Endocrinology and Metabolism

Review Articles

Thyroid
Diagnosis and Management of Thyroid Disease during Pregnancy and Postpartum: 2023 Revised Korean Thyroid Association Guidelines: Hwa Young Ahn, Ka Hee Yi; Endocrinol Metab. 2023;38(3):289-294. Published online June 9, 2023; DOI: https://doi.org/10.3803/EnM.2023.1696

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Thyroid hormone plays a critical role in fetal growth and development, and thyroid dysfunction during pregnancy is associated with several adverse outcomes, such as miscarriage and preterm birth. In this review, we introduce and explain three major changes in the revised Korean Thyroid Association (KTA) guidelines for the diagnosis and management of thyroid disease during pregnancy: first, the normal range of thyroid-stimulating hormone (TSH) during pregnancy; second, the treatment of subclinical hypothyroidism; and third, the management of euthyroid pregnant women with positive thyroid autoantibodies. The revised KTA guidelines adopt 4.0 mIU/L as the upper limit of TSH in the first trimester. A TSH level between 4.0 and 10.0 mIU/L, combined with free thyroxine (T4) within the normal range, is defined as subclinical hypothyroidism, and a TSH level over 10 mIU/L is defined as overt hypothyroidism regardless of the free T4 level. Levothyroxine treatment is recommended when the TSH level is higher than 4 mIU/L in subclinical hypothyroidism, regardless of thyroid peroxidase antibody positivity. However, thyroid hormone therapy to prevent miscarriage is not recommended in thyroid autoantibody-positive women with normal thyroid function.

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Use of thyroid hormones in hypothyroid and euthyroid patients: A survey of members of the Endocrine Society of Australia
Nicole Lafontaine, Suzanne J. Brown, Petros Perros, Enrico Papini, Endre V. Nagy, Roberto Attanasio, Laszlo Hegedüs, John P. Walsh
Clinical Endocrinology.2024; 100(5): 477. CrossRef
Management of Subclinical Hypothyroidism: A Focus on Proven Health Effects in the 2023 Korean Thyroid Association Guidelines
Eu Jeong Ku, Won Sang Yoo, Hyun Kyung Chung
Endocrinology and Metabolism.2023; 38(4): 381. CrossRef
Maternal isolated hypothyroxinemia in the first trimester is not associated with adverse pregnancy outcomes, except for macrosomia: a prospective cohort study in China
Jing Du, Linong Ji, Xiaomei Zhang, Ning Yuan, Jianbin Sun, Dan Zhao
Frontiers in Endocrinology.2023;[Epub] CrossRef

Miscellaneous
Clinical Characteristics, Management, and Potential Biomarkers of Endocrine Dysfunction Induced by Immune Checkpoint Inhibitors: Shintaro Iwama, Tomoko Kobayashi, Hiroshi Arima; Endocrinol Metab. 2021;36(2):312-321. Published online April 27, 2021; DOI: https://doi.org/10.3803/EnM.2021.1007

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Immune-related adverse events (irAEs) affecting the endocrine glands are among the most frequent irAEs induced by immune checkpoint inhibitors (ICIs) and include hypopituitarism, primary adrenal insufficiency, thyrotoxicosis, hypothyroidism, hypoparathyroidism, and type 1 diabetes mellitus. Since the incidence and clinical features of endocrine irAEs vary according to the ICI used, it is important to understand the characteristics of these irAEs and to manage each one appropriately. Since some endocrine irAEs, including adrenal crisis and diabetic ketoacidosis, are potentially life-threatening, predicting the risk of endocrine irAEs before their onset is critical. Several autoantibodies have been detected in patients who develop endocrine irAEs, among which anti-thyroid antibodies may be predictive biomarkers of thyroid dysfunction. In this review, we describe the clinical features of each endocrine irAE induced by ICIs and discuss their potential biomarkers, including autoantibodies.

