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Plasma total homocysteine levels in hyperthyroid and hypothyroid patients.

We found a higher plasma concentration of total homocysteine (tHcy), an independent risk factor for cardiovascular disease, in patients with hypothyroidism (mean, 16.3 micromol/L; 95% confidence interval [CI], 14.7 to 17.9 micromol/L) than in healthy controls (mean, 10.5 micromol/L; 95% CI, 10.1 to 10.9 micromol/L). The tHcy level of hyperthyroid patients did not differ significantly from that of the controls. Serum creatinine was higher in hypothyroid patients and lower in hyperthyroid patients than in controls, whereas serum folate was higher in hyperthyroid patients compared with the two other groups. In multivariate analysis, these differences did not explain the higher tHcy concentration in hypothyroidism. We confirmed the observation of elevated serum cholesterol in hypothyroidism, which together with the hyperhomocysteinemia may contribute to an accelerated atherogenesis in these patients.

Adult↗

Potentiation of 1,1-dichloroethylene hepatotoxicity: comparative effects of hyperthyroidism and fasting.

The responses of fed, fasted, and hyperthyroid (T4) Sprague-Dawley male rats to 50 mg 1,1-dichloroethylene (1,1-DCE)/kg were compared. Hyperthyroid rats received three sc injections of thyroxine (100 micrograms/100 g) at 48-hr intervals; all other rats were sham-injected. 1,1-DCE was given po in mineral oil 24 hr after the last T4 dose; controls received only mineral oil. Animals were killed at 2, 4, and 8 hr. Liver GSH contents were lowered about 55% by both fasting and T4 while GSH transferase activities were lowered about 20% by fasting and 35% by T4. Only T4 pretreatment lowered alcohol dehydrogenase activities. Liver injury (i.e., serum glutamate pyruvate transaminase, histology) after 1,1-DCE was minimal in fed rats, moderate in fasted rats, and intermediate in T4 rats. Fasted rats showed a more pronounced depletion of liver GSH after 1,1-DCE than T4 rats and only in fasted rats did the toxicant decrease activities of the detoxification enzymes. Hypoglycemia after 1,1-DCE occurred in fed rats, but more rapidly in T4 rats. In contrast, fasted rats unexpectedly became hyperglycemic after the toxicant. Patterns of body temperature change after the toxicant, which might be due to its metabolites, were dissimilar. Hypothermia was not observed in fed rats, was only transiently evident in T4 rats, but occurred rapidly within 1 hr in fasted rats and steadily became more severe. The dissimilar patterns of liver enzyme and body temperature and serum glucose change after the toxicant in the three groups are indicative of different pathways of injury potentiation by fasting and hyperthyroidism.

Alcohol Dehydrogenase↗

Cancer incidence and mortality after radioiodine treatment for hyperthyroidism: a population-based cohort study.

BACKGROUND: Radioiodine is used increasingly as first-line treatment for hyperthyroidism, but concerns remain about subsequent risk of cancer, especially in those treated at a young age. We investigated cancer incidence and mortality in patients treated with radioiodine for hyperthyroidism. METHODS: We did a population-based study in 7417 patients treated in Birmingham, UK, between 1950 and 1991. We compared details of all cancer diagnoses and deaths in 1971-91 from the UK Office for National Statistics with data on cancer incidence and mortality for England and Wales specific for age, sex, and period. FINDINGS: During 72,073 person-years of follow-up, 634 cancer diagnoses were made, compared with an expected number of 761 (standardised incidence ratio [SIR] 0.83 [95% CI 0.77-0.90]). The relative risk of cancer mortality was also decreased (observed cancer deaths 448, expected 499; standardised mortality ratio [SMR] 0.90 [0.82-0.98]). Incidence of cancers of the pancreas, bronchus, trachea, bladder, and lymphatic and haemopoietic systems was lowered. Mortality from cancers at all these sites was also reduced but findings were significant only for bronchus and trachea. There were significant increases in incidence and mortality for cancers of the small bowel (SIR 4.81 [2.16-10.72], SMR 7.03 [3.16-15.66]) and thyroid (SIR 3.25 [1.69-6.25], SMR 2.78 [1.16-6.67]), although absolute risk of these cancers was small. INTERPRETATION: The decrease in overall cancer incidence and mortality in those treated for hyperthyroidism with radioiodine is reassuring. The absolute risk of cancers of the small bowel and thyroid remain low, but the increased relative risk shows the need for long-term vigilance in those receiving radioiodine.

