THU246 What’s The Importance of GAD Antibodies In Patients With Stiff Person Syndrome

Abstract

Abstract Disclosure: A. Barnett: None. G. Elshimy: None. Introduction: Stiff Person Syndrome (SPS) has a strong autoimmune component with positive serology for GAD-65 antibody as one of the diagnostic criteria. GAD is an enzyme selectively concentrated in neurons secreting the neurotransmitter gamma-aminobutyric acid (GABA) but is also present in pancreatic beta cells. Hence, insulin-dependent diabetes mellitus (LADA) can develop in patients with SPS. We present two cases that highlight the importance of this association and the difference in the time of onset to ensure appropriate screening. Case: Our first case was a 46-year-old female with systemic sclerosis and SPS that was diagnosed with steroid-induced diabetes in 2012 with HbA1c 8.7% (4.3-6.1%). Her GAD-65 antibody was significantly elevated at 1971 (less than 2nmol/L). For almost 8 years, the patient only required insulin therapy while on high dose steroids, but eventually developed persistent hyperglycemia requiring insulin therapy. Her C-peptide was 0.49 (0.78-5.19ng/mL) with plasma glucose of 201 (74-106mg/dL), consistent with beta-cell dysfunction. The second case was a 60-year-old female with a 20-year history of SPS who was diagnosed with type 2 diabetes in 2014 after receiving high doses of steroids while undergoing chemotherapy for breast cancer. She was initially well-controlled on oral medications until 2 years after her initial diabetes diagnosis where her HbA1c increased rapidly to 8.1% (4.8-5.9%). At that time, she was started on insulin therapy and antibody testing was pursued which showed positive GAD-65 antibody greater than 250 (less than 5IU/mL) consistent with LADA. She had a negative IA-2 antibody undetectable. Due to other autoimmune associations, she was also screened for thyroid disease revealing an elevated TPO-antibody with a normal TSH 4.02 that is being monitored. Discussion: SPS is associated with autoantibodies and other autoimmune disorders including but not limited to type 1 diabetes, anti-thyroglobulin antibodies and anti-parietal cell antibodies. In both cases, the diagnosis of SPS preceded the onset of diabetes then with a latent “honeymoon” phase not requiring long-term insulin therapy for years, most consistent with LADA. However, there are exacerbating factors including high-dose steroids which could be misleading and result in diagnosing these patients with type 2 diabetes initially. It should be taken into consideration that there is variability in the time of onset of beta-cell dysfunction, which varied from 2 to 8 years in our patients. Hence, the recognition of the correlation of autoimmune-mediated diabetes and the variable time course to insulin deficiency is critical for the continued monitoring in patients with SPS. Physicians should be aware of the importance of screening patients with SPS for type 1 diabetes mellitus and differentiate it from steroid-induced type 2 diabetes to avoid developing diabetic ketoacidosis in these patients. Presentation: Thursday, June 15, 2023