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PubMedDate not supplied

[Agranulocytosis and acute coronary syndrome in apathetic hyperthyroidism].

INTRODUCTION: Tissue expose to excessive levels of circulating thyroid hormones results in thyrotoxicosis. In most cases, thyrotoxicosis is due to hyperactivity of the thyroid gland. Cardiovascular and myopathic manifestations are predominant clinical features in most hyperthyroid patients, aged 60 years and older. Some of patients have apathetic hyperthyroidism which presents with weight loss, small goiter, severe depression and without clinical features of increased sympathetic activity [3, 6]. About 50% of patients with cardiovascular manifestations have no evidence of underlying heart disease. Cardiac problems resolve when euthyroid state is established [3]. Three treatment modalities are available in hyperthyroidism, namely medicament therapy, surgery and radioactive iodine. Antithyroid drug therapy complications, can be mild such as rash, which is managed without cessation of therapy by antihistamines administration. On the other hand, very serious complications such as agranulocytosis, necessitate immediate discontinuation of the medication and appropriate treatment. Although extremely rear, it is life-threatening with highly variable recovery time. CASE REPORT: A 62-year-old woman with recurrent hyperthyroidism was admitted after treatment of agranulocytosis due to antithyroid drugs in another institution with G-CSF. The patient presented with clinical features of apathetic hyperthyroidism with extremely elevated thyroid hormone levels (total and free T4) and suppressed TSH. Radioactive iodine (5 mCi) was administered after increased thyroid uptake was confirmed. Echocardiography on admission was normal. ECG revealed moderately inverted T waves in standard and V1, V2 precordial leads. Laboratory analysis revealed mild normocytic anemia with normal white blood cell count, hypokaliemia and normal concentration of creatine phosphokinase, lactic dehydrogenase and mildly elevated aspartate transminase in sera. Chest X-ray was consistent with pulmonary emphysema. Because the worsening of ECG changes she was transferred to Coronary unit. The diagnosis of non-Q myocardial infarction was confirmed and treatment with nitrates and beta-adrenergic antagonists was instituted. Four weeks later she became euthyroid and coronarography was performed. Subepicardial coronary arteries were normal (Figure 1). She was dismissed, and still euthyroid three months later. DISCUSSION: Agranulocytosis is very rare but very serious complication of antithyroid drug therapy. It can be detected in about 0.1-1% patients during the first three months of treatment. Sudden appearance, heralded by sore throat and fever, prompt physicians to seek white blood cell and differential count [1-3]. Confirmation of diagnosis urges cessation of drug therapy and appropriate antibiotic treatment. Recently, it was reported that recombinant human granulocyte colony-stimulating factor (rhG-CSF) is to be effective in shortening the recovery time in the neutropenic patients undergoing chemotherapy and also in patients with other types of neutropenia [5]. Tamai at al. [7] confirmed positive outcome in 34 patients treated with rhG-CSF compared to corticosteroid treatment. Hematologic laboratory abnormalities disappear 7-10 days after session of therapy. Patients completely recover two to three weeks later. Fatal outcome was also described [1-5]. Thyroid hormones have profound effects on cardiovascular physiology, especially on heart rate, cardiac output and systemic vascular resistance. In patients with hyperthyroidism, cardiac output is much higher than in normal persons. This is the result of direct effect of thyroid hormones on cardiac muscle contractility, heart rate and decrease in systemic vascular resistance. Excessive thyroid hormone secretion increases cardiac Na-K-activated plasma membrane ATP-ase and sarcoplasmic reticulum Ca-activated ATP-ase with resultant in increase myocardial contractility [6, 9]. Sinus tachycardia is the most common rhythm disorder in hyperthyroidism, but paroxysmal tachycardia and atrial fibrillation are not rare. This can be explained by increased heart rate, cardiac output, blood volume, coronary artery flow and peripheral oxygen consumption in thyrotoxicosis [9]. Patients with coronary arteriosclerosis can develop angina pectoris during thyrotoxic stage, which can be explained by imbalance between cardiac demand and supply. Myocardial damage is often in thyrotoxic patients with chronic hart failure, together with myocardial infarction in patients without coronary disease [2,6]. Congestive heart failure and atrial fibrillation are relatively resistant to digitalis treatment because of high metabolic turn over of medication and excessive myocardial irritability in hyperthyroidism [6]. Cardiovascular and myopathic manifestations predominate in older hyperthyroid patients (over 60 years) and some of them can have only few symptoms of hyperthyroidism [1-3]. Thyrotoxic state characterized by fatigue, apathy, extreme weakness, low-grade fever and sometimes congestive heart failure are designated as apathetic hyperthyroidism. Such patients have small goiters, mild tachycardia and often cool and dry skin with few eye signs [6]. Patients with subclinical hyperthyroidism are at increased risk for atrial fibrillation [9]. Unstable angina and non-Q myocardial infarction (non ST elevation) are acute manifestation of coronary artery disease. The acute coronary syndrome of unstable angina, non-Q myocardial infarction and Q-wave myocardial infarction have atherosclerotic lesions of the coronary arteries as a common pathogenic substrate. Erosions or ruptures of unstable atherosclerotic plaque triggered pathophysiologic processes, resulted in thrombus formation at the site of arterial injury. This leads to abrupt reduction or cessation through the affected vessel. Clinical manifestations of unstable angina and non-Q myocardial infarction are similar and diagnosis of non-Q myocardial infarction is made on the basis of elevated serum markers indicative of cardiac necrosis, detected in peripheral circulation. Acute coronary syndrome ranging from unstable angina to myocardial infarction an non-Q myocardial infarction represents increasingly severe manifestations of the same pathophysiologic processes [10,11]. In conclusion, these 62-year-old woman presented with apathetic form of recurrent hyperthyroidism associated with two serious complications, life-threatening agranulocytosis and acute coronary syndrome.

