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Quantitative thyroid scintigraphy for the differentiation of Graves' disease and hyperthyroid autoimmune thyroiditis.

AIM: The TCTUs (global (99m)Tc-pertechnetate thyroid uptake under suppression) can be used as an estimate of the iodine clearance of non-TSH regulated tissue. High TCTUs levels are characteristic for Graves' disease (GD). Decreased uptake has been described in autoimmune thyroiditis (AIT). However, systematically investigated data in a larger series of AIT-patients with subclinical or overt hyperthyroidism are not published so far. The purpose of this study is the evaluation of the TCTUs in the differentiation between AIT and GD in patients with hyperthyroidism. METHODS: We determined the TCTUs in 59 patients with untreated hyperthyroid GD and in 51 patients with AIT who had subclinical or manifest hyperthyroidism without medication. Patients with GD were characterized by the presence of hyperthyroidism, decreased echogenicity of the thyroid, elevation of TSH-receptor autoantibodies (TRAb). AIT was defined by a decreased echogenicity of the thyroid, absence of elevated TSH-receptor autoantibodies (TRAb), autoantibodies against the thyroid peroxidase (anti-TPO) and spontaneous remission or development of subclinical hypothyroidism within 3 months. RESULTS: Thyroid volumes of patients with AIT were significantly lower than those of patients with GD (p <0.05). TRAb levels were significantly higher in GD-patients (median: 19.5 U/ml; range: 15.3-35 U/ml) than in AIT-patients (median: 1.3 U/ml; range: 0-4.1 U/ml). 73% (38/59) of patients with GD had elevated anti-TPO levels. In these patients anti-TPO levels (median: 768 U/l; range: 83-6397 U/l) were not significantly different from anti-TPO levels of patients with AIT (median: 834 U/l; range: 107-8675 U/l; p = 0.17). TCTUs values of patients with AIT were significantly lower (p <0.05; median: 0.9%; range: 0.1-3.2%) than those of patients with GD (median: 5.7%; range: 1.9-28.3%). CONCLUSION: In our patients quantitative thyroid scintigraphy with (99m)TcO(4)(-) offered rapid and reliable differentiation between hyperthyroid GD and AIT.

Diagnosis, Differential↗

Longitudinal changes of bone density and bone resorption in hyperthyroid girls during treatment.

Low bone mineral density (BMD) and increased bone turnover are common features of untreated hyperthyroidism in adult patients. The effect of treatment on BMD is still controversial. BMD and bone metabolism in hyperthyroid children have not been thoroughly investigated. In the present study, we measured spinal and whole body BMD by dual-energy X-ray absorptiometry in a group of 13 girls (aged 5.0-14.9 years) at diagnosis of hyperthyroidism. The bone resorption rate was assessed by urine measurement of N-terminal telopeptide of type I collagen (NTX). Hyperthyroid patients have been studied longitudinally during treatment. BMD values and NTX urine concentrations have been also determined in 155 healthy Caucasian girls (aged 2.4-24.2 years). Spinal and whole body bone density measurements were significantly lower compared with healthy controls in untreated hyperthyroid girls, after correction for differences in age and anthropometric measurements (p </= 0.033). Bone density measurements obtained after 12 and 24 months of treatment were no longer different from those of healthy girls. NTX urine levels at diagnosis of thyrotoxicosis were significantly higher than those found in healthy controls (p < 0.0001); 6 months after treatment, the urine levels did not show significant differences, and they remained stable after 12 and 24 months of therapy. Inverse correlations at diagnosis were found between serum-free thyroxine (FT4) serum levels and spinal (r = -0.42) and whole body bone density (r = -0.41); FT4 and free triiodothyronine serum levels directly correlated with the NTX concentration (r = 0. 77, and r = 0.71, respectively). In conclusion, the results of the present study demonstrate that low bone density values and high bone resorption rates are found in hyperthyroid children and adolescents at diagnosis of the disease. Our data also demonstrate that antithyroid treatment is able to reduce dramatically the bone resorption and to increase significantly both spinal and total body BMD, granting physiologic conditions for the achievement of the best obtainable peak bone mass.

