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Pharmacokinetics of propranolol used for suppressing tachycardia in hyperthyroidism.

The aim of this study was to investigate the pharmacokinetics of propranolol in patients with hyperthyroidism, and its effect on heart rate (HR) using 24 hour-ECG monitoring. Subjects included 9 patients with hyperthyroidism (group H) and 9 euthyroid patients with hypertension selected as the control group (group C). All patients took propranolol at a dosage of 10 mg, 3 times a day for 7 days. Plasma propranolol concentrations were measured on the 7th day of its administration by the HPLC method. Twenty-four hour-ECG monitoring was recorded twice before and after treatment with propranolol. The mean reduction in the minimum HR was 10.7 +/- 3.6 (11.9 +/- 3.6%) in group H and 5.0 +/- 1.6 (9.5 +/- 3.0%) bpm in group C. That in the average HR was 12.2 +/- 3.7 (11.3 +/- 3.1%) in group H and 9.2 +/- 2.2 bpm (13.7 +/- 3.2%) in group C. That in the maximum HR was 16.9 +/- 5.2 (10.9 +/- 3.1%) in group H and 24.4 +/- 2.4 bpm (21.9 +/- 2.1%) in group C. The peak concentration of propranolol in plasma was 10.8 +/- 2.4 ng/ml in group H and 55.3 +/- 14.3 ng/ml in group C (p < 0.01). There was a linear correlation between the reduction in the hourly maximum heart rate and the peak plasma propranolol concentration in group H. Cardiovascular manifestations in hyperthyroid patients were related to sympathetic hypersensitivity and their improvement was not fully obtained by small doses of propranolol.

Adult↗

Reversible left ventricular dysfunction "takotsubo" cardiomyopathy associated with hyperthyroidism.

Myocardial stunning with hyperthyroidism is rare. A 79-year old woman with hyperthyroidism was admitted to our hospital complaining of palpitations due to paroxysmal atrial fibrillation. An echocardiogram showed akinesis of the apical wall which was not observed 2 weeks before admission. Cardiac catheterization performed in the acute phase showed normal coronary arteries and no evidence of provocative spasms. The wall motion abnormality disappeared entirely after 1 week in hospital. We report a case of transient left ventricular dysfunction, so called "takotsubo" cardiomyopathy, associated with hyperthyroidism.

3-Iodobenzylguanidine↗

[Bone effects of the association hyperthyroidism-castration of adult female rats].

The relationship between thyroid, gonads and bone morphology was investigated in 5 month-old Wistar rats, castrated and kept in hyperthyroid or euthyroid state for periods of 30, 60 and 90 days. A non-castrated control group was maintained in the same condition. At the end of each period, plasma concentrations of free T4, progesterone and estradiol were measured. The bones from each group were submitted to radiological and histological analysis. Hyperthyroidism in intact rats caused variation in bone morphology throughout the experiment, leading to loss of trabecular bone tissue at day 60, due to increased bone resorption. At day 90 there was no bone loss, because the increase in bone resorption was accompanied by higher bone apposition. In castrated euthyroid rats reduction in progesterone levels inhibited the bone apposition, causing a slight loss of trabecular bone tissue in vertebrae and alveolar bone at day 30, which was intensified at days 60 and 90, affecting cortical bone tissue. The administration of thyroxine to castrated rats reversed osteopenia at days 30 and 60, which did not occur at day 90 when bone loss was more extensive. In conclusion, hypoprogesteronism and hypoestrogenism alter bone metabolism and the bone response to hyperthyroidism depends on the plasma profile of sex steroids, time of exposure and bone tissue configuration.

Animals↗

Congenital hyperthyroidism: autopsy report.

