Thymine 7-hydroxylase from Neurospora crassa. Substrate specificity studies.

A partially purified preparation of thymine 7-hydroxylase (thymine, 2-oxoglutarate : oxygen oxidoreductase (7-hydroxylating), EC 1.14.11.6) from Neurospora crassa was incubated with a number of pyrimidines chemically related to tyymine. 1. Pyrimidines with oxygen or sulfur substituents on atoms Nos. 2 and 4 as well as an alkyl group on atom Nos. 1 or 5 were substrates. 2. Km values were determined for 1-methyluracil, 1-ethyluracil, thymine, 6-azathymine, 1-methylthymine, 1-ethylthymine, 5-formyluracil and 5-hydroxymethyluracil. 3. Uracil was identified as one of the metabolites after incubation with 1-methyluracil. The one-carbon metabolite has not been characterized. 4. Several pyrimidines with polar groups on atoms Nos. 2 and 4 were inhibitory. 5. Addition of 1-methyluracil, 1-methylthymine, 1-ethylthymine or 5-hydroxymethyluracil to incubations with thymine and 2-oxo[1-14C1]glutarate did not result in additional formation of 14CO2, indicating that the same enzyme acts on the different compounds. It has previously been found (Bankel, L., Holme, E., Lindstedt, G. and Lindstedt, S. (1972) FEBS Lett. 21, 135-138) that a mutant strain of N. crassa which is devoid of thymine 7-hydroxylase activity also lacks ability to perform the coupled oxygenation of 2-oxoglutarate and 1-methyluracil, 5-hydroxymethyluracil and 5-formyluracil, respectively. It is concluded that one and the same oxygenase is responsible for the activities studied.

The pituitary-gonadal axis and health in elderly men: a study of men born in 1913.

The results of recent studies suggest that a relative hypogonadism in men is associated with several established risk factors for prevalent diseases. Therefore, we determined total and free testosterone, luteinizing hormone (LH), and sex-hormone binding globulin (SHBG) in a cohort of randomly selected men (n = 659) at 67 years of age. These data were analyzed cross-sectionally in relation to blood glucose and serum insulin, which were measured while fasting and after an oral glucose tolerance test, in addition to plasma lipids and blood pressure. The data were also analyzed in relation to impaired glucose tolerance (IGT) and diabetes, which were discovered at examination or earlier diagnosis. Risk factors for the development of diabetes up to 80 years of age were analyzed with univariate and multivariate statistics. Total and free testosterone and SHBG concentrations correlated negatively with glucose and insulin values; total testosterone and SHBG, with triglycerides; and SHBG, with blood pressure (from P < 0.05 to P < 0.01). Men with IGT or newly diagnosed diabetes had higher BMI values (26.2 +/- 0.31 and 27.0 +/- 0.59 [mean +/- SE], respectively) and waist circumference (99.0 +/- 1.03 and 100.5 +/- 1.57) than nondiabetic men (BMI, 25.1 +/- 0.14; waist circumference, 95.4 +/- 0.47; P < 0.05), indicating abdominal obesity. Such men and men with previously diagnosed diabetes had, in general, lower total and free testosterone and SHBG levels, while those for LH were not different. In multivariate analyses that included BMI, waist-to-hip ratio, total and free testosterone, and SHBG, the remaining independent predictors for the development of diabetes were low total testosterone (P = 0.015) and, on the borderline, low SHBG (P = 0.053). In relation to nondiabetic men, the risk ratio for mortality, myocardial infarction, and stroke increased gradually and significantly from 1.18 to 1.68, from 1.51 to 1.78, and from 1.72 to 2.46 in men with IGT, newly diagnosed diabetes, and previously known diabetes, respectively. It was concluded that low testosterone and SHBG concentrations in elderly men are associated with established risk factors for diabetes and in established diabetes. Moreover, low testosterone levels independently predict the risk of developing diabetes. In different degrees of expression, the diabetic state predicts strongly (and gradually mortality from) myocardial infarction and stroke. It has been suggested that a relative hypogonadism might be a primary event, because other studies have shown that testosterone deficiency is followed by insulin resistance, which is ameliorated by testosterone substitution. The data suggest that the relative hypogonadism involved might be of both central and peripheral origin.

