Patients Developed Thyroid Dysfunction Research Articles

Magnitude and time course of urinary iodine excretion in patients after amiodarone therapy.

Amiodarone is a source of iodine excess that may persist in the body for long time after its withdrawal. The aim of the present analysis was to evaluate the magnitude and long-term time course of 24-h urinary iodine (UI) excretion in patients on antiarrhythmic therapy with amiodarone. 24-h UI excretion and thyroid function were evaluated in 67 patients on amiodarone therapy. All patients were clinically and biochemically euthyroid before starting treatment and were followed-up by 6-month measurements of 24-h UI excretion and plasma thyroid hormones levels. Upon amiodarone withdrawal, normal range of UI was achieved after a mean time of 15.2±7.7 months. Since amiodarone initiation, 20 patients developed thyroid dysfunction. No differences were observed in terms of treatment length or median UI levels between patients remaining euthyroid and those developing thyroid dysfunction: median UI in the euthyroid group was 8094 µg/24 h (Interquartile Range [IQR]: 4082-10766) vs. 10851 µg/24 h (IQR: 8529-12804) in the thyroid dysfunction group at 6 months (P=0.176) and 8651 µg/24 h (IQR: 6924-11574) vs. 8551 µg/24 h (IQR: 4916-13580) at one year from amiodarone initiation (P=0.886). The occurrence of thyroid dysfunction was equally distributed among patients taking amiodarone for more than one year versus those under treatment for less than one year. These results confirm the long-lasting total-body iodine stores and consequent excretion in patients after amiodarone withdrawal. These long-lasting iodine stores might be taken into special account in patients necessitating therapy with radioactive iodine and for long-term monitoring of thyroid function after amiodarone discontinuation.

SAT453 Endocrine Related Adverse Events Of Immune Checkpoint Inhibitors In Cancer Patients Visiting Tertiary Care Center In Saudi Arabia

Abstract Disclosure: A.M. Alqahtani: None. A.S. Alghassab: None. L.A. Alghamdi: None. M. Almalki: None. Introduction: Immune checkpoint inhibitors (ICIs) have been approved for the treatment of a different types of cancers. Those agents may result in exaggerated immune response leading to numerous toxicities referred to as immune-related adverse events particularly endocrinopathies affecting most commonly the thyroid and pituitary glands. Methods: We carried out a retrospective analysis of endocrine dysfunction in cancer patients receiving immune checkpoint inhibitors therapy namely pembrolizumab, nivolumab and ipilimumab between July 2018 and July 2022. A total of 123 patients were included in this analysis. We reviewed pituitary-, thyroid-, and adrenal-related hormone test results, as well as the clinical perspective of patients, to identify and characterize cases of hypophysitis, hypothyroidism, thyroiditis, and adrenal dysfunction. Results: A total of 123 patients were included in our study. Among them, Female participants were 67 (54.5%) and males were 56 (45.5%) with mean age of 53.7 years. Majority of the included patients (91.1%) received single agent and only 8.9% received combination therapy. The most used ICI in our cohort was pembrolizumab 73.9% followed by nivolumab 17.8% and the combination of either one of them (beside ipilimumab) was used in 8.9% of the time. The most frequent indication for ICIs was breast cancer (27.6%) followed by lung cancer (19.5%) and metastatic renal cell carcinoma (8.9%). The average number of cycles was 12 cycles, and the average duration of treatment was 12 months. The total incidence of all endocrinopathies was 22.7%. Out of 123 patients, 24 patients developed thyroid dysfunction in term of thyroiditis (1), subclinical hypothyroidism (7) or overt hypothyroidism (16). Hypophysitis occurred in one patient only. There was no occurrence of new onset diabetes mellitus in all groups. Pembrolizumab is thought to be the culprit in 18 patients of thyroid dysfunction and the patient who developed hypophysitis. Nivolumab was responsible about 4 cases of thyroid dysfunction. The rest of the cases were attributed to the combination therapy. The mean TSH level at the time of hypothyroidism diagnosis (overt hypothyroidism and subclinical hypothyroidism) was 95.8 mIU/L. And the mean free thyroxine level in overt hypothyroidism group was 6.3 pmol/L. Conclusion: Our cohort demonstrated an increased risk of thyroid dysfunction among cancer patients who receive immune checkpoint inhibitors. Pituitary dysfunction is infrequent adverse effect of these agents. Endocrine assessment is recommended prior to initiation of therapy and periodically afterward. Special attention should be given to pituitary dysfunction as it might be overlooked due to non-specific symptoms. Presentation: Saturday, June 17, 2023

Thyroid dysfunction after immune checkpoint inhibitor treatment in a single-center Chinese cohort: a retrospective study.

