Case report: Progressive organ-threatening IgG4-related disease despite conventional immunosuppression: lessons from a 5-year longitudinal follow-up

Objective To describe the 5-year clinical course of a patient who progressed from IgG4-related dacryoadenitis and sialadenitis (IgG4-DS) to IgG4-related hypophysitis (IgG4-RH) and retroperitoneal fibrosis, evaluating the clinical course and treatment response to conventional immunosuppressive therapy through longitudinal clinical, serological, endocrine, and magnetic resonance imaging (MRI) assessments. Methods Clinical records were retrospectively reviewed, focusing on disease progression after treatment discontinuation, responses to sequential conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and long-term pituitary endocrine outcomes. Results During 5 years of follow-up, a 44-year-old man with IgG4-DS developed partial anterior hypopituitarism, central diabetes insipidus, and retroperitoneal fibrosis following two episodes of unplanned treatment discontinuation. Serial MRI demonstrated progressive pituitary stalk thickening accompanied by heterogeneous enhancement. The maximum stalk diameter was 4.0 mm at diagnosis (May 2023), decreased to 3.6 mm during maintenance therapy (September 2024), increased to 8.5 mm at relapse (March 2025), and decreased to 7.0 mm after treatment modification (November 2025). Glucocorticoids combined with sequential csDMARDs controlled acute inflammation but failed to prevent permanent gonadal and posterior pituitary dysfunction. Serum IgG4 reached a peak of 38,100 mg/L, and its re-elevation preceded both clinical and radiological relapse. At the last assessment in January 2026, serum IgG4 remained elevated at 4,594 mg/L, with persistent hypogonadism and central diabetes insipidus. Conclusions Disease progression occurred mainly during treatment interruption, while residual activity persisted despite conventional csDMARDs. The relative contributions of treatment non-adherence and limited treatment efficacy remain uncertain. Combined serum IgG4 and MRI monitoring may aid early detection of relapse, but this requires validation in larger cohorts.