Effect of various beta-adrenolytic drugs on heart rate and changes in left-ventricular systolic time intervals in patients with hyperthyroidism and simple goiter

The effects of a short-term application of various beta-adrenolytic drugs on heart rate and on the changes in subperiods of left ventricle contraction have been studied in 71 patients with untreated hyperthyroidism and in 72 patients with simple goiter. The following drugs were used: propranolol, metoprolol, atenolol, pindolol, nadolol and acebutolol. It was found that those betaadrenolytic drugs which have no sympathomimetic action cause a significant decrease in heart rate both in patients with hyperthyroidism and in those with simple goiter. The effect of these drugs on heart rate was not related to the changes in blood serum concentrations of thyroxine and triiodothyronine. None of the drugs tested influenced appreciably the contraction subperiods of left heart ventricle, both in the patients with hyperthyroidism and in those with simple goiter.     

Effect of Epoprostenol on The Thyroid Gland: Enlargement and Secretion of Thyroid Hormone

ObjectiveTo demonstrate the direct stimulation of thyroid tissue in the absence of thyroid-stimulating immunoglobulin after exposure to epoprostenol.MethodsSeronegative thyrotoxicosis, diffuse goiter, and homogeneous uptake on thyroid scintigraphy were noted in a patient with pulmonary arterial hypertension (PAH) being treated with intravenously administered epoprostenol (prostaglandin I₂ or PGI₂). More cases with similar characteristics were identified on review of the thyroid function in patients with PAH who were treated with this medication. Fifty-four adult patients with PAH were studied. The study subjects were divided into 2 groups based on whether they were treated with PGI₂ or not. Thyroid functions were reviewed, and the prevalence of thyroid disease was assessed. We then compared the prevalence of hyperthyroidism in our study subjects with the prevalence of hyperthyroidism in the general female population using data from published studies.ResultsWe noted a high prevalence (3 of 45 or 6.7%) of thyroid-stimulating immunoglobulin-negative thyrotoxicosis in adults with preexisting PAH being treated with epoprostenol (PGI₂) in the absence of other mechanisms or drugs to explain the hyperthyroidism. The prevalence of hyperthyroidism in our study population was significantly greater (P < .01 by χ² analysis) than that in the general female population in other published reports.ConclusionThe data suggest that epoprostenol is a medication associated with stimulation of thyroid tissue, goiter formation, and hyperthyroidism. Patients receiving this drug need to undergo close follow-up for the development of thyrotoxicosis and goiter. (Endocr Pract. 2009; 15:116-121)     

Effect of propranolol on glucose disposal rate in patients with hyperthyroidism

The effect of propranolol treatment (60 mg per day, three days) on glucose disposal rate (K-value) was investigated in nine patients with hyperthyroidism. K-value was improved in 4 cases and aggravated in 5 cases. The fasting levels of plasma free fatty acids (FFA) before the administration of propranolol in the improved cases were significantly higher than those in the aggravated cases. The propranolol treatment markedly reduced FFA levels only in the improved cases. These results suggest that the impaired glucose tolerance frequently seen in hyperthyroidism patients could be partly attributed to the increased level of plasma FFA.     

Arterial hypertension associated with hyper and hypothyroidism]

45 patients with hyper and hypothyroidism in the time 1989-1990 were observed. The Graves' disease was diagnosed in 29 and rather in the younger patients, but 16 had the toxic nodular goiter and those were elderly. In 27 the hypertension was secondary (symptomatic) and after the successful treatment of the hyperthyroidism was completely controlled. In 14 cases the hypertension was primary (essential) and the application of the hypotensive drugs was also necessary. Among 4 patients with primary hypothyroidism and associated hypertension and coronary insufficiency the early treatment by the thyroid preparation was successful: the blood pressure was lowered and the coronary insufficiency was improved; but if the replacement therapy was stopped and the hypothyroidism was relapsed, the blood pressure was increases and the coronary insufficiency was aggravated. Conclusions: 1. The secondary (symptomatic) hypertension associated with the hyperthyroidism may be controlled by successful treatment of the thyrotoxicosis, but the primary (essential) must be treated by the hypotensive drugs also. 2. The early treatment of the hypothyroidism may control the associated hypertension and the coronary insufficiency. 3. Graves' disease is associated mostly with symptomatic hypertension, in nodular toxic goiter in most of the cases the essential hypertension was established.     

