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PubMed1995

Differential influences of carnitine palmitoyltransferase-1 inhibition and hyperthyroidism on cardiac growth and sarcoplasmic reticulum phosphorylation.

To characterize interventions resulting in 'physiological' growth of the heart, Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) had hyperthyroidism induced (0.05 mg.kg-1.day-1 triiodothyronine for 6 days) or were treated with a high dose of the carnitine palmitoyltransferase-1 inhibitor, etomoxir (15 mg.kg-1.day-1 for 5 weeks). Etomoxir increased cardiac growth evenly, but hyperthyroidism resulted in an over-proportional higher right ventricular weight. Both interventions increased the proportion of the myosin isozyme V1. The rate of sarcoplasmic reticulum (SR) Ca2+ uptake was increased to a greater extent in hyperthyroid rats than in etomoxir-treated rats (P < 0.05). Left ventricular levels of immunoreactive phospholamban (semiquantitative ELISA) were moderately decreased (P < 0.05) in hyperthyroid rats but not in etomoxir-treated rats. The protein kinase A-catalyzed in vitro 32P-incorporation into the SR Ca2+ pump modulator phospholamban was greatly reduced (P < 0.05) in hyperthyroid rats, indicating an increased in vivo phosphorylation. Etomoxir did not affect phospholamban phosphorylation in WKY rats. Thus, both a higher in vivo phospholamban phosphorylation state and a greater number of active Ca2+ pumps contributed to an increased rate of SR Ca2+ uptake in hyperthyroidism. The etomoxir treatment primarily increased the number of active Ca2+ pumps. A scheme is proposed focusing on long-term vs short-term regulation of the SR Ca2+ pump/phospholamban system in diseased states.

Animals↗
PubMed1987

The selective beta 1-blocking agent metoprolol compared with antithyroid drug and thyroxine as preoperative treatment of patients with hyperthyroidism. Results from a prospective, randomized study.

Despite the increasing use of beta-blocking agents alone as preoperative treatment of patients with hyperthyroidism, there are no controlled clinical studies in which this regimen has been compared with a more conventional preoperative treatment. Thirty patients with newly diagnosed and untreated hyperthyroidism were randomized to preoperative treatment with methimazole in combination with thyroxine (Group I) or the beta 1-blocking agent metoprolol (Group II). Metoprolol was used since it has been demonstrated that the beneficial effect of beta-blockade in hyperthyroidism is mainly due to beta 1-blockade. The preoperative, intraoperative, and postoperative courses in the two groups were compared, and patients were followed up for 1 year after thyroidectomy. At the time of diagnosis, serum concentration of triiodothyronine (T3) was 6.1 +/- 0.59 nmol/L in Group I and 5.7 +/- 0.66 nmol/L in Group II (reference interval 1.5-3.0 nmol/L). Clinical improvement during preoperative treatment was similar in the two groups of patients, but serum T3 was normalized only in Group I. The median length of preoperative treatment was 12 weeks in Group I and 5 weeks in Group II (p less than 0.01). There were no serious adverse effects of the drugs during preoperative preparation in either treatment group. Operating time, consistency and vascularity of the thyroid gland, and intraoperative blood loss were similar in the two groups. No anesthesiologic or cardiovascular complications occurred during operation in either group. One patient in Group I (7%) and three patients in Group II (20%) had clinical signs of hyperthyroid function during the first postoperative day. These symptoms were abolished by the administration of small doses of metoprolol, and no case of thyroid storm occurred. Postoperative hypocalcemia or recurrent laryngeal nerve paralysis did not occur in either group. During the first postoperative year, hypothyroidism developed in two patients in Group I (13%) and in six patients in Group II (40%). No patient had recurrent hyperthyroidism. The results suggest that metoprolol can be used as sole preoperative treatment of patients with hyperthyroidism without serious intra- or postoperative complications. Although the data indicate that the risk of postoperative hypothyroidism is higher after preoperative treatment with metoprolol than with an antithyroid drug, a longer follow-up period than 1 year is needed to draw conclusions regarding late results.

Adult↗
PubMed2001

Oxygen consumption in patients with hyperthyroidism before and after treatment with beta-blockade versus thyrostatic treatment: a prospective randomized study.