Thyroid dysfunction is a common adverse event after immune checkpoint inhibitor (ICI) therapy. The clinical manifestations of thyroid immune-related adverse events (irAEs) are variable and the underlying mechanisms remain unclear. To identify the clinical and biochemical characteristics of Chinese patients with ICI-related thyroid dysfunction. We retrospectively reviewed patients with carcinoma who received ICI therapy and underwent evaluation of thyroid function during hospitalization at Peking Union Medical College Hospital between January 1, 2017 and December 31, 2020. Clinical and biochemical features were analyzed in patients who developed ICI-related thyroid dysfunction. Survival analyses were performed to determine the effect of thyroid autoantibodies on thyroid abnormalities and the impact of thyroid irAEs on clinical outcomes. The cohort included 270 patients with a median follow-up of 17.7 months; 120 (44%) of these patients developed thyroid dysfunction on immunotherapy. The most common thyroid irAE was overt hypothyroidism (with/without transient thyrotoxicosis), which occurred in 38% of patients (n = 45), followed by subclinical thyrotoxicosis (n = 42), subclinical hypothyroidism (n = 27), and isolated overt thyrotoxicosis (n = 6). The median time to first clinical presentation was 49 days (interquartile range 23, 93) for thyrotoxicosis and 98 days (interquartile range 51, 172) for hypothyroidism. In patients treated with PD-1 inhibitors, hypothyroidism was strongly associated with younger age (odds ratio [OR] 0.44, 95% confidence interval [CI] 0.29-0.67; P < 0.001), previous thyroid disease (OR 4.30, 95% CI 1.54-11.99; P = 0.005), and a higher baseline thyroid-stimulating hormone level (OR 2.76, 95% CI 1.80-4.23; P < 0.001). Thyrotoxicosis was only associated with the baseline thyroid-stimulating hormone (TSH) level (OR 0.59, 95% CI 0.37-0.94; P = 0.025). Thyroid dysfunction after initiation of ICI therapy was associated with better progression-free survival (hazard ratio [HR] 0.61, 95% CI 0.44-0.86; P = 0.005) and overall survival (hazard ratio 0.67, 95% CI 0.45-0.99; P = 0.046). Anti-thyroglobulin antibody positivity increased the risk of thyroid irAEs. The occurrence of thyroid irAEs with diverse phenotypes is common. Distinct clinical and biochemical characteristics suggest heterogeneity among different subgroups of thyroid dysfunction, which requires further research to explore the under mechanism.

One-year follow-up of thyroid function in 23 infants with Prader- Willi syndrome at a single center in China.

Endocrine disorders are common in patients with Prader-Willi syndrome (PWS). Whether hypothyroidism is present in patients with PWS, and especially infants and young children, remains unclear. The aims of this study were to evaluate thyroid function in patients with PWS, to assess the prevalence of thyroid dysfunction, and to evaluate the effect of growth hormone on thyroid function. Subjects were 23 patients with PWS ages 3 months to 3 years who were followed for up to one year. Four patients were lost to follow-up after the first visit. The remaining 19 patients were treated with recombinant human growth hormone (rhGH). PWS was diagnosed based on a genetic analysis. Free thyroxine (FT4), free triiodothyronine (FT3), and thyroid-stimulating hormone (TSH) levels were evaluated before and after growth hormone treatment. A total of 9 patients (9/23 = 39.1%) developed abnormal thyroid function. Five out of 23 patients (21.7%) had abnormal thyroid function before growth hormone treatment. Four patients developed thyroid dysfunction during the 3- to 9-month period of rhGH treatment. Of the 9 patients with abnormal thyroid function, 7 (5 boys, 2 girls) had central hypothyroidism, and the other 2 patients had subclinical hypothyroidism. TSH levels were higher in patients with PWS due to maternal uniparental disomy (UPD) than in patients with PWS due to a 15q11-q13 deletion. The prevalence of hypothyroidism was high in infants and young children with PWS. Thyroid function should be regularly monitored in patients with PWS at both diagnosis and follow-up.

Thyroid dysfunction and survival in cancer patients treated with immune checkpoint inhibitors: analyses from a large single tertiary cancer center database

Purpose We aimed to assess the incidence, clinical and biochemical course of immunotherapy-induced thyroiditis and its implication on patients’ survival, based on an extensive clinical experience from a tertiary cancer center. Methods Analyses were based on data from the electronic medical records of cancer patients treated with CPIs. Data included demographic characteristics, cancer type, Thyroid function tests (TFT), and survival. Results Thyroid function tests were available for 934 patients. After excluding patients with impaired baseline TFT or levothyroxine treatment, 754 euthyroid patients were included in the core analyses. Of those, 301 (39.9%) patients developed thyroid dysfunction (‘thyroiditis’). Thyroiditis was more prevalent in patients with renal cell carcinoma than other types of cancer. Survival rates were comparable in patients who developed thyroiditis and in those who did not. during the 5 years follow-up period, there was a non-significant trend toward improved survival in patients who developed TD in four predefined groups: melanoma, lung cancer, renal cell carcinoma, and transitional cell carcinoma. Nevertheless, we observed a highly significant survival benefit for patients with renal cell carcinoma who developed TD (HR = 0.19, 95% CI 0.06–0.60; p = 0.005). Conclusions Thyroiditis is common, often asymptomatic, and is more prevalent in patients treated with combinations of nivolumab and PD-L1 inhibitors, and in patients with renal cell carcinoma. Thyroiditis was associated with a trend for a survival benefit, particularly in patients with renal cell carcinoma.