Aged↗

Changes in vascular reactivity induced by acute hyperthyroidism in isolated rat aortae.

Hyperthyroidism was induced by subcutaneous injections of L-thyroxine (T(4)) (500 mg/kg/day) for 3 days in order to study whether adrenergic and muscarinic receptor-mediated vascular responses alter at an early stage of the disease. T(4) treatment was sufficient to induce a significant degree of thyroid weight loss, tachycardia, cardiac hypertrophy, and an elevation in serum T(4) levels. The tension of aortic ring preparations isolated from rats was measured isometrically to investigate the influence of acute hyperthyroidism. The contractions induced by norepinephrine (NE) were significantly suppressed in aortic rings from rats treated with T(4) compared with control rats. N(G)-nitro-L-arginine (L-NOARG), an inhibitor of nitric oxide synthase (NOS), significantly enhanced NE-induced contraction in aortic rings from both control and T(4)-treated rats, and the enhancement was greater in rats treated with T(4) than control rats. The relaxations induced by either acetylcholine (ACh) or sodium nitroprusside (SNP) were also significantly enhanced by T(4) treatment. L-NOARG abolished the relaxation induced by ACh in aortic rings from both control and T(4)-treated rats. L-NOARG shifted SNP-induced relaxation curves of aortic rings from those of control rats to the left, but not with rats treated with T(4). T(4) treatment showed no influence on the amount of endothelial NOS (eNOS) protein. These results suggest that vascular responses alter at an early stage of hyperthyroidism and that it may be due to a modification in the NO system which is independent from the amount of eNOS protein.

Acetylcholine↗

Hepatic glutathione biosynthetic capacity in hyperthyroid rats.

The influence of hyperthyroidism on the capacity of the liver to synthesize glutathione (GSH) was evaluated as a possible mechanism of depletion of the tripeptide. For this purpose, the effect of daily doses of 0.1 mg 3, 3',5-tri-iodothyronine (T3)/kg for 3 consecutive days on hepatic GSH biosynthetic capacity was assessed by a combined assay measuring gamma-glutamylcysteinyl synthase and GSH synthase simultaneously. T3 treatment induced a significant 56% depletion of liver GSH in parallel with an increase in the rate of GSH synthesis, the latter effect being completely abolished by L-buthionine sulfoximine. According to these data, the fractional rate of hepatic GSH turnover exhibited a 3.2-fold enhancement in hyperthyroid rats compared to control animals. It is concluded that the enhanced GSH utilization in the liver of hyperthyroid rats previously observed [Fernández et al., Endocrinology 129, 85-91, 1991], is accompanied by an increment in GSH synthesis that is insufficient to sustain the basal levels of the tripeptide observed in euthyroid animals, thus establishing a low steady-state content of GSH in the tissue.

Animals↗

Hyperthyroid-induced chorea in an adolescent girl.

Hyperthyroidism is invariably accompanied by nervous system dysfunctions. Irritability, emotional lability and hyperkinesia are the signs and symptoms most frequently observed. Chorea or choreoathetosis are only rarely associated with hyperthyroidism. It is the purpose of this work to describe the case of a young girl in whom chorea was the main manifestation of thyrotoxicosis. The chorea receded and disappeared as the patient became euthyroid. Hyperthyroidism, therefore, is to be considered an unusual cause of chorea and every patient with choreiform movements should be examined also for thyroid function.

Adolescent↗

Treatment of hyperthyroidism with radioactive iodine.

Treatment of hyperthyroidism with RAI has been performed for more than a half century with efficacy and safety. For its optimal use, the physician must employ appropriate patient selection criteria and clinical judgment concerning pretreatment patient preparation. The dose of the 131I needed remains an area of uncertainty and debate; thus far, it has not been possible to resolve the trade-off between efficient definitive cure of hyperthyroidism and the high incidence of post-therapy hypothyroidism. Early side effects are uncommon and readily manageable. Other than the need for long-term monitoring and, in most cases, lifelong L-T4 treatment, late adverse consequences of this treatment remain only conjectural. The available follow-up studies support the current majority opinion of North American thyroid specialists that RAI treatment is an excellent choice for most hyperthyroid patients.

Antithyroid Agents↗

Management guidelines for hyperthyroidism.