Low sex-hormone-binding globulin concentration as independent risk factor for development of NIDDM. 12-yr follow-up of population study of women in Gothenburg, Sweden.

Serum sex-hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) concentrations were evaluated as risk factors for the development of non-insulin-dependent diabetes mellitus (NIDDM), myocardial infarction, stroke, and premature death in a prospective study of 1462 randomly selected women, aged 38-60 yr, over 12 yr of observation. In multivariate analysis, taking only age into consideration as a confounding factor, low initial concentration of SHBG was significantly correlated to the incidence of NIDDM and stroke, and high initial concentration of CBG was correlated to the incidence of NIDDM. There were also significant correlations between SHBG and CBG concentrations on one hand and possible risk factors for the end points studied, such as serum triglycerides, serum cholesterol, fasting blood glucose, body mass, body mass index, waist/hip ratio, smoking habits, and systolic blood pressure, on the other. When these possible confounders, in addition to age, were taken into consideration in multivariate analyses, only the inverse significant correlation between SHBG and NIDDM remained. The increased incidence of diabetes was confined to the lowest quintile of SHBG values, where it was 5-fold higher than in the remaining group. This incidence was further increased to 8- and 11-fold in the lowest 10 and 5% of the values, respectively. We conclude that SHBG is a uniquely strong independent risk factor for the development of NIDDM in women.

The risk of cardiovascular death in elderly patients with possible heart failure. Results from a 6-year follow-up of a Swedish primary care population.

UNLABELLED: Little is known about the prognosis and clinical variables influencing the prognosis among elderly patients in primary health care with mild to moderate heart failure. AIM: To evaluate the risk of cardiovascular mortality in elderly patients with symptoms of heart failure with respect to systolic and diastolic function, and functional impairment. To evaluate prognostic determinants and to risk-stratify the patients. METHODS: A cardiologist examined 510 patients, out of 548 invited, attending primary care for symptoms of dyspnoea, fatigue and/or peripheral oedema and assessed New York Heart Association (NYHA) functional class. Examination by Doppler echocardiography was done in 454 patients, 56 patients being excluded because of, e.g., atrial fibrillation. Abnormal systolic function was defined as ejection fraction<40%. The diastolic function was evaluated using the mitral inflow and pulmonary venous flow variables. Different clinical and echocardiographic variables were analysed using a Cox regression analysis to identify those most influencing the risk of cardiovascular mortality. CONCLUSION: Abnormal systolic and/or diastolic function was found in 219 patients (48% of the 454 patients who could be echocardiographically completely investigated). The follow-up period was 6 years. Total mortality was 20%, and cardiovascular mortality was 14% (70% of total mortality). Cardiovascular mortality was high in patients with severely impaired functional capacity and ejection fraction<40% at the start of the study. Risk variables identified were male gender, diabetes mellitus, impaired functional capacity and abnormal cardiac function by echocardiography. A prognostic score model using simple clinical variables (gender, NYHA class, cardiac function) was developed to assess the risk of cardiovascular death in order to identify patients with high, moderate or low risk. In a ROC curve analysis, the AUC for clinical variables was only 0.75, whereas the AUC for clinical variables and echocardiography was 0.78, indicating that the additional prognostic information obtained by Doppler echocardiography was rather small.

Risk of cardiovascular death in elderly patients with possible heart failure. B-type natriuretic peptide (BNP) and the aminoterminal fragment of ProBNP (N-terminal proBNP) as prognostic indicators in a 6-year follow-up of a primary care population.

