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Regional changes in myocyte size and number in propranolol-treated hyperthyroid rats.

The effects of beta-adrenergic blockade and hyperthyroidism on cardiac myocyte structure was examined. Isolated myocytes were prepared from controls and rats treated for 10 weeks with desiccated thyroid hormone (T), propranolol, and desiccated thyroid hormone plus propranolol (TP). Cells were collected from the right and left ventricle. Cell volume was measured with a Coulter Channelyzer system. Cell length was measured directly using a phase microscope. Myocyte cross-sectional area was calculated from cell volume/length. In addition, hearts from animals in each group were perfusion-fixed and myocyte volume percent was determined morphometrically from tissue sections. The number of right and left ventricular myocytes was calculated using data from isolated cells and whole-sectioned tissue. Propranolol normalized heart rate in hyperthyroid rats. Heart weight to body weight ratios were elevated to a similar extent in both T and TP groups. Compared with controls, myocyte volume was increased (p less than 0.01) in each region of T and TP. Right ventricles had a greater degree of myocyte hypertrophy than left ventricles in both rat groups treated with thyroid hormones. Cell length was increased (p less than 0.01) in T and TP. Most of the myocyte hypertrophy, however, was due to an increase in cross-sectional area. Although volume was unchanged with propranolol treatment alone, myocytes from each region had an increase in length (p less than 0.01) and a reduction in cross-sectional area (N.S.). Myocyte number was slightly reduced in each treatment group, but changes were not statistically significant. In conclusion, thyroid hormones stimulate myocyte hypertrophy by increasing both length and cross-sectional area. Propranolol modifies myocyte dimensions in both euthyroid and hyperthyroid rats, but does not prevent thyroid hormone induced cardiac hypertrophy.

Animals↗

[Ultrasensitive TSH : a new diagnostic approach to hyperthyroidism].

The value of new ultrasensitive and rapid immunoradiometric assay of thyroid stimulating hormone (TSH) for the diagnosis of hyperthyroidism was assessed in 130 patients with suspected hyperthyroidism and in 330 controls. The diagnosis was established by the clinical evaluation, thyroid scintigraphy and serum concentrations of thyroid hormones. Using the ROC (Receiver Operating Characteristic) curve methodology which allows the optimization of sensitivity and specificity, the physician can choose the "Cut-off" value between hyperthyroidism and euthyroidism. Two points of the curve seem to be interesting : using the "cut-off" value of 0.1 mUI/l, sensitivity is 0.98 and specificity is 0.98 ; using the "cut-off" value of 0.3 mUI/l, sensitivity is 1.00 and specificity is 0.92. Using the association TSH and FT4 (Free Thyroxin), sensitivity is 0.94 and specificity is 0.99. Sixty four per cent of euthyroid patients with TSH under 0.3 mUI/l have one or several hot nodules and only two have no thyroid disease. A TRH (Thyrotrophin Releasing Hormone) test was carried out in 63 patients with suspected thyrotoxicosis : basal and TRH stimulated TSH levels were under 0.1 mUI/l. This immunoradiometric assay for TSH may simplify the approach to thyroid function testing in patients with suspected thyrotoxicosis : a basal TSH under 0.3 mUI/l is sufficient to confirm a clinical suspicion of thyrotoxicosis without TRH test within four hours. In a department devoted to testing thyroid function, this new method provides a great benefit in cost and work.

Antibodies, Monoclonal↗

Symptom rating scale for assessing hyperthyroidism.

A hyperthyroid symptom scale (HSS) was designed and administered to ten subjects with untreated Graves' disease. All subjects had clinical and chemical evidence of hyperthyroidism and reproducible HSS scores of 20 or more points. During sequential treatments with propranolol hydrochloride (phase 2) followed by propylthiouracil (phase 3) there was a significant decline in the HSS scores at each phase. Accompanying the decrease in HSS scores was a decrease in heart rate, but there was no change in thyroid function test results at phase 2 and a decrease in heart rate, thyroid function test results, and goiter size at phase 3. This new scale includes ten categories of symptoms, it is sensitive to changes in both the adrenergic and metabolic components of hyperthyroidism, and it is useful in the clinical assessment and management of patients with thyrotoxicosis.

Adult↗

[Hyperthyroidism and atrioventricular block. Pathogenic hypothesis. Apropos of a case and review of the literature].

