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Plasma C-peptide response to oral glucose load in hyperthyroidism.

Aim of the present study was to evaluate the pancreatic beta cell response to oral glucose load in a group of patients with hyperthyroidism. For this purpose plasma C-peptide at fasting and after a 100 g oral glucose load was measured in 8 newly-diagnosed untreated hyperthyroid patients with fasting normoglycemia, and 8 sex-, age-, and weight-matched healthy controls. As compared to healthy subjects, patients with hyperthyroidism showed higher plasma glucose levels (incremental area 5405 +/- 742 vs 2729 +/- 539 mg/dl x 180 min, p less than 0.05), and slightly reduced plasma C-peptide concentrations (incremental area 166 +/- 12 vs 182 +/- 36 pmol/ml x 180 min, p = NS) following oral glucose load. The ratios between plasma C-peptide and plasma glucose incremental areas were lower in hyperthyroid patients than in controls (3.66 +/- 0.85 vs 10.41 +/- 3.08, p less than 0.05). These data suggest that hyperthyroidism is characterized by a decreased pancreatic beta cell response to oral glucose load.

Administration, Oral↗

Bone mineralization and calciotropic hormones in children with hyperthyroidism. Effects of methimazole therapy.

We studied bone mineralization and calcium homeostasis in two children with hyperthyroidism before and during 3 yr of methimazole therapy in order to evaluate the effects of thyrotoxicosis and its therapy on mineral metabolism. Case 1, female, 4.1 year old with hyperthyroidism from 6 months. Biochemical data: increased thyroid function, phosphate and osteocalcin, decreased 1,25(OH)2D levels. X-ray: severe osteoporosis; bone mineral content (BMC) -23.0%, BMC/BW -25.1%. Case 2, female, 7.4 year old with hyperthyroidism from 9 months. Biochemical data: thyroid function, ionized calcium and osteocalcin were increased, 1,25(OH)2D and intact PTH were decreased. X-ray: severe osteoporosis: BMC -32.8%, BMC/BW -36.0. After the patients were euthyroid, they showed an increase of 1,25(OH)2D and intact PTH into normal values and a fall in calcium and phosphate. Osteocalcin levels returned in normal range one yr after first evaluation. Bone mineral analysis showed no variation of BMC and BMC/BW in the first 6 months of therapy and an increase in the following 6 months. In the following two years BMC and BMC/BW rose to normal range. Our study provides further evidence that in hyperthyroidism an altered mineral homeostasis is present with a reversible disturbance in vitamin D metabolism. We found that the return to euthyroidism was associated with a normalization of mineral homeostasis and with a recovery of bone mineralization. Osteocalcin assay may be an useful index to monitor bone metabolism in hyperthyroidism.

Absorptiometry, Photon↗

Evaluation of central motor conduction in hypothyroid and hyperthyroid patients.

Deficiency or excess of thyroid hormones is associated with central nervous system (CNS) disturbances. Although the CNS involvement either in hypothyroidism or in hyperthyroidism have previously been shown on the basis of visual, auditory and somatosensory evoked potentials studies, less is known about the function of central motor pathways in both disorders. We studied the motor evoked potentials (MEPs) following the magnetic stimulation of the motor cortex and spinal roots in 20 patients with hypothyroidism and in 19 patients with hyperthyroidism both before treatment and after they became euthyroid and compared with findings in 20 age-, sex- and height-matched control subjects. Disease duration (expressed as time from diagnosis of diseases to the time of neurological testing) is less than one month in both disorders. Central motor conduction time (CMCT) was determined as the differences between MEPs latencies after cortical and spinal stimulation. The mean CMCTs before treatment in hypothyroid patients (8.31 +/- 1.52 msec.) and in hyperthyroid patients (7.92 +/- 1.06 msec.) were significantly prolonged as compared to those in normal controls (6.82 +/- 0.83 msec. p = 0.002 and p = 0.004, respectively). Four of the 20 (20.0%) hypothyroid patients and 2 of 19 (10.5%) hyperthyroid patients had abnormal CMCT (values exceeding mean +2.5 SD of normal control). The mean CMCT values in both groups were not significantly decreased after euthyroidism was achieved, although a tendency of the decrease in CMCT was observed. Improvement of CMCT abnormalities was observed in 1 of 4 hypothyroid patients and in one of 2 patients with hyperthyroidism, who had CMCT abnormalities before treatments, after they became euthyroid. No correlation was found between CMCT and free T3, free T4, or TSH levels as well as the onset age, the severity of the diseases or the disease duration in both disorders. We conclude that abnormal CMCT could be documented in few patients in both disorders. However, these alterations could not be improved completely after restoration of euthyrodism. Thus, it remains to be determined if long-term treatment would completely improve CMCT abnormalities in both disorders. Since abnormal CMCT values in both disorders were observed only in few patients, our results also suggest that CMCT measurement does not have, at present time, a clinical usefulness to assess the peripheral action of thyroid hormones. Thus, the data obtained need a more extensive evaluation.