Adolescent↗

[The parathyroid function in patients with hyperthyroidism].

The parameters of calcium metabolism were determined in 22 patients with untreated hyperthyroidism (5 males and 17 females) and 5 control subjects. Hypercalcemia was found in the patients with hyperthyroidism in comparison with the control subjects (serum Ca: 10.0 +/- 0.56 vs. 9.0 +/- 0.18, p less than 0.001 and Ca++: 5.1 +/- 0.28 vs. 4.6 +/- 0.15 mg/dl, p less than 0.001, mean +/- SD). Although the urinary excretion of calcium was decreased in many patients, abnormalities of phosphate metabolism were not found in this study. The parameters of bone resorption, urinary hydroxyproline, serum alkaline phosphatase and acid phosphatase, were increased in all patients with hyperthyroidism. Serum immunoreactive PTH was decreased (0.23 +/- 0.05 vs. 0.29 +/- 0.05 ngEq/ml, p less than 0.05). In vitamin D metabolites, 25-OH-D did not differ from the control (16.9 +/- 7.76 vs. 17.9 +/- 5.52 ng/ml), 1,25-(OH)2D showed a tendency to decrease (32.6 +/- 19.53 vs. 37.2 +/- 13.75 pg/ml) and 24,25-(OH)2D was obviously increased (5.57 +/- 3.582 vs. 1.73 +/- 0.619 ng/ml, p less than 0.001) in the hyperthyroid patients. Thus, the parathyroid function was suppressed in the patients with hyperthyroidism, and hypercalcemia in hyperthyroidism was suggested to be due to the direct action of thyroid hormone upon the bone.

Adult↗

Exogenous subclinical hyperthyroidism during adolescence: effect on peak bone mass.

BACKGROUND: Chronic subclinical hyperthyroidism induced by suppressive doses of L-thyroxine (L-T4) therapy, so-called exogenous subclinical hyperthyroidism, may cause diminished bone mass in postmenopausal women. The effect of subclinical hyperthyroidism during childhood and adolescence on peak bone mass, however, has not been evaluated. OBJECTIVE: To determine whether exogenous subclinical hyperthyroidism during adolescence, the period of critical bone mass acquisition, would reduce peak bone mass. PATIENTS AND METHODS: Eighteen female adolescents and young adults with Hashimoto's thyroiditis and euthyroid goiter (aged 22.4 +/- 4.4 years) who had been treated with suppressive doses of L-T4, 127.5 +/- 23.7 microg/day, during adolescence (age at onset of subclinical hyperthyroidism, 14.2 +/- 1.5 years) for 6.3 +/- 3.4 years were enrolled in the study. Twenty-nine healthy female volunteers matched for age, weight, height and body mass index served as the controls. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry. RESULTS: BMD of the lumbar spine, radius, Ward's triangle and total body were comparable in the two groups. In contrast, BMD of the femoral neck, trochanter and shaft of patients was slightly higher than those of controls. There were no correlations between BMD values and clinical parameters. CONCLUSION: Exogenous subclinical hyperthyroidism during adolescence has no demonstrable detrimental effect on peak bone mass attainment.

Adolescent↗

Mechanism of creatinuria in experimental hyperthyroidism.

Using rats pre-labelled by [14C]creatine injection, the mechanism of creatinuria induced by experimental hyperthyroidism during a 20 day treatment period has been examined. The excess creatine excretion is the result of increased release of creatine from muscle and increased excretion of creatine synthesized de novo. The increased excretion of newly synthesized creatine in hyperthyroidism appears to occur because of decreased creatine uptake by muscle, an increased rate of creatine synthesis, or a combination of both factors. The radioactive creatine content of hyperthyroid skeletal muscle was reduced at the time of death indicating an increased rated of creatine loss during the treatment period. In spite of the increased loss of labelled creatine, the specific activity of creatine obtained from hyperthyroid skeletal muscle was higher than control. This finding is probably due to decreased uptake of unlabelled creatine by hyperthyroid skeletal muscle during the treatment period. In contrast to skeletal muscle, the radioactive creatine content of hyperthyroid myocardium was higher than control at the time of death suggesting a decreased rate of creatine loss during the treatment period.

