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PubMed2001

Renin-angiotensin system contribution to cardiac hypertrophy in experimental hyperthyroidism: an echocardiographic study.

The objective of this study was to evaluate, using echocardiography, the involvement of the renin-angiotensin system (RAS) in left ventricular (LV) hypertrophy development in experimental hyperthyroidism. Thyrotoxicosis was produced by a daily intraperitoneal injection of L-thyroxine (T4), 0.1 mg/kg per day for 15 days in Wistar rats. Control (euthyroid) rats received intraperitoneal daily injection of the thyroxine solvent. Two series of experiments were performed. In the first series, euthyroid (n = 10) and hyperthyroid (n = 14) rats were surgically prepared with a femoral artery catheter. After a 3-day recovery period, blood pressure and heart rate were measured and blood samples were collected in conscious and unrestrained rats. In the second series of experiment, measurement of LV geometry was realized with two-dimensional time-movement echocardiography on the 15th day of treatment in control conditions and after long-term treatment with the angiotensin II type I receptor antagonist valsartan (10 mg/kg per day for 15 days) in both euthyroid and hyperthyroid rats. The dose and duration of T4 treatment was sufficient to induce a significant degree of hyperthyroidism with characteristic features including tachycardia, systolic hypertension, myocardial hypertrophy, hyperthermia, and weight loss. In addition, we measured an increase in free fractions of thyroid hormones, and a threefold increase in plasma renin activity. Echocardiographic examinations in rats revealed a strong correlation between LV weight and echocardiographic LV mass. Hyperthyroid rats exhibited an increased LV mass with a marked increase in the LV end-diastolic posterior wall and septal thickness. Chronic treatment with valsartan prevented this concentric LV hypertrophy (p < 0.01), with full prevention of the LV posterior wall hypertrophy (p < 0.001) and decreased LV septal hypertrophy (p < 0.05). In conclusion, the cardiovascular alterations of hyperthyroidism were reproduced with thyroid hormone injections in rats. Activation of the RAS in hyperthyroid rats was accompanied by increased LV mass. Using valsartan, we demonstrated that the RAS impinged on the LV remodelling in our experimental hyperthyroidism model. A chronic treatment with an angiotensin II type I receptor antagonist prevented the development of the concentric LV hypertrophy associated with thyrotoxicosis.

Animals↗
PubMed1979

Development of ketonemia in fasting patients with hyperthyroidism.

Concentrations of ketone bodies, free fatty acids, glycerol, lactate, glucose, insulin, glucagon and cortisol were determined 6-hourly during 36 hours of fasting in 4 hyperthyroid patients and in 4 euthyroid controls. The concentrations of ketone bodies were elevated in hyperthyroid patients from the beginning and increased during fasting more rapidly and to higher values as compared to the controls. After 6 hours of fasting the blood ketone concentrations were 1.1--1.8 mM in hyperthyroid patients and 0.3--0.6 mM in the controls. After 36 hours the concentrations had increased to about 3.5 mM and 1.4 mM in hyperthyroid and control subjects, respectively. The concentrations of free fatty acids were identical in the groups compared postprandially, but increased significantly more in the hyperthyroid patients than in the controls during fasting. The glycerol concentration was higher in the hyperthyroid group throughout the observation period. The concentrations of insulin were slightly higher in the hyperthyroid group than in the control, whereas the concentrations of the "ketogenic" hormones, glucagon and cortisol were identical in the compared groups. It is concluded that hyperthyroidism leads to an increased tendency to ketosis, that is partly explained by increased concentrations of free fatty acids and that might also involve a direct action of long term thyroid hormone excess on enzyme activities (e.g. carnitine acyltransferase in liver).

Adult↗
PubMed1994

Impaired prolactin response to arginine in patients with hyperthyroidism.