Acetylation phenotype and the changes in selected indicators of calcium-phosphate metabolism in patients with hyperthyroidism treated with propranolol

The occurrence of acetylation phenotype has been studied in 76 patients with untreated hyperthyroidism. In 23 of these patients having the "fast" and in 42 having the "slow" acetylation phenotype the selected parameters of calcium-phosphate metabolism have been determined before, during and after propranolol therapy lasting six days. Propranolol was administered at a dose of 160 milligrams daily. A significant decrease in the blood serum level of calcium and urinary calcium excretion following propranolol administration was found only in patients with hypercalcemia and hypercalciuria. On the other hand, a significant decrease in the urinary excretion of hydroxyproline was observed in all the patients with hyperthyroidism treated with propranolol. The effect of propranolol on the measured parameters of calcium-phosphorus metabolism was similar in hyperthyroid patients with both "fast" and "slow" acetylation phenotypes, what suggests that it does not depend on the N-acetyltransferase activity.     

Haemodynamic effects of beta-adrenergic blockade in hyperthyroid patients with and without heart failure.

Haemodynamic studies were performed in 10 patients with uncomplicated thyrotoxicosis and seven with thyrotoxic cardiac failure. The cardiac output of those with uncomplicated hyperthyroidism was higher than normal at rest. After 2 mg of intravenous propranolol there was a 13% fall but the level was still higher than normal. In patients with thyrotoxic cardiac failure the resting cardiac output was normal, but it fell after propranolol by 30% to subnormal levels. In both groups there was an increase in right heart pressures and fall in the rate of increase in arterial pressure, which indicated a decrease in myocardial contractility. These results indicate that increased autonomic activity is a compensatory phenomenon in hyperthyroid heart failure and that its abolition by beta-blocking drugs has a deleterious effect on cardiac function. They are therefore contraindicated in patients with thyrotoxic heart failure.     

Effect of propranolol on electrophysiologic features of the heart in patients with hyperthyroidism]

The effect of increasing doses of intravenously administered propranolol on electrophysiological features of heart was studied in 17 patients with untreated hyperthyroidism by using the transesophageal stimulation method. A positive and dose-dependent effect of propranolol on the studied parameters was found with the normalization of the majority of disturbances taking place after the administration of 6 mg of propranolol. This dose was safe and well tolerated by the patients. The sensitivity of the auriculo-ventricular junction to propranolol was less pronounced during the stimulated rhythm than during the sinus rhythm.     

Attenuation of hypotensive effect of propranolol and thiazide diuretics by indomethacin.

The effects of 100 mg indomethacin daily for three weeks on blood pressure and urinary excretion of prostaglandin F2 alpha were studied in a double-blind, placebo-controlled comparison of two groups of patients with essential hypertension, eight receiving propranolol and seven thiazide diuretics. Compared with placebo, adding indomethacin to the patients'' established antihypertensive treatment increased blood pressure by 14/5 Hg supine and 16/9 mm Hg erect in the patients receiving propranolol, and by 13/9 mm Hg supine and 16/9 mm Hg erect in the patients receiving thiazide diuretics (all p less than or equal to 0.05). The excretion of the major urinary metabolite of prostaglandin F2 alpha was reduced by 67% in the propranolol-treated patients and by 57% in those receiving a thiazide diuretic. Body weight increased by 0 . 8 kg (propranolol) and 1 . 1 kg (thiazide diuretic) when indomethacin was given, but there were no significant changes in creatinine clearance, urinary sodium excretion, or packed cell volume in either treatment group. These results suggest that products formed by the arachidonic acid cyclo-oxygenase contribute to the regulation of blood pressure during treatment with both propranolol and thiazide diuretics. Inhibition of the cyclo-oxygenase with indomethacin partially antagonises the hypotensive effect of these drugs.     

