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[The influence of hyperthyroidism and glucocorticosteroid treatment on bone metabolism in patients with Graves' disease and ophthalmopathy].

UNLABELLED: The aim of the study was to assess influence of hyperthyroidism and glucocorticosteroid treatment on changes of bone turnover markers in patients with Graves' disease and thyroid ophthalmopathy (TO). MATERIAL AND METHODS: Three groups of patients were included in the study. Group I was composed of 26 euthyroid Graves' disease patients with TO suitable for steroid treatment. Group II included 14 hyperthyroid Graves' patients without TO treated medically with anti-thyroid drugs. Group III (control group) included 20 healthy volunteers. Levels of the bone formation marker, i.e. bone-specific alkaline phosphatase (BALP) and the bone resorption marker, i.e. deoxypyridinoline (DPD) were measured in the group I before steroid treatment administration, after 3 methylprednisolone i.v. pulses and after completing the oral prednisone treatment. In the group II levels of BALP and DPD were assessed twice: before treatment of hyperthyroidism and after 6 months since euthyroid state had been achieved. In the group III levels of BALP and DPD were measured once in the basal conditions. RESULTS: Mean initial levels of BALP in groups I and II did not differ significantly and were increased when compared to healthy volunteers. In the group I a transient significant decrease in BALP levels after 3 i.v. pulses of methylprednisolone was observed, followed by a significant increase in BALP after completing the oral prednisone therapy. The achievement of euthyroid state in Graves' patients (II) did not influence significantly BALP values. In the group I initial DPD levels were significantly lower than those in group II and higher than those in the control group (III). During steroid treatment of TO (group I) no dynamic changes of DPD levels were observed. The achievement of euthyroid state in group II was accompanied by a significant decrease in DPD levels, which were however than those in the control group. CONCLUSIONS: 1. In hyperthyroid state is associated with the profound stimulation of bone resorption, and to a lesser extent of bone formation. 2. The achievement of euthyroid state causes a rapid inhibition of bone resorption and maintains a compensatory stimulation of bone formation. 3. Glucocorticosteroid treatment with methylprednisolone i.v. pulses and orally administered prednisone do not influence significantly the processes of bone formation and bone resorption.

Adult↗

Autoimmune and non-autoimmune hyperthyroidism in pediatric patients: a review and personal commentary on management.

Here we review the etiology, diagnosis, differential diagnosis, and clinical presentation of hyperthyroidism in neonates/infants, children, and adolescents and the standard and adjunct modalities used for its treatment. The most common cause of hyperthyroidism in pediatric patients is Graves' disease. The main options for its management include antithyroid drugs, surgery, and radioiodine therapy. Despite collective experience covering more than 4 decades in the management of hyperthyroidism in children, controversy still abounds regarding the choice of treatments. None of the current treatment options is ideal. Each has risks and selection should be tailored to individual patients, especially in view of the absence of large, prospective, randomized outcome studies. Finally, we discuss the diagnosis and management of less common causes of pediatric hyperthyroidism, including non-autoimmune causes in neonates, autonomously functioning thyroid adenomas, destructive thyroiditis, excessive or inappropriate thyroid-stimulating hormone production, excessive ingestion of thyroid hormone and exposure to large, stable iodine loads.

Adolescent↗

[Two cases of acute hepatitis E in patients with hyperthyroidism].

Acute hepatitis E occur commonly as outbreaks in endemic areas, but can occur sporadically in other part of the world. Acute hepatitis E has been reported rarely in Korea. A case of concurrent acute hepatitis E virus (HEV) infection and hyperthyroidism was reported in an inactive hepatitis B surface antigen carrier. We experienced two cases of concomitant acute HEV infection in patients with hyperthyroidism. The first case had acute HEV infection with subclinical hyperthyroidism while taking propylthiouracil. The second case suffered from acute HEV infection in a patient with Graves' disease intractable to propylthiouracil. Herein, we suggest the possible association between HEV infection and hyperthyroidism.