Animals↗

Hyperthyroidism and thyroid carcinoma.

Twenty-two of 251 patients with differentiated thyroid carcinoma suffered from or had a history of hyperthyroidism. They were hyperthyroid with a diffuse goitre (N = 4), a diffuse goitre with a cold nodule (N = 10), a multinodular goitre (N = 6), and an autonomous adenoma (N = 2). Among the 22 patients, more than one fourth had an occult thyroid carcinoma with a diameter of 1 cm or less, those with the papillary tumour types, less frequently had lymph node metastases than the total group of patients with papillary carcinomas (13.3 vs 35.6%). The clinical courses of the 22 patients resembled those of the other thyroid carcinoma patients whose age and initial findings were comparable. In 643 patients who underwent surgery for hyperthyroidism the incidence of thyroid carcinoma was 2.3%. The increase in coincidence of hyperthyroidism and thyroid carcinoma repeatedly reported in recent years is probably ascribable primarily to extensive and improved diagnostics and not to a direct connection between hyperthyroidism and development of thyroid carcinoma. On the other hand, our findings do confirm that, even in the presence of hyperthyroidism, all thyroid nodules require careful diagnostics for exclusion of malignancy.

Adenocarcinoma↗

Muscle bioenergetic impairment in hyperthyroid man: a study by 31P NMR spectroscopy.

Phosphorus nuclear magnetic resonance spectroscopy was used to investigate muscle bioenergetics in 9 hyperthyroid patients who were compared with 9 normal subjects. Using the thenar muscle group as reference, the inorganic phosphate, phosphocreatine and intracellular pH were calculated at rest, during aerobic exercise (0.13 w) and post-exercise recovery. No difference was found at rest. After 5 min of exercise, the hyperthyroid patients exhibited a more important phosphocreatine depletion (41.2 +/- 8.2 vs 31.1% +/- 6.5, p less than 0.02) and a larger pH fall (6.65 +/- 0.04 vs 7.01 +/- 0.10, p less than 0.001) than the control subjects. The phosphocreatine recovery rate was not significantly different in hyperthyroid patients and control subjects. These results suggest that exercise requires more ATP in hyperthyroid patients than in normal subjects and that there is excessive dependence on glycolytic metabolism for ATP synthesis in hyperthyroidism. Phosphocreatine resynthesis, reflecting the oxidative metabolism, is not increased. These metabolic disturbances could also supply a partial explanation to the frequent exercise intolerance in hyperthyroid patients.

Adenosine Triphosphate↗

Galanin does not affect the growth hormone-releasing hormone-stimulated growth hormone secretion in patients with hyperthyroidism.

Patients with hyperthyroidism have reduced spontaneous and stimulated growth hormone (GH) secretion. The aim of our study was to evaluate the effects of galanin, a novel neuropeptide which stimulates GH secretion in man, on the GH response to GHRH in patients with hyperthyroidism. Eight untreated hyperthyroid patients with Graves' disease (6F, 2M, aged 25-50 years) and six healthy volunteers (3F, 3M, aged 27-76 years) underwent from -10 to 30 min in random order: (i) porcine galanin, iv, 500 micrograms in 100 ml saline; or (ii) saline, iv, 100 ml. A bolus of human GHRH(1-29)NH2, 100 micrograms, was injected iv at 0 min. Hyperthyroid patients showed blunted GH peaks after GHRH+saline (10.2 +/- 2.5 micrograms/l) compared to normal subjects (20.7 +/- 4.8 micrograms/l, p < 0.05). GH peaks after GHRH+galanin were also significantly lower in hyperthyroid subjects (12.5 +/- 3 micrograms/l) compared to normal subjects (43.8 +/- 6 micrograms/l, p < 0.05). That galanin is not able to reverse the blunted GH response to GHRH in hyperthyroidism suggests that hyperthyroxinemia may either increase the somatostatin release by the hypothalamus or directly affect the pituitary GH secretory capacity.

