Material and Methods. In female mice of the C57BL/6 line (n = 20) was created a model of melanoma B16/F10 growth during of hyperthyroidism, which was induced by daily intraperitoneal administration of liothyronine sodium (T3) for a long time and confirmed by determining the content of thyroid-stimulating hormone and triiodothyronine in the blood using the radioimmune method. On the 5th day of T3 administration, the melanoma was transplanted. ECG was recorded non-invasively (ecgTUN- NEL, ecgAVG software, emka TECHNOLOGIES, France) on the 1st and 3rd days of T3 administration, in groups with a tumor – on the 6th day after its transplantation.Results. Pathological changes were revealed: in the group with hyperthyroidism – rhythm irregularity, decrease the amplitude of P and T below the isoline, widening of the QRS, on the 3rd day – the death of 1 mouse was noted due to large-focal myocardial infarction; in the group with melanoma – only sinus arrhythmia and decreased heart rate; in the group with a combination of pathologies – an almost normal ECG, with the exception of an increase in P amplitude and a slight increase in QRS.Conclusion. Already in the early stages of hyperthyroidism or tumor growth, there was a violation of myocardial depolarization/ repolarization processes, capable of causing even death of the animal. In case of comorbidity, the majority of ECG parameters normalized, indicating the inclusion of compensatory mechanisms in the interaction of pathologies. The results demonstrate the need for a deeper study of the mechanisms of interaction of several simultaneously existing pathologies in the body.

A Review of Testing for Distinguishing Hashimoto's Thyroiditis in the Hyperthyroid Stage and Grave's Disease.

Hashimoto's thyroiditis (HT) and Graves' disease (GD) are two very common autoimmune thyroid diseases (AITD). In this review, we use "HT in the hyperthyroidism stage" to refer to early HT with clinical manifestations of hyperthyroidism. In clinical practice, it is not easy to distinguish between HT in the hyperthyroidism stage and GD as they exhibit very similar clinical symptoms. The current literature lacks so far studies that systematically compare and summarize hyperthyroidism due to HT and GD from varied aspects. It is necessary to focus on all the clinical indices of HT in the hyperthyroidism stage and GD, for accurate diagnosis. Multiple databases such as PubMed, CNKI, WF Data, and CQVIP Data were used to search the literature concerning HT in the hyperthyroidism stage and GD. The information extracted from the relevant literature was summarized and further analyzed. To differentially diagnose hyperthyroidism as HT or GD, it is recommended to first focus on serological tests, followed by imaging tests, as well as the thyroid I131 uptake index. In pathology, fine needle aspiration cytology (FNAC) is the gold standard for the differential diagnosis of HT and GD. Test results from cellular immunology and genetics could also be used to accurately diagnose between the two diseases, which may be further developed and studied in the future. In this paper, we reviewed and summarized the difference between HT in the hyperthyroidism stage and GD from the following six aspects: blood tests, imaging, thyroid I131 uptake, pathology, cellular immunology, and genetics.

Cardiovascular Complications of Hyperthyroidism

Thyrotoxicosis is a clinical syndrome caused by an excess of thyroid hormones circulating in the body. Myocardium and blood arteries have thyroid hormone receptors; hence, an increase or decrease in thyroid hormone levels can alter cardiovascular function. Cardiovascular complications are obvious in-patient with hyperthyroidism. Palpitations, tachycardia, exercise intolerance, dyspnea with exertion, expanded pulse pressure, and on occasion atrial fibrillation are associated with hyperthyroidism, excessive endogenous thyroid hormone production, and thyrotoxicosis, the condition caused by excess thyroid hormone. In the early stages of hyperthyroidism, a high cardiac output and hypertrophy of the left ventricle are observed, followed by biventricular dilatation and congestive heart failure. Atrial fibrillation and pulmonary arterial hypertension can contribute to the higher morbidity associated with untreated hyperthyroidism. Therefore, early and effective treatment of hyperthyroidism is required to prevent thyrotoxic cardiomyopathy.

