Pregnancy is often associated with improvement in autoimmune diseases, whereas autoimmune activity may newly emerge or worsen after pregnancy loss or delivery. In individuals with pre-existing autoimmunity, the post-pregnancy period may unmask previously silent disease. Stiff-person syndrome (SPS) and autoimmune diabetes share glutamic acid decarboxylase 65 (GAD65) as a common autoantigen, although endocrine involvement may remain clinically unrecognized for prolonged periods.
Case Presentation
A 27-year-old woman with GAD65-associated stiff-person syndrome (SPS) and autoimmune Hashimoto thyroiditis was referred after hyperglycemia was identified following early pregnancy loss.
Neurologic symptoms began at age 14 with episodic neck stiffness initially attributed to hemiplegic migraines, progressing to axial rigidity and painful spasms. SPS was diagnosed at age 23. At diagnosis, serum GAD65 autoantibodies were markedly elevated at 2,100 nmol/L (reference < 0.02 nmol/L), with cerebrospinal fluid positivity of 2.02 nmol/L. She achieved partial improvement with benzodiazepines, muscle relaxants, and botulinum toxin. Immunotherapy with intravenous immunoglobulin and rituximab was initiated but discontinued in anticipation of pregnancy.
She subsequently experienced a nonviable first-trimester pregnancy requiring dilation and curettage. Post-pregnancy-loss evaluation revealed hemoglobin A1c 8.1% (reference < 5.6%), increased from 5.4% measured six months earlier, without classic hyperglycemic symptoms. Fasting glucose was 134 mg/dL with a measurable C-peptide of 2.2 ng/mL. Over the same interval, GAD65 antibody titers increased from 330,700 to 911,200 IU/mL (reference < 5 IU/mL). Thyroid function remained euthyroid with persistent thyroid peroxidase antibody positivity. Autoimmune diabetes was diagnosed, and continuous glucose monitoring with basal–bolus insulin therapy was initiated. FDG PET/CT imaging to evaluate for a paraneoplastic etiology is pending.
Discussion
SPS is associated with high-titer GAD65 autoantibodies, which are also central to autoimmune diabetes. Despite this shared autoantigen, pancreatic involvement may remain clinically silent for years. In this patient, glycemic stability prior to pregnancy contrasted sharply with the post-pregnancy-loss period, during which autoimmune diabetes became clinically evident despite preserved C-peptide and absence of classic symptoms. This temporal association highlights a vulnerable period during which latent autoimmune disease may emerge.
Conclusion
This case demonstrates the emergence of clinically silent autoimmune diabetes following early pregnancy loss in a patient with GAD65-associated SPS. Heightened metabolic surveillance should be considered in the post-pregnancy period for patients with neurologic autoimmunity, even in the absence of symptoms.
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