Agranulocytosis↗

PubMed1989

Significance of latent hyperthyroidism.

In euthyroidism the circadian rhythm and pulsatility of TSH is well known. With regard to hyperthyroidism only very preliminary data were described. In this study we investigated the secretion pattern of the pituitary-thyroid axis hormones during 24 h in latent and overt hyperthyroidism and in euthyroidism with regard to common and different properties. Blood was obtained for 24 h at 10-min intervals. In euthyroidism we found intraindividually three overlapping patterns of TSH, which are different in amplitude and frequency and can be found interindividually, too. These patterns are equal to the circadian rhythm, pulsatile secretion and lastly to the methodic rustle. The circadian rhythm in latent hyperthyroidism is distinctly suppressed and in overt hyperthyroidism totally. Whereas in latent hyperthyroidism pulsatile secretion is extant, in overt hyperthyroidism the TSH pulses are absent. To record the patients' TSH circadian rhythm with only three blood samples, we defined the TSH-Triplex. In young as well as in elderly healthy volunteers it demonstrated significantly higher TSH levels at midnight (at 24:00 h) than it did at 4 p.m. and 8 a.m. The present study shows a significantly different TSH pattern in latent hyperthyroidism compared to euthyroidism. It should be discussed whether latent hyperthyroidism could be defined as hyperthyroidism stage I. On the other hand, latent hyperthyroidism could be an illness with its own cause, different from hyperthyroidism. Our data suggest that the laboratory findings of latent hyperthyroidism in each age are non-physiological. However, the cause for this disorder is unclear until now; hence further investigations are necessary.

Adult↗

PubMed2002

Bone remodelling markers and serum cytokines in patients with hyperthyroidism.

OBJECTIVE: This study was designed in order to evaluate bone turnover with bone formation and resorption markers in hyperthyroidism and its possible relationship with serum cytokines interleukin 6 (IL-6) and tumour necrosis-alpha (TNF-alpha), levels of thyroid hormones and thyroid autoantibodies. DESIGN AND PATIENTS: Twenty-six hyperthyroid patients including nine with Graves' disease, 14 with toxic multi-nodular disease and three toxic adenoma were studied. Twenty normal subjects served as the control group. MEASUREMENTS: Serum calcium, phosphorus, total and bone-specific alkaline phosphatase, procollagen type 1-C peptide (PICP), osteocalcin, IL-6 and TNF-alpha measurements were performed and deoxypyridinoline (free DPD), calcium, phosphorus and creatinine levels were measured in fasting morning urine specimens of all hyperthyroid patients and all controls. Also, serum total and free T3 and T4 and TSH were analysed and thyroid antiperoxidase and antithyroglobulin antibodies were determined in sera of hyperthyroid patients. Patients with hyperthyroidism received propylthiouracil treatment until the achievement of euthyroidism and then serum cytokine levels were remeasured. RESULTS: Mean serum values of osteocalcin, total and bone-specific alkaline phosphatase were all significantly higher in hyperthyroid patients than in normal controls. PICP levels were not significantly different between these two groups. Urinary deoxypyridinoline levels were markedly elevated in hyperthyroid patients compared to the control group. There was a significant positive correlation between urinary free DPD levels and serum free T3, free T4 and T4 levels. Serum free T4 levels also correlated with urinary calcium levels. Serum IL-6 values were significantly higher in hyperthyroid patients compared to control group. TNF-alpha levels were slightly lower in patients with hyperthyroidism. No significant correlation was found between bone remodelling markers and serum cytokines. Serum Il-6 levels were correlated positively with age. After the treatment period both IL-6 and TNF-alpha returned to levels comparable with euthyroid controls. CONCLUSION: Bone turnover is increased in favour of resorption and the rate of resorption is associated with the levels of thyroid hormones in hyperthyroidism. The increase in the levels of serum IL-6 in hyperthyroidism is not related directly with bone resorption seen in hyperthyroidism.

Adult↗

PubMed2001

Differential effect of hyperthyroidism on rat epididymal glycosidases.

