Risk Of Thyroid Dysfunction Research Articles

Association Between Thyroid Function and Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

PurposeChronic obstructive pulmonary disease (COPD) was the fourth leading cause of death in the world. Many studies have shown that COPD often exists with thyroid dysfunction; however, the relationship between thyroid function and COPD is often ignored in clinical. We retrospectively analyze the serum thyroid hormone levels in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and explore the association between thyroid function and AECOPD.MethodsThe study included patients hospitalized for AECOPD in our institution between January 2018 and September 2020. Patients with AECOPD were divided into moderate-to-severe and very severe groups based on lung function, and into normal and abnormal thyroid function groups based on thyroid hormone levels. Collected data and compared data between groups to identify risk factors for thyroid dysfunction in patients with AECOPD.ResultsThe cohort included 97 in the moderate-to-severe group (72.39%) and 37 in the very severe group (27.61%). Compared with the very severe group, the moderate-to-severe group had higher triglyceride (P=0.017), high-density lipoprotein (P<0.05), partial pressure of carbon dioxide (PaCO2; P<0.05), and serum thyroid-stimulating hormone (TSH; P<0.001). FEV1 as a percentage of the predicted value (FEV1%pred) was positively correlated with TSH and FT3 (r=0.329, r=0.192, respectively, both P<0.05). Duration of hospitalization was negatively correlated with TSH (r=−0.256, P=0.003). Among the 134 subjects, 98 (73.13%) had normal thyroid function and 36 (26.87%) had abnormal thyroid function. The two groups significantly differed regarding forced vital capacity (FVC), forced expiratory volume in 1 second, FEV1%pred, and albumin level. Logistic regression analysis showed that high FVC correlated with a low risk of thyroid dysfunction in AECOPD.ConclusionIn patients with AECOPD, TSH is related to lung function and duration of hospitalization, and high FVC reduces the risk of thyroid dysfunction.

Reference values and the effect of clinical parameters on thyroid hormone levels during early pregnancy.

Objective: Thyroid dysfunction is a common endocrine problem during pregnancy; correct diagnosis and appropriate treatments are essential to avoid adverse pregnancy outcomes. Besides, it is vital to identify and quantify the major risk factors for gestational thyroid dysfunction, including thyroid autoimmunity, human chorionic gonadotropin (HCG) concentration, body mass index (BMI) and parity. The study objective was to establish reference ranges during early pregnancy and to explore the relationship between risk factors and thyroid stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyroxine (FT3).Design, patients and measurements: To establish the reference ranges of thyroid hormone during early pregnancy in China and to identify the risk factors for thyroid dysfunction, woman in the first trimester of pregnancy (4–12 weeks gestation) were recruited. After excluding thyroid peroxidase antibody (TPO-Ab) positive and/or thyroglobulin antibody (TG-Ab) positive women, previous thyroid disease, a lack of iodine intake, reference values were calculated by 2.5th to 97.5th percentiles.Results: After exclusion of TPO-Ab and/or TG-Ab positive women, reference values were as follows: TSH, 0.11–3.67 mIU/l; FT3, 3.19–5.91 pmol/l; FT4 10.95–16.79 pmol/l. Higher BMI was associated with lower FT4 concentrations (P=0.005). In multiple regression analysis, TSH was significantly and positively associated with TG (P=0.03). Maternal parity and maternal age may be risk factors for the abnormal thyroidal response to hCG concentrations.Conclusions: Our study defined first trimester-specific reference ranges for serum TSH, FT4, FT3 in a Chinese population, and demonstrated that BMI ≥23kg/m2, maternal parity ≥3 and maternal age ≥30 years may increase the risk of thyroid dysfunction.

The association between serum TSH concentration whithin the normal range and nutritional status in euthyroid pregnant women at the first trimester of gestation.