Evaluation of the phagocytic activity of peripheral blood neutrophils in patients with hyperthyroidism

In 80 women with hyperthyroidism (40 with diagnosed Graves disease and 40 with hyperactive nodular goiter) the following tests related to the function of peripheral blood neutrophils have been carried out: 1. nitrotetrazolium blue (NRT) reduction test. 2. evaluation of phagocyting activity by using latex particles and living bacteria cells, and 3. determination of immunoglobulin concentration and the C3 component of the complement in blood serum. The following features were found in the patients with hyperthyroidism: 1. the elevated values of the index of spontaneous NBT reduction which return to normal following the treatment with propranolol or metizol lasting 14 days, 2. a decrease in the phagocyting activity of neutrophils occurring with stimulation of phagocytosis by both the latex particles and bacteria cells. 3. the return to normal values of the index of neutrophils phagocyting the latex particles following two-week treatment with propranolol or metizol. It was concluded that in patients with hyperthyroidism the changes in NRT reduction and phagocyting activity of peripheral blood neutrophils return to normal following the two-week treatment of these patients with both propranolol and metizol.     

10 years of successful treatment with dextrothyroxine in a girl with TSH-induced hyperthyroidism.

14 years ago, a 5.7-year-old healthy girl was treated with desiccated thyroid for a goiter and elevated TSH levels. The goiter disappeared and TSH levels were normalized. However, hyperthyroidism appeared. Without therapy, the goiter reappeared and hyperthyroidism aggravated. Based on hormone values, TSH-induced hyperthyroidism was diagnosed. After exclusion of neoplastic TSH secretion, treatment with dextrothyroxine (DT4) was initiated at age of 10 years and continued during the last 10 years (except for short periods). The girl became euthyroid, has no goiter and normal TSH values. Since thyrotrophs and peripheral tissues are probably normally sensitive to T4, we postulate that her hypothalamopituitary-thyroid control is operating on a higher set point level for T4.     

Thyroid cancer in patients with hyperthyroidism

Thyroid cancer can be associated with thyrotoxicosis caused by Graves' disease, toxic multinodular goiter, or autonomously functioning thyroid adenoma. The objective of this study was to summarize current evidence regarding the association of thyroid cancer and hyperthyroidism, particularly with respect to the type of hyperthyroidism found in some patients, and whether this affects the outcome of the patient. A PubMed search was performed up to August 2011. Articles were identified using combinations of the following keywords/phrases: thyroid cancer, papillary thyroid cancer, follicular thyroid cancer, medullary thyroid cancer, anaplastic thyroid cancer, hyperthyroidism, Graves' disease, auto-nomous adenoma, toxic thyroid nodule, and toxic multinodular goiter. Original research papers, case reports, and review articles were included. We concluded that the incidence, as well as the prognosis of thyroid cancer associated with hyperthyroidism is a matter of debate. It seems that Graves' disease is associated with larger, multifocal, and potentially more aggressive thyroid cancer than single hot nodules or multinodular toxic goiter. Patients with Graves' and thyroid nodules are at higher risk to develop thyroid cancer compared to patients with diffuse goiter. Every suspicious nodule associated with hyperthyroidism should be evaluated carefully.     

Effect of autonomic blockers on the heart rate of intact rats and animals with artificial hyperthyroidism.

The effect of various autonomic blockers on the heart rate (from the ECG recording) of intact rats and of animals with experimental hyperthyroidism induced by the administration of dried thyroid was studied. In intact rats, the heart rate fell significantly (by 22%) during the first week after the peroral administration of propranolol (0.05% in food), but trimepranol (0.02%), reserpine (0.001%) and guanethidine (0.1%) had no effect (in a suplementary experment, a small, but statistically significant decrease was also found after trimepranol). In experimental hyperthyroidism, using the same blocker doses, the heart rate fell significantly after propranolol (by 23%), trimepranol (22%), reserpine (16%) and, in a preliminary experiment, guanethidine (19%). On injecting 0.05 mg propranolol intravenously, the maximum drop in the heart rate in intact rats was 22%, while in hyperthyroidism it was hardly more than half this value (at all the intervals from 2 to 30 minutes the decrease was statistically significant). Practolol, in a dose of 0.3 mg i.v., was less effective -- in intact rats the heart rate fell by not more than 12% (at all the intervals from 2 to 30 minutes the decrease was significant), but in hyperthyroidism the drop was slower and statistically non-significant. The results do not furnish an unequivocal answer to the question of the role of adrenergic regulation of the heart rate under physiological conditions and in experimental hyperthyroidism in rats.     