The impact of hyperthyroidism on epididymal glycosidases was studied in albino rats. Hyperthyroidism was induced in Wistar rats aged 30 days by daily injection of T4 (25 microg/100 g body weight/day intramuscularly) for 30 or 60 days; control rats were injected with vehicle (alkaline saline, pH 7.8). One set of hyperthyroid rats was reverted to euthyroid status by withdrawing T4 treatment after 30 days of hyperthyroidism. To asses the direct effect of thyroid hormone on epididymal hexosaminidases, caput, corpus and cauda tissues were stimulated with 25, 50 or 100 ng/mL T3 for 24 h, after an initial culture of 24 h. The activity of beta-glucosidase decreased in caput, corpus and cauda epididymis of hyperthyroid rats. beta-Galactosidase activity increased in the caput epididymis irrespective of the duration of hyperthyroidism. While a similar decrease occurred in the corpus and cauda epididymis in the 30 day hyperthyroid group, an opposite trend was observed in 60 day hyperthyroid rats. Caput beta-N-acetylglucosaminidase activities increased at both time points, whereas activity decreased in the corpus and cauda in 30 day, but increased in 60 day hyperthyroid rats. Hyperthyroidism consistently increased caput and corpus beta-N-acetylgalactosaminidase activity irrespective of the duration. Cauda epididymal beta-N-acetylgalactosaminidase activity was decreased in 30 day and increased in 60 day hyperthyroid rats. Hyperthyroidism induced changes in caput beta-galactosidase, beta-N-acetylgalactosaminidases, corpus beta-N-acetylglucosaminidase and cauda beta-N-acetylgalactosaminidase which were irreversible while the remaining actvities were brought back to normal when T4 treatment was withdrawn. In vitro studies showed that T3 stimulates epididymal hexosaminidases (beta-N-acetylglucosaminidase and beta-N-acetylgalactosaminidase) irrespective of the dose. These data suggest that thyroid hormones have a specific and direct influence on glycosidases in specific regions of the epididymis.

Animals↗

PubMed1999

Hyperthyroidism facilitates cardiac fatty acid oxidation through altered regulation of cardiac carnitine palmitoyltransferase: studies in vivo and with cardiac myocytes.

The aim was to establish whether increased cardiac fatty acid oxidation in hyperthyroidism is due to direct alterations in cardiac metabolism which favour fatty acid oxidation and/or whether normal regulatory links between changes in glucose supply and fatty acid oxidation are dysfunctional. Euthyroid rats were sampled in the absorptive state or after 48 h starvation. Rats were rendered hyperthyroid by injection of tri-iodothyronine (1000 microg/kg body wt. per day; 3 days). We evaluated the regulatory significance of direct effects of hyperthyroidism by measuring rates of palmitate oxidation in the absence or presence of glucose using cardiac myocytes. The results were examined in relation to the activity/regulatory characteristics of cardiac carnitine palmitoyltransferase (CPT) estimated by measuring rates of [3H]palmitoylcarnitine formation from [3H]carnitine and palmitoyl-CoA by isolated mitochondria. To define the involvement of other hormones, we examined whether hyperthyroidism altered basal or agonist-stimulated cardiac cAMP concentrations in cardiac myocytes and whether the effects of hyperthyroidism could be reversed by 24 h exposure to insulin infused subcutaneously (2 i. u. per day; Alzet osmotic pumps). Rates of 14C-palmitate oxidation (to 14CO2) by cardiac myocytes were significantly increased (1.6 fold; P< 0.05) by hyperthyroidism, whereas the percentage suppression of palmitate oxidation by glucose was greatly diminished. Cardiac CPT activities in mitochondria from hyperthyroid rats were 2-fold higher and the susceptibility of cardiac CPT activity to inhibition by malonyl-CoA was decreased. These effects were not mimicked by 48 h starvation. The decreased susceptibility of cardiac CPT activities to malonyl-CoA inhibition in hyperthyroid rats was normalised by 24 h exposure to elevated insulin concentration. Acute insulin addition did not influence the response to glucose in cardiac myocytes from euthyroid or hyperthyroid rats and basal and agonist-stimulated cAMP concentrations were unaffected by hyperthyroidism in vivo. The data provide insight into possible mechanisms by which hyperthyroidism facilitates fatty acid oxidation by the myocardium, identifying changes in cardiac CPT activity and malonyl-CoA sensitivity that would be predicted to render cardiac fatty acid oxidation less sensitive to external factors influencing malonyl-CoA content, and thereby to favour fatty acid oxidation. The increased CPT activity observed in response to hyperthyroidism may be a consequence of an impaired action of insulin but occurs through a cAMP-independent mechanism.

Animals↗

PubMed2005

Multivariate analysis of risk factors for feline hyperthyroidism in New Zealand.

