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No damaging effect of chemotherapy in addition to radiotherapy on the thyroid axis in young adult survivors of childhood cancer.

Late effects of treatment for childhood cancer on the thyroid axis are ascribed predominantly to radiotherapy. Whether chemotherapy has an additional detrimental effect is still unclear. Our aim was to evaluate this effect in young adult survivors of a broad spectrum of childhood cancers. The thyroid axis in 205 childhood cancer survivors was evaluated in relation to former use of chemotherapy and radiotherapy (cranial, cranio-spinal, cervical, mediastinal, or thoracic). The mean follow-up time was 17.5 yr. Damage to the thyroid axis was found in 55 patients (26.8%). Thirty-seven patients (18%) had thyroidal disease. Diagnoses varied from TSH elevation to papillary carcinoma. After multivariate analysis, high risk radiation field, irradiation dose, and the diagnosis of non-Hodgkin lymphoma/Hodgkin's disease were found to be significant risk factors for developing thyroid disease. Treatment with chemotherapy did not have an additional negative effect on the thyroid axis. For the development of central (pituitary or hypothalamic) thyroid dysfunction, patients with a brain tumor were at increased risk. Chemotherapy for childhood cancer does not contribute to the damage on the thyroid axis inflicted by radiotherapy during young adulthood.

Adolescent↗

Thyrotoxicosis after gastric bypass surgery prompting operative re-exploration.

In the last 10 years, gastric bypass has become an increasingly common operation performed by general surgeons. The complications resulting from this procedure can be life-threatening and are often difficult to diagnose, particularly in the immediate postoperative period. We detail a case of thyrotoxicosis manifesting on postoperative day 1 which presented with symptoms mimicking an anastomotic leak. The patient underwent a negative laparoscopy before the thyroid dysfunction was diagnosed. There is no evidence that bariatric surgery carries a greater risk of postoperative thyrotoxicosis than any other non-thyroid operation. Many of the symptoms of thyrotoxicosis, however, are similar to those of other surgery-related complications, and it should be immediately considered in the differential diagnosis of a postoperative bariatric patient with tachycardia and fever. Failure to rule out this condition may lead to unnecessary surgery.

Adult↗

[Inter-regional differences in dysthyroidism due to amiodarone: comparison of spontaneous notifications in Aquitaine, Midi-Pyrenees and Languedoc-Roussillon].

Amiodarone hydrochloride is used in the treatment of ventricular and supraventricular arrhythmias. Because of its iodinated structure, thyroid dysfunction can occur during amiodarone therapy. The reported overall incidence is variable (2-24 per cent) and depends on several factors (past thyroid history, daily iodine intake,...). The present retrospective (1990-97) study was performed using the French pharmacovigilance database in order to compare the frequency of hypo- and hyperthyroidism in three areas in the South of France: Midi-Pyrénées, Aquitaine and Languedoc-Roussillon. For each case, the following data were recorded: age, sex, dysthyroidism history, dosage, duration and indication of amiodarone and delay to onset of dysthyroidism. We collected respectively 37, 50 and 9 cases of hypothyroidism in Midi-Pyrénées, Aquitaine and Languedoc-Roussillon and 20, 69 and 11 cases of hyperthyroidism respectively in the same areas. These data show the predominance of reported amiodarone-induced hyperthyroidism in Aquitaine and Languedoc-Roussillon. Hypothyroidism seems more frequent in Midi-Pyrénées, a non-maritime area. The sex ratio (male/female) was significantly different for the occurrence of hypothyroidism in Midi-Pyrénées (1.8 versus 0.5 in Aquitaine and 0.8 in Languedoc-Roussillon). The delay to onset of hypothyroidism was significantly shorter in Midi-Pyrénées (17.1 months +/- 24.5) when compared with Aquitaine (28.7 +/- 28.1) or Languedoc-Roussillon (43.4 +/- 45). Our results show an interregional difference in the occurrence of hypo/hyperthyroidism due to amiodarone.

Adverse Drug Reaction Reporting Systems↗

[Clinical implications of occurrence of antithyroid antibodies in pregnant women and in the postpartum period].