Amiodarone-associated thyroid dysfunction in adult patients with congenital heart disease: a nationwide health insurance data analysis including &amp;gt;50.000 individuals

Abstract Background Arrhythmias are common in adult patients with congenital heart disease (ACHD). Amiodarone is widely used as an antiarrhythmic agent. Thyroid dysfunction represents a serious complication of amiodarone treatment. Systematic data on the prevalence of thyroid dysfunction, risk factors for complications and treatment options are lacking. Purpose Based on data from one of the largest German Health Insurance Companies (BARMER GEK, approx. 9 million members), we performed a retrospective analysis investigating the rate of thyroid complications under active amiodarone therapy in ACHD patients and a comparison group of cardiac patients without congenital heart disease on amiodarone between 2005 and 2018. Result Overall, 910 ACHD (34% female; median age 66 y; CHD complexity mild, moderate, severe in 64.6%, 23.6%,11.8%, respectively) and 49,782 non-ACHD patients (37% female, median age 73.4 y) received prescriptions for amiodarone without documented pre-existing thyroid disease or use of thyroid medication. Over a treatment period of 184,770 patient-years, 10,874 incidents of thyroid dysfunction occurred in the non-ACHD and 201 in the ACHD cohort, corresponding to an event-rate of 6% and 5.3% per patient year, respectively. Overall, 23.5% of the ACHD patients developed thyroid dysfunction (56.71% hypothyroidism, 43.3% hyperthyroidism). Risk factors for developing thyroid dysfunction on time dependent Cox-analysis were female gender (hazard ratio [HR] 1.44, 95% CI: 1.39–1.50; p&amp;lt;0.001), lower patient age (HR: 0.96 per 10 years, 95% CI: 0.94–0.98, p&amp;lt;0.001) renal dysfunction (HR 1.24, 95% CI: 1.19–1.29, p&amp;lt;0.001), history of alcohol abuse (HR 1.17, 95% CI: 1.07–1.27, p,0.001) and smoking (HR 1.12, 95% CI: 1.06–1.19, p&amp;lt;0.001). Congenital heart disease itself was not associated with a higher risk of thyroid dysfunction (HR 0.96, 95% CI: 0.83–1.10, p=0.53). Within the ACHD group, patients with complex disease had a significantly higher risk of thyroid dysfunction (HR 1.5, 95% CI: 1.00–2.25, p=0.049) compared to patients with simple diagnoses. Once thyroid disease occurred, 48.5% of patients were continued on amiodarone therapy, 12.8% of patients underwent an electrophysiologic procedure and only 2.1% of patients received class I antiarrhythmics. Specific thyroid therapy included thyroxine (62.6% of hypothyroid patients) or thiamazole (22.6% of hyperthyroid patients). Only 2.3% of patients required surgery or radiotherapy within 6 months after thyroid dysfunction. Conclusion Amiodarone-associated thyroid dysfunction is a frequent complication in ACHD patients. Overall, one in 4 ACHD patients on amiodarone developed thyroid dysfunction in our study. In itself, ACHD does not seem to increase the risk of thyroid dysfunction. However, female gender, complexity of disease, younger age and renal dysfunction emerged as independent risk factors. When amiodarone therapy can not be avoided, close follow-up and regular thyroid function tests are recommended. Funding Acknowledgement Type of funding source: None

History of Radiation to the Neck Increases the Risk of Denovo Thyroid Dysfunction after Receiving Immune Checkpoint Inhibitors

Thyroid dysfunction is a common endocrine side effect of immune checkpoint inhibitors (ICI). We designed a retrospective study, including patients who received ICI for any cancer at our institution. Thyroid-stimulating hormone (TSH), free T4 levels, and time to development of thyroid dysfunction were measured, and medication used to treat thyroid dysfunction were identified. We reviewed the charts of 104 patients with complete records obtained from our tumor registry. A total of 91 patients were included in the analysis, after excluding 13 patients with a pre-existing thyroid disorder. Twenty-eight (30.77%) patients developed thyroid dysfunction after starting ICI. Race (p-0.048), age (p-0.014), history of radiation therapy (RT) to the neck (p-0.004), history of RT to the chest (p-0.012), and history of venous thrombosis (p-0.004) were significantly associated with thyroid dysfunction on univariate analysis. For multivariate analysis, the history of RT to the neck, adjusted for age, race, and sex, was significantly associated with thyroid dysfunction (adjusted OR-9.64, 95%CI: 1.88, 49.36, p-0.007). In patients receiving ICI for any type of cancer, the previous history of RT to the neck was significantly associated with the development of thyroid dysfunction after starting ICI.

