-
International Journal of Molecular... Mar 2023With the aging of the population, malignancies are becoming common complications in patients with rheumatoid arthritis (RA), particularly in elderly patients. Such... (Review)
Review
With the aging of the population, malignancies are becoming common complications in patients with rheumatoid arthritis (RA), particularly in elderly patients. Such malignancies often interfere with RA treatment. Among several therapeutic agents, immune checkpoint inhibitors (ICIs) which antagonize immunological brakes on T lymphocytes have emerged as a promising treatment option for a variety of malignancies. In parallel, evidence has accumulated that ICIs are associated with numerous immune-related adverse events (irAEs), such as hypophysitis, myocarditis, pneumonitis, and colitis. Moreover, ICIs not only exacerbate pre-existing autoimmune diseases, but also cause de novo rheumatic disease-like symptoms, such as arthritis, myositis, and vasculitis, which are currently termed rheumatic irAEs. Rheumatic irAEs differ from classical rheumatic diseases in multiple aspects, and treatment should be individualized based on the severity. Close collaboration with oncologists is critical for preventing irreversible organ damage. This review summarizes the current evidence regarding the mechanisms and management of rheumatic irAEs with focus on arthritis, myositis, and vasculitis. Based on these findings, potential therapeutic strategies against rheumatic irAEs are discussed.
Topics: Humans; Aged; Immune Checkpoint Inhibitors; Rheumatic Diseases; Arthritis, Rheumatoid; Neoplasms; Myositis; Vasculitis
PubMed: 36982715
DOI: 10.3390/ijms24065643 -
Pituitary Feb 2022Immune checkpoint inhibitors can cause various immune-related adverse events including secondary hypophysitis. We compared clinical characteristics of...
OBJECTIVE
Immune checkpoint inhibitors can cause various immune-related adverse events including secondary hypophysitis. We compared clinical characteristics of immunotherapy-induced hypophysitis (IIH) and primary hypophysitis (PH) DESIGN: Retrospective multicenter cohort study including 56 patients with IIH and 60 patients with PH.
METHODS
All patients underwent extensive endocrine testing. Data on age, gender, symptoms, endocrine dysfunction, MRI, immunotherapeutic agents and autoimmune diseases were collected.
RESULTS
Median time of follow-up was 18 months in IIH and 69 months in PH. The median time from initiation of immunotherapy to IIH diagnosis was 3 months. IIH affected males more frequently than PH (p < 0.001) and led to more impaired pituitary axes in males (p < 0.001). The distribution of deficient adenohypophysial axes was comparable between both entities, however, central hypocortisolism was more frequent (p < 0.001) and diabetes insipidus considerably less frequent in IIH (p < 0.001). Symptoms were similar except that visual impairment occurred more rarely in IIH (p < 0.001). 20 % of IIH patients reported no symptoms at all. Regarding MRI, pituitary stalk thickening was less frequent in IIH (p = 0.009). Concomitant autoimmune diseases were more prevalent in PH patients before the diagnosis of hypophysitis (p = 0.003) and more frequent in IIH during follow-up (p = 0.002).
CONCLUSIONS
Clinically, IIH and PH present with similar symptoms. Diabetes insipidus very rarely occurs in IIH. Central hypocortisolism, in contrast, is a typical feature of IIH. Preexisting autoimmunity seems not to be indicative of developing IIH.
Topics: Cohort Studies; Humans; Hypophysitis; Immunotherapy; Ipilimumab; Male; Retrospective Studies
PubMed: 34518996
DOI: 10.1007/s11102-021-01182-z -
Acta Neurochirurgica Aug 2022IgG4-related hypophysitis (IgG4-RH) is a rare chronic inflammatory condition of the pituitary gland. This study reports the presentation, management and outcomes for...
PURPOSE
IgG4-related hypophysitis (IgG4-RH) is a rare chronic inflammatory condition of the pituitary gland. This study reports the presentation, management and outcomes for patients with histologically proven IgG4-related hypophysitis.
METHODS
A prospectively maintained electronic database was searched over a 14-year period from 1 January 2007 to 31 December 2020 at a single academic centre to identify all patients with a histological diagnosis of IgG4-RH. A retrospective case note review from electronic health records was conducted for each case to extract data on their presentation, management and outcomes.
RESULTS
A total of 8 patients (5 male) with a median age of 51 years were identified. The most common presenting symptoms were headache (4/8; 50%), fatigue (3/8; 37.5%) and visual impairment (2/8; 25%). Three patients were initially treated with high-dose steroids aiming for reduction of the pituitary mass. However, ultimately all patients underwent transsphenoidal surgery. Post-operative changes included radiological reduction in pituitary mass in all patients that had imaging (7/7; 100%), improvement in vision (1/2; 50%), residual thick pituitary stalk (5/7; 71.4%), persistent anterior hypopituitarism (4/8; 50%) and panhypopopituitarism including diabetes insipidus (3/8; 37.5%).