Antithyroid antibodies are classified to immunoglobulin G. It is a varied group of antibodies as there are antibodies against TSH-receptor, against thyroid peroxidase and also against thyroglobulin. Pregnancy is a period in which the titres of antibodies decrease to protect fetus from abortion; but just after delivery they increase again. The clinical implications of this fact are varied and concern not only the thyroid gland but also other organs. Postpartum thyroid dysfunction (PPD) is one,possible disturbance due to presence of antithyroid antibodies. It can be divided into two various types: a) postpartum thyroiditis, b) Graves'-Basedow disease after delivery. Postpartum thyroiditis (PPT) is an example of autoimmune disease connected with many different factors such as genetic or environmental, but the most important factor is the presence of antibodies against thyroid peroxidase. PPT occurs in 50% of women with high titre of these antibodies. Higher risk of PPT also occurs within women with type I diabetes mellitus in comparison with the population, as well as within women-smokers. It is also proved that women with high titres of antibodies against TSH-receptor are more likely to suffer from Graves'-Basedow disease after delivery. The pathogenesis of postpartum depression is multifactorial. The occurrence of stressful life events (marital disharmony, housing and socioeconomic problems) and some biological factors (e.g. previous psychiatric illnesses) are strongly associated with postpartum depression. Some authors also said that postpartum depression depends on the presence of antithyroid antibodies during pregnancy. It is believed that cytokines which are released during the autoimmune process can affect the central nervous system and can determine changes in behavior. Some authors suggest that changes in concentration of thyroid hormones during the natural history of PPT can be connected with depression after delivery. It is also reported that high titres of antithyroid antibodies are linked with pregnancy loss but the results are not uniform.

Autoantibodies↗

Effects of long-term amiodarone treatment on thyroid function.

Serum determinations of total T4, total T3, reverse T3, free T3 index, free T4, free T4 index, TBG, T4/TBG ratio, TSH and cholesterol were carried out on 18 euthyroid patients with coronary heart disease. Serum samples were obtained before treatment and after 15 days, 2, 4, 6, 8, 10, 12, 14 and 16 months of treatment with amiodarone (400 mg/day). Patients were divided into two groups, according to patterns of TSH response to thyrotrophin-releasing hormone (TRH): (I) patients with normal responses (n = 12), and (II) patients with subnormal responses (n = 6). Patients of group I showed total T4, free T4 and reverse T3 increments and total T3 and free T3 index decreases, whereas patients of group II were distinguished by the absence of T3 decreases and a rise in free T4 levels that showed a significant correlation with a drop in serum cholesterol (r = -0.767; p. less than 0.001). No patient of either group showed clinical signs of thyroid dysfunction. These results show that the appearance of hormonal patterns of hyperthyroidism is unpredictable and very frequent in patients with no previous thyroid abnormalities undergoing long-term treatment with the drug.

Aged↗

[Progressive external ophthalmoplegia and Hashimoto's thyroiditis].

Signs of moderately increased metabolism in a patient with progressive external ophthalmoplegia and mitochondrial anomalies on muscle biopsy revealed the presence of Hashimoto's thyroiditis. The relations between ophthalmoplegia plus and thyroid dysfunction are discussed.

Adult↗

Cystatin C: unsuited to use as a marker of kidney function in the intensive care unit.

: We read with interest the article by Villa and coworkers 1 advocating the use of cystatin C as a measure of glomerular filtration rate (GFR) in critically ill patients. However, we should like to draw attention to several flaws in this study. First, Villa and coworkers compared cystatin C with creatinine as a measure of GFR, using body surface corrected creatinine clearance as, what they call, a 'gold standard'. However, in the Discussion section of that report inulin and iothalamate clearances are mentioned as gold standards, but they were not used by these investigators. The use of body surface area corrected creatinine clearance is questionable in both obese and excessively lean individuals because the correlation between surface area and lean body mass may be lost. Both types of patients are frequently encountered in intensive care. Second, Villa and coworkers employ a cutoff of 80 ml/min to identify renal dysfunction, whereas a value of 50 ml/min is generally accepted 2. This could have a major influence on the presented results. Third, patients with thyroid disorders or on corticosteroid therapy were excluded. Almost all patients with critical illness have low tri-iodothyronine values because of changes in thyroid hormone metabolism ('nonthyroidal illness'), thus making recognition of thyroid disorders problematic. Finally, we showed 3 that, in patients with thyroid dysfunction, cystatin C is not a suitable measure of GFR. In hypothyroidism creatinine levels are elevated but cystatin C levels are low, whereas in hyperthyroidism creatinine levels are low and cystatin C levels elevated. Taken together, we disagree with the authors that cystatin C could be used as a marker of GFR in intensive care patients.