Citations

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Clinical characteristics and potential biomarkers of thyroid and pituitary immune-related adverse events
Tomoko Kobayashi, Shintaro Iwama, Hiroshi Arima
Endocrine Journal.2024; 71(1): 23. CrossRef
A case of rapidly progressive insulin-dependent diabetes mellitus without islet autoantibodies developed over two years after the first dose of nivolumab
Kota Nishihama, Yuko Okano, Chisa Inoue, Kanako Maki, Kazuhito Eguchi, Soichiro Tanaka, Atsuro Takeshita, Mei Uemura, Taro Yasuma, Toshinari Suzuki, Esteban C. Gabazza, Yutaka Yano
Diabetology International.2024;[Epub] CrossRef
Endocrinopathies Associated With Immune Checkpoint Inhibitor Use
Anupam Kotwal, Randol Kennedy, Nupur Kikani, Sonali Thosani, Whitney Goldner, Afreen Shariff
Endocrine Practice.2024;[Epub] CrossRef
Recovery from insulin dependence in immune checkpoint inhibitor‐associated diabetes mellitus: A case report
Marie Okubo, Yuji Hataya, Kanta Fujimoto, Toshio Iwakura, Naoki Matsuoka
Journal of Diabetes Investigation.2023; 14(1): 147. CrossRef
Case Report: A Rising Cause of New-Onset Endocrinopathies After Immunotherapy
Charity Tan, Sarah Hendricks, Kristina Hernandez, Martha Benavides, Rupinderjit Samra
The Journal for Nurse Practitioners.2023; 19(5): 104582. CrossRef
Risk of Thyroid Dysfunction in PD-1 Blockade Is Stratified by the Pattern of TgAb and TPOAb Positivity at Baseline
Xin Zhou, Shintaro Iwama, Tomoko Kobayashi, Masahiko Ando, Hiroshi Arima
The Journal of Clinical Endocrinology & Metabolism.2023; 108(10): e1056. CrossRef
Severe thyrotoxicosis induced by tislelizumab: a case report and literature review
Liman Huo, Chao Wang, Haixia Ding, Xuelian Shi, Bin Shan, Ruoying Zhou, Ping Liang, Juan Hou
Frontiers in Oncology.2023;[Epub] CrossRef
Life-Threatening Endocrinological Immune-Related Adverse Events of Immune Checkpoint Inhibitor Therapy
Aleksandra Basek, Grzegorz K. Jakubiak, Grzegorz Cieślar, Agata Stanek
Cancers.2023; 15(24): 5786. CrossRef
Increased Risk of Thyroid Dysfunction by PD-1 and CTLA-4 Blockade in Patients Without Thyroid Autoantibodies at Baseline
Shintaro Iwama, Tomoko Kobayashi, Yoshinori Yasuda, Takayuki Okuji, Masaaki Ito, Masahiko Ando, Xin Zhou, Ayana Yamagami, Takeshi Onoue, Yohei Kawaguchi, Takashi Miyata, Mariko Sugiyama, Hiroshi Takagi, Daisuke Hagiwara, Hidetaka Suga, Ryoichi Banno, Tets
The Journal of Clinical Endocrinology & Metabolism.2022; 107(4): e1620. CrossRef
Biomarkers and risk factors for the early prediction of immune-related adverse events: a review
Ying Zhang, Xiaoling Zhang, Weiling Li, Yunyi Du, Wenqing Hu, Jun Zhao
Human Vaccines & Immunotherapeutics.2022;[Epub] CrossRef
Immune Checkpoint Inhibitors as a Threat to the Hypothalamus–Pituitary Axis: A Completed Puzzle
Agnese Barnabei, Andrea Corsello, Rosa Maria Paragliola, Giovanni Maria Iannantuono, Luca Falzone, Salvatore Maria Corsello, Francesco Torino
Cancers.2022; 14(4): 1057. CrossRef
Elevated TSH Level, TgAb, and Prior Use of Ramucirumab or TKIs as Risk Factors for Thyroid Dysfunction in PD-L1 Blockade
Tomoko Kobayashi, Shintaro Iwama, Ayana Yamagami, Yoshinori Yasuda, Takayuki Okuji, Masaaki Ito, Xin Zhou, Masahiko Ando, Takeshi Onoue, Takashi Miyata, Mariko Sugiyama, Daisuke Hagiwara, Hidetaka Suga, Ryoichi Banno, Tetsunari Hase, Masahiro Morise, Taka
The Journal of Clinical Endocrinology & Metabolism.2022; 107(10): e4115. CrossRef
Preconditioning of the immune system modulates the response of papillary thyroid cancer to immune checkpoint inhibitors
Fabiana Pani, Yoshinori Yasuda, Sylvie T Rousseau, Kevin C Bermea, Solmaz Roshanmehr, Rulin Wang, Srinivasan Yegnasubramanian, Patrizio Caturegli, Luigi Adamo
Journal for ImmunoTherapy of Cancer.2022; 10(12): e005538. CrossRef
Survival benefit of endocrine dysfunction following immune checkpoint inhibitors for nonthyroidal cancers
Anupam Kotwal, Mabel Ryder
Current Opinion in Endocrinology, Diabetes & Obesity.2021; 28(5): 517. CrossRef