CONCLUSIONS
IgG4-RH is an increasingly recognised entity presenting with a variety of symptoms and signs. Clinical presentation is similar to other forms of hypophysitis. It is therefore important to consider IgG4-RH as a differential and to have a low threshold for pituitary biopsy, the diagnostic gold standard. The diagnosis of IgG4-RH will guide decisions for additional workup for IgG4-related disease, multi-disciplinary team involvement and follow-up.
Topics: Autoimmune Hypophysitis; Humans; Immunoglobulin G; Male; Middle Aged; Pituitary Diseases; Pituitary Gland; Retrospective Studies
PubMed: 35532784
DOI: 10.1007/s00701-022-05231-9 -
Journal of Mid-life Health 2022Lymphocytic hypophysitis (LYH) is a rare inflammatory disease in which lymphoplasmacytic infiltration of the pituitary gland can potentially lead to panhypopituitarism....
Lymphocytic hypophysitis (LYH) is a rare inflammatory disease in which lymphoplasmacytic infiltration of the pituitary gland can potentially lead to panhypopituitarism. This entity was first recognized in 1962 by Goudie and Pinkerton. We report the case of a 36-year-old nonpregnant female operated for a presumed nonsecreting pituitary adenoma. On intraoperative squash cytology and histology of excision biopsy confirmed the diagnosis of LYH. Review of the literature shows that most reported cases have occurred in women during pregnancy or during postpartum period. Many were accurately diagnosed only after biopsy or at necropsy. It is suspected to be an autoimmune endocrinopathy as concomitant lymphocytic infiltration of the thyroid and pituitary glands has been noted and antipituitary antibodies have been found in some instances. Clinically and radiologically, LYH may mimic a nonsecretory pituitary adenoma. Intraoperative diagnosis may prevent unnecessary excision of potentially functioning pituitary.
PubMed: 36950203
DOI: 10.4103/jmh.jmh_32_21 -
Endocrine Journal Nov 2020Autoimmunity contributes to the pathogenesis of hypophysitis, a chronic inflammatory disease in the pituitary gland. Although primary hypophysitis is rare, the number of... (Review)
Review
Autoimmunity contributes to the pathogenesis of hypophysitis, a chronic inflammatory disease in the pituitary gland. Although primary hypophysitis is rare, the number of pituitary dysfunction cases induced by immune checkpoint inhibitors (ICIs) is increasing. While it is difficult to prove the involvement of autoimmunity in the pituitary glands, circulating anti-pituitary antibodies (APAs) can be measured by indirect immunofluorescence and used as a surrogate marker of pituitary autoimmunity. APAs are present in several pituitary diseases, including lymphocytic adenohypophysitis, lymphocytic infundibulo-neurohypophysitis (LINH), IgG4-related hypophysitis, and pituitary dysfunction induced by ICIs. Mass spectrometry analysis of antigens targeted by APAs clarified rabphilin-3A as an autoantigen in LINH. This demonstrates that APAs can be applied as a probe to identify novel autoantigens in other pituitary autoimmune diseases, including pituitary dysfunction induced by ICIs, which can aid in biomarker discovery.
Topics: Animals; Autoantibodies; Autoimmune Hypophysitis; Biomarkers; Fluorescent Antibody Technique, Indirect; Humans; Immune Checkpoint Inhibitors; Immunoglobulin G4-Related Disease; Pituitary Gland
PubMed: 33055452
DOI: 10.1507/endocrj.EJ20-0436 -
Endocrinology, Diabetes & Metabolism... Dec 2019Durvalumab is a programmed cell death ligand 1 inhibitor, which is now approved in Australia for use in non-small-cell lung and urothelial cancers. Autoimmune diabetes...
SUMMARY
Durvalumab is a programmed cell death ligand 1 inhibitor, which is now approved in Australia for use in non-small-cell lung and urothelial cancers. Autoimmune diabetes is a rare immune-related adverse effect associated with the use of immune checkpoint inhibitor therapy. It is now being increasingly described reflecting the wider use of immune checkpoint inhibitor therapy. We report the case of a 49-year-old female who presented with polyuria, polydipsia and weight loss, 3 months following the commencement of durvalumab. On admission, she was in severe diabetic ketoacidosis with venous glucose: 20.1 mmol/L, pH: 7.14, bicarbonate 11.2 mmol/L and serum beta hydroxybutyrate: >8.0 mmol/L. She had no personal or family history of diabetes or autoimmune disease. Her HbA1c was 7.8% and her glutamic acid decarboxylase (GAD) antibodies were mildly elevated at 2.2 mU/L (reference range: <2 mU/L) with negative zinc transporter 8 (ZnT8) and islet cell (ICA) antibodies. Her fasting C-peptide was low at 86 pmol/L (reference range: 200-1200) with a corresponding serum glucose of 21.9 mmol/L. She was promptly stabilised with an insulin infusion in intensive care and discharged on basal bolus insulin. Durvalumab was recommenced once her glycaemic control had stabilised. Thyroid function tests at the time of admission were within normal limits with negative thyroid autoantibodies. Four weeks post discharge, repeat thyroid function tests revealed hypothyroidism, with an elevated thyroid-stimulating hormone (TSH) at 6.39 mIU/L (reference range: 0.40-4.80) and low free T4: 5.9 pmol/L (reference range: 8.0-16.0). These findings persisted with repeat testing despite an absence of clinical symptoms. Treatment with levothyroxine was commenced after excluding adrenal insufficiency (early morning cortisol: 339 nmol/L) and hypophysitis (normal pituitary on MRI).