Acute Disease↗

[Effects of maternal hyperthyroidism and antithyroid drug therapy on thyroid function of newborn infants].

OBJECTIVE: To evaluate the relationship between the incidence of abnormal thyroid function of newborns and maternal hyperthyroidism with antithyroid drug therapy. METHOD: The clinical data of 35 neonates born to mothers with hyperthyroidism from 1983 to 2003 in Peking Union Medical College Hospital were retrospectively analyzed. According to the maternal thyroid function and the antithyroid drugs taken during pregnancy, subjects were divided into different groups. RESULTS: The proportion of abnormal thyroid function in newborn was 48.6% (17/35). The prevalences of primary hypothyroidism, subclinical hypothyroidism, hypothyroxinemia, and central hypothyroidism were 29.4%, 29.4%, 35.3%, and 5.9%, respectively. The incidence of abnormal thyroid function of neonates whose mothers did not take the antithyroid drugs (ATDs) until the third trimester of pregnancy was significantly higher than those without and with ATDs during the first or second trimester (P < 0.01). The incidence of abnormal thyroid function significantly increased in premature neonates, neonates whose mothers with modest or heavy pregnant hypertension, or neonates whose core serum thyroid-stimulating hormone or serum anti-thyroid peroxidase antibodies levels were abnormal. CONCLUSION: The risk of abnormal thyroid function of infants whose hyperthyroid mothers did not take ATDs until the third trimester of pregnancy may be increased. Prompt diagnosis and appropriate treatment of hyperthyroidism in pregnant women are essential for the prevention of neonatal thyroid functional abnormality.

Adult↗

[Insulin resistance assessed with HOMA-IR in hyperthyroid patients].

UNLABELLED: Hyperthyroidism may influence sensitivity to insulin. The aim of study was to assess insulin resistance in hyperthyroid patients in correlation with the plasma free thyroxine (FT4) and thyreotropin (TSH) concentrations. MATERIAL AND METHODS: The study group consisted of 15 hyperthyroid patients (11 females, 4 males, mean age 50, 6 +/- 12, 36 yrs.). The controls were 17 healthy individuals (6 females, 11 males, mean age 55, 12 +/- 14, 17 yrs.). In the study group the mean FT4 was 33.1 +/- 20.1 pmol/l, TSH 0.034 +/- 0.066 pmol/l, glucose 5.00 +/- 0.56 mmol/l, insulin 7.19 +/- 3.59 microU/mL. In the controls respectively: 16.2 +/- 1.8 pmol/l, 1.24 +/- 1.07 pmol/l, 5.04 +/- 0.62 mmol/l, 7.24 +/- 4.06 microU/mL. Insulin resistance was calculated with HOMA-IR model, and the results were in the study group: mean 1.63 +/- 0.85, range from 0.46 to 3.67, median 1.38; in the controls respectively: 1.69 +/- 1.08, range from 0.36 to 4.47, median 1.42. RESULTS: Insulin resistance did not differ significantly between the groups (p=0.8860). FT4 and TSH did not influence insulin resistance in either group, the correlations were insignificant: for FT4 and for TSH p=0.5100 and p=0.5601 in the study group, and p=0.172 and p=0.4509 in the controls, respectively. CONCLUSION: Hyperthyroidism did not influence insulin resistance assessed with HOMA-IR model in vivo.

Body Mass Index↗

Elderly patients with suppressed serum TSH but normal free thyroid hormone levels usually have mild thyroid overactivity and are at increased risk of developing overt hyperthyroidism.

