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Development of thyroid autoimmunity after administration of recombinant human interferon-alpha 2b for chronic viral hepatitis.

To investigate the frequency and clinical characteristics of autoantibody formation and development of autoimmune thyroid disease after interferon therapy, we measured the autoantibodies to thyrotropin receptor (TBII), thyroglobulin (ATA), and microsomal antigen (AMA) in 28 patients with histologically proven chronic viral hepatitis [25 males, three females; mean age 38.7 +/- 8.7 (SD) yr] receiving recombinant interferon-alpha 2b (IFN-alpha) treatment. Twenty patients with chronic hepatitis B (positive for HBsAg, HBeAg, and HBV DNA) and eight patients with chronic hepatitis C (positive for anti-HCV and HCV RNA) received IFN-alpha, 3 million units subcutaneously, three times a week for 6 months. Before, during, and up to 6 months after IFN-alpha therapy, thyroid hormone levels and titers of AMA, ATA, and TBII were measured every 2 months. None of them had thyroid dysfunction or antithyroid autoantibodies before IFN-alpha treatment. A 34-yr-old male patient developed Graves' disease during the last month of therapy. He required long-term antithyroid medications, even after discontinuation of IFN-alpha. Another 44-yr-old female patient developed AMA during IFN-alpha treatment; however, thyroid function remained normal and goiter did not develop in this patient. No other patient developed thyroid autoantibodies and thyroid dysfunction. In summary, only a small minority of patients will develop thyroid autoimmunity during IFN-alpha therapy, and much less often with this low dose of IFN-alpha.

Adult↗

Thyroid abnormalities in lithium-treated patients with bipolar affective disorder.

The thyroid functions of 42 subjects with bipolar affective disorder receiving regular lithium therapy were analysed and their thyroid glands were examined by ultrasonography. Following the receipt of lithium therapy (duration 4-156 months), three subjects displayed subclinical hypothyroidism (7.1%), three subclinical hyperthyroidism (7.1%) and one hyperthyroidism (2.4%). Moreover, goitre was detected in 16 (38.1%) subjects. An increase in the conversion of free thyroxine (T4) to free tri-iodothyrosine (T3), which is an indication of mild thyroid dysfunction, was identified in 20 (47.6%) subjects, and was mostly seen in male subjects under 40 years of age and in those having weight gain. In conclusion, some thyroid dysfunctions were observed in the patients treated with lithium.

Adolescent↗

[Thyroid peroxidase antibodies and thyroid diseases in children and adolescents with newly diagnosed type I diabetes].

The objective of the authors was to evaluate the prevalence of TPO Ab and thyroid diseases in children with newly diagnosed type 1 diabetes. The examination included 153 patients (85/55.6% girls) from southeast Poland aged 11 months to do 17.4 years (mean age 9.5 +/- 3.9 years). Apart from clinical assessment, all children had determinations made of serum TPO Ab, FT4 and TSH, while thyroid ultra sound was performed in each patients with abnormal thyroid morphology and/or positive TPO Ab titter. Positive TPO Ab was detected in 45 patients (29.4%). In this group 26 had isolated serum TPO Ab elevation, 18 had Hashimoto's disease, 1 Graves's disease. Another 12 children (7.8%) were demonstrated to have euthyroid goiter. Thyroid abnormalities were thus seen in 37.2% children with newly diagnosed type 1 diabetes. No association was demonstrated between the prevalence of thyroid abnormalities and sex. Children with subclinical stage of autoimmune thyreoiditis were significantly younger in comparison to patients with Hashimoto's disease (8.9 +/- 4.2 vs. 12.0 +/- 3.1 years) and had significantly lower serum TPO Ab and TSH levels (314.2 +/- 232.4 vs. 2076.8 +/- 1300.8 U/ml, 1.7 +/- 0.82 vs. 4.1 +/- 2.9 ulU/ml, respectively). Thyroid dysfunction was detected in 7 (4.6%) children with newly diagnosed type 1 diabetes. In comparison to the entire group with positive serum TPO Ab titer in these 7 children the percentage of patients with thyroid dysfunction was significantly higher (15.5%). Six patients were hypothyroid and 1 had hyperthyreosis. The present results justify the need for comprehensive screening for thyroid disorders in all children with newly diagnosed type 1 diabetes.

Adolescent↗

Reproductive impairment in the Florida panther: nature or nurture?