Anti-thyroid drugs, surgery and radioiodine all represent effective forms of treatment for Graves' hyperthyroidism. There is, however, little consensus regarding the treatment of choice for specific cases. This lack of consensus prompted the development of guidelines for good practice in the management of hyperthyroidism for the United Kingdom. This chapter describes the process of development of this United Kingdom consensus statement, and associated audit measures, and highlights outstanding contentious issues in the management of Graves' hyperthyroidism.

Antithyroid Agents↗

Acute psychotic state due to hyperthyroidism following excision of a mandible bone tumor: a case report.

The etiology of psychotic symptoms that emerge following surgery needs to be sought to allow physicians to provide effective treatment. We present the case of a patient who developed hyperthyroidism shortly after excision of a mandible bone tumor and discuss its clinical features, course, and management. A 48-year-old female without previous thyroid disease accidentally found a tumor over her left mandible bone and underwent excision of the tumor. Soon after surgery, she suffered from anxiety, mood swings, insomnia, and even auditory hallucinations. Through careful differential diagnosis and a series of examinations, she was shown to be in a hyperthyroid state. Her condition improved after short-term use of haloperidol, lithium, and methimazole. Her thyroid function recovered and she was free from any psychiatric symptoms during the 1-year follow-up. Hyperthyroidism following surgery is not uncommon and its possibility should be considered when making differential diagnoses.

Acute Disease↗

Pregnancy complicated with pulmonary edema due to hyperthyroidism.

Hyperthyroidism is one of the most common causes of cardiac failure. Blood volume expands greatly during pregnancy, especially after the last part of the second trimester. Such expansion exacerbates the symptoms of heart failure and accelerates the development of pulmonary edema when abnormal thyroid function is not well controlled. Two cases of pregnancy complicated with congestive heart failure and pulmonary edema due to hyperthyroidism are reported here. Both patients did not receive treatment for hyperthyroidism during pregnancy, and both sought clinical help during the third trimester. The clinical problems were resolved by medical management before delivery.

Adult↗

Myosin and SERCA isoform expression in denervated slow-twitch muscle of euthyroid and hyperthyroid rabbits.

Changes in the isoform patterns of myosin heavy chains (MHC) and Ca2+-ATPase (SERCA) were studied in long-term (72 days) denervated slow-twitch soleus muscles of euthyroid and hyperthyroid rabbits. MHC isoforms were separated electrophoretically. SERCA isoforms were assessed by electrophoretic separation of the trypsin-digested and phosphorylated fragments. Denervation led to pronounced slow-to-fast transitions with increases in the fast MHC and fast SERCA1a isoforms. Hyperthyroidism had no significant effect on the denervation-induced changes in SERCA isoforms, but led to slight increases in the relative concentrations of the fast MHC isoforms. A high correlation existed between the relative concentrations of slow myosin and SERCA2a in both innervated euthyroid and hyperthyroid soleus muscles. This correlation, however, seems to be less tight in denervated soleus muscles.

Animals↗

Coordinated fast-to-slow transitions of myosin and SERCA isoforms in chronically stimulated muscles of euthyroid and hyperthyroid rabbits.

Changes in the patterns of myosin heavy chain (MHC) isoforms, isomyosins, and Ca(2+)-ATPase (SERCA) isoforms were studied in long-term (72 d) stimulated fast-twitch extensor digitorum longus (EDL) and tibialis anterior (TA) muscles of euthyroid and hyperthyroid rabbits. The chronic low-frequency stimulation-induced fast-to-slow transitions in MHC isoforms, isomyosins and SERCA isoforms were pronounced in muscles from euthyroid rabbits, but less pronounced in muscles from hyperthyroid rabbits. Thus, hyperthyroidism counteracted to same extent the stimulation-induced fast-to-slow transition. Analyses of all parameters were performed on the same individual muscles, providing information on the co-ordinated expression of SERCA and myosin isoforms. A high correlation (r = 0.97) was detected between relative concentrations of slow SERCA2a and slow MHCI isoforms. This correlation persisted under all experimental conditions, suggesting a co-ordinated expression of slow myosin and Ca(2+)-ATPase isoforms. Conversely, fast SERCA1a was correlated to fast myosin isoforms as a whole.

Animals↗

Effect of hypo- and hyperthyroid states on phospholipid composition in developing rat heart.

