Correction Of Thyrotoxicosis Research Articles

Brown adipose tissue influences adiponectin and thyroid hormone changes during Graves’ disease therapy

ABSTRACT Thyroid hormones (TH), adiponectin and brown adipose tissue (BAT) are regulators of energy homoeostasis. Influence of BAT activity on the relationship between TH and adiponectin remains unexplored. The aim of the study was to identify the relationship between TH and adiponectin and to clarify the impact of active BAT on the metabolic effects of adiponectin before and after the correction of thyrotoxicosis. Twenty-one patients with newly diagnosed hyperthyroidism from Graves’ disease were recruited. A titration dosing regimen of thionamide anti-thyroid drug (ATD) was used to establish euthyroidism over 12–24 weeks. Anthropometric, biochemical and adipocytokine parameters were measured before and after control of hyperthyroidism. BAT activity was quantified by fusion 18 F-fluorodeoxyglucose (18 F-FDG) PET/MR imaging, and patients were grouped based on BAT status. Plasma adiponectin level was significantly increased following correction of hyperthyroidism in the overall sample. Free thyroxine (FT4) was also identified as a predictor of adiponectin level in thyroid dysfunction. However, significant changes in adiponectin level and correlations involving adiponectin were absent in BAT-positive patients but maintained in BAT-negative patients. BAT activity diminishes the correlative relationship with body composition and abolishes TH and adiponectin relationships when transitioning from a hyperthyroid to euthyroid state.

Amiodarone-induced thyrotoxicosis type 2: predictors and treatment options

Amiodarone-induced type 2 thyrotoxicosis remains a significant problem of modern endocrinology and cardiology. The unique pharmacological character and multifaceted properties of amiodarone explain its high prescription frequency and the leading position among antiarrhythmic drugs. In its turn, cytotoxicity and supra-physiological iodine content in the drug increase the risk of drug-induced destructive thyroiditis. The development of thyrotoxicosis leads to recurrence of cardiac arrhythmias, increased left ventricular dysfunction and manifestations of chronic heart failure. Correct identification of the type of thyrotoxicosis determines the subsequent patient management strategy. Glucocorticoids have been recognized as the first-line treatment among the possible therapy options. Rapid correction of thyrotoxicosis is crucial, especially in elderly patients with severe heart disease. Of interest for practical medicine is the search for specific predictors (deep understanding of the pathogenetic mechanisms) and new possibilities of therapy for amiodarone-induced thyrotoxicosis type 2.

HYPERTHYROIDISM AND ATRIAL FIBRILLATION

Review on a problem of the development of atrial fibrillation in patients with thyrotoxicosis is presented. Thyrotoxicosis is one of the most frequent endocrine diseases, conceding only to a diabetes mellitus. The most frequent reasons of hyperthyroidism are Graves’ disease and functional thyroid autonomy. The authors give an analysis of data on the cardiac effects of thyrotoxicosis, features of heart remodeling under the influence of thyroid hyperfunction, prevalence of atrial fibrillation in thyrotoxicosis, depending on age, as well as the possibility of restoring sinus rhythm in the combination of these diseases. Particular attention is paid to the effect on the heart of subclinical thyrotoxicosis, which is defined as a dysfunction of the thyroid gland, characterized by low serum concentration of thyrotropin, normal values of free thyroxine and free triiodothyronine. Subclinical hyperthyroidism is also capable of causing heart remodeling and diastolic dysfunction. Prevalence of thyrotoxicosis in elderly people is higher in areas of iodine deficiency; it is relevant for our country due to the large territory of iodine deficiency. In elderly patients, the cardiac effects of thyrotoxicosis prevail in the clinical picture, that makes it difficult to diagnose endocrine disorders, and correction of thyrotoxicosis is critically important for the successful control of the heart rhythm. The article also discusses the problem of thyrotoxic cardiomyopathy, caused by the toxic effect of excess thyroid hormones: features of this heart disorder, factors affecting its formation, clinical significance and contribution to the development of rhythm disturbances. The greatest significance is the development of atrial fibrillation as a result of thyrotox-icosis in older patients who already have various cardiovascular diseases. Atrial fibrillation is the most frequent heart rhythm disorder in thyrotoxicosis. The main cause of arrhythmia in hyperthyroidism is the simultaneous existence of frequent focal impulses and circular motions of the excitation wave – the mechanism re-entry. Successful treatment of atrial fibrillation in patients with thyrotoxicosis is possible only when euthyroidism is achieved. In most cases, after the elimination of thyrotoxicosis, a spontaneous restoration of the sinus rhythm is observed. The chances of sinus rhythm restoration are lower in elderly patients with concomitant organic diseases of the myocardium or long-term atrial fibrillation. Moreover, even radically cured thyrotoxicosis leads to deterioration in the life prognosis.