Biomarkers↗

Retrospective analysis of prognostic factors affecting the thyroid functional status after subtotal thyroidectomy for Graves' disease.

To determine the factors causing thyroid dysfunction after surgery for Graves' disease, we studied 321 patients who underwent subtotal thyroidectomy during the 7-year period from 1981 to 1987. Thyroid functional status was evaluated biochemically and the patients were divided into four categories: recurrent hyperthyroidism, euthyroidism, latent hypothyroidism, and hypothyroidism. The following factors were analyzed: sex, age at onset of the disease, indication for surgery, serum titer of antimicrosomal hemagglutination antibody (MCHA), weight of resected thyroid tissue, size of remnant thyroid relative to body surface area, pathological findings of lymphoid follicles, and lymphocytic infiltration in the thyroid tissue. Probabilities of failure (recurrent hyperthyroidism and hypothyroidism) were estimated by the Kaplan-Meier method. Prognostic factors for failure were identified by using Cox's proportional hazards model. The incidence of hyperthyroidism and hypothyroidism 5 years after subtotal thyroidectomy was 16.2% and 9.6%, respectively. Significant factors for hyperthyroidism were relatively large thyroid remnant, high serum titer of MCHA (greater than or equal to 1:3200), and age at onset of the disease less than 20 years. The significant factor for hypothyroidism was severe lymphocytic infiltration. The level of postoperative thyroid stimulating hormone (TSH)-binding inhibition immunoglobulins (TBII) in patients with recurrence was significantly higher than in patients in remission. It is reasonable to determine the amount of remnant thyroid tissue in relation to patient body surface area. Although subtotal thyroidectomy can induce immunological remission by reduction of antigen, if the remission disappears, that is if TBII increases, recurrence of hyperthyroidism may develop even in patients without the unfavorable factors.

Adolescent↗

Selenium administration does not cause thyroid insufficiency in subjects with mild iodine deficiency and sufficient selenium intake.

Selenium is a trace element essential for the activity of type I 5'-deiodinase which converts thyroxine (T4) to 3,5,3'-triiodothyronine (T3). In iodine deficient hypothyroid children at low selenium dietary intake the supplementation of selenium induced a significant decrement of serum FT4 and T4 concentrations and an increase of serum TSH concentrations. Since in western countries selenium tablets begin to be largely consumed as a diet integrator, we have administered 100 micrograms/day of selenium as selenium methionine to 8 euthyroid female subjects with a positive iodine-perchlorate discharge test who had a previous episode of subacute or postpartum thyroiditis. We have studied subjects with positive iodine-perchlorate discharge test since the test indicates the existence of a subtle defect of thyroid hormone synthesis and therefore these subjects are prone to develop thyroid dysfunction. In contrast to previous findings in hypothyroid children at low iodine and selenium dietary intake, the supplementation of selenium did not decompensate thyroid hormone synthesis of euthyroid subjects with reduced thyroid iodine organification. The lack of any effect of selenium on thyroid hormone synthesis even in subjects with subtle thyroid hormone synthesis defect may be due to the fact that these subjects had a sufficient selenium dietary intake before selenium supplementation and an only marginally reduced dietary iodine intake.

Adult↗

Thyroid diseases and cerebrovascular disease.

