IgG4-related hypophysitis and AVP-deficiency: A unique presentation and literature review

Abstract

Background

Immunoglobulin G4-related disease (IgG4-RD) is an autoimmune condition in which IgG4-positive plasma cells locally or systemically infiltrate tissues and cause damage through inflammation and fibrosis. While IgG4-RD has been reported in nearly every organ, it preferentially manifests as retroperitoneal fibrosis, Mikulicz disease of the salivary glands, and autoimmune pancreatitis. Involvement of the pituitary gland, causing IgG4-related hypophysitis (IgG4-RH), is an infrequently encountered manifestation of the disease.

Case presentation

In this case, a 56-year-old female who presents for positional dizziness is ultimately found to have IgG4-RH. The patient developed symptoms of polydipsia and polyuria along with diffuse headaches within a month of her initial presentation. Serum and urine studies were suggestive of diabetes insipidus (DI). She improved on desmopressin (DDAVP) therapy suggesting AVP-deficiency (AVP-D). Her prolactin was found to be elevated, and brain MRI revealed diffuse thickening of the pituitary stalk with enhancement. Additional workup for systemic disease with CT, lumbar puncture, and PET scan was unremarkable. Autoimmune workup showed elevated ANA and serum IgG4, and a course of high-dose IV steroids was initiated for suspected IgG4-RH. She experienced significant clinical improvement of dizziness, polyuria, polydipsia, which enhanced her sleep quality. Despite therapy, her brain MRI remains unchanged, prolactin levels remain elevated, and she continues DDAVP therapy for persisting DI.

Discussion

The clinical manifestations of IgG4-RH are variable, contributing to the difficulty in diagnosis of this disease. Clinical presentations of IgG4-RH include diabetes insipidus (DI), anterior hypopituitarism, or visual disturbances due to mass effect of the pituitary. Definitive diagnosis requires histopathologic evaluation of the pituitary via biopsy, manifesting a high proportion of IgG4-positive cells. Non-invasive diagnostic methods, such as the Leporati criteria, are widely accepted and were utilized for the diagnosis of this patient. These criteria included MRI findings, elevated serum IgG4, and clinical response to steroids. The current cornerstone of treatment is glucocorticoids and targeted hormone replacement with or without the use of immunomodulators. However, there is limited follow-up of patients with insufficient data on treatment response and remission.

Conclusions

IgG4-RD can have many manifestations including as it presented in this case. Improving awareness and diagnostic tools for this disease is important for swift identification and management. Treatment options are limited to glucocorticoids and targeted hormone replacement with few data on immunomodulators. This case illustrates the need for further investigation into treatment outcomes and prognosis of this disease, and development of more targeted treatment modalities.