PSAT322 A "Natural Thyroid Booster" Induced Hyperthyroidism

Abstract Background In the recent years market got filled with a variety of freely available and not FDA regulated supplements that claim to ensure thyroid gland "support", "activation", "boost", "restoration", "drive", "edge", "strength" and a midst of other positive effects. These supplements are often not considered as medications and often are not reported during medication reconciliation. We present a case of hyperthyroidism in a patient using a supplement containing potassium iodide Clinical Case 54-year-old male with newly diagnosed atrial fibrillation in Feb 2021 presented in September 2021 with non-ST elevation myocardial infarction. He continued to have persistent atrial fibrillation. At presentation TSH was nearly suppressed at 0.02 MIU/ml, FT4 was normal at 1.6 ng/dl, TT3 increased at 241 ng/dL. During endocrinology evaluation in October 2021 thyroid function values remained the same, TSI and TRAB were negative and TGAB were increased at 8 IU/ml. Imaging studies were not consistent with thyroiditis (heterogenous and hypervascular gland on ultrasound, normal RAI), a possibility of antibody negative Graves’ disease was entertained, however thyroid function tests in November 2021 were quite different and showed elevated TSH of 71 MIU/L, FT4 low at 0.3 ng/dl, low TT3 at 48 ng/dl. At this time patient recalled being on thyroid supplement in the recent past, per patient he did not realize that it was relevant information to disclose to the physician. He was on "Thyroid PX" from September 2020 to February 2021 per recommendation from naturopathic doctor for symptomatic subclinical hypothyroidism when in September 2020 TSH was noticed to be mildly elevated at 6.73 MIU/ml, FT4 normal at 1. 0 ng/dl and TT3 normal at 99 ng/dl. Conclusion This case represents an example of thyroid supplement use related thyrotoxicosis. He was taking "megadoses" (80 times the recommended daily dose) of iodine that likely have caused Jod-Basedow phenomenon, which is a hyperthyroidism following exposure to the excess of iodine. Among documented ingredients of "Thyroid PX" are potassium iodide, cholecalciferol, methylcobalamim, Ashwagandha root, Ginger root, Nettle leaf and others. Each capsule contains 6000mcg of Potassium Iodide (daily dose – 2 capsules) with recommended daily iodine dose for adults of 150mcg. Hyperthyroid stage was followed by the stage of profound hypothyroidism. The patient could have been predisposed to Jod-Basedow phenomenon due to Hashimoto thyroiditis. This illustrates an importance of obtaining detailed history of use of any/thyroid supplements in all patients with unexplained hyperthyroidism. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

MECHANISMS OF THE FORMATION OF MOTOR-SECRETORY DISORDERS IN PATIENTS WITH GERD WITH CONCOMITANT AIT

The aim: The aim of this work was to study the effect of thyroid hormones on motor-secretory dysfunction in patients with GERD with concomitant AIT. Materials and methods: The study involved three groups of patients: with isolated GERD, GERD with AIT at the stage of hypothyroidism and GERD with AIT at the stage of hyperthyroidism. The control group consisted of 15 practically healthy individuals. GERD and AIT were diagnosed on the basis of ICD-10. All patients underwent a comprehensive examination, including ultrasound examination of the motor-evacuation function of the esophagus and stomach. Quality of life of patients was assessed by using the GIQLI questionnaire. Results: The most expressed complaints and low quality of life are observed among patients with combined pathology. The results of pH-metry indicate more severe course of GERD among patients with concomitant AIT. The most pronounced decrease in the tone of the lower esophageal sphincter and increased regurgitation were observed in the second group. Conclusions: 1. It was found that more reliable motor-secretory disorders were observed among patients with GERD with concomitant AIT. 2. A close correlation was established between the severity of the clinical picture, the level of increased thyroid hormones and the degree of impairment of motor-secretory disorders among patients with GERD with concomitant AIT; 3. The results obtained indicate that changes in the metabolism of thyroid hormones are one of the factors involved in the mechanisms of GERD formation.