Background:Follow-up studies have shown an increased risk of thyroid dysfunction in individuals with normal serum thyroid-stimulating hormone (TSH) levels. Furthermore, the possible consequences of minor differences in thyroid function (without achieving poor thyroid function) in the risk of weight gain during pregnancy are questionable, too. The production of TSH is under the hypothalamus–pituitary control, and food is one of the most effective environmental agents that control hypothalamic–pituitary–thyroid axis activity. Regarding the few available studies, we assessed the association of minor variations of TSH concentrations and nutritional status in the first trimester of pregnancy.Materials and Methods:This cross-sectional descriptive and analytical study was performed on 150 primiparous healthy women. Demographic and family characteristics were collected using a researcher-administered questionnaire. Nutrients intake were extracted from a 72-h recall, and physical activity scores were determined by the pregnancy physical activity scale.Results:The prepregnancy body mass index (BMI) (β =0.022, P = 0.004) and participants' weight at 6–10 weeks of gestation (β =0.006, P = 0.024) were positively associated with TSH concentrations, while total physical activity score was negatively correlated (β = ‒0.006, P = 0.047). We did not find any significant association between TSH values and energy-adjusted nutrients intake (P > 0.05).Conclusion:We suggest that differences in TSH concentrations within normal range in the first trimester are correlated with gaining weight, physical activity level, and prepregnancy BMI. TSH concentration and consequently thyroid function may influence on gestational weight gain or vice versa.

Función tiroidea en el recién nacido prematuro con edad gestacional igual o menor a 32 semanas

IntroductionPreterm newborns (PN) have a higher risk of thyroid dysfunction than term newborns (TN). This condition may go unnoticed in neonatal screening due to a late elevation of thyrotropin (TSH) in these patients. ObjectiveEvaluate thyroid function in the second week of life in PN of < 32 weeks gestation (WG), and to identify factors associated to its alteration. Patients and methodsA retrospective study was performed in neonates of < 32 weeks gestation (WG), in whom thyroid function was determined. An analysis was performed on thyroxine (T4L) and TSH levels, as well as their association with perinatal and neonatal outcomes. ResultsThe study included a total of 358 patients with mean gestational age (GA) of 29.3 weeks, and mean birth weight (BW) 1127 grams. A linear correlation was found between T4L and BW (correlation coefficient (R) 0.356; p < 0.001) and GA (R = 0.442; p < 0.001). TSH values were associated with small for gestational age (SGA 5.3 mU/L [1.5-37]; non-SGA 2.89 mU/L [0.2-19.5]; p < 0.001), inotropic support (Yes 3.98 mU/L [0.6-22.9]; No 3.16 mU/L [0.2-37]; p = 0.019) and BW (R = -0.249; p < 0.001). Nine (2.5%) patients were treated with levothyroxine, of whom six were SGA. ConclusionsThyroid function analysis in the second week of life helps to identify asymptomatic newborns with risk of thyroid dysfunction. SGA newborns are at higher risk of thyroid function alterations.

Primary thyroid dysfunction after single intravenous iodinated contrast exposure in young children: a propensity score matched analysis.

Data suggest an increased risk of thyroid dysfunction following iodine-based contrast material (IBCM) in children. To estimate the prevalence of thyroid stimulating hormone (TSH) abnormalities following exposure to a single dose of intravenous IBCM during computed tomography (CT) in young children. Inpatients ≤24months of age who underwent a single CT with intravenous IBCM (exposed cohort) or abdominal ultrasound (US) (unexposed cohort) examination and had a TSH value obtained within 90days after imaging between January 2009 to November 2018 were identified. Propensity score matching with 20 variables was performed. Primary thyroid dysfunction was defined by abnormally high or low TSH value. Multivariable logistic regression identified risk factors, including intravenous IBCM, for thyroid dysfunction. From the eligible 4,215 imaging examinations, 114 unique patients were included in the propensity matched population (n=57 per group). Thyroid dysfunction was identified in 14% (8/57) and 7% (4/57) of the IBCM-exposed and IBCM-unexposed cohorts, respectively. No patient in either cohort was started on thyroid hormone supplementation within the 3months after imaging. Intravenous IBCM exposure was not a significant predictor of thyroid dysfunction on univariable (odds ratio [OR]=2.16, 95% confidence interval [CI]=0.61-7.64, P=0.23) or multivariable (OR=2.61, 95% CI=0.65-10.55, P=0.18) analyses. Significant independent predictors of post-imaging thyroid dysfunction included height (OR=1.25, P=0.0095) and trisomy 21 (OR=4.04, P=0.019). Hospitalized children ≤24months of age who received a single dose of intravenous IBCM for CT examination had a similar prevalence of TSH abnormalities compared to a propensity score matched group who underwent abdominal US. One dose of intravenous IBCM likely does not cause prolonged TSH abnormalities; however, larger studies are needed.