We report the autopsy of a stillborn fetus with congenital hyperthyroidism born to a mother with untreated Graves' disease, whose cause of death was congestive heart failure. The major findings concerned the skull, thyroid, heart, and placenta. The cranial sutures were closed, with overlapping skull bones. The thyroid was increased in volume and had intense blood congestion. Histological examination showed hyperactive follicles. The heart was enlarged and softened, with dilated cavities and hemorrhagic suffusions in the epicardium. The placenta had infarctions that involved at least 20% of its surface, and the vessels of the umbilical cord were fully exposed due to a decrease in Wharton's jelly. Hyperthyroidism was confirmed by the maternal clinical data, the fetal findings of exophthalmia, craniosynostosis, and goiter with signs of follicular hyperactivity. Craniosynostosis is caused by the anabolic action of thyroid hormones in bone formation during the initial stages of development. The delayed initiation of treatment in the present case contributed to the severity of fetal hyperthyroidism and consequent fetal death.

Adult↗

Effects of osteoporotic cytokines in ovary-intact and ovariectomised rats with induced hyperthyroidism; is skeletal responsiveness to thyroid hormone altered in estrogen deficiency?

This experimental study was designed to examine the effects of hyperthyroidism on osteoporotic cytokines such as interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha in the physiological concentrations and in the deficiency of estrogen. We investigated the effects of thyroid hormones on cytokines and bone metabolism in L-thyroxine induced ovary-intact and ovariectomised rats, as levels of cytokines were increased in hyperthyroidism. The rats were divided into three groups. In the first group, L-thyroxine-induced hyperthyroid rats were ovariectomised (OVX), while the OVX rats were administered L-thyroxine in the second group. The third group received sham-operation. Blood samples taken from the tail vein of rats were analyzed for plasma T3, T4, TSH and serum IL-1beta, IL-6, TNFalpha, calcium (Ca), phosphorous (P), parathyroid hormone (PTH), alkaline phosphatase (ALP), bone-specific alkaline phosphatase (b-ALP). L-thyroxine administration increased the cytokines, ALP and b-ALP and decreased PTH, while there was no change in Ca and P. However, the ovariectomy of these rats did not change the levels of cytokines, Ca, P, PTH, ALP, and b-ALP. In ovariectomised rats, the cytokines, ALP and b-ALP increased but not Ca and P conversely, PTH decreased. L-thyroxine administration to ovariectomised rats did not change the levels of cytokines, Ca, P, PTH, ALP and b-ALP. In sham-operated rats there was no change in any of the parameters compared with initial values. Thyroid hormones may not be effective on bone metabolism in estrogen deficiency.

Animals↗

Impairment of glucose tolerance in hyperthyroid cats.

Intravenous glucose tolerance tests were performed in eight adult cats before and after a 4-week treatment with thyroxine. The untreated cats had a mean fasting blood glucose concentration of 7.7 +/- 0.3 mmol/l and a mean fasting insulin concentration of 88 +/- 31 pmol/l which were not significantly different from mean fasting glucose and insulin concentrations after 4 weeks of thyroxine administration (6.9 +/- 0.2 mmol/l and 101 +/- 28 pmol/l respectively). At 120 min after glucose injection, the glucose concentration in untreated cats returned to baseline concentrations as did the insulin concentration. However, in the hyperthyroid cats both glucose and insulin concentrations were significantly (P less than 0.001) higher (13.6 +/- 0.8 mmol/l and 245 +/- 17 pmol/l respectively) in comparison with the baseline and untreated cats. The t1/2 for glucose disappearance was significantly higher in the cats rendered hyperthyroid, and the glucose disposal rate constant (K) was significantly lower in this group. It is concluded that hyperthyroidism in cats leads to impairment of glucose tolerance possibly due to peripheral insulin resistance.

Animals↗

Influence of maternal hyperthyroidism in the rat on the expression of neuronal and astrocytic cytoskeletal proteins in fetal brain.