The clinical and biochemical characteristics of 15 elderly patients with low levels of thyrotrophin (TSH) (< 0.1 mU/L) but normal free tri-iodothyronine (T3) and free thyroxine (T4) (group S) were compared with 10 euthyroid subjects (group E) and 10 hyperthyroid patients (group T). Free T3 and free T4 were significantly higher (p < 0.05) in group S (6.3 +/- 0.5 and 18.6 +/- 1.0 pmol/l, respectively) than in group E (4.6 +/- 0.3, 12.6 +/- 0.6). In common with elderly hyperthyroid patients (group T), patients in group S had few signs or symptoms of thyrotoxicosis, but the Wayne score (clinical index of hyperthyroidism) was higher in group S than in euthyroid subjects (p < 0.05). Thyroid microsomal, thyroglobulin or thyrotrophin receptor antibodies were common in group T (n = 9) but not in groups S (n = 2) or E (n = 1). This suggests a low prevalence of Graves' disease in group S compared to group T. Combined thyrotrophin releasing hormone (TRH; 200 micrograms i.v.) and gonadotrophin releasing hormone (GnRH; 100 micrograms i.v.) tests were performed; no cases of low TSH due to hypopituitarism were identified in group S. During a mean of 7.9 (4-12) months of observation TSH reverted to the normal range (> 0.2 mU/L) in 7 of 15 patients in group S; thyroid hormone concentrations rose above the normal range in four, however, only two patients required treatment for hyperthyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Brown adipose tissue cell respiration in hypo- and hyperthyroidism after stimulation with selective and non selective beta-adrenergic agonists.

Brown adipocyte respiration was measured in isolated cells from hypothyroid, hyperthyroid and euthyroid Sprague-Dawley male rats. Hypothyroidism was induced by providing drinking water containing methimazole and hyperthyroidism was induced by addition of thyroid powder to the diet. Brown adipose tissue (BAT) cells were isolated by collagenase digestion and oxygen consumption (VO2) was measured by Clark type oxygen electrodes. BAT cell respiration was stimulated by selective and nonselective beta-adrenergic agonists: BRL 35135A (BRL) and Isoprenaline (ISO). Basal BAT cells respiration did not differ according to thyroid status. Maximal VO2 responses of BAT adipocytes from hypothyroid rats were significantly lower than in euthyroidism after ISO and BRL. The reduced response was more marked for ISO than for BRL. The thermogenic sensitivity was significantly greater in euthyroid than is hypothyroid cells for ISO, but not for BRL. The euthyroid-hyperthyroid differences were not significantly different. These results suggest: basal respiration of BAT cells in hypo- and hyperthyroidism does not reflect the overall changes in whole body metabolism; the decreased thermogenic response in hypothyroidism might be due to decreased beta-adrenoceptor numbers and/or decreased intracellular thyroxine-triiodothyronine conversion; changes in sensitivity to ISO and BRL in vitro reflect the changes seen in VO2 in vivo.

Adipose Tissue, Brown↗

A case of transient central hyperthyroidism.

BACKGROUND: Thionamides are the main therapeutic arsenal for treating hyperthyroidism. Perhaps the first case of a patient who developed a transient pituitary hyperthyroidism after discontinuation of a lengthy intake of a thionamide is reported. CASE REPORT: A 48-year-old woman presented with menstrual irregularities when hypothyroidism with pituitary enlargement was detected. She had been undergoing treatment with methimazole for Graves's hyperthyroidism since the age of 34. Three months after discontinuation of methimazole she presented with clinical and laboratory evidence of thyrotoxicosis, with elevated thyroid-stimulating hormone (TSH) levels and blunted response to thyrotropin releasing hormone (TRH). This secondary hyperthyroidism was self-limited and resolved a few months later. CONCLUSIONS: Chronic primary hypothyroidism caused by lengthy use of thionamides can result in pituitary hyperplasia and transient thyrotrope dysfunction.

Anti-Anxiety Agents↗

[Mitral valve prolapse associated with Basedow's disease and active hyperthyroidism. Preliminary report].

We performed 2 dimensional echocardiograms to investigate the presence of mitral valve prolapse (MVP) in 21 patients with Graves disease and active hyperthyroidism. 22 healthy subjects were used as a control group. The incidence of MVP was 24% (n = 5) in hyperthyroid patients compared to 5% (n = 1) in normals (NS by Fisher's exact test). Age, T3 and T4 levels were similar in hyperthyroid patients with and without MVP, but the clinical course was longer in the former. A study in a larger group of patients may help establish the increased incidence of MVP in hyperthyroidism.