Original Article

Clinical Study
Changes in Thyroid Peroxidase and Thyroglobulin Antibodies Might Be Associated with Graves' Disease Relapse after Antithyroid Drug Therapy: Yun Mi Choi, Mi Kyung Kwak, Sang Mo Hong, Eun-Gyoung Hong; Endocrinol Metab. 2019;34(3):268-274. Published online September 26, 2019; DOI: https://doi.org/10.3803/EnM.2019.34.3.268

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Background

Graves' disease (GD) is an autoimmune thyroid disorder caused by antibodies stimulating the thyrotropin (TSH) receptor. TSH receptor antibody (TRAb) measurement is useful for predicting GD relapse after antithyroid drug (ATD) treatment. However, the association of other thyroid autoantibodies with GD relapse remains obscure.

Methods

This retrospective study enrolled patients with GD who were initially treated with ATD. TRAb, thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) were measured at the initial diagnosis and at the time of ATD discontinuation.

Results

A total of 55 patients were enrolled. The mean age was 49.7 years, and 39 patients (70.9%) were female. Antibody positivity at diagnosis was 90.9%, 69.1%, and 61.9% for TRAb, TPOAb, TgAb, respectively. Median ATD treatment period was 15.1 months. At the time of ATD withdrawal, TRAb titers decreased uniformly overall. Conversely, TPOAb and TgAb showed various changes. After withdrawal of ATD, 19 patients (34.5%) experienced relapse. No clinical features or laboratory results were significantly related to relapse in the overall patient group. However, in the TPOAb positive group at diagnosis, increasing titer of TPOAb or TgAb after ATD treatment was significantly and independently related to relapse free survival (TPOAb: hazard ratio [HR], 17.99; 95% confidence interval [CI], 1.66 to 195.43; P=0.02) (TgAb: HR, 5.73; 95% CI, 1.21 to 27.26; P=0.03).

Conclusion

Changes in TPOAb or TgAb titers during treatment might be useful for predicting relapse after ATD treatment in patients with positive TPOAb at diagnosis.