Maternal hypothyroidism during pregnancy impairs brain function in human and rat offspring, but little is known regarding the influence of maternal hyperthyroidism on neurodevelopment. We have previously shown that the expression of neuronal and glial differentiation markers in fetal brain is compromised in hypothyroid rat dam pregnancies and have now therefore extended this investigation to hyperthyroid rat dams. Study groups comprised partially thyroidectomised dams, implanted with osmotic pumps infusing either vehicle (TX dams) or a supraphysiological dose of thyroxine (T4) (HYPER dams), and euthyroid dams infused with vehicle (N dams). Cytoskeletal protein abundance was determined in fetal brain at 21 days of gestation by immunoblot analysis. Relative to N dams, circulating total T4 levels were reduced to around one-third in TX dams but were doubled in HYPER dams. Fetal brain weight was increased in HYPER dams, whereas litter size and fetal body weight were reduced in TX dams. Glial fibrillary acidic protein expression was similar in HYPER and TX dams, being reduced in both cases relative to N dams. alpha-Internexin (INX) abundance was reduced in HYPER dams and increased in TX dams, whereas neurofilament 68 (NF68) exhibited increased abundance in HYPER dams. Furthermore, INX was inversely related to - and NF68 directly related to - maternal serum total T4 levels, independently of fetal brain weight. In conclusion, maternal hyperthyroidism compromises the expression of neuronal cytoskeletal proteins in late fetal brain, suggestive of a pattern of accelerated neuronal differentiation.

Analysis of Variance↗

Prothrombin, activated partial thromboplastin, and proteins induced by vitamin K absence or antagonists clotting times in 20 hyperthyroid cats before and after methimazole treatment.

The effect of daily doses of 5-15 mg of methimazole on the platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), and proteins induced by vitamin K absence or antagonists (PIVKA) clotting time in 20 hyperthyroid cats was determined. No significant (P > .05) difference was found in median platelet count. PT, APTT, or PIVKA clotting time before treatment compared to median values at 2-6 weeks or > or =7-12 weeks of methimazole treatment. No cat had a prolonged APTT at any time. At 2-6 weeks of methimazole treatment, 1 cat each developed thrombocytopenia or prolonged PIVKA clotting time despite initially normal values. Three cats had abnormal coagulation tests (prolonged PT [n = 1] and PIVKA clotting time [n = 3]) before treatment that fluctuated during treatment. Excluding the 3 cats that had abnormal PIVKA clotting time before treatment, prolonged PIVKA clotting time developed in 6% (1/17; 95% confidence interval, 0-28%) cats treated with methimazole for 2-6 weeks. Seemingly. doses of methimazole commonly used to treat hyperthyroidism in cats do not cause alteration in PT and APTT, and only rarely prolong PIVKA clotting time. Nevertheless, abnormal PIVKA clotting time may explain bleeding tendencies unassociated with thrombocytopenia in methimazole-treated hyperthyroid cats.

Animals↗

Long-term health and predictors of survival for hyperthyroid cats treated with iodine 131.

Two hundred thirty-one cats treated with radioactive iodine at the Texas Veterinary Medical Teaching Hospital were followed for a median of 25 months by means of an ambidirectional (prospective, retrospective) cohort study design. Cox proportional hazards models were used to determine predictors of survival based on data at the time of hyperthyroid diagnosis (collected retrospectively) and found that only age at diagnosis and sex of the cat were predictors of survival. Increasing age (for each year of age, relative risk [RR] = 1.2, 95% confidence interval [CI] = 1.1-1.3) and being male (RR = 0.68, 95% CI = 0.5-0.9) increased likelihood of death. Tables predicting survival after diagnosis and treatment of hyperthyroidism for various age and sex combinations were created. In addition, Cox proportional hazard models were run with all data available at the end of the study (collected retrospectively and prospectively) including number and type of major health problems reported at the time of death or censoring. In this model, significant factors were age at diagnosis, sex, and either type of major health problem or number of health problems. Cats with renal disease or cancer were more likely not to survive and increasing from none to 2 health problems also decreased survival. Renal problems and cancer were the most common health problems at the time of death or censoring. This study provides estimates of duration of survival for cats successfully treated for hyperthyroidism with radioactive iodine, which can be useful in assisting with client treatment decisions.

