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Current Opinion in Ophthalmology Nov 2018IgG4-related disease (IgG4-RD) is increasingly recognized as a fibroinflammatory disease with a plethora of organ-specific manifestations but a particular predilection... (Review)
Review
PURPOSE OF REVIEW
IgG4-related disease (IgG4-RD) is increasingly recognized as a fibroinflammatory disease with a plethora of organ-specific manifestations but a particular predilection for head and neck tissues, including the nervous system. This review discusses general features and organ-specific presentations of IgG4-RD as well as treatment considerations, particularly emphasizing features of neuro-ophthalmic interest.
RECENT FINDINGS
IgG4-RD is emerging as a common cause of several fibroinflammatory disorders in the head and neck that were previously considered idiopathic, such as sclerosing orbital pseudotumor, orbital myositis, hypophysitis, and hypertrophic pachymeningitis. New and unusual presentations continue to be described, including a number of vascular manifestations. Substantial progress has been made in elucidating the cell types involved in IgG4-RD, and new pathogenic models are being proposed. Although clinicopathologic correlation remains the cornerstone of diagnosis, ancillary tests such as flow cytometry for circulating plasmablasts and PET-computed tomography have high sensitivity, and certain radiologic features are recognized to be particularly suggestive, such as infraorbital nerve enlargement in IgG4-RD orbitopathy. IgG4-RD often responds to steroids but incomplete responses and relapses are common. Rituximab is emerging as a promising new therapy.
SUMMARY
The current review summarizes manifestations of IgG4RD that are of particular relevance to neuro-ophthalmic practice.
Topics: Autoimmune Diseases; Autoimmune Hypophysitis; Diagnostic Techniques, Ophthalmological; Flow Cytometry; Humans; Immunoglobulin G; Meningitis; Orbital Myositis; Orbital Pseudotumor; Positron-Emission Tomography; Tomography, X-Ray Computed
PubMed: 30199519
DOI: 10.1097/ICU.0000000000000523 -
Best Practice & Research. Clinical... Apr 2019Hypophysitis is a rare entity characterized by inflammation of the pituitary gland and its stalk that can cause hypopituitarism and/or mass effect. Etiology can be... (Review)
Review
Hypophysitis is a rare entity characterized by inflammation of the pituitary gland and its stalk that can cause hypopituitarism and/or mass effect. Etiology can be categorized as primary or secondary to systemic disease, but may also be classified according to anatomical and hispathological criteria. Newly recognized causes of hypophysits have been described, mainly secondary to immunomodulatory medications and IgG4-related disease. Diagnosis is based on clinical, laboratory and imaging data, whereas pituitary biopsy, though rarely indicated, may provide a definitive histological diagnosis. For the clinician, obtaining a broad clinical and drug history, and performing a thorough physical examination is essential. Management of hypophysitis includes hormone replacement therapy if hypopituitarism is present and control of the consequences of the inflammatory pituitary mass (e.g. compression of the optic chiasm) using high-dose glucocorticoids, whereas pituitary surgery is reserved for those unresponsive to medical therapy and/or have progressive disease. However, there remains an unmet need for controlled studies to inform clinical practice.
Topics: Autoimmune Hypophysitis; Glucocorticoids; Humans; Hypophysitis; Hypopituitarism; Immunoglobulin G; Inflammation; Pituitary Diseases; Pituitary Gland
PubMed: 31078416
DOI: 10.1016/j.beem.2019.04.010 -
Pituitary Feb 2016Advances in immunotherapy have transformed the management of metastatic melanoma and generated encouraging results in the treatment of other malignancies. Autoimmune... (Review)
Review
INTRODUCTION
Advances in immunotherapy have transformed the management of metastatic melanoma and generated encouraging results in the treatment of other malignancies. Autoimmune side effects from these agents, termed immune-related adverse events (IRAEs), are diverse and can include multiple endocrinopathies. Ipilimumab-induced hypophysitis (IH) is a recently recognized endocrine IRAE.
METHODS
This review summarizes published data and experience from our center on the incidence, presentation and management, and proposed mechanisms for immunotherapy-related hypophysitis, with a focus on patients treated with ipilimumab (Ipi).