Adult↗

Severe hyperthyroidism due to metastatic papillary thyroid carcinoma with favorable outcome.

A case of extremely severe hyperthyroidism due to bone metastasis of papillary thyroid cancer is described. Hyperthyroidism began in this patient soon after the discovery of pelvic metastasis and worsened after total thyroidectomy and after the first dose of radioiodine. The administration of methimazole, prednisone and multiple, fractioned and small doses of radioiodine cured the hyperthyroidism and stabilized the neoplastic growth. Hyperthyroidism lasted for at least six months and hypothyroidism appeared only after seven months. Thus, the fractionation of the doses of radioiodine together with antithyroid drugs appears to be an effective treatment in patients with hyperthyroidism due to metastatic thyroid cancer.

Aged↗

Cytogenetic damage after 131-iodine treatment for hyperthyroidism and thyroid cancer. A study using the micronucleus test.

To detect the incidence and persistence of potential chromosome damage induced by iodine-131 therapy, we applied the cytokinesis-block micronucleus assay to peripheral blood lymphocytes from hyperthyroidism and thyroid cancer patients treated with 131I. Two groups of patients were evaluated in a longitudinal study; one group was composed of 47 hyperthyroid patients and the other of 39 thyroid cancer patients. In the hyperthyroidism group, the micronuclei frequency was determined before 131I therapy and 1 week, 1 month and 3 months after it. Furthermore, an additional sample was taken from a subgroup of 17 hyperthyroidism patients 6 months after treatment. In the thyroid cancer group, the analysis was also conducted over time, and four samples were studied: before treatment and 1 week, 6 months and 1 year later. Simultaneously, a cross-sectional study was performed with 70 control subjects and 54 thyroid cancer patients who had received the last therapeutic dose 1-6 years before the present study. In the hyperthyroidism group a significant increase in the micronuclei average was found over time. In the sample obtained 6 months after therapy, the micronuclei mean frequency was practically the same as in the sample taken 3 months before. In the thyroid cancer group a twofold increase in the frequency of micronuclei was seen 1 week after therapy. Although this value decreased across time, the micronuclei frequency obtained 1 year after 131I therapy remained higher than the value found before it. Concerning the data from the cross-sectional study, a significant increase in the frequency of micronuclei was detected in the subgroup of thyroid cancer patients treated between 1 and 3 years before the current study. These results indicate that exposure to 131I therapy induces chromosome damage in peripheral lymphocytes and that the cytokinesis-block micronucleus assay is sensitive enough to detect the genetic damage by exposure to sufficiently high levels of radiation from internal radioactive sources.

Adolescent↗

Development of hyperthyroidism in a patient with idiopathic nephrotic syndrome.