Thyroid Function in 35 Patients with Gitelman Syndrome

Objective. In this study, we aimed to analyze thyroid function and related risk factors for thyroid dysfunction in 35 patients with Gitelman syndrome (GS). Methods. This study included 35 patients with GS who were referred to West China Hospital of Sichuan University from Aug 2013 to Jan 2018. General patient characteristics were collected, and thyroid function was assessed. To evaluate the potential contribution of hypokalemia to thyroid dysfunction, 636 patients who were clinically diagnosed with primary aldosteronism (PA) during the same period were included as the control group; these patients were divided into a hypokalemia group ( N = 528 ) and a normokalemia group ( N = 108 ). Logistic regression was used to screen for significant determinants of thyroid dysfunction in the GS patients. Results. Patients with GS had a significantly different prevalence of subclinical hypothyroidism, hypothyroidism, and hyperthyroidism than patients with hypokalemic PA and normokalemic PA (28.6%, 2.9%, and 11.4% vs. 15.5%, 6.1%, and 0.7% vs. 8.3%, 4.6%, and 2.8%, P &lt; 0.001 ). No significant difference was observed in the distribution of thyroid function between the hypokalemic PA group and the normokalemic PA group ( P &gt; 0.05 ). No significant differences were seen in the positive rates of thyrotropin receptor antibody (TRAb), thyroglobulin antibody (TGAb), and thyroid peroxidase antibody (TPOAb) among the three groups ( P &gt; 0.05 ). In the logistic regression, only sex (OR, 7.4; 95% CI, 1.555-35.479; P = 0.012 ) was significantly correlated with thyroid dysfunction in GS patients. Conclusion. GS is complicated with a greater rate of thyroid dysfunction than primary aldosteronism. The risk of thyroid dysfunction in female patients with GS is higher than that in male patients.

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

Iodine contrast prior to or during pregnancy and neonatal thyroid function: a systematic review.

Thyroid dysfunction is a known side effect of iodinated contrast media. There is some evidence to suggest that iodinated contrast media administered to pregnant women may cause thyroid dysfunction not only in themselves but also in their offspring. Here, we systematically evaluated literature on the use of iodinated contrast media prior to or during pregnancy on the offspring's thyroid function. Systematic review of published literature. Relevant studies were identified by PubMed, EMBASE and The Cochrane Library up to June 5, 2020. All study designs, reporting on the foetal or neonatal thyroid function after exposure to iodinated contrast media prior to or during pregnancy, were included. We undertook random effects meta-analysis and pooled the estimates as proportions with 95% CIs. We identified 402 articles, of which 26 were included. Six studies reported (n = 369) on exposure to iodinated contrast media prior to pregnancy by hysterosalpingography and 20 studies (n = 670) on exposure to these media during pregnancy by amniofetography, urography or CT. There was low to high risk of bias. The proportion of (transient) neonatal thyroid dysfunction was 0.0% (95% CI: 0.0-2.9% based on 3 studies) for hysterosalpingography, 2.25% (95% CI: 0.03-6.55% based on 2 studies) for amniofetography and 0.0% (95% CI: 0.0-0.02% based on 5 studies) for CT. There was a tendency towards an increased risk of thyroid dysfunction with higher amounts of contrast used. Exposure to iodinated contrast media prior to or during pregnancy may increase the risk of thyroid dysfunction in offspring. We recommend keeping the amount of contrast used as low as possible.