BACKGROUND AND PURPOSE: Acute cerebral ischemia has been described in different diseases of the thyroid gland, and not only as a result of thyrotoxic atrial fibrillation and cardioembolic stroke. The purpose of this review is to summarize the studies on the relationship between thyroid diseases and cerebrovascular diseases, discussing the main findings for overt hyperthyroidism and hypothyroidism, as well as for subclinical thyroid dysfunction. SUMMARY OF REVIEW: In overt hyperthyroidism, cardioembolic stroke is clearly associated to thyrotoxic atrial fibrillation, and in subclinical hyperthyroidism with serum thyroid-stimulating hormone levels <0.1 mU/L, the incidence of atrial fibrillation is increased. Although in vitro and in vivo studies indicate a hypercoagulability state in hyperthyroidism, there is insufficient evidence to prove that this state leads to an increased risk of cardiac emboli. However, the hypothesis that overt hyperthyroidism may cause acute cerebral venous thrombosis is intriguing. Possible associations between hyperthyroidism and Moyamoya or Giant cell arteritis have only been described in case reports. There is enough evidence that overt hypothyroidism is associated with several traditional and newer atherosclerotic risk factors, especially hypertension, hyperlipidemia, and hyperhomocysteinemia. For subclinical hypothyroidism, these associations are less certain. Hypothyroidism has been associated with signs of aortic or coronary atherosclerosis, but no case-control or cohort studies have ever investigated hypothyroidism as a possible risk factor for atherothrombotic stroke. CONCLUSIONS: Hyperthyroidism is associated with atrial fibrillation and cardioembolic stroke. Hypothyroidism is associated with a worse cardiovascular risk factor profile and leads to progression of atherosclerosis. Associations between hyperthyroidism and acute cerebral venous thrombosis, Moyamoya, and Giant cell arteritis have been suggested, but sound evidence is lacking. Additional studies are needed to clarify these issues.

Antiphospholipid Syndrome↗

The effects of amiodarone on the thyroid.

Amiodarone is a benzofuranic-derivative iodine-rich drug widely used for the treatment of tachyarrhythmias and, to a lesser extent, of ischemic heart disease. It often causes changes in thyroid function tests (typically an increase in serum T(4) and rT(3), and a decrease in serum T(3), concentrations), mainly related to the inhibition of 5'-deiodinase activity, resulting in a decrease in the generation of T(3) from T(4) and a decrease in the clearance of rT(3). In 14-18% of amiodarone-treated patients, there is overt thyroid dysfunction, either amiodarone-induced thyrotoxicosis (AIT) or amiodarone-induced hypothyroidism (AIH). Both AIT and AIH may develop either in apparently normal thyroid glands or in glands with preexisting, clinically silent abnormalities. Preexisting Hashimoto's thyroiditis is a definite risk factor for the occurrence of AIH. The pathogenesis of iodine-induced AIH is related to a failure to escape from the acute Wolff-Chaikoff effect due to defects in thyroid hormonogenesis, and, in patients with positive thyroid autoantibody tests, to concomitant Hashimoto's thyroiditis. AIT is primarily related to excess iodine-induced thyroid hormone synthesis in an abnormal thyroid gland (type I AIT) or to amiodarone-related destructive thyroiditis (type II AIT), but mixed forms frequently exist. Treatment of AIH consists of L-T(4) replacement while continuing amiodarone therapy; alternatively, if feasible, amiodarone can be discontinued, especially in the absence of thyroid abnormalities, and the natural course toward euthyroidism can be accelerated by a short course of potassium perchlorate treatment. In type I AIT the main medical treatment consists of the simultaneous administration of thionamides and potassium perchlorate, while in type II AIT, glucocorticoids are the most useful therapeutic option. Mixed forms are best treated with a combination of thionamides, potassium perchlorate, and glucocorticoids. Radioiodine therapy is usually not feasible due to the low thyroidal radioiodine uptake, while thyroidectomy can be performed in cases resistant to medical therapy, with a slightly increased surgical risk.

Amiodarone↗

The role of complement in the pathogenesis of postpartum thyroiditis.

