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Antioxidant-sensitive shortening of ventricular action potential in hyperthyroid rats is independent of lipid peroxidation.

The effects of substances able to reduce peroxidative processes on thyroid hormone-induced electrophysiological changes in ventricular muscle fibres were examined. For this study, 60 day old euthyroid and hyperthyroid rats were used. One group of hyperthyroid rats was untreated and the others were treated with vitamin E, N-acetylcysteine, and cholesterol, respectively. Hyperthyroidism was elicited by 10 day treatment with daily i.p. injections of triiodothyronine (10 microg/100 g body weight). Vitamin E and N-acetylcysteine were administered for 10 days by daily i.m. injections (20 mg/100 g body weight) and daily i.p. injections (100 mg/100 g body weight), respectively. Cholesterol was administered by cholesterol-supplemented diet (4%) from day 30. Hyperthyroidism induced a decrease in the whole antioxidant capacity and an increase in both lipid peroxidation and susceptibility to oxidative stress. Vitamin E and N-acetylcysteine administration to hyperthyroid rats led to reduction in lipid peroxidation and susceptibility to oxidative stress and to increase in antioxidant level, while the diet addition of cholesterol decreased lipid peroxidation but did not modify the other parameters. The hyperthyroid state was also associated with a decrease in the duration of the ventricular action potential recorded in vitro. The vitamin E and N-acetylcysteine administration attenuated the thyroid hormone-induced changes in action potential duration, which was however, significantly different from that of the euthyroid rats. In contrast, cholesterol supplementation did not modify the electrical activity of hyperthyroid heart. These results demonstrate that the triiodothyronine effects on ventricular electrophysiological properties are mediated, at least in part, through a membrane modification involving a free radical mechanism. Moreover, they indicate that the antioxidant-sensitive shortening of action potential duration induced by thyroid hormone is likely independent of enhanced peroxidative processes in sarcolemmal membrane.

Acetylcysteine↗

Kinetics of drug action in disease states. XXXI. Effect of experimental hyperthyroidism on the hypnotic activity of a benzodiazepine (oxazepam) in rats.

This investigation was designed to determine the effect of experimental hyperthyroidism on the hypnotic activity of a benzodiazepine and on the binding characteristics of the benzodiazepine receptor complex. Rats were made hyperthyroid by subcutaneous implantation of slow release pellets containing L-thyroxine. This treatment produced the characteristic symptoms of hyperthyroidism: increased serum thyroxine concentrations, increased heart weight and body temperature, and decreased serum protein concentrations. The hyperthyroid rats and a parallel group of normal animals (with drug-free pellets implanted subcutaneously) were slowly infused intravenously with oxazepam until they lost their righting reflex. The hyperthyroid rats required a significantly larger dose of the benzodiazepine and their total serum and cerebrospinal fluid concentrations of oxazepam (but not the serum concentration of free drug and the brain concentration) at the onset of loss of the righting reflex were modestly but statistically significantly lower than those of the normal rats. The receptor density and affinity for diazepam in hyperthyroid rats were not significantly different from those of the normal animals. Hyperthyroidism apparently affects the pharmacokinetics of oxazepam but has, at best, only a small effect on the pharmacodynamics (hypnotic activity) of the drug.

Animals↗

Dissociation of leptin and body weight in hyperthyroid patients after radioiodine treatment.

OBJECTIVE: Leptin regulates energy production rates and body weight, which are frequently altered in hyperthyroidism. Data on a possible interaction between leptin and thyroid hormones are controversial. We assessed leptin serum concentrations, BMI, proportional fat tissue mass and thyroid hormones in hyperthyroid patients in a long-term follow-up after radioiodine therapy. DESIGN: The study included 28 hyperthyroid patients (mean age 66 y) before and up to one y after radioiodine therapy. Leptin and thyroid hormones, general parameters, BMI, proportional fat tissue (PFT) measurements by DEXA and thyroid morphology were recorded. Twenty-four age-matched euthyroid individuals (mean age 63 y) served as controls. RESULTS: At baseline, leptin concentrations were significantly decreased in all hyperthyroid patients as compared to controls. One year after radioiodine therapy, 71% of the patients were euthyroid (group A) and 29% remained hyperthyroid (group B). BMI and PFT increased in both groups. While leptin concentrations remained low in group B, they normalised in group A after 6 to 12 months. Changes in leptin and thyroid hormone concentrations were positively correlated in group A patients (r=0.49, P=0.03) but not in patients remaining hyperthyroid. CONCLUSION: Our data indicate a dissociation in the regulation of plasma leptin and BMI as well as proportional fat tissue in hyperthyroid patients which may be attributable to differences in lean and adipose mass weight gain after radioiodine therapy or direct influences of thyroid hormones on leptin regulation. International Journal of Obesity (2001) 25, 115-120

