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Best Practice & Research. Clinical... May 2022Immune checkpoint inhibitors are being prescribed increasingly widely for a range of malignancies. They are effective at treating certain cancers, but also have... (Review)
Review
Immune checkpoint inhibitors are being prescribed increasingly widely for a range of malignancies. They are effective at treating certain cancers, but also have significant side effects. Evidence suggests that efficacy is greatest in patients who experience one or more immune-related adverse events (irAEs). Common irAEs include skin and hepatic reactions, and a range of immune-related endocrinopathies. These include hypophysitis, thyroid disease, and autoimmune diabetes mellitus, and rarer endocrinopathies such as primary adrenal insufficiency, diabetes insipidus, parathyroid disease, autoimmune polyglandular syndrome, lipodystrophy, and ACTH-dependent Cushing's syndrome. Herein, we review the current literature related to these rarer immunotherapy-induced endocrinopathies.
Topics: Diabetes Insipidus; Diabetes Mellitus; Endocrine System Diseases; Humans; Hypophysitis; Immune Checkpoint Inhibitors; Immunotherapy; Lipodystrophy; Neoplasms
PubMed: 35382989
DOI: 10.1016/j.beem.2022.101635 -
ESMO Open Feb 2021Immune checkpoint inhibitors (ICIs) are antibodies that target certain immune checkpoints (ICs), such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed... (Review)
Review
Immune checkpoint inhibitors (ICIs) are antibodies that target certain immune checkpoints (ICs), such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed death 1 (PD-1) or its ligand (PD-L1), and have emerged as a powerful new tool for oncologists. As these immune checkpoints are crucial for immunological self-tolerance, such therapies can trigger autoimmune adverse effects. Endocrine complications are among the most common, including hypophysitis, thyroid dysfunction, diabetes mellitus and primary adrenal insufficiency, while autoimmune polyendocrine syndrome type 2 (APS-2) may also present. The aim of this article is to critically appraise the literature and present (i) the biological role and function of the main ICs, (ii) the use of ICIs in the treatment of various cancer types, (iii) the endocrine complications of cancer immunotherapy with ICIs and (iv) practical recommendations for screening and management of patients with such endocrinopathies in everyday clinical practice.
Topics: Endocrine System; Endocrine System Diseases; Humans; Hypophysitis; Immune Checkpoint Inhibitors; Immunotherapy
PubMed: 33399077
DOI: 10.1016/j.esmoop.2020.100011 -
Archives of Medical Science : AMS 2023This meta-analysis was performed to analyze the clinical presentation, magnetic resonance imaging (MRI) characteristics, and the management of lymphocytic hypophysitis... (Review)
Review
INTRODUCTION
This meta-analysis was performed to analyze the clinical presentation, magnetic resonance imaging (MRI) characteristics, and the management of lymphocytic hypophysitis (LYH).
MATERIAL AND METHODS
Four different databases were searched from January 2010 to December 2020, two researchers independently conducted literature screening, data extraction, and quality evaluation. We used a random effects meta-analysis to calculate summary relative risks with 95% CI.
RESULTS
This meta-analysis showed that the percentage of women among LYH patients was 78%. LYH was associated with pregnancy in 15% of female patients, with headache (49%) and symptoms of central diabetes insipidus (CDI) (45%) being the most frequent presentation. In 24% of LYH patients, there was an association with another autoimmune disease. The incidence of secondary hypogonadism, secondary hypoadrenalism, secondary hypothyroidism, and growth hormone deficit was 54%, 49%, 43%, and 22%, respectively. Pituitary contrast enhancement (63%), symmetrical pituitary enlargement (60%), thickening of the pituitary stalk (58%), sella mass or suprasellar extension (58%), and loss of posterior pituitary hyperintensity (50%) were typical MRI findings. Regarding LYH treatment, the percentage of patients who had observation or hormone replacement, steroid therapy, and surgery was 43%, 36%, and 34%, respectively.
CONCLUSIONS
It is of great significance to fully understand the clinical characteristics of lymphocytic hypophysitis, reduce missed diagnosis and misdiagnosis, avoid unnecessary surgery and maintain normal pituitary function.
PubMed: 37560735
DOI: 10.5114/aoms/144628 -
Experimental and Clinical Endocrinology... Jan 2024To investigate the autoimmune and genetic relationship between primary hypophysitis (PH) and celiac disease (CD).
AIM
To investigate the autoimmune and genetic relationship between primary hypophysitis (PH) and celiac disease (CD).