The aim of this study was to examine the effect of hypo- and hyperthyroidism on the phospholipid composition in developing rat heart. The hypothyroid state (PTU) was induced by 0.05% 6-n-propyl-2-thiouracil in drinking water given to nursing mothers from the postnatal day 2-21. The hyperthyroidism (T3) was made by daily injection of 3,3',5-triiodo-L-thyronine (10 microg/100 g body wt) to newborns in the same time period. Age matched intact littermates were taken as euthyroid controls. PTU decreased the concentration of total phospholipids (PL), choline phosphoglycerides (PC), ethanolamine phosphoglycerides (PE) and diphosphatidylglycerol (DPG) and increased the proportion of plasmalogen component of PE (PLPE). T3 increased the concentration of PL, PC, PE, DPG and decreased PLPE in comparison with euthyroid controls. The ratio of saturated/unsaturated fatty acids (FA) in PE was decreased in PTU and increased in T3 group. The ratio of n-6/n-3 polyunsaturated FA in PC, PE and phosphatidylinositol (PI) was increased in PTU due to increase of 18:2n-6 and decrease of 22:6n-3 proportion. T3 decreased this ratio because of decline in 20:4n-6 and rise in 22:6n-3 proportion. Both hypo- and hyperthyroidism decreased the ratio of 20:4n-6/18:2n-6 in the majority of phospholipids. PTU decreased the unsaturation index in PC, PI and phosphatidylserine. It is concluded that thyroid state plays an essential role in the development of membrane phospholipid components in cardiac membranes during the early postnatal period.

Animals↗

TSH-induced hyperthyroidism caused by a pituitary tumor.

BACKGROUND: A 45-year-old man presented with frontal headache and visual disturbances to our clinic. For the previous 5 years, he had been receiving treatment for long-lasting mild hyperthyroidism with antithyroid therapy, but therapy had not been carefully followed. During the last 2 years he had also complained of erectile dysfunction and loss of libido. On physical examination, he had a small goiter, normal skin, no Graves' ophthalmopathy, normal BMI, and reduced testis volume and pubic hair. INVESTIGATIONS: Serum levels of free T3 and T4, serum prolactin, testosterone, serum gonadotropins, insulin-like growth factor 1, adrenocorticotropic hormone, and cortisol were measured. MRI scan, TSH-releasing hormone test, and T3 suppression test were carried out. Levels of pituitary glycoprotein hormone alpha-subunit and sex-hormone-binding protein were also measured. DIAGNOSIS: Hyperthyroidism caused by a mixed pituitary adenoma that secretes prolactin and TSH. MANAGEMENT: Trans-sphenoidal resection of the pituitary tumor. After surgery, T3 suppression test failed to completely suppress TSH secretion, which suggested a persistence of residual adenomatous cells. Hyperthyroidism and hypogonadism recurred after 5 years, therefore, treatment with lanreotide was initiated, and resulted in complete resolution of signs and symptoms of the disease.

Adenoma↗

Phosphatidate phosphohydrolase and palmitoyl-coenzyme A hydrolase in cardiac subcellular fractions of hyperthyroid rabbits and cardiomyopathic hamsters.

Activities of phosphatidate phosphohydrolase and palmitoyl-CoA hydrolase were determined in cardiac subcellular fractions prepared from rabbits which has received tri-iodothyronine and from hamsters with hereditary cardiomyopathy (strain BIO 14.6). 1. Both mitochondrial and microsomal fractions of hyperthyroid rabbit hearts produced 4-5 times as much diacylglycerol 3-phosphate from glycerol 3-phosphate and palmitate as did those of euthyroid hearts. 2. Phosphatidate phosphohydrolase, measured with phosphatidate emulsion, was activated by 1mm-Mg(2+) in all but the mitochondrial fraction of euthyroid rabbit hearts. The activation was more pronounced in subcellular fractions isolated from hyperthyroid hearts, so that the measured activities were significantly increased above those of the controls. The highest activity was found in the microsomal and lysosomal fractions. 3. In the absence of Mg(2+) during incubation, the difference in phosphohydrolase activities between eu- and hyper-thyroid states was not significant. 4. The phosphohydrolase of subcellular fractions of control hamsters did not respond to addition of 0.5-8.0mm-Mg(2+). The enzyme from cardiomyopathic hearts was slightly inhibited by this bivalent cation and therefore significant increases in activity were observed only in the absence of Mg(2+) from the assay system. 5. The rate of reaction by soluble phosphatidate phosphohydrolase was similar regardless of the nature of the substrate. Both when microsomal-bound phosphatidate was used as the substrate and when phosphatidate suspension was used, the activity of soluble enzyme was lower than that of the microsomal and lysosomal enzymes measured with phosphatidate suspension; this was especially so when the assay was carried out in the absence of Mg(2+). Neither tri-iodothyronine nor cardiomyopathy influenced the soluble phosphohydrolase activity in the two species. 6. Neither tri-iodothyronine nor cardiomyopathy significantly changed palmitoyl-CoA hydrolase activities in subcellular fractions. 7. Microsomal diacylglycerol acyltransferase and myocardial triacylglycerol content were also unchanged in the hyperthyroid state.