OBJECTIVE: Reduced PRL responses to TRH or dopamine antagonists have been described in hyperthyroid patients. Arginine stimulates PRL secretion through pathways other than the activation of TRH receptors or dopamine-dependent mechanisms. We therefore investigated PRL responses to arginine in patients with hyperthyroidism. DESIGN: L-Arginine (30 g infused over 30 minutes) was administered at time zero. SUBJECTS: Sixteen patients with untreated hyperthyroidism due to Graves' disease (8 female and 8 male), with a mean age (+/- SE) of 31.3 +/- 1.4 years (range 23-42), and 12 normal subjects (6 female and 6 male, ages 30.1 +/- 2.1 years, range 22-47) were studied. MEASUREMENTS: Prolactin was measured by RIA between -30 and 120 minutes, at 15-minute intervals. RESULTS: Basal PRL levels were similar in the hyperthyroid patients and normal control subjects. The hyperthyroid women showed blunted PRL responses compared to normal women (peak PRL levels, 364 +/- 44 mU/l, vs 760 +/- 156, P < 0.02). PRL responses to arginine, small but clearly detectable in normal men, were completely abolished in hyperthyroid men (peak PRL levels, 248 +/- 48 mU/l, vs 112 +/- 14, P < 0.01). CONCLUSIONS: PRL responses to arginine are impaired in hyperthyroid patients. Therefore, arginine should be added to the list of PRL stimuli whose responses are blunted in hyperthyroidism. Inhibition of PRL gene expression, and thus reduced pituitary PRL synthesis and storage, may explain why PRL responses to all secretagogues are reduced in these patients.

Adult↗
PubMed1980

Plasma cyclic nucleotide responses to insulin-induced hypoglycaemia and methacholine in patients with hyperthyroidism.

The effect of insulin-induced hypoglycaemia and methacholine on plasma cAMP and cGMP levels was studied in normal volunteers, hyperthyroid and hypothyroid patients. A significant positive correlation existed between the maximal increase in plasma cAMP and the maximal decrease in plasma glucose in normals during insulin-induced hypoglycaemia. Therefore, the plasma cAMP response is considered to be dependent on the degree of hypoglycaemia, rather than the dose of insulin. The cAMP response to hypoglycaemia was significantly higher in hyperthyroid patient, and was lower in patients with hypothyroidism than in normals. The cAMP response of the hyperthyroid patients was normalized when their hyperthyroidism was controlled after 3 months of treatment. The plasma level of cGMP was slightly elevated during hypoglycaemia, but there was no significant difference between controls and hyperthyroid patients. The cGMP response to methacholine, which is probably mediated by cholinergic receptors, was significantly potentiated in hyperthyroid patients. The cAMP response, which is presumably dependent on endogenous catecholamines secreted during methacholine-induced hypotension, was also enhanced in hyperthyroid patients. It is likely that beta-adrenergic receptor responses and cholinergic receptor responses are both enhanced in hyperthyroidism.

Adolescent↗
PubMed1989

Pharmacokinetics and dromotropic activity of ajmaline in rats with hyperthyroidism.

1. The pharmacokinetics and the dromotropic action (increased PQ interval) of intravenously administered ajmaline (2 mg kg-1) were studied in hyperthyroid rats with sinus tachycardia. The hyperthyroidism was induced by intraperitoneal injection of 3,5,3'-triiodo-L-thyronine (0.5 mg kg-1) for 4 days. 2. The change in the ajmaline concentration in whole blood could be described by a biexponential equation. The steady state distribution volume of ajmaline decreased from 4.81 l kg-1 in control rats to 3.80 l kg-1 in hyperthyroid rats and the total body blood clearance was slightly higher in hyperthyroid rats than in control rats. 3. Ajmaline exhibited a saturable binding to rat plasma proteins, and one kind of binding site was found in the observed range of concentrations. The binding capacity was 2 fold higher in hyperthyroid rats than in control rats. 4. On the basis of the plasma unbound concentration, ajmaline exhibited an increased negative dromotropic activity in hyperthyroid rats compared with control rats. 5. A positive correlation was found between the pacing rate and the dromotropic action of ajmaline on atrioventricular conduction in isolated perfused hearts. There was no significant difference in the rate-dependence of the effect of ajmaline on the heart between control and hyperthyroid rats. 6. Our findings suggest that the increased dromotropic activity of ajmaline is mainly due to the increased heart rate in hyperthyroid rats.