Prevalence and Predictors of Thyroid Dysfunction Among Type 2 Diabetic Patients: A Case-Control Study.

BackgroundType 2 diabetes mellitus (T2DM) and thyroid disorders are common endocrine disorders. This case–control study aims to determine the prevalence and predictors of thyroid disorders in T2DM patients.MethodsA total of 998 T2DM patients attending a tertiary hospital were included and underwent investigations for thyroid function: thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3); and glycated hemoglobin (HbA1c). They were compared with 343 non-diabetic subjects as controls.ResultsA total of 1341 participants were included in the study. The mean age ± SD was 60.14 ± 12.21, and 47.9% were females. Among T2DM patients, 140 (14%) were known to have thyroid disorders; and as a direct result of screening, 126 (12.6%) new cases of thyroid disorder were diagnosed. Thus, the overall prevalence of thyroid disorders was found to be 26.7% in T2DM patients which significantly higher than the controls (13.7%), (p˂0.001). Subclinical hypothyroidism was the most common one. Using logistic regression, after adjusting for age, gender, obesity, smoking, anemia, presence of goiter, disease duration, and poorly controlled, the risk factors for thyroid dysfunction among T2DM patients were an age of ≥50 years with an adjusted OR of 3.895 (95% CI 2.151–7.052, p<0.001); female gender (OR 1.757, 95% CI 1.123–2.747, p=0.013); goiter (OR 2.904, 95% CI 1.118–7.547, p=0.029), and HbA1c>7% (OR 2.553, 95% CI 1.472–4.429, p=0.001). However, there were no significant associations between thyroid disorders and complications or duration of diabetes (p>0.050).ConclusionA high prevalence of thyroid disorders was reported in T2DM patients. Therefore, we suggest that diabetic patients should be routinely screened for thyroid dysfunction. Old age, female gender, goiter, and poorly controlled diabetes found to be risk factors for thyroid dysfunction among T2DM patients. Consequently, appropriate management and control of diabetes may lower the risk of thyroid dysfunction and vice versa.

Status of Thyroid Function among Patients of National Medical College and Teaching Hospital

Background: Thyroid dysfunction is one of the most common endocrinopathies after Diabetes Mellitus. Thyroid dysfunction is defined as the alteration in Thyroid Stimulating Hormone (TSH) with normal or abnormal thyroid hormones. Nepalese population have a high risk for thyroid dysfunction with a high prevalence of iodine deficiency.&#x0D; Objective: To study the prevalence of thyroid dysfunction among the patients visiting National Medical College, Birgunj, Nepal for checkup and suggested to assess thyroid function.&#x0D; Materials and Methods: The hospital-based study was conducted in Central Laboratory, National Medical College and Teaching Hospital (NMCTH), Birgunj in collaboration with the Department of Biochemistry. Total 7040 patients visiting Central Laboratory for thyroid function assessment were included in the study between July 2017 to December 2019. The venous blood sample was collected and serum-free triiodothyronine(fT3), free tetraiodothyronine(fT4) and thyroid stimulating hormone (TSH) was estimated by Chemiluminescence Immunoassay (CLIA) method using Access 2 Beckman Coulter analyser. (Beckman Coulter Inc., California, USA).&#x0D; Results: Among 7040 subjects under study, 2138(30%) were found to have thyroid dysfunction with 13% having subclinical hypothyroidism, about 8% of overt hypothyroidism, about 4% with subclinical hyperthyroidism and 5% with overt hyperthyroidism. Majority of the thyroid dysfunction study group belonged to the 16-30 years age group followed by 31-45 years. Mean±SE for TSH, fT4 and fT3 levels show statistically significant differences in different thyroid disorders.&#x0D; Conclusion: The study revealed a high prevalence of subclinical hypothyroidism followed by overt hypothyroidism among the patients visiting National Medical College and Teaching Hospital, Birgunj, Nepal. A higher percentage of females were found to have thyroid dysfunction compared to male.