Autoimmune thyroiditis with systemic idiopathic fibrosis in horses

The article deals with the autopsy materials of the Friesian breed domestic horse (Equus ferus caballus). It presents the research on tissues’ and organs’ histological examination as well as materials from the case record. New nosology for this species and breed has been revealed for the first time for the animal under examination. It was chronic inflammatory thyroid disease of the autoimmune genesis in the hyperthyroid stage which caused the systemic idiopathic fibrosis. Previously this nosology was neither revealed nor described in the Russian and foreign literature sources. The article presents materials from the case record where animal’s clinical condition has been assessed. The description of pathoanatomical and morphological changes in the thyroid tissues in the detected autoimmune thyroiditis and associated pathological processes in the organs and tissues of the studied animal was given. The systemic idiopathic fibrosis associated with thyroiditis condition was described. The features of the blood serum metabolic profile according to the enzymes content, substrates and minerals were presented. The assessment of the thyroid gland endocrine status of total thyroxine (tT4) and total triiodothyronine (tT3) has been made. The level of which was 184.0 nmol/l and 7.9 nmol/l respectively. The data indicating the presence of an autoimmune process in relation to thyroid antigens have been traced. The level of antibodies to thyroglobulin and antibodies to thyroperoxidase was 9.7 IU/ml and 98 IU/ml respectively.

HASHIMOTO’S THYROIDITIS HYPERTHYROID STAGE

Preliminary: Hashimoto thyroiditis (chronic autoimmune thyroiditis) is the most common cause of hypothyroidism in iodine- sufficient areas of the world, but can sometimes show hyperthyroidism. Case: A 39-year-old female was referred due to shortness of breath and tremor, four hours before hospitalization. There was nausea, chest pain, cold chills and palpitation. She was diagnosed with Hashimoto’s thyroiditis and routinely received tyrosol, propanolol and dexamethasone. Physical examination: cervical mass, afebrile, blood pressure 130/70 mmHg, pulse rate 110 x/minute and respiratory rate 20 x /minute. Laboratory examinations showed WBC 7.53 x 109/L, Hb 11.0 g/dL and platelet count 168 x 109/L. Chest X-Ray: negative for infiltrates. Several laboratory tests were performed, abnormal results were as follows: FT4 2.96 ng/dL (increased), TSH 0.003 uIU/mL (decreased), anti-TPO (antithyroid microsomal antibody) 306 IU/ml (increased), Ig E 213.6 IU/mL (increased). Peripheral blood smear, coagulation test, serum electrolytes, liver function tests, renal function tests, urinalysis, CEA and Ca 125 were within normal limits. A thyroid ultrasound resulted in a benign lesion. Fine Needle Aspiration Biopsy concluded in lymphocytic Hashimoto’s thyroiditis. Echocardiography showed hyperthyroid heart disease. Discussion: Due to an increase in anti-TPO and FT4, a decrease in TSH and lymphocytic thyroiditis from FNAB, this patient was diagnosed with Hashimoto’s Thyroiditis Hyperthyroid Stage. Conclusion: Thyroid function tests and thyroid antibody tests must be monitored to decide whether it is hyperthyroid or hypothyroid stage of Hashimoto thyroiditis.

An early stage in T4-induced hyperthyroidism is related to systemic oxidative stress but does not influence the pentose cycle in erythrocytes and systemic inflammatory status.