Postpartum thyroiditis (PPT) affects half of the 10% of women who have elevated circulating thyroid autoantibodies during the postpartum year. Because of the similarities between PPT and Hashimoto's thyroiditis, the pathogenic role of complement in PPT has been investigated. Complement fixation by thyroid peroxidase antibodies (TPO Abs) (expressed as log reciprocal titer) in serum from euthyroid TPO Ab-positive women (n = 29) was 0.91 at 1 month postpartum and increased to 1.45 by 12 months postpartum; complement C3 activation, measured by enzyme-linked immunosorbent assay, in a similar group of women (n = 75) was 0.05 at delivery and increased to 0.33 by 6 months postpartum. In women with PPT, there was greater TPO Ab-related complement activation during the postpartum year; complement fixation increased from 1.00 at 1 month postpartum to 1.48 at 4 months postpartum (P < 0.005) (n = 25), and C3 activation increased from 0.11 at delivery to 0.63 at 6 months postpartum (P < 0.005) (n = 73). Bioactive TPO Ab (TPO Ab x C3 index) was significantly higher in PPT women (55 kilo international units of activity (kIU)/L at 6 months postpartum) (Hashimoto range, 30-108 kIU/L) compared with euthyroid TPO Ab-positive women (< 9 kIU/L at all time points; P < 0.005). Serum samples from TPO Ab-negative control women showed no interaction with complement in either assay at any time during the postpartum year (complement fixation < 0.7; complement C3 activation index < 0.01). This detailed examination of the role of complement in the pathogenesis of PPT shows that TPO Ab-driven complement fixation is a marker for thyroid dysfunction in TPO Ab-positive women. The levels of bioactive TPO Ab in PPT fall within the range seen in Hashimoto's thyroiditis, suggesting similarities in their pathology.

Autoantibodies↗

The effect of thyroxine administration on lipid peroxidation in different tissues of rats with hypothyroidism.

Thyroid dysfunctions bring about pathological changes in different organs of the body. Findings obtained from in vivo and in vitro studies point out that thyroid hormones have a strong impact on oxidative stress. The present study was conducted to demonstrate how high-dose thyroxin administration for one week affected oxidative damage formed in experimental hypothyroidism. The study was carried out with 30 Spraque-Dawley species male rats. The experimental animals were divided into 3 groups (Group 1, control; Group 2, hypothyroidism; Group 3, hypothyroidism + thyroxine administration). Malondialdehyde (MDA) and glutathione (GSH) levels were determined in cerebral, hepatic and cardiac tissues after the experimental period. MDA and GSH levels in cerebral, hepatic and cardiac tissues of hypothyroidism + thyroxine supplemented group were higher than those in the control and hypothyroidism groups (p<0.001). The same parameters were higher in the control group than those in the hypothyroidism group (p<0.001). The results of the present study show that hypothyroidism reduced the oxidative damage in cerebral, hepatic and cardiac tissues of rats. However, high-dose thyroxine administration in addition to induced hypothyroidism increased oxidative damage in the same tissues and that this damage could not be prevented despite the increase in the antioxidant system activity.

Animals↗

[Thyroid disorders associated with interferon treatment in patients with chronic viral hepatitis or multiple sclerosis].

BACKGROUND: Alpha and beta interferon (IFN-alpha and beta) treatment is associated with the synthesis of thyroid autoantibodies and the development of autoimmune thyroid diseases. METHODS AND RESULTS: We have retrospectively evaluated their effect in patients with chronic viral hepatitis (CH) (n = 118) and multiple esclerosis (ME) (n = 10). Thyroid dysfunction has been detected in 7.4% of patients, and seroconversion in 4.7%. CONCLUSIONS: Pre-treatment antithyroid antibodies do not predispose to altered thyroid function, after IFN therapy; their presence should not contraindicate IFN treatment.

Acute Disease↗

Incidence of autoimmune thyroiditis in interferon-alpha treated and untreated patients with chronic hepatitis C virus infection.

OBJECTIVES: To clarify the relationship between interferon-alpha (IFN-alpha) therapy and autoimmune thyroiditis in chronic hepatitis C virus (HCV) infection, we investigated a selected number of patients without basal thyroid dysfunctions. MATERIALS AND METHODS: 130 patients (average age: 20-70), with chronic HCV infection and without basal clinical and laboratory signs of autoimmune thyroiditis were divided into two groups: IFN-alpha treated (A) and untreated (B) patients. Group A received IFN-alpha (three million U.I./3 times a week) for six months; group B was followed for the same period. Thyroid peroxidase and thyroglobulin autoantibodies were measured by radioimmunoassay; thyroid function was measured by radioimmunoassay (free thyroxine and triiodothyronine) and immunoradiometric assay (thyroid stimulating hormone). RESULTS: After a 6-month period, thyroid autoantibodies positivity was documented in 21.1% of group A and in 10.3% of group B patients, both statistically relevant (p<0.001 and p<0.011, respectively). The comparison between the two groups was not statistically relevant (p=0.142). CONCLUSIONS: Our study showed a prevalence of de novo thyroid autoimmunity in chronic HCV patients treated with IFN-alpha, confirming previous data in literature. The lack of a significant difference between treated and untreated patients strongly suggests that the anti-thyroid autoimmune response is linked to the HCV infection itself. Moreover, IFN-alpha therapy probably does not represent a risk factor in renewing the autoimmune processes of the thyroid gland. Thyroid function and autoantibodies must be systematically monitored in patients with HCV infection, especially in female and IFN-alpha treated population, not only to verify the possible thyroid abnormalities but also to rule out concomitant autoimmune diseases.