AIM: To search for putative risk factors for feline hyperthyroidism in New Zealand, using a case-control study. METHODS: A questionnaire-based case-control study involving the owners of 375 cats in New Zealand (125 hyperthyroid cats, 125 randomly selected control cats, and 125 age- and sex-matched control cats) was conducted to examine associations between potential risk factors and occurrence of feline hyperthyroidism. Data were collected between December 1996 and February 1998, relative to cat and owner demography and medical history, cats' indoor and outdoor environments, and cats' diets. A range of statistical techniques was employed to analyse the data, including descriptive analyses, univariate logistic regression for each variable and multivariate stepwise forward logistic regression. RESULTS: Multivariate analysis revealed that affected cats were more likely to be female (odds ratio (OR)=3.3; 95% confidence interval (CI)=1.2-9.0) and older than unaffected random control cats. Purebred cats were at a much lower risk of being diagnosed as hyperthyroid than were domestic short- and long-haired cats (OR=0.01; 95% CI=0.001-0.20). If more than one cat was present in a household, hyperthyroidism was less likely to be identified (OR=0.15; 95% CI=0.05-0.44) compared with single-cat households. Hyperthyroid cats were 6.6 times more likely (95% CI=1.8-23.9) to be reported to sleep predominantly on the floor than control cats. Cats whose bedding was regularly treated with anti-flea products appeared to be at a considerably higher risk for hyperthyroidism (OR=57.6; 95% CI=3.8-->200); and, to a lesser extent, so were cats living in households where fly sprays were reported to be used regularly (OR=3.3; 95% CI=1.2-9.3). The interaction between drinking water from puddles and regular use of organic garden fertilisers, such as compost or animal manure, was associated with a 5.3-fold (95% CI=1.1-25.6) increase in the risk of cats being diagnosed with the disease. Hyperthyroid cats were twice as likely (95% CI=0.3-12.9) to have eaten at least half of their daily food requirements as canned commercial cat food compared with unaffected cats. Cats exposed to a variety of flavours of canned cat food were more likely to be diagnosed with hyperthyroidism than were those fed only one flavour (OR=3.8; 95% CI=1.5-9.6). The presence of dental disorders was associated with a 5.5-fold increase in the risk of being diagnosed as hyperthyroid and this association was independent of the cat's age (95% CI=1.7-17.5). CONCLUSIONS: The results of this study support and extend those in several earlier reports and show that cats in New Zealand are, in many respects, similar to cats in Europe and North America in terms of their susceptibility to hyperthyroidism. The finding that female cats are predisposed to hyperthyroidism is at variance with most previously published work. It remains unclear which, if any, of the identified disease associations are causal, so further studies of this increasingly prevalent feline endocrinopathy are warranted.

Animals↗

PubMed2004

Bone mineral density in hyperthyroidism.

OBJECTIVE: To investigate whether previous hyperthyroidism is a cause of permanent secondary osteoporosis. DESIGN AND PATIENTS: In this cross-sectional study, 164 women with untreated or previously treated overt and symptomatic hyperthyroidism were examined 0-31 years after the initial episode of hyperthyroidism and its treatment, and were compared with a control group of 79 age-matched women without previous history of hyperthyroidism. Subjects with current or previous metabolic bone disease, any antiresorptive treatment for osteoporosis or treatments and habits known to affect bone metabolism were excluded. MEASUREMENTS: The age of the first manifestation of the disease, the age at the measurement of bone mineral density (BMD) at the spine and femoral neck and the interval between diagnosis and treatment of hyperthyroidism and BMD measurement were recorded and the Z-scores and T-scores of BMD were analysed. RESULTS: Untreated hyperthyroidism and hyperthyroidism up to 3 years after its diagnosis and treatment were associated with decreased BMD. Three or more years after the first episode of the disease the mean Z-score at both skeletal sites was near zero and not different from the controls. The age at which hyperthyroidism was manifested for the first time had no effect on the final outcome. Women affected at a young age (13-30 years) had a more pronounced loss of BMD when examined untreated or early (< 3 years) after diagnosis, but a BMD significantly above zero if examined later (> 3 years). Older women (aged 51-70 years) showed a similar pattern, although the differences were not significant. Middle-aged subjects (31-50 years) had the smallest loss of BMD during the first 3 years. Analysis of T-scores of former hyperthyroid women aged > or = 51 years showed no significantly different relative risk (RR) for osteoporosis in comparison with the controls. However, the study was not powered enough to give meaningful RR results. CONCLUSIONS: Overt symptomatic hyperthyroidism is associated with decreased BMD during the first 3 years after diagnosis and treatment of the disease. After this interval, former hyperthyroid women have a Z-score near zero and not different from women without a history of the disease, apparently because of recovery of the bone density lost early during the course of the disease. Symptomatic hyperthyroidism does not seem to be a cause of long-lasting osteoporosis, and the age of the patient during the first episode is irrelevant.

Adult↗

PubMed1992

Hyperthyroidism selectively modified a transient potassium current in rabbit ventricular and atrial myocytes.

