A848 | Journal of the Endocrine Society | doi: 10.1210/jendso/bvab048 A848 J Endocrine Soc, Volume 5, Issue Supplement_1, April-May 2021 Introduction: Thyroid immune-related adverse events (irAEs) occur frequently after immune checkpoint inhib- itor (ICI) cancer therapy, but their risk factors and po- tential infuence on survival need further investigation. Methods: We performed a retrospective single-center cohort study of adult cancer patients who received ICIs including CTLA-4, PD-1, PD-L1 inhibitors from 12/1/2012- 12/31/2019. Patients who developed thyroid irAEs after ex- cluding surgical or ablative hypothyroidism were included. Survival analysis was performed by Kaplan-Meier curves and Cox-proportional hazards model. Results: Thyroid irAEs occurred in 145 (17.4%) of 834 ICI-treated patients (median age 64.9 y, 43.4% females) during a median fol- low-up of 11.6 mo. New-onset thyroid dysfunction occurred in 118 (14.2%), of which 55 presented with thyrotoxicosis (32 progressed to hypothyroidism, 22 returned to euthyroid state, 1 had Graves’ disease). Worsening of pre-existing au- toimmune hypothyroidism (≥50% increase in levothyroxine dose) occurred in 27 (3.2%). Of those with new-onset thy- roid dysfunction, 79 (67%) required levothyroxine eventu- ally. Patients with thyroid irAE had similar age, sex and cancer type as compared to those without but had higher median pre-treatment TSH [2.4 vs. 1.7 mIU/L (p<0.0001); multivariable OR for TSH ≥2.4 mIU/L of 2 (95% CI 1.3, 3.2; p=0.004)] and higher frequency of autoimmune disease history [26.9% vs. 14.8% (p=0.0009); multivariable OR of 2 (95% CI 1.2, 3.5; p=0.013)]. Thyroid irAEs occurred after a median of 2.4 mo from ICI, most frequently with PD-1/ PD-L1 inhibitor. Thyroid irAEs were associated with better median overall survival [38.8 mo (95% CI 26.6, not reached) vs. 18.9 (95% CI 14.2, 24.8); p<0.0001] which persisted on restricting to patients with new-onset thyroid dysfunction [40.1 mo (95% CI 26.6, not reached) vs. 18.8 (95% CI 13.6, 24.8); p<0.0001]. On multivariable analysis, thyroid irAEs had HR for mortality of 0.51 (95% CI 0.37, 0.71; p<0.0001), which persisted on restricting to new-onset thyroid dysfunc- tion [HR 0.48 (95% CI 0.34, 0.69; p<0.0001)]. Conclusions: Thyroid irAEs frequently occur after PD-1/PD-L1 inhibitor therapy, presenting as hypothyroidism or thyrotoxicosis usually progressing to hypothyroidism. Higher TSH even within normal range and autoimmune disease history may be risk factors for thyroid irAE. Improved survival with thyroid irAEs suggests these could be a marker for anti- tumor activity. Thyroid THYROID AUTOIMMUNITY, COVID-19 & THYROID DISEASE What Are the Common Characteristics of Pediatric Patients With Antibody Negative Primary Hypothyroidism? Rasha Alradadi, MBBS 1 , Erica A. Eugster, MD 2 . 1 Taibah University, almadinah, Saudi Arabia, 2 Indiana University Schl of Medical, Indianapolis, IN, USA. Background: The most common cause of acquired pri- mary hypothyroidism is autoimmune thyroiditis which is typically associated with positive anti-thyroid peroxidase and/or anti-thyroglobulin antibodies. However, some chil- dren present with primary hypothyroidism and negative antibodies. Whether there are differences between patients with acquired primary hypothyroidism who have positive vs negative anti-thyroid antibodies has not been systemati- cally examined. Aim:To defne the characteristics of patients with primary hypothyroidism and negative antibodies. Methods: A retrospective chart review of patients with hypothyroidism seen in the pediatric endocrine clinic at Riley Hospital for Children in Indianapolis, Indiana from August 2016 until December 2019 was performed. Variables examined included age at diagnosis, signs and symptoms at presentation, height, weight, BMI, TSH, FT4, T4, thyroid peroxidase and anti-thyroglobulin antibodies, family history of thyroid disease, physical exam at diag- nosis, and associated diseases. Results: Of 173 patients aged 10.6 ± 3.9 years, 128 (74%) had positive antibodies and 44 (26%) had negative antibodies. Of those with posi- tive antibodies, 80 % were female and 20% were male. Of those with negative antibodies, 53% were female and 47% were male. No differences were seen in the incidence of obe- sity or Down syndrome in patients with positive antibodies compared with those who had negative antibodies. A posi- tive family history of thyroid disease was present in 45% of those with positive antibodies and in 22% of those with negative antibodies, P=0.006 Fifty-eight patients (45%) with positive antibodies reported excessive fatigue and 40 (31%) had a goiter. In contrast, 10 (22.7%) who had nega- tive antibodies reported mild intermittent fatigue, P=0.006 and 7 (15.9 %) had a goiter, P=0.04 The average TSH in the antibody positive group was 129± 230 mcu/ml compared with 48 ± 131 mcu/ml in those with negative antibodies, p=0.04. A trend was also noted for a lower FT4 in those with positive antibodies (0.68±0.37 vs 0.85±0.27, p=0.050) No other differences in baseline characteristics were seen between patients with negative vs positive antibodies. Conclusion: Patients with positive anti-thyroid antibodies had more severe hypothyroidism and were more likely to report extreme fatigue than those with negative antibodies. It is unknown why some children with acquired primary hypothyroidism presumed due to autoimmune thyroid di- sease have negative antibodies. Long-term follow-up will be needed to determine whether the natural history of thyroid disease in children with primary hypothyroidism is associ- ated with antibody status. Thyroid THYROID BIOLOGY, HYPOTHALAMIC-PITUITARY- THYROID AXIS Alert for TSH Measurement in High-Risk Pregnancies in Brazil Lívia Marcela Santos, MD 1 , Déborah Buso Piccinalli Marietto, MD 2 , Juliana Miyuki Miura, MD 2 , Luisa Lacaz Martins Megale, MD 2 , Gabriela Terzian Ganadjian, MD 2 , Leonardo Azevedo Alvares, MD 3 , Priscila Rodrigues Leite Oyama, MS 2 , Thiago Limoli Bueno, MD 2 , Roberta Frota Villas boas, MD 2 . 1 UNIFESP, Sao Paulo SP, Brazil, 2 São Camilo, São Paulo SP, Brazil, 3 USP, SAO PAULO, Brazil. Introduction: The hypothyroidism during pregnancy can lead to alterations in fetal neurological formation and has metabolic impact on pregnant women. If not diagnosed and treated it can cause complications during pregnancy and childbirth, besides causing changes in fetal formation. The Downloaded from https://academic.oup.com/jes/article/5/Supplement_1/A848/6241255 by guest on 30 March 2022