We present a 13-year-old boy who developed hyperthyroidism during the clinical course of idiopathic nephrotic syndrome treated with glucocorticoid. He had a second relapse of minimal change nephrotic syndrome, and complete remission of nephrotic syndrome was achieved immediately with oral glucocorticoid. However, when the steroid dosage was reduced, signs of hyperthyroidism such as systolic hypertension and tachycardia were observed. Laboratory findings revealed thyroid-stimulating hormone (TSH) below 0.05 microU/ml, free tri-iodothyronine of 16.1 pg/ml, free thyroxine of 5.6 ng/dl, and anti-TSH receptor antibody of 90%. Thus, a diagnosis of hyperthyroidism was made and treatment with thiamazol was started. Massive proteinuria may decrease the activity of hyperthyroidism due to urinary loss of thyroid hormones. A decrease in glucocorticoid dosage may also be involved in the development of hyperthyroidism due to a reduced immunosuppressive effect.

Administration, Oral↗

Hyperthyroidism affects lipid metabolism in lactating and suckling rats.

Two per thousand pregnant women have hyperthyroidism (HT), and although the symptoms are attenuated during pregnancy, they rebound after delivery, affecting infant development. To examine the effects of hyperthyroidism on lactation, we studied lipid metabolism in maternal mammary glands and livers of hyperthyroid rats and their pups. Thyroxine (10 microg/100 g body weight/d) or vehicle-treated rats were made pregnant 2 wk after commencement of treatment and sacrificed on days 7, 14, and 21 of lactation with the litters. Circulating triiodothyronine and tetraiodothyronine concentrations in the HT mothers were increased on all days. Hepatic esterified cholesterol (EC) and free cholesterol (FC) and triglyceride (TG) concentrations were diminished on days 14 and 21. Lipid synthesis, measured by incorporation of [3H]H2O into EC, FC, and TG, fatty acid synthase, and acetyl CoA carboxylase activities increased at day 14, while incorporation into FC and EC decreased at days 7 and 21, respectively. Mammary FC and TG concentrations were diminished at day 14; incorporation of [3H]H2O into TG decreased at days 7 and 21, and incorporation of [3H]H2O into FC increased at day 14. In the HT pups, growth rate was diminished, tetraiodothyronine concentration rose at days 7 and 14 of lactation, and triiodothyronine increased only at day 14. Liver TG concentrations increased at day 7 and fell at day 14, while FC increased at day 14 and only acetyl CoA carboxylase activity fell at day 14. Thus, hyperthyroidism changed maternal liver and mammary lipid metabolism, with decreased lipid concentration in spite of increased liver rate of synthesis and decreases in mammary synthesis. These changes, along with the mild hyperthyroidism of the litters, may have contributed to their reduced growth rate.

Acetyl-CoA Carboxylase↗

Mitral valve prolapse and hyperthyroidism: effect of patient selection.

Patients with mitral valve prolapse and hyperthyroidism have common symptoms; the most outstanding symptom is palpitation. To determine whether or not common symptoms contributed to the reported association of these conditions, we evaluated 220 patients with symptomatic mitral valve prolapse and 216 first-degree relatives in 72 families; 65 relatives with mitral valve prolapse and 151 relatives without mitral valve prolapse, all greater than or equal to 16 years of age. Thirty subjects, aged 49 +/- 13 years (p less than 0.025 vs entire study group), had thyroid disease (23 subjects had definite thyroid disease, seven subjects had probable); 27 of 30 subjects with thyroid disease (90%) were female (p less than 0.005). The age- and sex-adjusted prevalence of hyperthyroidism was significantly higher in probands with mitral valve prolapse than in family members without mitral valve prolapse (3.5% vs 0%, p = 0.03), while an intermediate prevalence of hyperthyroidism (2.2%) was observed in family members with mitral valve prolapse. Thus, the prevalence of hyperthyroidism is increased among symptomatic patients with mitral valve prolapse as compared to family members without mitral valve prolapse, but the prevalence of thyroid conditions is similar among family members with or without this condition. These findings are explained by the effect of common symptoms on clinical detection of both mitral valve prolapse and hyperthyroidism.

Adolescent↗

Effect of beta adrenoceptors and thyroid hormones on velocity and acceleration of peripheral arterial flow in hyperthyroidism.