Ajmaline↗
PubMed1991

Influence of hyperthyroidism on maximal shortening velocity and myosin isoform distribution in skeletal muscles.

The objectives of this study were 1) to examine the effects of hyperthyroidism on the myosin isoform distribution in slow and fast skeletal muscle, 2) to explore how these effects were manifested with respect to the force-velocity relationship and maximal shortening velocity, and 3) to contrast two different techniques of measuring maximal shortening velocity under normal and hyperthyroid conditions. Adult female Sprague-Dawley rats were randomly assigned to one of two groups: control (n = 8) or hyperthyroid (n = 8). Hyperthyroidism was induced by injections of 3,3',5-triiodo-L-thyronine every other day for 20 wk. We found that hyperthyroidism produced a significant shift in the myosin isoform distribution of the soleus but not the plantaris. The relative amount of the slow myosin isoform was reduced from a control value of 93 to 69% in the hyperthyroid condition. In contrast, both the intermediate and fast myosin-3 isoform pools were substantially increased (P less than 0.001) by approximately fourfold. Hyperthyroidism produced an increase in the maximal shortening velocity of the soleus as measured either by the slack test (+57%; P less than 0.001) or by extrapolation of force-velocity data (+33%; P less than 0.001). The hyperthyroid condition did not, however, affect the mechanical properties of the plantaris.

Adenosine Triphosphate↗
PubMed1975

Metabolic clearance and blood production rates of estradiol in hyperthyroidism.

The metabolic clearance rate of 17beta-estradiol (MCR2), the plasma levels of 17beta-estradiol (E2)1, sex-steroid binding globulin (SSBG), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured in 10 hyperthyroid subjects (7 men and 3 women). The blood production rate of 17beta-estradiol (PB2) was calculated for all subjects. Nine of the 10 hyperthyroid subjects had a decreased MCR2 which returned towards normal in 5 of the 6 subjects restudied following therapy. In all 10 subjects the levels of SSBG were increased when they were hyperthyroid and returned toward normal with therapy. It is concluded that the decrease in MCR2 is largely due to the increased binding of 17beta-estradiol to SSBG. In 7 of the 10 hyperthyroid the plasma E2 concentrations were normal whereas 3 had slightly elevated levels. In 8 of the 10 hyperthyroid the PB2 was within the normal range. Only 2 hyperthyroid subjects had slightly elevated PB2. In the 6 subjects who were restudied after therapy, there was no consistent change in PB2 which remained in the normal range in all cases. It is concluded that the MCR2 is decreased in most subjects with hyperthyroidism in association with an increase of SSBG. Despite this change in MCR2 there is no significant change in PB2. The increase in SSBG levels in hyperthyroidism appears to be a direct effect of the elevation of thyroid hormone activity and is not mediated through estrogen.

Estradiol↗
PubMed1980

Altered glucoregulatory response to physiological infusions of epinephrine and glucagon in hyperthyroidism.