Biochemical follow-up of nonfunctioning benign thyroid nodules.

For the biochemical follow-up of benign thyroid nodules, some authors recommend periodic lifelong measurement of thyroid-stimulating hormone (TSH) to assess for the development of toxic nodules over time. The purpose of this retrospective study was to assess the incidence of thyroid dysfunction over time in patients with benign thyroid nodule(s), with a normal TSH at diagnosis and to identify any factors that may predict biochemical dysfunction over time. Medical records of patients with the diagnosis of thyroid nodule(s) between January 2011 and August 2014 were reviewed. Patients who had TSH measurement within 1year of initial diagnostic ultrasound (US) were included. One-hundred fifty-seven patients identified with thyroid nodule(s) satisfied inclusion criteria. At a median follow-up of 45 (34-63) months, 13 (8.3%) patients developed thyroid dysfunction. The mean initial TSH in the group which developed subclinical hyperthyroidism (0.65mIU/mL) was statistically different from the group that did not develop thyroid dysfunction (1.37mIU/mL, P: 0.007). More patients with TSH <1mIU/L developed thyroid dysfunction as compared to subjects with TSH ≥1 mIU/L (P: .022). There was no significant difference in the incidence of thyroid dysfunction on the basis of gender, race, smoking status, TPO Ab positivity and number of nodules at diagnosis. We recommend re-examining the current practice and clinical utility of frequent TSH monitoring in all patients with thyroid nodules, particularly if initial TSH level is ≥1mIU/L.

Anti-thyroid antibodies and thyroid echo pattern at baseline as risk factors for thyroid dysfunction induced by anti-programmed cell death-1 antibodies: a prospective study

BackgroundAnti-programmed cell death-1 (PD-1) antibodies can cause thyroid dysfunction. However, no predictive biomarkers enabling stratification of thyroid dysfunction risk have been identified.MethodsA total of 209 patients treated with an anti-PD-1 antibody were evaluated for anti-thyroid antibodies at baseline and prospectively for thyroid function every 6 weeks for 24 weeks after treatment initiation, and then observed until the visits stopped. Thyroid ultrasonography was performed if the patient was positive for anti-thyroid antibodies at baseline.ResultsOf the 209 patients, 19 (9.1%) developed thyroid dysfunction (destructive thyroiditis or hypothyroidism). The cumulative incidence of thyroid dysfunction was significantly higher in patients who were positive vs. negative for anti-thyroid antibodies (15/44 [34.1%] vs. 4/165 [2.4%], p < 0.001). Forty-two patients positive for anti-thyroid antibodies at baseline were divided into two groups according to the presence of an irregular echo pattern. The cumulative incidence of thyroid dysfunction was significantly higher in those with an irregular vs. a regular echo pattern (13/23 [56.5%] vs. 1/19 [5.3%], p = 0.001). None of the patients developed thyroid dysfunction after the initial 24-week period.ConclusionsThe risk of thyroid dysfunction induced by anti-PD-1 antibodies can be predicted by evaluation of anti-thyroid antibodies and the thyroid echo pattern at baseline.Trial registrationUMIN000019024.

Late effects after hematopoietic stem cell transplantation for β-thalassemia major: the French national experience.

In this retrospective study, we evaluate long-term complications in nearly all β-thalassemia-major patients who successfully received allogeneic hematopoietic stem cell transplantation in France. Ninety-nine patients were analyzed with a median age of 5.9 years at transplantation. The median duration of clinical follow up was 12 years. All conditioning regimens were myeloablative, most were based on busulfan combined with cyclophosphamide, and more than 90% of patients underwent a transplant from a matched sibling donor. After transplantation, 11% of patients developed thyroid dysfunction, 5% diabetes, and 2% heart failure. Hypogonadism was present in 56% of females and 14% of males. Female patients who went on to normal puberty after transplant were significantly younger at transplantation than those who experienced delayed puberty (median age 2.5 vs. 8.7 years). Fertility was preserved in 9 of 27 females aged 20 years or older and 2 other patients became pregnant following oocyte donation. In addition to patient’s age and higher serum ferritin levels at transplantation, time elapsed since transplant was significantly associated with decreased height growth in multivariate analysis. Weight growth increased after transplantation particularly in females, 36% of adults being overweight at last evaluation. A comprehensive long-term monitoring, especially of endocrine late effects, is required after hematopoietic stem cell transplantation for thalassemia.