METHODS
The study was retrospective and patients with PH followed in our clinic between 2007 and 2022 were evaluated. Clinical, endocrinologic, pathologic, and radiologic findings and treatment modalities were assessed. Patients diagnosed with CD in the Gastroenterology outpatient clinic in 2020-2022 were included in the study as a control group. Information such as sociodemographic data, year of diagnosis, human leukocyte antigen (HLA) DQ2/8 information, CD-specific antibody levels, pathologic results of duodenal biopsy, treatment received, follow-up status, additional diseases, hormone use, and surgical history was obtained from patient records at PH.In patients diagnosed with PH, a duodenal biopsy was obtained, and the tissue was examined for CD by experienced pathologists. Anti-pituitary antibody (APA) and anti-arginine-vasopressin (AAVP) antibody levels of individuals with PH and CD were measured.
RESULTS
The study included 19 patients with lymphocytic hypophysitis, 30 celiac patients, and 30 healthy controls. When patients diagnosed with lymphocytic hypophysitis were examined by duodenal biopsy, no evidence of CD was found in the pathologic findings. The detection rate of HLA-DQ2/8 was 80% in celiac patients and 42% in PH (p=0.044). (APA and AAVP antibodies associated with PH were tested in two separate groups of patients and in the control group. APA and anti-arginine vasopressin (AAVP) levels in PH, CD and healthy controls, respectively M [IQR]: 542 [178-607];164 [125-243]; 82 [74-107] ng/dL (p=0.001), 174 [52-218]; 60 [47-82]; 59 [48-76] ng/dL (p=0.008) were detected. The presence of an HLA-DQ2/8 haplotype correlates with posterior hypophysitis and panhypophysitis (r=0.598, p=0.04 and r=0.657, p=0.02, respectively).
CONCLUSION
Although patients with PH were found to have significant levels of HLA-DQ2/8, no CD was found in the tissue. Higher levels of pituitary antibodies were detected in celiac patients compared with healthy controls, but no hypophysitis clinic was observed at follow-up. Although these findings suggest that the two diseases may share a common genetic and autoimmune basis, the development of the disease may be partially explained by exposure to environmental factors.
Topics: Humans; Celiac Disease; Retrospective Studies; Autoimmune Hypophysitis; Haplotypes; Vasopressins
PubMed: 37977557
DOI: 10.1055/a-2213-4375 -
Annual Review of Medicine Jan 2021Immune checkpoint inhibitors (CPIs) reverse immune suppression that is thought to allow malignant growth. Despite remarkable efficacy in a subset of cancers, their use... (Review)
Review
Immune checkpoint inhibitors (CPIs) reverse immune suppression that is thought to allow malignant growth. Despite remarkable efficacy in a subset of cancers, their use is accompanied by immune-related adverse events, including endocrinopathies such as hypophysitis, thyroid dysfunction, diabetes, and adrenalitis. These conditions are heterogenous, with differing incidence across CPI types, but are unified by the acuity and extremity of tissue-specific organ failure. Their occurrence may be associated with beneficial tumor control. Further understanding of the risk factors and mechanisms of these endocrine immunotoxicities can help optimize CPI use as well as improve understanding of spontaneous autoimmune diseases.
Topics: Autoimmune Diseases; Autoimmunity; Endocrine System Diseases; Humans; Immune Checkpoint Inhibitors
PubMed: 32886542
DOI: 10.1146/annurev-med-050219-034237 -
The Journal of International Medical... Mar 2020Autoimmune hypothalamitis (AHT) is a rare inflammatory disorder that involves the hypothalamus. It remains unclear whether autoimmune hypophysitis (AH) and AHT represent...
OBJECTIVE
Autoimmune hypothalamitis (AHT) is a rare inflammatory disorder that involves the hypothalamus. It remains unclear whether autoimmune hypophysitis (AH) and AHT represent different diseases or different aspects of the same disease. Thus, further investigation of AHT is required.
METHODS
A retrospective review of medical and pathological records of AHT patients from the Chinese PLA General Hospital were examined from January 1, 2005 to May 1, 2017. Clinical data, treatments, and outcomes were investigated.
RESULTS
Five female patients were identified (median age, 42.6 years). Symptoms included central diabetes insipidus, hypopituitarism, hyperprolactinemia, headache, and hypothalamic syndrome. The following hormonal deficits were noted: follicle-stimulating hormone, luteinizing hormone, adrenocorticotropic hormone, thyroid stimulating hormone, and growth hormone. One patient underwent high-dose methylprednisolone pulse treatment (HDMPT) and azathioprine plus intensity modulated radiation therapy (IMRT), and two patients underwent HDMPT and two rounds of replacement therapy. During follow-up, one patient died because of non-compliance with therapy and the others were in remission or they recovered.
CONCLUSIONS
AHT had similar MRI results, pathology, and treatment compared with AH. Thus, it may be a subtype of AH, and AHT patients may also show hypothalamic syndrome.
