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Antioxidants in patients with hyperthyroidism.

Hyperthyroidism is a hypermetabolic state accompanied by increased oxygen utilization, increased production of reactive oxygen species and consequentially measurable changes in antioxidative factors. Therefore, the activities of whole blood glutathione peroxidase (GPx) and erythrocyte superoxide dismutase (SOD), total antioxidant status (TAS) in serum and erythrocytes, and serum urate and transferrrin concentrations were determined in 70 women: 14 with newly diagnosed Graves' disease (group A); 28 with hyperthyroidism on therapy with methimazole (group B, divided into two subgroups, B1 and B2) and 28 healthy women (group C). In comparison with control group C, GPx activity was significantly decreased in all patient groups (p < 0.05), whereas SOD activity was significantly decreased in group A (p < 0.01) and significantly increased in group B (p < 0.01). In comparison with the control group, serum TAS activity was significantly decreased in group A, and erythrocyte TAS activity in all patient groups. Study results suggest that the impaired antioxidative factor balance leads to the development and presence of oxidative stress in women with hyperthyroidism. The severity of these alterations, considered contradictory by some authors, appears to depend on the use of therapy.

Adult↗

Hyperthyroidism in children: an Indian experience.

During the period 1986-1993, 24 children with hyperthyroidism were referred to us for management. Two of them had factitious hyperthyroidism, one toxic nodular goiter and another neonatal Graves' disease. Twenty children (6M, 14F) had Graves' disease. Their age at presentation was 10.86 +/- 2.02 years and duration of symptoms ranged from 2.5 months to 7 years. Neuropsychiatric manifestations, such as hyperkinesis, irritability, excitability and behavioral problems, were the most common initial presenting symptoms (90%). Goiter of varying grades was present in 18 children. Eye involvement of mild or moderate intensity was present in 85% and cardiac involvement in 30%. Serum free thyroxine and triiodothyronine levels were high and radioactive iodine uptake was elevated. All of them received carbimazole 0.5-0.7 mg/kg in three divided doses. Seventeen responded to therapy over a period of time while three did not. On withdrawal, six of the responders relapsed. Hyperthyroidism in children is rare and when it occurs it is almost always due to Graves' disease. The prominence of neuropsychiatric symptoms, insidious onset and absence of severe infiltrative ophthalmopathy differentiates it from the adult type of disease. Prolonged medical therapy is needed to induce good continued remission.

Adolescent↗

Effective methimazole dose for childhood Graves' disease and use of free triiodothyronine combined with concurrent thyroid-stimulating hormone level to identify mild hyperthyroidism and delayed pituitary recovery.

Appropriate methimazole dosing for initial treatment of childhood Graves' disease is uncertain. A retrospective chart review was performed on 5 to 17 year-old children treated for Graves' disease. Patients were divided into two groups depending on initial methimazole dosing: low-dose and high-dose regimens using <0.5 mg/kg/day and >0.5 mg/kg/day, respectively. The low-dose regimen was effective in 5/12 (42%) of patients and the high-dose regimen was effective in 27/33 (82%) of patients (p = 0.016). There was also a statistically significant dose/time interaction for levels of free thyroxine (T4) (p = 0.025). During treatment, 63.3% of diagnosable samples showed unambiguous hyperthyroidism or triiodothyronine (T3) toxicosis, 16.7% elevated free T3 with normal free T4 and T3 levels, indicating borderline hyperthyroidism, and 20% showed thyroid-stimulating hormone (TSH) suppression with normal or low levels of free T4 and free T3, indicating delayed recovery of pituitary TSH secretion. Free T3 levels combined with concurrent TSH levels permit differentiation of mild hyperthyroidism from delayed pituitary recovery.

Adolescent↗

Glucose tolerance and insulin secretion in hyperthyroidism.

