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Tissue sources of serum alkaline phosphatase in 34 hyperthyroid cats: a qualitative and quantitative study.

The concentration of serum alkaline phosphatase (SALP) is commonly elevated in hyperthyroid cats. Agarose gel electrophoresis, in tris -barbital-sodium barbital buffer, with and without the separation enhancer neuraminidase, was used to investigate the sources of the constituent isoenzymes of SALP in serum samples from 34 hyperthyroid cats, comparing them to sera from five healthy cats and to tissue homogenates from liver, kidney, bone and duodenum. Contrary to previous reports, treatment of serum with neuraminidase made differentiation of the various isoenzymes more difficult to achieve. A single band corresponding to the liver isoenzyme (LALP) was found in 100 per cent of healthy cats. Eighty-eight per cent of the hyperthyroid cats showed two bands, corresponding to the liver and bone (BALP) isoenzymes while 12 per cent showed a LALP band alone. In hyperthyroid cats, there was a significant correlation between the serum L-thyroxine concentrations and the SALP concentrations. These findings suggest pathological changes in both bone and liver in most cases of feline thyrotoxicosis.

Alkaline Phosphatase↗

Carbohydrate metabolism in thyrotoxicosis: studies on insulin secretion before and after remission from the hyperthyroid state.

The effects of thyrotoxicosis on insulin secretion were studied in 11 patients with Graves' disease and compared with the results obtained in 6 of the patients after they had attained clinical remission. Constant glucose infusion (CGI) and acute tolbutamide infusion (AIT) tests were chosen to investigate beta-cell function. For similar means of fasting plasma glucose, basal plasma insulin mean was significantly higher during thyrotoxicosis. During AIT, mean peak insulin was obtained earlier in the hyperthyroid state (2 min) than after remission (4 min), being its level higher in the hyperthyroid state. During CGI, early insulin responses to similar plasma glucose increments, were comparable for both hyper and euthyroid subjects. After 10 minutes of CGI, insulin concentrations in the hyperthyroid state did not increase as in the euthyroid state in spite of comparable increments of plasma glucose, being similar plateau insulin levels attained thereafter. These results suggest the presence of an insulin-resistant state in hyperthyroidism which may either disappear during a chronic glucose infusion and/or be accompanied by a deficient late glucose-induced insulin release.

Adolescent↗

[Serum level and urinary excretion of 14C-thiamozol in patients with hyperthyroidism (author's transl)].

2-(14C) Thiamazol (Favistan) was administered intravenously in a therapeutically subthreshold dose to seven control subjects and five patients with hyperthyroidism. In both groups the reduction of plasma radioactivity occurred with at least two exponentials. Half-life was calculated to be 35 minutes for the faster and 28 hours for the slower process in the control group, and 12 minutes and about 20 hours, respectively, in the hyperthyroid patients. Forty-eight hour urinary excretion of the injected radioactive material was about 80% for the hyperthyroid patients and 87% for the control subjects. Maximal activity in urine occurred about six hours after injection. There was practically no demonstrable plasma-protein binding of the drug in in-vitro experiments. As the pharmacokinetics of the drug are not influenced in thyroid disease, there is apparently no need to adapt thyrostatic dosage in hyperthyroid states.

Adult↗

The effect of diltiazem on the manifestations of hyperthyroidism and thyroid function tests.

The aim of this study is to evaluate the effect of diltiazem on the symptoms and signs of hyperthyroidism and thyroid function tests and to assess whether diltiazem can be used associated with an anti-thyroid drug, propylthiouracil. Twenty-two patients with hyperthyroidism were included in a prospective, randomized and placebo controlled study. Group 1 (n:12) patients received diltiazem, 60 mg twice a day, for 30 days. Group 2 (n:10) patients received placebo for 30 days. The patients in both groups were given propylthiouracil, 100 mg three times a day, for the last 20 days of the study period. The patients remained in the hospital during the first 10 days. A standardized hyperthyroid symptom score (HSS) and thyroid function tests including thyroid-stimulating hormone (TSH), free thyroxine (free T4), free triiodothyronine (free T3), total thyroxine (T4) and total triiodothyronine (T3) were evaluated before and after 10 and 30 days of the study period. HSS decreased from 27.80 +/- 4.54 to 22.51 +/- 4.04 after 10 days of diltiazem therapy in Group 1 (p < 0.01). But there was no change in HSS in Group 2 (p > 0.01). No significant changes in thyroid function tests have occurred in both groups after 10 days of treatment. Diltiazem can be used in patients with hyperthyroidism to alleviate adrenergic manifestations. It can also be safely combined with propylthiouracil.