Myositis Associated with the Decline of Thyroid Hormone Levels in Thyrotoxicosis: A Syndrome?

Musculoskeletal complaints are common in patients with thyroid dysfunction. Both thyrotoxic and hypothyroid myopathy have been well described, and there are distinct presentations, laboratory findings, and clinical outcomes between the two groups. Myopathy has also been reported in hyperthyroid patients only after beginning treatment, suggesting that relative hypothyroidism may also contribute to musculoskeletal disease. A confounding factor in these cases was that these patients were on antithyroid drugs that may also have direct effects on the muscle, irrespective of the rate of decline in thyroid hormone levels. We report a patient with Graves' disease who developed myalgias with elevated creatine kinase levels after total thyroidectomy. Addition of triiodothyronine quickly resolved her symptoms and creatine kinase levels, whereas discontinuation of triiodothyronine, despite having normal to elevated total thyroxine levels, led to a relapse. Myositis after correction of thyrotoxicosis may constitute a syndrome that should be assessed for in hyperthyroid patients complaining of myalgias after starting treatment.

Long-term outcome of thyroid function after amiodarone-induced thyrotoxicosis, as compared to subacute thyroiditis

Two main forms of amiodarone- induced thyrotoxicosis (AIT) exist: type 1 AIT is a condition of true hyperthyroidism developing in patients with pre-existing thyroid disorders, and usually requires thyroid ablative treatment. On the other hand, type 2 AIT is a form of destructive thyroiditis occurring in normal thyroids, the management of which usually consists in glucocorticoid treatment. To assess the long-term outcome of thyroid function in a prospective study of type 2 AIT patients, as compared to patients with De Quervain's subacute thyroiditis (SAT). Sixty consecutive patients with type 2 AIT were evaluated during oral glucocorticoid treatment (oral prednisone 30 mg/day, gradually tapered and withdrawn over a 3-month period) and followed for 38+/-4 months (range 6-72) thereafter. Sixty consecutive patients with SAT, referred to our Institutes during the same period and treated with the same therapeutic schedule, served as controls. Type 2 AIT patients were older (p<0.0001) and showed a larger male preponderance (M:F 3.6:1 vs 0.5:1, p<0.0001) than SAT patients. Mean serum free T4 (FT4) and free T3 (FT3) concentrations at diagnosis were increased in both conditions, but higher in type 2 AIT than in SAT (FT4 47.6+/-18.8 and 29.6+/-8.3 pmol/l, respectively, p<0.0001; FT3 15.4+/-7.0 and 11.2+/-3.0 pmol/l, respectively, p<0.001). Correction of thyrotoxicosis was obtained in all patients in both groups, but restoration of euthyroidism occurred earlier in SAT than in type 2 AIT (p=0.006). Ten type 2 AIT patients (17%) and 3 SAT patients (5%, p<0.03) became permanently hypothyroid after glucocorticoid withdrawal and required levothyroxine replacement. A relevant proportion of type 2 AIT patients develop permanent hypothyroidism after correction of thyrotoxicosis. Thus, periodic surveillance of thyroid status is required after type 2 AIT.

Free and protein bound leptin are distinct and independently controlled factors in energy regulation.