To evaluate the glucose tolerance and insulin secretion in hyperthyroidism patients were examined in the toxic state and after they had been made euthyroid. Fasting values: In 42 untreated patients the glucose- and insulin concentrations in serum were significantly elevated. In 24 treated patients the glucose concentrations became normal, while the insulin concentrations remained elevated. Oral-glucose-tolerance test: In 20 untreated patients the glucose- and insulin responses were significantly increased. In 8 treated patients the glucose response became normal, while the insulin response remained unchanged. Intravenous-glucose-tolerance test: In 28 untreated patients the K-values were significantly decreased and the insulin response increased. In 23 treated patients the K-values rose significantly, but the insulin response remained unchanged. Intravenous-tolbutamide test: In 41 untreated patients the glucose concentration decreased significantly compared with the controls, and the insulin responses were significantly increased. In 23 treated patients the glucose concentrations decreased even more, while the insulin response remained unchanged. The results indicate enhanced sensitivity or an increase in the mass of beta-cells in hyperthyroidism. The glucose tolerance tests point to an increased peripheral insulin resistance. The normalized glucose tolerance and still enhanced insulin secretion during treatment support the assumption, that hyperthyroidism causes an increase in the beta-cell mass.

Administration, Oral↗

A TSH secreting pituitary tumour causing hyperthyroidism: presentation of a case and review of the literature.

A 45 year old male with a 12 year history of mild hyperthyroidism and a pituitary tumour is presented. He had both clinical and laboratory evidence of hyperthyroidism and his serum TSH was persistently and markedly elevated. A TRH test resulted in no further rise in serum TSH. No evidence of pituitary or peripheral endocrine deficiencies existed and prolactin levels were normal. Craniotomy was performed and a pituitary adenoma was removed. On light microscopy, it was mostly composed of chromophobes. However, occasional granulated cells were observed, and on electron microscopy, most of the cells contained fine granules, which suggested possible thyrotroph origin of the tumour. One week post-operatively the patient's serum TSH returned to normal. Again, TRH produced no response in TSH. The patient became hypothyroid by clinical and laboratory findings and is currently on thyroid replacement therapy. The previously reported TSH secreting tumours associated with hyperthyroidism are reviewed.

Adenoma, Chromophobe↗

The effects of tetraiodothyroacetic and triiodothyroacetic acids on thyroid function in euthyroid and hyperthyroid subjects.

The effects of tetraiodothyroacetic (Tetrac) and triiodothyroacetic acids (Triac) on thyroid function have been investigated in euthyroid and hyperthyroid subjects. 50, 100, 200, 400 or 800 micrograms of Triac were administered to 8 euthyroid volunteers three times (tds) over a 24 hour period. 3 X 800 micrograms Triac/24 h was sufficient to cause a significant reduction in serum T3. Tetrac, given as an iv bolus of 3600 microgram, produced a sustained reduction in serum T3 for up to 4 days after the injection. Intermediate doses of Tetrac (1200 micrograms) or Triac (400 micrograms tds) significantly reduced the TSH response to TRH (66% and 43% respectively). Seven hyperthyroid patients received Triac 200 micrograms tds for 2 days, and in 2, a rapid decrease in serum T3 was seen. Similar changes in serum T3 were also produced with iodide administration. The results suggest that 1) in euthyroidism, Tetrac and Triac act directly at the pituitary level to inhibit the TSH response to TRH; 2) in some cases of hyperthyroidism, Triac produces a block in T3 secretion by virtue of the iodide produced by its metabolism.

Administration, Oral↗

Insulin release and carbohydrate tolerance in hyperthyroid patients during non-selective or selective beta-1-adrenoceptor blockade.

The insulin release and the glucose disappearance rate (K-value) during an iv glucose tolerance test were evaluated in 20 hyperthyroid patients before and during treatment with either a non-selective (propranolol, n = 10) or a selective (metoprolol, n = 10) beta-1-adrenoceptor blocking agent. Mean daily doses were 240 mg of propranolol and 280 mg of metoprolol, administered four times daily for 10 to 14 days. The insulin increase after glucose injection remained unchanged during treatment with each drug. Fasting blood glucose concentrations and the K-values were not altered during treatment. Sixteen patients were re-investigated 10 to 36 weeks later when euthyroid due to treatment by surgery, thyrostatic drugs or radioiodine. In the euthyroid state mean serum insulin concentrations after the glucose load were not significantly different from the values found when the patients were hyperthyroid. However, mean fasting blood glucose concentrations decreased from 5.5 mmol/l to 5.0 (P less than 0.01) and the mean K-value increased from 1.5 to 2.0 (P less than 0.05) when the patients were euthyroid. It is concluded that short-term treatment of hyperthyroid patients with non-selective or selective beta-1-adrenoceptor blocking agents does not impair the glucose stimulated insulin secretion or the carbohydrate tolerance.

