Title : IgG4-related hypophysitis: A unique presentation of a rare disease
Abstract:
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. The most common presentation of IgG4-RH includes diabetes insipidus (DI), anterior hypopituitarisms, or visual disturbances due to mass effect of the pituitary. A study in 2021 reported 115 cases of IgG4-RH in which 70 patients had DI and 86 patients had anterior hypopituitarism hormonal dysfunction [1]. IgG4-RH usually causes granulomatous inflammatory lesions in the pituitary; a high proportion of IgG4+ plasma cells are the hallmark findings in biopsy to establish a definite diagnosis. The current cornerstone of treatment is glucocorticoids with or without the use of immunomodulators; however, there is limited follow-up of patients with insufficient data on treatment response and remission. This report discusses the unique case of a 56-year-old female who initially presented in the summer of 2023 with positional dizziness. Within a month of initial presentation, she developed increased thirst and excessive urination along with diffuse headaches. Upon further evaluation by her primary care physician, she was found to have hypernatremia. Subsequent labs were significant for low urine osmolality, high serum osmolality, and high plasma sodium, consistent with DI. Due to the suspicion of central DI, the patient was started on desmopressin (DDAVP) and both the polydipsia and polyuria decreased. Brain MRI revealed diffuse thickening of the pituitary stalk with enhancement. CT chest, abdomen, and pelvis showed no significant abnormality. The patient was referred to neurology for further workup which included an unrevealing lumbar puncture and PET scan did not show any other area of inflammation that could be biopsied. Further labs, however, were significant for elevated serum IgG4 level and the patient was started on a trial of high-dose steroids for possible IgG4-RH. Patient completed IV steroids and continued oral prednisone taper. Treatment was complicated by steroid-induced myopathy leading to premature termination of the prednisone taper. However, the patient experienced significant clinical improvement and no longer required DDAVP after steroid treatment although repeat brain MRI findings remained unchanged. Throughout the course of this case, the patient did not display signs or symptoms of anterior hypopituitarism and had normal TSH, free T4, and ACTH. Serum prolactin has been increasing throughout the duration of management from 60 to 155 ng/mL. While improved, serum sodium, serum osmolality, and urine osmolality remain elevated. Increasing awareness of this rare disease manifestation is important to ensure swift diagnosis and management. Treatment options are currently limited to glucocorticoids and targeted hormone replacement with few data on the efficacy of immunomodulators. This case illustrates the need for further investigation into treatment outcomes and prognosis, and development of more targeted treatment modalities. [1] Amirbaigloo, A., Esfahanian, F., Mouodi, M. et al. IgG4-related hypophysitis. Endocrine 73, 270–291 (2021). https://doi.org/10.1007/s12020-021-02714-0.
Audience Take Away Notes:
- Increase awareness regarding IgG4-related hypophysitis, a rare manifestation of autoimmune IgG4-related disease
- Incorporate the discussed disease into clinical differentials with use of the Leporati diagnostic criteria
- Motivate further reporting of cases to bolster the literature base and our knowledge on this rare disease
- Encourage investigation of more targeted treatment options
