Hypophysitis (Including IgG4 and Immunotherapy)

Abstract

Hypophysitis is characterized by inflammation of the pituitary gland that can be primary (PH) or secondary (SH) to other diseases or following drug administration. It may also be classified according to anatomical and histopathological criteria, leading to variable degrees of hypopituitarism and/or compressive symptoms to nearby structures. There has recently been an increase in the number of hypophysitis cases, raising the interest on the spectrum of its pathogenesis, clinical, biochemical/endocrinological, and imaging features. However, the use of conventional biomarkers, including currently utilized pituitary autoantibodies, has relatively limited diagnostic accuracy. Lymphocytic hypophysitis (LH) is the commonest cause of PH, whereas IgG4-related hypophysitis is increasingly being recognized. Histiocytosis and granulomatous diseases are the most frequent causes of SH, although infections and lymphoma have also been reported. The increasing use of immune checkpoint inhibitors in oncology is associated with a high incidence of hypophysitis, providing further understanding of its pathogenesis. Hy-pophysitis can occur silently and be easily missed, potentially leading to substantial morbidity or mortality due to adrenal insufficiency, requiring a high index of clinical suspicion and timely initiation of appropriate treatment. In most cases of LH or drug-induced hypophysitis, active surveillance along with replacement of established hormonal deficiencies is needed. In the presence of compressive and/or evolving symptoms, treatment with glucocorticoids either alone or in combination with other immunosuppressive agents can be used. Surgical decompression is reserved for nonresponsive cases with threatened vital structures. Timely diagnosis and intervention are important to minimize disease-related morbidity and mortality. We aimed to review current concepts and recent developments in the pathogenesis, diagnosis, and management of hypophysitis.

<p>Managing Ipilimumab-Induced Hypophysitis: Challenges and Current Therapeutic Strategies</p>

“…6,34 The median time to onset of symptoms of hypophysitis after initiation of treatment with ipilimumab is 9 weeks while there are cases of hypophysitis diagnosed 19 months after first ipilimumab infusion suggesting a long-term monitoring is required in such cases. 14,22 The combination of CTLA-4 with anti-PD-1 agents is associated with earlier development of hypophysitis. 35…”

“…[9][10][11][12][13] Hypophysitis refers to inflammation of the pituitary gland and is categorized, according to histopathology, as lymphocytic, granulomatous, xanthomatous, necrotizing and IgG4 plasmacytic hypophysitis and/or its etiology to primary and secondary that is related to systemic diseases, infections or pharmacological agents. 14,15 It is a relatively rare disease with an annual incidence of 1/9,000,000 while lymphocytic hypophysitis is the most common form and constitutes approximately 71.8% of all cases of primary hypophysitis. 15,16 However, following the development of the new immune checkpoint therapies, its frequency has significantly increased.…”

Xanthomatous Hypophysitis Presenting in An Adolescent Girl: A Long-Term Follow-Up of A Rare Case and Review of The Literature

“…Hypophysitis is an inflammatory condition of the pituitary that can mimic a neoplastic lesion (1)(2)(3)(4)(5)(6). Primary hypophysitis refers to isolated inflammation of the pituitary not associated with other secondary causes.…”

“…Primary hypophysitis refers to isolated inflammation of the pituitary not associated with other secondary causes. It is rare with an incidence estimated at 1 in 7-9 million and less than 100 cases reported in children (1)(2)(3)(4)(5)(6).…”

“…Histopathology subtypes include lymphocytic (commonest), granulomatous, xanthomatous, plasmacytic, necrotising or a mixed picture (1)(2)(3)(4)(5)(6). Xanthomatous hypophysitis is the rarest with only 34 definite reported cases (7)(8)(9)(10)(11).…”