Absorptiometry, Photon↗

Effect of a protein-free diet on muscle protein turnover and nitrogen conservation in euthyroid and hyperthyroid rats.

Although protein turnover in skeletal muscle is increased in hyperthyroidism and decreased in hypothyroidism, a deficient protein intake tends to increase serum T3 (tri-iodothyronine) while decreasing muscle protein turnover. To determine whether this diet-induced decrease in protein turnover can occur independent of thyroid status, we have examined muscle protein turnover and nitrogen conservation in hyperthyroid rats fed on a protein-free diet. After inducing hyperthyroidism by giving 20 micrograms of T3/100g body wt. daily for 7 days, groups of euthyroid and hyperthyroid animals were divided into subgroups fed on basal and protein-free diets. Muscle protein turnover was measured by N tau-methylhistidine excretion and [14C]tyrosine infusion. Urinary nitrogen output of euthyroid and hyperthyroid animals fed on the protein-free diet was also measured. Although hyperthyroidism increased the baseline rates of muscle protein synthesis and degradation, it did not prevent a decrease in these values in response to protein depletion. Furthermore, hyperthyroid rats showed greatly decreased nitrogen excretion in response to the protein-free diet, although not to values for euthyroid rats. These findings suggest that protein depletion made the experimental animals less responsive to the protein-catabolic effects of T3.

Animals↗

Brain chemiluminescence and oxidative stress in hyperthyroid rats.

Newborn Wistar rats were made hyperthyroid by injection of tri-iodothyronine and assayed for survival, brain oxygen uptake, brain chemiluminescence and activity of antioxidant enzymes. Brain chemiluminescence was measured (1) by removing the parietal bones or (2) through the translucid parietal bones. Control animals showed a brain chemiluminescence of 130 +/- 12 c.p.s./cm2 and 99 +/- 10 c.p.s./cm2 for procedures (1) and (2) respectively. Hyperthyroid rats showed increases in the spontaneous brain photoemission of 46 and 70% compared with controls, measured by procedures 1 and 2 respectively. The hyperthyroid state did not modify the oxygen-dependent chemiluminescence of brain homogenates. The hyperthyroid animals showed a 30% increase in the oxygen uptake of brain slices and a dramatic shortening of life-span to about 16 weeks. Superoxide dismutase (the Cu-Zn enzyme), catalase and Se-dependent glutathione peroxidase activities of brain homogenates were increased by 18, 36 and 30% respectively in the hyperthyroid animals. Isolated brain mitochondria produced 0.18-0.20 nmol of H2O2/min per mg of protein in state 4 in the presence of succinate as substrate. No difference was observed between control and hyperthyroid animals. It is concluded that hyperthyroidism leads to hypermetabolism and oxidative stress in the brain. The increased levels of oxygen and peroxyl radicals may contribute to premature ageing in these animals.

Animals↗

The effect of the treatment of hypothyroidism and hyperthyroidism on plasma lipids and apolipoproteins AI, AII and E.