OBJECTIVE: To evaluate randomly the effect of thyrostatic treatment (tiamazole) versus selective (metoprolol) and nonselective beta-blockade (propranolol) on whole-body energy metabolism in women with hyperthyroidism. SUMMARY BACKGROUND DATA: beta-blockade is used as an alternative to thyrostatic drugs in the preoperative treatment of patients with hyperthyroidism. beta-blockers have well-established symptomatic effects, but in contrast to antithyroid drugs beta-blockade is thought to lack direct effects on the increased metabolism in hyperthyroidism. METHODS: Whole-body oxygen consumption and carbon dioxide production was measured in a semiopen canopy system with paramagnetic O2 and infrared CO2 sensors. A constant flow generator and the gas-dilution method for calculation of gas flow were used. Anabolic parameters were body weight, triceps skinfold, and arm muscle circumference. RESULTS: Tiamazole normalized oxygen consumption and induced signs of anabolism with improved nutritional state. Metroprolol did not affect oxygen consumption. Propranolol reduced elevated oxygen consumption by 54%. Body weight and other anthropometric assessments were stable after specific and nonspecific beta-blockade, which also led to symptomatic relief in approximately 90% of the patients. CONCLUSION: Tiamazole was the most effective drug to oppose the adverse effects of hyperthyroidism. Therefore, thyrostatic agents are recommended for preoperative treatments of patients with severe catabolic hyperthyroidism. Whenever beta-blockers are chosen for treatment of hyperthyroidism, propranolol (beta 1 + beta 2) has an advantage because it reduces the metabolic rate, whereas selective beta 1-blockade seemed to provide only symptomatic relief, related to the normalization of heart rate.

Adrenergic beta-Antagonists↗
PubMed1997

Hyperthyroidism in pregnancy.

The prevalence of hyperthyroidism in pregnancy is about 0.2%. The most common cause is Graves' disease. Maternal, fetal, and neonatal morbidity and mortality may be reduced to a minimum with careful attention to the clinical symptoms and interpretation of thyroid tests. Ideally, hyperthyroid women should be rendered euthyroid before considering conception. The incidence of maternal and neonatal morbidity is significantly higher in those patients whose hyperthyroidism is not medically controlled. Even the incidence of thyroid storm is high in women who are under poor medical supervision in the presence of a medical or obstetric complication. Maternal morbidity includes a higher incidence of toxemia, premature delivery, placenta abruptio, congestive heart failure, and thyroid crisis. In some series, anemia and infections were also reported. Neonatal morbidity includes SGA neonates, intrauterine growth retardation, LBW infants, and prematurity. Fetal goiter and transient neonatal hypothyroidism is occasionally reported in infants of mothers who have been overtreated with ATD. Propylthiouracil and MMI are equally effective in controlling the disease. In most patients, symptoms improved and thyroid tests returned to normal in 3-8 weeks after initiation of therapy. Resistance to ATD is extremely rare, most cases are caused by patient poor compliance. Surgery for the treatment of hyperthyroidism is reserved for the unusual patient who is allergic to both ATD; to those who have large goiters; to those who require large doses of ATD; or to those patients who poorly comply. Fetal and neonatal hyperthyroidism can be predicted in the majority of cases by the previous maternal medical and obstetric history and by the proper interpretation of thyroid tests. Finally, hyperthyroidism may recur in the postpartum period.

Antithyroid Agents↗
PubMed2006

Atrial angiotensinase activity in hypothyroid, euthyroid, and hyperthyroid rats.

Thyroid dysfunction produces marked cardiovascular responses. Hypothyroidism and hyperthyroidism cause important changes in the circulating renin-angiotensin system (RAS). Modifications in cardiac RAS have also been involved in cardiovascular alterations. Studies have revealed that thyroid hormones activate some components of cardiac RAS. Angiotensin (Ang) peptides are regulated by the activity of several aminopeptidases (AP) called angiotensinases. Previous results in our laboratory have demonstrated that thyroid dysfunction altered angiotensinase activities in hypothalamus, pituitary, and kidney. In the present study, we investigated the relationship between thyroid status and local angiotensinase activities in the atrium of hypothyroid, euthyroid, and hyperthyroid adult male rats. We have determined fluorometrically soluble and membrane-bound alanyl, glutamyl, and aspartyl aminopeptidase activities using naphthylamide derivatives as substrates. These activities have been, respectively, involved in the metabolism of Ang III to Ang IV, Ang II to Ang III, and Ang I to des-Asp Ang I. Hyperthyroidism was induced with subcutaneous injections of tetraiodothyronine (300 microg/kg/day), and the hypothyroid rats were obtained with 0.03% methimazole via the drinking water. Compared with that in euthyroid rats, a highly significant increase (by 50%) of soluble aspartyl aminopeptidase activity (P < 0.001) was observed in the atrium of hyperthyroid and hypothyroid animals. In membrane fractions, T4 treatment produced an increase in alanyl aminopeptidase (37%; P < 0.05) and aspartyl aminopeptidase activities (30%; P < 0.01). These results suggest higher formation of des-Asp Ang I in both hypothyroid and hyperthyroid rats but also suggest higher metabolism of Ang III to Ang IV in hyperthyroid animals, which is in agreement with the described alterations of cardiac RAS after thyroid dysfunction.