Antithyroid Agents↗

Angiotensinase activity in hypothalamus and pituitary of hypothyroid, euthyroid and hyperthyroid adult male rats.

A local renin-angiotensin system (RAS) that may be involved in their regulatory functions has been identified in hypothalamus and pituitary. Altered thyroid status induces modifications in the secretory function of hypothalamus and pituitary. However, few studies have analyzed the role of the RAS in hypothalamus and, to our knowledge, there is no data on the pituitary RAS during thyroid dysfunction. In the present study, angiotensinase activities (glutamyl, aspartyl and alanyl aminopeptidase: GluAP, AspAP and AlaAP, respectively) were studied in hypothalamus and in the anterior and posterior lobes of pituitary of euthyroid, hypothyroid and hyperthyroid adult male rats. In the anterior pituitary, compared with euthyroid and hyperthyroid rats, hypothyroid animals showed a highly significant increase of GluAP and AspAP activities; the percentage increase in GluAP was markedly higher than the percentage increase in AspAP. This suggests an increased metabolism of angiotensin (Ang) I and Ang II to des-Asp 1-Ang I and Ang III, respectively. We also observed an increase of Ang III-degrading activity (AlaAP) in the hypothalamus of hyperthyroid rats in soluble fraction. Increased Ang I and Ang II metabolism in the anterior pituitary of hypothyroid rats and increased metabolism of Ang III in the hypothalamus of hyperthyroid animals may be related to alterations in the secretory function of hypothalamus and pituitary in these thyroid dysfunctions.

Animals↗

Therapy of hyperthyroidism.

Hyperthyroidism is a common disorder and affects approximately 2 % of women and 0.2 % of men. The review focuses on the therapy of overt hyperthyroidism with special emphasis on treatment strategies in Germany and Europe. Current treatment schedules for the different causes of hyperthyroidism are described and new therapeutic aspects are discussed. Special sections deal with the treatment of hyperthyroidism in pregnancy, neonates and children, and the treatment of thyrotoxic storm.

Antithyroid Agents↗

[Prevalence of latent and manifest hyperthyroidism in an iodine-deficient area: non-selected patient population admitted for CT studies with iodine-containing contrast agents].

PURPOSE: To evaluate the prevalence of latent and manifest hyperthyroidism in a non-selected group of patients admitted for contrast enhanced CT studies blood samples were tested for the levels of thyroid-stimulating hormone (TSH). MATERIAL AND METHODS: TSH blood levels were obtained in 548 consecutive patients who were scheduled for contrast-enhanced (Iopromide; 300 mg iodine/ml) CT scanning. In case of TSH levels < 0.4 mU/l, blood samples were also tested for triiodothyronine (T3) and tetraiodothyronine (T4) blood levels, and treatment with Irenat (sodium perchlorate) was commenced before scanning. In case of TSH levels < 0.1 mU/l, CT scanning was not performed but further evaluation of the thyroid function was initiated. RESULTS: TSH blood levels ranged from 0.4 to 7.5 mU/l in 512 patients, and 36 patients (6.6%) had TSH blood levels < 0.4 mU/l and 9 patients blood levels < 0.1 mU/l, with 32 of those patients (5.8%) having regular T3 and T4 blood levels consistent with latent hyperthyroidism. In 4 patients (0.8%), T3 or T4 blood levels were increased consistent with manifest hyperthyroidism. CONCLUSION: In South Germany, the prevalence of latent or manifest hyperthyroidism in a non-selected patient group is high. Therefore TSH blood levels should be obtained prior to contrast-enhanced CT studies.

Adult↗

Serum bone Gla protein (BGP) during treatment of hyperthyroidism and hypothyroidism. A longitudinal study.

Serum bone gamma-carboxyglutamic acid-containing (Gla) protein (BGP) was measured before and with initially 2 weeks, later 4-8 weeks intervals for 20-58 weeks during treatment of patients with hyperthyroidism (n = 10) and hypothyroidism (n = 4). Biochemical euthyroidism was obtained in the hyperthyroid patients after a median of 3 weeks (range 1-8 weeks), and in the hypothyroid patients after a median of 17 weeks (range 10-27 weeks). Serum BGP levels closely followed the thyroid state, being high respectively low in the hyperthyroid and hypothyroid state and reaching a stable plateau just at the time biochemical euthyroidism was obtained. These data suggest that osteoblastic activity is enhanced in hyperthyroidism and reduced in hypothyroidism, and that normalization occurs in close conjunction with the normalization of the thyroid state, without any delay, indicating a direct effect on the function of the excisting osteoblasts by the thyroid hormones.

