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PubMed1978

Plasma protein binding of propranolol and isoprenaline in hyperthyroidism and hypothyroidism.

1. The possibility that thyroid disease might result in alterations in the plasma proteins binding of drugs has been investigated by studying the binding of propranolol and isoprenaline in patients with hyperthyroidism and hypothyroidism. 2. Plasma protein binding of propranolol and isoprenaline has been measured in seven hyperthyroid patients and ten hypothyroid patients. Plasma binding was estimated by equilibrium dialysis at 37 degree C using triatiated propranolol and isoprenaline, both when the patients had thyroid dysfunction and again when they were euthyroid. 3. In the hyperthyroid group, mean propranolol binding varied from 86 +/- 1.7% when hyperthyroid to 88.4 +/- 0.8% when euthyroid. The comparable isoprenaline figures were 65.1 +/- 3.2% and 68.1 +/- 1.4% respectively. Neither difference was significant. 4. Isoprenaline binding was significantly lower (64.3 +/- 1.6%) when patients were hypothyroid than when they became euthyroid (68.8 +/- 1.2%). Propranolol binding was not altered by hypothyroidism. 5. It is concluded that clinically important alterations in free drug concentrations of propranolol or isoprenaline do not occur in hyperthyroidism or hypothyroidism.

Adult↗
PubMed1981

The influence of age, smoking and hyperthyroidism on plasma propranolol steady state concentration.

1 Plasma propranolol steady state concentration (Css) was determined during chronic dosage (160 mg/day) in 22 hyperthyroid patients (aged 16-75 years, 11 smokers, 11 non-smokers) and again following treatment when euthyroid. 2 There was a positive correlation between plasma propranolol Css and age in patients both when hyperthyroid (r = 0.74, P less than 0.01) and when euthyroid (r = 0.58, P less than 0.05). 3 Plasma propranolol Css in hyperthyroid patients were lower (P less than 0.05) in smokers than in non-smokers. 4 Following correction of hyperthyroidism there was a significant increase (P less than 0.01) in both the plasma propranolol Css and degree of plasma protein binding of propranolol. 5 Hyperthyroidism and smoking are known to increase the rate of drug metabolism and it is suggested that these variables may give rise to or accentuate an age related reduction in propranolol clearance.

Adolescent↗
PubMed1982

Cardiovascular responses in hyperthyroidism before and during beta-adrenoceptor blockade: evidence against adrenergic hypersensitivity.

The relationship between the sympathetic nervous system and cardiovascular responses has been studied indirectly in ten hyperthyroid patients and age matched euthyroid controls. Nyctohemeral variations in heart rate, and heart rate and blood pressure responses to exercise were measured before and during beta-blockade with slow-release propranolol. Both groups showed a parallel variation in heart rate over 24 h, with an increase in heart rate inthe hyperthyroid group that was the same during the day (27.9 +/- 0.95 beats/min) and during the night (26.7 +/- 0.75 beats/min). Similarly, the increase in resting heart rate (32.7 +/- 4.4 beats/min) in the hyperthyroid group was close to the increase in peak exercise-induced heart rate (25.0 +/- 4.7 beats/min). Adequate beta-blockade was achieved in all subjects as evidenced by a percentage reduction in peak exercise heart rate of 25-45%. Propranolol caused a greater reduction in daytime than night-time heart rate in both groups and blunted the response to exercise. Following beta-blockade, the mean percentage reduction in heart rate and systolic blood pressure during exercise, and heart rate responses over 24 h were similar in hyperthyroid and euthyroid groups. The closest correlation between thyroid hormone levels and heart rate was that of serum total tri-iodothyronine (T3) and nocturnal heart rate during beta-blockade (r=0.92; P less than 0.0001). It is concluded that excess circulating thyroid hormones exert a direct effect on the cardiovascular system additive to the sympathetic nervous system and that there is no evidence of adrenergic hypersensitivity in hyperthyroidism.

Adult↗
PubMed1982

Nocturnal natriuresis in hyperthyroidism.

