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Pharmaceuticals (Basel, Switzerland) Apr 2022Checkpoint inhibitors (CPI) represent a novel therapeutical strategy with a high efficacy both in solid and hematological cancers. They act by reactivating the immune... (Review)
Review
Checkpoint inhibitors (CPI) represent a novel therapeutical strategy with a high efficacy both in solid and hematological cancers. They act by reactivating the immune system against neoplastic cells but may, in turn, cause immune-related adverse events (IRAEs) involving several organs with variable frequency and severity. Up to 10% of CPI-treated patients experience hematological IRAEs, mainly cytopenias. The differential diagnosis is challenging due to underlying disease, previous treatments and the variable liability of available tests (i.e., the direct antiglobulin test, anti-platelet antibodies, etc.). Among extra-hematological IRAEs, cutaneous and endocrine ones are the most frequent (up to 30-50%), ranging from mild (pruritus, eczema and thyroid dysfunctions) to severe forms (bullous disorders, hypophysitis and diabetes), mostly requiring topic or replacement therapy. Gastroenteric and kidney toxicities occur in about 5% of patients, biopsies may support the diagnosis, and immunosuppressive treatment is required in severe cases. Finally, neurologic and cardiologic IRAEs, although rare, may be life-threatening and require prompt intervention. By reviewing the most recent literature on post-CPI IRAEs, it emerged that clinical suspicion and monitoring of laboratory markers of organ damage is pivotal to a prompt diagnosis. In severe cases, CPI should be discontinued and immunosuppressive therapy started, whilst rechallenge is anecdotal and should be carefully evaluated.
PubMed: 35631383
DOI: 10.3390/ph15050557 -
Cancers Jan 2022Immune checkpoint inhibitors (ICIs) have improved survival in patients affected by several solid tumours at the cost of new autoimmune adverse events. Endocrine toxicity... (Review)
Review
Immune checkpoint inhibitors (ICIs) have improved survival in patients affected by several solid tumours at the cost of new autoimmune adverse events. Endocrine toxicity is frequently reported in patients treated with these agents, mainly as thyroid dysfunction and hypophysitis. Primary adrenal insufficiency is reported in 1-2% of patients receiving a single ICI, but its rate is approximately 5% in patients treated with a combination of two ICIs. The clinical presentation of adrenal insufficiency may be insidious due to symptoms that are not specific. The same symptoms in cancer patients are frequently multifactorial, rendering the early diagnosis of adrenal insufficiency challenging in this group of patients. As adrenal insufficiency can be fatal if not rapidly diagnosed and treated, oncologists should be aware of its clinical presentations to timely involve endocrinologists to offer patients the appropriate management. In parallel, it is essential to educate patients, their caregivers, and relatives, providing them with detailed information about the risk of adrenal insufficiency and how to manage alarming symptoms at their onset. Finally, large collaborative trials are needed to develop appropriate tests to assess better the personal risk of drug-induced adrenal insufficiency and its early diagnosis and treatment, not only in cancer patients.
PubMed: 35158860
DOI: 10.3390/cancers14030593 -
Acta Medica Portuguesa Mar 2022Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that increase the efficiency of the immune system in the destruction of neoplastic cells. In recent years,... (Review)
Review
INTRODUCTION
Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that increase the efficiency of the immune system in the destruction of neoplastic cells. In recent years, these drugs have been increasingly used in the treatment of many neoplasms in advanced stages. However, the change in the regulation of the immune system induced by these drugs has the potential adverse effect of inducing autoimmunity in practically all organ systems. Endocrinopathies are one of the most common autoimmune adverse eventsof these drugs.
MATERIAL AND METHODS
Non-systematic review of endocrinopathies reported in the context of treatment with ICIs. A search was carried out on PubMed until January 31st, 2020, and articles were selected based on their relevance and excluded in case of redundant content. The following search terms were used: "immune checkpoint inhibitor" and "endocrinopathy" / "endocrine system diseases" / "pituitary" / "thyroid" / "diabetes" / "adrenal" / "parathyroid".