Aged↗

Plasma atrial natriuretic peptide, plasma renin activity and aldosterone during treatment of hyperthyroidism due to Graves' disease.

Plasma atrial natriuretic peptide (ANP), plasma renin activity (PRA) and aldosterone were consecutively measured during methimazole treatment in patients with hyperthyroidism due to Graves' disease. ANP values of untreated hyperthyroid patients varied greatly from patient to patient, but decreased progressively with a decrease of serum thyroid hormone concentration during methimazole treatment. PRA was elevated in hyperthyroid patients but less aldosterone was secreted as evidenced by lower aldosterone/PRA ratio in these patients than in normal subjects and in hypertensive patients treated with thiazide. In addition, aldosterone/PRA ratio increased progressively with a decrease of ANP during methimazole treatment. The data indicated that ANP secretion was increased and ANP thus secreted depressed aldosterone secretion in hyperthyroid patients. Propranolol depressed pulse rate but failed to affect ANP secretion. It is suggested that thyroid hormone specifically acts on myocytes to stimulate ANP secretion but physiologic significance of such increased ANP secretion remains to be solved.

Adolescent↗

Plasma renin activity, active and inactive renin concentrations, and their responses to beta 1-adrenoceptor blockade with metoprolol in hyperthyroidism.

Plasma renin activity (PRA), plasma renin concentration (PRC), inactive renin concentration (IRC) and total renin concentration (TRC) were measured in 31 normal controls and in 8 patients with hyperthyroidism. TRC was determined as angiotensin I generated with sheep renin substrate after an acid activation of plasma. The angiotensin I of non-acidified plasma was expressed as PRC. IRC was calculated as TRC minus PRC. The mean values for PRA, PRC, IRC and TRC were significantly (P less than 0.05 to P less than 0.01) higher in the hyperthyroid patients than in the normal or euthyroid controls. The administration of a beta 1-adrenergic blocker, metoprolol (120 mg/day for 14 days), produced a significant (P less than 0.05 to P less than 0.01) fall in levels of T4, PRA and TRC, and reduced the active renin ratio calculated from PRC/TRC significantly (P less than 0.025), as compared to the pretreatment values. Our observations support the idea that the higher PRA in hyperthyroidism is due to an increased secretion of renin. Furthermore, the results may indicate that the conversion of inactive to active renin is accelerated in hyperthyroidism, possibly by an increased sympathetic activity.

Adult↗

An elevation of BUN/creatinine ratio in patients with hyperthyroidism.

Blood urea nitrogen (BUN/creatinine ratio was abnormally high (24.8 +/- 0.6) in untreated hyperthyroid patients due to both increase in BUN and decrease in creatinine concentration. BUN, creatinine and BUN/creatinine ratio were all completely normalized after restoration of euthyroid status. On the other hand, BUN/creatinine ratio was slightly suppressed in hypothyroidism before treatment and it was reversed by thyroxine treatment (12.6 +/- 4.0 and 16.3 +/- 3.3, before and after treatment, respectively). An age-related increase in BUN/creatinine ratio, which was primarily due to an age-related increase in BUN, was also found in hyperthyroid subjects (21.9 +/- 2.8 vs 27.7 +/- 9.0; first vs fifth decade) and in normal controls (13.7 +/- 2.8 vs 16.0 +/- 2.9; first vs fifth decade). To elucidate reasons for abnormal increase in BUN/creatinine ratio in hyperthyroidism, measurement of cardiac output and kinetic analysis on urea nitrogen (UN) and creatinine were performed. The results indicated a marked increase in cardiac output. Serum creatine concentration was clearly increased in hyperthyroid patients. Thus, serum creatinine concentration was suppressed due to a decrease in creatinine synthesis and an increase in renal creatinine excretion. BUN was high, primarily due to an increase in UN production secondary to excessive protein catabolism together with insufficient excretion of UN.

Adolescent↗

["Hyperthyroiditis" (author's transl)].