Acetylation phenotype and serum levels of T3 and T4 in patients with hypertension treated with propranolol

The acetylation phenotype has been investigated in 76 patients with untreated hyperthyroidism. In 65 of these patients including 23 with fast and 42 with slow acetylation phenotype, the blood serum concentrations of thyroxine and triiodothyronine were determined before and after propranolol therapy involving propranolol administration of a dose of 160 mg per day for 6 days. The occurrence of the fast acetylation phenotype among the patients with hyperthyroidism was similar to that found in the healthy population. Propranolol therapy caused a significant decrease in the blood serum concentration of triiodothyronine only in the patients with the slow acetylation phenotype.     

D-propranolol and DL-propranolol both decrease conversion of L-thyroxine to L-triiodothyronine.

The effects of propranolol (DL-propranolol) and D-propranolol on thyroid hormone metabolism were studied in six euthyroid volunteers receiving L-thyroxine (T4) and six hypothyroid patients receiving T4 replacement. D-propranolol as well as propranolol decreased L-triiodothyronine (T3) concentrations and the ratio of T3 to T4 in the euthyroid subjects, and D-propranolol decreased these variables in the subjects with hypothyroidism (propranolol was not given to this group). It is concluded from this study and from parallel invitro investigations that the effect of propranolol on the conversion of T4 to T3 is unrelated to its beta-adrenergic blocking activity, and that at low therapeutic doses propranolol may exert appreciable "membrane-stabilising" effects in vivo.     

Changes in plasma fibronectin levels in thyroid diseases

The plasma levels of fibronectin (Fn) have been measured in normal subjects and in patients with thyroid diseases. The mean plasma Fn levels in 62 normal adults was 32.0 +/- 6.0 mg/dl, whereas it was elevated to 62.6 +/- 16.1 mg/dl (mean +/- SD) in 25 patients with hyperthyroidism and decreased to 19.2 +/- 8.0 mg/dl in 9 patients with hypothyroidism. The 9 patients with simple goiter have normal values of 29.1 +/- 8.0 mg/dl. With the administration of anti-thyroid drugs, plasma Fn levels normalized, with a time lag, in parallel with normalization of the thyroid function. Positive correlation was obtained between Fn levels and serum levels of triiodothyronine (T3) and thyroxine (T4). The present findings indicate that measurement of plasma Fn both in the basal state and during treatment provides evidence of altered Fn metabolism in thyroid diseases and serves to follow up the effect of treatment.     

Intérêt du dosage de la thyroglobulinémie chez les sujets porteurs du goitre en zones de déficience iodée au Bénin

In the present study, we analyze the results of thyroid hormones and thyroglobulinemia of 162 patients with goiter living in the departments of Collines and Donga, known to be areas of iodine deficiency in Benin. These results are compared with those of 85 healthy subjects living in the same departments. This study is a cross-sectional analytical study carried out from 1st July 2009 to 30th June 2010. The population of patients consisted of seven males and 155 females. The average age was of 45.7 years. Most of the patients were suffering of simple goiter. Only six of them had thyroid nodules. The diagnosis of biological hyperthyroidism was positive for 20 patients; 16 of them had subclinical hypothyroidism and four clinical hyperthyroidism. One case of clinical hypothyroidism was found. All other 141 patients were biologically normal (euthyroidism). Seventeen of the patients (including six patients presenting a thyroid nodule) had a normal thyroglobulin rate. Hyperthyroglobulinemia was observed in all other 145 patients. These results suggest that patients with goiter in zone of iodine deficiency are biologically euthyroid with hyper-thyroglobulinemia. Thyroglobulin dosage is then recommended, especially when nodules are perceptible.     

