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Best Practice & Research. Clinical... May 2022Pituitary autoimmunity is one of the principal causes of hypopituitarism. Additionally, hypophysitis is one of the immune-related adverse events associated with... (Review)
Review
Pituitary autoimmunity is one of the principal causes of hypopituitarism. Additionally, hypophysitis is one of the immune-related adverse events associated with immunotherapy. Recent case-oriented research has revealed a novel type of autoimmune hypophysitis, anti-PIT-1 hypophysitis, related to isolated adrenocorticotropic hormone (ACTH) deficiency and immune checkpoint inhibitor-related hypophysitis, as a form of paraneoplastic syndrome. Under these conditions, the ectopic expression of pituitary antigens present in tumors evokes a breakdown of immune tolerance, resulting in the production of autoantibodies and autoreactive cytotoxic T cells that specifically harm pituitary cells. Consequently, an innovative clinical entity of paraneoplastic autoimmune hypophysitis has been purported. This novel concept and its underlying mechanisms provide clues for understanding the pathogenesis of autoimmune pituitary diseases and can be applied to other autoimmune diseases. This review discusses the etiology of paraneoplastic autoimmune hypophysitis and its future.
Topics: Adrenocorticotropic Hormone; Autoantibodies; Autoimmune Diseases; Autoimmune Hypophysitis; Endocrine System Diseases; Genetic Diseases, Inborn; Humans; Hypoglycemia; Hypophysitis; Pituitary Diseases
PubMed: 34876362
DOI: 10.1016/j.beem.2021.101601 -
Endocrine Practice : Official Journal... Sep 2022Hypophysitis is considered a rare inflammatory disease of the pituitary gland. For a long time, primary autoimmune hypophysitis has stood out as the most relevant type... (Review)
Review
OBJECTIVE
Hypophysitis is considered a rare inflammatory disease of the pituitary gland. For a long time, primary autoimmune hypophysitis has stood out as the most relevant type of hypophysitis. However, with the advent of immunotherapy for the treatment of malignancies and identification of hypophysitis as an immune-related adverse event, hypophysitis has garnered increasing interest and recognition. Therefore, awareness, early recognition, and appropriate management are becoming important as the indication for immunomodulatory therapies broaden.
METHODS
In this review, we discuss the epidemiology, diagnosis, and treatment of hypophysitis with a focus on recent data and highlight subtypes of particular interest while recognizing the gaps in knowledge that remain.
RESULTS
Regardless of cause, symptoms and signs of hypophysitis may be related to mass effect (headache and visual disturbance) and hormonal disruption that warrant prompt evaluation. In the vast majority of cases, a diagnosis of hypophysitis can be made presumptively in the appropriate clinical context with radiologic findings consistent with hypophysitis and after the exclusion of other causes.
CONCLUSION
Although subtle differences currently exist in management and outcome expectations between primary and secondary causes of hypophysitis, universally, treatment is aimed at symptom management and hormonal replacement therapy.
Topics: Autoimmune Hypophysitis; Headache; Hormone Replacement Therapy; Humans; Hypophysitis; Pituitary Gland
PubMed: 35779833
DOI: 10.1016/j.eprac.2022.06.009 -
Endocrine Reviews Aug 2005Autoimmune (lymphocytic) hypophysitis is a rare disease that should be considered in the differential diagnosis of any nonsecreting pituitary mass, especially when... (Review)
Review
Autoimmune (lymphocytic) hypophysitis is a rare disease that should be considered in the differential diagnosis of any nonsecreting pituitary mass, especially when occurring during pregnancy or postpartum. We have analyzed 370 articles published from January 1962 to October 2004 and identified a total of 379 patients with primary lymphocytic hypophysitis. The present review synthesizes the clinical and research data reported in this body of scientific literature.