CONCLUSION
Hypophysitis occurs in a significant minority of patients treated with Ipi, in contrast to the relative rarity of idiopathic autoimmune hypophysitis or hypophysitis after treatment with other immunotherapies. Recently published cohorts have described the clinical presentation and management of IH and longitudinal outcomes in these patients. Additional studies with Ipi and other emerging agents have helped identify potential risk factors for the development of immunotherapy-related hypophysitis and possible underlying mechanisms for IH. Clarification of the mechanism(s) for IH may enhance our understanding of idiopathic autoimmune hypophysitis and could have potential therapeutic applications.
Topics: Antibodies, Monoclonal; CTLA-4 Antigen; Humans; Hypophysitis; Immunotherapy; Ipilimumab
PubMed: 26186958
DOI: 10.1007/s11102-015-0671-4 -
Radiologic Clinics of North America May 2021Neurologic injury arises from treatment of central nervous system malignancies as result of direct toxic effects or indirect vascular, autoimmune, or infectious effects.... (Review)
Review
Neurologic injury arises from treatment of central nervous system malignancies as result of direct toxic effects or indirect vascular, autoimmune, or infectious effects. Multimodality treatment may potentiate both therapeutic and toxic effects. Symptoms range from mild to severe and permanent. Injuries can be immediate or delayed. Many early complications are nonspecific. Other early and delayed neurologic injuries, such as posterior reversible encephalopathy syndrome, dural sinus thrombosis, infarctions, myelopathy, leukoencephalopathy, and hypophysitis, have unique imaging features. This article reviews treatment options for neurologic malignancies and common and uncommon neurologic injuries that can result from treatment, focusing on radiologic features.
Topics: Adult; Brain; Brain Neoplasms; Chemotherapy-Related Cognitive Impairment; Child; Combined Modality Therapy; Diagnostic Imaging; Humans; Immunotherapy; Neurocognitive Disorders; Radiation Injuries
PubMed: 33926687
DOI: 10.1016/j.rcl.2021.01.008 -
Pituitary Apr 2017IgG4-related hypophysitis is a rare disease, with only 34 cases published in English (2015). Available short reviews may not present complete details of IgG4-related... (Review)
Review
PURPOSE
IgG4-related hypophysitis is a rare disease, with only 34 cases published in English (2015). Available short reviews may not present complete details of IgG4-related hypophysitis. We aimed to survey case reports of IgG4-related hypophysitis, including abstracts of scientific meetings, in English and Japanese.
METHODS
We searched for information about IgG4-related hypophysitis in PubMed and Igakuchuozasshi (Japan Medical Abstracts Society). Among 104 case reports found, we reviewed 84 fulfilling Leporati's diagnostic criteria.
RESULTS
The mean ± SD age of onset was 64.2 ± 13.9, 67.5 ± 9.8, and 56.4 ± 18.6 years for all subjects, men, and women, respectively. Men:women was 2.4:1. On magnetic resonance imaging, pituitary, stalk, and pituitary-stalk mass were observed at frequencies of 14.3, 21.4, and 64.3%, respectively. Manifestations were anterior hypopituitarism in 26.2% (22 cases), central diabetes insipidus in 17.9% (15 cases), and panhypopituitarism in 52.4% (44 cases). The median level of serum IgG4 was 264.5 mg/dL for all subjects, 405 mg/dL for men, and 226 mg/dL for women. The mean number of IgG4-related systemic diseases was 2.7 ± 1.5 in all subjects, 3.0 ± 1.5 in men, and 1.8 ± 1.1 in women. Among the IgG4-related diseases, retroperitoneal fibrosis was the most frequent (26.2%), followed by salivary gland diseases (25%). Glucocorticoid therapy was generally effective, except for two cases that received replacement doses. There were significant differences between sexes in terms of age, serum IgG4 levels, and number of IgG4-related diseases.
CONCLUSION
IgG4-related hypophysitis may have different clinical characteristics between genders. This survey may lack some information because the Japanese abstracts did not contain certain details.
Topics: Aged; Autoimmune Hypophysitis; Diabetes Insipidus; Female; Glucocorticoids; Humans; Hypopituitarism; Immunoglobulin G; Male; Middle Aged; Retroperitoneal Fibrosis
PubMed: 27812776
DOI: 10.1007/s11102-016-0773-7 -
Frontiers in Endocrinology 2023Immune checkpoint inhibitors (ICIs) have increasingly been the mainstay of treatment for numerous malignancies. However, due to their association with autoimmunity, ICIs... (Review)
Review
Immune checkpoint inhibitors (ICIs) have increasingly been the mainstay of treatment for numerous malignancies. However, due to their association with autoimmunity, ICIs have resulted in a variety of side effects that involve multiple organs including the endocrine system. In this review article, we describe our current understanding of the autoimmune endocrinopathies as a result of the use of ICIs. We will review the epidemiology, pathophysiology, clinical presentation, diagnosis, and management of the most commonly encountered endocrinopathies, including thyroiditis, hypophysitis, Type 1 diabetes, adrenalitis, and central diabetes insipidus.