Characterization and implications of thyroid dysfunction induced by immune checkpoint inhibitors in real-life clinical practice: a long-term prospective study from a referral institution.

Autoimmune diseases are typically associated with immune checkpoints blockade. This study aims at assessing, in real-life clinical practice, the prevalence and impact of thyroid disorders induced by immune checkpoint inhibitors. 52 patients (30 F; age 61±13years) with advanced melanoma treated with ipilimumab (3mg/kg i.v./3weeks; 4 doses) were included. For disease progression, 29 (16 F) of them received nivolumab (3mg/kg i.v./2weeks) or pembrolizumab (2mg/kg i.v./3weeks). Thyroid function and autoimmunity were assessed before, after 6weeks, at the end of ipilimumab, as well as before and every 3months during nivolumab/pembrolizumab treatment. During ipilimumab, 7 (4 F) patients developed thyroid dysfunction (4 thyroiditis, 1 associated with hypothyroidism; 2 thyrotoxicosis in a previously euthyroid multinodular goiter; 1 hypothyroidism worsened). During PD1 inhibitors, 7 patients (3 F) developed hypothyroidism with severe manifestations in 6 of them; 3 patients suffered from euthyroid autoimmune thyroiditis from baseline, one after ipilimumab; 2 patients developed after transient thyrotoxicosis. Mean follow-up after anti-CTLA4 inhibitors treatment was 36±28months. Thyroid disorders occurred 45.1±20.8 and 151±67days after the initiation of CTLA4 and PD1 inhibitors, respectively. Autoimmune disorders and BRAF mutation were associated with a better clinical response to CTLA4 followed by PD1 treatment. Immune checkpoint blockade is burdened by a high incidence of autoimmune thyroid dysfunction, which is often severe. Therefore, early and careful monitoring and, eventually, treatment are crucial to prevent the negative impact of thyroid dysfunction on the clinical outcome.

Antibody-mediated thyroid dysfunction during T-cell checkpoint blockade in patients with non-small-cell lung cancer

Programmed cell death protein-1 (PD-1) blockade therapies have demonstrated durable responses and prolonged survival in a variety of malignancies. Treatment is generally well tolerated although immune-related adverse events (irAEs) can occur. Autoimmune thyroid dysfunction is among the most common irAE, but an assessment of the clinical, mechanistic, and immunologic features has not been previously described. Patients with advanced non-small-cell lung cancer (NSCLC) treated with pembrolizumab at Memorial Sloan Kettering Cancer Center (n = 51) as part of KEYNOTE-001 (NCT01295827) were included. Thyroid function test and anti-thyroid antibodies were assessed prospectively at each study visit, beginning before the first treatment. Frequency of development of thyroid dysfunction, association with anti-thyroid antibodies, clinical course, and relationship with progression-free survival and overall survival to treatment with pembrolizumab was evaluated. Of 51 patients treated, 3 were hypothyroid and 48 were not at baseline. Ten of 48 [21%, 95% confidence interval (CI) 10% to 35%] patients developed thyroid dysfunction requiring thyroid replacement. Anti-thyroid antibodies were present in 8 of 10 patients who developed thyroid dysfunction, compared with 3 of 38 who did not (80% versus 8%, P < 0.0001). Thyroid dysfunction occurred early (median, 42 days) in the pembrolizumab course, and a majority (6 of 10 patients) experienced brief, transient hyperthyroidism preceding the onset of hypothyroidism; no persistent hyperthyroidism occurred. Both hyperthyroidism and hypothyroidism were largely asymptomatic. Overall survival with pembrolizumab was significantly longer in subjects who developed thyroid dysfunction (hazard ratio, 0.29; 95% CI 0.09-0.94; P = 0.04). Thyroid dysfunction during pembrolizumab treatment of NSCLC is common and is characterized by early-onset, frequently preceded by transient hyperthyroidism, closely associated with anti-thyroid antibodies, and may be associated with improved outcomes. The presence of antibody-mediated toxicity in T-cell-directed therapy suggests an under-recognized impact of PD-1 biology in modulating humoral immunity.

Can thyroid volume predict thyroid dysfunction in patients with systemic sclerosis? A prospective cross-sectional study from a tertiary care center in North West India.