Hyperthyroidism causes many injuries in its target organs and the consequences are reflected systemically. As systemic alterations in hyperthyroidism at earlier stages have received partial attention, this study aimed to investigate systemic redox and inflammatory status at an early stage of T4-induced hyperthyroidism. Male Wistar rats were assigned to control and hyperthyroid groups (n = 7/group). The hyperthyroid group received L-thyroxine (12 mg/L) in their drinking water for 14 days whereas control group received only the vehicle. Body weight was measured on the 1st and 14th day of the protocol. On the 14th day, animals were anaesthetized. Blood was then collected from the retro-orbital venous plexus and then the animals were euthanised. The blood was separated into plasma and erythrocytes. Plasma was used to measure ROS levels, sulfhydryl compounds, IL-10, TNF-α and LDH levels; erythrocytes were used for the analysis of thioredoxin reductase activity, glutaredoxin content, and pentose cycle enzymes (total G6PD, G6PD and 6PGD). Hyperthyroid animals presented body weight gain and final body weight reduction, which was associated with increased ROS levels and decreased sulfhydryl content in plasma. Thioredoxin reductase activity, glutaredoxin content, and pentose cycle enzymes levels in erythrocytes, as well as IL-10, TNF-α and LDH plasma levels were unaltered. Taken together, our results suggest an impairment in corporal mass associated with systemic oxidative stress at this stage of hyperthyroidism. Meanwhile, the pentose cycle was not influenced and systemic inflammation and tissue damage seem to be absent at this stage of hyperthyroidism.

Sclerostin and bone metabolism markers in hyperthyroidism before treatment and interrelations between them.

Sclerostin, which is a glycoprotein produced by osteocytes, reduces the formation of bones by inhibiting the Wnt signal pathway. Thyroid hormones are related with Wnt signal pathway and it has been reported that increased thyroid hormones in hyperthyroidism fasten epiphysis maturation in childhood, and increase the risk of bone fractures by stimulating the bone loss in adults. The aim of this study was to examine the sclerostin serum levels, the relation between sclerostin and thyroid hormones as well as the biochemical markers of the bone metabolism in patients with hyperthyroidism (including multinodular goiter and Graves' disease), whose treatments have not started yet. No difference was found in the serum sclerostin levels between the hyperthyroidism group (n=24) and the control group (n=24) (p=0.452). The serum osteocalcin levels and 24-hour urinary phosphorus excretion were found to be higher in the hyperthyroid group than in the control group (p<0.001, p=0.009). A positive correlation was determined between the sclerostin and bone alkaline phosphatase levels (p<0.001); a negative correlation between the osteocalcin and thyroid stimulating hormone (TSH) (p<0.05); a positive correlation between the osteocalcin and thyroid hormones (FT3,FT4) (p<0.001); and a positive correlation between the deoxypyridinoline and hydroxyproline (p<0.001). No correlation was determined between sclerostin and TSH,FT3,FT4 (p>0.05). Therefore, we consider that a long-term study that covers the pre-post treatment stages of hyperthyroidism, including both the destruction and construction of the skeleton would be more enlightening. Moreover, the assessment of the synthesis of sclerostin in the bone tissue and in the serum level might show differences.

Serum concentrations of HGF and IL-8 in patients with active Graves' orbitopathy before and after methylprednisolone therapy.

IntroductionGraves’ disease is the most common cause of hyperthyroidism, and orbitopathy is the most frequent extrathyroidal manifestation of Graves’ disease. The aims of this study were as follows: (1) to evaluate the serum concentration of HGF and IL-8 in the blood of newly diagnosed Graves’ disease patients with the first episode of active GO and healthy controls; (2) to estimate the influence of the thyroid function (euthyreosis vs. hyperthyreosis) on HGF and IL-8 blood levels in patients with active GO; (3) to evaluate the influence of intravenous (i.v.) methylprednisolone (MP) pulse therapy and additional oral MP treatment on HGF and IL-8 blood levels in patients with active GO.Patients and methodsThirty-nine Graves’ disease patients with the first episode of clinically active GO (Group A) were enrolled in the study. To estimate the influence of the thyroid function on serum concentrations of the studied proangiogenic factors, Group A was divided into Group A I (n = 18) in euthyroid and Group A II (n = 21) in hyperthyroid stage of Graves’ disease in moderate-to-severe stage of GO. The control group consisted of 20 healthy volunteers age- and sex-matched to the GO group. Concentrations of the studied proangiogenic factors in serum samples were measured by an enzyme-linked immunosorbent assay before (Group A) and after (Group A1) intensive pulse i.v.MP treatment and 1 month after the end of additional oral MP treatment (Group A2).ResultsWe found a significant increase in serum concentrations of studied factors in the GO group before immunosuppressive therapy when compared with the control group and decrease after i.v.MP treatment. One month after the end of additional oral MP treatment (Group A2), serum concentrations of HGF and IL-8 still decreased and no significant difference was observed in HGF and IL-8 concentrations when compared with the control group. We did not find the difference in serum concentration of the studied proangiogenic factors between patients in euthyroid and hyperthyroid stage of Graves’ disease before MP therapy.ConclusionsSerum HGF and IL-8 concentrations are elevated in Graves’ disease patients with active Graves’ orbitopathy as compared to the healthy control group. Successful management of active Graves’ orbitopathy with glucocorticoids is associated with a decrease in HGF and IL-8 serum concentrations.