1. Transient outward potassium currents (I(t)) were compared in single cardiac myocytes obtained from normal and hyperthyroid rabbits. Currents were recorded using the suction electrode whole-cell voltage clamp technique. 2. In ventricular myocytes from hyperthyroid animals (at 22 degrees C and a stimulation rate of 0.2 Hz), I(t) was 4- to 5-fold larger than in normal myocytes, in a potential range of -20 to +60 mV. As in normal myocytes, I(t) in hyperthyroid myocytes was calcium insensitive, and was more than 90% suppressed by 2 mM 4-aminopyridine. 3. The increase in I(t) was observed over a wide range of stimulation rates, even at rates sufficiently slow to enable complete reactivation of the I(t) channels. However, there was a major change in the rate dependence of I(t) in hyperthyroid myocytes, with significant I(t) current still present at rates (e.g. 1-2 Hz) at which it is normally completely suppressed. 4. The augmentation of I(t) in the hyperthyroid myocytes could not be accounted for by changes in the voltage dependence or the kinetics of channel activation or inactivation. There was no change in the reversal potential of I(t), implying no change in the selectivity of the channel. 5. Single-channel activity was recorded using the cell-attached mode of recording. In myocytes from hyperthyroid rabbit we observed the following: (a) active patches (often containing two channels) were obtained more frequently in comparison to control; (b) the unitary conductance of the channel was the same; (c) single-channel openings persisted at high stimulation rates. 6. In contrast to hyperthyroid ventricular cells, I(t) in atrial cells from the same hearts was not substantially changed. 7. The rate dependence of I(t) in atrial cells was also unaffected by hyperthyroidism, in contrast to the large changes observed in ventricular cells. Thus, in atrial cells from hyperthyroid hearts the current was totally suppressed at rates of 1-2 Hz, as in euthyroid conditions. 8. Single-channel recordings in the cell-attached mode showed a unitary conductance similar to that found in normal atrial cells. Channel activity was suppressed at 2 Hz, in contrast to hyperthyroid ventricular cells. 9. In conclusion, I(t) is drastically changed in hyperthyroid rabbit ventricle cells. The changes are in the magnitude of the macroscopic current and its rate dependence. Since the unitary conductance is unchanged (and the peak open probabilities are normally high at positive membrane potential(s) the number of active channels in the membrane must be increased. In atrial cells from the same hyperthyroid hearts no changes are apparent.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

PubMed1991

Species differences in myocardial beta-adrenergic receptor regulation in response to hyperthyroidism.

The coupling between myocardial beta-adrenergic receptors, adenylate cyclase activity, and the in vivo cardiac response to catecholamines is controversial in hyperthyroidism. The possibility of species differences in beta-adrenoceptor regulation after thyroxine treatment was studied in dogs and in rats. In dogs instrumented with a left ventricular (LV) pressure micromanometer, hyperthyroidism was induced by L-thyroxine (0.5 mg/kg/day i.v. for 10 days). After hyperthyroidism, heart rate was increased to 167 +/- 10 beats/min (control, 107 +/- 8 beats/min; p less than 0.005) with an increase of peak LV dP/dt from 4,243 +/- 471 to 6,105 +/- 862 mm Hg/sec (p less than 0.01). LV response to injection of increasing doses of isoproterenol and dobutamine was not significantly different before and after induction of the hyperthyroid state, as shown by the unchanged slopes of the LV peak dP/dt versus the log of the dose of isoproterenol and dobutamine. Bmax of beta-receptors measured in crude membranes using 3H-CGP 12177 and in homogenates using 125I-cyanopindolol was not increased in hyperthyroid animals as compared with a control group. Basal adenylate cyclase activity was not different in control and hyperthyroid dogs (32 +/- 3 versus 29 +/- 3 pmol/mg/min), and maximal adenylate cyclase activity response to isoproterenol was similar in control and hyperthyroid dogs. In contrast, in rats subjected to hyperthyroidism (0.5 mg/kg/day i.p. L-thyroxine for 10 days), Bmax of adrenoceptors measured using the same methods was significantly increased as compared with control (+72.5% using 3H-CGP 12177 and +41% using 125I-cyanopindolol, but adenylate cyclase activity was not increased in hyperthyroid rats. We conclude that both adenylate cyclase activity and LV response to catecholamines are not increased by thyroxine-induced hyperthyroidism in dogs and that, in contrast with rats, beta-adrenergic density is not increased in hyperthyroid dogs. This indicates a species difference in myocardial beta-adrenoceptor regulation in response to hyperthyroidism.

Adenylyl Cyclases↗

PubMed1980

Enhanced contractile response and protein kinase activation to threshold levels of beta-adrenergic stimulation in hyperthyroid rat heart.

