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Journal of Personalized Medicine Jul 2023Hypophysitis, a rare inflammatory disorder of the pituitary gland, has seen an uptick in reported cases in recent years. Our objective is to summarize the most recent... (Review)
Review
Hypophysitis, a rare inflammatory disorder of the pituitary gland, has seen an uptick in reported cases in recent years. Our objective is to summarize the most recent research on the etiopathogenesis, molecular mechanisms, and genetics of both primary and secondary hypophysitis. Primary autoimmune hypophysitis (PAH): During the acute phase of the disease, the pituitary gland in enlarged due to the infiltration of T and B lymphocytes. The chronic phase is characterized by progressive and irreversible pituitary atrophy. APA may play a role in the management, diagnosis, and prognosis of PAH. Specific autoantibodies such as anti-GH, anti-PIT-1, and anti-T-PIT have been found in patients with hypophysitis and hypopituitarism. A recent study suggested that a mechanism of escaping clonal deletion and mounting an immune response against self antigens can explain the unusual nature of the immune response observed in PAH patients. A cytokine array shows the presence of gamma-interferon and interleukin-17. Patients carrying mutations in the PIT1 or PROP1 genes may present PAH. Individuals carrying the HLA DQ8 haplotype are four times more likely to develop PAH. Immune checkpoint inhibitors induce hypophysitis (IIHs): IIHs is an increasingly frequent toxicity of in patients on treatment with inhibitors targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death-1 (PD-1). ICIs inhibit the CTLA-4 pathway, leading to overactivation of T lymphocytes. The binding of PD-1/PD-L1 suppresses the activity of T cells, promotes the conversion of T-helpers into T-regulatory cells, and activates pro-survival signaling pathways in cancer cells. Cytokines play a crucial role in IIHs. B-cell infiltration has been observed in IIHs, suggesting that antibody-mediated pituitary injury may contribute. Genetic polymorphisms of CTLA-4 and PD-1 genes can increase the risk of IIHs. HLA alleles may also be involved in the onset of IIHs; this HLA association presents a possible alternative mechanistic hypothesis. IIHs may also be linked to a paraneoplastic syndrome triggered by ectopic expression of pituitary specific antigens. SARS-CoV-2-related hypophysitis: Recently, the literature has reported occurrences of hypophysitis associated with the SARS-CoV-2 virus; long COVID-19 may also present as infundibulo-neuro-hypophysitis. The virus enters the central nervous system because of its distinct interaction with angiotensin-converting enzyme receptors via spike proteins binding the capillary endothelium, and it directly damages the pituitary cells. The effect of SARS-CoV-2 can occur indirectly through inflammation and the release of cytokines. The exact mechanism remains ambiguous. The available data on endocrine complications associated with the SARS-CoV-2 vaccine are scant. Nonetheless, isolated cases of hypophysitis have been documented. Treatment of hypophysitis: Glucocorticoids are the cornerstone in managing primary hypophysitis, given their targeted action on inflammation. A better understanding of the etiopathogenesis and molecular mechanism of hypophysitis can lead to more effective and personalized treatment strategies.
PubMed: 37623461
DOI: 10.3390/jpm13081210 -
International Journal of Molecular... Mar 2023Inflammatory disease of the pituitary gland is known as hypophysitis. There are multiple histological subtypes, the most common being lymphocytic, and the pathogenesis... (Review)
Review
Inflammatory disease of the pituitary gland is known as hypophysitis. There are multiple histological subtypes, the most common being lymphocytic, and the pathogenesis is variable and diverse. Hypophysitis can be primary and idiopathic or autoimmune related, or secondary to local lesions, systemic disease, medications, and more. Although hypophysitis was previously accepted as an exceedingly rare diagnosis, a greater understanding of the disease process and new insights into possible etiologic sources have contributed to an increased frequency of recognition. This review provides an overview of hypophysitis, its causes, and detection strategies and management.
Topics: Humans; Hypophysitis; Pituitary Gland; Lymphocytes
PubMed: 36982990
DOI: 10.3390/ijms24065917 -
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 -
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 -
AJNR. American Journal of Neuroradiology Sep 2022Granulomatous hypophysitis is a rare inflammatory condition of the pituitary gland with an imaging appearance that can overlap with that of pituitary adenoma.... (Review)
Review
BACKGROUND AND PURPOSE
Granulomatous hypophysitis is a rare inflammatory condition of the pituitary gland with an imaging appearance that can overlap with that of pituitary adenoma. Differentiating the two before surgical resection can have important treatment implications. The purpose of our study was to determine whether it was possible to differentiate between granulomatous hypophysitis and pituitary adenoma on the basis of diffuse enhancing infrasellar basisphenoid bone marrow.
MATERIALS AND METHODS
We present 3 cases, initially thought to be pituitary adenomas, that were pathology-proved granulomatous hypophysitis. The preoperative MR images were reviewed for diffuse, enhancing infrasellar basisphenoid bone marrow. For comparison, we reviewed 100 cases of pathology-proved pituitary adenoma for the same finding. Additionally, imaging findings including the sphenoid sinus pneumatization pattern, clinical history, laboratory values, and pathology results were reviewed.
RESULTS
All 3 cases of granulomatous hypophysitis had diffuse enhancing infrasellar basisphenoid bone marrow. Conversely, this was not seen in any of the 100 pituitary adenomas. The patients with granulomatous hypophysitis were all women. Two patients had idiopathic granulomatous hypophysitis, and 1 had secondary granulomatous hypophysitis with sarcoidosis. Of the 100 patients with pituitary adenomas, 67 were women. The basisphenoid pneumatization patterns was as follows: 15 (type 2), 40 (type 3), and 45 (type 4).
CONCLUSIONS
We present 3 cases of granulomatous hypophysitis with diffuse enhancement of the infrasellar basisphenoid bone marrow that was not seen in our 100 cases of pituitary adenomas. This imaging feature may be valuable for suggesting a diagnosis of granulomatous hypophysitis and avoiding surgical resection of what might otherwise be misdiagnosed as a pituitary adenoma.
Topics: Humans; Female; Male; Pituitary Neoplasms; Diagnosis, Differential; Hypophysitis; Pituitary Gland; Autoimmune Hypophysitis; Magnetic Resonance Imaging
PubMed: 36007945
DOI: 10.3174/ajnr.A7618 -
Indian Pediatrics Jan 2021
Topics: Autoimmune Hypophysitis; Humans; Lupus Erythematosus, Systemic
PubMed: 33452786
DOI: No ID Found