Adult↗

[Atrial fibrillation in a cohort of the elderly: etiopathogenic role of occult hyperthyroidism and diagnostic and therapeutic considerations. Results of the CASTEL (CArdiovascular STudy in the ELderly)].

This work was performed in order to evaluate the weight of hyperthyroidism on the genesis of atrial fibrillation in elderly subjects. The data are from the CASTEL (CArdiovascular STudy in the ELderly), an epidemiologic study performed in a town of northern Italy (Castelfranco Veneto), whose 3088 elderly subjects were called and 2254 enrolled for a 7-year intervention trial. From 2224 elderly persons examined in the present study, 90 had atrial fibrillation (AF) as determined by the presence of Minnesota Code 8-3; the other 2134 were used as control population. In the 90 with AF and in the randomly chosen controls, the thyroid function was studied by means of the TRH-test. Taking into consideration an increase of TSH greater than 0.5 or greater than or greater than 1 muUI/ml over the basal value after TRH administration, 5.5% of subjects with atrial fibrillation had a suppressed response (i.e. hyperthyroidism); taking into consideration a peak value of TSH greater than or equal to 2.3 muUI/ml irrespective to the basal value, the prevalence of hyperthyroidism was higher (17.8%), but not different than in control subjects. In conclusion, hyperthyroidism is frequent in elderly subjects but it does not play a role in the pathophysiology of AF. On the contrary, AF may be explained in the majority of cases by concomitant cardiovascular disease, i.e. left atrial enlargement, arterial hypertension, myocardial ischemia, and heart failure.

Aged↗

[Cardiac manifestations of hyperthyroidism in the elderly].

PURPOSE: To evaluate the cardiocirculatory abnormalities of hyperthyroidism in the elderly. PATIENTS AND METHODS: Twenty-four hyperthyroid patients, 18 women and six men, aged 60 to 87 (average 73.5) years were studied. Seventeen (70.9%) patients had associated cardiocirculatory diseases. The evaluation was made on clinical grounds complemented by electrocardiographic, radiologic, phonomechanocardiographic and echocardiographic examinations. RESULTS: Cardiocirculatory symptoms were observed in 17 (70.9%) patients and congestive heart failure in nine (37.5%) of them. The electrocardiogram was abnormal in 20 (83.3%) patients and the tachyarrhythmias were the commonest abnormality (62.5%). Eight (33.3%) patients had chronic atrial fibrillation and five (20.8%) had sinus tachycardia. There was no significant statistical difference on the electrocardiograms of patients with and without cardiocirculatory abnormalities. Cardiomegaly was significantly more prevalent in hyperthyroid patients, with (64.7%) or without (57.1%) cardiocirculatory abnormalities, than in normal elderly (23.9%). Left ventricular performance was studied in 14 patients through the systolic quotient and was found normal or high in 12 (85.7%). The percentage of fractional shortening (delta D%) was higher than 30 in all patients. None of the patients was found to have symmetric or asymmetric hypertrophic cardiomyopathy and mitral valve prolapse on echocardiogram. CONCLUSION: Hyperthyroidism in the elderly patient determines frequently cardiocirculatory abnormalities that may be misdiagnosed with those caused by the ageing process or by associated cardiopathies. This diagnosis should be suspected in all elderly patients having tachyarrhythmias and/or cardiac failure resistant to usual therapy, mainly in patients without clear cardiocirculatory pathology.

Aged↗

Hyperthyroidism associated with a thyroid adenoma in a dog.

Hyperthyroidism associated with thyroid adenoma was diagnosed in a dog. Typical clinical signs of hyperthyroidism were resolved with surgical excision of the adenoma. Hyperthyroidism in dogs usually is associated with thyroid carcinoma, which has a poor prognosis. This case emphasizes the importance of obtaining a histologic diagnosis of thyroid tumors in hyperthyroid dogs before giving a prognosis.