Age Factors↗

The impact of propylthiouracil therapy on lipid peroxidation and antioxidant status parameters in hyperthyroid patients.

This study was performed on 17 hyperthyroid patients and 15 healthy controls. The patients were under propylthiouracil (PTU) therapy at a dosage of 3 x 100 mg/day for one month. Blood samples, taken at the beginning and on the 30th day of therapy, were analyzed for hormonal parameters (T3, T4, TSH), lipid peroxidation endproduct [thiobarbituric acid reactive substances (TBARS)] and antioxidant status parameters: glutathione (GSH), glutathione peroxidase (GSH-Px) and CuZn superoxide dismutase (CuZn SOD). Hyperthyroid patients were observed to have significantly higher TBARS, GSH and CuZn SOD levels than controls (P < 0.05, P < 0.001, P < 0.001, respectively). PTU therapy caused a relief in oxidative stress as reflected by significantly decreased TBARS levels (P < 0.001) and a selective modification in the antioxidant status parameters: significant decreases in GSH and CuZn SOD levels (P < 0.001) and a significant increase in GSH Px (P < 0.01) activity. Our findings suggest a selective modification of the antioxidative profile in hyperthyroidism. PTU should also be considered as an in vivo antioxidant, in addition to its antithyroid action.

Adult↗

Dilated cardiomyopathy associated with hyperthyroidism.

We report a case of dilated cardiomyopathy with hyperthyroidism. A 28-year-old man was admitted because of congestive heart failure and atrial fibrillation, and was newly diagnosed as having hyperthyroidism. Despite administration of antithyroid medication, he developed recurrent congestive heart failure. An echocardiogram revealed a moderately dilated left ventricle with diffuse hypokinesis. Though his thyroid function normalized, the patient's cardiac dysfunction did not improve. Beta-blocker therapy was begun with subsequent improvement in clinical symptoms. This suggests that beta-blocker treatment may be effective in patients with atrial fibrillation associated with cardiomyopathy and hyperthyroidism.

Adrenergic beta-Antagonists↗

Two cases of systemic lupus erythematosus associated with hyperthyroidism.

We have experienced two cases (Case 1: 21-year-old female, Case 2: 26-year-old female) of systemic lupus erythematosus (SLE) associated with hyperthyroidism. Case 1 had been treated with methimazole (MMI) and betamethasone for approximately two years. Although thyroid function improved with the treatment, laboratory data of SLE deteriorated. She was successfully treated with betamethasone alone. Case 2, who had severe side effect (severe hemorrhage due to gastric ulcer) during prednisolone treatment for SLE, was found to have an additional hyperthyroidism. She was treated with intermittent prednisolone administration alone. Physical findings as well as laboratory data of both SLE and hyperthyroidism improved by the therapy.

Adult↗

Hyperthyroidism associated with autoimmune hemolytic anemia and periodic paralysis: a report of a case in which antihyperthyroid therapy alone was effective against hemolysis.

We describe a case of a 29-year-old man with hyperthyroidism associated with autoimmune hemolytic anemia and periodic paralysis. Euthyroidism, which was achieved by propylthiouracil, brought inhibition of hemolysis and amelioration of anemia in spite of continuously positive direct and indirect Coombs' tests. Neither adrenocortical steroid nor blood transfusion was administered. Since indirect monospecific Coombs' test was negative against anti-human complements serum, the membrane of red blood cells may be less fragile. This is one reason why hemolysis was inhibited by anti-hyperthyroid therapy only. This may indicate that the hyperdynamic circulatory state secondary to hyperthyroidism plays an important role in the destruction of red blood cells which were coated by anti-red blood cell antibody.

Adult↗

Hyperthyroidism causes mechanical insufficiency of myocardium with possibly increased SR Ca2+-ATPase activity.