Serum Concentration of VEGF and PDGF-AA in Patients with Active Thyroid Orbitopathy before and after Immunosuppressive Therapy

Thyroid orbitopathy (TO) is the most frequent extrathyroid manifestation of Graves' disease. The aim of this study was to evaluate the serum concentration of Vascular Endothelial Growth Factor (VEGF), Plated-Derived Growth Factor-AA (PDGF-AA) in the blood of patients with active OT before and after immunosuppressive therapy. The study was performed in group of 39 patients with clinically active TO (Group A) in euthyroid (n=18, Group A I) and hyperthyroid (n=21, Group A II) stage of Graves' disease in moderate or severe stage of TO. Control group consist of 20 healthy age-matched control subjects. Concentration of studied proangiogenic factors in serum samples were measured by an enzyme linked immunosorbent assay (ELISA) before (group A) and after (group A1) intensive pulse methylprednisolone treatment and one month after the end of additional oral methylprednisolone treatment (Group A2). We have found significant increased serum levels of VEGF in patients with TO (reg-ardless to treatment) when compared with control group (542.4±328.1 pg/ml vs. 94.6±55.3 pg/ml, p=0.0002) and increased serum levels of -PDGF-AA in patients before treatment (3 173.6±1 480.3 pg/ml) in comparison with controls (1 768.9±520.0 pg/ml) and patients after intensive pulse methyloprednisolone treatment (2 325.9±1 456.8 pg/ml). One month after the end of additional oral methylprednisolone treatment (Group A2) concentration of PDGF-AA still decreased and were was not significant difference with value in control group (1 853.1±795.4 vs. 1 769.9±520.0 pg/ml, p=0.99). Serum concentration of VEGF was still significantly higher compared with control. We have not observed difference in serum concentration of studied proangiogenic factors between patients in euthyroid or hyperthyroid stage of Graves' disease. RESULTS of the present study confirm the fact that angiogenesis could play a role in pathogenesis of thyroid orbitopathy.

Adrenocortical reserves in hyperthyroidism

Explicit data regarding the changes in adrenocortical reserves during hyperthyroidism do not exist. We aimed to document the capability (response) of adrenal gland to secrete cortisol and DHEA-S during hyperthyroidism compared to euthyroidism, and to describe factors associated with these responses. A standard-dose (0.25 mg/i.v.) ACTH stimulation test was performed to the same patients before hyperthyroidism treatment, and after attainment of euthyroidism. Baseline cortisol (Cor(0)), DHEA-S (DHEA-S(0)), cortisol binding globulin (CBG), ACTH, calculated free cortisol (by Coolen's equation = CFC), free cortisol index (FCI), 60-min cortisol (Cor(60)), and DHEA-S (DHEA-S(60)), delta cortisol (ΔCor), delta DHEA-S (ΔDHEA-S) responses were evaluated. Forty-one patients [22 females, 49.5 ± 15.2 years old, 32 Graves disease, nine toxic nodular goiter] had similar Cor(0), DHEA-S(0), CFC, FCI, and DHEA-S(60) in hyperthyroid and euthyroid states. Cor(60), ΔCor, and ΔDHEA-S were lower in hyperthyroidism. In four (10 %) patients the peak ACTH-stimulated cortisol values were lower than 18 μg/dL. When the test repeated after attainment of euthyroidism, all of the patients had normal cortisol response. Regression analysis demonstrated an independent association of Cor(60) with free T3 in hyperthyroidism. However, the predictors of CFC, FCI, and DHEA-S levels were serum creatinine levels in hyperthyroidism, and both creatinine and transaminase levels in euthyroidism. ACTH-stimulated peak cortisol, delta cortisol, and delta DHEA-S levels are decreased during hyperthyroidism, probably due to increased turnover. Since about 10 % of the subjects with hyperthyroidism are at risk for adrenal insufficiency, clinicians dealing with Graves' disease should be alert to the possibility of adrenal insufficiency during hyperthyroid stage.