Brachial artery flow patterns were studied in 10 hyperthyroid and 10 normal subjects. Mean blood velocity and flow were evaluated by pulsed Doppler, and peak systolic acceleration was calculated by computer-assisted digitization of the instantaneous velocity curve. Compared to control subjects, hyperthyroid patients had higher velocity and flow (p less than 0.01, p less than 0.02) and higher peak systolic acceleration (p less than 0.01). In hyperthyroid patients, measurements were repeated after (1) mechanical exclusion of the hand from brachial circulation, (2) short-term beta-blocker treatment and (3) inducement of the euthyroid state. Exclusion of the hand reduced velocity and flow (p less than 0.001) but did not change peak systolic acceleration. Beta blockade induced disparate changes of velocity and flow but reduced peak systolic acceleration (p less than 0.05). In the euthyroid state, decreased blood velocity (p less than 0.01), flow (p less than 0.02) and acceleration (p less than 0.02) were observed. A hyperkinetic arterial circulation consisting of an increase in both velocity and acceleration is thus observable in hyperthyroidism. Hand exclusion showed that velocity seems to be influenced by peripheral factors while beta blockade suggests that acceleration is dependent of beta 1 adrenoceptors. Comparison between euthyroidism and hyperthyroidism indicates that both mean blood velocity and peak systolic acceleration are influenced by thyroid hormones.

Adrenergic beta-Antagonists↗

Five patients with iodine-induced hyperthyroidism.

Iodine-induced hyperthyroidism has been frequently described when iodine is introduced into an iodine-deficient area. However, it may also occur in patients with and without previous thyroid disease residing in iodine-sufficient areas. Five patients with iodine-induced hyperthyroidism seen in a 12-month period are described. All were exposed to iodine in the form of commonly used drugs (Betadine, Iodo-Niacin, amiodarone, and radiographic contrast dyes). The cause of iodine-induced hyperthyroidism is unclear, but it is probably more common in patients with goiters containing previously existing areas of autonomous function or iodine-poor thyroglobulin. Iodine-induced hyperthyroidism usually abates after iodine withdrawal in patients with multinodular goiters or normal thyroid glands. The hyperthyroidism is usually treated with beta-blockers and antithyroid thionamide drugs, although reinstitution of iodine to block thyroid hormone release or corticosteroids occasionally may be necessary. Iodine-containing drugs should be given with caution to patients with underlying thyroid disease.

Adult↗

Long-term weight regulation in treated hyperthyroid and hypothyroid subjects.

Body weight regulation after treatment was studied in 87 hyperthyroid and 18 hypothyroid subjects. Mean body weight was 83.9 percent of the premorbid weight at the time of initial treatment for hyperthyroidism and 102.5 percent at 96 months following treatment. Mean (+/- SD) post-treatment weight difference from baseline was 3.4 +/- 18.6 pounds at 96 months (n = 44). Early weight gain was greatest in subjects in whom thyroxine values normalized quickly. Hyperthyroid subjects from whom a body mass index could be calculated (n = 45) were divided into two groups. The obese group had a greater mean weight loss (35.2 +/- 15.0 pounds versus 21.2 +/- 9.9 pounds, p less than 0.001) and a lower weight (percent of baseline weight) at the time of treatment for hyperthyroidism (81.6 +/- 7.7 percent versus 86.0 +/- 5.1 percent, p less than 0.05). Subjects with thyroxine levels of 20 micrograms/dl or more had higher premorbid body weights and greater weight loss from baseline than subjects with thyroxine values below 20 micrograms/dl. Hypothyroid subjects showed a small decline in mean body weight over the first six months of treatment but returned to pretreatment weight by 24 months. In the absence of significant metabolic derangement, body weight is regulated within narrow limits over many years. Effective treatment of hyperthyroidism is accompanied by weight gain.

Adult↗

Increased glucose transporter (GLUT4) protein expression in hyperthyroidism.