Adult↗

Cardiac triiodothyronine nuclear receptor binding capacities in amiodarone-treated, hypo- and hyperthyroid rats.

Parameters that are assumed to be under direct control by thyroid hormonal state were evaluated in amiodarone-treated, hypo- and hyperthyroid rats. Special attention was paid to evaluating similarities between hypothyroid and amiodarone-treated rats, with special focus on myocardial nuclear triiodothyronine (T3) receptor binding characteristics. Rats were rendered hypothyroid by adding KClO4 to the drinking water for 6 weeks (N = 14). Hyperthyroidism was induced by adding 0.003% L-thyroxine to the drinking water for 6 weeks (N = 14). Fourteen rats were treated orally for 6 weeks with amiodarone, whereas 14 rats served as untreated controls. Equilibrium binding characteristics for T3 nuclear receptors were determined by means of a simple and rapid method with excellent reproducibility and sensitivity. Body temperature and heart rate were lowered in hypothyroid and amiodarone-treated rats. Maximum binding capacities of beta-adrenergic receptors were reduced by 39% and 14% (p < 0.05) in hypothyroid and amiodarone-treated rats, respectively, and increased by 28% (p < 0.05) in hyperthyroid rats. Maximum binding capacities for voltage-operated Ca2+ channels were increased by 35% and 16% in hypothyroid and amiodarone-treated rats (p < 0.05), respectively, and decreased by 24% in hyperthyroid rats (p < 0.05). Maximum binding capacities for T3 receptors (expressed per unit of DNA) were reduced by 39% and 32% in hypothyroid and amiodarone-treated rats (p < 0.05), respectively, and increased by 63% in hyperthyroid rats (p < 0.05). In hypothyroid and amiodarone-treated rats, myocardial T3 content was extremely reduced (less than 0.05 nmol/kg and 0.06 +/- 0.08 nmol/kg, respectively, compared with control levels of 1.55 +/- 0.46 nmol/kg). In vitro competition studies of amiodarone and its desethyl analogue revealed that both drugs are potentially capable of displacing T3 from its nuclear receptor at concentrations close to what are considered therapeutic drug levels. Myocardial nuclear T3 receptor maximum binding capacities decreased to a similar degree in hypothyroid and amiodarone-treated rats and increased in hyperthyroid rats. Several other similarities between hypothyroid and amiodarone-treated rats suggest that amiodarone may act by inducing a state of thyroid hormonal resistance.

Amiodarone↗

Increased risk of affective disorder following hospitalisation with hyperthyroidism - a register-based study.

OBJECTIVE: The pattern of comorbidity between thyroid disorders and affective disorder is not fully known. We assessed whether hospitalisation with hyperthyroidism was a risk factor for hospitalisation with affective disorder and evaluated the temporal relationship between these events. DESIGN: A historical prospective cohort study comparing patients with hyperthyroidism with patients with non-toxic goitre or osteoarthritis, using existing data from Danish registers. The observational period was from 1 January 1977 to 31 December 1999. METHODS: Three study cohorts were identified by their International Classification of Diseases (ICD) diagnoses at discharge from hospital and consisted of all patients with a first hospital admission with the index diagnoses of hyperthyroidism, osteoarthritis, or non-toxic goitre. Later admissions to psychiatric hospital wards with discharge ICD diagnoses of affective disorder were used as events of interest. Rates of re-admission were estimated using competing risks models in survival analyses. Age, sex, substance abuse, and calendar time were included as co-variables. RESULTS: A study sample of 183 647 patients discharged with an index diagnosis was identified. In total 1374 events occurred in the observational period. An index diagnosis of hyperthyroidism was associated with an increased risk of hospitalisation with affective disorder for both sexes and for all age-bands investigated, compared with the other index diagnoses. The risk was greatest in the first six months after index hospitalisation (rate ratio, 95% confidence interval: 3.60 (2.58-5.04)). CONCLUSIONS: Patients hospitalised with hyperthyroidism are at greater risk of re-admission with depressive disorder or bipolar disorder than control patients. This suggests that hyperthyroidism is associated with long-term mood disturbances.