UNLABELLED: Heart failure is common in the elderly population and carries a serious prognosis. We evaluated EDTA-plasma B-type natriuretic peptide (brain natriuretic peptide, BNP) and the aminoterminal fragment of proBNP (N-terminal proBNP) as prognostic markers in elderly primary care patients with symptoms of heart failure. METHODS: From 474 patients attending primary care for symptoms of dyspnea, fatigue and/or peripheral edema, blood was sampled in plastic tubes containing EDTA to measure BNP by non-extraction immunoradiometric assay and N-terminal proBNP by non-extraction radioimmunoassay. Patients were evaluated with respect to history and function by NYHA classification and Doppler echocardiography. Follow-up time was 6 years. Cox regression analysis was performed to identify the weight of risk variables. CONCLUSION: Total 6-year mortality was 20% (102 patients out of 510), and cardiovascular (CV) mortality was 14% (71 patients, 70% of total mortality). BNP and N-terminal proBNP were essentially equally useful as prognostic markers. In patients with the highest quartiles of plasma concentration of BNP and N-terminal proBNP, respectively, the risk of cardiovascular mortality was 10 and 4.8 times, respectively, higher than that in those in the lowest quartile. Peptide concentrations varied widely within all functional groups including those with normal echocardiographic findings. Plasma concentrations of BNP and N-terminal proBNP give important prognostic information concerning risk of cardiovascular mortality. Cost-effective "clinical pathways" should be outlined for patients with elevated peptide concentrations.

Morbidity, mortality, and quality of life for patients treated with levothyroxine.

In a population study of 1462 middle-aged women initiated in 1968 and 1969 we identified 29 women treated with levothyroxine from 1 to 28 years. In a 12-year follow-up in 1980 and 1981 we investigated the subjects for end-point myocardial infarction, diabetes mellitus, stroke, cancer, and death (the status of 99.7% of the initial participants was established). The women treated with levothyroxine showed no increase in morbidity or mortality. Of the 24 women still receiving levothyroxine in 1980 and 1981, 22 had serum thyrotropin and triiodothyronine concentrations with-in reference limits. These individuals were compared with the 968 women from the population study having no history of thyroid disease, and appeared identical as to laboratory and clinical data, with the exception of a slightly higher body mass, taller stature, and lower serum cholesterol concentration. The treated group did not differ in a life quality estimate based on 19 questions regarding life satisfaction and sensory function. We conclude that the levothyroxine-treated woman suffers no side effects from her life-long therapy.

Clinical significance of low serum thyrotropin concentration by chemiluminometric assay in 85-year-old women and men.

The prevalence and causes of low serum thyrotropin concentration were studied in 886 individuals at age 85 years (601 women and 285 men). All participants were subject to detailed clinical and biochemical evaluation, including determination of serum thyrotropin and free thyroxine concentrations by chemiluminometric assays. Samples with thyrotropin concentrations below 0.20 mU/L or above 6.0 mU/L and/or free thryoxine concentrations above 22.0 pmol/L were selected for further assays. These selected individuals were followed-up during 3 years. Of 18 individuals without thyroid hormone treatment who had thyrotropin concentrations less than 0.20 pmol/L (13 below 0.10 pmol/L), only two were proved to be hyperthyroid; in another three, hyperthyroidism could not be excluded. The results indicate that most elderly individuals with low serum thyrotropin concentrations are not hyperthyroid and that abnormal thyroxine-binding globulin (in conjunction with drug treatment or nonthyroidal illness) is not a common cause of low thyrotropin concentration.

Carbohydrate-deficient transferrin is associated with insulin sensitivity in hypertensive men.

An elevated concentration of carbohydrate-deficient transferrin in serum (CDT) has been reported to indicate excessive ethanol consumption. However, in hypertensive men, we found low values for diagnostic sensitivity and specificity. Furthermore, in the individuals with high CDT values, the concentrations of serum triglycerides and blood glucose were low rather than high, indicating that factors related to insulin/glucose metabolism may be operative. The current study addresses this issue by examining 48 patients with treated hypertension and at least 1 of following: hypercholesterolemia, history of smoking, and diabetes mellitus. We determined serum CDT, fasting plasma insulin, and glucose disposal rate during hyperinsulinemic euglycemic clamp. Seven patients had elevated CDT concentrations. This group of patients had higher glucose disposal rates than the others (mean difference, 19 mumol/min.kg lean body mass; 95% confidence interval, 5-33 mumol/min.kg lean body mass; P = 0.0096), but did not differ in body mass index or alcohol intake. Serum CDT correlated positively with glucose disposal rate (r = 0.55; P = 0.0004) and negatively with fasting plasma insulin (r = -0.43; P = 0.0039). These relationships remained after exclusion of 8 patients with diabetes mellitus and adjustment for potentially confounding factors. We conclude that the serum CDT concentrations in our patients were associated with insulin sensitivity.