Excessive thyroxine enhances susceptibility to apoptosis and decreases contractility of cardiomyocytes

Excessive thyroid hormone induces cardiac hypertrophy and promotes heart failure in patients with hyperthyroidism, but the mechanism remains elusive. Rats were orally administered with levothyroxine (100 μg/kg, T 4) for 4 weeks to induce hyperthyroidism. The calculated stroke volume decreased and the shortening amplitude–frequency relationship in unloaded contraction of isolated cardiomyocytes was negative in T 4-treated rats. Apoptotic rates increased and DNA laddering was also detectable in T 4-treated rat hearts. By contrast, in primary cultured cardiomyocytes, T 3 induced dose-dependent hypertrophy but did not affect the apoptotic rate. Angiotensin II further increased the apoptotic rate of T 3-induced hypertrophied cardiomyocytes. The apoptotic rate was dependent on the extent of cardiomyocyte hypertrophy. These results suggest that cardiac contractility is enhanced during the early stage of hyperthyroidism, but decreased during the late stage of hyperthyroidism. The hypertrophied cardiomyocytes were also susceptible to apoptotic stimulation by angiotensin II. Depressed cardiac contractility and enhanced apoptosis may lead to heart failure in hypertrophied myocardium.

Comparison of muscarinic receptor- and β-adrenoceptor-mediated vasorelaxation between euthyroid and acute hyperthyroid rats

Hyperthyroidism was induced by subcutaneous injections of l-thyroxine (T 4) (0.5 mg/kg/day) for 3 days in order to investigate the effects of acute hyperthyroidism on the vasorelaxing responses to isoprenaline and acetylcholine in isolated rat aortae. In the aortae, there was no significant difference in isoprenaline-induced relaxation between hyperthyroid and control rats, however acetylcholine-induced relaxation was significantly greater in hyperthyroid rats than in control rats. N G-nitro- l-arginine (L-NOARG), an inhibitor of nitric oxide (NO) synthase, reduced isoprenaline- and acetylcholine-induced relaxations in both hyperthyroid and control rats and in the presence of L-NOARG no significant difference in the acetylcholine-induced relaxation was seen between the two groups of rats. Indomethacin, a cyclo-oxygenase inhibitor, had no significant influence on both isoprenaline- and acetylcholine-induced relaxations in both control and hyperthyroid rats. 17-Octadecynoic acid (17-ODYA), a cytochrome P-450 mono-oxygenase inhibitor, reduced the both isoprenaline- and acetylcholine-induced relaxation in both hyperthyroid and control rats, and acetylcholine-induced relaxation was still greater in hyperthyroid rats than in control rats. These results indicate that an acute hyperthyroidism significantly enhances muscarinic receptor- but not adrenoceptor-mediated relaxations of the aortae and L-NOARG abolished an enhancement by acute hyperthyroidism of muscarinic receptor-mediated relaxation, suggesting that the effects may be due to an alteration in muscarinic receptor-mediated NO systems of the aortae at early stage of hyperthyroidism.