To study the mechanism of altered glucose homeostasis in hyperthyroidism, the effects of a 2-h physiological infusion of epinephrine (0.05 microgram/kg x min) or glucagon (3 ng/kg x min) on glucose kinetics and glucoregulatory hormones were determined in nine normal subjects and five untreated hyperthyroid patients. Under basal conditions, hyperthyroid patients exhibited increased glucose turnover (2.2 +/- 0.09 vs. 1.62 +/- 0.1 mg/kg x min in normals), a modest hyperglycemia, hyperglucagonemia, and normal levels of plasma insulin, cortisol, and GH. In normal subjects, epinephrine induced a sustained increase in plasma glucose (45 mg/dl), reflecting a transient 100% rise in glucose output, and a sustained 28% decrease in glucose clearance. In hyperthyroid patients, the rise in plasma glucose was significantly lower (22 mg/dl) due to a smaller but sustained increase in glucose output (45%) and the lack of a fall in glucose clearance. Plasma insulin rose to a peak 80% higher than baseline in hyperthyroid patients, whereas in normals it initially declined and then rose to levels 50% higher than basal. Plasma glucagon displayed only minor changes in both groups. Glucagon infusion induced similar increments in plasma glucagon levels in the two groups (120-150 pg/ml). Insulin, cortisol, and GH remained unchanged. Plasma glucose rose by 4 mg/dl in hyperthyroid patients and by 11 mg/dl in normal subjects. The net increments were significantly lower in the former group (P < 0.05-0.01). Glucose output increased by 40% in normals and returned to baseline by 75 min, whereas it increased by only 15% in hyperthyroid patients and remained above baseline until the end of the infusion. Glucagon had no appreciable effect on glucose clearance in either group. We conclude that hyperthyroidism is characterized by 1) increased glucose turnover and hyperglucagonemia in the basal state, 2) a reduced glucemic response to physiological infusions of epinephrine and glucagon, 3) a sustained response of glucose production to epinephrine and glucagon, and 4) the lack of epinephrine-induced suppression of glucose clearance, presumably due to an exaggerated response of insulin secretion to epinephrine.

Adult↗
PubMed1984

Protein metabolism in skeletal muscle tissue from hyperthyroid patients after preoperative treatment with antithyroid drug or selective beta-blocking agent. Results from a prospective, randomized study.

Protein metabolism in skeletal muscle tissue was studied in three groups of patients undergoing thyroid surgery: group I (n = 8), hyperthyroid patients preoperatively treated with an antithyroid drug and T4; group II (n = 8), hyperthyroid patients preoperatively treated with the beta 1-selective adrenoreceptor blocking agent metoprolol; group III (n = 5), euthyroid patients operated on for nodular goiter or adenoma. The study was prospective and hyperthyroid patients were randomly allocated to one of the two preoperative regimens. During operation a biopsy was taken from the sternohyoid muscle and rates of protein synthesis and degradation were measured in incubated muscle tissue. Clinical improvement was equal in the two groups of hyperthyroid patients during preoperative treatment but serum T3 concentrations remained elevated in patients treated with metoprolol. Thus, these patients were biochemically hyperthyroid at the time of operation. The rate of protein degradation was significantly higher in hyperthyroid patients treated with metoprolol than in patients of groups I and III. A significant positive correlation was found between serum T3 and rate of protein degradation in skeletal muscle. Protein synthesis rates were similar in the three groups of patients. This study demonstrated for the first time increased proteolysis in skeletal muscle tissue from patients with high serum T3 concentrations. The results indicate that changes of skeletal muscle protein metabolism in hyperthyroid patients are not normalized by beta 1-blockade despite the fact that this treatment effectively controlled symptoms and signs of hyperthyroidism.

Adrenergic beta-Antagonists↗
PubMed1993

Alterations in the kinetics of C-peptide and insulin secretion in hyperthyroidism.

Previous studies investigating the mechanisms underlying the hyperinsulinemia observed in hyperthyroid subjects have demonstrated increased, normal, or reduced insulin secretory rates when peripheral concentrations of C-peptide were used as a marker of beta-cell function. In this study, using individually derived C-peptide kinetic parameters, insulin secretion rates were calculated directly from plasma C-peptide concentrations in 13 hyperthyroid and 13 euthyroid control subjects matched for age, weight, and sex. Eight subjects in each group were studied during a 24-h period in which they ate three mixed meals, whereas the remaining five were studied during a 3-h hyperglycemic clamp. Although insulin secretory rates under basal conditions in both groups were similar, the hyperthyroid group had an enhanced insulin secretory response to meals and, accordingly, the total amount of insulin secreted over 24 h was significantly greater (P < 0.02) in this group. Insulin secretory rates were also 50% higher in the hyperthyroid subjects during the hyperglycemic clamp at a time when glucose levels in both groups were comparable. Despite these differences in secretion, the C-peptide concentrations were not significantly different. Analysis of C-peptide clearance kinetics using multivariate analysis demonstrated that the mean clearance rate of C-peptide was significantly increased (P < 0.02) in the hyperthyroid group. Thus, stimulated insulin secretion rates are significantly increased in thyrotoxicosis possibly reflecting an increased sensitivity of the beta-cell to glucose in subjects who are hyperthyroid. However, due to the rapid clearance of C-peptide from the circulation in the setting of hyperthyroidism, differences in beta-cell secretory responses between hyperthyroid and euthyroid subjects may not be evident by measurement of C-peptide levels alone.