Typical signs of so-called hyperthyroiditis are hyperthyroidism, low iodine uptake by the thyroid, absence of local, general or humoral signs of inflammation, and absence of significant antibody titres against thyroid tissue. These features are illustrated by the case report of a 51-year-old man. Since the course of hyperthyroidism is short and has a good prognosis, the importance of the diagnosis lies in avoiding unnecessary therapeutic measures. This cause of hyperthyroidism can be recognized only by including tests of intrathyroid iodine metabolism among diagnostic procedures.

Antibodies↗

Administration of thyroxine in treated Graves' disease. Effects on the level of antibodies to thyroid-stimulating hormone receptors and on the risk of recurrence of hyperthyroidism.

BACKGROUND: Antibodies to thyroid-stimulating hormone (TSH) receptors that stimulate the thyroid gland cause hyperthyroidism in patients with Graves' disease, and their production during antithyroid drug treatment is an important determinant of the course of the disease. One factor that might contribute to the persistent production of antibodies to TSH receptors is stimulation of the release of thyroid antigens by TSH during antithyroid drug therapy. We therefore studied the effect of the suppression of TSH secretion by thyroxine on the levels of antibodies to TSH receptors after thyroid hormone secretion had been normalized by methimazole. METHODS AND RESULTS: The levels of antibodies to TSH receptors were measured during treatment with methimazole, either alone or in combination with thyroxine, in 109 patients with hyperthyroidism due to Graves' disease. The patients first received 30 mg of methimazole daily for six months. All were euthyroid after six months, and their mean (+/- SD) level of antibodies to TSH receptors decreased from 64 +/- 9 percent to 25 +/- 15 percent (P less than 0.01; normal, 2.9 +/- 1.4 percent). Sixty patients then received 100 micrograms of thyroxine and 10 mg of methimazole and 49 received placebo and 10 mg of methimazole daily for one year. In the thyroxine-treated group, the mean serum thyroxine concentration increased from 108 +/- 16 nmol per liter to 145 +/- 11 nmol per liter (P less than 0.01), and the level of antibodies to TSH receptors decreased from 28 +/- 10 percent to 10 +/- 3 percent after one month of combination therapy. In the patients who received placebo and methimazole, the mean serum thyroxine concentration decreased and the level of antibodies to TSH receptors did not change. Methimazole, but not thyroxine or placebo, was discontinued in each group 1 1/2 years after the beginning of treatment. The level of antibodies to TSH receptors further decreased (from 6.6 +/- 3.2 percent at the time methimazole was discontinued to 2.1 +/- 1.2 percent one year later) in the patients who continued to receive thyroxine, but it increased (from 9.1 +/- 4.8 percent to 17.3 +/- 5.8 percent during the same period) in the patients who received placebo. One patient in the thyroxine-treated group (1.7 percent) and 17 patients in the placebo group (34.7 percent) had recurrences of hyperthyroidism within three years after the discontinuation of methimazole. CONCLUSIONS: The administration of thyroxine during antithyroid drug treatment decreases both the production of antibodies to TSH receptors and the frequency of recurrence of hyperthyroidism.

Adolescent↗

Mortality after the treatment of hyperthyroidism with radioactive iodine.

BACKGROUND: Hyperthyroidism affects many organ systems, but the effects are usually considered reversible. The long-term effects of hyperthyroidism on mortality are not known. METHODS: We conducted a population-based study of mortality in a cohort of 7209 subjects with hyperthyroidism who were treated with radioactive iodine in Birmingham, United Kingdom, between 1950 and 1989. The vital status of the subjects was determined on March 1, 1996, and causes of death were ascertained for those who had died. The data on the causes of death were compared with data on age-specific mortality in England and Wales. The standardized mortality ratio was used as a measure of relative risk, and the effect of covariates on mortality was assessed by regression analysis. RESULTS: During 105,028 person-years of follow-up, 3611 subjects died; the expected number of deaths was 3186 (standardized mortality ratio, 1.1; 95 percent confidence interval, 1.1 to 1.2; P<0.001). The risk was increased for deaths due to thyroid disease (106 excess deaths; standardized mortality ratio, 24.8; 95 percent confidence interval, 20.4 to 29.9), cardiovascular disease (240 excess deaths; standardized mortality ratio, 1.2; 95 percent confidence interval, 1.2 to 1.3), and cerebrovascular disease (159 excess deaths; standardized mortality ratio, 1.4; 95 percent confidence interval, 1.2 to 1.5), as well as fracture of the femur (26 excess deaths; standardized mortality ratio, 2.9; 95 percent confidence interval, 2.0 to 3.9). The excess mortality was most evident in the first year after radioiodine therapy and declined thereafter. CONCLUSIONS: Among patients with hyperthyroidism treated with radioiodine, mortality from all causes and mortality due to cardiovascular and cerebrovascular disease and fracture are increased.