Liver toxicity as a limiting factor to the increasing use of immune checkpoint inhibitors.

SummaryImmune checkpoint inhibitors (ICIs) improve clinical outcomes in patients suffering from different types of cancer. Liver toxicity is one of the immune-related adverse events associated with immunotherapy; although not common, its management is challenging as it is extremely heterogeneous in terms of presentation and severity. Differences in the development and evolution of ICI-related toxicity in healthy or cirrhotic livers have not yet been elucidated. Assessing causality is key to diagnosing ICI-induced liver toxicity; liver biopsies can assist not only in the differential diagnosis but also in assessing the severity of histological liver damage. The current classification of severity overestimates the grade of liver injury and needs to be revised to reflect the views of hepatologists. Spontaneous improvements in ICI-related liver toxicity have been reported, so corticosteroid therapy should probably be individualised not systematic. The reintroduction of ICIs in a patient with previous immune-mediated hepatitis may be possible, but the risk/benefit ratio should be considered, as the risk factors for hepatitis recurrence are currently unclear. The management of these patients, requiring a balance between efficacy, toxicity and specific treatments, necessitates multidisciplinary collaboration. The incidence of immune-related liver toxicity will continue to rise based on the increasing use of ICIs for most cancers, mandating improved understanding and management of this complication.

Iodine status during pregnancy and at 6 weeks, 6, 12 and 18 months post-partum.

Iodine deficiency during pregnancy and in the post‐partum period may lead to impaired child development. Our aim is to describe iodine status longitudinally in women from pregnancy until 18 months post‐partum. Furthermore, we explore whether iodine status is associated with dietary intake, iodine‐containing supplement use and breastfeeding status from pregnancy until 18 months post‐partum. We also assess the correlation between maternal iodine status 18 months post‐partum and child iodine status at 18 months of age. Iodine status was measured by urinary iodine concentration (UIC) during pregnancy (n = 1,004), 6 weeks post‐partum (n = 915), 6 months post‐partum (n = 849), 12 months post‐partum (n = 733) and 18 months post‐partum (n = 714). The toddlers' UIC was assessed at 18 months of age (n = 416). Demographic variables and dietary data (food frequency questionnaire) were collected during pregnancy, and dietary data and breastfeeding practices were collected at all time points post‐partum. We found that iodine status was insufficient in both pregnant and post‐partum women. The UIC was at its lowermost 6 weeks post‐partum and gradually improved with increasing time post‐partum. Intake of milk and use of iodine‐containing supplements significantly increased the odds of having a UIC above 100 μg/L. Neither the mothers' UIC, vegetarian practice, nor exclusion of milk and dairy products were associated with the toddlers UIC 18 months post‐partum. Women who exclude milk and dairy products from their diets and/or do not use iodine‐containing supplements may be at risk of iodine deficiency. The women possibly also have an increased risk of thyroid dysfunction and for conceiving children with nonoptimal developmental status.

Thyroid Toxicity Following Immune Checkpoint Inhibitor Treatment in Advanced Cancer.