Adult↗
PubMed2001

Radioiodine treatment of hyperthyroidism-prognostic factors for outcome.

There is little consensus regarding the most appropriate dose regimen for radioiodine (131I) in the treatment of hyperthyroidism. We audited 813 consecutive hyperthyroid patients treated with radioiodine to compare the efficacy of 2 fixed-dose regimens used within our center (185 megabequerels, 370 megabequerels) and to explore factors that may predict outcome. Patients were categorized into 3 diagnostic groups: Graves' disease, toxic nodular goiter, and hyperthyroidism of indeterminate etiology. Cure after a single dose of 131I was investigated and defined as euthyroid off all treatment for 6 months or T4 replacement for biochemical hypothyroidism in all groups. As expected, patients given a single dose of 370 megabequerels had a higher cure rate than those given 185 megabequerels, (84.6% vs. 66.6%, P < 0.0001) but an increase in hypothyroidism incidence at 1 yr (60.8% vs. 41.3%, P < 0.0001). There was no difference in cure rate between the groups with Graves' disease and those with toxic nodular goiter (69.5% vs. 71.4%; P, not significant), but Graves' patients had a higher incidence of hypothyroidism (54.5% vs. 31.7%, P < 0.0001). Males had a lower cure rate than females (67.6% vs. 76.7%, P = 0.02), whereas younger patients (<40 yr) had a lower cure rate than patients over 40 yr old (68.9% vs. 79.3%, P < 0.001). Patients with more severe hyperthyroidism (P < 0.0001) and with goiters of medium or large size (P < 0.0001) were less likely to be cured after a single dose of 131I. The use of antithyroid drugs, during a period 2 wk before or after 131I, resulted in a significant reduction in cure rate in patients given 185 megabequerels 131I (P < 0.01) but not 370 megabequerels. Logistic regression analysis showed dose, gender, goiters of medium or large size, and severity of hyperthyroidism to be significant independent prognostic factors for cure after a single dose of 131I. We have demonstrated that a single fixed dose of 370 megabequerels 131I is highly effective in curing toxic nodular hyperthyroidism as well as Graves' hyperthyroidism. Because male patients and those with more severe hyperthyroidism and medium or large-sized goiters are less likely to respond to a single dose of radioiodine, we suggest that the value of higher fixed initial doses of radioiodine should be evaluated in these patient categories with lower cure rates.

Adolescent↗
PubMed1996

Low efficiency of oxygen utilization during exercise in hyperthyroidism.

STUDY OBJECTIVE: The mechanism of exercise intolerance in hyperthyroidism has not been fully elucidated. This study was undertaken to determine if hyperthyroidism reduced the efficiency of sub-maximal exercise. STUDY DESIGN: We measured cardiorespiratory variables up to the anaerobic threshold (AT) during ramp-loading cycle ergometry in 12 patients (New York Heart Association functional class II or III). Studies were performed in the hyperthyroid state and repeated in the euthyroid state after 10 months of medical treatment. In 10-W steps from rest to the AT, we measured oxygen uptake (VO2) as a measure of total body work rate, and pressure rate product (PRP) as a measure of cardiac work rate. Loading watts at AT divided by the increment of Vo2 from rest to the AT (delta Watt/delta VO2) was calculated as an index of work efficiency (where delta means the increment of each value from rest to the AT). RESULTS: VO2 and PRP at the AT were not significantly different between hyperthyroid and euthyroid states (VO2, 16.6 +/- 3.0 vs 17.5 +/- 2.3 mL/min/kg; PRP, 229 +/- 41 vs 218 +/- 28 x 10(2) mm Hg/min). However, loading watts at the AT were significantly lower in the hyperthyroid than the euthyroid state (28 +/- 22 vs 60 +/- 14 W: p < 0.01). VO2 and PRP while hyperthyroid were significantly higher than when euthyroid at every 10-W step during ramp-loading exercise. Furthermore, delta Watt/delta VO2 was significantly lower in hyperthyroid than euthyroid states (p < 0.001). There was a significant inverse correlation-ship between triiodothyronine and delta Watt/delta Vo2 (r = -0.654, p < 0.001). CONCLUSION: Hyperthyroidism causes low work efficiency, which may limit exercise tolerance.