OBJECTIVE: Although lipid abnormalities are well described in hypothyroidism, effects on apolipoproteins are less well understood. The aim of this study was to examine the effects of thyroid dysfunction on plasma lipids and apolipoproteins. DESIGN: A prospective study of lipids and apolipoproteins before and after treatment of hypothyroidism and hyperthyroidism. PATIENTS: Eighteen patients with hypothyroidism and 5 patients with hyperthyroidism were included. MEASUREMENTS: Plasma cholesterol, triglycerides, HDL cholesterol, apo AI, apo AII, and apo E were measured before and after treatment of the thyroid abnormality. RESULTS: Total and HDL cholesterol, apo AI and apo E decreased with treatment of hypothyroidism, while triglycerides and apo AII levels were unchanged. The total/HDL cholesterol and LDL/HDL cholesterol ratios also decreased with treatment of hypothyroidism. In contrast, treatment of hyperthyroidism was associated with an increase in total and HDL cholesterol, and apo AI. Triglycerides, apo AII and Apo E were unchanged by treatment of hyperthyroidism. The total/HDL cholesterol and the LDL/HDL cholesterol ratios increased with treatment of hyperthyroidism. CONCLUSIONS: Hypothyroidism and hyperthyroidism have opposite effects on plasma lipids and apolipoproteins. In hypothyroidism, total and HDL cholesterol, total/HDL cholesterol ratio, apo AI and apo E are elevated. The increase in apo AI without a concomitant increase in apo AII suggests selective elevation of HDL2. In contrast, hyperthyroidism is associated with decreased total and HDL cholesterol, total/HDL cholesterol ratio, and apo AI levels. These effects are reversible with treatment of the underlying thyroid disorder.

Adult↗

Bone turnover and cortical bone mineral density in the distal radius in patients with hyperthyroidism being treated with antithyroid drugs for various periods of time.

OBJECTIVE: Whether patients, who have lost bone mass, can be restored to age-matched control levels by some means is still controversial. We investigated how the thyroid status after antithyroid drug therapy for various periods of time affects bone metabolism in patients with hyperthyroidism by assessing currently used biochemical markers of bone turnover and distal radius bone mineral density (BMD). DESIGN AND PATIENTS: The biochemical markers of bone turnover and BMD at the distal one third of the radius were measured in 79 women with hyperthyroidism treated with antithyroid drugs for various periods of time. The patients were divided into two groups according to thyroid function at the time of study: a hyperthyroid group (serum thyroid stimulating hormone (TSH) < 0.4 mU/l) and an euthyroid group (TSH 0.4-4.0 mU/l). Second, each group was further divided according to the duration of therapy: short-term (less than 3 years) and long-term (3 or more years). MEASUREMENTS: Urinary type I collagen degradation products (CTx) were measured by the CrossLapsTM ELISA kit. Urinary pyridinoline (Pyr) and deoxypyridinoline (Dpyr) were measured by high performance liquid chromatography (HPLC) after acid hydrolysis. Serum N-mid osteocalcin (OCN-mid) was measured by a recently developed enzyme-linked immunosorbent assay. Serum alkaline phosphatase (ALP) was determined by routine laboratory methods. Bone mineral density (BMD) at the distal one third of the radius was measured using dual energy X-ray absorptiometry (DEXA; DCS-600EX, Aloka, Tokyo). RESULTS: There were statistically significant positive correlations of FT3 and FT4 with the biochemical markers of bone turnover. There were significant negative correlations between the biochemical markers and BMD only in patients undergoing long-term therapy. In a comparison between hyperthyroid and euthyroid groups based on duration of treatment (long-term and short-term), and in a comparison without regard for length of treatment (all patients), it was evident that ALP and CTx levels were significantly higher in the hyperthyroid than in the euthyroid groups. Significantly lower BMD Z-scores in the hyperthyroid group compared to those in the euthyroid group were observed only in patients undergoing long-term therapy. CONCLUSIONS: Urinary type I collagen degradation products were a sensitive marker for evaluating the bone turnover in patients with hyperthyroidism. Our data suggested that it might be important to control the levels of TSH within normal ranges during long-term antithyroid drug therapy in order to prevent bone loss.

Adult↗

Effect of maternal hyperthyroidism during late pregnancy on the risk of neonatal low birth weight.