Background: Inhibitory antibodies against cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed cell death-1 (PD-1) have antitumor efficacy and are now standard of care in the management of multiple cancer subtypes. However, the use is complicated by the development of autoimmunity, which can occur in multiple organ systems. Thyroiditis is the most common immune-related adverse event. Summary: Immune checkpoint inhibitor (ICI)-associated thyroiditis affects over 10% of treated patients. PD-1 inhibitors are associated with greater risk of thyroid dysfunction relative to CTLA-4 inhibitors, although the highest risk occurs with combined anti-CTLA-4 and anti-PD-1 treatment. Onset is typically rapid, within weeks to months and both hyperthyroidism and hypothyroidism can occur. The most frequent pattern of thyroid dysfunction is transient hyperthyroidism with evolution to hypothyroidism over four to six weeks. Most cases are asymptomatic and resolve without dedicated treatment. There is no sex or age predominance, and predictive risk factors have not been reliably identified. Thyroid autoantibodies are variably present and are not clearly related to the risk or progression of thyroid dysfunction following treatment with an ICI. Observational data suggest that development of ICI-associated thyroiditis may predict improved survival. Conclusions: ICI-associated thyroiditis is a distinct clinical entity. Mechanisms underlying etiology remain largely unknown. Awareness among health professionals is important to limit morbidity and avoid unnecessary periods of untreated hypothyroidism.

MON-LB016 Tyrosine Kinase Inhibitor Induced Hypothyroidism in Pediatric and Young Adult Population: An Institutional Review

Tyrosine Kinase Inhibitor Induced Hypothyroidism in Pediatric and Young Adult Population: An institutional reviewBackground:Tyrosine kinase inhibitors (TKIs) are a class of molecular targeted therapies approved for the treatment of several hematological and solid tumors in pediatric population. Thyroid dysfunction, most commonly primary hypothyroidism, is a well described adverse effect in adults. There is no available data in the pediatric population regarding the risk of thyroid dysfunction with the use of TKIs.Objective:To document the incidence of hypothyroidism in the pediatric and young adult patients on TKI therapy.Methods:A retrospective chart review including patients’ ≤ 21 years of age who had been treated with at least 1 of 10 predetermined TKIs for malignancy was performed. Demographics, TKI use and duration, thyroid hormone labs, and history of head/neck radiation were collected. We excluded patients with pre-existing thyroid disease prior to start of TKI therapy. Thyroid dysfunction was defined as TSH >5mcIU/mL during TKI therapy. Results:A total of 152 patients who were treated with TKIs for malignancy were identified. The mean age was 12.4 years (SD 6.5). About 20% of patients had therapy with multiple TKI drugs. A total of 24 patients were noted to have TSH elevation >5mcIU/ml of which 19 had a TSH >10 mcIU/mL or low free T4. Fourteen patients were started on levothyroxine. Average duration of TKI therapy prior to development of thyroid dysfunction was 6.7 months but over half developed hypothyroidism within 3 months of initiation of TKI therapy. Cabozantinib and pazopanib were responsible for 70% of TKI associated cases of thyroid dysfunction.Conclusion:This is the first report of incidence of primary hypothyroidism in pediatric and young adult patients treated with TKIs. Thyroid dysfunction can develop in the first few months of therapy and often is clinically significant. Early recognition and treatment of this complication will be important for patient care especially as use of these class of drugs increase.

SUN-431 Case Finding Versus Routine Screening of Thyroid Dysfunction in Pregnancy