Many of the remaining members of the endangered Florida panther (Felis concolor coryi) population suffer from one or more of a variety of physiological, reproductive, endocrine, and immune system defects including congenital heart defects, abnormal sperm, low sperm density, cryptorchidism, thyroid dysfunction, and possible immunosuppression. Mercury contamination, determined to be the cause of death of a female panther in 1989, was presented as the likely cause of thyroid dysfunction. As genetic diversity in the species was less than expected, all of the other abnormalities have been attributed to inbreeding. However, exposure to a variety of chemical compounds, especially those that have been identified as environmental endocrine disrupters (including mercury, p,p'-DDE, and polychlorinated biphenyls), has elicited all of the listed abnormalities in other species. A number of these contaminants are present in South Florida. An exposure pathway has been identified, and evidence presented in this paper, including the fact that there appears to be no significant difference between serum estradiol levels in males and females, suggests that many male panthers may have been demasculinized and feminized as a result of either prenatal or postnatal exposure. Thus, regardless of the effects of inbreeding, current evidence seems to indicate that environmental contaminants may be a major factor contributing to reproductive impairment in the Florida panther population.

Animals↗

Adiponectin levels and cardiovascular risk factors in hypothyroidism and hyperthyroidism.

OBJECTIVE: Adiponectin, an adipose tissue-derived hormone, has been reported to have anti-inflammatory and anti-atherogenic effects. The physiological effect of adiponectin on the metabolic changes and its relation with cardiovascular risk factors in thyroid dysfunction states is still not clear. The aim of the study was to evaluate plasma adiponectin level and its relation to cardiovascular risk factors in patients with thyroid dysfunction. PATIENTS AND MEASUREMENTS: Sixty-seven patients with hypothyroidism, 56 patients with hyperthyroidism and 52 age- and sex-matched euthyroid subjects were enrolled in the study. Adiponectin, C-reactive protein (CRP), homocysteine (Hcy), lipid parameters, Lipoprotein(a) [Lp (a)], Apolipoprotein (Apo) A, Apo B and fibrinogen levels were measured in all subjects. Insulin sensitivity was determined using the Homeostasis Model Assessment (HOMA-IR). RESULTS: Circulating adiponectin levels were not different between the groups (16.2 +/- 5.0, 15.1 +/- 3.7, 15.9 +/- 4.8 ng/ml; hypothyroid, hyperthyroid, euthyroid group, respectively). Plasma adiponectin levels correlated negatively with body mass index (BMI) and HOMA-IR index and positively with high-density lipoprotein cholesterol (HDL-C) in all groups. There was a significant correlation between adiponectin and CRP levels in both hypothyroid and hyperthyroid groups. In all groups, adiponectin levels did not correlate with age, systolic blood pressure, diastolic blood pressure and thyroid hormones. Multiple regression analysis revealed BMI and HDL-C levels to be the most important predictors of circulating adiponectin levels. CONCLUSIONS: Plasma adiponectin levels are associated with BMI and HDL-C levels in patients with hypothyroidism and hyperthyroidism. But there is not a direct relation of adiponectin with thyroid hormones in these patients.

Adiponectin↗

[Changes of thyroid and adrenocortical functions after bone marrow transplantation with MAC conditioning regimen in leukemia patients].

OBJECTIVE: To investigate the effect of MAC conditioning regimen on endocrine glands function in leukemia patients after bone marrow transplantation(BMT). METHODS: Thyroid and adrenocortical functions were assayed by radioimmunoassay (RIA) in 26 leukemia patients before and after BMT. RESULTS: All patients had normal thyroid and adrenocortical functions before BMT. As compared with that pre BMT, the median serum TSH levels were increased at 1, 3 and 6 months post BMT(P < 0.01). This thyroid dysfunctions were found in 7 of 26 patients, 6 of whom were recovered at 6 months post BMT. CONCLUSION: There was little effect of MAC conditioning regimen on adrenocortical function. Thyroid dysfunctions were found in 28% of the patients after BMT, and normalized in a short period without replacement therapy.

Adolescent↗

Management of amiodarone-induced thyrotoxicosis.