We have studied skeletal muscle glucose uptake by perfused hindquarter preparations from rats treated with thyroxine. Basal glucose uptake (in the absence of insulin) was approximately 2 fold higher in muscle of hyperthyroid rats compared to controls. Insulin (10(-7) M) stimulated glucose uptake 4.0 and 6.8 fold in the 10 day and 30 day controls rats, respectively. Maximal glucose uptake (10(-7) M insulin) was not different in control and hyperthyroid rats and thus insulin responsiveness in the hyperthyroid animals was reduced to 2.5 fold stimulation. The abundance of the insulin-sensitive glucose transporter protein (muscle/fat, GLUT-4), measured by Western blot analysis using polyclonal antisera, was higher in skeletal muscle from both groups of hyperthyroid rats. These studies indicate that thyroid hormones increase basal glucose uptake in skeletal muscle and this is due, at least in part, to an increment of GLUT-4 isoform. Increased expression of muscle glucose transporter proteins may be responsible for the increased peripheral glucose utilization seen in hyperthyroidism.

Animals↗

Hormone regulation of cardiac energy metabolism. I. Creatine transport across cell membranes of euthyroid and hyperthyroid rat heart.

Hyperthyroid rat heart was studied with the purpose of identifying the mechanism for the significant decrease in total creatine (free creatine plus phosphocreatine) observed in this pathology and its consequences on heart function. Administration of L-thyroxine in doses of 50-100 micrograms/100 g of body weight during a week resulted in a reversible decrease of the total creatine by 40-50%. Simultaneously, remarkable changes in the creatine transport system across the cardiac cell membranes were observed: both the maximal rate of its active uptake and its passive movement along its concentration gradient were enhanced. In euthyroid hearts, the parameters of creatine uptake (Km approximately or equal to 0.05 mM, Vmax = 20 nmole/min/g dry weight) were similar to those for skeletal muscle and the passive movement of creatine was negligible. In hyperthyroid hearts the latter rate was enhanced to 0.4 mumole min/g dry weight, this showing reversible damages in the cell membrane structure induced by L-thyroxine. This conclusion is consistent with observed penetration of colloidal lanthanum into the cells of hyperthyroid hearts. Perfusion of hyperthyroid rat hearts with 50 mM creatine significantly restored creatine content in the cells, Hyperthyroid hearts with decreased creatine content were found to develop ischemic contracture more rapidly and in higher extent than the euthyroid hearts. Increased sensitivity to ischemic damage may be related to decreased efficiency of energy channeling via phosphocreatine pathway.

Animals↗

Mental and physical state in subclinical hyperthyroidism: investigations in a normal working population.

We investigated whether subclinically hyperthyroid individuals selected from a nonpatient working population exhibit similar impairments to those found in studies with patients. Sixteen subclinically hyperthyroid subjects without apparent reason (SH-0) and 15 subclinically hyperthyroid subjects on levothyroxine (SH-T4) were compared with 27 euthyroid controls with respect to signs and symptoms of hyperthyroidism, sleep, depressivity, ability to concentrate, anxiety, and other dimensions of well-being. We found that SH-T4 exhibited significantly higher TT4 levels, TT4/TBG ratios, and more palpitations than controls. Furthermore, they slept less. The SH-0 subjects reported being in a better mood and less touchy than controls. Psychometric results of all groups were within the normal range. A comparison of this study to previous studies reveals that TT4 levels or TT4/TBG ratios may play a crucial role in the development of the predominantly nervous symptoms in subclinical hyperthyroidism. Possible reasons for the discrepancies between results in hospital and nonhospital settings are discussed.

Adult↗

Intestinal motor activity in experimental hyperthyroidism in conscious dogs.

The small intestinal motor effects of experimental hyperthyroidism were studied in 8 conscious dogs to reveal possible mechanisms of accelerated small bowel transit in hyperthyroidism. Six strain gauge transducers were implanted on the small intestine of each dog. Long-term hyperthyroidism was induced by subcutaneous administration of 100 and 200 micrograms/kg.day of thyroxin. Application of thyroxin did not interrupt the cyclic fasting motor activity. Thyroxin (100 micrograms/kg.day) caused a slight increase in the period of the migrating motor complex (p less than 0.05). The maximum contractile frequency rose dose-dependently up to 11% (p less than 0.05). During phase 2 and the digestive state the contraction frequency increased up to 29% and 27%, respectively (p less than 0.05). More contractions occurred in groups during the digestive state in hyperthyroidism. Half of the dogs showed giant migrating contractions during thyroxin administration, whereas those contractions were not observed during the control period. We conclude that fasted and postprandial intestinal motility is changed in experimental hyperthyroidism. Acceleration of small bowel transit may be caused by changes in contractile pattern of phase 2 and the digestive state or by the increased frequency of giant migrating contractions.

