Observational Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Oct 6, 2019; 7(19): 2942-2952
Published online Oct 6, 2019. doi: 10.12998/wjcc.v7.i19.2942
Association of stiff-person syndrome with autoimmune endocrine diseases
Yi-Yin Lee, I-Wen Chen, Szu-Tah Chen, Chih-Ching Wang
Yi-Yin Lee, I-Wen Chen, Szu-Tah Chen, Chih-Ching Wang, Department of Internal Medicine, Division of Endocrinology and Metabolism, Chang Gung Memorial Hospital, Taoyuan City 333, Taiwan
Author contributions: Lee YY wrote the manuscript, analyzed the data, and contributed to discussion; Wang CC analyzed the data and contributed to discussion; Chen IW and Chen ST contributed to discussion and reviewed/edited the manuscript; Wang CC is the guarantor of this work, has full access to all the data in the study, and takes responsibility for the integrity of the data.
Institutional review board statement: The study was reviewed and approved by the Chang Gung Memorial Hospital Institutional Review Board.
Informed consent statement: This study was approved by the Institutional Review Board of Chang Gung Memorial Hospital, and informed consent was not required because that data was drawn from observing behavior and did not contain identifiable information.
Conflict-of-interest statement: The authors report no relevant conflicts of interest.
Data sharing statement: The authors confirm that the data supporting the findings of this study are available within the article.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Chih-Ching Wang, MD, Attending Doctor, Endocrinologist, Department of Internal Medicine, Division of Endocrinology and Metabolism, Chang Gung Memorial Hospital, No. 5, Fuxing Street, Guishan District, Taoyuan City 333, Taiwan. p122020223@cgmh.org.tw
Telephone: +886-3-3281200 Fax: +886-3-3288257
Received: June 27, 2019
Peer-review started: June 29, 2019
First decision: July 31, 2019
Revised: August 14, 2019
Accepted: August 27, 2019
Article in press: August 27, 2019
Published online: October 6, 2019

Stiff-person syndrome (SPS) and its subtype, stiff limb syndrome (SLS), are rare neurological disorders characterized by progressive muscular rigidity and spasms. Glutamic acid decarboxylase (GAD) is the enzyme that catalyzes the production of γ-aminobutyric acid (GABA), a major inhibitory neurotransmitter of the central nervous system. SPS is an autoimmune disease triggered by anti-glutamic acid decarboxylase antibody (anti-GAD Ab). Clinically, anti-GAD Ab is associated with SPS, type 1 diabetes mellitus (T1DM), and other autoimmune diseases.


To investigate the link of autoimmune endocrine disorders with anti-GAD Ab in SPS subjects.


This retrospective study was approved by the Institutional Review Board of Chang Gung Memorial Hospital, Taiwan. We collected the patients with SPS from January 2001 to June 2018. By reviewing 14 patients from medical records, we analyzed the clinical findings with coexisting autoimmune diseases, particularly diabetes mellitus and thyroid disease, which are associated with anti-GAD antibody titers or other immunological test results (anti-thyroid peroxidase and anti-nuclear antibodies). We also evaluated malignancies, major complications, and reported treatment to improve symptoms. Anti-GAD antibodies were measured using radioimmunoassay and enzyme-linked immunosorbent assay (ELISA). The cut-off values of these tests are < 1 U/mL and < 5 U/mL, respectively.


The median age of all patients was 39.3 (range, 28.0-54.0) years with a median follow-up period of 6.0 (2.7-13.3) years. Five (35.7%) patients were female; twelve (85.7%) were diagnosed with classic SPS and two (14.3%) with SLS. The median age of onset of symptoms was 35.0 (26.0-56.0) years with a median follow-up duration of 9.0 (2.1-14.9) years in the classic SPS group; the SLS group had a median age of onset of 46.7 years and a shorter follow-up duration of 4.3 years. Among nine classic SPS patients who underwent the anti-GAD Ab test, three were anti-GAD Ab seropositive and each of these three patients also had T1DM, latent autoimmune diabetes in adults, and autoimmune thyroid disease, respectively. In contrast, other rare autoimmune diseases co-existed in six anti-GAD Ab seronegative SPS patients. None of the SLS patients had additional autoimmune diseases.


While typical clinical symptoms are crucial for the diagnosis of SPS, the presence of anti-GAD autoantibody may consolidate the diagnosis and predict the association with other autoimmune diseases.

Keywords: Stiff-person syndrome, Glutamic acid decarboxylase antibody, Autoimmune disease, Type 1 diabetes mellitus, Latent autoimmune diabetes in adults, Autoimmune thyroid disease

Core tip: Stiff-person syndrome (SPS) is an uncommon disorder that causes significant disability. Presence of typical clinical symptoms and anti-glutamic acid decarboxylase antibody are important clues for diagnosis. Several autoimmune diseases can be screened with related autoantibodies in SPS patients, and early diagnosis and appropriate treatment are significant to improve the prognosis of SPS. Recognizing these comorbid conditions can help avoid missing or delaying diagnosis in SPS patients.