Background:Thyroid dysfunction in pregnancy is associated several adverse outcomes. This has triggered a debate about whether universal screening should be implemented. Despite recommendations against universal screening, the clinical practice of many caregivers may differ. We aimed to assess the sensitivity of using targeted high-risk case finding for diagnosing thyroid dysfunction in pregnancy compared to routine screening in pregnant Saudi women, and to evaluate if gestational diabetes (GDM) specifically affected the risk.Methods:A cross-sectional study in two hospitals under the Ministry of National Guards Health affairs of Saudi Arabia; King Abdulaziz Hospital, Al-Ahsa, and Imam Abdulrahman bin Faisal Hospital, Dammam. Pregnant ladies attending the Family medicine, Obstetrics and Gynecology, and Endocrinology clinics in both hospitals were assessed by the caring physician based on a check list for risk stratification for thyroid dysfunction as per the 2012 Endocrine society clinical practice guidelines for management of thyroid dysfunction in pregnancy. Presence of one risk factor defined high risk. All patients had a routine serum TSH measured as universal screening is commonly practiced in both institutions, the physician doing the risk stratification was not aware of the TSH result. Sensitivity and specificity for the case finding approach was calculated using and abnormal TSH value as the gold standard for presence of thyroid dysfunction. The institutions lab reference TSH 0.35 – 4.94 mIU/L was used as cutoff.Results:1571 pregnant women were included in the study; mean age 29.3± 6.2 years, 396 (23.5%) were primigravida. The mean TSH value was 1.898 ± 1.459 mlU/L. 1178 (75%) pregnant women had an indication for screening based on presence of at least one risk factor, of which 95 (8.1%) tested abnormal for TSH. 393 women had no risk factors, of which 379 (96.4%) had normal TSH, (Chi square 9.3, p-value 0.002). [Sensitivity 87.2%, (95%CI 79.4% – 92.8%), Specificity 25.9%, (95%CI 23.7% – 28.3%)]. Total abnormal TSH values was 109 (6.9%), 43 were abnormal high (i.e. hypothyroid); of which 40 screened positive by case finding approach [Sensitivity 93.02%, (95%CI 80.9% – 98.5%), Specificity 25.52%, (95%CI 23.4% – 27.8%)]. Moreover, 178 (11.3%) women screened positive for GDM at some stage in pregnancy out of which only 5 (2.8%) had an abnormal TSH value, while of the 1393 pregnant women who screened negative for GDM 1289 (92.5%) had a normal TSH value, (Chi square 5.3, p-value 0.02). [Sensitivity 4.6%, (95%CI 1.5% – 10.4%), Specificity 88.2%, (95%CI 86.4% – 89.8%)].Conclusion:Targeted high-risk case finding predicts thyroid dysfunction in pregnant Saudi women with high sensitivity supporting its utility in screening our pregnant population. Gestational diabetes is highly prevalent in Saudi women, but does not increase risk of thyroid dysfunction in pregnancy.

The Genetic Basis of Thyroid Function: Novel Findings and New Approaches.

Genetic factors are major determinants of thyroid function. Over the last two decades, multiple genetic variants have been associated with variations in normal range thyroid function tests. Most recently, a large-scale genome-wide association study (GWAS) doubled the number of known variants associated with normal range thyrotropin (TSH) and free thyroxine (FT4) levels. This review summarizes the results of genetic association studies on normal range thyroid function and explores how these genetic variants can be used in future studies to improve our understanding of thyroid hormone regulation and disease. Serum TSH and FT4 levels are determined by multiple genetic variants on virtually all levels of the hypothalamus-pituitary-thyroid (HPT) axis. Functional follow-up studies on top of GWAS hits has the potential to discover new key players in thyroid hormone regulation, as exemplified by the identification of the thyroid hormone transporter SLC17A4 and the metabolizing enzyme AADAT. Translational studies may use these genetic variants to investigate causal associations between thyroid function and various outcomes in Mendelian Randomization (MR) studies, to identify individuals with an increased risk of thyroid dysfunction, and to predict the individual HPT axis setpoint. Recent genetic studies have greatly improved our understanding of the genetic basis of thyroid function, and have revealed novel pathways involved in its regulation. In addition, these findings have paved the way for various lines of research that can improve our understanding of thyroid hormone regulation and thyroid diseases, as well as the potential use of these markers in future clinical practice.

Iodinated contrast media and their effect on thyroid function - Routines and practices among diagnostic imaging departments in Norway.