Animals↗
PubMed1995

Is previous hyperthyroidism still a risk factor for osteoporosis in post-menopausal women?

OBJECTIVE: Hyperthyroidism is a risk factor for osteoporosis, but the relative contributions of the episode of hyperthyroidism and thyroxine replacement for subsequent hyperthyroidism remain uncertain. In this study we have measured bone mineral density (BMD) in post-menopausal women with a previous history of hyperthyroidism, comparing those requiring thyroxine therapy with those remaining euthyroid and with an historical local control population. DESIGN: Cross-sectional study. PATIENTS: One hundred and six post-menopausal women with a previous history of hyperthyroidism. These were divided into four groups: treated with radioiodine, remaining euthyroid (group RU, n = 15); treated with radioiodine, receiving thyroxine for at least 5 years (group RT, n = 46); treated with surgery, remaining euthyroid (group SU, n = 21); treated with surgery, receiving thyroxine for at least 5 years (group ST, n = 24). There were 102 control subjects. MEASUREMENT: Forearm bone mineral density at distal and ultradistal sites as measured by single-photon absorptiometry. RESULTS: Results were expressed as 'Z-scores' i.e. number of standard deviations from the mean of a 5-year age-band from the local control population. Mean Z-scores at distal and ultradistal sites were as follows: -0.61 and -0.81 in group RU; -0.58 and -0.56 in group RT; -0.27 and -0.30 in group SU; -0.81 and -0.57 in group ST. Patients in groups RU, RT and ST but not SU had significantly lower BMD than controls. CONCLUSION: Post-menopausal women with previous hyperthyroidism treated with radioiodine have reduced BMD, whether or not receiving thyroxine. They should be targeted for densitometry and protective therapy with oestrogen should be considered. Those treated with surgery appear to be at less risk; this may be because most are diagnosed and treated whilst premenopausal. Thyroxine may have a deleterious effect in this group; longitudinal studies would provide further clarification.

Aged↗
PubMed2004

Long-term follow-up study of radioiodine treatment of hyperthyroidism.

OBJECTIVE: To determine the cumulative incidence of hypothyroidism during long-term follow-up in patients treated for hyperthyroidism by radioactive iodine (131)I (RAI) therapy, the significance of clinical factors in predicting the development of hypothyroidism, and the outcome after a fixed 7 mCi (259 MBq) dose of RAI. DESIGN: Prospective cohort study of patients treated for hyperthyroidism by RAI. PATIENTS AND MEASUREMENTS: Since 1965, details on 2043 patients treated by RAI therapy in Tampere University Hospital were entered into a computerized register. Following RAI treatment, thyroid status was monitored every 1-3 months during the first year, and subsequently at 1-3-year intervals until June 2002 or until the patient died or moved out of the Tampere University Hospital district. results The cumulative incidence of hypothyroidism in patients with Graves' disease and toxic multinodular goitre at 1, 10 and 25 years was 24%vs. 4%, 59%vs. 15% and 82%vs. 32%, respectively. In a Cox regression model, previous partial thyroidectomy [risk ratio (RR) = 1.63 in patients with Graves' disease and RR = 1.59 in those with toxic multinodular goitre] and age at the first RAI treatment (RR = 0.998 and RR = 0.996 per year) were statistically significantly associated with the development of hypothyroidism both in patients with Graves' disease and in those with toxic multinodular goitre. Antithyroid medication preceding RAI therapy (RR = 0.47) decreased and female gender (RR = 1.53) increased the risk of hypothyroidism only in patients with Graves' disease. Administration of a single dose of RAI resulted in the control of hyperthyroidism in 75% of patients, while two to six RAI treatments were needed in 25% of patients to achieve either a hypothyroid or a euthyroid state in both groups. None of the clinical factors studied was associated with the remission rate either in patients with Graves' disease or in those with toxic multinodular goitre. The remission rate did not differ between the patients who received a dose of RAI calculated according to the uptake of RAI and thyroid size and those who received an empirical dose of RAI. The fixed 7 mCi (259 MBq) dose of RAI cured 80% of patients. CONCLUSION: RAI treatment is effective in treating hyperthyroidism in patients with Graves' disease, but hypothyroidism will develop in 82% of patients in 25 years. Because the development of hypothyroidism seems to be inevitable and unpredictable by any clinical factors, the objective of RAI treatment should be to minimize the persistence of hyperthyroidism with the simplest possible form of treatment. We recommend a fixed 7 mCi dose of RAI to be used as the first empirical dose in the treatment of hyperthyroidism, at least in Graves' disease.