Methimazole-induced hypothyroidism paradoxically decreases homocysteine

Clinical hypothyroidism is associated with hyperhomocysteinemia, whereas the opposite is seen in hyperthyroidism. The effects of mild thyroid dysfunction on homocysteine concentrations are not known. We performed the following study to investigate this. Total homocysteine, vitamins B 6 and B 12, folate, fibrinogen, plasminogen activator inhibitor type 1, and lipids were measured in 11 subjects at baseline and after methionine loading. Subjects began methimazole (MMI), 40 mg daily, and were restudied during 2 stages of hypothyroidism. Liothyronine was added and subjects were restudied once thyrotropin normalized. Methimazole was stopped and studies were repeated during 2 stages of hyperthyroidism. Data were analyzed using repeated-measures analysis of variance. Post-methionine homocysteine decreased in each hypothyroid study compared with baseline (28.8 ± 10.7, 27.5 ± 9.9 vs 34.4 ± 9.2 μmol/L, respectively). In addition, both fasting and post-methionine homocysteine decreased in the euthyroid/MMI study arm compared with baseline despite equivalent thyrotropin values (fasting, 7.5 ± 3.0 vs 8.8 ± 3.5 μmol/L, P < .05; and post-methionine, 27.2 ± 10.6 vs 34.4 ± 9.2 μmol/L, P < .05, respectively). Fasting homocysteine decreased in the first hyperthyroidism study arm compared with baseline (6.6 ± 2.3 vs 8.8 ± 3.5 μmol/L, P < .05) and post-methionine homocysteine decreased in both hyperthyroid arms compared with baseline (25.2 ± 8.1, 24.2 ± 10 vs 34.4 ± 9.2 μmol/L, P < .05 respectively). In conclusion, mild thyroid dysfunction changes homocysteine metabolism. Unexpectedly, our results suggest a homocysteine-lowering effect of MMI.

Myocardial ultrastructure in cardiac hypertrophy induced by thyroid hormone?an acute study in rats

The early responses of the myocardium ultrastructure under thyroid dysfunction conditions, hemodynamic parameters, cardiac hypertrophy and ultrastructural evaluations were performed in hypothyroid and hyperthyroid rats submitted to different doses [T4-25 and T4-100; 0.025 mg and 0.1 mg kg(-1) body weight (BW).per day, respectively)]. All groups were treated for 7 days. The animals were sacrificed, the hearts were excised and weighed and the left ventricle tissue samples were processed for transmission election microscopy. Systolic blood pressure (SBP) was not altered by administration of T4. An increased heart rate and ratio of heart weight to body weight (HW/BW) were found in the hyperthyroid rats. However, the SBP and HW/BW decreased significantly in hypothyroid rats. No significant ultrastructural alterations were detected when the hypothyroid and T4-25 groups were compared with the control group. Alterations of cardiomyocytes nuclei of these groups were also not detected. Notably, disorganization of intercellular junctions was observed in many cardiomyocytes of T4-100 group. The present results indicate that in the early stages of hyperthyroidism, the cardiac hypertrophy development was mainly due to direct effects of thyroid hormone. Despite cardiac hypertrophy development, there is no ultrastructural evidence of myocardial degeneration.

Serum osteocalcin levels in hyperthyroidism before and after antithyroid therapy.

Hyperthyroidism is characterized by accelerated bone turnover, caused from direct stimulation of bone cells by increased thyroid hormones. In this study, we aimed to investigate serum osteocalcin levels as a bone formation marker, before antithyroid (propylthiouracil) therapy at hyperthyroid stage and after antithyroid therapy at euthyroid stage of the patients. Twenty four hyperthyroid patients (18 females, 6 males) and 20 (13 females, 7 males) healthy controls were included into this study. Blood and urine samples were taken before medical treatment at hyperthyroid state, and after the antithyroid therapy until the patients reached the euthyroid state. Serum alkaline phosphatase, osteocalcin, calcium, phosphorus, Free T3, Free T4, TSH and urine calcium/creatinine levels were assessed. We found a significant decrease in serum osteocalcin (p=0.006), urinary calcium/creatinine (p=0.004), and serum phosphorus (p=0.038) levels in euthyroid state in comparison to hyperthyroid state. The increases in serum bone formation marker osteocalcin and bone resorption marker urinary calcium/creatinine levels in hyperthyroid state compared to euthyroid state in our study confirmed that hyperthyroid patients have high bone turnover. We conclude that, hyperthyroid patients has high bone turnover of formation and resorption even after attainment of euthyroidism. Osteocalcin and urine calcium/creatinine are sensitive markers in documenting bone remodeling during treatment of hyperthyroidism.