Topics: Animals; Autoimmune Diseases; Disease Models, Animal; Female; Humans; Pituitary Diseases; Pregnancy; Pregnancy Complications
PubMed: 15634713
DOI: 10.1210/er.2004-0011 -
Handbook of Clinical Neurology 2014Autoimmune hypophysitis, often referred to as lymphocytic hypophysitis, is defined as an inflammatory condition of the pituitary gland of autoimmune etiology that leads... (Review)
Review
Autoimmune hypophysitis, often referred to as lymphocytic hypophysitis, is defined as an inflammatory condition of the pituitary gland of autoimmune etiology that leads to pituitary dysfunction. However, the pathogenesis of autoimmune hypophysitis is still incompletely defined. Although pathogenic autoantibodies in autoimmune hypophysitis have not yet been reported, it has been suggested that several antibodies may be closely related to pathogenesis. Novel clinical entities that are associated with hypophysitis, such as IgG4-related hypophysitis and anti-PIT-1 antibody syndrome, have recently been reported. The findings demonstrate the heterogeneity of the disease and provide important clues for understanding the pathogenesis and definition of hypophysitis, as well as the significance of antipituitary antibodies. This review focuses on new developments in autoimmune hypophysitis.
Topics: Animals; Autoantibodies; Autoimmune Hypophysitis; Humans; Pituitary Diseases; Pituitary Gland
PubMed: 25248604
DOI: 10.1016/B978-0-444-59602-4.00029-0 -
The Journal of Clinical Endocrinology... Jan 2022Hypophysitis is defined as inflammation of the pituitary gland that is primary or secondary to a local or systemic process. Differential diagnosis is broad (including... (Review)
Review
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 sellar tumors or cysts, systemic diseases, and infection or drug-induced causes. Novel pathologies such as immunoglobulin G4-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, as well as 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.
Topics: Adult; Aged; Autoimmunity; Diagnosis, Differential; Female; Humans; Hypophysitis; Magnetic Resonance Imaging; Male; Pituitary Gland; Rare Diseases
PubMed: 34528683
DOI: 10.1210/clinem/dgab672 -
Handbook of Clinical Neurology 2021Once central diabetes insipidus (CDI) has been diagnosed, every effort should be made to reveal its underlying cause. Autoimmune CDI should be considered in the... (Review)
Review
Once central diabetes insipidus (CDI) has been diagnosed, every effort should be made to reveal its underlying cause. Autoimmune CDI should be considered in the differential diagnosis of idiopathic CDI and also of mass lesions of the sella region. An autoimmune etiology of CDI was first suggested in 1983 by the detection of autoantibodies to hypothalamic vasopressin-producing cells (AVPcAb) in adults and also in children with the disease, using the indirect immunofluorescence test. The major autoantigen for autoimmune CDI has now been recognized as rabphilin-3A, a protein of secretory vesicles of the neurohypophyseal system. The detection of autoantibodies to rabphilin-3A by Western blotting or of AVPcAb provides strong evidence for the diagnosis of autoimmune CDI. Autoimmune CDI is recognized mostly in patients who had also been diagnosed with endocrine autoimmune disorders. The radiological and morphological correlate with autoimmune DI is lymphocytic infundibuloneurohypophysitis (LINH) as detected by magnetic resonance imaging and biopsies that show massive infiltration of the posterior pituitary and the infundibulum with lymphocytes and some plasma cells, and fibrosis in the later stages of the disease. LINH may be associated with lymphocytic anterior hypophysitis. Both may either appear spontaneously or on treatment with immune checkpoint inhibitors.