Adrenergic beta-Antagonists↗

Effects of propylthiouracil and relatively small doses of iodide on early phase treatment of hyperthyroidism.

In order to compare the acute effects of three methods of treatment in hyperthyroid patients with diffuse goitre, values of thyroxine (T4), triiodothyronine (T3) in serum, T3-resin uptake (T3-U), free thyroxine index (FT4I) and free triiodothyronine index (FT3I) were employed as thyroid function parameters. In iodide (I-) group given iodine (3 or 6 mg/day) as iodinated lecithine once daily, the parameters were reduced acutely within one week after the start of treatment, reaching a plateau during the next week. In contrast to the changes in I- group, the thyroid function was decreased gradually and consistently for two weeks in the propylthiouracil (PTU 300 mg/day) group. In PT1+I- (300 mg/PTU plus 3 or 6 mg/iodide/day) group, the parameters were reduced acutely and progressively for two weeks. These results indicate that PTU+I- therapy is much more effective than PTU or I- alone in early phase treatment of hyperthyroidism. Another new finding was that the thyroid function increased again during the later addition of PTU (300 mg/day) in the patients treated with I- (3 or 6 mg/day) for one or two weeks. The well-known escape phenomenon from iodide inhibition took place counteracted the effect of PTU. Since blocking of thyroidal secretion by I- is only transient while synthesis of T3 and T4 continues, leading to greater amount of hormone stored in the gland, the treatment of hyperthyroidism with I- alone is a risky procedure.

Adolescent↗

Preclinical hyperthyroidism--a graded condition.

In 65 consecutive surgical patients with multinodular goitre and with preclinical hyperthyroidism (TRH-resistant suppression of TSH in the presence of normal circulating thyroid hormones) the individual values of the FT4-index (FT4-I) and FT3-index (FT3-I) showed a wide range form low normal to high normal with mean values not differing from those in TRH-responsive goitre patients and from controls. Thirty-five patients underwent repeated pre-operative TRH tests: 11 (group A) were TRH-unresponsive on one occasion, and TRH-responsive at another time. Fifteen (group B) were TRH-unresponsive on two occasions. Nine patients (group C) were preclinically hyperthyroid on one occasion and had supranormal individual thyroid hormone concentrations at another time. In multinodular goitre patients with preclinical hyperthyroidism a significant T3 increase was observed after oral TRH. In spite of a TRH-resistant suppression of TSH small amounts of TSH are thus still secreted. The degree of TSH suppression may be the result of a varying degree and pattern of continued, fluctuating or elapsed increase in thyroid hormone supply. The T3 response to oral TRH depends not only on the degree of TSH suppression, but also subtlely on the thyroidal reserve: in euthyroid TRH-TSH negative goitre patients a decrease of the TSH-regulated follicular mass by goitre resection abolished the pre-operatively significant T3 response to TRH during the post-operative phase of transient TSH deficiency.

Goiter, Nodular↗

Hyperthyroidism and acromegaly caused by a pituitary TSH- and GH-secreting tumour.

A female patient with acromegaly, TSH-induced hyperthyroidism and a large eosinophilic pituitary adenoma is reported. Granules in the adenoma cells were by immunohistochemical methods shown to contain GH and with monoclonal TSH-antibodies it was shown that 5-10 per cent of the cells secreted TSH. The basal serum TSH was elevated in the hyperthyroid phases and was not suppressible by exogenous T3 but decreased markedly with dexamethasone. There was a small subnormal rise in serum TSH after TRH injection which was totally suppressed by T3 (but not dexamethasone). L-dopa, bromocriptine and somatostatin caused a 20-30 per cent decrease in serum TSH. The alpha-subunit concentration was also elevated and was equally depressed by bromocriptine and somatostatin. The urinary excretion of TRH was within reference limits. This mixed tumour obviously secreted an excess of both GH and TSH causing acromegaly and hyperthyroidism.

Acromegaly↗

Urine TRH immunoreactivity in hypothyroid and hyperthyroid patients.