Adult↗

Percutaneous transvenous mitral commissurotomy in patients with mitral stenosis and coexistent hyperthyroidism.

Percutaneous transvenous mitral commissurotomy (PTMC) was performed successfully without complications in 3 patients with severe mitral stenosis and hyperthyroidism. All 3 patients had pliable, noncalcified mitral valves. One patient who had been treated with methimazole for 6 months was still in a hyperthyroid state when she presented with intractable congestive heart failure and was found to have severe mitral stenosis. The heart failure improved immediately after PTMC, but the patient remained in New York Heart Association functional class 2 until a euthyroid state was achieved with I131 therapy. In the other 2 patients, hyperthyroidism was unsuspected at the time of PTMC. Unexpectedly suboptimal symptom improvement led to the diagnosis of hyperthyroidism 1 month after the intervention. In all 3 patients, PTMC resulted in an immediate hemodynamic and clinical improvement. However, complete clinical improvement occurred only when euthyroid state was achieved after antithyroid treatment. The present study suggests that PTMC is a safe and effective intervention modality in patients with coexisting hyperthyroidism and severe mitral stenosis. The procedure may be considered a therapeutic option in patients with hyperthyroidism and severe mitral stenosis.

Adult↗

Dietary omega 6 fatty acids and the effects of hyperthyroidism in mice.

The influence of the type of dietary fat on the effects of thyroid hormones was investigated in mice. Hyperthyroidism was achieved by providing thyroid hormones (T3 and T4) in the drinking water. Both hyperthyroid and euthyroid mice (Mus musculus) were fed isoenergetic diets containing 18% (w/w) total lipid but differing in fatty acid composition. Diets were either low in the polyunsaturated linoleic acid (18:2, omega 6) and high in saturated fatty acids (SFAs) or low in saturated fats and high in the polyunsaturated fatty acid (PUFA), linoleic acid. Treatments were maintained for 21-22 days. Plasma thyroid hormone levels, standard metabolic rate (SMR), changes in body mass, specific activities of malic enzyme (ME), Na-K-ATPase and glycerolphosphate dehydrogenase (GPDH) of the liver were measured. Fatty acid composition of the liver phospholipids was also determined. Levels of T3 (15-17 nM) and T4 (250-255 nM) were significantly higher in the respective hyperthyroid groups. There was no significant influence of the diet on hormone levels. Hyperthyroidism increased the SMR 37-44% above the euthyroid levels. A significant body weight loss of 14-18% was observed in hyperthyroid mice on the PUFA diet but not in those on the SFA diet. PUFA diet significantly reduced the activity of ME but had no effect on Na-K-ATPase or GPDH activity. Activities of Na-K-ATPase and GPDH were significantly elevated in all hyperthyroid groups. Mice on T4 and PUFA diet showed a highly significant 399% increase in GPDH activity above the euthyroid level.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Selective modification of insulin action in adipose tissue by hyperthyroidism.