Adenoma↗

[Significance of assaying serum bone GLA protein level in patients with hyperthyroidism].

The serum BGP level was assayed in patients with hyperthyroidism (untreated and remittent cases). The mean serum BGP concentration was 8.7 +/- 2.5 ng/ml in 54 patients with untreated hyperthyroidism, which was significantly higher than normal range (4.8 +/- 1.3 ng/ml P less than 0.01). Serum BGP had a significant positive correlation with the concentration of T3 and T4, while serum AKP had no correlation with circulating thyroid hormone levels. In the patients with hyperthyroidism, serum T3 and T4 decreased significantly after the first month of methimazole treatment, and fluctuated within the normal range since then. Serum BGP did not show significant change during the first six months of treatment, although they were eventually reduced significantly at the end of six months. These results suggest that serum BGP measurement is a valuable marker of bone metabolism alteration during hyperthyroidism.

Adult↗

Pharmacokinetics and clinical effects of atenolol in therapy of hyperthyroidism.

The pharmacokinetics of atenolol and the effect of the drug on the clinical and laboratory features of hyperthyroidism were studied in 23 patients with hyperthyroidism. In the hyperthyroid state, the time to peak plasma concentration (Tmax) occurred significantly earlier, the elimination half-life was significantly shorter, and the areas under the curve were also significantly less compared to the euthyroid state, but there was no significant difference in peak plasma concentrations (Cmax) between these states. Administration of atenolol once daily resulted in marked clinical improvement in 2 to 4 weeks. The clinical index of thyrotoxic symptoms and signs decreased from 23.2 +/- 10.8 to 8.4 +/- 5.3 (p less than 0.005). Pulse similarly decreased significantly from 93.9 +/- 15.7 to 77.8 +/- 10.5. In contrast to the marked clinical improvement, there was no change in any of the serum concentrations of thyroid hormones T4, free T4, T3 and free T3 at the time of maximal clinical effect compared to pretreatment values. These data show that the beneficial effect of atenolol in hyperthyroidism is not due to changes in thyroid hormone metabolism.

Administration, Oral↗

Hyperthyroidism, inappropriate plasma TSH and pituitary adenoma in three patients, two receiving long-term phenothiazine therapy.

Hypersecretion of TSH by a pituitary adenoma is thought to be a rare form of hyperthyroidism. We describe three such patients, each of whom presented with clinical hyperthyroidism and a diffuse goitre, without eye signs or dermatopathy. Two were receiving long-term phenothiazine, one of these was also acromegalic. Plasma thyroxine, free T4 and tri-iodothyronine were repeatedly raised in each; plasma TSH was grossly elevated in one and inappropriately normal in the other two. Plasma TSH did not rise in response to thyrotrophin-releasing hormone or metoclopramide and was not suppressed by L-dopa in any patient. Anti-thyrotrophin receptor antibodies were undetectable. Skull radiographs showed erosion and expansion of the pituitary fossa and CT scans confirmed a pituitary mass in each patient. A pituitary adenoma was removed by transphenoidal surgery in two patients and a TSH-secreting adenoma was confirmed by immunocytochemical staining and electron microscopy. Both patients were clinically euthyroid post-operatively but still had evidence of TSH excess. Pituitary surgery was technically unsuccessful in the third patient. Although two patients had hyperthyroidism of long duration, all three were diagnosed within one year of the introduction of a sensitive TSH assay to our laboratory. A TSH-secreting pituitary adenoma may be a more common cause of hyperthyroidism than has been believed.

Adenoma↗

Effects of hypothyroidism and hyperthyroidism on thermogenic responses to selective and nonselective beta-adrenergic agonists in rats.