LEARNING POINTS
Durvalumab use is rarely associated with fulminant autoimmune diabetes, presenting with severe DKA. Multiple endocrinopathies can co-exist with the use of a single immune checkpoint inhibitors; thus, patients should be regularly monitored. Regular blood glucose levels should be performed on routine pathology on all patients on immune checkpoint inhibitor. Clinician awareness of immunotherapy-related diabetes needs to increase in an attempt to detect hyperglycaemia early and prevent DKA.
PubMed: 31829972
DOI: 10.1530/EDM-19-0098 -
Surgical Neurology International 2022Immunoglobulin (Ig)G4-related disease is a systemic fibroinflammatory disease characterized by dense infiltration of IgG4-positive plasma cells in the affected tissue(s)...
BACKGROUND
Immunoglobulin (Ig)G4-related disease is a systemic fibroinflammatory disease characterized by dense infiltration of IgG4-positive plasma cells in the affected tissue(s) with or without elevated plasma levels of IgG4. Hypophysitis itself is a very rare disease with reported prevalence in the operative specimens are around 0.2-0.88%. IgG4-related hypophysitis (IgG4-RH) may account for a substantial percentage of cases previously regarded as idiopathic hypophysitis.
METHODS
This study is a registry-based, retrospective, and cohort study from a tertiary care hospital in North India. The medical records and clinical data of biopsy-proven and suspected IgG4-RH patients registered were retrospectively analyzed. Treatment outcome of cases was also explored during this analysis.
RESULTS
Two thousand and six sellar area space-occupying lesions have been operated-on since 2006, among them only four patients had IgG4-RH on histopathological specimen. One case was diagnosed on clinical suspicion. Mean age of the patients was 31.8 ± 6.32 years. Most frequent presenting complaint was headaches. Extracranial manifestations were present in four patients. The most common pituitary dysfunction was cortisol deficiency. 18 F-fluorodeoxyglucose positron emission tomography (18F FDG PET) was helpful in three cases for diagnosis of hypophysitis and other organ involvement. Classical histological findings with storiform fibrosis, obliterative phlebitis seen in two cases, and IgG4-positive plasma cell infiltration were positive in four cases. Surgery was the primary modality of treatment in all four cases. Only one patient received steroids as a primary therapeutic modality.
CONCLUSION
IgG4-RH is rare. High index of suspicion is required to diagnosis the case precisely. FDG PET is helpful in diagnosing hypophysitis and extrapituitary lesions.
PubMed: 36600729
DOI: 10.25259/SNI_1013_2022 -
Medicina 2023Primary hypophysitis (PH) is a rare disease that represents a challenge among differential diagnosis and management. Our aim was to describe clinical characteristics,...
INTRODUCTION
Primary hypophysitis (PH) is a rare disease that represents a challenge among differential diagnosis and management. Our aim was to describe clinical characteristics, diagnostic criteria and different treatment outcomes in patients with PH. Multicentric, retrospective study. Clinical presentation, endocrine function, magnetic resonance imaging findings, visual field defects at diagnosis and treatment outcomes were recorded.
METHODS
Twenty-eight patients (23 women), with PH were included. Median age: 37.
RESULTS
The most frequent symptoms: headache: 68%, polyuria-polydipsia: 50% and visual disturbances: 48%. At diagnosis, anterior pituitary deficiency was present in 71%, being hypogonadotrophic hypogonadism the most frequent manifestation. The radiological findings: symmetric lesion: 78.5%, homogeneous enhancement: 78.5% and pituitary stalk thickening: 70%. Association with pregnancy or puerperium was found in 4/23 women (17%). Fourteen patients did not receive any treatment ("wait and see" group), 8 underwent surgery for mass reduction or resection and 6 were treated with immunosuppression therapy. Among 15 patients with histopathological diagnosis, 9 were lymphocytic hypophysitis, 5 IgG4 related hypophysitis and 1 xanthomatous hypophysitis. Thirteen were diagnosed by established clinical criteria. Mass reduction was observed in 43% of "wait and see group" patients, 62.5% of operated patients and 50% with immunosuppression therapy. Compressive symptoms showed improvement in the 3 groups, with modest effect on anterior pituitary function, diabetes insipidus did not resolve in any patients.
DISCUSSION
In patients without severe compressive symptoms, we adopted a "wait and see" approach. In patients with uncertain diagnosis of PH or severe compressive symptoms, transsphenoidal surgery was the best option.
Topics: Pregnancy; Humans; Female; Adult; Retrospective Studies; Hypophysitis; Pituitary Gland; Hypopituitarism; Autoimmune Hypophysitis; Magnetic Resonance Imaging
PubMed: 37870332
DOI: No ID Found -
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