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The endocrine system
Published in C. Simon Herrington, Muir's Textbook of Pathology, 2020
Isolated inflammatory disease affecting the pituitary gland is rare. The gland may be affected by acute inflammation either in the brain or from direct extension of infection from neighbouring structures. Granulomatous inflammation may involve the gland directly or lead to hypopituitarism if it affects the hypothalamus. Autoimmune hypophysitis is rare compared with autoimmune disease of other endocrine glands.
Neuroendocrine disease
Published in Philip E. Harris, Pierre-Marc G. Bouloux, Endocrinology in Clinical Practice, 2014
There is an association between autoimmune hypophysitis and other autoimmune conditions, such as autoimmune thyroid disease (AITD).45 Circulating antipituitary antibodies occur in autoimmune hypophysitis and in other autoimmune conditions, but their sensitivity and specificity are poor.
Endocrine complications of celiac disease: a case report and review of the literature
Published in Endocrine Research, 2019
Marcella D. Walker, Haley M. Zylberberg, Peter H. R. Green, Michael S. Katz
In addition to the associations of CD with AIT, TIDM, and Addison’s disease, CD has rarely been described in association with idiopathic hypoparathyroidism and autoimmune hypophysitis in separate isolated reports or case series.150–154 One study suggested a potential mechanism linking hypoparathyroidism and untreated CD cross-reactivity between CD-specific EMA antibodies and parathyroid tissue leading to parathyroid atrophy.155 This mechanism, however, has not been confirmed. Further, a more recent systematic investigation reported no increased risk of CD in patients with idiopathic hypoparathyroidism.150 The association between CD and autoimmune hypophysitis has not been well defined to date.
Recent insights into the pathogenesis of autoimmune hypophysitis
Published in Expert Review of Clinical Immunology, 2021
Francesco Frasca, Tommaso Piticchio, Rosario Le Moli, Roberta Malaguarnera, Alfredo Campennì, Salvatore Cannavò, Rosaria Maddalena Ruggeri
The term autoimmune hypophysitis includes a large spectrum of either primary or secondary disorders as well as iatrogenic conditions, characterized by lymphocytic infiltration of the anterior and/or posterior pituitary, sometimes involving the hypothalamus, each with distinct features. LYH has been known for a long time, and it is characterized by lymphocytic infiltration of the pituitary gland and by the presence of circulating APAs and AHAs, clearly indicating that an autoimmune process is responsible for pituitary damage and dysfunction. Anti-PIT-1 hypophysitis is a newly described form characterized by acquired hormones deficiencies as a consequence of the appearance of autoantibodies against PIT-1 in the context of neoplastic disorders. Autoimmunity is also the underlying cause of other emerging forms of hypophysitis, like IgG-4-related disease and immune checkpoint inhibitors-induced forms, and it may take part in the course in some other hypothalamic–pituitary disorders, including infectious diseases. Finally, during the recent COVID-19 outbreak hypothalamus-pituitary axis involvement has been proposed as a consequence of either direct or indirect effects of SARS-CoV-2 infection on the gland, in line with data from the literature showing that COVID-19 may cause endocrine disorders through both autoimmune mechanisms and direct organ damage. For a correct diagnosis and timely treatment without residual functional deficits, it is still necessary to understand various aspects of the pathogenesis of these multiple forms of hypophysitis. This has become of extreme importance to clinicians in recent years by the exponential increase in the number of new diagnoses of hypophysitis, due to greater knowledge of the medical awareness, better imaging and laboratory diagnostic tools and mostly for the increase in immune-mediated secondary forms related to ICI, infections, systemic diseases and neoplasms.
Immune checkpoint inhibitor-induced inflammatory arthritis: identification and management
Published in Expert Review of Clinical Immunology, 2020
Sandra G. Williams, Arash Mollaeian, James D. Katz, Sarthak Gupta
However, along with the benefits of ICIs, their use has been associated with significant toxicities due to overactivation of the immune system and resultant autoimmunity. This phenomenon, frequently labeled ‘immune-related adverse events’ (irAEs), presents a novel and challenging area in clinical management of oncology patients [16–18]. It has been estimated that as many as 90% of patients participating in clinical trials experience irAEs [9], although serious irAEs are somewhat less frequent. irAEs may affect various organs including lungs, liver, intestines, skin, and joints; with some patients having multi-organ involvement. Whether these adverse events are a beneficial and necessary part of an anti-tumor response is still unclear [19–21–22]. For example, historically, vitiligo was recognized as a good prognostic sign in patients with metastatic melanoma [23]. This continues to be the case with ICI therapy: vitiligo-like skin reactions coincide with anti-tumor activity [24,25]. However, while there is a mechanistic link between tumor response and vitiligo, this has not been established for most irAEs, and some events appear to be due to off-target effects of T-cell activation. Recently, interest in the mechanistic underpinnings of irAEs has led to the demonstration of cross-reactive T cell clones in the skin and lungs of patients treated for NSCLC who also developed autoimmune skin toxicity [26], further supporting a direct link between the tumor response and irAEs. In some cases, diseases that were vanishingly rare (e.g., autoimmune hypophysitis) have now become relatively common [27,28]. That being said, autoantibodies associated with traditional autoimmune diseases – including those associated with autoimmune hepatitis, endocrinopathies, neurologic diseases, and rheumatic diseases – are often absent in the corresponding irAE [29–30–31–32]. Interestingly, recent studies have identified novel autoantibodies that appear to be associated with the development of ICI-induced pneumonitis and hypophysitis [33]. Finally, the histopathologic findings may be quite distinct from traditional autoimmune pathology; examples include ICI-associated myositis [34–35–36], colitis [37], sicca complex [38], and vitiligo [39]. Taken together, these observations highlight that while irAEs may mimic known autoimmune diseases, they are in many cases novel and distinct entities. In short, many patients who present with rheumatic irAEs may not satisfy standard diagnostic and classification criteria for traditional rheumatic diseases [32]. While our understanding of these diseases has increased dramatically since they were first recognized, there is much yet to learn about their immunopathogenesis and optimal management.