Adult↗

A more appropriate algorithm of thyroid function test in diagnosis of hyperthyroidism for Thai patients.

BACKGROUND: Thyroid function test is an essential tool in the diagnosis of thyroid dysfunction. To date, it is still controversial which diagnostic algorithm is best applicable to clinically hyperthyroidism patients. OBJECTIVE: To compare various algorithms of thyroid function tests in the diagnosis of hyperthyroidism. METHOD: Patients from the endocrine clinic, King Chulalongkorn Memorial Hospital were investigated for thyroid function tests (T3, T4, FT3, FT4 and TSH). Hyperthyroidism was defined as an elevated either FT3 or FT4 with suppressed TSH. The authors compared the effectiveness in hyperthyroidism diagnosis among algorithms by using sensitivity, specificity, positive predictive value and negative predictive value. RESULTS: Of all 452 patients in the present study, 94.24 percent were women. There were 206 hyperthyroidism, 30 subclinical hyperthyroidism, 1 subclinical hypothyroidism, 8 primary hypothyroidism and 207 normal subjects. The incidence of T3 toxicosis was 16.02% while that of T4 toxicosis was 2.16%. After the effectiveness analysis of these algorithms, FT3 and TSH is the most optimal test with 97.57% sensitivity and 100% specificity. Compared to FT4 and TSH, it gave 83.98% sensitivity and 100% specificity. CONCLUSION: According to the high incidence of T3 toxicosis in the present study, FT3 and TSH should be the initial test for diagnosis of hyperthyroid patients in an outpatient setting and FT4 should be measured subsequently in case of suspected T4 toxicosis.

Adult↗

Euthyroid hyperthyroxinemia and rapid cycling affective disorder: case report.

A 32-year-old woman with rapid cycling bipolar illness had numerous clinical problems throughout 19 affective episodes and six hospital admissions within 34 months. Persistent hyperthyroxinemia, always associated with manic episodes, led to a diagnostic work-up that ruled out a primary thyroid dysfunction and pointed to oral contraceptives, appetite suppressants, and psychiatric illness as likely causes of elevated T4 values. The contention that an underlying thyroid hypofunction is the basis of rapid cycling is questioned. The extent to which a bipolar disorder increases T4 levels and the role of euthyroid hyperthyroxinemia in the pathogenesis of rapid cycling are discussed.

Adult↗

Assessment of thyroid function with hormone assays.

Measurement of serum thyroid hormone and TSH levels provide diagnostic information in the majority of patients with thyroid dysfunction. The test strategy in hyperthyroidism differs from that in hypothyroidism. Serum T4 is a good test for hyperthyroidism in patients with normal thyroid hormone-binding protein levels. When binding proteins are abnormal serum free T4 is a much more accurate test for hyperthyroidism than serum T4. Serum T3 and the TSH response to TRH are useful tests for the early diagnosis of hyperthyroidism. Serum TSH is a very sensitive indicator of primary hypothyroidism rising already at the subclinical stage of the disease. Serum T4 and free T4, but not serum T3, are useful for the verification of clinical hypothyroidism. Determination of the TRH-stimulated TSH level is important for the differential diagnosis of pituitary and hypothalamic hypothyroidism. It is imperative to recognize that thyroid tests are often abnormal in various non-thyroidal diseases and that administration of drugs can affect these tests. Serum rT3 is of some value for the assessment of thyroid function in patients with non-thyroidal disease.

Humans↗