RESULTS
Endocrinopathies with all classes of ICIs (anti-CTLA-4, anti-PD-1, anti-PD-L1) have been reported. Thyroid dysfunction is the most frequently reported endocrinopathy, mainly with anti-PD-1 and anti-PD-L1. Hypophysitis is the most prevalent with anti-CTLA-4. The incidence of autoimmune diabetes in this context is increasing, mainly with anti-PD-1 and anti-PD-L1. Rare cases of primary adrenal insufficiency, Graves' disease and primary hypoparathyroidism have also been reported.
CONCLUSION
Knowing the spectrum of endocrinopathies triggered by ICI, as well as their clinical features, diagnosis and treatment criteria is essential, given its high prevalence and the increasing number of cancer patients treated with these new drugs.
Topics: Antineoplastic Agents, Immunological; Endocrine System Diseases; Humans; Hypophysitis; Immune Checkpoint Inhibitors; Immunotherapy; Neoplasms
PubMed: 35077347
DOI: 10.20344/amp.13673 -
European Journal of Endocrinology Apr 2020Hypopituitarism is caused by various insults to the pituitary, such as hypothalamic and pituitary tumors, inflammation, autoimmunity, vascular injury, genetic... (Review)
Review
Hypopituitarism is caused by various insults to the pituitary, such as hypothalamic and pituitary tumors, inflammation, autoimmunity, vascular injury, genetic abnormalities, irradiation, and trauma. Recently, it has been found that autoimmunity to the pituitary involves many pathological conditions associated with specific or non-specific hormone deficiencies in the gland. This review discusses the recent findings on the underlying mechanism of autoimmune hypopituitarism particularly of lymphocytic hypophysitis, IgG4-related hypophysitis, immune checkpoint inhibitor-induced hypophysitis, anti-PIT-1 hypophysitis, and isolated ACTH deficiency.
Topics: Autoimmune Diseases; Autoimmune Hypophysitis; Endocrinology; Humans; Hypopituitarism
PubMed: 31999621
DOI: 10.1530/EJE-19-1051 -
Journal of Pediatric Endocrinology &... Mar 2021IgG4-related hypophysitis is a novel clinical disease entity, which is typically seen in the sixth decade of life and is typically complicated by hypopituitarism. We...
OBJECTIVES
IgG4-related hypophysitis is a novel clinical disease entity, which is typically seen in the sixth decade of life and is typically complicated by hypopituitarism. We describe an adolescent female with IgG4-related hypophysitis with normal pituitary function and summarize the relevant literature.
CASE PRESENTATION
A 11.8-year-old girl presented with headache and left VI cranial nerve palsy. MRI brain identified an enlarged pituitary gland. Endocrine investigations revealed normal pituitary function. She underwent a transsphenoidal biopsy of the pituitary gland, and histological examination confirmed the diagnosis of IgG4-related hypophysitis. Serum IgG4 concentrations were normal and no evidence of other organ involvement was found. Although the patient tested strongly positive for TB on an interferon gamma release assay, pituitary biopsy was negative for granuloma formation and acid-fast bacilli (Ziehl-Neelson staining). IgG4-related hypophysitis was treated with oral prednisolone and mycophenolate-mofetil with a good response.
CONCLUSIONS
We describe to the best of our knowledge, the youngest patient in the published literature with IgG4-related hypophysitis presenting without pituitary insufficiency. A literature review identified only five cases of IgG4-related hypophysitis in adolescence. Serum IgG4 concentrations were normal in all, except one of the adolescent patients reported so far, and appear unhelpful in diagnosis in this age group.