Topics: Humans; Immune Checkpoint Inhibitors; Endocrine System; Endocrine System Diseases; Adrenal Gland Diseases; Neoplasms; Drug-Related Side Effects and Adverse Reactions
PubMed: 37251665
DOI: 10.3389/fendo.2023.1157805 -
Journal of Gastroenterology and... Apr 2015Ipilimumab has been shown to improve overall survival in patients with advanced melanoma. Ipilimumab acts through immune-modulation, and is recognized to cause... (Review)
Review
Ipilimumab has been shown to improve overall survival in patients with advanced melanoma. Ipilimumab acts through immune-modulation, and is recognized to cause potentially severe immune-related adverse events (irAEs) including dermatitis, colitis, thyroiditis, hypophysitis, and hepatitis. The acceptance of ipilimumab as a treatment for metastatic melanoma means patients will continue to be treated with this agent and gastroenterologists will be increasingly called upon to assist in managing severe autoimmune-related hepatitis and colitis. To date, the recommendations for managing irAEs secondary to ipilimumab have been steroids at a moderate dose of prednisolone (1 mg/kg) as well as immunosuppressive agents such as mycophenolate mofetil (MMF) for steroid-refractory hepatitis and infliximab in the management of corticosteroid-refractory colitis. However, the dosing and the duration of immunosuppressive therapy have not been systematically studied in the setting of treating ipilimumab-induced irAEs. Therefore, additional immune-modifying agents and/or a change in dosing may be required to manage severe irAEs unresponsive to existing treatment recommendations. We describe a treatment paradigm illustrated by a series of five patients who experienced irAEs. In three cases of metastatic melanoma, ipilimumab-induced hepatitis was successfully treated with high-dose parenteral pulsed methylprednisolone. In two other melanoma patients with ipilimumab-induced colitis, one patient had satisfactory resolution of his colitis with high-dose corticosteroid therapy alone and the other patient required infliximab infusion. We have reviewed the current literature and management algorithms for ipilimumab-induced irAEs. Treatment options and the rationale for their use are discussed, including the use of pulsed high-dose steroids, MMF, azathioprine and calcineurin inhibitors.
Topics: Antibodies, Monoclonal; Azathioprine; Calcineurin Inhibitors; Chemical and Drug Induced Liver Injury; Colitis; Glucocorticoids; Humans; Immunosuppressive Agents; Infliximab; Ipilimumab; Melanoma; Methylprednisolone; Mycophenolic Acid; Patient Care Team; Prednisolone; Pulse Therapy, Drug
PubMed: 25641691
DOI: 10.1111/jgh.12888 -
Endocrine Journal Jun 2023Paraneoplastic syndromes are defined by symptoms or signs resulting from damage to organs or tissues that are remote from the site of malignant neoplasms or its...
Paraneoplastic syndromes are defined by symptoms or signs resulting from damage to organs or tissues that are remote from the site of malignant neoplasms or its metastasis. They are due to tumor secretion of functional hormones or peptides or are related to immune cross-reactivity with the host tissue. In particular, paraneoplastic endocrine syndromes are mainly caused by ectopic hormone production by the tumor such as PTHrP in humoral hypercalcemia in malignancy and ACTH in ectopic ACTH syndrome. Recently, it has been reported that a specific form of hypophysitis is caused as an immune-mediated paraneoplastic syndrome; paraneoplastic autoimmune hypophysitis, in which an ectopic pituitary antigen expression in the tumor evoked autoimmunity against pituitary-specific antigens, resulting in hypophysitis and exhibiting the injury of specific anterior pituitary cells by cytotoxic T cells. This novel clinical entity, paraneoplastic autoimmune hypophysitis consists of several conditions such as anti-PIT-1 hypophysitis and a part of isolated ACTH deficiency and immune checkpoint inhibitor-related hypophysitis with common mechanisms. These conditions can explain at least in part, the underlying mechanisms of acquired specific pituitary hormone deficiencies. In addition, it is important to apply a comprehensive discipline of onco-immuno-endocrinology to understand the pathophysiology and this approach; the expansion and application of immune-mediated paraneoplastic syndrome to endocrine diseases may give a new clue to understand pathophysiology of the autoimmunity against endocrine organs.
