Pituitary IgG4 inflammatory infiltrates: a shared finding in different pituitary conditions

Over the last decade, IgG4-related hypophysitis (IgG4-RH) has been increasingly recognised as a manifestation of IgG4-related disease (IgG4-RD). Concurrently, several cases of 'isolated IgG4-RH' have been reported, without any features of typical manifestations of IgG4-RD. Furthermore, IgG4 histological inflammatory infiltrates are being reported in other pituitary pathologies leading to some diagnostic confusion as to the possibility of it being a manifestation of IgG4-RD. This paper examines recent published cases of IgG4-RH to provide an updated understanding of the clinical landscape of IgG4 inflammatory changes in the pituitary gland, with a particular focus on isolated IgG4-RH. Literature review of all detailed case reports or case series of IgG4-RH reported between 2014 and 2025 was conducted. IgG4 inflammatory infiltrates are defined as the presence >10 IgG4-positive cells per high-power field and/or >40% IgG4 plasma cells with storiform fibrosis. Cases were divided into three groups: isolated IgG4-RH, IgG4-RH-associated IgG4-RD ​and IgG4 inflammatory infiltrates with cystic and other pituitary pathologies. Nineteen cases of isolated IgG4-RH and 12 cases of IgG4-RH-associated IgG4-RD have been reported since 2014. The group with isolated IgG4-RH was significantly different from that with IgG4-RH-associated IgG4-RD, with a female preponderance of 3.8:1 and younger age (mean 39 years versus 60 years). Fourteen cases of typical IgG4 inflammatory infiltrates were also documented in other pituitary lesions; most notably these were Rathke's cleft cysts. The findings of IgG4 inflammatory infiltrates in the pituitary gland can be found in numerous pituitary pathologies. Isolated IgG4-RH disproportionately affects younger females and generally necessitates medical therapies: it may be a form of lymphocytic hypophysitis rather than a forme fruste of IgG4-RH associated with IgG4-RD. Histopathology of IgG4 inflammatory infiltrates in the pituitary gland is non-diagnostic: it requires histopathologists, endocrinologists and neurosurgeons to consider the clinical status and radiological findings in each case to clarify the diagnosis.