The contractile response measured as maximum rate of force development to a near threshold concentration of isoproterenol (1 nM) was enhanced in perfused interventricular septa from hyperthyroid (128+/-4% control) compared with euthyroid rats (105+/-2%, P < 0.01). This enhanced contractile response was accompanied by a significant activation of cyclic (c)AMP-dependent protein kinase (protein kinase activity ratio increased from 0.159+/-0.008 to 0.218+/-0.019, P < 0.005, although no significant changes from base line occurred in euthyroid septa, 0.152+/-0.007-0.179+/-0.012). No difference between hyperthyroid and euthyroid hearts was observed in the contractile response to 0.1 mM dibutyryl cAMP (126.5+/-2.5% and 122.0+/-9.2% in hyperthyroid and euthyroid, respectively), and the magnitude of the response to dibutyryl cAMP was comparable with that observed in the hyperthyroid group with 1 nM isoproterenol. These results suggest that the mechanism for enhanced protein kinase activation and contractile response to low concentrations of isoproterenol in the hyperthyroid heart is at or proximal to cAMP generation. The maximum contractile response to isoproterenol (0.5 muM), however, was decreased in hyperthyroid myocardium (192+/-13%) compared with euthyroid (291+/-37%, P < 0.05). Both protein kinase activity ratio (0.356+/-0.017 and 0.344+/-0.013) and the maximum contractile response to Ca(++) (335+/-15 and 340+/-12% control in hyperthyroid and euthyroid, respectively) were similar, suggesting that the mechanism of the diminished maximum response was distal to protein kinase activation but not a function of an altered Ca(++)-troponin interaction. The diminished maximum rate of force development response in the hyperthyroid hearts was accompanied by significantly less shortening of the contraction duration that was 85.6+/-2.1% control in hyperthyroid vs. 66+/-2.8% control in euthyroid, P < 0.001. Although the basal rate of Ca(++) accumulation was greater in microsomes isolated from hyperthyroid than from euthyroid hearts, there was significantly less additional stimulation of Ca(++) accumulation in response to exogenous cAMP and protein kinase in hyperthyroid compared with euthyroid hearts. This reduction may explain the diminished effect of isoproterenol on the shortening of contraction duration in hyperthyroid compared with the euthyroid myocardium, and may explain, at least in part, the diminished maximum contractile response to isoproterenol.

Adrenergic beta-Agonists↗

PubMed1980

Impaired pancreatic alpha-cell response in hyperthyroidism.

Recently, we observed that in hyperthyroid patients, plasma glucagon was not adequately suppressed by an oral glucose load, suggesting altered pancreatic alpha-cell sensitivity. To further assess pancreatic alpha-cell function in hyperthyroidism, plasma glucose, glucagon, and insulin resonses to a protein meal were determined in normal subjects and hyperthyroid patients. Fasting plasma glucose was normal in hyperthyroid patients. A protein meal produced an increase in plasma glucose levels in hyperthyroid patients, whereas in normal subjects protein feeding was followed by a decline in blood glucose levels. Basal glucagon was markedly elevated in three of nine hyperthyroid patients, whereas in the remaining six, fasting plasma glucagon was unaltered. In both groups, protein feeding induced a glucagon rise; however, the increment was significantly smaller in hyperthyroid patients. In hyperthyroidism, fasting plasma insulin was raised and the insulin response to a protein meal was exaggerated. Furthermore, the insulin elevations were sustained and did not return to the basal level by 180 min as observed in normal subjects. We conclude that 1) the plasma glucagon response to a protein meal is blunted in hyperthyroidism, a finding which confirms our recent observation of decreased sensitivity of the pancreatic alpha-cell in hyperthyroidism; 2) fasting hyperinsulinemia with simultaneous euglycemia is consistent with the presence of insulin resistance in hyperthyroidism; and 3) the sustained and exaggerated plasma insulin rise after ingestion of a protein meal suggests hypersensitivity of the pancreatic beta-cell in hyperthyroidism.

Adolescent↗

PubMedDate not supplied

Effect of hyperthyroidism on insulin-like growth factor-I (IGF-I) and IGF-binding proteins in adolescent children.

A study was performed on adolescent hyperthyroid patients to determine the effects of hyperthyroidism on insulin-like growth factor (IGF)-I and its binding proteins. Serum concentrations of immunoreactive total and free IGF-I, and IGF binding protein (IGFBP)-2 and IGFBP-3 were determined before and after correction of hyperthyroidism in eight patients with Grave's disease and compared to control patients matched for age, sex and pubertal stage. The concentration of serum total IGF-I was not significantly different in the hyperthyroid state and euthyroid state, and did not differ significantly from euthyroid controls. IGFBP-2 levels were elevated three-fold in hyperthyroid patients at the time of diagnosis of hyperthyroidism compared to control subjects, and fell significantly during treatment. There was also a significant positive correlation between serum IGFBP-2 concentrations and thyroxine (T4) concentrations in all subjects. Serum IGFBP-3 concentrations were also elevated in hyperthyroid subjects and normalized with correction of the hyperthyroidism. There was also a positive correlation between serum T4 and IGFBP-3 concentrations in all subjects. Despite the hyperthyroid-induced elevations in IGFBP-2 and -3, no significant difference in the serum concentration of free IGF-I before or after correction of the hyperthyroid condition was observed. We conclude that hyperthyroidism does not cause alterations in the serum concentrations of either free or total IGF-I. However, both serum IGFBP-2 and IGFBP-3 concentrations were elevated during hyperthyroidism and correlated with serum T4 levels. These abnormalities reversed with normalization of thyroid function.

Adolescent↗

PubMed2001

Haemodynamic changes following treatment of subclinical and overt hyperthyroidism.