The authors report the case of a 26-year old male patient who had Graves' disease with a first degree atrioventricular block (AVB) and intermittent episodes of a second degree AVB of the Lucciani-Wenckebach type. These disorders of conduction had features characteristic of a nodal block and disappeared after treatment of the hyperthyroidism. The pathogenesis of atrioventricular conduction disorders in hyperthyroidism remains controverted. The authors put forward the following hypothesis: under the influence of thyroid hormones in excessive amounts, the autonomic nervous system would act by reciprocal excitation and exacerbate a patent or latent hypervagotonia which was pre-existent to the hyperthyroidism. This hypothesis needs to be tested by intracardiac electrophysiological studies with atrial stimulation.

Adult↗

Biliary excretion of acetaminophen in diabetic and hyperthyroid rats.

In streptozotocin-induced diabetic rats the biliary excretion of total acetaminophen (AA) was reduced to 14.1% of the dose (100 mg/kg i.v.) as compared to 24.6% in controls. This was due to a significant decrease in the amounts of AA-sulfate and AA-glucuronide, whereas the AA-GSH excretion was not altered. These effects were paralleled by a marked decrease in the bile flow in diabetic rats. In hyperthyroid rats (pretreated with 0.1 mg/kg T3 for 4 days) no significant alterations in the total AA or AA-conjugate excretion into bile were observed; moreover bile flow in hyperthyroid rats was in the same range as for controls. In all, known changes in hepatic microsomal or cytosolic enzyme and cosubstrate concentrations during the diabetic or hyperthyroid state do not at all correlate with their influence on the biliary excretion of AA and its conjugates.

Acetaminophen↗

[Surgical preparation in hyperthyroidism and therapy of thyrotoxic crisis].

Any type of hyperthyroidism with an indication for surgical treatment requires adequate medical preparation. A major reason for this postulate is avoidance of hyperthyroid crisis. Medical control of severe hyperthyoidism is best achieved by antithyroid drugs, mild cases of thyroid autonomy maybe sufficiently pretreated by beta-adrenergic blockers. Hyperthyroid crisis due to iodine contamination of a goiter with a considerable mass of autonomously functioning tissue may require acute and early surgery if medical control fails or does not show improvement within a few days.

Humans↗

Autoantibodies in feline hyperthyroidism.

Thyroid autoantibodies have been demonstrated by indirect immunofluorescence in the sera of 10 of 29 (34 per cent) cats with hyperthyroidism. Antinuclear factor, rare in healthy cats, was found in a further four animals. Twenty-eight of the cats had a palpable goitre at first presentation. In 16 cases the goitre was unilateral, while in the others it was bilateral. Lymphocytic infiltration was present in nine of the 27 (33 per cent) thyroids examined histologically. Five of the sera gave a particularly strong reaction for thyroid antibodies. Four of these cases had bilateral goitres and lymphocytic infiltrations were found in four of the five thyroids (P less than 0.05). Twenty-one of the cats were followed up for a mean period of 11 months after operation, during which time three cats developed recurrent hyperthyroidism. Two had bilateral goitres with lymphocytic infiltration and the serum of both was strongly positive for thyroid microsomal antibodies. The third had unilateral goitre with lymphocytic infiltration and serum which was positive for antinuclear factor. In this case, the recurrence involved the lobe which had been previously operated on. Some cases of feline hyperthyroidism may be immunologically mediated and the condition is thus a potential model for some aspects of autoimmune thyrotoxicosis in man.

Animals↗

Hyperthyroidism following hypothyroidism. Data on six cases.

Hypothyroidism complicated by spontaneous hyperthyroidism is an interesting but rare occurrence in the spectrum of autoimmune thyroid disorders. We report data on six patients who had hyperthyroidism two to 20 years (mean, eight years) after the diagnosis of hypothyroidism. In three patients, triiodothyronine toxicosis accounted for the hyperthyroid symptoms. The presence of thyroid antibodies and lymphocytic infiltration in the thyroid gland points to an autoimmune mechanism. It is believed that this phenomenon occurs more often than is recognized.

Adult↗

Diagnostic performance of sensitive measurements of serum thyrotropin during severe nonthyroidal illness: their role in the diagnosis of hyperthyroidism.