OBJECTIVE: Hyperthyroidism in pregnancy occurs with a prevalence of 0.05--0.2% and has been shown to affect neonatal outcomes. Fetal weight increases markedly during the third trimester of pregnancy. This retrospective study was performed to examine the effect of maternal hyperthyroidism during late pregnancy on neonatal birth weight (NBW). DESIGN: Medical and obstetric records of 293 pregnant women with present and past history of hyperthyroidism were retrospectively reviewed. PATIENTS: There were 188 records of 181 patients with adequate data for inclusion in the analysis. The patients were divided into two groups according to the maternal thyroid function during the third trimester of pregnancy: hyperthyroidism (HT; 35 cases) and euthyroidism (ET; 153 cases). MEASUREMENTS: Maternal thyroid function tests were periodically evaluated before and during the third trimester of pregnancy. Neonatal thyroid function tests and birth weight of the newborn infants were also assessed. RESULTS: There was no significant difference of maternal age between HT and ET groups mean +/- SD (27.6 +/- 5.5 vs. 29.2 +/- 5.4 years). The NBW of the HT group was not significantly different from that of the ET group (2880 +/- 590 vs. 3019 +/- 426 g). However, the prevalence of infants with low birth weight (LBW) defined as NBW of lower than 2500 g in HT group was 22.9% which was significantly higher than the 9.8% in the ET group (P = 0.039, OR = 2.7, 95%CI = 1.1--7.1) and 9.7% of infants born to healthy mothers at Siriraj Hospital (control group) between 1991 and 1995 (P = 0.01, OR = 2.7, 95%CI = 1.3--6.1). The 90% CI for the true difference between the prevalence of LBW infants born to ET and HT mothers was 0.7--25.4. There was no significant difference in the prevalence of LBW infants in ET and control groups. Multiple logistic regression analyses showed that maternal hyperthyroidism during the third trimester of pregnancy was an independent factor associated with increased prevalence of LBW infants (P = 0.037, OR = 4.1, 95%CI = 1.1--15.0). CONCLUSIONS: Maternal hyperthyroidism during the third trimester of pregnancy independently increases the risk of low birth weight by 4.1-fold. Appropriate management of hyperthyroidism throughout pregnancy is essential in the prevention of this undesirable neonatal outcome.

Adult↗

Thyroid scintigraphy in hyperthyroidism.

Thyroid scintigraphy is a nuclear medicine procedure that produces a visual display of functional thyroid tissue based on the selective uptake of various radionuclides by thyroid tissue. Thyroid scintigraphy provides valuable information regarding both thyroid anatomy and physiology and can play an integral role in the diagnosis and management of cats with hyperthyroidism. Thyroid scintigraphy allows the direct visualization of the functional adenomatous thyroid tissue responsible for the development of hyperthyroidism. For this reason, thyroid scintigraphy will allow the diagnosis of hyperthyroidism before laboratory tests are consistently abnormal. Thyroid scintigraphy can also exclude a diagnosis of hyperthyroidism in cats with thyroid hormone elevations of nonthyroidal origin. Thyroid scintigraphy provides an additional method for determining the relative severity of thyroid disease that is less affected by the presence of concurrent nonthyroidal illness than laboratory evaluations. When treating hyperthyroid cats with radioiodine, the lowest effective dose should be administered. In an effort to administer the lowest radioiodine dose possible, the volume of adenomatous thyroid tissue present in the individual hyperthyroid cat should be considered. Thyroid scintigraphy provides an excellent method for evaluating the size of hyperfunctional thyroid tissue that is not limited by the presence of ectopic or intrathoracic thyroid tissue. Thyroid scintigraphy also provides valuable information in the diagnosis and evaluation of hyperthyroid cats with thyroid carcinoma.

Animals↗

Association of hyperthyroidism with serum leptin levels.

The present study was undertaken to determine whether thyroid hormones affect serum leptin levels in patients with hyperthyroidism. In 32 female patients with hyperthyroidism and 30 body mass index (BMI)-matched control subjects, there was no difference in serum leptin concentrations (9.0+/-1.0 v 8.2+/-0.9 microg/L). The serum leptin levels were compared with the expected values for serum leptin derived from the corresponding BMI with the formula for the control subjects (serum leptin [micrograms per liter] = 0.976 x BMI [kilograms per square meter] - 11.933, P < .001) and are expressed as the percent deviation (%leptin). There was a weak but significant positive correlation between serum free thyroxine (T4) levels and %leptin in the combined analysis of patients with hyperthyroidism and control subjects (r = .28, P < .05). Multiple regression analysis also revealed the independent contribution of free T4 levels to serum leptin. Antithyroid therapy ameliorated the hyperthyroidism and increased the BMI by 7.8% and the percent body fat by 9.9% in a subgroup of 21 patients with hyperthyroidism. However, serum leptin levels did not change during the 2-month therapeutic period (from 9.8+/-1.4 to 8.7+/-1.0 microg/L), and accordingly, %leptin significantly decreased from 133%+/-16% to 98%+/-11% (P < .05). A total of 6 months of observation in 12 hyperthyroid patients showed the same alterations in the anthropometric indexes, serum leptin, and %leptin. These results indicate that serum leptin is slightly increased in subjects with moderate hyperthyroidism, possibly due to the direct action of thyroid hormone, and the levels decline in accordance with the attainment of euthyroidism.