Treatment of adults with growth hormone (GH) deficiency with recombinant human GH.

In a double blind, cross-over placebo-controlled trial, we studied the effects of 26 weeks of replacement therapy with recombinant human GH on body composition, metabolic parameters, and well-being in 10 patients with adult-onset GH deficiency (GHD). All patients received appropriate thyroid, adrenal, and gonadal replacement therapy. The dose of recombinant human GH was 0.25-0.5 U/kg.week (0.013-0.026 mg/kg.day) and was administered sc daily at bedtime. One patient was withdrawn from the study because of edema and atrial fibrillation. Body composition was estimated with three independent methods: computed tomography, bioelectric impedance, and total body potassium combined with total body water assessments. The Comprehensive Psychological Rating Scale and the Symptom Check List-90 were used to assess any change in psychopathology. After 26 weeks of treatment, adipose tissue (AT) mass decreased 4.7 kg (P < 0.001). Subcutaneous AT decreased by an average of 13%, whereas visceral AT was reduced by 30%. Muscle volume increased by 2.5 kg (5%; P < 0.05). According to the four-compartment model derived from assessments of total body potassium and total body water, body cell mass and extracellular fluid volume increased significantly by 1.6 and 3.0 kg, whereas body fat decreased by 6.1 kg. Results obtained by the bioelectric impedance technique were similar. The mean (+/- SD) concentrations of insulin-like growth factor-I increased from 0.26 (0.06) at baseline to 2.56 (1.55) and 2.09 (1.03) kU/L after 6 and 26 weeks of treatment. Calcium and serum phosphate, osteocalcin, and procollagen-III concentrations were significantly higher, and intact PTH concentrations were reduced after 6 and 26 weeks of treatment, respectively. Total and free T3 concentrations were significantly increased after 6 and 26 weeks of treatment, whereas free T4 concentrations were reduced at 6 weeks, but after 26 weeks, free T4 concentrations had returned to pretreatment values. Finally, after 26 weeks of treatment, there was a decrease in the Comprehensive Psychological Rating Scale score (P < 0.05). The results show that GH replacement in GHD adults results in marked alterations in body composition, fat distribution, and bone and mineral metabolism and reduces psychiatric symptoms. Finally, we conclude that the observed beneficial effects of replacement therapy with GH are of sufficient magnitude to consider treatment of GHD adults.

Alpha-2-adrenoceptor sensitivity in early alcohol withdrawal.

Growth hormone (GH), blood pressure, and pulse rate responses to clonidine (100 micrograms IV) were studied three times during the first week of alcohol withdrawal in 19 alcohol-dependent patients. Fifteen healthy men were used as controls. The results suggest reduced sensitivity of the alpha-2-adrenoceptors involved in GH secretion for at least 1 week after the end of alcohol intake. In contrast, very short-lasting subsensitivity was found in the alpha-2-adrenoceptors regulating blood pressure.

Independent relationship between microalbuminuria and plasminogen activator inhibitor-1 activity (PAI-1) activity in clinically healthy 58-year-old men.