Acid Phosphatase↗

Regulation of hepatic fructose 2,6-bisphosphate concentrations and lipogenesis after re-feeding in euthyroid and hyperthyroid rats. A regulatory role for glycogenesis.

The time courses of restoration of fructose 2,6-bisphosphate (Fru-2,6-P2) concentrations and rates of lipogenesis after chow re-feeding were correlated with glycogen concentrations and rates of glycogen synthesis in livers of 48 h-starved euthyroid and hyperthyroid rats. Although a regulatory function for glycogen in the regulation of Fru-2,6-P2 concentrations was excluded, an inverse relationship between rates of glycogenesis and Fru-2,6-P2 concentrations indicated a role for glycogenesis in the suppression of Fru-2,6-P2 concentrations during the early (0-4 h) period of re-feeding. There was also a negative correlation between rates of glycogenesis and lipogenesis, and a positive correlation between glycogen concentrations and the lipogenic rate. Decreased rates of glycogenesis in hyperthyroid rats were associated with increased rates of lipogenesis. The response of Fru-2,6-P2 to changes in the glycogenic rate was modified by hyperthyroidism, although a negative correlation was again observed.

Animals↗

Effects of hyperthyroidism on the sensitivity of glycolysis and glycogen synthesis to insulin in the soleus muscle of the rat.

1. The effects of hyperthyroidism on the sensitivity and responsiveness of glycolysis and glycogen synthesis to insulin were investigated in the isolated incubated soleus muscle of the rat. 2. Hyperthyroidism, which was induced by administration of tri-iodothyronine (T3) to rats for 2, 5 or 10 days, increased fasting plasma concentrations of glucose, insulin and free fatty acids. 3. Administration of T3 for 2 or 5 days increased the rates of glycolysis at all insulin concentrations studied: this was due to increased rates of both glucose phosphorylation and glycogen breakdown, but there was no effect of T3 on the sensitivity of glycolysis to insulin. However, administration of T3 for 10 days increased the sensitivity of the rate of glycolysis to insulin. 4. The concentration of adenosine in the gastrocnemius muscles of the rats was not different from controls after 5 days, but it was markedly decreased after 10 days of T3 administration. If these changes are indicative of changes in the soleus muscle, the increased sensitivity of glycolysis to insulin found after 10 days' T3 administration could be due to the decrease in the concentration of adenosine. 5. Administration of T3 decreased the sensitivity of glycogen synthesis to insulin and the glycogen content of the soleus muscles. This may explain the decreased rates of non-oxidative glucose disposal found in spontaneous and experimental hyperthyroidism in man. 6. The rates of glucose oxidation did not change after 2 days, but they were increased after 5 and 10 days of T3 administration.

Adenosine↗

Effects of hyperthyroidism and hypothyroidism on glutamine metabolism by skeletal muscle of the rat.

1. The effects of hyperthyroidism and hypothyroidism on the concentrations of glutamine and other amino acids in the muscle and plasma and on the rates of glutamine and alanine release from incubated isolated stripped soleus muscle of the rat were investigated. 2. Hyperthyroidism decreased the concentration of glutamine in soleus muscle but was without effect on that in the gastrocnemius muscle or in the plasma. Hyperthyroidism also increased markedly the rate of release of glutamine from the incubated soleus muscle. 3. Hypothyroidism decreased the concentrations of glutamine in the gastrocnemius muscle and plasma but was without effect on that in soleus muscle. Hypothyroidism also decreased markedly the rate of glutamine release from the incubated soleus muscle. 4. Thyroid status was found to have marked effects on the rate of glutamine release by skeletal muscle per se, and may be important in the control of this process in both physiological and pathological conditions.

Alanine↗