OBJECTIVE: Hyperthyroidism has profound effects on the cardiovascular system, including reduced systemic vascular resistance (SVR) due to relaxation of vascular smooth muscle cells, enhanced heart rate (HR) and cardiac output (CO) due to an increase in cardiac diastolic relaxation, contractility and heart rate. Subclinical hyperthyroidism is characterised by reduced serum TSH levels despite free thyroxine (T4) and tri-iodothyronine (T3) estimates within the reference range, in subjects with no obvious symptoms of hyperthyroidism. We measured haemodynamic changes (using impedance cardiography) in subjects with endogenous subclinical hyperthyroidism in order to elucidate whether these patients had signs of excess thyroid hormone at the tissue level. DESIGN: The patients were otherwise healthy women with a multinodular goitre (n=6; age 47-81 years; serum TSH 0.006-0.090 mU/l and normal free T4 and T3 estimates), studied before and after normalisation of TSH (0.280-1.120 mU/l) by means of radioiodine treatment, and they were compared with 9 overt hyperthyroid patients (2 with multinodular goitre and 7 with Graves' disease) in the untreated state and after euthyroidism had been obtained. RESULTS: Treatment of the subclinical hyperthyroid women resulted in 11% reduction in HR (P<0.02), 19% reduction in CO from (means+/-s.d.) 6.93+/-2.15 l/min to 5.58+/-1.94 l/min (P<0.05), and 30% increase in SVR (P<0.02). Similar but more pronounced changes were seen in the hyperthyroid group: 17% reduction in HR, 25% reduction in CO and 46% increase in SVR (all at least P<0.05). Taking all 15 patients together, thyroid function (as measured by free T3 index (FT3I) or TSH) correlated significantly to the haemodynamic parameters as follows: the higher the thyroid function the lower the mean arterial pressure and SVR, and the higher the CO and central aortic compliance (stroke volume/pulse pressure) (P<0.05). Plasma norepinephrine increased significantly after treatment of the overt hyperthyroid patients, whereas epinephrine did not change, and no changes were seen among subclinical hyperthyroid patients. CONCLUSION: Treatment of endogenous subclinical hyperthyroidism resulted in significant changes in several haemodynamic parameters regarding the heart and the vascular system, compatible with some degree of excess tissue exposure to thyroid hormones in the untreated state. Our data favour more aggressive treatment of these patients, and endogenous subclinical hyperthyroidism might be regarded as a mild form of hyperthyroidism.

Adult↗

PubMedDate not supplied

[Effects of hyperthyroidism on bone mass in women of reproductive age].

INTRODUCTION: Hyperthyroidism is one of the most frequent endocrinopathies in women of reproductive age. Consequently, increased risk of osteoporosis may be expected. MATERIAL AND METHODS: The research has included a group of 30 hyperthyroid women and a control group of 30 healthy women of reproductive age. Age and some clinical characteristics were analyzed, as well as some anthropometric parameters. Bone mass parameters were determined by measuring bone mineral density using ultrasound devices (SAHARA-Hologic). RESULTS: Bone mass parameters in hyperthyroid women are significantly lower than in controls (BUA: 63.25+/-12.17; 69.73+/-10.02 dB/MHz respectively; SOS: 1523.90+/-24.47; 1540.19+/-26.59 m/s respec. QUI/STIFF 79.78+/-13.95; 89.09+/-13.99% respec.) Duration of hyperthyroidism affects bone density and reduces it. DISCUSSION: Obtained results were expected, having in mind that hyperthyroidism is a condition characterized by increased bone catabolic rate. Also, negative correlation between the duration of hyperthyroidism and bone mass parameters (BUA, SOS) was expected, because it is logical that consolidation of bone mass in adult life cannot be maintained in circumstances in which metabolic rate is increased. During hyperthyroidism, bone loss is expected. In order to confirm this, future studies of bone markers are necessary. CONCLUSION: Based on results obtained in the study, the following conclusions were made: hyperthyroidism is accompanied by decreased values of bone mass parameters; this effect depends on duration of hyperthyroidism. We confirmed that hyperthyroidism may be the cause of decrease in bone mass, particularly if it lasts more than a year. To prevent osteoporosis in women of reproductive age with hyperthyroidism and involutional osteoporosis later in life, early diagnosis and effective therapy of hyperthyroidism is imperative.

Adult↗

PubMed2005

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

Hyperthyroidism was induced by subcutaneous injections of L-thyroxine (T4) (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.

Acetylcholine↗

PubMed2006

Cardiovascular manifestations of hyperthyroidism before and after antithyroid therapy: a matched case-control study.