The aim of this cross-sectional study was to investigate the relationship between low-grade albuminuria (microalbuminuria) and factors of the coagulation- and fibrinolysis systems in 104 clinically healthy 58-year-old men recruited from the general population. Urinary albumin excretion was significantly associated with body mass index, systolic and diastolic blood pressure, plasminogen activator inhibitor (PAI)-1 activity, tissue plasminogen activator (tPA) antigen, tPA activity (negatively) and protein S (P<0.05). There were no associations between urinary albumin excretion and antithrombin III, fibrinogen, protein C, thrombin/antithrombin factor or von Willebrand factor. In multiple regression analysis urinary albumin excretion was independently and significantly associated with PAI-1 activity and systolic blood pressure (P<0.05). In conclusion we report that urinary albumin excretion was independently and significantly associated with PAI-1 activity in clinically healthy 58-year-old men. This relationship may contribute to the previously reported increased cardiovascular morbidity in subjects with microalbuminuria.

Systemic radionuclide therapy using indium-111-DTPA-D-Phe1-octreotide in midgut carcinoid syndrome.

A 55-yr-old woman with a midgut carcinoid syndrome due to metastatic spread of an ileal tumor to the liver, paraortic and mediastinal lymph nodes and to the skeleton was given systemic radionuclide therapy with 111In-DTPA-D-Phe1-octreotide. Before therapy, dosimetric calculations were performed on whole-body scintigraphs and 111In retention was shown to be long-lasting. Excretion was mainly seen during the first 24 hr after injection; thereafter whole-body retention remained stationary at 30%. Indium-111 activity in tumor biopsies and blood was measured using a gamma counter. Very high tumor-to-blood ratios were obtained: 150 for the primary tumor and 400-650 for liver metastases, which further justified radiation therapy. Indium-111-DTPA-D-Phe1-octreotide treatment was given on three separate occasions (3.0, 3.5 and 3.1 GBq) 8 and 4 wk apart. After each therapy, the patient experienced facial flush and pain over the skeletal lesions followed by symptomatic relief, even though no objective tumor regression was found radiologically after 5 mo. After initiation of octreotide treatment, there was a 14% reduction of the main tumor marker, urinary 5-HIAA. After three subsequent radionuclide therapies, there was a further 31% reduction of 5-HIAA levels. No adverse reactions, other than a slight decrease in leukocyte counts, were seen. The mean absorbed radiation dose after the three treatments was estimated to be about 10-12 Gy in liver metastases and 3-6 Gy in other tumors, depending on the size and location of the metastases. Assuming internalization of 111In into tumor cells and a radiobiological effect from short range Auger and conversion electrons, there might be a therapeutic effect on the tumor.

Guanfacine as an alpha-2-agonist inducer of growth hormone secretion--a comparison with clonidine.

Doses of 0.5 mg and 1.0 mg of the alpha-2-adrenoceptor agonist guanfacine (GUA) and NaCl were administered intravenously (IV) in a randomized order to 18 healthy male subjects. GUA induced growth hormone (GH) secretion in a dose-dependent manner without affecting blood pressure or heart rate or inducing sedation. The effects of GUA 1.5 mg i.v. was compared with those of another alpha-2-adrenoceptor agonist, clonidine (CLON) 150 micrograms i.v. in six other male volunteers. Both alpha-2-agonists increased GH to similar levels. CLON reduced both systolic and diastolic blood pressure levels, whereas GUA reduced only systolic levels. Sedation was significantly more pronounced after CLON. The results suggest that the GUA/GH-test (1.5 mg GUA i.v.) may be an alternative to the CLON/GH-test in neuroendocrine assessment of alpha-2-adrenoceptor sensitivity.

Treatment-resistant mania with primary hypothyroidism: a case of recovery after levothyroxine.

A manic-depressive woman was unresponsive to treatment with lithium and neuroleptics during a period of mania. Additional levothyroxine treatment of her primary hypothyroidism resulted in rapid and complete recovery from her mania.

Effects of long-term antihypertensive treatment and aging on renal function and albumin excretion in primary hypertension.