Female↗
PubMed1988

Amiodarone-induced hyperthyroidism: assessment of the predictive value of biochemical testing and response to combined therapy using propylthiouracil and potassium perchlorate.

In order to assess the value of thyroid function testing during amiodarone therapy, we reviewed all available tests in 128 patients treated with this drug. Nine patients (7.0%) developed biochemical hyperthyroidism with elevation of both free thyroxine index (FT4I) and free triiodothyronine index (FT3I) and marked suppression of serum thyroid stimulating hormone (TSH) after 1-46 months of therapy; six of these nine patients had clear clinical evidence of thyroid overactivity. Where serial tests were available before development of hyperthyroidism, this complication developed suddenly, despite previously stable normal indices of thyroid function, and could not be predicted by currently-available biochemical tests such as T4, T3, sensitive TSH, thyroglobulin or sex hormone binding globulin (SHBG) assays. Clinical features such as unexplained weight loss, proximal myopathy, exacerbation of arrhythmia, or heat intolerance appear to be the key to prompt diagnosis of this complication. Hyperthyroxinemia without T3 excess was found in 32.8% of patients without progression to true hyperthyroidism. Serum TSH remained detectable by sensitive assay in 17 out of 18 patients with amiodarone-induced euthyroid hyperthyroxinemia and was significantly higher than in patients with equivalent hyperthyroxinemia due to thyroxine therapy. Serial levels of SHBG were higher in patients with true hyperthyroidism than in those with euthyroid hyperthyroxinemia. The effect of combined treatment with propylthiouracil (800 mg/day) and potassium perchlorate (800 mg/day) was evaluated in five of the six clinically hyperthyroid patients. Biochemical euthyroidism was achieved after 7-19 weeks, a response slower than previously reported, indicating that this drug combination does not result uniformly in prompt resolution of amiodarone-induced hyperthyroidism.

Adolescent↗
PubMed2006

Radioiodine therapy in hyperthyroid disease: poorer outcome in patients with high 24 hours radioiodine uptake.

PURPOSE: To evaluate the importance of 24 h radioiodine uptake (24 h RIU) for the outcome of radioiodine treatment of hyperthyroidism. METHODS: Retrospective analysis of 72 patients who underwent radioiodine treatment for toxic goiter at our outpatient clinic [29 diffuse goiters (DG), 30 toxic multinodular goiters (TMG) and 13 toxic adenomas (TA)]. Thyroid status was determined by TSH, fT3 and fT4 levels, and outcome was rendered successful when hyperthyroidism was absent. Relation between low 24 h RIU (below median) or high 24 h RIU (above or equal to median) and outcome was evaluated. RESULTS: Of patients with DG and low 24 h RIU, 15% remained hyperthyroid, as opposed to 56% of patients with DG and high 24 h RIU (P<0.05). Of patients with TMG and low 24 h RIU, none remained hyperthyroid, as opposed to 44% of patients with TMG and high 24 h RIU (P<0.01). Of patients with TA and low 24 h RIU, none remained hyperthyroid, as opposed to 43% of patients with TA and high 24 h RIU (NS, P = 0.19). CONCLUSION: In patients with hyperthyroid disease treated with radioiodine the outcome is poorer for patients with high 24 h RIU compared with low 24 h RIU measured prior to treatment when the radioiodine dose is calculated on the basis of 24 h RIU.

Dose-Response Relationship, Radiation↗
PubMed2006

Results of thyroidectomy in 101 cats with hyperthyroidism.