Topics: Adult; Autoimmune Diseases; Autoimmune Hypophysitis; Child; Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Diabetes Mellitus, Type 1; Humans; Magnetic Resonance Imaging; Pituitary Gland, Posterior
PubMed: 34238458
DOI: 10.1016/B978-0-12-820683-6.00015-4 -
QJM : Monthly Journal of the... Jan 2022
Topics: Autoimmune Diseases; Autoimmune Hypophysitis; Humans; Pituitary Diseases; Pituitary Gland
PubMed: 34373912
DOI: 10.1093/qjmed/hcab218 -
The Lancet. Oncology Feb 2018
Topics: Adenocarcinoma of Lung; Adrenal Cortex Hormones; Aged, 80 and over; Antineoplastic Agents, Immunological; Autoimmune Hypophysitis; Follow-Up Studies; Humans; Ipilimumab; Magnetic Resonance Imaging; Male; Pituitary Gland; Rare Diseases; Risk Assessment; Severity of Illness Index; Treatment Outcome
PubMed: 29413466
DOI: 10.1016/S1470-2045(17)30577-6 -
Reviews in Endocrine & Metabolic... Dec 2018The pituitary gland and the hypothalamus can be affected by autoimmune-mediated structural and functional disruption. These autoimmune-mediated diseases occur more... (Review)
Review
The pituitary gland and the hypothalamus can be affected by autoimmune-mediated structural and functional disruption. These autoimmune-mediated diseases occur more commonly in females and are often found during pregnancy or in the post-partum period. Autoimmune diseases can either affect parts of the pituitary or hypothalamus, or can involve both sellar and suprasellar structures. Most of these cases comprise primary hypophysitis (PRH). Over the years, there has been a tremendous increase in the number of reported PRH cases and related disorders, including hypophysitis induced by immune checkpoint inhibitors. With this increasing data, more light is being shed on the spectrum of clinical presentations, biochemical and imaging abnormalities of these disorders. Regardless, these disorders are still relatively rare. The clinical presentation can vary vastly, based on the type of pituitary cell or the area of the suprasellar region affected. The severity can range from clinically silent disease to progressive and rapid deterioration and death, likely due to unrecognized central adrenal insufficiency. Although biopsy remains a gold standard for diagnosing these disorders, the current standard of practice is biochemical assessment for hormonal deficiencies and imaging studies. In several instances, these disorders spontaneously resolve, but medical or surgical intervention might be necessary to treat symptomatic disease. Due to the subtlety and a vast spectrum of clinical manifestations which could often be asymptomatic, and the rarity of the occurrence of these diseases in clinical practice, the diagnosis can be easily missed which could potentially lead to substantial morbidity or mortality. Therefore, it is crucial to have a strong clinical suspicion and pursue timely biochemical and imaging studies to initiate prompt treatment. In this article, we review the various autoimmune conditions that affect the sellar and suprasellar structures, their diagnostic approach and management of these disorders.
Topics: Animals; Autoimmune Diseases; Autoimmune Hypophysitis; Humans; Hypophysitis
PubMed: 30547288
DOI: 10.1007/s11154-018-9480-1 -
Expert Review of Clinical Immunology Nov 2021Hypophysitis is an inflammation of the pituitary gland and a rare case of hypopituitarism. Despite the expanding spectrum of histological variants and causative agents,... (Review)
Review
INTRODUCTION
Hypophysitis is an inflammation of the pituitary gland and a rare case of hypopituitarism. Despite the expanding spectrum of histological variants and causative agents, its pathogenesis is far to be fully understood. The present review is focused on recent evidence concerning the pathogenesis of autoimmune hypophysitis by searching through online databases like MEDLINE and Scopus up to May 2021.
AREAS COVERED
Hypophysitis frequently develops in the context of a strong autoimmune background, including a wide spectrum of subtypes ranging from the commonest form of lymphocytic hypophysitis to the newly described and less common IgG4-, anti-PIT-1, and ICI-induced forms. A peculiar combination of genetic predisposition, pituitary damage and immunological setting represents the pathogenetic basis of autoimmune hypophysitis, which is characterized by diffuse infiltration of the gland by lymphocytes and variable degrees of fibrosis followed by pituitary cell destruction. Anti-pituitary antibodies (APA) have been described in sera from patients suffering from autoimmune hypophysitis, though their pathophysiological significance remains largely unknown and their diagnostic value limited.
EXPERT OPINION
In recent years hypophysitis has gained interest due to the increased number of new diagnoses and the recognition of novel subtypes. Further studies could lead to improvements in biochemical/immunological diagnosis and targeted treatments.
Topics: Autoimmune Hypophysitis; Humans; Hypophysitis; Immunoglobulin G; Pituitary Diseases; Pituitary Gland
PubMed: 34464545
DOI: 10.1080/1744666X.2021.1974297