Amiodarone is used increasingly in a number of cardiac conditions. Amiodarone is heavily iodinated and can cause thyroid dysfunction. The diagnosis of amiodarone-induced thyrotoxicosis remains difficult and more common causes of thyrotoxicosis need to be considered and excluded. Amiodarone has a significant side effect profile, which includes thyroid dysfunction. Amiodarone is an effective drug and its withdrawal may have significant impact on a patient's already fragile cardiac status. There are three different types of amiodarone-induced thyrotoxicosis (AIT) (I, II and mixed). Identification of the different subtypes of AIT allows a rational and appropriate management strategy to be chosen. Type I occurs in patients with underlying thyroid disease, whilst type II is thought to result from a destructive thyroiditis. Differentiation is based on clinical grounds together with investigations, which can include thyroid function test, radioiodine uptake scanning, measurement of interleukin-6 levels and colour flow Doppler sonography. Amiodarone should be discontinued in both types of AIT if the indication for its use is not a life-threatening cardiac condition. The management of type I centres around antithyroid drugs to control thyrotoxicosis and later consideration of more definitive treatment. Type II AIT responds to steroid therapy, although antithyroid drugs may be useful if symptoms are severe. Therapeutic options for refractory cases of AIT include surgery, radioiodine and plasmapheresis.

Adrenal Cortex Hormones↗

[Central congenital hypothyroidism due to Graves' disease in the mother].

Two male twins were born at a gestational age of 30 weeks. Five days after delivery, the mother was diagnosed with Graves' disease. The thyroid function in the neonates was therefore evaluated, which led to the detection of central congenital hypothyroidism (central CHT), even though the neonatal CHT-screening had been reported to be normal. Both boys were treated with thyroxine up to the age of nine months. It was then established that their development had been uneventful. Maternal Graves' disease can, due to the presence of anti-thyroid stimulating hormone (TSH) receptor antibodies and the maternal use of anti-thyroid drugs, result in thyroid dysfunction in the neonate. Neonates born to mothers with Graves' disease are at risk of developing central CHT. This occurs especially in children of mothers who are not treated or are inadequately treated during pregnancy. In view of the importance of thyroid hormone for brain development, children with central CHT are at risk for neurodevelopmental problems if thyroid dysfunction is not detected and treated early. The Dutch screening for congenital hypothyroidism is based on thyroxine (T4), TSH and thyroid-binding globulin. This makes it possible to detect central CHT. However, in prematurely born infants this disease may be missed because in this subgroup, referral is only based on increased TSH levels, which may not be present.

Adult↗

Effects of thyroid hormone on the cardiovascular system.

Increased or reduced action of thyroid hormone on certain molecular pathways in the heart and vasculature causes relevant cardiovascular derangements. It is well established that overt hyperthyroidism induces a hyperdynamic cardiovascular state (high cardiac output with low systemic vascular resistance), which is associated with a faster heart rate, enhanced left ventricular (LV) systolic and diastolic function, and increased prevalence of supraventricular tachyarrhythmias - namely, atrial fibrillation - whereas overt hypothyroidism is characterized by the opposite changes. However, whether changes in cardiac performance associated with overt thyroid dysfunction are due mainly to alterations of myocardial contractility or to loading conditions remains unclear. Extensive evidence indicates that the cardiovascular system responds to the minimal but persistent changes in circulating thyroid hormone levels, which are typical of individuals with subclinical thyroid dysfunction. Subclinical hyperthyroidism is associated with increased heart rate, atrial arrhythmias, increased LV mass, impaired ventricular relaxation, reduced exercise performance, and increased risk of cardiovascular mortality. Subclinical hypothyroidism is associated with impaired LV diastolic function and subtle systolic dysfunction and an enhanced risk for atherosclerosis and myocardial infarction. Because all cardiovascular abnormalities are reversed by restoration of euthyroidism ("subclinical hypothyroidism") or blunted by beta-blockade and L-thyroxine (L-T4) dose tailoring ("subclinical hyperthyroidism"), timely treatment is advisable in an attempt to avoid adverse cardiovascular effects. Interestingly, some data indicate that patients with acute and chronic cardiovascular disorders and those undergoing cardiac surgery may have altered peripheral thyroid hormone metabolism that, in turn, may contribute to altered cardiac function. Preliminary clinical investigations suggest that administration of thyroid hormone or its analogue 3,5-diiodothyropropionic acid greatly benefits these patients, highlighting the potential role of thyroid hormone treatment in patients with acute and chronic cardiovascular disease.

Cardiovascular Diseases↗

Surgery in patients with endocrine dysfunction.

Patients with diabetes mellitus, thyroid dysfunction, and adrenal suppression from exogenous steroid therapy frequently undergo surgery. An understanding of the pathophysiology of these disorders enables the medical consultant to have valuable input into the preoperative evaluation and perioperative management of these patients. This article serves as a practical guide in following such patients through surgery, thereby decreasing overall morbidity and mortality.

Endocrine System Diseases↗

Hypothalamic-pituitary-adrenal and -thyroid axis dysfunctions and decrements in the availability of L-tryptophan as biological markers of suicidal ideation in major depressed females.