Serum thyrotropin (TSH) concentrations were measured serially in 14 heart-transplant recipients (group 1) and 21 patients undergoing coronary artery bypass surgery (group 2), all without thyroid disease, and randomly in 158 patients hospitalized for various other nonthyroidal illnesses, including 144 judged euthyroid (group 3), six with increased FT4 and (or) T3 (group 4), and eight classified hypothyroid by conventional tests. The serial measurements indicated profound fluctuations. In group 1, TSH was subnormal in 21% of studies and increased in 10%. In group 2, corresponding abnormalities were found in 7% and 13%, respectively. Transiently low or high TSH tended to be associated with normal free thyroxin (FT4), prolonged subnormal TSH (greater than 1 week) with subnormal FT4. By contrast, subnormal TSH plus elevated FT4, or high TSH plus low FT4, were not encountered, making it unlikely that they occur by chance in severely ill patients who are not also hyper- or hypothyroid. In group 3, a suppressed TSH (plus borderline high FT4, T3/FT3) identified four cases of subclinical hyperthyroidism; however, another 11% of patients had subnormal and 10% had above-normal TSH, paired with normal FT4 and no evidence of thyroid disease. In group 4, suppressed TSH confirmed hyperthyroidism in five of six patients, and all in group 5 had increased TSH. We conclude that, in the hospital setting, sensitive TSH measurement can help to detect or confirm mild hyperthyroidism, but the positive predictive value of TSH alone may be as low as 35%.

Adult↗

The role of precision in determining the performance of a thyrotropin assay in diagnosing hyperthyroidism.

We examined the relationship between analytical sensitivity, precision at the lower limit of the reference interval, and diagnostic performance in hyperthyroidism for one radioimmunoassay and five immunometric assay kits for thyrotropin. The analytical sensitivity of these kits extended from 0.05 to 1.56 milli-int. units/L. Diagnostic efficiencies of the immunometric assays, in discriminating between euthyroidism and hyperthyroidism, ranged between 93% and 98%. There was a highly significant correlation (r = 0.99, P less than 0.001) between analytical sensitivity and diagnostic efficiency. The between-assay coefficients of variations, at the lower limit of the reference interval, ranged from 26% to 87%. There was no correlation (r = 0.36) between precision, at this concentration, and diagnostic efficiency. We conclude that analytical sensitivity and not precision is the major determinant in controlling the diagnostic performance of a thyrotropin assay in hyperthyroidism.

Humans↗

[Results of radioiodine treatment of patients with immunogenic and non-immunogenic hyperthyroidism using different focal doses].

The aim of this study was to check the efficacy of radioiodine (131I) therapy (RIT) in a large number of patients (n = 506) suffering from immunogenic or non-immunogenic hyperthyroidism (Graves' disease, Plummer's disease). Since there is no causal cure for immunogenic hyperthyroidism RIT provides, like all other modalities, only a moderate rate of success which is clearly dose-related. Applying 60 Gy, normal thyroid function can be achieved in only 54% of the cases. A dose of 150 Gy succeeds in 86% of the cases. The solitary decompensated autonomous adenoma (DAA) can be eliminated surgically as well as by RIT with a high degree of success (95%). Contrary to surgery, RIT does not have any noticeable early or late morbidity. The high rate of success of RIT in patients with DAA could be confirmed in two groups with different follow-up periods (16 and 65 months). As expected, the rate of hypothyroidism increased from 11% in the early group to 23% in the late group. Multinodular autonomous adenomas can be eliminated successfully using RIT as well. The concept to apply a dose of 400 Gy to the total functional autonomous tissue as determined by ultrasound yields better results (95%) than 150 Gy to the whole thyroid gland as measured by ultrasound (88%). The rate of hypothyroidism as shown by these results (up to a maximum of 62% after RIT of Graves' disease using 150 Gy) is the lesser evil compared to remaining or recurrent hyperthyroidism since these patients can be treated with thyroid hormones without problems.

Adenoma↗

Thyroid size and goitre frequency in hyperthyroidism.

Thyroid function, the clinical occurrence of goitre and thyroid gland volume, ultrasonically determined, were investigated in 310 consecutive untreated patients with hyperthyroidism. Of 173 patients with Graves' disease (39%), 67 had no goitre, while 53 patients (31%) had a normal thyroid volume. Twenty-three of 91 patients with multinodular glands (25%) had no goitre and ten patients (11%) had a normal thyroid volume. Of 46 patients with solitary autonomous nodules (7%), three had no goitre while six (13%) had a normal thyroid volume. Out of all the hyperthyroid patients (30%), 93 had no clinically detectable goitre, and 69 (22%) had a normal thyroid volume. The lack of a goitre in a large portion of patients with hyperthyroidism could be responsible for delayed diagnosis and subsequent treatment of these patients.

Adolescent↗

[Leukocyte function in patients with hyperthyroidism].