Adult↗
PubMed1984

[Serum angiotensin I converting enzyme activity in patients with hyperthyroidism and hypothyroidism: relation to renin and aldosterone].

In order to ascertain whether angiotensin I converting enzyme (ACE) activity might be regulated by thyroid hormone, serum ACE activity was measured in a variety of thyroid states, including hyperthyroid and hypothyroid subjects. In addition, the correlation of serum ACE activity to plasma renin activity (PRA) and plasma aldosterone concentration (PAC) was evaluated in these patients. In hyperthyroid patients, the mean (+/- SD) serum ACE activity was 32.7 +/- 6.7 U/ml (n = 30), which was significantly higher than that in hypothyroid patients (20.4 +/- 4.3 U/ml, n = 7, p less than 0.001) and in normal subjects (22.5 +/- 3.4 U/ml, n = 51, p less than 0.001). No significant difference in serum ACE activity was found between the hypothyroid patients and normal subjects. There was a significant positive correlation between serum ACE activity and PRA (r = 0.524, n = 30, p less than 0.01) and also between serum ACE activity and PAC (r = 0.473, n = 30, p less than 0.01) in the patients with hyperthyroidism. By contrast, no significant relationship was observed between serum ACE activity and thyroid hormones (r = 0.115, for T3; r = 0.143, for T4) in hyperthyroid patients. Treatment with furosemide (1 mg/kg i.v.) and upright posture (2h) significantly increased PRA, PAC and serum ACE activity in both hyperthyroid patients and normal subjects, but not in hypothyroid patients. There was a significant positive correlation between changes in serum ACE activity and in PRA (r = 0.418, n = 23, p less than 0.05) in response to the treatment in hyperthyroid patients, while no significant relationship was observed between them in either hypothyroid patients (r = 0.216, n = 6, p less than 0.10) or normal subjects (r = 0.620, n = 10, 0.05 less than p less than 0.01). In one patient with hyperthyroidism, administration of propranolol decreased PRA from 3.4 to 2.3 ng/ml/h, corresponding to an apparent decrease in serum ACE activity from 38.7 to 29.6 U/ml. From these results, it is suggested that serum ACE activity in the hyperthyroid state is modulated by the renin-angiotensin system rather than by thyroid hormone.

Adult↗
PubMed1986

[Responses of plasma bradykinin and the renin angiotensin axis to angiotensin II in hyperthyroid patients].

The present investigation was undertaken to elucidate the possible interplay between the circulating kinin(s) and the renin angiotensin axis in hyperthyroidism. The responsiveness of plasma aldosterone (p-Ald), kinin (p-BK), plasma renin activity (PRA) and serum angiotensin converting enzyme activity (ACEA) to infusion of angiotensin II at a dose of 4, 8 and 16 ng/kg.min. was asessed in 15 hyperthyroid patients and 10 euthyroid controls. There was impaired angiotensin II induced response of blood pressure in hyperthyroid patients, and basal concentrations of p-Ald were 7.7 +/- 3.8 ng/dl in euthyroid controls and 12.6 +/- 3.1 ng/dl in hyperthyroid patients (p less than 0.05). As compared to the euthyroid controls, the hyperthyroid patients showed a reduced response of plasma aldosterone to angiotensin II infusion. Angiotensin II infusion increased p-BK from basal levels of 19.1 +/- 8.2 pg/ml to 31.0 +/- 7.8 pg/ml (p less than 0.05) only in hyperthyroid patients and did not increase ACEA in either group. Next, the effects of a single administration of captopril (50 mg p.o.) on blood pressure and p-BK in hyperthyroid patients and euthyroid controls were studied. In the two groups blood pressure was not changed by captopril, but p-BK increased significantly. The present results do not support the view that there may be a direct linkage between the kallikrein kinin system and the renin angiotensin axis mediated by kininase II or angiotensin converting enzyme in human peripheral blood. Also it is unlikely that kinin may play a role in the mechanism of reduced responsiveness of aldosterone and blood pressure to angiotensin II in hyperthyroidism.