Several neurochemical correlates of suicide were recently detected. Some authors found increased disorders in the hypothalamic-pituitary-adrenal (HPA) and -thyroid (HPT) axes and disturbances in serotonergic neurotransmission in suicidal patients. In order to investigate the biological correlates of suicidal ideation, we measured the following: basal thyrotropin-secreting hormone (TSH), free thyroxine (FT4), pre- and postdexamethasone cortisol, adrenocorticotropic hormone (ACTH) levels, the circulating concentrations of total L-tryptophan (L-TRP) and the ratio between L-TRP and competing amino acids (CAA). The subjects were 17 suicidal and 17 nonsuicidal major depressed females matched for age and severity of illness. We found no significant differences in any of the above-mentioned biological data between patients with suicidal ideation and those without.

Adrenocorticotropic Hormone↗

Inverse correlation between thyroid function and hemostatic markers for coronary heart disease in obese children and adolescents.

BACKGROUND: Childhood obesity may be associated with thyroid dysfunction. Both obesity and hypothyroidism are related to increased risk of coronary heart disease (CHD) in adults through high levels of serum lipids and/or hemostatic abnormalities. OBJECTIVE: To investigate a possible relationship between thyroid function and hemostatic markers for CHD in obese children and adolescents. STUDY DESIGN: Thirty-nine obese children and adolescents were investigated for thyroid function and markers for CHD after overnight fast. Thyroid hormones were measured by radioimmunoassay. Factor VII coagulant activity (VIIc) and factor VIII coagulant activity (VIIIc) were determined using one stage clotting assays; fibrinogen was measured according to the method of Clauss; von Willebrand factor antigen (vWF-Ag), tissue type plasminogen activator antigen (tPA-Ag), and plasminogen activator inhibitor-1 antigen (PAI-1-Ag) were determined by ELISA. RESULTS: We found a significant inverse correlation between fT4 and factor VIIc (r = -0.33, p = 0.03) and fibrinogen (r = -0.35, p = 0.02), which remained significant after adjustment for body fat mass. Factor VIIIc (r = -0.26, p = 0.066) and vWF-Ag (r = -0.28, p = 0.053) tended to be correlated negatively to fT4. fT4 did not correlate with tPA-Ag and PAI-1-Ag. fT3 was inversely related to factor VIIc (r = -0.3, p = 0.039), which was not independent of body fat mass, and showed a less impressive negative correlation with fibrinogen (r = -0.27, p = 0.058). fT3 did not correlate with vWF-Ag, tPA-Ag, or PAI-1-Ag. There was no relationship between TSH and the determined hemostatic markers. CONCLUSION: Our study demonstrates a close relationship between thyroid function and hemostatic markers for CHD in obese children and adolescents and suggests that thyroid dysfunction is associated with an unfavorable hemostatic state even in pediatric patients.

Adolescent↗

Increased prevalence of thyroid autoantibodies and subclinical thyroid failure in relatives of patients with overt endocrine disease-associated diabetes but not type 1 diabetes alone.

The purpose of this study was to determine the prevalence of thyroperoxidase (TPO) and thyroglobulin (Tg) antibodies, using a sensitive and specific radioimmunoassay method in a large cohort of 254 first-degree relatives of Type 1 diabetic patients with or without other autoimmune endocrinopathy, and to evaluate the predictive value of thyroid antibodies for impaired thyroid function in these groups. TPO and Tg antibodies were found at similar frequencies (12%) in the 254 relatives, and both antibodies were present in 23 cases (9%). Seven subjects displayed subclinical thyroid dysfunction without an abnormal free T4 level. Among first-degree relatives of probands with Type 1 diabetes alone, TPO or Tg antibodies were found in 8 subjects (6%), including 6 with both antibodies. The prevalence of TPO antibodies was significantly greater among relatives of TPO-positive than TPO-negative probands (p < 0.01). In relatives of diabetic patients with other endocrinopathy, frequencies of TPO (20%), Tg (19%) and a combination of both antibodies (15%) were significantly higher than in relatives of Type 1 diabetic patients without endocrinopathy (p < 0.001). TSH levels were abnormal in only one relative of the group without endocrinopathy but occurred in 6 relatives of the proband with overt endocrinopathy-associated diabetes (p < 0.02) in marked association with TPO antibodies (p < 10(-4). It is concluded that relatives of probands with overt endocrine autoimmune disease-associated diabetes, unlike those of probands with diabetes alone, showed increased prevalence of thyroid antibodies and thyroid dysfunction. These results argue for a different risk of thyroid autoimmunity and clinical disease in families of diabetic patients without or with overt endocrine disease. A screening of thyroid autoimmunity is highly recommended for the latter group.