Topics: Adult; Autoimmune Hypophysitis; Female; Humans; Hypopituitarism; Methylprednisolone; Pituitary Diseases; Retrospective Studies
PubMed: 31779500
DOI: 10.1177/0300060519887832 -
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 -
Frontiers in Endocrinology 2021Autoimmune diabetes is a rare but severe endocrine toxicity induced by immune checkpoint inhibitor (ICI) treatment. It is unclear if ICI causes selective islet toxicity...
Autoimmune diabetes is a rare but severe endocrine toxicity induced by immune checkpoint inhibitor (ICI) treatment. It is unclear if ICI causes selective islet toxicity or non-selective pancreas toxicity. We analyzed 11 patients treated with ICI who developed ICI-related autoimmune diabetes. Eight patients had lipase and/or amylase tested on the same day of diagnosis of autoimmune diabetes. Among them, 75% (6/8) had normal lipase and 100% (6/6) had normal amylase. There was no correlation between glucose level at onset and biochemical pancreatitis. We characterized the clinical features of ICI-induced autoimmune diabetes. Fifty-five percent (6/11) of patients tested positive for GAD65 autoantibodies, and 55% (6/11) developed diabetic ketoacidosis at manifestation of hyperglycemia. In all 11 patients, C-peptide levels were low in the presence of hyperglycemia. ICI-induced thyroiditis was found in 64% (7/11), of which 36% (4/11) were newly diagnosed with thyroiditis while the remaining 27% (3/11) had pre-existing hypothyroidism followed by ICI-induced thyroiditis. Additionally, 27% (3/11), developed ICI-induced hypophysitis. Thyroiditis and autoimmune diabetes coexisted in all patients with ICI-induced hypophysitis. The median time from ICI treatment to the onset of autoimmune diabetes was 11 weeks. Our data suggest that few patients had coexistent ICI-induced autoimmune diabetes and pancreatitis, suggesting ICI mainly caused selective islet toxicity.
Topics: Adult; Aged; Autoimmune Pancreatitis; Diabetes Mellitus, Type 1; Female; Humans; Immune Checkpoint Inhibitors; Male; Middle Aged; Retrospective Studies
PubMed: 33927691
DOI: 10.3389/fendo.2021.620522 -
Best Practice & Research. Clinical... May 2022Recent advances in tumor immunology have enabled to develop immune checkpoint inhibitors and to save many patients with advanced cancer. Various endocrine diseases are... (Review)
Review
Recent advances in tumor immunology have enabled to develop immune checkpoint inhibitors and to save many patients with advanced cancer. Various endocrine diseases are caused by autoimmune mechanisms; it is important to understand that many endocrine organs are targeted by autoimmunity. In addition, some of malignant tumors ectopically produce hormones and lead to a clinically relevant ectopic hormone syndrome as an endocrine paraneoplastic syndrome. Thus, interplay between oncology, immunology, and endocrinology is important. We have defined a new clinical entity "paraneoplastic autoimmune hypophysitis" as "hypophysitis associated with autoimmunity against pituitary antigens caused by an ectopic expression of these antigens in the tumor and resulting in a breakdown of immune tolerance". To understand the pathophysiology of paraneoplastic autoimmune hypophysitis requires a fusion of the fields of oncology, immunology, and endocrinology; therefore, I propose a new concept of Onco-Immuno-Endocrinology.
Topics: Autoantibodies; Autoimmune Hypophysitis; Endocrine System Diseases; Endocrinology; Humans; Hypophysitis; Neoplasms; Pituitary Diseases
PubMed: 35525821
DOI: 10.1016/j.beem.2022.101663 -
Cancers Aug 2020In recent years, we have observed significant progress in cancer treatment associated with the development of immunotherapy. A programmed cell death 1 molecule (PD-1) on... (Review)
Review
In recent years, we have observed significant progress in cancer treatment associated with the development of immunotherapy. A programmed cell death 1 molecule (PD-1) on the surface of T lymphocytes may be stimulated via a specific PD-ligand 1 (PD-L1), which inhibits lymphocyte activation and leads to apoptosis. Some malignant cells are characterized by high PD-L1 expression. Nivolumab, an anti-PD-1 antibody, blocks the interaction between PD-1 and its ligands and inhibits the signaling pathway by preventing the tumor-derived PD-L1 from blocking T lymphocytes. In patients with non-small cell lung cancer (NSCLC), it is used either in monotherapy or in combination with other drugs. Immunotherapy is associated with the possibility of immune-related adverse effects (irAE) including endocrinopathies (3-23%). Thyroid disorders are the most common, with severity rarely exceeding grade 2. Hypophysitis, adrenal insufficiency and diabetes are possible complications which require immediate treatment. Individuals with autoimmune diseases diagnosed prior to immunotherapy are at risk of its exacerbation. In the management of patients receiving immunotherapy, evaluation of history of autoimmune diseases, awareness and early diagnosis of irAE are crucial and may affect treatment outcomes.
PubMed: 32824462
DOI: 10.3390/cancers12082314