We measured urine flow and the renal excretion of total solute, sodium, potassium and calcium in eleven patients with hyperthyroidism before and after treatment. Mean nocturnal sodium excretion was significantly greater (P less than 0.05) during hyperthyroidism and was unaccompanied by any significant alterations in day time or 24-h values. As a result of this nocturnal natriuresis in hyperthyroidism significant changes were noted in the ratios of day/night sodium excretion (P less than 0.005) and urinary flow (P less than 0.05). The change in ratio of day/night sodium excretion resulting from treatment of hyperthyroidism was shown to correlate significantly with the change in plasma total triiodothyronine (r=0.73, P less than 0.01). Twenty-four hour urinary calcium output was significantly greater (P less than 0.02) in hyperthyroidism but there was no significant alteration in the day/night pattern of excretion.

Adult↗
PubMed1983

Serum calcium concentration in hyperthyroidism at diagnosis and after treatment.

In a large, mainly outpatient, series of hyperthyroid patients who attended a district general hospital the serum concentrations of calcium and albumin were measured before and in many cases after treatment. The calcium level (mean +/- SD) before treatment (2.41 +/- 0.21 mmol/l, n = 437) was significantly higher (P less than 0.01) than afterwards (2.36 +/- 0.15 mmol/l, n = 232) and the albumin level rose when the patients became euthyroid (from 40.5 +/- 3.1 g/l to 44.0 +/- 2.4 g/l; P less than 0.01). After treatment neither value differed from those of an unselected group of out-patients. The usual relation between the serum concentrations of calcium and albumin did not hold in the hyperthyroid subjects but reverted to normal on treatment; the variation, probably due to an increase in ionized calcium, leads to an overestimate of the 'corrected calcium' when conventional methods are used to calculate this figure. Thus, using a conventional formula 8.5% of our hyperthyroid patients would appear to have a calcium greater than 2.65 mmol/l (normal mean plus 2 standard deviations) whereas using a correction factor specific for the hyperthyroid situation the figure is reduced to 5.7% which is only twice the expected proportion. The calcium level was significantly greater (P less than 0.001) in those patients in whom initial T3 concentration was high (greater than 7.2 nmol/l). There was no effect of T4 upon serum calcium which could not be accounted for by the action of T3. In this series of 437 patients there was no case of symptomatic hypercalcaemia. The maximum value was 2.80 mmol/l in a patient with coincident primary hyperparathyroidism. Significant hypercalcaemia is rare in hyperthyroidism.

Adolescent↗
PubMed1984

Serum triiodothyronine and hyperthyroidism in a population sample of women.

The serum T3 assay has been regarded as the most sensitive single test for hyperthyroidism although impaired conversion of T4 to T3 in non-thyroidal illness (NTI) might decrease its diagnostic sensitivity. The present report gives experience from the T3 assay in middle-aged females under conditions similar to those in a general health survey. The assays were performed during two periods with an interval of six years. In 1974-75 we studied a representative sample (n = 1283) of women of ages 44, 52, 56, 60 and 66 years in Göteborg, Sweden. Individuals with serum T3 concentration greater than mean + 2.5 SD were selected for a follow-up study (n = 21). Of 16 individuals with no previous thyroid disease and no present treatment with thyroid hormones or oestrogens, 14 were subjected to a TRH-stimulation test giving a normal TSH response in 10 cases having T3 concentrations up to mean + 3.5 SD. Four women with serum T3 concentration greater than or equal to mean + 3.5 SD had previously unrecognized autonomous function thyroid function, of whom two developed hyperthyroidism after two years. The original population sample was reinvestigated after six years in 1980-81 (n = 1138) together with an additional sample of women giving a total sample of 1422 women of ages 26, 38, 50, 58, 62, 66 and 72 years. Of the females studied in 1974-75 eight had developed hyperthyroidism between the two studies; three of these had raised serum T3 at the investigation in 1974-75. No case of hyperthyroidism had been missed by the T3 assay in the 1974-75 study. Of individuals with serum T3 greater than or equal to mean + 2.5 SD selected for a follow-up (n = 29) at least five were found to have previously unrecognized thyroid autonomy. We found a raised serum T3 to be associated with hyperthyroid (n = 2) and euthyroid Graves' disease, autonomously functioning thyroid adenoma(s), possible painless subacute thyroiditis, possible thyrotoxicosis factitia, diminished thyroid reserve and thyroid substitution therapy.