Relationship between clinical classification of hyperthyroidism for three grades of severity and level of triiodothyronine (T3) and thyroxine (T4) concentrations in serum]

The aim of the study was to assess the relationship between the clinical classification of hyperthyroidism based on the 3-degree score system and T3 and T4 serum concentration. 161 patients with Graves disease or toxic goiter were studied. By comparing the number of scores separating the 3 subgroups in relation to the severity of disease with T3 and T4 serum concentration of tyreotoxic patients we found a very high statistically significant correlation. We also found the marked (by +50%) statistically significant increase in the serum T3 concentration related to the degree of hyperthyroidism severity.     

High dose propranolol in the treatment of angina pectoris: relationship of dose to blood levels and hemodynamic consequences

Propranolol blood levels and the effect of these levels on hemodynamic parameters were evaluated in 25 patients with coronary artery disease undergoing cardiac catheterization and coronary angiography. Fifteen patients were receiving high doses of propranolol (320--1920 mg/day) while ten patients were receiving conventional doses (80--240 mg/day). The high dose propranolol group had significantly higher plasma propranolol levels than the conventional dose group (788 +/- 134 SD vs. 43 +/- 7.2 ng/ml SD), and there was a direct linear relationship between propranolol dose and plasma drug levels (r = 0.85, P < 0.001). There were no significant differences between high and conventional dose propranolol groups in terms of all hemodynamic parameters measured, namely ejection fraction, ventricular volume, cardiac index, or peripheral vascular resistance. Despite high drug dosage and blood levels, only mild side effects were seen.     

Function of the serotoninergic system of the thyrotoxic thyroid

The state of serotoninergic system in thyrotoxic and euthyroid gland were compared. It was shown that in patients with hyperthyroidism (diffuse toxic goiter) serotonin and 5-hydroxytryptophan content, velocity and the latter uptake were augmented. The authors stress the role of the delay in serotonin oxidative deamination as one of the reasons for increased serotonin content in thyrotoxic thyroid gland. Possible ways of increasing intrathyroid serotonin accumulation and its role in the development of thyroid hyperfunction are discussed.     

Effect of meal and propranolol on whole body and splanchnic oxygen consumption in patients with cirrhosis

Our aim was to measure whole body energy expenditure after a mixed liquid meal, with and without simultaneous propranolol infusion, in patients with cirrhosis. We also wanted to investigate the effect of propranolol on substrate fluxes and oxygen uptake in the tissues drained by the hepatic vein and azygos vein in the postprandial period in these patients. Whole-body oxygen uptake, hepatic blood flow, hepatic venous pressure gradient and net-hepatic fluxes of oxygen, lactate, glucose, glycerol, and free fatty acids (FFA) were measured in 12 patients with alcoholic cirrhosis before and for 2 h after ingestion of a mixed liquid meal (700 kcal). Half of the patients (n = 6) were randomized to a treatment group receiving intravenous infusion of propranolol in combination with the meal. The meal-induced energy expenditure was significantly lower in patients given propranolol [15.0 +/- 18.9 vs. 67.0 +/- 26.1 kJ/120 min (means +/- SD), P < 0.01]. Meal-induced whole body oxygen uptake was lower in patients receiving propranolol (19.2 +/- 38 vs. 135.7 +/- 61 mmol/120 min, P < 0.01), and the meal-induced increase in splanchnic oxygen uptake was nonexistent when propranolol was administered in combination (-13.2 +/- 34.8 vs. 110.4 +/- 34.8 mmol/120 min, P = 0.04). Postprandially, the propranolol group had a tendency toward a reduced splanchnic glucose output, and the FFA uptake was significantly reduced. Propranolol reduces meal-induced whole body oxygen uptake and energy expenditure as well as splanchnic oxygen uptake. The splanchnic reduction in oxygen consumption can explain almost the entire reduction in whole body oxygen consumption.