Topics: Autoimmune Hypophysitis; Child; Female; Glucocorticoids; Humans; Immunoglobulin G
PubMed: 33675204
DOI: 10.1515/jpem-2020-0535 -
Der Pathologe May 2016Inflammatory findings in the pituitary glands account for approximately 1 % of operations in the sellar region. Primary inflammation (e.g. lymphocytic and idiopathic... (Review)
Review
Inflammatory findings in the pituitary glands account for approximately 1 % of operations in the sellar region. Primary inflammation (e.g. lymphocytic and idiopathic granulomatous hypophysitis) have to be differentiated from secondary types (e.g. concomittant inflammation with Rathke's cleft cysts, craniopharyngiomas and germinomas) and involvement of the pituitary in generalized inflammation (IgG4-related disease, sarcoidosis and septicopyemia). Langerhans cell histiocytosis also has to be considered for the differential diagnostics. Lymphocytic hypophysitis shows lymphocytic infiltrations of varying density, predominantly of the T‑cell type. Granulomatous hypophysitis has the features of sarcoidosis and can only be diagnosed by exclusion of generalized sarcoidosis. Secondary hypophysitis has a mixed cell infiltration, especially by histiocytic infiltration and predominantly originates from ruptures or bleeding from Rathke's cleft cysts. The frequently very sparse remnants of cyst epithelium should be confirmed by pankeratin immunostaining.
Topics: Autoimmune Hypophysitis; Central Nervous System Cysts; Diagnosis, Differential; Histiocytes; Humans; Hypophysitis; Pituitary Gland; Rupture, Spontaneous
PubMed: 27103256
DOI: 10.1007/s00292-016-0164-x -
Journal of Nippon Medical School =... May 2023Immune checkpoint inhibitors (ICIs) are widely used for various types of advanced cancers. Currently, three types of ICIs are clinically available, a monoclonal antibody... (Review)
Review
Immune checkpoint inhibitors (ICIs) are widely used for various types of advanced cancers. Currently, three types of ICIs are clinically available, a monoclonal antibody targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), and antibodies targeting the programmed cell death protein-1 (PD-1) and its ligand, programmed cell death ligand 1 (PD-L1). Although ICIs have improved the survival rates of several types of cancers, they induce immune-related adverse events (irAE) by their enhancement of immune responses. The pituitary gland is one of the common targets of irAE. In general, different clinical presentations of autoimmune pituitary dysfunctions are observed between anti-CTLA-4 and anti-PD-1/anti-PD-L1 antibodies, with anti-CTLA-4 inducing hypophysitis with multiple pituitary hormone deficiencies and targeting the PD-1/PD-L1 axis inducing isolated adrenocorticotropic hormone deficiency. This review describes the current understanding of the pathophysiology, clinical manifestation, and management of hypophysitis caused by ICIs.
Topics: Humans; Immune Checkpoint Inhibitors; Ligands; Antibodies, Monoclonal; Neoplasms; Hypophysitis; Immune System Diseases
PubMed: 36823122
DOI: 10.1272/jnms.JNMS.2023_90-215 -
Best Practice & Research. Clinical... Dec 2019Hypophysitis is a heterogeneous condition that leads to inflammation of the sella and/or suprasellar region, potentially resulting in hormonal deficiencies and/or mass... (Review)
Review
Hypophysitis is a heterogeneous condition that leads to inflammation of the sella and/or suprasellar region, potentially resulting in hormonal deficiencies and/or mass effects. A preponderance of hypophysitis subtypes have an underlying autoimmune aetiology. The overall incidence and prevalence of hypophysitis has dramatically increased over the past decade, mainly due to increased awareness of the condition in the medical community, improvements in imaging techniques, and a rise in the occurrence of certain forms of hypophysitis such as IgG4 hypophysitis (IgG4Hy) and immune checkpoint inhibitor induced hypophysitis (ICIHy). The clinical presentation varies from an asymptomatic condition to a fatal disease often as a result of electrolyte abnormalities due to glucocorticoid deficiency in the context of adrenal crisis from central adrenal insufficiency. Milder forms of hypophysitis are treated with replacement of deficient hormones while more acute presentations with mass effects require glucocorticoid therapy, immunosuppressive therapy or surgery. Timely diagnosis and interventions are keys to prevention of the lethal complications of this disease. In this review, we provide an update on the recent advances in the field of pituitary autoimmunity, with an emphasis on autoimmune hypophysitis and novel forms of hypophysitis such as anti-PIT1 hypophysitis, IgG4Hy and ICIHy.