Urine samples from 8 healthy subjects, from 16 patients with primary hypothyroidism and 8 patients with Graves' hyperthyroidism were pre-purified in SP-Sephadex-C-25 cation-exchange-chromatography, subjected to reverse phase high-pressure liquid chromatography (HPLC) with 0.01 M ammonium acetate pH 4 as a polar and propanol as a non-polar solvent with a 1%/min gradient and assayed in our TRH radioimmunoassay. Urine TRH-immunoreactivity levels were measured before and after 3 months of treatment with thyroxine or methimazole. The urine TRH-levels in healthy subjects were 5.5 +/- 1.4 ng/1 (mean +/- SEM, n = 8). In the hypothyroid patients, the urine TRH levels were 50.6 +/- 40 ng/1 before and 71.7 +/- 45.3 ng/1 after 3 months of treatment with thyroxine. These values did not significantly differ from those in healthy subjects. The large variations were due to highly elevated values in 3 patients. In 2 hypothyroid patients with initially high urine TRH values, 67 and 657 ng/1, urine TRH was measured 5 and 18 months later and was found to have decreased to 5 and 11 ng/1. In the hyperthyroid patients, urine TRH levels were 10.3 +/- 3.9 ng/1 before and 8.9 +/- 3.3 ng/1 after the treatment with methimazole and did not differ significantly from the levels in healthy subjects. After 3 months of treatment, the hyper- and the hypothyroid patients were euthyroid. Our results show, that, except in 2 hypothyroid patients, there does not appear to be any relationship between urine TRH levels and serum TSH or thyroid hormone levels in hypothyroid and hyperthyroid patients.

Chromatography, Gel↗

Hyperthyroidism following primary hypothyroidism in association with polyendocrine autoimmunity.

A 37 year old male with a strong family history of autoimmune disease presented with typical symptoms of hyperthyroidism. He had exophthalmos but no goitre. Hyperthyroidism was confirmed by failure of 131I neck uptake to suppress after 7 days treatment with triiodothyronine. Six years previously a diagnosis of primary hypothyroidism has been made. At diagnosis of hyperthyroidism, thyroglobulin antibodies, thyroidal microsomal antibodies and thyroid stimulating immunoglobulins were detected. The absence of thyroid growth stimulating immunoglobulins and presence of immunoglobulins blocking TSH-induced growth may account for the absence of goitre throughout. HLA -B8, -B, -DR3 and -DR4 genotypes, low C4 complement concentrations and islet cell autoantibodies were detected at the time of diagnosis and 1 year later diabetes mellitus developed.

Adult↗

Intellectual impairment after hyperthyroidism.

Electroencephalography (EEG) and neuropsychological tests empirically shown to be sensitive to diffuse cerebral damage were performed in 26 patients 10 years after successful treatment of hyperthyroidism and in a control group with non-toxic goitre. In the hyperthyroid state 81% had abnormal EEG before treatment, and 10 years after treatment 68% still had abnormal EEG compared with 41% in the control group (P less than 0.05). In 7 out of 11 neuropsychological tests the previously hyperthyroid patients showed significant impairment compared with the control group. Twenty-three per cent of the patients displayed marked to severe intellectual impairment, 31% moderate and 41% slight or no impairment compared with 0%, 31% and 69%, respectively, in the control group (P less than 0.05). Four patients had been granted disability pension on the basis of the intellectual dysfunction. Signs of intellectual impairment indicating irreversible brain dysfunction after thyrotoxicosis thus seem to be a frequent, although hitherto not generally recognized, finding.

Adult↗

Hyperthyroidism due to a thyroid-stimulating hormone (TSH)-secreting pituitary adenoma associated with functional hyperprolactinaemia. A case report.

This paper reports the case of a 31-year-old woman with hyperthyroidism, increased TSH and thyroid hormone levels, evidence of a pituitary adenoma, hyperprolactinaemia, amenorrhoea, and galactorrhoea. Following trans-sphenoidal pituitary adenomectomy, mild hyperthyroidism and increased TSH and alpha subunit levels persisted, whereas hyperprolactinaemia, amenorrhoea, and galactorrhoea disappeared. Serum TSH levels were not affected by administration of TRH, metochlopramide, domperidone, l-dopa or somatostatin. Serum TSH chromatography showed a normal pattern. Following a second trans-sphenoidal pituitary adenomectomy and radiotherapy, hyperthyroidism disappeared, and the TSH and alpha subunit levels returned to normal. Light microscopy showed no specific TSH immunostaining although electron microscopy revealed numerous secretory granules alined along the plasma membrane. The post-operative follow-up confirmed the presence of a TSH-secreting pituitary adenoma associated to functional hyperprolactinaemia.