In 20 patients with hyperthyroidism the behaviour of the agglomeration of leucocytes as well as of the adhesivity before and after the methimazol therapy was investigated. The agglomeration of leucocytes was directly inhibited neither by the overfunction of the thyroid gland nor by methimazol. By means of a stimulation test an undisturbed ability of leucocytic activation in hyperthyroidism could be proved. The adhesivity at the glass slide, however, was slightly restricted in untreated hyperthyroidism. It normalized under thyrostatic therapy.

Adolescent↗

[Absence of ultra-structural histological lesions of the myocardium in cardiac insufficiency of hyperthyroidism].

Myocardial failure may complicate hyperthyroidism. Some authors consider that preexisting myocardial lesions are necessary for its development. We studied a case of myocardial failure, presenting as a dilated cardiomyopathy, complicating hyperthyroidism in a 57 year old woman. She had a bio-clinical evaluation and a haemodynamic study with endomyocardial biopsy of the left ventricule. No valvular or coronary disease were noted. The light and ultra-microscopic aspects of the myocardium were within normal limits. We conclude that preexisting myocardial lesions are not essential to the development of myocardial failure complicating hyperthyroidism.

Female↗

[Surgical treatment of hyperthyroid struma: surgery results, postoperative long-term course and study of a factor connected with recurrences].

None of the 335 patients thyroidectomized for hyperthyroidism in our department of surgery between 1972 and 1982 died as a consequence of the operation. Reassessment of 226 of these patients by questionnaire 68 +/- 25 (SD) months after thyroidectomy revealed the following complications: postoperative paresis of the recurrent nerve (9%), persistent change of voice (2%), and persistent hypoparathyroidism (3.5%). 91 patients underwent a follow-up investigation 74 +/- 33 months after thyroidectomy. Only one had recurrent hyperthyroidism but 6 had a recurrence of the goiter. Patients with recurrent goiters had a significantly higher frequency of increased serum thyroglobulin levels than patients without goiters. These results emphasize the effectiveness of surgical therapy in hyperthyroidism, and suggest that serum thyroglobulin might be a useful predictor for goiter recurrence.

Adult↗

Sclerosing cholangitis associated with autoimmune hemolytic anemia and hyperthyroidism.

A patient presented with autoimmune hemolytic anemia and sclerosing cholangitis. Six years later he was found to be hyperthyroid. Although sclerosing cholangitis has been associated with other autoimmune disorders, it has not been reported in association with either autoimmune hemolytic anemia or hyperthyroidism. Sclerosing cholangitis is a chronic fibrosing inflammatory disease process which may include parts or all of the biliary tree including the gallbladder. Although this disorder has been reported to occur with a variety of autoimmune disorders, it has not been previously associated with autoimmune hemolytic anemia and hyperthyroidism.

Adolescent↗

[Structural changes in the gastric mucosa in experimental hyperthyroidism].

Using a structural and functional analysis experiments on rats have shown the morphological substrate of the impaired pepsin secretion in experimental hyperthyroidism. It has been established that enhancement of the proteolytic activity of gastric juice at early times of hyperthyroidism is linked with activation of biosynthetic processes in the chief gastric cells. Under the conditions of prolonged hyperthyroidism, the reduced proteolytic activity of gastric juice is caused by inhibition of both bioenergetic and biosynthetic processes in the chief cells.

Animals↗

Levels of serum thyroid-stimulating hormone in hyperthyroidism.

A modified thyroid-stimulating hormone (TSH) radioimmunoassay with particular sensitivity at the bottom end of the normal range was developed using dog serum in standard tubes and reduced quantities of TSH labeled with radioactive iodine (125I) and antiserum. The standard deviation of B0 points was 1%, implying an assay sensitivity of less than 0.1 microU/mL. This procedure was used to measure serum TSH levels in 32 normal subjects, 18 patients with hyperthyroidism, and seven patients with elevation of serum triiodothyronine (T3) levels. The range of values obtained from normal subjects was less than 0.1 to 4.1 microU/mL, with 97% of the subjects' values greater than 0.2 microU/mL. All of the hyperthyroid patients had values less than or equal to 0.2 microU/mL. Hence, the modified TSH assay was thought to be of use in distinguishing hyperthyroid from normal subjects. The TSH levels in subjects with elevated T3 levels ranged from less than 0.1 to 1.8 microU/mL. These results were thought to indicate heterogeneity within this group and suggest that only certain of these individuals merit the diagnosis of "T3 toxicosis."

Animals↗