Different time course of changes in sarcoplasmic reticulum and myosin isoforms in rat soleus muscle at early stage of hyperthyroidism.

We studied changes in the expression of myosin and sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA) and in Ca2+ uptake and release rates by the SR in rat slow-twitch soleus muscles treated with thyroid hormone (3,5,3'-triiodo-l-thyronine, T3) for 1, 3, 7 and 21 days. The content of fast SR Ca2+-ATPase isoform SERCA1a protein significantly increased as early as 3 days of T3 treatment, while a rise in fast myosin heavy chain isoforms was found only 21 days after the onset of T3 administration. T3-induced slow-to-fast transitions were much less pronounced in myosin light chain than in myosin heavy chain. Moreover, in vitro measurements of SR Ca2+-handling capacity with indo-1 indicated that increases in uptake rate preceded those of release rate (7 vs. 21 days). These data suggest that changes in the myosin and SERCA expressions seem not to occur in a coordinated manner at the early stage of hyperthyroidism and that intervention with T3 may temporarily produce slow-twitch type I fibres which contain, in addition to slow SERCA2a isoform, the appreciable amounts of fast SERCA1a isoform. Moreover, it is speculated that some fibres in the hyperthyroid soleus muscles may temporarily acquire unique contractile properties distinct from normal fast and slow fibres.

A fluctuation in adrenocepter- and muscarinic receptor-mediated blood pressure responses in acute hyperthyroid rats

Hyperthyroidism was induced by daily subcutaneous injections of l-thyroxine (T 4, 0.5 mg/kg/day) for 3 days, 1 week, or 2 weeks to study whether there is a fluctuation in adrenoceptor- and muscarinic receptor-mediated blood pressure responses at a hyperthyroid stage. T 4 treatment for 3 days or 1 week significantly suppressed the pressor response induced by norepinephrine (NE). The depressor responses induced by isoprenaline or acetylcholine (ACh) were increased by T 4 treatment for only 3 days. The pressor response induced by N G-nitro- l-arginine ( l-NA) was increased by T 4 treatment for only 3 days. Results suggest that adrenoceptor- and muscarinic receptor-mediated blood pressure responses fluctuate in hyperthyroidism caused by T 4 in rats, that the basal nitric oxide (NO) production and/or release are increased in hyperthyroid rats at an early stage of the disease.

Changes in vascular reactivity induced by acute hyperthyroidism in isolated rat aortae

Hyperthyroidism was induced by subcutaneous injections of l-thyroxine (T 4) (500 mg/kg/day) for 3 days in order to study whether adrenergic and muscarinic receptor-mediated vascular responses alter at an early stage of the disease. T 4 treatment was sufficient to induce a significant degree of thyroid weight loss, tachycardia, cardiac hypertrophy, and an elevation in serum T 4 levels. The tension of aortic ring preparations isolated from rats was measured isometrically to investigate the influence of acute hyperthyroidism. The contractions induced by norepinephrine (NE) were significantly suppressed in aortic rings from rats treated with T 4 compared with control rats. N G-nitro- l-arginine ( l-NOARG), an inhibitor of nitric oxide synthase (NOS), significantly enhanced NE-induced contraction in aortic rings from both control and T 4-treated rats, and the enhancement was greater in rats treated with T 4 than control rats. The relaxations induced by either acetylcholine (ACh) or sodium nitroprusside (SNP) were also significantly enhanced by T 4 treatment. l-NOARG abolished the relaxation induced by ACh in aortic rings from both control and T 4-treated rats. l-NOARG shifted SNP-induced relaxation curves of aortic rings from those of control rats to the left, but not with rats treated with T 4. T 4 treatment showed no influence on the amount of endothelial NOS (eNOS) protein. These results suggest that vascular responses alter at an early stage of hyperthyroidism and that it may be due to a modification in the NO system which is independent from the amount of eNOS protein.