Adipose Tissue↗

The influence of hyperthyroidism on the hypothalamic-pituitary-gonadal axis.

We have investigated the function of the hypothalamic-pituitary-gonadal (H-P-G)-axis in patients with severe, untreated Graves' disease. We studied 7 male and 6 female healthy volunteers, and 7 male and 7 female patients with Graves' disease. Hormone profiles were developed by blood sampling every 10 min for an 8 hour period. In women this was done in the early follicular phase of menstrual cycle. LH-, FSH-, and PRL levels were measured using immunoradiometric assays and testosterone (T), estradiol (E2), sex-hormone binding globulin (SHBG), and progesterone (P) were measured with standard assays. The pulsatility of LH, FSH and PRL was calculated using the programmes Pulsar, Cluster and Desade. The temporal relationship of plasma LH, FSH, and PRL pulses was also investigated using specific concordance analysis. Data were evaluated by means of non-parametric statistics. LH-secretion was increased in all hyperthyroid patients, while FSH-secretion was increased in hyperthyroid men only. Pulsatile characteristics of LH- and FSH-secretion (frequency, peak shape) in patients were not different from controls. No change in PRL-secretion was shown. Significant copulsatility occurred between LH and FSH, and LH and PRL. This was more pronounced in hyperthyroid than in healthy study subjects. Plasma levels of steroid hormones and sex-hormone-binding globulin were significantly (p<0.005) increased in hyperthyroid men. Free Androgen Index was significantly (p<0.005) decreased in hyperthyroid males. No other auto immune diseases were noticed. Our results indicate that the function of the H-P-G axis is not impaired in hyperthyroid patients, but gonadotropin levels are increased. Hyperthyroid men show relative primary gonadal insufficiency that may be due to exaggerated SHBG levels. The copulsatility of LH and FSH, and of LH and PRL was confirmed both in patients and controls.

Adult↗

Amelioration of some metabolic effects produced by hyperthyroidism in late pregnant rats and their fetuses. Effects on lipids and proteins.

We have studied the effect of 40-45 days administration of 1 mg/kg thyroxine on protein and lipid metabolism in liver, heart, lungs, kidneys and adrenal glands of virgin and 21-day pregnant rats and their fetuses and placentae. The chronic administration of thyroid hormone produced significant increases in serum T3 and T4 in both groups as well as in organ weights and protein concentrations in virgin rats, but much smaller modifications in pregnant ones. Hyperthyroidism decreased the weight of fetal livers and increased that of placentae; protein content was increased in all fetal organs. Hyperthyroidism induced increases in phospholipid concentrations in all the organs and in total lipids only in liver and heart of adult rats, which were not counteracted by pregnancy. Pregnant rats had increases in total lipids in liver and kidneys and in adrenal phospholipids. In hyperthyroid fetuses there was an increase in hepatic total lipids and no changes in phospholipids. Hepatic lipogenesis (measured by in vivo incorporation of 3H2O into lipids) was increased by hyperthyroidism in virgin and pregnant rats, but the increase was significantly smaller in the pregnant hyperthyroid rats compared with the virgin ones. Fetal lipogenesis in liver and lung was not changed. In addition, an increase was observed in lipogenic enzyme (fatty acid synthetase and glucose-6-phosphate dehydrogenase) activities in hyperthyroid virgin rats which was prevented by pregnancy. In fetuses only pulmonary glucose-6-phosphate dehydrogenase was increased when expressed in terms of tissue weight. Our results indicate that the metabolic effect of hyperthyroidism is attenuated in pregnant rats and their fetuses, when compared with adult virgin rats, in most of the parameters studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Abnormal left ventricular function in hyperthyroidism: evidence for a possible reversible cardiomyopathy.

