Hypophysitis is defined as inflammation of the pituitary gland that is primary or secondary to a local or systemic process. Differential diagnosis is broad (including primary tumors, metastases, and lympho-proliferative diseases) and multifaceted. Patients with hypophysitis typically present with headaches, some degree of anterior and/or posterior pituitary dysfunction, and enlargement of pituitary gland and/or stalk, as determined by imaging. Most hypophysitis causes are autoimmune, but other etiologies include inflammation secondary to cellar tumors or cysts, systemic diseases, and infection or drug-induced causes. Novel pathologies such as IgG4-related hypophysitis, immunotherapy-induced hypophysitis and paraneoplastic pituitary-directed autoimmunity are also included in a growing spectrum of this rare pituitary disease. Typical magnetic resonance imaging reveals stalk thickening and homogenous enlargement of the pituitary gland, however, imaging is not always specific. Diagnosis can be challenging and ultimately, only a pituitary biopsy can confirm hypophysitis type and rule out other etiologies. A presumptive diagnosis can be made often without biopsy. Detailed history and clinical examination are essential, notably for signs of underlying etiology with systemic manifestations. Hormone replacement and in selected cases careful observation is advised with imaging follow-up. High-dose glucocorticoids are initiated mainly to help reduce mass effect. A response may be observed in all auto-immune etiologies, but also in lymphoproliferative diseases, and as such should not be used for differential diagnosis. Surgery may be necessary in some cases to relieve mass effect and allow a definite diagnosis. Immunosuppressive therapy and radiation are sometimes also necessary in resistant cases.

OBJECTIVE: Immune checkpoint inhibitors can cause various immune-related adverse events including secondary hypophysitis. We compared clinical characteristics of immunotherapy-induced hypophysitis (IIH) and primary hypophysitis (PH) DESIGN: Retrospective multicenter cohort study including 56 patients with IIH and 60 patients with PH.
METHODS: All patients underwent extensive endocrine testing. Data on age, gender, symptoms, endocrine dysfunction, MRI, immunotherapeutic agents and autoimmune diseases were collected.
RESULTS: Median time of follow-up was 18 months in IIH and 69 months in PH. The median time from initiation of immunotherapy to IIH diagnosis was 3 months. IIH affected males more frequently than PH (p < 0.001) and led to more impaired pituitary axes in males (p < 0.001). The distribution of deficient adenohypophysial axes was comparable between both entities, however, central hypocortisolism was more frequent (p < 0.001) and diabetes insipidus considerably less frequent in IIH (p < 0.001). Symptoms were similar except that visual impairment occurred more rarely in IIH (p < 0.001). 20 % of IIH patients reported no symptoms at all. Regarding MRI, pituitary stalk thickening was less frequent in IIH (p = 0.009). Concomitant autoimmune diseases were more prevalent in PH patients before the diagnosis of hypophysitis (p = 0.003) and more frequent in IIH during follow-up (p = 0.002).
CONCLUSIONS: Clinically, IIH and PH present with similar symptoms. Diabetes insipidus very rarely occurs in IIH. Central hypocortisolism, in contrast, is a typical feature of IIH. Preexisting autoimmunity seems not to be indicative of developing IIH.