Leptin exerts important regulating effects on energy homeostasis and could have a central role in our understanding of obesity, diabetes mellitus and the metabolic syndrome. Leptin circulates in a free and protein bound form. The aim of the present study was to test whether both fractions of the leptin system can be selectively regulated and thus serve independent physiological roles. Using specific radioimmunoassays we measured both leptin components in relation to BMI in healthy subjects before and after weight reduction and in hyperthyroid patients during correction of thyrotoxicosis. In the latter group body composition and resting energy expenditure was monitored. In addition, we measured serum and cerebrospinal fluid concentrations of free and bound leptin in patients with neurological disorders. Under all conditions free leptin concentrations reflected body fat mass. Bound leptin concentrations decreased during weight reduction but also after treatment of hyperthyroidism despite an increase in fat mass. Direct measurement of resting energy expenditure and bound leptin in hyperthyroid patients and under thyrostatic treatment showed a significant positive correlation of both variables. In contrast to free leptin whose transport into the cerebrospinal fluid appears to be saturated at low physiological concentrations of serum free leptin, bound leptin concentrations in the cerebrospinal fluid increased in parallel to serum concentrations over the whole physiologically relevant range. Our data indicate a distinct role of free and bound leptin in the feedback regulating energy intake and expenditure and could have important implications for our understanding of the physiology and pathophysiology of leptin-dependent signalling.

Therapy of amiodarone-induced thyrotoxicosis and hypothyroidism

Pathogenesis, diagnostic procedures and therapy of amiodarone-induced thyrotoxicosis (AIT) and hypothyroidism (AIH) are briefly discussed. Diagnosis of AIT and AIT is based on the classical signs and symptoms of thyroid dysfunction, although oligosymptomatic cases may occur, and on laboratory tests such as TSH, fT4 und fT3. In AIT, radioiodine therapy usually is no option due to the high iodine content of amiodarone. Besides withdrawal of amiodarone, medical and surgical treatment remain the only modalities. If arrhythmia can be controlled by an alternative treatment, amiodarone should be discontinued although this will not immediately restore normal thyroid function. For medical treatment, thionamides, perchlorate (not available in Switzerland), steroids (mainly for type II and mixed forms of AIT) and lithium (only for severe cases) are available. Surgery is a valid therapeutical option for severe forms of AIT which cannot be controlled adequately by medical treatment. The main advantage of surgical therapy of AIT is the rapid correction of thyrotoxicosis combined with the possibility to continue amiodarone, if it is necessary and effective. With AIH, amiodarone does not have to be stopped, if indicated and effective, and L-thyroxine is the therapy of choice.

A reappraisal of the role of methimazole and other factors on the efficacy and outcome of radioiodine therapy of Graves’ hyperthyroidism

The outcome of radioiodine therapy of Graves' hyperthyroidism was retrospectively evaluated in 274 consecutive patients treated from 1975 to 1984. At 1-yr follow-up, permanent hypothyroidism occurred in 36.9% of patients and the cumulative incidence of hypothyroidism progressively increased up to 79.3% after 7-10 yr. At the end of the follow-up period, 148 patients (54%) were hypothyroid, 115 (42%) euthyroid and 11 (4%) still hyperthyroid. The prevalence of hypothyroidism was significantly higher in patients with small goiters (less than or equal to 50 g) than in those with large goiters (greater than 90 g). Moreover, hypothyroidism was more frequent in patients with high thyroglobulin antibodies titers (greater than or equal to 1:25,600) than in those with low titers or negative tests, and occurred earlier in the former group than in the latter ones Correction of thyrotoxicosis was obtained after the administration of a single dose of 131I in 187 patients (63.6%); 69 patients required two doses and 11 three or more doses. Seven patients refused further treatment with 131I after the first dose. In an effort to identify possible factors affecting the efficacy of 131I therapy, we evaluated the results obtained after the administration of the first dose of radioiodine. We found that large goiters, rapid iodide turnover and adjunctive therapy with methimazole shortly after radioiodine were associated with a higher rate of persistence of thyrotoxicosis, whereas an increased prevalence of hypothyroidism was observed in patients with small goiters and in those not treated with methimazole up to one week after 131I.(ABSTRACT TRUNCATED AT 250 WORDS)