Adolescent↗

Chronic administration of amiodarone and thyroid function: a follow-up study.

In order to evaluate the effects of amiodarone on thyroid function in chronically treated patients, 43 consecutive patients, who had been taking a mean weekly dose of 1420 +/- 488 mg for more than 9 months (mean 16.5 months), were studied. In a first evaluation, three patients with hypothyroidism and two with hyperthyroidism were discovered. In the remaining 38 patients, mean T4 (131 +/- 38 nmol/L) and rT3 (0.85 +/- 0.3 nmol/L) levels were significantly higher than reference values (p less than 0.05 and p less than 0.001, respectively), and mean T3 levels (1.89 +/- 0.73 nmol/L) were significantly lower (p less than 0.001). Thirteen patients showed hyperresponsiveness to thyrotropin-releasing hormone (TRH) stimulation testing. In a second evaluation, performed 12 to 18 months later, two new cases of hypothyroidism were discovered. T3 levels showed significantly lower values (p less than 0.02) than in the first evaluation, whereas basal thyroid-stimulating hormone levels and levels 30 and 60 minutes after TRH stimulation were significantly higher than those in the first evaluation (p less than 0.001). Five new hyperresponders to TRH were found. In the present series, the progressive appearance of clinical thyroid dysfunction with an elevated total incidence (16%) is demonstrated. Moreover, a progressively high prevalence of hyperresponsiveness to TRH stimulation is shown. These findings indicate that chronic amiodarone administration may carry a high risk of thyroid dysfunction.

Adult↗

[The effects of amiodaron on the thyroid function].

The use of several groups of medications may result in thyroid dysfunction including thyrotoxicosis or hypothyroidism of various degree (from subclinical to full-clinical syndrome). The mentioned disturbances may develop either on the basis of normal euthyroid gland or may overlap the previously-existing oceult changes (first of all different forms of autoimmune thyroiditis). Amiodarone is a widely used anti-arrythmic drug with considerable potential to cause thyroid dysfunction because of its 35% iodine content. Besides amiodarone particles are known to inhibit T4 to T3 conversion, they work as inhibitors of nuclear receptors for thyroid hormones, exert cytotoxic effect and induce immune/inflammatory process in thyroid gland. Both thyrotoxicosis (AIT - amiodarone induced thyrotoxicosis) and hypothyroidism (AIH - amiodarone induce hypothyroidism) may develop during amiodarone therapy. AIT appears to occur more frequently in geographical areas with low iodine intake, whereas AIH is more frequent in iodine-sufficient areas. Two forms of AIT are known. Their differentiation is very important for further therapeutical procedures. Because thyrotoxicosis and hypothyroidism symptoms during amiodarone therapy are scanty, there is need for periodic determination of thyroid function. Normal ranges for amiodarone patients differ from those for the rest of population. They are presented in this review. Treatment of AIT is very complicated. Sometimes there is need to use few methods together, especially when amiodarone treatment can not be stopped.

Amiodarone↗

The clinical features of diabetes with coexisting autoimmune thyroid disease.

A study was made of the clinical features of diabetics with coexisting Graves' disease (n = 117) or primary hypothyroidism (n = 98). Those with Graves' disease developed thyroid dysfunction and diabetes at an earlier age than patients with primary hypothyroidism. There was, however, no difference between the two groups in respect of sex ratio nor proportion of subjects requiring insulin treatment. In contrast to the general diabetic population, 87% of diabetics with thyroid disease were female, 56% required insulin treatment and of patients requiring insulin from diagnosis, the median age at diagnosis of diabetes was 36 years. A strong correlation was observed between age at diagnosis of diabetes and that of hyperthyroidism (r = 0.71, p less than 0.001) or hypothyroidism (r = 0.65, p less than 0.001). With increasing age at diagnosis of diabetes the interval between diagnosis of diabetes and thyroid disease diminished. The mean +/- SEM interval between diagnosis of diabetes and that of thyroid dysfunction was longer in hypothyroid (6.7 +/- 1.2 years) than in hyperthyroid diabetics (-2.4 +/- 1.2 years). Neither insulin-dependent nor non-insulin dependent diabetics with associated thyroid disease exhibited a significant seasonal variation in diagnosis or symptomatic onset of diabetes. It is conceivable that where diabetes accompanies autoimmune thyroid disease in the same patient, both conditions may share a common and coincident pathogenesis which is unrelated to acute environmental influences.

Adolescent↗