Adenoma↗

Testosterone and its binding in hyperthyroid women before and under antithyroid drug therapy.

The serum concentrations of the different forms of circulating testosterone, total testosterone, free testosterone and non-sex-hormone binding globulin bound testosterone (albumin bound + free fractions) which is considered as the bioavailable hormone, were measured in 15 hyperthyroid women before and after anti-thyroid drug therapy and in 15 age-matched healthy women. Sex-hormone binding globulin and albumin were quantified. Total testosterone was significantly higher in hyperthyroid women before treatment, whereas free testosterone and non sex-hormone binding globulin bound testosterone were significantly decreased. After recovery, all the parameters returned to the normal range. In hyperthyroid patients, the variations in the different fractions of testosterone can be related to the rise of sex-hormone binding globulin. These variations could be explained by the displacement of the equilibrium defined by the binding equation.

Adult↗

The effects of propranolol and verapamil on hyperthyroid heart symptoms and function, assessed by systolic time intervals.

The effects of acute and chronic administration of propranolol and verapamil on heart rate and systolic time intervals were studied in 10 hyperthyroid patients and 10 normal subjects, both groups without signs of cardiovascular or pulmonary disease. In normal subjects iv propranolol reduced heart rate significantly, and both drugs increased the total electromechanical systole significantly without difference between the drugs. This effect was insignificant when the drugs were given orally. In hyperthyroid patients both drugs reduced heart rate significantly in acute and chronic administration, and no difference between the two drugs was found. Neither drug altered cardiac contractility as assessed by systolic time intervals. These results indicate that the metabolic effects of thyroid hormone on contractility were unaltered and unblocked by the drugs. None of the participants developed signs of heart failure. Verapamil can thus be used as an alternative to propranolol in the treatment of tachycardia in hyperthyroidism.

Administration, Oral↗

Expression of nitric oxide synthase III in human thyroid follicular cells: evidence for increased expression in hyperthyroidism.

Nitric oxide mediates a wide array of cellular functions in many tissues. It is generated by three known isoforms of nitric oxide synthases (NOS). Recently, the endothelial isoform, NOSIII, was shown to be abundantly expressed in the rat thyroid gland and its expression increased in goitrous glands. In this study, we analyzed whether NOSIII is expressed in human thyroid tissue and whether levels of expression vary in different states of thyroid gland function. Semiquantitative RT-PCR was used to assess variations in NOSIII gene expression in seven patients with Graves' disease, one with a TSH-receptor germline mutation and six hypothyroid patients (Hashimoto's thyroiditis). Protein expression and subcellular localization were determined by immunohistochemistry (two normal thyroids, five multinodular goiters, ten hyperthyroid patients and two hypothyroid patients). NOSIII mRNA was detected in all samples: the levels were significantly higher in tissues from hyperthyroid patients compared with euthyroid and hypothyroid patients. NOSIII immunoreactivity was detected in vascular endothelial cells, but was also found in thyroid follicular cells. In patients with Graves' disease, the immunostaining was diffusely enhanced in all follicular cells. A more intense signal was observed in toxic adenomas and in samples obtained from a patient with severe hyperthyroidism due to an activating mutation in the TSH receptor. In multinodular goiters, large follicles displayed a weak signal whereas small proliferative follicles showed intense immunoreactivity near the apical plasma membrane. In hypothyroid patients, NOSIII immunoreactivity was barely detectable. In summary, NOSIII is expressed both in endothelial cells and thyroid follicular cells. The endothelial localization of NOSIII is consistent with a role for nitric oxide in the vascular control of the thyroid. NOSIII expression in thyroid follicular cells and the variations in its immunoreactivity suggest a possible role for nitric oxide in thyrocyte function and/or growth.

Humans↗

Dendritic cells produce interleukin-12 in hyperthyroid mice.

We previously reported that serum interleukin-12 (IL-12) levels were significantly increased in patients with hyperthyroid Graves' disease and in normal subjects after administration of thyroid hormone. In the present study, we investigated which cells produce IL-12 and the interactions between IL-12 and thyroid hormones, using a hyperthyroid mouse model. Thyroid hormones induced IL-12 production, and IL-12 was mainly produced by dendritic cells outside the thyroid glands in a hyperthyroid state.

Animals↗