Adult↗
PubMed1986

Pharmacokinetics of methimazole in normal subjects and hyperthyroid patients.

Serum and urinary concentrations of methimazole (MMI) were measured by high-performance liquid chromatography (HPLC) with an electrochemical detector (ECD) in 10 normal subjects and 43 hyperthyroid patients after intravenous and oral administration of the drug. The pharmacokinetic parameters of MMI were estimated in 5 normal subjects and 15 hyperthyroid patients according to a two-compartment model after intravenous injection of a 10 mg dose. The mean half-life of the distribution phase (T1/2 alpha) was 2.7 +/- 1.0 h (mean +/- SD) and 3.1 +/- 1.4 h and that of the slower-phase (T1/2 beta) was 20.7 +/- 9.6 h and 18.5 +/- 12.9 h in normal subjects and hyperthyroid patients, respectively. There were no significant differences between pharmacokinetic parameters of normal subjects and those of hyperthyroid patients. No correlations between free T4 index (FT4I) and pharmacokinetic parameters were observed. Maximum serum MMI concentrations (Cmax) (213 +/- 84 and 299 +/- 92 ng/ml) were attained 1.8 +/- 1.4 h and 2.3 +/- 0.8 h after a single dose of 10 mg in 5 normal subjects and in 15 hyperthyroid patients, respectively. In hyperthyroid patients the time taken to reach the peak concentration (Tmax) after a single dose of 10 mg was similar to that after a single 15 mg and 30 mg dose. The pharmacokinetic parameters, except Cmax and the area under the curve (AUC), were not affected by the administered dose and those, except Cmax, were not affected by the thyroid function. All urine was collected at intervals of 3 h for the first 12 h and then at 24 h and 48 h after intravenous and oral administration of MMI. In all subjects, MMI rapidly appeared in the urine and the rate of excretion was highest in the first 3 h. The cumulative urinary excretion of MMI was 5.5-8.5% of administered doses in normal subjects and hyperthyroid patients. These findings in the present study are compatible with the assumption that the extent of absorption of MMI is high, if not complete, and hyperthyroidism does not affect the kinetics of MMI, and that interindividual variation is observed in the time taken to reach the peak concentration after oral administration.

Administration, Oral↗
PubMed1991

Diagnostic relevance of suppressed basal concentrations of TSH compared with the negative TRH test in detection and exclusion of hyperthyroidism.

To evaluate the sensitivity of basal TSH concentrations as determined by an "ultrasensitive" IRMA-assay (RIA-gnost h-TSH-monoclonal, Behring) versus a "negative" TRH test (defined as an increment of TSH less than or equal to 0.2 mU/l 20 min after administration of 400 micrograms TRH iv) in the diagnosis of hyperthyroidism we examined 193 consecutive patients from our thyroid outpatient clinic: 34 patients displayed hyperthyroidism (total T4: 184.4 +/- 26.0 mumol/l, effective thyroxine index: 1.25 +/- 0.08), whereas 12 had isolated T3-hyperthyroidism (total T3: 3.47 +/- 0.48 nmol/l). Employing the producer's definition of subnormal ("suppressed") bTSH concentrations (less than or equal to 0.1 mU/l), only 19 (41.3%) hyperthyroid patients would have been detected; on the other hand, one euthyroid patient would have been recognized false positively as hyperthyroid. Using the TRH test as criterion led to the correct diagnosis in 42 (sensitivity: 91.3%) hyperthyroid patients, whereas two had low bTSH concentrations (less than or equal to 0.5 mU/l), but a normal TSH response to TRH (greater than 2.0 mU/l). Raising the threshold concentration to 0.2 and, subsequently, to 0.4 mU TSH/l increased the number of correct results to 38 (sensitivity: 82.6%) and 43 (93.5%), respectively. This was associated with a concomitant decrease in specificity in the diagnosis of hyperthyroidism from 93.7 (0.1 mU/l) to 27.9% (0.4 mU/l). In conclusion, despite ultrasensitive methods for estimation of low TSH concentrations, the TRH test remains an irreplaceable tool for the correct diagnosis of hyperthyroidism.

