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Endocrine Journal Jun 2023Paraneoplastic syndromes are defined by symptoms or signs resulting from damage to organs or tissues that are remote from the site of malignant neoplasms or its...
Paraneoplastic syndromes are defined by symptoms or signs resulting from damage to organs or tissues that are remote from the site of malignant neoplasms or its metastasis. They are due to tumor secretion of functional hormones or peptides or are related to immune cross-reactivity with the host tissue. In particular, paraneoplastic endocrine syndromes are mainly caused by ectopic hormone production by the tumor such as PTHrP in humoral hypercalcemia in malignancy and ACTH in ectopic ACTH syndrome. Recently, it has been reported that a specific form of hypophysitis is caused as an immune-mediated paraneoplastic syndrome; paraneoplastic autoimmune hypophysitis, in which an ectopic pituitary antigen expression in the tumor evoked autoimmunity against pituitary-specific antigens, resulting in hypophysitis and exhibiting the injury of specific anterior pituitary cells by cytotoxic T cells. This novel clinical entity, paraneoplastic autoimmune hypophysitis consists of several conditions such as anti-PIT-1 hypophysitis and a part of isolated ACTH deficiency and immune checkpoint inhibitor-related hypophysitis with common mechanisms. These conditions can explain at least in part, the underlying mechanisms of acquired specific pituitary hormone deficiencies. In addition, it is important to apply a comprehensive discipline of onco-immuno-endocrinology to understand the pathophysiology and this approach; the expansion and application of immune-mediated paraneoplastic syndrome to endocrine diseases may give a new clue to understand pathophysiology of the autoimmunity against endocrine organs.
Topics: Humans; Autoimmune Hypophysitis; Paraneoplastic Endocrine Syndromes; Autoantibodies; Hypophysitis; Paraneoplastic Syndromes; Neoplasms; Adrenocorticotropic Hormone
PubMed: 37045779
DOI: 10.1507/endocrj.EJ23-0050 -
Journal of Personalized Medicine Feb 2023Immune checkpoint inhibitor hypophysitis (IIHs) is an emerging problem in cancer patients treated with immune checkpoint inhibitors (ICIs). We aimed to describe the...
BACKGROUND
Immune checkpoint inhibitor hypophysitis (IIHs) is an emerging problem in cancer patients treated with immune checkpoint inhibitors (ICIs). We aimed to describe the clinical and molecular features of a multicenter series of IIHs.
METHODS
Demographic and clinical features were retrospectively collected for all cases. Anti-pituitary and anti-hypothalamus autoantibodies were also measured.
RESULTS
Nine patients were included. Six patients were treated with nivolumab and three with ipilimumab. Secondary hypoadrenalism was diagnosed in all patients. Pituitary MRI showed pituitary enlargement in two cases and no abnormalities in the other seven. Anti-pituitary antibodies were positive in 57.1% of cases and anti-hypothalamus antibodies in 85.7% of cases. Multidisciplinary treatments were established by a neuroendocrinologist and oncologists: all patients were treated with hydrocortisone replacement; ICI was withdrawn in two cases. At follow-up, hypoadrenalism persisted in all cases. Pituitary enlargement on MRI spontaneously recovered in the two affected patients. We found that the typical features of hypophysitis involved more frequently females and patients treated with ipilimumab.
CONCLUSIONS
Although this study did not clarify if autoimmune secondary hypoadrenalism and ICI hypophysitis on brain imaging are two sides of the same disease, our preliminary data underline the need for molecular studies of IIHs and of autoimmune ICIs-related hypopituitarism.
PubMed: 36983597
DOI: 10.3390/jpm13030415 -
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 -
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 -
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 -
Neuro-ophthalmology (Aeolus Press) 2023Lymphocytic hypophysitis (LH) is a neuroendocrine disorder characterised by autoimmune inflammation of the pituitary gland with resultant pituitary dysfunction. Rarely,...
Lymphocytic hypophysitis (LH) is a neuroendocrine disorder characterised by autoimmune inflammation of the pituitary gland with resultant pituitary dysfunction. Rarely, the presenting symptom can be diplopia due to irritation of the third, fourth, or sixth cranial nerves secondary to cavernous sinus involvement of the mass or increased intracranial pressure. We describe the case of a healthy, 20-year-old female with a pupillary sparing third nerve palsy, who was subsequently diagnosed with LH after an endoscopic transsphenoidal biopsy of the mass. She was treated with hormone replacement therapy and corticosteroids, resulting in full resolution of symptoms with no recurrence to date. To our knowledge, this is the first report of a third nerve palsy due to definitive biopsy proven LH. Despite its rarity, the unique presentation and favourable evolution of this case should aid clinicians in its timely recognition, appropriate workup, and treatment.
PubMed: 36891401
DOI: 10.1080/01658107.2022.2146143 -
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 -
BMC Endocrine Disorders Feb 2023The development of an effective vaccine is a powerful tool to contain the global spread of coronavirus disease 2019 (COVID-19). Still, it raises potential safety...
BACKGROUND
The development of an effective vaccine is a powerful tool to contain the global spread of coronavirus disease 2019 (COVID-19). Still, it raises potential safety concerns about the subsequent enhancement of associated immunopathology. Increasing evidence shows that the endocrine system, including the hypophysis, may be involved in COVID-19. Moreover, occasional but increasing reports of endocrine disorders involving the thyroid have been reported after the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. Among them, a few cases encompass the pituitary. Here we report a rare case of central diabetes insipidus following SARS-CoV-2 vaccination.
CASE PRESENTATION
We report a 59-year-old female patient with a 25-year history of Crohn's disease in long-term remission, who presented with sudden onset of polyuria eight weeks after administration of an mRNA SARS-CoV-2 vaccination. Laboratory evaluation was consistent with isolated central diabetes insipidus. Magnetic resonance imaging displayed involvement of the infundibulum and the posterior hypophysis. Eighteen months after the vaccination, she is still under desmopressin treatment and had stable pituitary stalk thickening on magnetic resonance imaging. Although Crohn's disease-associated hypophysitis has been reported, it is scarce. In the absence of other recognizable causes of hypophysitis, we believe the involvement of the hypophysis in our patient may have been triggered by the SARS-CoV-2 vaccine.
CONCLUSIONS
We report a rare case of central diabetes insipidus potentially associated with SARS-CoV-2 mRNA vaccination. Further studies are needed to understand better the mechanisms underlying autoimmune endocrinopathies development in the context of COVID-19 infection and SARS-CoV-2 vaccination.
Topics: Female; Humans; Middle Aged; COVID-19 Vaccines; BNT162 Vaccine; Diabetes Insipidus, Neurogenic; SARS-CoV-2; Crohn Disease; COVID-19; Hypophysitis; Disease Progression; Diabetes Mellitus; mRNA Vaccines
PubMed: 36810011
DOI: 10.1186/s12902-023-01296-4 -
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 -
International Journal of Molecular... Nov 2022Autoimmune hypophysitis (AH) is an autoimmune disease of the pituitary for which the pathogenesis is incompletely known. AH is often treated with corticosteroids;...
Autoimmune hypophysitis (AH) is an autoimmune disease of the pituitary for which the pathogenesis is incompletely known. AH is often treated with corticosteroids; however, steroids may lead to considerable side effects. