SUMMARY The effect of hypothyroidism on left ventricular function at rest and during exercise was studied in nine patients without demonstrable cardiovascular disease who had had total thyroidectomy and ablative radioiodine treatment for thyroid cancer. Radionuclide ventriculography and simultaneous right heart catheterisation were performed while the patients were hypothyroid two weeks after stopping triiodothyronine treatment (to permit routine screening for metastases) and while they were euthyroid on thyroxine replacement treatment. When the patients were hypothyroid, cardiac output, stroke volume, and end diastolic volume at rest were all lower and peripheral resistance was higher than when they were euthyroid. Pulmonary capillary wedge pressure, right atrial pressure, heart rate, left ventricular ejection fraction, and the systolic pressure:volume relation of the left ventricle, which was used as an estimate of the contractile state, were not significantly different when the patients were hypothyroid or euthyroid. During exercise, heart rate, cardiac output, end diastolic volume, and stroke volume were higher when the patients were euthyroid than when they were hypothyroid. Again, pulmonary capillary wedge pressure, ejection fraction, and the systolic pressure:volume relation were similar in both thyroid states.The data suggest that the alterations in cardiac performance seen in short term hypothyroidism are primarily related to changes in loading conditions and exercise heart rate; they do not suggest that acute thyroid hormone deficiency has a major effect on the contractile properties of the myocardium.Thyroid hormone deficiency is known to affect the heart.`13 Although exercise intolerance is a classic feature of hypothyroidism, most studies have focused on the contractile function of the heart at rest' and little attention has been paid to the performance of the left ventricle during exercise.Some radionuclide studies assessed the response of the ejection fraction to stress in hypothyroid patients.7' The ejection fraction is widely accepted as a useful measure of ventricular performance'0 but it has limitations. Because it is the ratio of two physiological variables the size of the left ventricular chamber can change considerably without causing a significant change in ejection fraction. So the Requests for reprints to Dr Siegfried Wieshammer, Cardiology Section, Department of Internal Medicine, University of Ulm, Steinhovelstraf3e 9, D-7900 Ulm, Federal Republic of Germany.Accepted for publication 9 November 1987 haemodynamic consequences of hypothyroidism are only incompletely evaluated by the response of the ejection fraction to stress, and for a more comprehensive assessment left ventricular volumes and pressures must be measured. More importantly, the ejection fraction is dependent not only on the intrinsic contractile state of the heart but also on the preload and afterload." Changes in loading conditions seem to be especially important when thyroid function is abnormal'2 and, therefore, it is u...
Objective: The aim of this study was to examine the metabolism of a simple dose, intravenously administered TRH bolus of 200 mg, in patients with euthyroid sick syndrome (ESS). Patients and Methods:A TRH test was performed on ten ESS patients and ten controls upon admission (d1) and after recovery (d2). Blood samples were collected at 0, 10, 20 and 30 min after TRH injection. We analyzed the volume of distribution (V d ), the plasma clearance rate (PCR), the fractional clearance rate (FCR), the half-life (t 1=2 ) and the TSH response to the injection of TRH. Results: All patients had lower tri-iodothyronine (T 3 ) levels compared with controls (0:9 Ϯ 0:1 nmol/l vs 1:9 Ϯ 0:1 nmol/l; P < 0.0001; mean Ϯ S.D.; paired t-test). In addition, the V d (16:7 Ϯ 5:9/l vs 30:6 Ϯ 0:6/l; P < 0.0005) and PCR (2:0 Ϯ 0:80 l/min vs 3:3 Ϯ 0:25 l/min; P < 0.0005) were found statistically lowered in patients than in controls, whereas FCR (0:119 Ϯ 0:01 per min vs 0:110 Ϯ 0:01 per min; P < 0.025) was found increased in patients as opposed to controls. The t 1=2 of exogenously administered TRH was increased in ESS compared with controls (7:2 Ϯ 0:7 min vs 6:3 Ϯ 0:6 min; P < 0.005). TSH response to TRH was found significantly repressed at 10, 20 and 30 min after TRH injection. On d2, these findings had reverted to normal and no changes regarding the kinetics of TRH and the response of TSH could be detected between patients and controls. Conclusions:The results demonstrate an impairment of TRH metabolism in ESS. The findings may suggest altered enzymatic activity, responsible for TRH degradation in states of acute ESS. These changes might be involved in the pathogenesis of ESS and represent part of an adaptive mechanism to this syndrome.
The influence of dopamine as compared with dobutamine on glucose homeostasis has been assessed in thyroidectomized euthyroid rats. Both sympathomimetic agents were given intravenously over 6 h at four dosages, varying from 2 to 30 micrograms.kg-1.min-1. Immediately before the end of the infusion period, serum concentrations of glucose and insulin as well as plasma glucagon concentrations were measured. Dobutamine infusions did not exert any influence on these parameters. At a dose of 7.5 micrograms.kg-1.min-1, dopamine infusion caused a decrease in glucose concentrations, accompanied by a rise of glucagon and insulin levels. Glucose levels were significantly increased in the presence of unaltered insulin and decreasing glucagon levels at higher dopamine doses. The rise in glucose levels was reversed by 8 micrograms.kg-1.min-1 and inverted to a decrease by 12 micrograms.kg-1.min-1 of the alpha-adrenergic blocking agent phentolamine, simultaneously infused with 15 micrograms.kg-1.min-1 dopamine, while the insulin levels were increased and glucagon levels remained elevated. These findings demonstrate that dopamine acts on glucoregulation divergently, according to the dosage applied. The data suggest that dopamine rather than dobutamine treatment may disturb glucose homeostasis.
The pharmacokinetics of thyrotropin-releasing hormone (TRH) were assessed following an i.v. injection in blood of ten hyperthyroid, ten hypothyroid, and six normal subjects. A single-compartment model was employed. After methanol extraction, TRH concentrations were analyzed using a specific radioimmunoassay technique combined with fast protein liquid chromatography (FPLC). As for the basal levels of TRH, no differences were observed in either study group. Peak concentrations were always present two min after the injection of TRH. In the euthyroid subjects, TRH blood levels had a half-life (t1/2) of 6.5 +/- 0.41 min, mean +/- SD, while t1/2 was 7.2 +/- 0.62 min in the hyperthyroid and t1/2 was 12 +/- 1.67 min (p less than 0.001) in the hypothyroid patients. The metabolic clearance rate (MCR) (82.2 +/- 15.3 liters/m2/day vs. 89.8 +/- 17.2) and the volume of distribution (Vd) (7.1 +/- 4.2 liters vs. 7.3 +/- 3.4) were approximately the same in the normal subjects and in the hyperthyroid group. MCR (66.2 +/- 15.3 liters/m2/day) and Vd (6.2 +/- 3.3 liters) were found to be lower in the hypothyroid patients. In FPLC, when TRH was added to plasma, it eluted in one peak. Blood samples taken 5 min after TRH i.v. injection had an elution profile of 9.94 ml. These data indicate that 1) TRH has a very short half-life, 2) hypothyroidism can prolong the t1/2 of exogenous TRH, and 3) when TRH should be used in clinical studies, the function of the thyroid gland has to be taken into consideration.
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