Association of type 1 stiff-person syndrome and insulinoma: a case report and narrative review

Abstract

Introduction: Stiff-person syndrome (SPS) is a rare neurological disorder that causes progressive muscle rigidity, gait disturbances, and functional impairment; type 1 is autoimmune, with positive anti-GAD antibodies (Ab), while type 2 is paraneoplastic and associated with antiamphiphysin Ab.

Case presentation: A 41-year-old man with a silent medical history presented with stiffness and functional impairment; after numerous rheumatological and neurological investigations, he was diagnosed with SPS, with evidence of high titer anti-GAD Ab. After treatment with benzodiazepines was started, the patient began to experience episodes of confusion, which persisted even after reducing the dosage. During one of these episodes, he was admitted to the emergency department and a glucose level of 26 mg/dL was found. Differential diagnosis led to detection of an insulin-secreting neuroendocrine tumor of the pancreas; thus, a paraneoplastic origin of SPS was hypothesized. However, antiamphiphysin Ab were negative, anti-GAD Ab were persistently elevated, and symptoms only transiently improved after removal of the tumor.

Conclusion: This is the first case, to our knowledge, demonstrating association between type 1 SPS and insulinoma, along with describing partial and transient improvement of neurological symptoms after resolution of the associated hypoglycemic syndrome.

Keywords: Autoimmune disease; Neuroendocrine tumor; Paraneoplastic; SPS.

Fig. 1

Antibodies in stiff-person syndrome spectrum disorders (SPSD) and most common clinical subtypes (GAD: glutamic acid decarboxylase; GlyR: glycine receptor)

Fig. 2

Well-differentiated tumor of the pancreas with an organoid growth (A) producing insulin in most neoplastic cells (B) (top right: a control islet of Langherans contains insulin positive cells). The tumor is composed of medium-sized cells with minimal atypia (C) and, in the presented case, had a low Ki67 proliferative index of approximately 5% in hot spot areas (D)