Adult↗
PubMed1984

Enhanced gluconeogenic capacity from glycerol in hyperthyroid man: evidence in favour of a beta-adrenergic mechanism.

We have previously shown that gluconeogenesis, assessed by glycerol clearance, is increased in hyperthyroid man. The mechanism underlying this change is uncertain but many of the metabolic changes found in hyperthyroidism are thought to be due to increased catecholamine sensitivity of peripheral tissues. To test the hypothesis that enhanced gluconeogenic capacity from glycerol in hyperthyroidism might be mediated via a beta-adrenergic mechanism we have estimated glycerol clearance in thyrotoxic subjects before and during treatment with a non-selective beta-adrenergic blocking drug propranolol (Inderal LA). Control subjects of similar age and weight were also tested. In hyperthyroid subjects, blood glucose and blood glycerol concentrations were increased but blood lactate, pyruvate and alanine concentrations were normal. Glycerol clearance was increased and followed a double exponential decay with a shortened second component half-time. Endogenous glycerol production was increased three fold. Following beta-blockade blood glucose and blood glycerol concentrations fell although blood glucose concentrations remained above normal values. Glycerol clearance and endogenous glycerol production were also decreased but remained significantly higher than in control subjects. Serum thyroxine and serum triiodothyronine concentrations showed no significant change although mean values fell by 10% and 17% respectively. We conclude that the increase in gluconeogenic capacity from glycerol in hyperthyroid subjects is mediated in part by a beta-adrenergic mechanism.

Adult↗
PubMed1993

Bone mineral density in patients with hyperthyroidism measured by dual energy X-ray absorptiometry.

OBJECTIVE: We assessed the changes of bone mass in patients with hyperthyroidism by measuring bone mineral density using a new method, dual energy X-ray absorptiometry. DESIGN: The values of bone mineral density in patients with hyperthyroidism were compared with data obtained from the controls, and we assessed the correlation analysis between bone mineral density and several metabolic parameters. PATIENTS: We studied 52 Japanese patients with hyperthyroidism (20 males, 32 females). Healthy normal subjects served to establish the mean bone mineral density in the healthy Japanese population (Shiraki et al. 1991). MEASUREMENT: Bone mineral density was assessed by the measurement of lumbar vertebrae and femur by dual energy X-ray absorptiometry. The bone mineral density of vertebrae for each patient was calculated as the percentage of the mean value (% bone mineral density) obtained from an age and sex-matched control group. Blood was drawn to measure the levels of serum calcium, phosphorus, creatinine, alkaline phosphatase, free T3, free T4, TSH, TSH receptor antibody, parathyroid hormone, and serum osteocalcin. RESULTS: The percentage bone mineral density of vertebrae in patients was 92.6 as compared with that of normal controls, and was inversely correlated with serum TSH receptor antibody, osteocalcin, and alkaline phosphatase. CONCLUSIONS: These findings suggest that bone mineral density is decreased in patients with hyperthyroidism and that TSH receptor antibody, osteocalcin, and alkaline phosphatase are sensitive markers of bone metabolism alterations in hyperthyroidism.

Absorptiometry, Photon↗
PubMed1993

Bone mineral density in patients with endogenous subclinical hyperthyroidism: is this thyroid status a risk factor for osteoporosis?

OBJECTIVE: The aim of the present study was to elucidate whether endogenous subclinical hyperthyroidism due to a solitary autonomously functioning thyroid nodule affects bone metabolism and is a risk factor for osteoporosis. DESIGN: In a cross-sectional study measurements of bone mineral density were performed in premenopausal and post-menopausal women. Patients were categorized into non-toxic nodular goitre (n = 32), subclinical hyperthyroid (n = 37) and toxic solitary autonomous thyroid nodule (n = 22) subgroups and the results were compared with those of sex and age-matched control reference population (n = 68). MEASUREMENTS: Lumbar spine and femoral neck bone mineral densities were measured by dual energy X-ray absorptiometry. Single-photon absorptiometry was applied to the measurement of bone mineral content in the midshaft of the radius. RESULTS: In the non-toxic nodular goitre group, bone densities for all the scanned sites did not differ from the sex and age-matched reference population. At the L2-4 scanning site a significant decrease in the bone mineral density could be observed only in the toxic nodular goitre group and this decrease was more marked in the postmenopausal (P < 0.001) than in the premenopausal females (P < 0.05). At the femoral neck and midshaft radius the mean densitometric values were slightly, but significantly, lower only in the post-menopausal subclinical hyperthyroid group compared with the reference population (P < 0.01). The bone mineral density of the femoral neck, as well as the bone mineral content of the midshaft radius, was significantly decreased in both the premenopausal and post-menopausal patients with a toxic solitary nodule. CONCLUSION: This study indicates that the bone mineral density of the lumbar spine, femoral neck and the midshaft of the radius are not significantly decreased in premenopausal patients with endogenous subclinical hyperthyroidism resulting from a solitary autonomously functioning thyroid nodule. Conversely, findings hint at the possibility that long-lasting endogenous subclinical hyperthyroidism may be a contributing factor to the development of osteoporosis in some post-menopausal women, mostly at sites where cortical bone preponderates.