Previous studies have documented an association between thyroid dysfunction, predominant hypothyroidism, and antibody positivity in patients with systemic sclerosis (SSc). There are no studies reporting the relationship between thyroid volume and thyroid functions in patients with SSc. This study was conducted to correlate thyroid dysfunction with thyroid volume as measured on ultrasound and antibody positivity. Complete thyroid workup was done in 106 patients of SSc which included thyroid function test, antithyroid peroxidase (TPO) antibody, antithyroid-stimulating hormone receptor (TSHR) antibody, antithyroglobulin antibody, and thyroid ultrasound to assess thyroid volume, echogenicity and blood flow, and fine needle aspiration cytology of suspicious thyroid lesions. Prevalence of subclinical hypothyroidism was 8.5 %, overt hypothyroidism 1.9 %, subclinical hyperthyroidism 2.8 %, and overt hyperthyroidism in 0.9 % of the patients. Antithyroid peroxidase antibody was positive in 16 %, anti-TSH receptor antibody in 5.7 %, and antithyroglobulin antibody in none of the patients. Thyroid volume was in the range of atrophy (<4.5 ml) in 57.5 % patients, echogenicity altered in 15.1 %, and blood flow increased in 15.1 %. Thyroid volume correlated strongly with the pulmonary function test (FEV1). Routine thyroid ultrasound and thyroid function tests may be included in the workup of patients with SSc for the early detection of hypothyroidism since a small but significant percentage of patients developed thyroid dysfunction. Antithyroid antibodies may not correlate with the thyroid functions and hence should not be recommended.

Prevalence of Thyroid Autoantibodies in Children, Adolescents and Young Adults with Type 1 Diabetes in Kuwait

Objective: To investigate the prevalence of thyroid autoimmunity among children and adolescents with type 1 diabetes in Kuwait. Subjects and Methods: In a mixed cross-sectional and longitudinal study, anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-TG) were measured in 232 subjects (118 males and 114 females) with type 1 diabetes. Results: The mean age of the total study population was 10.9 ± 3.6 years (range 1-21), and the median diabetes duration was 3.9 years (range 0-16). At the initial screening, 57 out of 232 (24.6%) patients had positive antibodies, and of the remaining 175 patients, who were antibody negative,131 (74.3%) were followed up for 4-9 years. 23 out of these 131 (17.7%) patients became antibody positive, with a cumulative prevalence of elevated antibodies of 34.5%. Anti-TPO was present in 34 (14.7%), anti-TG in 23 (9.9%) and both antibodies in 23 (9.9%) patients. Thyroid antibodies presented early within the first 5 years of the onset of diabetes (63.2 vs. 36.8%, p < 0.05). The prevalence of elevated thyroid antibodies increased after the onset of puberty in both females and males (p < 0.0001). A total of 58.7% of the patients with positive antibodies were females compared to 41% males (p < 0.0001). The basal thyroid-stimulating hormone was higher in subjects with positive antibodies (5.1 ± 10.7 mIU/l) compared to those who were antibody negative (1.79 ± 0.87 mIU/l, p < 0.001). Furthermore, 30 out of 232 (12.9%) patients developed thyroid dysfunction. Conclusion: In this study, a high prevalence of thyroid autoimmune antibodies was found in patients either at the onset of type 1 diabetes or within the 4-9 years of follow-up.

THYROID DYSFUNCTION

Hepatitis C is a burning issue. Prevalence of hepatitis C virus reported in Pakistanis 5% with areas of high infection in different cities and subsets of population. Objectives: Tofind out the frequency of thyroid related dysfunctions in chronic hepatitis C patients on Peg-Interferon Alpha-2a and Ribavirin therapy. Study Design: A prospective cohort study. Placeand Duration of Study: Hepatitis Center DHQ teaching hospital Sahiwal from July 2013 to June2014. Material and Methods: We studied 100 patients of chronic HCV infection with baselinelevel of TSH,T3 and T4. Baseline serum ALT and serum AST were also measured. Patients wereput on Peg-Interferon Alpha-2a (180 ug) weekly and Ribavirin (800 to 1000 mg/d) for 24weeks.All patients were followed up for thyroid dysfunction at weeks 0, 12, 18 and 24. Result: Outof 100 treated patients 65 were female and 35 were male. Fifteen (15%) patients developedthyroid dysfunction and out of these 15 patients (11 female [73.3%] and 4 male [26.7%]).Ten (66.6%) out of 15 patients developed hypothyroidism and 5(33.3%) out of 15 patientsdeveloped hyperthyroidism. Seven (70%) out of 10 patients who developed hypothyroidismneeded levothyroxine therapy. Two (40%) out of 5 patients who developed hyperthyroidismneeded carbimazol therapy for their symptoms and disease control. All patients completedhepatitis C treatment with combined Peg-Interferon Alpha-2a and Ribavirin therapy.