Topics: Humans; Autoimmune Hypophysitis; Paraneoplastic Endocrine Syndromes; Autoantibodies; Hypophysitis; Paraneoplastic Syndromes; Neoplasms; Adrenocorticotropic Hormone
PubMed: 37045779
DOI: 10.1507/endocrj.EJ23-0050 -
Medicina 2021Since their approval in 2011, immune checkpoint inhibitors (ICPis) are increasingly used to treat several advanced cancers. ICPis target certain cellular molecules that... (Review)
Review
Since their approval in 2011, immune checkpoint inhibitors (ICPis) are increasingly used to treat several advanced cancers. ICPis target certain cellular molecules that regulate immune response resulting in antitumor activity. The use of these new agents needs careful monitoring since they brought a whole new spectrum of adverse events. In this review, we aim to describe different endocrine dysfunctions induced by ICPis and to underline the importance of diagnosing and managing these adverse effects. Immune-related endocrine toxicities include thyroid dysfunction, hypophysitis and, less frequently, type 1 diabetes, primary adrenal insufficiency and hypoparathyroidism. Diagnosis of endocrine adverse events related to ICPis therapy can be challenging due to nonspecific manifestations in an oncological scenario and difficulties in the biochemical evaluation. Despite the fact that these endocrine adverse events could lead to life-threatening consequences, the availability of effective replacement treatment enables continuing therapy and together with an interdisciplinary approach will impact positively on survival.
Topics: Endocrine System Diseases; Humans; Hypophysitis; Immune Checkpoint Inhibitors; Immunotherapy; Neoplasms
PubMed: 33906146
DOI: No ID Found -
European Journal of Endocrinology Sep 2018Hypophysitis is a rare condition characterised by inflammation of the pituitary gland, usually resulting in hypopituitarism and pituitary enlargement. Pituitary... (Review)
Review
Hypophysitis is a rare condition characterised by inflammation of the pituitary gland, usually resulting in hypopituitarism and pituitary enlargement. Pituitary inflammation can occur as a primary hypophysitis (most commonly lymphocytic, granulomatous or xanthomatous disease) or as secondary hypophysitis (as a result of systemic diseases, immunotherapy or alternative sella-based pathologies). Hypophysitis can be classified using anatomical, histopathological and aetiological criteria. Non-invasive diagnosis of hypophysitis remains elusive, and the use of currently available serum anti-pituitary antibodies are limited by low sensitivity and specificity. Newer serum markers such as anti-rabphilin 3A are yet to show consistent diagnostic value and are not yet commercially available. Traditionally considered a very rare condition, the recent recognition of IgG4-related disease and hypophysitis as a consequence of use of immune modulatory therapy has resulted in increased understanding of the pathophysiology of hypophysitis. Modern imaging techniques, histological classification and immune profiling are improving the accuracy of the diagnosis of the patient with hypophysitis. The objective of this review is to bring readers up-to-date with current understanding of conditions presenting as hypophysitis, focussing on recent advances and areas for future development. We describe the presenting features, investigation and diagnostic approach of the patient with likely hypophysitis, including existing conventional techniques and those in the research/development arena. Hypophysitis usually results in acute and persistent pituitary hormone deficiency requiring long-term replacement. Management of hypophysitis includes control of the inflammatory pituitary mass using a variety of treatment strategies including surgery and medical therapy. Glucocorticoids remain the mainstay of medical treatment but other immunosuppressive agents (e.g. azathioprine, rituximab) show benefit in some cases, but there is a need for controlled studies to inform practice.
Topics: Autoimmune Hypophysitis; Female; Glucocorticoids; Histiocytosis, Langerhans-Cell; Humans; Hypophysitis; Immunoglobulin G; Immunotherapy; Magnetic Resonance Imaging; Male; Neurosurgical Procedures; Pituitary Gland; Pituitary Hormones, Anterior; Pregnancy; Pregnancy Complications; Xanthomatosis
PubMed: 29880706
DOI: 10.1530/EJE-17-0009