Adult↗
PubMed1994

Exercise performance in children with hyperthyroidism.

An attempt was made to define exercise performance in children with untreated hyperthyroidism using treadmill stress testing. Data were obtained for five female patients and the results were compared with those obtained for 16 normal female subjects. There were no significant differences at rest between the hyperthyroidism group and the control group in oxygen uptake, minute ventilation and respiratory rate. On the other hand, heart rate in the hyperthyroidism group was significantly higher than that in the control group. During exercise, there were significant differences between the two groups in oxygen uptake, heart rate, minute ventilation and respiratory rate. Hyperthyroid patients did not show an abrupt increase in heart rate during the first 30 s of exercise. Exercise stress testing can therefore reveal cardiopulmonary abnormalities that are not evident at rest in children with hyperthyroidism.

Adolescent↗
PubMed2006

Subnormal energy expenditure: a putative causal factor in the weight gain induced by treatment of hyperthyroidism.

AIMS: To examine the causes of weight gain occurring as an adverse effect of treatment of hyperthyroidism. METHODS: We measured 24-h energy expenditure (EE), body composition and spontaneous physical activity (SPA) in eight patients before and 1 year after treatment of hyperthyroidism was initiated, and eight controls. RESULTS: One year after initiation of treatment thyrotropin was normalized, thyroid hormones had fallen to the lower end of the reference range and fat mass had increased by 3.5 kg (p < 0.001). Twenty-four hour EE adjusted for fat-free mass (FFM) was 15% higher in hyperthyroid patients before treatment than in controls (p = 0.003), and treatment decreased 24-h EE by 1.9 MJ/day (p = 0.001). After treatment, 24-h EE, adjusted for FFM, was similar to the controls. Multiple regression analyses showed that the suppressed EE could partly be attributed to an iatrogenic suppression of thyroid hormones, resulting in lower sleeping EE. Twenty-four hour SPA was normal in the hyperthyroid state, but decreased after treatment by 21% (p = 0.045), to a level not significantly different, but still below that of the controls. CONCLUSIONS: The study suggests that weight gain during treatment of hyperthyroidism might be due to subnormal levels of EE and SPA caused by a suppression of the thyroid hormone to a level in the lower end of the normal range.

Body Composition↗
PubMed1981

Effect of hypo- and hyperthyroidism on hexokinase in the developing cerebellum of the rat.

Total hexokinase levels (units/g tissue) have been measured during postnatal development of the cerebellum in control, hypothyroid, and hyperthyroid rats. In addition. distribution of hexokinase in the developing cerebellum has been observed with an immunofluorescence method. Hypothyroidism delays the normally observed postnatal increase in total hexokinase activity, whereas hyperthyroidism accelerates the increase. In normal animals, hexokinase levels in maturing Purkinje cells pass through a transient increase, with maximal levels at approximately 8 days postnatally followed by rapid decline to relatively low levels by 12 days; hypothyroidism delays this transient increase and subsequent decline, but hyperthyroidism does not appear to affect markedly the timing of this phenomenon. Cerebellar glomeruli are relatively enriched in hexokinase content, as judged by their intense fluorescence. Hypothyroidism delays the development of intensely stained glomeruli. Hyperthyroidism did not appear to cause precocious increase in numbers of glomeruli but may have increased the rate at which the hexokinase was assimilated by newly formed glomeruli. The effects of hypo- and hyperthyroidism on total cerebellar hexokinase levels are interpreted in terms of the effect of thyroid hormone on the biochemical maturation of synaptic structures rich in hexokinase.

