Hypophysitis

Hypophysitis is defined as the presence of any inflammatory process of the pituitary gland, that may involve the anterior lobe, the posterior lobe and/or the infundibulum. A rare localized or predominant involvement of the hypothalamus has been reported as “hypothalamitis.” The etiopathogenesis of hypophysitis is complex (Caturegli et al., 2005, 2008). Pituitary inflammatory infiltration was first recognized in Brissaud et al. (1908), while associated aspects (i.e., pituitary atrophy, concomitant extra-pituitary autoimmune (AI) disorders and the temporal association with pregnancy) were described in 1962 in an autopsy report of a young female who died of postsurgical adrenal crisis 14 months after delivery in a context of hypopituitarism (Goudie and Pinkerton, 1962). Soon after, the first experimental animal model of AI hypophysitis was reported (Levine, 1967), followed by the identification of autoantibodies against PRL-secreting pituitary cells (Bottazzo et al., 1975). Then, the clinical, histological, and radiological features of different forms of hypophysitis have been progressively characterized (Carpinteri et al., 2009; Guaraldi et al., 2017). Nowadays, the term “hypophysitis” encompasses a broad variety of primary and secondary inflammatory diseases, some of which are being increasingly recognized. In particular, in the last decade, hypophysitis has emerged as a frequent complication of anticancer immunotherapy, raising interest far outside the limited community of pituitary specialists. Hypophysitis in the setting of the systemic IgG4-related (IgG4-R) inflammatory syndrome or infective disorders in immunocompromised patients have also gained interest among physicians in different fields of internal medicine. As most of these disorders can be suspected according to the clinical context, the indications for diagnostic neurosurgery have decreased over time, but histopathological diagnosis remains a cornerstone in many cases. The clinical implications of hypopituitarism, in particular the risk of adrenal insufficiency, which is more common than in pituitary masses of noninflammatory origin, are relevant and should be promptly recognized and treated in order to prevent morbidity and mortality. Diabetes insipidus and mass effects are additional issues in affected patients. This article presents a synthetic update on the physiopathology, clinical presentation, diagnosis, and treatment of the different forms of hypophysitis, in order to provide a useful tool for any practitioner who may need to recognize and manage this condition in clinical practice.