Analysis of thyroid dysfunction and influencing factors in chronic hepatitis C patients treated with peg-IFNa-2a and ribavirin

To analyze the frequency of thyroid dysfunction and determine its influencing factors in chronic hepatitis C (CHC) patients treated with pegylated-interferon alpha (peg-IFNa)-2a and ribavirin (RBV) combination therapy. A total of 194 CHC patients were treated with peg-IFNa-2a and RBV for 48 weeks. Development of thyroid dysfunction was recorded. Clinical and biological factors from pre-treatment (baseline) to post-treatment were statistically analyzed to determine correlation with thyroid dysfunction in this patient population. Fifty-two (26.80%) of 194 peg-IFNa-2a/RBV-treated patients developed thyroid dysfunction. Dysfunction severity ranged from hyperthyroidism (n = 1, 0.52%) and hypothyroidism (n = 10, 5.15%) to subclinical hyperthyroidism (n = 4, 2.06%) and subclinical hypothyroidism (n = 37, 19.07%). The dysfunction rate was significantly higher after peg-IFNa-2a/RBV treatment (26.80% vs. 12.37% at baseline, x2 = 12.829, P less than 0.05, odds ratio (OR) = 0.386, 95% confidence interval (CI): 0.226-0.657), in females (33.00% vs. 20.21% in males, P less than 0.05, 95% CI: 1.016-3.040), and in thyroid auto-antibody positive patients (64.29% vs. 23.89% in negative patients, P less than 0.05, 95% CI: 1.681-36.183). Early virological response did not have any significant effect on dysfunction rate (23.00% vs. 30.85% no early virological response, x2 = 1.522, P more than 0.05) nor did end of treatment response (27.19% vs. 26.25% no response at end of treatment, x2 = 0.021, P more than 0.05). Patients who developed thyroid dysfunction had higher interleukin (IL)-6 at baseline (i.e. before peg-IFNa-2a/RBV treatment) (27.08+/-14.90 vs. 11.65+/-5.46 in patients who maintained normal thyroid function, t = 3.127, P less than 0.05, 95% CI: 5.28-25.58). IL-6 levels were not significantly different between the two groups at 24 weeks (6.30+/-2.47 vs. 6.81+/-2.80, t = 0.352, P more than 0.05). IL-6 levels before and after 48 weeks of treatment in normal thyroid function patients were 27.08+/-14.90 and 6.30+/-2.47, t = 3.632, P less than 0.05, and in thyroid dysfunction patients were 11.65+/-5.46 and 6.81+/-2.80, t = 1.997, P more than 0.05. Peg-IFNa-2a/RBV combination therapy may cause thyroid dysfunction, especially hypothyroidism, in CHC patients. Female sex and thyroid auto-antibody positivity may put CHC patients at higher risk of developing thyroid dysfunction during peg-IFNa-2a/RBV therapy. Elevated IL-6 may be a predictive marker of peg-IFNa-2a/RBV-induced thyroid dysfunction.

Thyroid Function Abnormalities In Adults Following Haematopoetic Stem Cell Transplant (HSCT).

AbstractAbstract 1305Purpose/Rationale The risk of thyroid dysfunction following stem cell transplant with myeloablative conditioning including total body irradiation (TBI) is well established. However, the impact of reduced intensity, non TBI-based containing regimens is not well defined. Patients and Methods:821 consecutive adult patients (520 male, 301 female), who underwent stem cell transplantation at a single centre between 1999 and 2007 were included in this retrospective analysis. The median age at transplant was 54 years (range 16–71 yrs). Patients received either myeloablative allogeneic (n=138), reduced intensity (RIC) allogeneic (n=104) or autologous (n=579) procedures; the source of stem cells was bone marrow (n=98), HPC-A (n=695) or both (n=28). Of the allogeneic transplants, 122 were from an HLA identical sibling and 120 from a matched unrelated donor. All of the myeloablative patients received TBI as part of the conditioning protocol, reduced intensity allogeneic procedures was performed using non-TBI based conditioning (mainly fludarabine, melphalan and alemtuzumab) and most (91%) of the autologous transplants were performed using high dose chemotherapy. The majority of allogeneic procedures were as treatment for acute leukaemia, whilst the autologous transplants were predominantly used as treatment for either myeloma or lymphoma. Patients were evaluated to identify the incidence and risk factors for the development of hypothyroidism using competing risk analysis. All patients who had biochemical evidence of hypothyroidism at any point with routine annual screening were included. Results:In the entire cohort, 40 patients developed thyroid dysfunction (22 allograft and 18 autograft). The risk of developing thyroid dysfunction was 5.6% at 4yr., and 6.5% at 10 yr. Thyroid dysfunction developed at a median of 1.9 yr. (range: 1–7.7 yr.). In univariate analysis, the risk of developing thyroid dysfunction was significantly greater in allograft recipients vs autograft recipients (10%-myeloablative, 9%-RIC vs 3% auto, p=0.006) and in patients who developed any degree of GvHD (10% - GvHD vs. 3.6% - no GvHD p= 0.003). There was no effect of time since transplant, sex of donor or recipient, age and primary disease. In multivariate analysis, allogeneic transplantation (HR: 3.7, 95% CI: 1.2–11.7, p=0.03) and TBI conditioning (RR: 1.6, 95% CI: 1.02–3.1, p=0.045) were independently associated with increased risk of thyroid dysfunction. Conclusion:The results of this series demonstrate a significant risk of thyroid dysfunction following non TBI based reduced intensity allogeneic stem cell transplantation that was equivalent to that observed following TBI based myeloablative procedures. The risk was greater than that in recipients of chemotherapy based autologous transplants suggesting that this is not a result of the conditioning chemotherapy. The presence or absence of GvHD represents one possible explanation for this observation and although a significantly higher incidence of thyroid dysfunction was observed in patients who developed GvHD (acute or chronic) this potential association was not confirmed on multivariate analysis. These findings warrant further investigation and suggest that all allogeneic transplant recipients should undergo regular assessment of thyroid function irrespective of the conditioning protocol employed. Disclosures:No relevant conflicts of interest to declare.