IntroductionIn order to minimise adverse effects or patient injuries related to the effect of iodinated contrast media (ICM) on the thyroid, international guidelines and research recommend developing routines for identification and management of patients at risk of developing a thyroid dysfunction. This study aimed to investigate thyroid‐related ICM administration practices among diagnostic imaging departments in Norway.MethodsThe cross‐sectional survey included 24 hospitals and 75 respondents with a 69% response rate. The survey covered practices for assessment and management of at‐risk patients and the participants’ perceived rationale for the routines.ResultsThe use of written checklists as recommended by international guidelines was quite modest (15%) and the respondents preferred various methods to identify risk and contraindications. Only 20% reported checking for any scheduled thyroid‐scintigraphy and/or radioactive‐iodine therapy. 42% indicated that they did not have thyroid‐related ICM routines, and the main perceived reason was lack of knowledge on the topic. Radiographers and radiologists expressed uncertainty about each other’s roles and routines.ConclusionThis study revealed the need of optimisation of routines regarding ICM administration to patients at risk for thyroid dysfunction.

Screening for thyroid disease in patients with type 2 diabetes mellitus: An evaluation of current practice.

United Kingdom national guidelines do not recommend routine testing for thyroid disease in people with type 2 diabetes mellitus (T2DM). However, some studies suggest an increased risk of thyroid dysfunction in T2DM. The aim of this study was to evaluate the current practice of screening for thyroid disease in patients with T2DM. Patients with pre-existing T2DM (n = 339) were selected from records for routine glycated haemoglobin testing performed in December 2008. Using routinely collected primary/secondary care data from 2009 to 2017, we examined longitudinal thyroid-stimulating hormone and free thyroxine requests to determine the overall proportion of patients screened for thyroid dysfunction and the time interval between thyroid tests requested. Thirty-three patients (9.7%) had pre-existing thyroid disease. Of the remaining 306 patients, 96.4% had at least one thyroid test during the follow-up period. When the time interval between tests was evaluated in these patients, there was a discrete peak in thyroid function test requests at 12 months, consistent with routine annual testing. Most requests (77%) originated from a general practice setting. Contrary to current guidelines, we have provided evidence suggestive of regular screening for thyroid dysfunction in patients with T2DM, particularly in general practice. The appropriateness of this practice remains unclear, but may warrant further examination to assess the clinical benefits of screening, balanced against cost.

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.

Comparing the Incidence of Thyroid Dysfunction in Pediatric Subjects after HSCT with Reduced Intensity Vs. Myeloablative Conditioning

Introduction Subjects who undergo hematopoietic stem cell transplant (HSCT) are at increased risk for thyroid dysfunction. Few studies compare myeloablative (MAC) and reduced intensity (RIC) conditioning regimens. Objectives Describe the prevalence, incidence, and risk factors for thyroid disorder in pediatric and young adult subjects one year after HSCT after implementation of a universal screening program. Methods We performed a retrospective chart review of 167 subjects who were transplanted from June 2016 to August 2018 at CCHMC and underwent prospective universal late effects screening. One hundred forty-one subjects surviving to 1 year after HSCT were included. Results One hundred nine subjects had documented TSH values at least 9 months after HSCT. Median followup for screened subjects was 669 days (range, 271-1166). Subjects with documented TSH were similar to the overall cohort. Eight subjects had thyroid disorders prior to transplant, and ten developed thyroid disorders after transplant. Of these ten, none had chronic graft-versus-host disease (cGvHD), one had acute GvHD, and one had received TBI (Table 1). The median time to detection of a thyroid disorder was 430 days (range, 231-790) after transplant. One subject developed Hashimoto thyroiditis, one developed Graves disease, seven developed primary hypothyroidism without evidence of autoimmunity, and one developed pazopanib-associated hypothyroidism. This subject developed fatigue, prompting thyroid evaluation; however, the remaining nine patients were clinically euthyroid at diagnosis. Of the 31 subjects at risk who received RIC, 1 (3.2%) developed a new thyroid disorder, compared to 9 of 69 (13.0%) subjects who received MAC (p=0.167). Overall, 10.9% of subjects at risk for thyroid dysfunction after HSCT developed new disease. Conclusion Thyroid dysfunction remains a significant risk after HSCT, particularly after myeloablative conditioning. Annual screening beginning at one year from HSCT is recommended to improve early detection rates, especially since the majority of subjects detected in our analysis had no symptoms of new thyroid disease.