Cardiovascular Diseases↗

Influence of hyperthyroidism induced at prepuberty on the epididymal lipids, number and motility of spermatozoa in rats.

Fifteen prepubertal rats were divided into 3 groups of 5 each: (1) hyperthyroid group (TH), the rats were treated with thyroxine (T4) (25 micrograms/100g body weight/day) for 60 days from the age of day 31 to day 90; (2) T4-withdrawal group (TH-T4), the rats were given T4 for 30 days from the age of day 31 to day 60 and then the T4 treatment was withdrawn for the following 30 days from the age of day 61 to day 90 and the animals were given vehicle during this period; and (3) control group, the rats were given vehicle for 60 days from the age of day 31 to day 90. All were killed at the age of day 91. Serum levels of testosterone, T4 and triiodothyronine increased in the TH group (P < 0.001). The levels decreased to the euthyroid status in the TH-T4 group. Hyperthyroidism caused various changes in the levels of epididymal lipids. The levels changed further or were restored differentially in the TH-T4 group. The number of spermatozoa decreased, in caput epididymis (CpE) as well as in cauda epididymis (CdE), in the TH group (P < 0.001). The number was not restored in the TH-T4 group. The forward motility of the spermatozoa, determined in CdE, decreased in the TH group (P < 0.001) and was not restored in the TH-T4 group. The study showed that chronic hyperthyroidism, induced at the prepubertal age, causes various changes in epididymal lipid composition and sperm parameters. The study may be helpful in revealing the reasons for male infertility in hyperthyroid patients.

Animals↗

The combined effects of Trigonella and Allium extracts in the regulation of hyperthyroidism in rats.

The combined effects of Trigonella foenum-graecum and Allium sativum extracts were evaluated for their ameliorative potential in the L-thyroxine-induced hyperthyroidic rat model to contribute to an understanding of interaction between the two extracts. The investigation was carried out using two different doses. A comparison was made with the response of individual plant extracts at the previously studied effective dose in adult Wistar rats rendered hyperthyroidic by daily injections of L-thyroxine (300 microg/kg body wt., s.c.). Propylthiouracil (PTU), an antithyroid drug, was used as a reference compound. Alterations in serum triiodothyronine (T3), thyroxine (T4), glucose, hepatic glucose-6-phosphatase (G-6-Pase) and oxygen consumption were studied as end parameters. Superoxide dismutase (SOD), catalase (CAT) activities, lipid peroxidation (LPO) and reduced glutathione (GSH) were examined to reveal any toxic effects of the drugs. The combined effects of Trigonella and Allium at 200 and 500 mg/kg body wt. respectively, were equipotent as compared to the individual extracts in lowering the serum concentrations of T3 and T4 in hyperthyroidic rats. Our findings reveal that some plant extracts in combination may not always prove to be synergistic. It is therefore suggested that Trigonella foenum-graecum and Allium sativum extracts may be used individually and not together in the regulation of hyperthyroidism.

Animals↗

Erythrocyte creatine levels in hyperthyroidism.

The mechanism by which erythrocyte mean corpuscular volume (MCV) is decreased in hyperthyroidism is not known. One possible mechanism is premature aging of erythrocytes in the circulation. Since erythrocyte creatine has been shown to be a good marker of cell senescence, we determined this in hyperthyroid patients and control subjects to examine whether the decrease in MCV is related to senescence. Erythrocyte creatine levels were similar in both hyperthyroid patients and controls, suggesting that premature senescence of erythrocytes does not account for the lower MCV in hyperthyroidism.

Adult↗

Hyperthyroidism and thyroid cancer. A report of three cases.

In patients with hyperthyroidism and a palpable solitary nodule, the physician should be alert to the need for further evaluation before a method of therapy is chosen. In our opinion, surgery should be the treatment of choice for a hyperthyroid patient with a "cold" solitary thyroid nodule. We no longer believe that hyperthyroidism minimizes the possibility of coexistent thyroid carcinoma in hyperthyroid patients with hypofunctioning nodules. We would also suggest a reexamination of the concept of thyroid carcinoma being dependent on thyroid-stimulating hormone.

Adenocarcinoma, Papillary↗