Hyperthyroidism is known to affect multiple organ functions, and thyroid hormone has been known to improve myocardial function in a failing heart. The purpose of this study is to elucidate the functional and metabolic effects of thyroid hormone on myocardium in a rat model exposed to long-term excess thyroid hormone, particularly focusing on the SR Ca(2+)-ATPase (SERCA2) function. 3,5,3'-Triiodo-L-thyronine (T3), or the vehicle, was subcutaneously given for 4 weeks (T3 and control [C] group). Bolus I.V. Thapsigargin (TG) was used to test the SERCA2 function (C-TG and T3-TG) in Langendorff perfused heart. Myocardial functions such as LV-developed pressure (LVDP; mmHg), +/- dP/dt (mmHg/s), tau (ms), and oxygen consumption (MVO(2); ml/min/g wt) were measured. SERCA2 and GLUT4 protein level were also evaluated by Western immunoblotting. Left ventricle to body weight (LV/BW) ratio was significantly higher in the T3 group. Both negative dP/dt and tau were significantly decreased by TG. It is interesting that the decrement of negative dP/dt and tau attained by TG was significantly larger in the hyperthyroid group (T3-TG) than in a normal heart (C-TG). SERCA2 and GLUT4 protein levels were not significantly different between control and the T3 group. We conclude that prolonged exposure to thyroid hormone causes hypertrophy of the myocardium and an augmentation of the SR Ca(2+) ATPase activity. Care must be taken in hyperthyroid heart during the ischemia-reperfusion process where the SRECA2 function is inhibited.

Animals↗

Increased insulin action and clearance in hyperthyroid newly diagnosed IDDM patient. Restoration to normal with antithyroid treatment.

In a patient with hyperthyroidism and newly diagnosed insulin-dependent diabetes mellitus (IDDM), insulin action and clearance were studied before the initiation of antithyroid treatment and at 3-mo intervals for 1 yr thereafter. The sequential euglycemic clamp technique (5 mM) was used with insulin infusion rates of 0.5, 1.0, 2.0, and 5.0 mU.kg-1.min-1 in four steps of 2 h. The data were compared with nine control subjects and nine newly diagnosed euthyroid IDDM patients treated with insulin for 0.5 mo. Insulin sensitivity was increased in the patients (ED50 40 vs. 52 mU/L, range 43-70, in controls and 70 mU/L, range 59-120, in IDDM subjects). Insulin responsiveness was markedly elevated; the steady-state glucose infusion rate (SSGIR) of step 4 was 104 vs. 64 mumol.kg-1.min-1 (range 50-79) in controls and 61 mumol.kg-1.min-1 (range 47-69) in IDDM subjects. Insulin clearance was elevated in all steps (1-3, 20-23 vs. 9-15 ml.kg-1.min-1; 4, 18 vs. 6-12 ml.kg-1.min-1 in control and IDDM subjects). Parallel to the normalization of thyroid metabolism, insulin action (ED50 60 mU/L, SSGIR in step 4, 51 mumol.kg-1.min-1) and insulin clearance (steps 1-3, 11-14 ml.kg-1.min-1; step 4, 7 ml.kg-1.min-1) returned to the normal range in 6 mo. Both remained within the normal range until 12 mo. In the patient with newly diagnosed IDDM, the initial marked increases of insulin action and clearance were due to coexistent hyperthyroidism. With the amelioration of the hyperthyroid state, both processes became normal. The parallelism between insulin action and clearance suggests a functional relationship.

Adult↗

Relationship between orally administered dose, surface emission rate for gamma radiation, and urine radioactivity in radioiodine-treated hyperthyroid cats.