OBJECTIVE: To describe outcome after thyroidectomy in hyperthyroid cats, with emphasis on peri- and postsurgical complications and recurrence. STUDY DESIGN: Retrospective study. ANIMALS: One hundred and one hyperthyroid cats. METHODS: Diagnostic work-up included preoperative measurement of plasma calcium, sodium, potassium, urea, and creatinine concentrations, and thyroid scintigraphy. A modified intracapsular dissection technique was performed. Postoperatively, parathyroid gland function was evaluated by measuring plasma calcium concentration several times daily. Outcome was obtained by standard telephone questionnaire. RESULTS: Thyroid scintigraphy revealed ectopic hyperplastic thyroid tissue (EHTT) in 9 cats. Preoperatively, 29 of 91 cats had hypokalemia. Two cats died within 3 days after surgery and 5 of 86 cats developed postoperative transient hypocalcemia. On histologic examination, thyroid carcinoma was identified in 3 of 88 cats. Hyperthyroidism recurred in 5 cats between 3 and 59 months; 4 of these cats had EHTT preoperatively. The difference in recurrence rate between hyperthyroid cats with and without EHTT was significant (P<.001). CONCLUSION: Complications were uncommon after thyroidectomy performed by an experienced surgeon when combined with an anesthetic regimen associated with minimal adverse cardiovascular effects. Hyperthyroid cats with EHTT had a significantly higher chance of recurrence. CLINICAL RELEVANCE: Thyroidectomy is associated with a low incidence of surgical complications and is an effective treatment for hyperthyroid cats when radioactive iodine therapy is not available. Preoperative thyroid scintigraphy is advised. Surgery is not recommended when EHTT is present, because of a higher chance of developing recurrent disease.

Animals↗
PubMedDate not supplied

Use of the thyrotropin releasing hormone stimulation test to diagnose mild hyperthyroidism in cats.

We evaluated serum T4 and T3 concentrations before and after administration of thyrotropin releasing hormone (TRH) in 35 cats with mild to moderate hyperthyroidism, 15 cats with nonthyroidal disease, and 31 clinically normal cats. The TRH stimulation test was performed by collecting blood for serum T4 and T3 determinations before and 4 hours after IV administration of 0.1 mg/kg TRH. Mean basal serum thyroid hormone concentrations in hyperthyroid cats were significantly (P < .05) higher than concentrations in normal cats and in those with nonthyroidal disease, but there was considerable overlap among the 3 groups. After administration of TRH, mean serum T4 concentrations increased significantly in all groups of cats, whereas mean T3 concentrations increased significantly in normal cats and in those with nonthyroidal disease, but not in cats with hyperthyroidism. The absolute difference between mean basal and TRH-stimulated serum concentrations of T4 in cats with hyperthyroidism (10.7 nmol/L) was significantly lower than the difference in the cats with nonthyroidal disease (20.0 nmol/L) and in clinically normal cats (28.3 nmol/L), but there was considerable overlap in values among groups. The mean value for relative change in serum T4 concentration after TRH was significantly lower in cats with hyperthyroidism (18.9%) than in those with nonthyroidal disease (110.0%) and in clinically normal cats (130.2%). Serum T4 concentrations increased by > 50% in all normal cats and cats with nonthyroidal disease, whereas only 4 (11.4%) of the 35 hyperthyroid cats had an increase of > 50% after TRH administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2005

Modulation of P-glycoprotein expression in hyperthyroid rat tissues.

P-glycoprotein (Pgp) is expressed in various normal tissues and plays an important role in drug absorption and disposition. In addition, it is supposed that alterations in the expression levels of Pgp are involved in the inter- and intraindividual variability of pharmacokinetics of many drugs. Since pharmacokinetic properties of various drugs are altered in patients with thyroid disorders, we examined the expression of Pgp and mdr1a/1b mRNA in the kidney, liver, jejunum, and ileum from euthyroid and hyperthyroid rats. Western blot analysis revealed that Pgp expression was markedly increased in the kidney and liver of hyperthyroid rats. In contrast, it was slightly increased in the jejunum and ileum. mdr1a/1b mRNA levels were significantly increased in the kidney of hyperthyroid rats. However, they were not increased in the liver as well as in the jejunum and ileum of hyperthyroid rats. Expression levels of bile salt export pump and mdr2 mRNA were also unchanged in hyperthyroid rat liver. Taken together, these findings suggest that thyroid hormone induces Pgp expression in a tissue-selective manner, and that the modulation of mdr1a/1b mRNA expression in the hyperthyroid state varies among tissues.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2006

Incidence, clinical characteristics and outcome of congestive heart failure as the initial presentation in patients with primary hyperthyroidism.