Adult↗
PubMed1992

Increased lymphocyte thermogenesis in hyperthyroid patients. Role of Na/K pump function. Evaluation of aerobic/anaerobic metabolism.

The role of the Na/K pump for the increased cell energy expenditure in hyperthyroidism was studied by measuring total lymphocyte heat production rate in samples with and without ouabain inhibition of Na/K ATP-ase. In addition, the relative contribution of aerobic processes to lymphocyte thermogenesis was calculated from oxygen consumption measurements. In 12 patients with clinical and laboratory hyperthyroidism total lymphocyte heat production rate was 3.19 +/- 0.21 pW/cell, significantly higher than in 7 patients with subclinical hyperthyroidism (2.14 +/- 0.11 pW/cell) and in 15 euthyroid subjects (2.26 +/- 0.11 pW/cell) (p less than 0.001). The relative decrease in lymphocyte heat production rate after ouabain, giving a quantitative measure of the activity of the Na/K ATP-ase and reflecting the importance of Na/K pump function for the overall rate of lymphocyte metabolism, was not significantly different between the groups: 19.5 +/- 3.6% in hyperthyroid patients, 14.2 +/- 2.3% in subclinical hyperthyroid patients and 17.8 +/- 3.1% in euthyroid subjects. According to the rate of lymphocyte oxygen consumption, aerobic processes represented 58.4 +/- 6.7% of total lymphocyte energy expenditure in hyperthyroid patients, not significantly different from subclinical hyperthyroidism (62.6 +/- 8.4%) or from euthyroidism (66.6 +/- 2.7%). These data do not support the hypothesis of a specific role of the Na/K pump function for the increased cell thermogenesis in hyperthyroidism and indicate a parallel stimulation of aerobic and anaerobic processes by thyroid hormone excess.

Adult↗
PubMed2000

Serum cytokine levels in autoimmune and non-autoimmune hyperthyroid states.

Although the role of interleukin-2 (IL-2) and interferon gamma (gammaIFN) is still poorly understood in hyperthyroid diseases, it is reasonable to assume that these cytokines may be present at higher levels in Graves' disease (GD) than in other primarily non-autoimmune thyroid diseases. In order to look for an easy method to distinguish GD from primarily non-autoimmune causes of hyperthyroidism, we compared 13 healthy individuals with 21 treated and untreated hyperthyroid GD patients and with 19 patients with hyperthyroidism due to other etiologies: 7 cases of multinodular goiter, 5 cases of excessive hormone replacement and 7 cases of amiodarone-associated hyperthyroidism. All patients presented low TSH levels and a dubious clinical thyroid state. We found a good correlation between TSH and serum IL-2 levels (r = 0.56; P<0.01). Serum IL-2 (P<0.01) and gammaIFN (P<0.01) levels were lower in the hyperthyroid group of patients than in control subjects, suggesting a depressed TH1 pattern in the T-cell subset of hyperthyroid patients. GD had normal IL-2 levels, while patients with other forms of thyrotoxicosis presented decreased IL-2 levels (P<0.05). There was no difference between treated and untreated GD patients. We suggest that the direct measurement of serum IL-2 level may help to confirm hyperthyroidism caused by GD.

Adolescent↗