Animals↗
PubMed1980

Absence of changes in drug disposition and catecholamine sensitivity in the hyperthyroid dog.

1 In order to study the relative contribution of hepatic drug metabolizing enzymes and hepatic blood flow to the clearance of drugs in the hyperthyroid state, the disposition kinetics of two model compounds (antipyrine and propranolol) were examined in thyroid-fed dogs as compared to euthyroid and phenobarbitone-pretreated animals. 2 In hyperthyroid dogs, the possibility of catecholamine hypersensitivity was evaluated by assessing the chronotropic response to isoprenaline and by constructing a drug concentration-effect (beta-blockade) relationship. 3 The plasma propranolol half-life (0.97 +/- 0.12 h) of the hyperthyroid animals did not differ significantly from either the euthyroid group or the phenobarbitone-pretreated group. This was observed with no significant change in the apparent volume of distribution among the three experimental groups. 4 Phenobarbitone pretreatment accelerated significantly the elimination of antipyrine (half-life, 1.09 +/- 0.15 h, P less than 0.01) as compared to the euthyroid (2.84 +/- 0.35 h) and the hyperthyroid groups (2.58 +/- 0.13 h), respectively, without any changes in the apparent volume of distribution in any group. 5 Neither the chronotropic responses to exogenously administered catecholamine, nor the antagonist concentration-effect relationships support the concept that the hyperthyroid state potentiates sensitivity of the receptor-effect system of the heart. 6 The data obtained from the present study fit best with the view that thyroid hormone excess alters neither the disposition of the model compounds used nor the catecholamine-sensitivity examined.

Animals↗
PubMedDate not supplied

Hyperthyroidism: a "curable" cause of congestive heart failure--three case reports and a review of the literature.

With the increasing incidence of coronary artery disease and the aging population, the prevalence of congestive heart failure (CHF) is increasing. In the majority of these cases the etiology is underlying coronary artery disease. Other less common causes of CHF include valvular heart disease, hypertension, alcoholic cardiomyopathy, and dilated cardiomyopathy. In addition, there are rare causes, one of which is hyperthyroidism. Hyperthyroidism can affect the cardiovascular system in a variety of ways. The cardiovascular manifestations range from sinus tachycardia to atrial fibrillation and from a high cardiac output state to CHF due to systolic left ventricular dysfunction. If the underlying hyperthyroidism is recognized and treated early the CHF in such cases can be cured. The authors present three cases of CHF due to systolic left ventricular dysfunction secondary to hyperthyroidism, which showed considerable improvement in the left ventricular function once the hyperthyroidism was treated.

Adult↗
PubMed1986

Hyperthyroidism in the elderly.

It is not uncommon for thyrotoxicosis to appear in an atypical manner in older patients. The classical symptoms are often absent. The disease is frequently characterized by cardiac, gastrointestinal, neuromuscular, and neuropsychiatric symptoms. As hyperthyroidism is readily amenable to effective treatment that can improve the quality of life, the clinical suspicion of this disease is always indicated and exclusion of this diagnosis should always be pursued. Recognizing the admittedly great difficulty in making, or even suspecting, the diagnosis of hyperthyroidism in the elderly, our rule is to test for hyperthyroidism in essentially all geriatric patients presenting chronic systemic symptoms or signs. On the other hand, we do not recommend community-wide screening of persons over 60 for hyperthyroidism. Community-wide screening falls far below the break-even point in cost-benefit analysis. The most sensible detector of hyperthyroidism now widely available is the serum free T3 index (FT3I), but it may be falsely normal because of the effect of systemic illness on extrathyroidal T4-to-T3 conversion. The advent of ultrasensitive methods for TSH may change these statements considerably. It may become the single screening procedure for both hyper- and hypothyroidism.

Aged↗
PubMed1989

Age-related changes of thyroid function and immunologic abnormalities in patients with hyperthyroidism due to Graves' disease.