Animals↗

Tissue lipoprotein lipase in the hyperthyroid rat. Effect of growth and aging.

The hydrolysis of lipoprotein triglycerides is catalyzed by lipoprotein lipase (LPL), an enzyme found in many tissues. We have examined tissue LPL activity (LPLA) in rats with experimentally-induced hyperthyroidism. In younger, lighter rats, hyperthyroidism was accompanied by a decrease in LPL in adipose tissue whereas heart and diaphragm muscle LPL activities were increased. These changes are consistent with the hypothesis that the hypercatabolism and increased beta-adrenergic activity of hyperthyroidism result in characteristic changes in tissue LPLA. In older, heavier hyperthyroid animals, however, adipose tissue LPLA was increased and heart and diaphragmatic LPLA were similar to control activities. Propranolol feeding abolished the thyroxine-induced increase in adipose tissue LPLA. In euthyroid animals of similar size the response of muscle LPLA to short-term starvation was also attenuated. These changes in tissue LPLA may provide a mechanism for shunting triglyceride fatty acids away from adipose tissue for utilization by muscle in the hyperthyroid state. During growth and aging, these adaptations are modified.

Adipose Tissue↗

Comparative response to parathyroid hormone in hyperthyroidism and hypothyroidism.

The effects of exogenous parathyroid hormone, administered for 3 days, were compared in six hyperthyroid and six hypothyroid subjects. Maximum increments were much greater in hyperthyroid than in hypothyroid subjects for serum calcium (3.5 mg/100 ml versus 1.6 mg/100 ml), urine calcium (476 mg versus 79 mg), urine hydroxyproline (56 mg versus 11 mg), and urine phosphorus (671 mg versus 192 mg). Maximum decrease in serum phosphorus (minus0.9 mg/100 ml versus minus 0.1 mg/100 ml) was also greater in hyperthyroid subjects. Serum parathyroid hormone immunoreactivity was significantly higher in hypothyroid subjects (0.48 ng/ml) that either normals (0.21 ng/ml) or hyperthyroid subjects (0.19 ng/ml). The data support the concept that excess thyroid hormone sensitizes and deficient thyroid hormone blunts the responsiveness of bone to parathyroid hormone. This may lead to a state of hypoparathyroidism in hyperthyroidism and hyperparathyroidism in hypothyroidism.

Adult↗

Gonadotropin response to luteinizing hormone releasing hormone in hyperthyroid patients with menstrual disturbances.

This study was designed to investigate the gonadotropin response to luteinizing hormone releasing hormone (LHRH) in patients with hyperthyroidism, as related to the presence or absence of menstrual disorders. Forty-one Japanese women with hyperthyroidism were separated into groups on the basis of the presence of a regular menstrual cycle, hypomenorrhea, or amenorrhea and further subdivided into the phase of the menstrual cycle at the time of testing. The findings in these groups were compared with those in normal subjects with respect to thyroid function, basal serum LH and FSH levels and serum LH and FSH responses to LHRH, and basal estradiol levels. Serum LH responses to LHRH were increased over normal subjects in those with hyperthyroidism regardless of the phase of the menstrual cycle and regardless of the presence or absence of menstrual disturbances. However, these augmented LH responses to LHRH were less marked in those with menstrual disorders than in those with regular menstruation. Both basal serum FSH and peak serum FSH response to LHRH were also increased in the follicular phase but not in the luteal phase of the cycle in hyperthyroid patients, regardless of menstrual function. These results suggest that high levels of circulating thyroid hormones augment the gonadotropin response to LHRH, and that increased LH and FSH secretion probably maintains the normal cyclic pituitary gonadal axis function in patients with hyperthyroidism.

Adult↗