OBJECTIVES: This study sought to prospectively evaluate the prevalence of cardiovascular abnormalities in patients with overt hyperthyroidism before and after antithyroid therapy. BACKGROUND: Overt hyperthyroidism is associated with recognized cardiovascular effects believed to be reversed by antithyroid therapy; however, increasing data suggest significant long-term cardiovascular mortality. METHODS: A total of 393 (312 women, 81 men) consecutive unselected patients with overt hyperthyroidism were recruited and compared with 393 age- and gender-matched euthyroid control subjects. Hyperthyroid patients were re-evaluated after antithyroid therapy. Findings in patients and matched control subjects were compared at presentation, after treatment when patients had subclinical hyperthyroidism biochemically, and when patients were rendered biochemically euthyroid. All had a structured cardiovascular history and examination, including measurements of blood pressure (BP) and pulse rate. All had resting 12-lead electrocardiogram and 24-h digital Holter monitoring of cardiac rhythm. RESULTS: A higher prevalence of cardiovascular symptoms and signs, as well as abnormal hemodynamic parameters, was noted among hyperthyroid patients at recruitment compared with control subjects. Cardiac dysrhythmias, especially supraventricular, were more prevalent among patients than among control subjects. Palpitation and dyspnea, postural decrease in systolic pressure, and atrial fibrillation (AF) remained more prevalent in treated hyperthyroid subjects with subclinical hyperthyroidism compared with control subjects, and remained more prevalent after restoration of euthyroidism. Predictors for successful reversion to sinus rhythm in those with AF associated with hyperthyroidism were lower BP measurements at recruitment and an initial hypothyroid state induced by antithyroid therapy. Mortality was higher in hyperthyroid subjects than in control subjects after a mean period of follow-up of 66.6 months. CONCLUSIONS: Cardiovascular abnormalities are common in patients with overt hyperthyroidism at presentation, but some persist despite effective antithyroid therapy.

Adolescent↗

PubMed1999

Metabolic effect of decreasing nonesterified fatty acid levels with acipimox in hyperthyroid patients.

Glucose intolerance is often found in patients with hyperthyroidism, but the pathogenetic mechanisms are not fully understood. Since lipolysis is increased in hyperthyroidism, elevated plasma nonesterified fatty acids (NEFAs) may contribute to abnormal glucose metabolism in hyperthyroidism. The aim of this study was to investigate whether decreasing the plasma NEFA level with acipimox can affect glucose metabolism in hyperthyroidism. We performed an intravenous glucose tolerance test (IVGTT) with acipimox 250 mg or placebo in six untreated hyperthyroid men and six age- and body mass index (BMI)-matched controls. Fasting plasma NEFA levels were significantly higher in the hyperthyroid patients versus the controls (997.0 +/- 303.4 v290.5 +/- 169.1 micromol/L, P < .001). Plasma NEFAs decreased rapidly with acipimox treatment in both controls and hyperthyroid patients. In the controls, the glucose disappearance constant (K(G)) was not different for acipimox treatment versus placebo (2.18 +/- 0.62 v 2.42 +/- 1.00% x min(-1)). In hyperthyroid patients, acipimox treatment increased the K(G) significantly compared with placebo treatment (2.44 +/- 0.84 v 1.58 +/- 0.37% x min(-1), P < .05). Changes in K(G) values with acipimox treatment were inversely correlated with changes in plasma NEFA levels (r = -.65, P < .05). Acipimox treatment increased the acute insulin response (AIR) in hyperthyroid patients (943 +/- 381 v 698 +/- 279 microU/mL x min, P < .05), whereas it did not change the AIR in controls. Changes in the AIR with acipimox treatment correlated significantly with changes in the K(G) (r = .70, P < .05). There was a weak correlation between changes in the AIR with acipimox treatment and changes in plasma NEFA levels (r = -.55, P = .06). In summary, decreasing the plasma NEFA level with acipimox in hyperthyroid patients increases both the K(G) and AIR during an IVGTT. These findings suggest that the abnormal glucose metabolism in hyperthyroidism could be attributed, at least in part, to the increase of plasma NEFA.

Administration, Oral↗

PubMed2003

Cardiac changes in subclinical and overt hyperthyroid women: retrospective study.

BACKGROUND: This retrospective and descriptive 4-year study was undertaken to describe cardiac changes in subclinical and overt hyperthyroidism. METHODS: We revised the charts of 386 consecutive cardiopathic women whose blood samples were referred to the Radioimmunoassay Laboratory to evaluate thyroid function from 1 January 1997 through 31 December 2000. RESULTS: After excluding women because euthyroid or hypothyroid, or taking amiodarone and women with hypertension, rheumatic disease, myocardial infarction, a total of 31 hyperthyroid women were thus selected for the study: 19 with subclinical hyperthyroidism and 12 with overt hyperthyroidism. The prevalence of atrial fibrillation did not differ between subclinical (48%) and overt (67%) hyperthyroid women, as well as left atrial dimension; the latter was larger in hyperthyroid (27.8+/-7.8 cm(2)/m(2)) than in control women (18.9+/-2.8 cm(2)/m(2)) (P<0.001). In the subclinical and overt hyperthyroidism, the heart rate (HR) was increased and left ventricular end diastolic (LVED) volume was reduced; in addition, only in overt hyperthyroidism, left ventricular (LV) mass was increased. A significant correlation between LV mass and free triiodothyronine was found. CONCLUSION: HR increase and LVED decrease, both in subclinical and overt hyperthyroidism, indicate a global impairment of diastolic heart performance, complicated in overt hyperthyroidism by LV concentric hypertrophy. So, in our opinion, subclinical hyperthyroidism, far from being considered a simple laboratory finding, in clinical practice should be taken into serious consideration.

Aged↗