Oxygen consumption (VO2) and mitochondrial guanosine diphosphate (GDP) binding of interscapular brown adipose tissue (BAT) were measured in hypothyroid, hyperthyroid and euthyroid rats after stimulations with selective and nonselective beta-adrenoceptor agonists: BRL 35135A (BRL) and Isoprenaline (ISO). Resting VO2, VO2 increment and mitochondrial GDP binding after beta-adrenergic stimulations were lower in hypothyroid rats than in the euthyroid group. The reduced responses were more marked for ISO than for BRL. Restion VO2 and VO2 increment after beta-adrenergic stimulations were higher in hyperthyroid rats than in the eurthyroid group; the increment was more marked for BRL than for ISO. In hyperthyroidism, mitochondrial GDP binding after BRL and after ISO was in the same magnitude; it was higher in the hyperthyroid than in the euthyroid group after BRL but not after ISO. The different thermogenic responses after ISO and BRL stimulations suggest that BRL is acting on a beta-adrenoceptor differing from the beta-1 and beta-2 adrenoceptors responsible for the effects of ISO. Activation of thermogenesis via the beta-3 adrenoceptor seems to be less dependent on the permissive levels of thyroid hormones than activation via beta-1 and/or beta-2 adrenoceptors. The beta-3 adrenoceptor may be more sensitive to increased levels of thyroid hormones.

Adipose Tissue, Brown↗

[Phosphorus-calcium metabolism in hyperthyroidism].

Because of the bone remodelling it induces, hyperthyroidism modifies the parameters of calcium-phosphorus metabolism. For a better determination of the mechanism involved, we studied 13 patients with Graves' disease compared with 13 controls. We measured the various parameters of calcium-phosphorus metabolism, notably the levels of parathormone, 25-hydroxycholecalciferol, 1-25 dihydroxycholecalciferol and ostocalcin; 8 patients were re-examined in euthyroidism. Total and corrected values of calcaemia (P less than 0.05 and P less than 0.01), phosphoreamie (P less than 0.01), alkaline phosphatase (P less than 0.01), calciuria (P less than 0.01) and hydroxyprolinuria (P less than 0.01) were significantly higher in patients with hyperthyroidism. Osteocalcin also was significantly increased (P less than 0.01) and correlated with thyroid hormone levels, thus confirming its usefulness as marker of bone remodelling in hyperthyroidism. Creatininaemia was significantly lowered (P less than 0.01). The intestinal absorption of calcium after injection of 1 g of calcium was reduced. Parathormone and 25-hydroxycholecalciferol levels were not significantly different in patients and in controls. In patients who were re-examined in euthyroidism, there was a significant increase in parathormone and in 1-25 dihydroxycholecalciferol levels (P less than 0.05). Thus, in situations of hyperthyroidism 2 elements contribute to a deficit in calcium balance: (a) a fall in parathormone level, consecutive to a rise in calcaemia, induces hypercalciuria; and (b) a fall in 1-25 dihydroxycholecalciferol level, consecutive to functional hypoparathyroidism and hyperphosphoraemia, results in a decrease of intestinal calcium absorption.

Adolescent↗

[Synthesis of phosphocreatine in heart mitochondria of rats with hyperthyroidism].

The mechanisms of the phosphocreatine/creatine ratio decrease in female Wistar rats with hyperthyroidism were studied. L-Thyroxin was injected to animals in doses of 50 and 100 micrograms/100 g of body weight, daily for 1 and 2 weeks. Oxidative phosphorylation and the rate of phosphocreatine synthesis were studied in isolated rat heart mitochondria. It was found that hyperthyroidism caused an increase in the ADP-activated mitochondrial respiration, whereas the coupling between electron transport and ADP phosphorylated remained at a constant level. Besides oxidative phosphorylation, activation, hyperthyroidism increased the rate of phosphocreatine synthesis at high values of the phosphocreatine/oxygen ratio. Thus, hyperthyroidism is unaccompanied by and significant changes in the coupling of mitochondrial creatine kinase with oxidative phosphorylation.

Adenosine Diphosphate↗