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Nature Reviews. Endocrinology Jul 2021Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that target two key signalling pathways related to T cell activation and exhaustion, by binding to and... (Review)
Review
Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that target two key signalling pathways related to T cell activation and exhaustion, by binding to and inhibiting cytotoxic T lymphocyte antigen 4 (CTLA4) or PD1 and its ligand PDL1. ICIs, such as nivolumab, pembrolizumab and ipilimumab, are approved for the treatment of numerous and diverse cancer types, in various combination regimens, and are now an established cornerstone of cancer therapeutics. Toxicities induced by ICIs are autoimmune in nature and are referred to as immune-related adverse events (irAEs); these events can affect any organ system in an unpredictable fashion. Importantly, irAEs can manifest as endocrinopathies involving the thyroid (hypothyroidism or thyrotoxicosis), pituitary (hypophysitis), adrenal glands (adrenal insufficiency) and pancreas (diabetes mellitus). These events are a frequent source of acute and persistent morbidity in patients treated with ICIs and can even be fatal. Over the past few years, there has been a growing understanding of the underlying pathogenesis of irAEs that has led to the development of more effective management strategies. Herein, we review the current understanding of the pathobiology, clinical manifestations and treatment approaches to endocrine toxicities arising from ICIs.
Topics: Antineoplastic Agents, Immunological; Drug-Related Side Effects and Adverse Reactions; Endocrine System Diseases; Humans; Immune Checkpoint Inhibitors; Immune System; Immunotherapy; Neoplasms
PubMed: 33875857
DOI: 10.1038/s41574-021-00484-3 -
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 -
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 -
Journal of the Neurological Sciences May 2021IgG4-related disease (IgG4-RD) is emerging as a fibro-inflammatory entity affecting multiple organs, including manifold neurologic manifestations. This review discusses... (Review)
Review
PURPOSE OF REVIEW
IgG4-related disease (IgG4-RD) is emerging as a fibro-inflammatory entity affecting multiple organs, including manifold neurologic manifestations. This review discusses general characteristics of IgG4-RD neurologic disease including epidemiology, histology, clinical picture and treatment approaches.
RECENT FINDINGS
IgG4-RD is increasingly recognized as an important underlying pathophysiology in multiple disorders of neurologic interest, including orbital inflammation, infundibulo-hypophysitis, hypertrophic pachymeningitis, and even in rare cases CNS parenchymal disease and cranial vascular involvement. These were previously considered idiopathic and unrelated to any systemic disease but now known to share a common histopathology. New knowledge regarding the pathogenesis, clinical features and epidemiology of IgG4 is emerging, and new neurological manifestations continue to be described. Diagnostic progress includes CT-PET imaging, the use of flow cytometry for plasmablast quantification, and the use of reverse passive latex agglutination aiming to overcome the prozone phenomenon. Histopathologic confirmation of IgG4-RD remains the gold standard method of diagnosis but new diagnostic criteria for systemic and organ-specific disease are being proposed. Though glucorticoids remain the mainstay of therapy, relapses and incomplete recovery are frequent. Rituximab is a promising treatment in IgG4-RD that is severe, refractory or glucocorticoid dependent. Initiation of immunosuppression at an early stage of disease should be considered in order to avoid development of refractory fibrosis.
SUMMARY
The current review emphasizes the neurologic manifestations of IgG4-RD.
Topics: Autoimmune Diseases; Humans; Immunoglobulin G; Immunoglobulin G4-Related Disease; Meningitis; Neurology; Plasma Cells
PubMed: 33845982
DOI: 10.1016/j.jns.2021.117420 -
Endocrine Aug 2021Hypophysitis is a rare pituitary inflammatory disorder classified in different ways. Immunoglobulin G4-related disease (IgG4-RD), also a rare disease is a systemic... (Review)
Review
Hypophysitis is a rare pituitary inflammatory disorder classified in different ways. Immunoglobulin G4-related disease (IgG4-RD), also a rare disease is a systemic fibro-inflammatory condition characterized by infiltration of tissue with IgG4-positive plasma cells; however prevalence of both of them probably is underestimated. In this paper, we present an Iranian patient with biopsy-proven IgG4-related hypophysitis and then review the clinical characteristics, laboratory, imaging, pathologic findings and therapeutic management as well as prognosis of 115 published cases of hypophysitis secondary to IgG4-related disease.
Topics: Autoimmune Hypophysitis; Humans; Hypophysitis; Iran; Pituitary Diseases; Pituitary Gland
PubMed: 33837927
DOI: 10.1007/s12020-021-02714-0 -
European Journal of Endocrinology Dec 2022Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment but are associated with significant autoimmune endocrinopathies that pose both diagnostic and...
Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment but are associated with significant autoimmune endocrinopathies that pose both diagnostic and treatment challenges. The aim of this guideline is to provide clinicians with the best possible evidence-based recommendations for treatment and follow-up of patients with ICI-induced endocrine side-effects based on the Grading of Recommendations Assessment, Development, and Evaluation system. As these drugs have been used for a relatively short time, large systematic investigations are scarce. A systematic approach to diagnosis, treatment, and follow-up is needed, including baseline tests of endocrine function before each treatment cycle. We conclude that there is no clear evidence for the benefit of high-dose glucocorticoids to treat endocrine toxicities with the possible exceptions of severe thyroid eye disease and hypophysitis affecting the visual apparatus. With the exception of thyroiditis, most endocrine dysfunctions appear to be permanent regardless of ICI discontinuation. Thus, the development of endocrinopathies does not dictate a need to stop ICI treatment.
Topics: Humans; Immune Checkpoint Inhibitors; Neoplasms; Endocrine System Diseases; Hypophysitis; Drug-Related Side Effects and Adverse Reactions
PubMed: 36149449
DOI: 10.1530/EJE-22-0689 -
Gan To Kagaku Ryoho. Cancer &... Jun 2020In recent years, the role ofimmune checkpoint inhibitors(ICIs)has become crucial in cancer therapy. However, ICIs are known to trigger a wide variety of autoimmune side...
In recent years, the role ofimmune checkpoint inhibitors(ICIs)has become crucial in cancer therapy. However, ICIs are known to trigger a wide variety of autoimmune side effects, termed immune-related adverse events(irAEs), which can influence multiple organs. Hypophysitis induced by ICIs, which is defined as the inflammation of the pituitary gland and is the cause ofhypopituitarism, is one ofthe important toxicities, because it can be life-threatening event when it is not diagnosed or managed properly. Therefore, ICIs-induced hypophysitis should be recognized as one ofthe oncologic emergencies. Symptoms, laboratory data, hormone level measurement, and pituitary magnetic resonance imaging are necessary for diagnosis. It should be taken into consideration that types of agents in ICIs have an effect on patterns of symptoms, onset timing, and hormone deficiencies. Replacement of appropriate hormones according to severity is fundamental strategy. Patient education especially about sick day rules is vital, because adrenal insufficiency secondary to adrenocorticotropic hormone deficiency usually remains permanently. There is no established predictive biomarker for irAEs yet. Thus, for an early awareness of the symptoms ofirAEs and a proper management in clinical practice, interprofessional collaboration among oncologists, endocrinologists, nurses, pharmacists, and other health care workers must be essential.
Topics: Endocrine System Diseases; Humans; Hypopituitarism
PubMed: 32541161
DOI: No ID Found