Adipose-tissue lipolysis (assessed from glycerol release) and glucose uptake were examined in parametrial and mesenteric adipocytes prepared from control or hyperthyroid rats in relation to changes in insulin sensitivity. Basal rates of lipolysis did not differ significantly between adipose-tissue depots. Lipolysis was maximally stimulated by noradrenaline at 1 microM, half-maximal anti-lipolytic effects of insulin were observed at approximately 11 microU/ ml insulin, and half-maximal stimulation of glucose uptake was observed at approximately 16 microU/ml insulin in adipocytes from both depots. Wortmannin caused a dose-dependent inhibition of the anti-lipolytic effect of insulin (150 microU/ml) on noradrenaline-stimulated lipolysis. Half-maximal effects of wortmannin were observed at 20-40 nM. The p70S6K inhibitor rapamycin and the mitogen-activated protein kinase kinase inhibitor PD098059 had no effects on noradrenaline-stimulated lipolysis. Hyperthyroidism increased basal rates of lipolysis and the maximal response of lipolysis to noradrenaline stimulation (3.1-fold, P < 0.001 and 2.1-fold, P < 0.05 respectively) in parametrial adipocytes. Hyperthyroidism markedly blunted the sensitivity of noradrenaline-stimulated lipolysis to half-maximal suppression by insulin in both parametrial and mesenteric adipocyte depots, and noradrenaline-stimulated lipolysis at a maximal insulin concentration remained significantly higher in adipocytes prepared from hyperthyroid rats compared with controls. Hyperthyroidism had no effect on basal and little effect on insulin-stimulated glucose uptake. Tri-iodothyronine administered at a low dose selectively influenced the anti-lipolytic action of insulin in parametrial adipocytes, and led to significantly less marked elevation in plasma non-esterified fatty acid concentrations in vivo. The results demonstrate a selective effect of hyperthyroidism to impair insulin's anti-lipolytic action, and are consistent with the operation of different downstream signalling mechanisms for the effects of insulin on adipocyte glucose transport and lipolysis.

Adipose Tissue↗

Evaluation of environmental, nutritional, and host factors in cats with hyperthyroidism.

The pathologic changes associated with hyperthyroidism (adenomatous hyperplasia, adenoma of the thyroid gland) have been well characterized in cats, but the pathogenesis of these changes remains unclear. In this research, we undertook a case-control study to search for potential risk factors for this disease. Owners of 379 hyperthyroid and 351 control cats were questioned about their cats' exposure to potential risk factors including breed, demographic factors, medical history, indoor environment, chemicals applied to the cat and environment, and diet. The association between these hypothesized risk factors and outcome of disease was evaluated by conditional logistic regression. Two genetically related cat breeds (ie, Siamese and Himalayan) were found to have diminished risk of developing hyperthyroidism. Cats that used litter had higher risk of developing hyperthyroidism than those that did not. Use of topical ectoparasite preparations was associated with increased risk of developing hyperthyroidism. Compared with cats that did not eat canned food, those that ate commercially prepared canned food had an approximate 2-fold increase in risk of disease. When these 4 variables (breed, use of cat litter, consumption of canned cat food, and use of topical ectoparasite preparations) from the univariate analysis were selected for further study as candidate risk factors and analyzed by multivariate conditional logistic regression, a persistent protective effect of breed (ie, Siamese or Himalayan) was found. In addition, results suggested a 2- to 3-fold increase in risk of developing hyperthyroidism among cats eating a diet composed mostly of canned cat food and a 3-fold increase in risk among those using cat litter. In contrast, the use of commercial flea products did not retain a strong association. The results of this study indicate that further research into dietary and other potentially important environmental factors (eg, cat litter) is warranted.

Animal Nutritional Physiological Phenomena↗

Primary hyperthyroidism induced erythropoietin-resistant anemia?

We describe a 26-year-old male hemodialysis patient with erythropoietin (EPO) resistant anemia associated with primary hyperthyroidism. Use of the anti-hyperthyroid drug, methimazole, led to improvement of his hyperthyroidism and anemia. Before the anti-hyperthyroid therapy, he had received transfusions to maintain an adequate hematocrit during recombinant human EPO therapy. After the therapy, his hyperthyroidism improved and his hematocrit gradually increased without any transfusion. These findings suggest that the patient's EPO resistant anemia was the result of primary hyperthyroidism, and that this complication is reversible if accurate treatment is given.

Adult↗

Age-related glucose intolerance in hyperthyroid patients.