The effects on renal function and urinary albumin excretion of 7 years of antihypertensive treatment compared to the effects of normal aging were studied in a random sample of 40 men with newly diagnosed primary hypertension and in 17 normotensive men of the same age, respectively. The hypertensives were treated with metoprolol either as monotherapy (n = 21) or combined with hydrochlorothiazide or hydralazine. Glomerular filtration rate (GFR; inulin clearance), renal blood flow (RBF; para-aminohippurate clearance), renal vascular resistance (RVR), and the 24 h urinary albumin excretion were determined. GFR was significantly reduced from 104 +/- 15 mL/min (mean +/- SD) to 86 +/- 20 mL/min (P < .001) in the hypertensive group, but the reduction was not significantly greater than in the normotensive group. As judged from the study of a subgroup of the hypertensives, most of the decrease in GFR occurred early as an immediate drug-induced, functionally explained decrease. The changes in RBF and RVR after 7 years of treatment did not differ significantly from those due to normal aging. RVR remained higher and RBF remained lower in the hypertensives than in the normotensives. The urinary albumin excretion in the hypertensives was significantly reduced after 7 years but remained higher than in the normotensives. In conclusion, the changes in renal function and hemodynamics seen after long-term treatment with metoprolol in primary hypertension were not significantly different from the changes caused by normal aging in normotensives.

Changes in dopamine receptor sensitivity in humans after heavy alcohol intake.

Dopamine (DA) sensitivity, assessed through maximal growth hormone (GH) response to stimulation by apomorphine (APO) (0.18-0.24 mg iv) was studied in 16 chronic alcoholics newly admitted after a period of heavy alcohol intake. Repeated hormonal tests were thereafter performed during a 2-month period under strictly controlled conditions to avoid relapse into alcohol consumption. Eight healthy volunteers with alcohol consumption slightly less than that of the general population were used as controls. It was found that DA sensitivity in the early abstinence phase was higher than later in the 2-month recovery period but not significantly different from control values. The relatively higher DA sensitivity in the early abstinence phase might be responsible for a lower threshold for psychotic symptoms and neuroleptic-induced extrapyramidal side effects. The results of this study give further evidence of a prolonged recovery phase after heavy alcohol intake.

Neuroendocrine evidence for increased responsiveness of dopamine receptors in humans following electroconvulsive therapy.

The previous finding that electroconvulsive therapy (ECT) enhances effects of dopamine (DA) agonists was further investigated in the present clinical experiment using neuroendocrine techniques. Apomorphine chloride (AP) (0.18-0.24 mg IV) induced stimulation of growth hormone (GH) and suppression of prolactin (PRL), as shown 2-3 days before and after ECT in mentally depressed patients (N = 12) and therapy-resistant parkinsonian patients with on-off phenomena (N = 9). AP-stimulated GH secretion was not significantly affected by ECT, whereas AP-induced suppression of PRL, expressed as percentage of baseline PRL levels, was significantly enhanced after ECT. Changes in clinical and hormonal parameters were not significantly correlated. Control patients not receiving ECT showed no significant changes in AP-induced GH secretion or PRL suppression in repeated investigations. The results support the view that ECT increases responsiveness of DA receptors and indicates that AP-induced suppression of PRL is a useful model to reflect these changes in humans.

Disodium pamidronate in the preoperative treatment of hypercalcemia in patients with primary hyperparathyroidism.