In order to clarify the reasons why hyperthyroidism due to Graves' disease is mild in aged patients compared to young patients, we examined the degree of hyperthyroidism and immune abnormalities in 371 untreated patients. The patients were divided into nine groups based on their age; groups A to I consisted of patients aged 0-9, 10-19, 20-29, 30-39, 40-49, 50-59, 60-69, 70-79, and 80-89 years, respectively. Serum thyroxine (T4), triiodo-thyronine (T3), and thyroglobulin levels were highest in group B (patients aged 10-19 years) and decreased progressively with advancing age. T3/T4 ratio was also highest in group B and decreased progressively with age. These data reconfirmed that the degree of hyperthyroidism is milder in older patients. The prevalence of positive microsomal and thyroglobulin antibodies was highest in group B (patients aged 10-19 years) and progressively lower in older groups, suggesting that an association with Hashimoto's thyroiditis is less prevalent in aged patients. We suggest that hyperthyroidism due to Graves' disease is mild in aged patients because responsiveness of the thyrocyte to the abnormal stimulator, thyrotropin-receptor antibody, may be reduced. Such reduced responsiveness may not be due to Hashimoto's thyroiditis, since the prevalence of antithyroid antibodies is lower in aged than in younger patients with hyperthyroidism due to Graves' disease.

Adolescent↗
PubMed1996

Differences in the signs and symptoms of hyperthyroidism in older and younger patients.

OBJECTIVES: To determine if aging modifies the clinical presentation of hyperthyroidism and the signs of thyrotoxicosis in older people. DESIGN: Prospective cohort study. SETTING: A French university hospital. SUBJECTS: Eighty-four new patients with overt hyperthyroidism confirmed chemically between January 1992 and January 1993. Controls were 68 older euthyroid patients matched to the older hyperthyroid patients. MEASUREMENTS: Comparison of 19 classical signs of hyperthyroidism between 34 older patients (> or = 70 years; mean age 80.2) and 50 younger patients (< or = 50 years; mean age 37.4). Older patients were also compared with controls (mean age 81.3). RESULTS: Three signs were found in more than 50% of older patients: tachycardia, fatigue, and weight loss. Seven signs were found significantly less frequently in older patients (P < .001): hyperactive reflexes, increased sweating, heat intolerance, tremor, nervousness, polydipsia, and increased appetite. Only anorexia (32% vs 4%) and atrial fibrillation (35% vs 2%) were more found frequently in older people (P < .001). A goiter was present in 94% of the younger and in 50% of the older patients (P < .001). The mean number of clinical signs found in the older subjects was significantly smaller than the number found in younger patients (6 vs 10.8; P < .001). Comparison with older controls showed three signs that were highly associated with thyrotoxicosis in older people: apathy (Odd ratio (OR): 14.8), tachycardia (OR: 11.2), and weight loss (OR: 8.7). CONCLUSION: This study confirms the paucity of clinical signs of hyperthyroidism in older adults. These results suggest the necessity of routine screening for thyroid disease in this age group.

Adult↗
PubMed1978

Correction of the biochemical effects of neonatal hypothyroidism by daily low doses of thyroxine. Comparative effects of hyperthyroidism and these corrections.

The purpose of the present communication was to study the corrective effects of low daily thyroxine doses, on the cerebellum biochemical maturation in propylthiouracile (PTU)-treated rats during the early postnatal life. The corrected hypothyroid animals were compared to the normal, hypo- and hyperthyroid ones. The protein, RNA and DNA cerebellar contents were evaluated at 6, 10, 14, 18 and 35 days old animals. At all ages hypothyroidism and hyperthyroidism decreased cerebellar protein, RNA and DNA contents, except in 35-day-old hyperthyroid animals, where DNA content returned to normal level. In these two experimental groups, protein/DNA and RNA/DNA ratios were higher than those of controls at 10 days and lower at 35 days. In hypothyroid animals treated by corrective doses of T4, cerebellar protein, RNA and DNA contents and DNA concentration were not different from hyperthyroid animal values at all stages, while protein/DNA and RNA/DNA ratios were higher than those of hyperthyroid animals. Administration of physiological doses of T4 to hypothyroid animals led to the same effects as higher doses in normal animals. Thus, neonatal hypothyroidism seems to lower the sensitivity threshold of the cerebellum to thyroid hormone effects.

Age Factors↗