Citations

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Enhanced predictive validity of integrative models for refractory hyperthyroidism considering baseline and early therapy characteristics: a prospective cohort study
Xinpan Wang, Tiantian Li, Yue Li, Qiuyi Wang, Yun Cai, Zhixiao Wang, Yun Shi, Tao Yang, Xuqin Zheng
Journal of Translational Medicine.2024;[Epub] CrossRef
Clinical significance of thyroglobulin antibodies and thyroid peroxidase antibodies in Graves’ disease: a cross-sectional study
Masahito Katahira, Taku Tsunekawa, Akira Mizoguchi, Mariko Yamaguchi, Kahori Tsuru, Hiromi Takashima, Ryoma Terada
Hormones.2023; 22(2): 253. CrossRef
The Clinical Implications of Anti-thyroid Peroxidase Antibodies in Graves’ Disease in Basrah
Emad S Alhubaish, Nassar T Alibrahim, Abbas A Mansour
Cureus.2023;[Epub] CrossRef
Influence of Thyroid Peroxidase Antibodies Serum Levels in Graves' Disease: A Retrospective Cohort Study
Maria L Guia Lopes, Carlos Tavares Bello, José P Cidade, Clotilde Limbert, Joao Sequeira Duarte
Cureus.2023;[Epub] CrossRef
Interpretation of Thyroid Autoantibodies in Hyperthyroidism
Han-Sang Baek, Dong-Jun Lim
The Korean Journal of Medicine.2023; 98(3): 132. CrossRef
Usefulness of Real-Time Quantitative Microvascular Ultrasonography for Differentiation of Graves’ Disease from Destructive Thyroiditis in Thyrotoxic Patients
Han-Sang Baek, Ji-Yeon Park, Chai-Ho Jeong, Jeonghoon Ha, Moo Il Kang, Dong-Jun Lim
Endocrinology and Metabolism.2022; 37(2): 323. CrossRef
Differential Diagnosis of Thyrotoxicosis by Machine Learning Models with Laboratory Findings
Jinyoung Kim, Han-Sang Baek, Jeonghoon Ha, Mee Kyoung Kim, Hyuk-Sang Kwon, Ki-Ho Song, Dong-Jun Lim, Ki-Hyun Baek
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The relationship between atherosclerotic disease and relapse during ATD treatment
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Frontiers in Cardiovascular Medicine.2022;[Epub] CrossRef
Programmed Cell Death-Ligand 1 (PD-L1) gene Single Nucleotide Polymorphism in Graves’ Disease and Hashimoto’s Thyroiditis in Korean Patients
Jee Hee Yoon, Min-ho Shin, Hee Nam Kim, Wonsuk Choi, Ji Yong Park, A Ram Hong, Hee Kyung Kim, Ho-Cheol Kang
Endocrinology and Metabolism.2021; 36(3): 599. CrossRef
Low frequency of IL-10-producing B cells and high density of ILC2s contribute to the pathological process in Graves’ disease, which may be related to elevated-TRAb levels
Xiaoyun Ji, Jie Wan, Rong Chen, Huixuan Wang, Lan Huang, Shwngjun Wang, Zhaoliang Su, Huaxi Xu
Autoimmunity.2020; 53(2): 78. CrossRef
Implication of VDR rs7975232 and FCGR2A rs1801274 gene polymorphisms in the risk and the prognosis of autoimmune thyroid diseases in the Tunisian population
S Mestiri, I Zaaber, I Nasr, H Marmouch
Balkan Journal of Medical Genetics.2020; 23(1): 69. CrossRef
Thyroid Peroxidase Antibody Positivity is Associated With Relapse-Free Survival Following Antithyroid Drug Treatment for Graves Disease
Christopher A. Muir, Graham R.D. Jones, Jerry R. Greenfield, Andrew Weissberger, Katherine Samaras
Endocrine Practice.2020; 26(9): 1026. CrossRef
Predicting the Risk of Graves Disease Relapse: Commentary on “Thyroid Peroxidase Antibody Positivity is Associated with Relapse-Free Survival Following Antithyroid Drug Treatment for Graves Disease”
D. Gallo, M.L. Tanda, E. Piantanida
Endocrine Practice.2020; 26(9): 1039. CrossRef

Review Article

Diabetes
Latent Autoimmune Diabetes in Adults: Current Status and New Horizons: Paolo Pozzilli, Silvia Pieralice; Endocrinol Metab. 2018;33(2):147-159. Published online June 21, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.2.147

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Autoimmune diabetes is a heterogeneous disease which can arise at any age. Subjects with adult-onset autoimmune diabetes who do not necessitate insulin-therapy for at least 6 months after diagnosis are demarcated as having latent autoimmune diabetes in adults (LADA). This condition is more heterogeneous than young-onset autoimmune diabetes and shares clinical and metabolic characteristics with both type 2 and type 1 diabetes. Patients with LADA are considered by having highly variable β-cell destruction, different degrees of insulin resistance and heterogeneous titre and pattern of islet autoantibody, suggesting different pathophysiological pathways partially explaining the heterogeneous phenotypes of LADA. To date the heterogeneity of LADA does not allow to establish a priori treatment algorithm and no specific guidelines for LADA therapy are available. These subjects are mostly treated as affected by type 2 diabetes, a factor that might lead to the progression to insulin-dependency quickly. A personalised medicine approach is necessary to attain optimal metabolic control and preserve β-cell function to decrease the risk of long-term diabetes complications. Recent data concerning the use of oral antidiabetic agents as dipeptidyl peptidase 4 inhibitors and glucagon-like peptide 1 receptor agonists indicate up-and-coming results in term of protect C-peptide levels and improving glycaemic control. This review summarises current knowledge on LADA, emphasising controversies regarding its pathophysiology and clinical features. Moreover, we discuss data available about novel therapeutic approaches that can be considered for prevention of β-cell loss in LADA.

Citations

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