The role of thyroid autoantibodies in the development of thyroid dysfunction in Taiwanese chronic hepatitis C patients with interferon‐alpha and ribavirin combination therapy

To investigate the role of thyroid autoantibodies in the development of thyroid dysfunction among chronic hepatitis C (CHC) patients receiving interferon-alpha (IFN-alpha) plus ribavirin (RBV) combination therapy, 95 Taiwanese naïve patients with baseline euthyroidism were enrolled. They were treated with IFN-alpha2b, 6 million units thrice weekly, plus RBV 1,000-1,200 mg daily for 24 weeks. Thyroid function, anti-thyroglobulin and antiperoxidase autoantibodies were tested at enrollment (M0), at the end-of-treatment (M6) and 6 months after end-of-treatment (M12). The percentages of thyroid autoantibodies were 8.4%, 11.6% and 9.5%, at M0, M6 and M12 respectively. Fourteen (14.7%) patients developed thyroid dysfunction at M6 or M12. Thyroid dysfunction occurred during treatment in five (62.5%) of the eight patients with baseline thyroid autoantibodies, which was significantly higher than nine (10.3%) of 87 patients without baseline thyroid autoantibodies (P = 0.0001). Among 14 patients who developed thyroid dysfunction, four (80.0%) of five patients with baseline thyroid autoantibodies recovered at M12, in contrast to two (25%) of eight without baseline thyroid autoantibodies recovered at M12 (P < 0.05). In conclusion, thyroid autoantibodies, either occurred before or during IFN-alpha plus RBV combination therapy, carry a high prediction of subsequent thyroid dysfunction. There also exists difference in the clinical manifestations of thyroid dysfunction in CHC patients treated with combination therapy.

Virologic factors related to interferon-alpha-induced thyroid dysfunction in patients with chronic hepatitis C.

Hepatitis C virus (HCV), being reported to be associated with a high prevalence of serological markers of autoimmunity in HCV-infected patients, and possibly sharing partial sequences in amino acid segments with thyroid tissue antigens, may be associated with interferon-alpha (IFN-alpha)-induced thyroid dysfunction in chronic hepatitis C patients. We conducted this study to clarify the issue. One hundred and fifty chronic hepatitis C patients with normal baseline thyroid function were treated with IFN-alpha 2a, 2b and n1 (3-6 million Units three times weekly for 24 weeks). Pretreatment sera were tested for HCV genotype and HCV RNA levels. Serum thyrotropin, total thyroxine and free thyroxine index were performed every 4 weeks for 24 weeks followed by every 8 weeks for another 24 weeks. Twenty-one (14.0%) patients developed early thyroid dysfunction (abnormal thyroid function during the first 3 months of therapy). Female gender, lower HCV RNA levels, IFN-alpha n1 and a lower IFN-alpha dose were significantly associated with early thyroid dysfunction. On multivariate analysis, gender, IFN-alpha preparation and HCV RNA levels were the significant factors associated with early thyroid dysfunction. Seven (4.7%) patients developed thyroid dysfunction during the second 3 months of IFN-alpha therapy. Taken together, 18.7% patients developed thyroid dysfunction. Female, mixed HCV genotype infection and lower HCV RNA levels were significantly associated with thyroid dysfunction. However, only gender remained significantly associated with IFN-alpha-induced thyroid dysfunction in multivariate analysis. The virologic features of HCV may be associated with thyroid dysfunction in chronic hepatitis C patients treated with IFN-alpha. Nevertheless, gender still plays the most important role in IFN-alpha-induced thyroid dysfunction.

Hypothyroïdie après traitement radiochirurgical des cancers de l'hypopharynx

In a series of 224 patients treated between 1980 and 1992 for hypopharyngeal carcinoma by surgery and post postoperative radiotherapy we found an overall 54% incidence of elevated TSH levels. Decreased FT4 levels were associated in about one-third of the patients. When thyroidectomy was performed, 71% of the patients developed thyroid dysfunction. Most TSH abnormalities (45%) occurred within two years of treatment. Nevertheless, long-term followup is indicated since those complications may be delayed. Hormonal replacement therapy is recommended for patients with elevated TSH.