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Frontiers in Endocrinology 2020Autoimmune hypophysitis (AH) is a primary autoimmune inflammatory disorder of the pituitary gland, which usually presents as a mass in the sella turcica. Systemic lupus... (Review)
Review
BACKGROUND
Autoimmune hypophysitis (AH) is a primary autoimmune inflammatory disorder of the pituitary gland, which usually presents as a mass in the sella turcica. Systemic lupus erythematosus (SLE) is another inflammatory disorder in which the immune system attacks healthy cells and tissues throughout the body. Although both diseases are autoimmune disorders, they rarely coexist, and the relationship between them is unclear.
CASE REPORT
A 66-year-old man was evaluated at the endocrinology clinic because of worsening fatigue, anorexia, drowsiness, and leg oedema. Examination revealed alertness impairment and lower limb oedema. Laboratory tests showed anterior pituitary hypofunction. The treatment approach, with glucocorticoids and immunosuppressive agents, resulted in long-term remission of symptoms of hypopituitarism and hyponatraemia.
CONCLUSIONS
Our case demonstrates a potential association between AH and SLE. AH may need to be considered in the evaluation of SLE patients with headache, hyperprolactinemia, a pituitary mass, and hypopituitarism.
Topics: Aged; Autoimmune Hypophysitis; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Male; Prognosis
PubMed: 33117291
DOI: 10.3389/fendo.2020.579436 -
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 -
Clinical Medicine Insights.... 2015Ipilimumab is a monoclonal antibody directed against CTLA4 T-lymphocyte antigen used as cancer therapy. Immune-related adverse events are common side effects and may... (Review)
Review
Ipilimumab is a monoclonal antibody directed against CTLA4 T-lymphocyte antigen used as cancer therapy. Immune-related adverse events are common side effects and may include hypophysitis-related hypopituitarism. The clinical features of six patients with ipilimumab-induced hypophysitis (IH) are described. The clinical features of IH reported in clinical trials, including the incidence of IH by gender and the likelihood of adrenal axis recovery, are summarized. Following the development of IH, most patients remain on glucocorticoid replacement despite efforts to withdraw therapy. Analysis of gender information in published clinical trials suggests that men are more prone to developing IH than women, and few patients fully recover the pituitary-adrenal axis function. Ipilimumab and other drugs within its class are likely to be used to treat many forms of cancer. Endocrinologists should anticipate a significant increase in the incidence of autoimmune hypophysitis. Strategies for early detection of IH and long-term management should be considered.
PubMed: 25861234
DOI: 10.4137/CMED.S22469 -
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 -
The Indian Journal of Medical Research May 2013
Topics: Adult; Autoimmune Diseases; Biopsy; Female; Humans; Pituitary Diseases; Pituitary Gland; Radiography
PubMed: 23760392
DOI: No ID Found -
Journal of Nippon Medical School =... 2017The number of cases of lymphocytic hypophysitis is small, although the condition is not rare. For optimal therapy, the correct diagnosis from imaging, immunological... (Review)
Review
The number of cases of lymphocytic hypophysitis is small, although the condition is not rare. For optimal therapy, the correct diagnosis from imaging, immunological studies, and pathological findings from a pituitary biopsy is important. Recently, anti-Rabphilin antibody has been proposed to be a biomarker for lymphocytic infundibulo-neurohypophysitis. Immunological disorders such as anti-Pit-1 antibody syndrome are similar to the pathogenesis of lymphocytic hypophysitis. Moreover, recent immune checkpoint blockade such ipilimumab has been shown to induce anti-CTLA-4-related hypophysitis. In the future, elucidating the immunological mechanism and establishing a suitable therapy will be necessary for accurate long-term prognosis.
Topics: Antineoplastic Agents, Immunological; Autoantibodies; Autoimmune Hypophysitis; Biomarkers; CTLA-4 Antigen; Diagnosis, Differential; Humans; Ipilimumab; Magnetic Resonance Imaging; Nerve Tissue Proteins; Pituitary Gland; Transcription Factor Pit-1
PubMed: 29142180
DOI: 10.1272/jnms.84.201 -
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 -
The Pan African Medical Journal 2020The aim of this study is to report a challengeable and rare case of autoimmune hypophysitis possibly induced by viral infections. A young pregnant female developed optic...
The aim of this study is to report a challengeable and rare case of autoimmune hypophysitis possibly induced by viral infections. A young pregnant female developed optic neuropathy due to enlarged sellar mass responsible for hypopituitarism. Investigations exclude neoplasia and systemic diseases. High level of sedimentation rate and magnetic resonance imaging (MRI) findings supported the diagnosis of autoimmune hypophysitis. The patient reported a history of bronchitis treated with antibiotics and corticosteroids and positive serologies for hepatitis B antigen (Hbs antigen), herpes simplex 1 and rubella. Final examination showed complete recovery of visual function and sellar archnoidocele after antiviral treatment and mild dose of corticosteroids.
Topics: Adrenal Cortex Hormones; Adult; Antiviral Agents; Autoimmune Hypophysitis; Female; Humans; Magnetic Resonance Imaging; Pregnancy; Pregnancy Complications; Virus Diseases
PubMed: 32774605
DOI: 10.11604/pamj.2020.36.28.22454 -
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