OBJECTIVE: To determine the relationship between surface emission rate of gamma radiation and urine concentration of I131 (urine radioactivity) during the period 7 to 21 days after oral or SC administration of I131 to hyperthyroid cats. ANIMALS: 47 hyperthyroid cats administered I131 PO and 24 hyperthyroid cats administered I131 SC. PROCEDURE: A dose of I131 (1.78 to 2.04 X 10(2) MBq [4.8 to 5.5 mCi]) was administered orally. Surface emission at the skin adjacent to the thyroid gland on days 7, 10, 14, 18, and 21 and number of counts/30 s in a urine sample (1 mL, obtained via cystocentesis) on days 7, 14, and 21 after oral administration were measured. Effective half-life (T1/2E) was derived for each point. Surface emission thresholds for maximum urine radioactivity values were established. A dose of I131 (1.48 X 10(2) MBq [4.0 mCi]) was administered SC. Urine radioactivity and surface emission rates for SC administration were compared with values for oral administration. RESULTS: The T1/2E for surface emissions and urine radioactivity progressively increased toward values for physical T1/2 over time. The T1/2E for surface emissions was 2.19 to 4.70 days, and T1/2E for urine radioactivity was 2.16 to 3.67 days. Surface emission rates had a clinically useful threshold relationship to maximum urine concentrations of I131. CONCLUSIONS AND CLINICAL RELEVANCE: Surface emission rates for cats administered I131 appeared useful in determining upper limits (threshold) of urine radioactivity and are a valid method to assess the time at which cats can be discharged after I131 administration.

Animals↗

Evaluation of relationships between pretreatment patient variables and duration of isolation for radioiodine-treated hyperthyroid cats.

OBJECTIVE: To determine relationships between commonly measured pretreatment variables and duration of isolation for unrestricted dismissal after oral administration of iodine 131 (131I) for treatment of hyperthyroidism in cats. ANIMALS: 149 hyperthyroid cats treated with 131I. PROCEDURE: A dose of 131I (2.9 to 6.04 mCi [1.07 to 2.23 x 10(8) Bq]) was administered orally to all cats after hyperthyroidism was confirmed by evaluation of serum total thyroxine (T4) concentrations. Forward stepwise regression analysis was used to determine whether pretreatment total T4 concentration, serum creatinine concentration, body weight, age, 131I dose, or concurrent administration of cardiac medication (specifically excluding thyroid suppression drugs) could be used as pretreatment predictors of duration of isolation in a clinical setting. Gamma radiation emission rate at dismissal was < 2.0 mR/h at skin surface over the thyroid region. RESULTS: Mean +/- SD duration of isolation was 16.67 +/- 4.42 days (95% confidence interval, 9.2 to 24.1 days). The regression equation for duration of isolation calculated on the basis of dose of 131I (duration of isolation [days] = 3.2 + [2.66 X mCi - 131I dose]) yielded a regression line with a 95% confidence interval of +/- 3.3 days; only 15% of the variation was explained. CONCLUSIONS AND CLINICAL RELEVANCE: A pretreatment estimate for duration of isolation could be determined only from an equation based on the orally administered dose of 131I. These findings suggest that administration of the lowest efficacious dose possible is the dominant factor in reduction of duration of isolation for cats treated with 131I.

Age Factors↗

Evaluation of dietary and environmental risk factors for hyperthyroidism in cats.

OBJECTIVE: To identify dietary and environmental risk factors for hyperthyroidism in cats. DESIGN: Case-control study. ANIMALS: 100 cats with hyperthyroidism and 163 control cats. PROCEDURE: Medical records were examined, and owners completed a mailed questionnaire. Data collected included information regarding demographic variables, environmental exposures, and diet, including preferred flavors of canned cat food. RESULTS: Case cats were significantly less likely to have been born recently than control cats. Housing; exposure to fertilizers, herbicides, or plant pesticides; regular use of flea products; and presence of a smoker in the home were not significantly associated with an increased risk of disease, but cats that preferred fish or liver and giblets flavors of canned cat food had an increased risk. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that cats that prefer to eat certain flavors of canned cat food may have a significantly increased risk of hyperthyroidism.

Age Factors↗