We assessed the effects of exercise and beta-adrenoceptor blockade on left ventricular ejection fraction (LVEF) measured by radionuclide ventriculography in nine patients with uncomplicated hyperthyroidism. Patients were studied in both the hyperthyroid and euthyroid states. The hyperthyroid state was characterized by a high LVEF at rest but--paradoxically--by a significant fall (P less than 0.01) in LVEF during exercise. At the same workload and at the same heart rate, patients had a restoration of the normal rise in LVEF during exercise when they were euthyroid. The LVEF was greater during exercise (P less than 0.02) when the patients were euthyroid than when they were hyperthyroid. Pretreatment with propranolol caused similar reductions in resting LVEF in the hyperthyroid and euthyroid states; the drug attenuated the rise in LVEF during exercise when the patients were euthyroid, but did not influence the exercise-induced reduction in LVEF in hyperthyroidism. The abnormal left ventricular function observed during exercise in hyperthyroidism suggests a reversible functional cardiomyopathy, independent of beta-adrenoceptor activation, that is presumably a direct effect of an excess in circulating thyroid hormones.

Adult↗

Validity of self-reported hyperthyroidism and hypothyroidism: comparison of self-reported questionnaire data with medical record review.

Studies that aim at identifying genes or environmental factors contributing to the development of autoimmune thyroid disease (AITD) demand that several hundred patients and control subjects be assessed. In these large studies, the laboratory methodology is often described in detail whereas little attention is given to an accurate description of the study population. Usually, a diagnosis of AITD in the control group is based on self-reported disease status. Although such studies have been criticized for diagnostic inaccuracy, no study has evaluated the validity of self-reported hyperthyroidism and hypothyroidism in detail. We have assessed the validity of self-reported hyperthyroidism and hypothyroidism in 401 twin pairs from among 6,628 same gender pairs, ages 18-41 years who participated in a nationwide questionnaire survey in 1994. The self-reported questionnaire data were compared with information from medical records and the 1/kappa coefficient, sensitivity, and specificity were determined. Overall, there was only a slight to fair agreement between the self-reported questionnaire data and medical record data as shown by kappa values of 0.18, 0.21, and 0.26 for hyperthyroidism and hypothyroidism as a group, hyperthyroidism and hypothyroidism, respectively. For both hyperthyroidism and hypothyroidism, the sensitivity of the self-reported diagnosis was 0.98, whereas the specificity was 0.57 and 0.67 for self-reported hyperthyroidism and hypothyroidism, respectively. In conclusion, the validity of self-reported hyperthyroidism and hypothyroidism is unsatisfactorily low. However, by combining self-reports with valid retrospective data on diagnostic findings it can be used as a sampling method in large epidemiological or genetic studies.

Humans↗

Fractures in patients with hyperthyroidism and hypothyroidism: a nationwide follow-up study in 16,249 patients.

AIM: To study fracture risk in patients with hyperthyroidism and hypothyroidism. SUBJECTS AND METHODS: All patients with hyperthyroidism or autoimmune hypothyroidism diagnosed for the first time between 1983 and 1996 in Denmark were identified through the National Patient Discharge Register. Each patient was compared with three age- and gender-matched controls randomly selected from the general population. Fracture occurrence before and after diagnosis was compared between patients and controls. RESULTS: 11,776 patients with hyperthyroidism (6301 patients with diffuse toxic goiter, mean age, 52.1 +/- 18.6 years, and 5475 with nodular toxic goiter, mean age, 60.4 +/- 15.9 years), and 4473 patients with hypothyroidism (mean age, 66.1 +/- 17.3) were identified. In patients with hyperthyroidism, fracture risk was only significantly increased around the time of diagnosis (incidence rate ratio [IRR] between 1.26 and 2.29), but decreased to normal levels after diagnosis. Surgical treatment of hyperthyroidism was associated with a decreased fracture risk after diagnosis (RR = 0.66, 95% confidence interval [CI]: 0.55-0.78). In hypothyroidism, fracture risk was significantly increased both before and after diagnosis with a peak around the time of diagnosis (IRR between 2.17 and 2.35). CONCLUSIONS: Fracture risk is increased in hyperthyroidism and hypothyroidism. Thyroid surgery seems associated with a decreased fracture risk in hyperthyroid patients.

Absorptiometry, Photon↗

Low incidence rate of overt hypothyroidism compared with hyperthyroidism in an area with moderately low iodine intake.