BACKGROUND: There are limited systematic data on the incidence, clinical characteristics and outcomes of congestive heart failure (CHF) in patients with hyperthyroidism. The aim of this study was to investigate the incidence, clinical characteristics and outcome of CHF as the initial presentation in patients with primary hyperthyroidism. METHODS: The prevalence, clinical characteristics and outcome of CHF was studied in 591 consecutive patients (mean (SD) age 45 (1) years, 140 men) who presented with primary hyperthyroidism. RESULTS: CHF was the presenting condition in 34 patients (5.8%) with hyperthyroidism. The presence of atrial fibrillation at presentation (OR 37.4, 95% CI 9.72 to 144.0, p<0.001) was an independent predictor for the occurrence of CHF. Of the 34 patients with CHF, 16 (47%) had systolic left ventricular dysfunction with left ventricular ejection fraction (LVEF)<50%. They were predominantly male (OR 26.6, 95% CI 2.6 to 272.5, p = 0.006) and had a lower serum thyroxine level (OR 0.93, 95% CI 0.87 to 0.99, p = 0.044) than patients with preserved left ventricular systolic function. In these patients, LVEF (55 (4)% vs 30 (2)%, p<0.001) and New York Heart Association functional class (1.2 (0.1) vs 2.5 (0.2), p<0.001) improved significantly 3 months after achieving euthyroid status. Systolic left ventricular dysfunction (mean (SD) LVEF 38 (4)%) persisted on long-term follow-up in five PATIENTS: no clinical parameter could be identified to predict the occurrence of this persistent cardiomyopathy (p>0.05). CONCLUSION: CHF was the initial clinical presentation in approximately 6% of patients with hyperthyroidism, and half of them had left ventricular systolic dysfunction. Symptoms of CHF subsided and LVEF improved after treatment for hyperthyroidism. Nonetheless, one-third of these patients developed persistent dilated cardiomyopathy.

Adolescent↗
PubMed1984

Hyperthyroidism and immune thrombocytopenia.

Hyperthyroidism and immune thrombocytopenia occurred concurrently in five patients; in a sixth, thyrotoxicosis developed after successful treatment of the thrombocytopenia. Correction of the hyperthyroidism was followed by a variable pattern of clinical response. In one case with mild asymptomatic thrombocytopenia spontaneous complete remission occurred. Two patients required adrenocorticosteroids to control severe thrombocytopenic purpura during the period of hyperthyroidism, after which complete remission occurred. Another patient with severe symptomatic thrombocytopenia remains with a partially compensated thrombocytolytic state but is without purpura and off all therapy. A fifth patient required splenectomy for drug-resistant thrombocytopenia and remains critically dependent on immunosuppressive therapy. The sixth patient had a relapse of immune thrombocytopenia with subsequent development of thyrotoxicosis but platelet count spontaneously returned to normal after correction of the hyperthyroidism. Pregnancy in two of these six patients was not associated with recurrence of either hyperthyroidism or thrombocytopenia. Management of symptomatic purpura in adults with co-existent hyperthyroidism may differ from that customarily employed since adrenocorticosteroid therapy may need to be extended until euthyroidism has been established before proceeding to splenectomy. When surgery is necessary, the risk of thyrotoxic storm should be anticipated, and the patient appropriately premedicated.

Adult↗
PubMed1993

Alpha-adrenergic modulation of transient outward current in hyperthyroid rabbit myocytes.

The alpha 1-adrenergic modulation of the transient outward potassium current (I(t)) was studied in single cardiac myocytes obtained from normal (euthyroid) and hyperthyroid rabbits. Rabbits were made hyperthyroid by four or five daily intraperitoneal injections of 0.4 mg/kg body wt thyroxine. Currents were recorded using the whole cell, suction-electrode, voltage-clamp method. It was found that the alpha-adrenergic agonist methoxamine attenuates I(t) in rabbit ventricular cells, as reported earlier for atrial cells. This attenuation is significantly reduced in the hyperthyroid state. For example, 0.2 mM reduces I(t) magnitude (at +20 mV) by close to 40% in euthyroid cells and by only 20% in the hyperthyroid cells. Half-maximal effective concentration values (extrapolated) are close to 0.4 mM in normal and 1 mM in hyperthyroid cells. Preliminary results show similar effects in atrial cells as well. These results may be related to a decrease in the density of membrane alpha-adrenergic receptors in hyperthyroid conditions, or to the induction of a new class of I(t) channels that is less sensitive to alpha-agonists.