Nine patients (median age, 81 years) with primary hyperparathyroidism were treated with intravenous infusions of disodium pamidronate (APD), which is a bisphosphonate drug. Six patients had severe hypercalcemia (serum calcium concentration, greater than 3 mmol/L) persisting after rehydration with saline and treatment with furosemide; three patients had moderate hypercalcemia with pronounced symptoms (serum calcium concentration 2.8 to 2.9 mmol/L). Three of the patients were considered to have hypercalcemic crises. In all patients, the raised serum calcium levels were lowered by the disodium pamidronate infusions. One week after a single infusion of 15 to 60 mg disodium pamidronate, six of the nine patients had serum calcium concentrations within the normal reference interval and two patients had slightly raised values. Transient asymptomatic hypocalcemia was noted in one patient. All patients tolerated the infusions well, and no side effects were noted. In the patients with verified parathyroid adenomas, a temporary increase in parathyroid hormone levels were observed concomitant with the drop in serum calcium level. The patient with parathyroid cancer displayed no such effect indicating an autonomous parathyroid hormone secretion from the parathyroid carcinoma tumor. The good effect of treatment with the osteoclast inhibitor disodium pamidronate on hypercalcemia caused by primary hyperparathyroidism suggests that this hypercalcemia is mainly due to an increased osteoclast activity. The number of patients in this series is yet too small to allow general conclusions. But the case histories in this series show that disodium pamidronate promises to be of value in different clinical situations for the treatment of severe hypercalcemia in patients with hyperparathyroidism. It can be used (1) preoperatively to investigate whether the patient's symptoms are related to the hypercalcemia, (2) in the treatment of hypercalcemic crises when "forced diuresis" has failed to normalize the serum calcium, (3) after unsuccessful parathyroid surgery when it can be used as a long-term treatment before reoperation, giving time for localization studies and healing of the scar reaction, and (4) in aged and fragile patients where it can be tried as an alternative to surgery.

Thyroid hormones and lipolysis in physically trained rats.

In rats a single bout of exercise resulted in increased triiodothyronine (T3), thyroxine (T4), and triiodothyronine/reverse triiodothyronine (T3/rT3) ratio 20 hr after exercise. The effect of norepinephrine on lipolysis in vitro was potentiated. In trained rats no changes were found in T4, T3, or rT3 concentrations. The T3/rT3 ratio as well as basal and stimulated TSH concentrations decreased in comparison with sedentary, freely eating rats. Moderate food restriction to produce a body weight similar to that of trained animals caused no changes in T4, T3, or rT3 concentrations but caused a decrease in T3/rT3 and in TSH levels. Training and moderate food restriction groups were not different. T3 in vitro caused a potentiation of catecholamine induced lipolysis in trained and food-restricted animals. With aging the serum concentration of T3 decreased and that of rT3 increased. Acute and chronic exercise both exert an effect on peripheral hormonal responses of lipolysis, while they have different and opposite effects on thyroid hormone concentrations. Physical training seems to have effects in this regard similar to those of moderate energy intake restriction. The results suggest that changes in peripheral effects of thyroid hormones during training should attract more attention.

Urinary excretion of 3-methylhistidine and creatinine and plasma concentrations of amino acids in hyperthyroid patients following preoperative treatment with antithyroid drug or beta-blocking agent: results from a prospective, randomized study.

The aim of this investigation was to compare the effects of a beta 1-selective adrenoceptor blocking agent and an antithyroid drug on urinary excretion of creatinine (Cr) and 3-methylhistidine (3-MH) and plasma concentrations of amino acids in hyperthyroid patients. beta-adrenoceptor blocking agents are increasingly used in the treatment of hyperthyroid patients, and the effects on clinical signs and symptoms mainly reflect beta 1-adrenoceptor blockade. The consequences of this treatment on metabolic alterations in hyperthyroidism are not fully known. In the present study, 30 hyperthyroid patients were randomized to preoperative treatment with the antithyroid drug methimazole + thyroxine (group I) or the beta 1-selective adrenoceptor blocking agent metoprolol (group II). Urinary excretion of Cr and 3-MH and plasma concentrations of amino acids were measured at the time of diagnosis, following preoperative treatment and 6 months postoperatively. Serum triiodothyronine (T3) was comparably elevated in the two groups of patients at the time of diagnosis and was normalized during preoperative treatment in group I but remained elevated during preoperative treatment in group II. Urinary excretion of creatinine was lower at the time of diagnosis than postoperatively, suggesting reduced muscle mass during hyperthyroidism. Urinary excretion of Cr increased during preoperative treatment in group I but was not significantly altered during treatment with metoprolol. The 3-MH/Cr ratio, which was higher at the time of diagnosis than postoperatively, indicating accelerated protein breakdown in skeletal muscle during hyperthyroidism, was reduced during preoperative treatment in group I but not in group II.(ABSTRACT TRUNCATED AT 250 WORDS)