In areas with relatively high iodine intake, the incidence rate of hypothyroidism is several-fold higher than that of hyperthyroidism. Recently, we found a similarly high prevalence rate of subclinical hypothyroidism compared with hyperthyroidism in a high iodine intake area, while a relatively low prevalence of subclinical hypothyroidism was observed in a low iodine intake area. In the present study we compared the incidence rate (newly diagnosed in primary care and at hospital) of overt hypothyroidism with that of hyperthyroidism in a well-defined geographical area in Jutland, Denmark, with an iodine intake around 60 microg/day. The number of personsxyears studied was 569,108. Data on hyperthyroidism have been published previously. The overall incidence of hypothyroidism was 13.5/100,000 per year (F/M 22.9/3.6), hyperthyroidism 38.7/100.000 per year (F/M 63.0/13.0). The incidence of hypothyroidism was steadily increasing with age up to 80/100,000 per year in subjects older than 70 years of age, but apart from congenital hypothyroidism it was lower than that of hyperthyroidism at all ages. The majority of patients (79%) was diagnosed to have spontaneous autoimmune hypothyroidism (16% with goiter, 84% with no thyroid visible or palpable). In conclusion, in an area with moderately low iodine intake, hypothyroidism was considerably less common than hyperthyroidism. This is in contrast to findings in high iodine intake areas. The iodine intake of an area seems to be of major importance for the pattern of thyroid disorders observed.

Adolescent↗

Metastatic follicular carcinoma associated with hyperthyroidism.

PURPOSE: A 68-year-old man with metastatic follicular thyroid carcinoma had T3 hyperthyroidism. MATERIAL AND METHODS: A bone scan showed intense uptake in the thyroid and multiple areas of increased uptake in the skeleton. Hyperthyroidism persisted after total thyroidectomy. Treatment with I-131 induced a transient state of euthyroidism lasting approximately 9 months. Further tumor growth and relapse of hyperthyroidism eventually occurred and the patient died 25 months after surgery. Molecular and cytogenetic analyses were performed. RESULTS: No mutations were detected of either of the thyrotropin receptor or of the alpha subunit of the stimulatory guanine-nucleotide-binding proteins. Hyperthyroidism was unlikely the result of thyroid-stimulating receptor antibodies. Comparative genomic hybridization analysis showed that the tumor was characterized by multiple chromosomal imbalances. CONCLUSIONS: This is an unusual case of follicular thyroid carcinoma with initial high I-131 uptake by the thyroid and bone metastases and concurrent hyperthyroidism. Despite the increased I-131 uptake in the tumor, I-131 treatment only transiently controlled the hyperthyroidism and had no effect on tumor size. The cause of hyperthyroidism remained unknown. T3 predominance was unlikely the result of type 2 deiodinase overexpression because loss of genetic material was demonstrated at chromosome 14 long arm, where type 2 deiodinase is mapped.

Adenocarcinoma, Follicular↗

Comparison between serum thyroxine and triiodothyronine estimation and the TRH test in the routine diagnosis of hyperthyroidism.

Serum T3 and T4 levels have been determined by a radioimmunoassay technique and the TRH test has been performed in 50 patients in whom hyperthyroidism could not be ruled out by the first clinical examination alone. Each patient was then further evaluated in order to establish the state of the thyroid function. The extent to which the determination of T3 or T4 could replace the TRH test in the routine diagnosis of hyperthyroisism was evaluated. The results showed that 26 of the 50 patients had normal thyroid function and 24 had hyperthyroidism. No patient in the normal groups and all but one in the hyperthyroid group had T3 levels above the upper normal limit (2 S.D.). Two of the patients in the normal group and 19 in the hyperthyroid group had T4 levels above the upper normal limit (2 S.D.). Twenty of the patients in the normal group showed a normal TSH response to TRH (increment is greater than 3.0 micronU/ml); the remaining 6 showed an impaired or absent response. Twenty of the hyperthyroid patients had no response and four had a slightly positive response to TRH. No hyperthyroid patient had a TSH response exceeding 3.0 micronU/ml. It is concluded that the determination of T3 is superior to both the determination of T4 and the TRH test for the laboratory discrimination between eu- and hyperthyroidism.

Adult↗