Animals↗
PubMed1996

Short- and long-term effects of neonatal hypo- and hyperthyroidism on coronary arterioles in rat.

Neonatal hypo- and hyperthyroid effects on coronary arteriolar geometry were examined in newborn male Sprague-Dawley rats treated for 12 or 28 days with either triiodothyronine or propylthiouracil. Long-term effects were assessed in weaned rats 52 days after stopping treatment. Influence of both neonatal conditions was more pronounced after 28 days. Neonatal hyperthyroidism induced cardiac hypertrophy; neonatal hypothyroidism attenuated cardiac growth. Hyperthyroid rats had similar arteriolar and capillary numerical densities and arteriolar length density but significantly greater (P < 0.05) total arteriolar length than control. Hypothyroid rats had similar arteriolar numerical and length densities, greater capillary numerical density (P < 0.05), but markedly lower total arteriolar length (P < 0.01) than control. Results suggest that neonatal hyperthyroidism stimulates arteriolar and capillary growth, whereas neonatal hypothyroidism attenuates arteriolar but not capillary growth. After cessation of treatment, total arteriolar length in previously hyperthyroid rats did not change despite increased cardiac mass, whereas previously hypothyroid rats demonstrated marked increases in both cardiac mass and total arteriolar length (P < 0.01). These results indicate a lasting inhibitory effect of early hyperthyroidism on subsequent arteriolar growth.

Animals↗
PubMed1997

Role of the renin-angiotensin system in cardiac hypertrophy induced in rats by hyperthyroidism.

This study was conducted to examine whether the renin-angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy without involving the sympathetic nervous system. Sprague-Dawley rats were divided into control-innervated, control-denervated, hyperthyroid-innervated, and hyperthyroid-denervated groups using intraperitoneal injections of thyroxine and 6-hydroxydopamine. After 8 wk, the heart-to-body weight ratio increased in hyperthyroid groups (63%), and this increase was only partially inhibited by sympathetic denervation. Radioimmunoassays and reverse transcription-polymerase chain reaction revealed increased cardiac levels of renin (33%) and angiotensin II (53%) and enhanced cardiac expression of renin mRNA (225%) in the hyperthyroid groups. These increases were unaffected by sympathetic denervation or 24-h bilateral nephrectomy. In addition, losartan and nicardipine decreased systolic blood pressure to the same extent, but only losartan caused regression of thyroxine-induced cardiac hypertrophy. These results suggest that thyroid hormone activates the cardiac renin-angiotensin system without involving the sympathetic nervous system or the circulating renin-angiotensin system; the activated renin-angiotensin system contributes to cardiac hypertrophy in hyperthyroidism.

Animals↗
PubMed2000

Single-channel activity and expression of atrial L-type Ca(2+) channels in patients with latent hyperthyroidism.

Patients with "latent hyperthyroidism" (suppressed thyroid-stimulating hormone and normal circulating thyroid hormones) are at risk to develop atrial fibrillation. In animal models, hyperthyroidism is associated with increased cardiac L-type Ca(2+) current. Therefore, we assessed L-type channel function and expression in right atria from patients undergoing cardiac surgery. Single L-type channels were studied in the cell-attached condition. Voltage dependence of gating was similar in patients with and without latent hyperthyroidism. With use of a pulse protocol leading to maximum channel availability, single-channel activity was further analyzed. Average peak current was significantly enhanced in latent hyperthyroidism, mainly because of an increased channel availability (P < 0.05). Protein expression was analyzed by Western blot. In latent hyperthyroidism, expression of Ca(2+) channel alpha(1)-subunits was increased more than threefold (P < 0.01). In contrast, sarco(endo)plasmic reticulum Ca(2+)-ATPase and phospholamban levels were not significantly changed. We only observed a trend toward increased sarco(endo)plasmic reticulum Ca(2+)-ATPase expression (P = 0.085). Function and expression of human atrial L-type Ca(2+) channels are increased in latent hyperthyroidism. These endocrine effects on the heart may be clinically relevant.

Blotting, Western↗