In an attempt to study age-related metabolic abnormalities, glucose intolerance and serum insulin were examined in normal subjects and hyperthyroid patients. For comparison, serum concentrations of thyroxine (T4), triiodothyronine (T3), and total cholesterol were also measured in normal subjects and hyperthyroid patients. Although serum T4 concentration remained unchanged, serum T3 concentration decreased significantly in an elderly group of normal subjects. Similarly, serum T4 did not change with age and serum T3 decreased slightly but progressively with age in hyperthyroid patients. In addition, serum total cholesterol concentration increased progressively with age in normal subjects. Oral glucose tolerance decreased with age in normal subjects despite the same timing, peak level attained, and total magnitude of insulin response for old and young subjects. Although the severity of hyperthyroidism decreases with age, age-related glucose intolerance was much more apparent in hyperthyroid patients because of the age-related decrease of basal concentration, the peak level attained, and the total magnitude of insulin response. It is suggested that age-related glucose intolerance is magnified by the hyperthyroid state.

Adolescent↗

Expression of inhibitory G proteins in adenomatous thyroid glands obtained from hyperthyroid cats.

OBJECTIVE: To identify within guanosine triphosphate-binding proteins (G proteins) the subset of inhibitory G proteins (G) that have decreased expression in adenomatous thyroid glands obtained from hyperthyroid cats. SAMPLE POPULATION: Adenomatous thyroid glands obtained from 5 hyperthyroid cats and normal thyroid glands obtained from 3 age-matched euthyroid cats. PROCEDURE: Expression of G(i1), G(i2), and G(i3) in enriched membrane preparations from thyroid glands was quantified by use of immunoblotting with G(i) subtype-specific antibodies. RESULTS: Expression of G(i2) was significantly decreased in tissues of hyperthyroid glands, compared with expression in normal thyroid tissue. Expression of G(i1) and G(i3) was not significantly different between normal thyroid tissues and tissues from hyperthyroid glands. CONCLUSIONS AND CLINICAL RELEVANCE: A decrease in G(i2) expression decreases inhibition of adenylyl cyclase and allows a relative increase in stimulatory G protein expression. This results in increased amounts of cAMP and subsequent unregulated mitogenesis and hormone production in hyperthyroid cells. Decreased G(i2) expression may explain excessive growth and function of the thyroid gland in cats with hyperthyroidism.

Adenylyl Cyclases↗

Free thyroid hormones and a third-generation TSH assay in the detection of hyperthyroidism during long-term thyroxine treatment in thyroid carcinoma patients.

We evaluated the value of serum-free thyroid hormone and thyrotropin (TSH) concentrations in the detection of peripheral hyperthyroidism during thyroxine suppression therapy. A total of 57 patients on a stable thyroxine dose and 70 controls participated in the study. Serum-free thyroxine (FT4), free triiodothyronine (FT3) and TSH were measured by immunoassays based on time-resolved fluorescence (Delfia). The assay for TSH was a modification of a third generation Delfia hTSH Ultra method. The patients were classified into euthyroid and hyperthyroid subgroups based on clinical signs and symptoms (Wayne index). Systolic time intervals (STI) were measured. The Wayne indices were higher among patients than controls (p < 0.0001). The STI results were similar in patients and controls. Only FT4 had the discriminatory power for classifying euthyroid and hyperthyroid patients according to discriminant analyses. The diagnostic value of FT4 was further assessed by calculating the area under the relative operating characteristic (ROC) curve. The area was 0.707 (SE 0.0918), which was significantly different from an area of 0.5, i.e. the area of a test of no value (p = 0.032). In conclusion, a high serum FT4 concentration indicates hyperthyroidism during long-term thyroxine treatment among thyroid carcinoma patients. Although the degree of TSH suppression can now be exactly monitored with new third generation TSH assays, hyperthyroidism cannot be defined using TSH concentration in thyroid carcinoma patients. Therefore, additional serum FT4 concentration assays are needed in the assessment of hyperthyroidism associated with TSH suppression therapy in thyroid carcinoma patients.

Adult↗