Topics: Autoimmune Hypophysitis; Autoimmunity; Diagnostic Techniques, Endocrine; Humans; Hypophysitis; Inflammation; Pituitary Diseases; Therapies, Investigational
PubMed: 31866206
DOI: 10.1016/j.beem.2019.101371 -
Ipilimumab treatment associated pituitary hypophysitis: clinical presentation and imaging diagnosis.Clinical Neurology and Neurosurgery Oct 2014Ipilimumab is an immunomodulating drug for use in treatment of unresectable or metastatic melanoma with autoimmune lymphocytic hypophysitis as a reported complication.... (Review)
Review
Ipilimumab is an immunomodulating drug for use in treatment of unresectable or metastatic melanoma with autoimmune lymphocytic hypophysitis as a reported complication. We describe three recent cases of ipilimumab associated autoimmune hypophysitis (IAH) at our institution, and provide a selected literature review showing its variable clinical presentation, imaging appearance and treatment in order to expedite early and appropriate IAH management. Patients had variable clinical presentation of hypophysitis, including headache, fatigue, visual changes, endocrinopathy, and/or hyponatremia. Contrast enhanced MRI showed symmetric pituitary gland and stalk enlargement in all of our cases and received a presumptive diagnosis of IAH. Following cessation of therapy and treatment there was normalization of pituitary morphology at follow-up MRI and return to clinical baseline. Varying clinical presentation can complicate the diagnosis of lymphocytic hypophysitis. One must be cognizant of its overall clinical and radiologic picture in patients receiving ipilimumab, now commonly used for the treatment of metastatic melanoma.
Topics: Antibodies, Monoclonal; Diagnostic Imaging; Humans; Hypopituitarism; Ipilimumab; Magnetic Resonance Imaging; Melanoma; Pituitary Gland
PubMed: 25127260
DOI: 10.1016/j.clineuro.2014.06.011 -
Minerva Endocrinologica Sep 2016Hypophysitis is generally accepted as an autoimmune disease which is characterized by inflammation and cellular infiltration of the pituitary gland. It can be either...
Hypophysitis is generally accepted as an autoimmune disease which is characterized by inflammation and cellular infiltration of the pituitary gland. It can be either primary or secondary. In this review, treatment of primary hypophysitis of various histological subtypes are discussed. Management of primary hypophysitis is usually symptomatic aiming to reduce the size of the pituitary mass and/or replace deficient pituitary hormones. Observation with replacement for deficient pituitary hormones can be applied in some group of patients. Keeping the complications of surgery in mind, surgical intervention should be limited to cases with severe and/or deteriorating compressive signs or cases with inconclusive findings of hypophysitis in whom treatment would be based on histopathological examination. The most commonly used drugs in the treatment of hypophysitis are glucocorticoids. They are able to reduce the size of the mass lesion with their anti-inflammatory effects and sometimes pituitary functions may also recover. However, there is no consensus about the optimal duration and dose of glucocorticoid use. When glucocorticoids and/or surgery fail, azathioprine, methotrexate, cyclosporin A and novel immunotherapies can be tried as third or forth line treatment. Radiotherapy and radiosurgery have been seldom used for treatment of hypophysitis in order to reduce the mass effect.
Topics: Autoimmune Hypophysitis; Combined Modality Therapy; Hormone Replacement Therapy; Humans; Immunotherapy; Pituitary Hormones
PubMed: 26963662
DOI: No ID Found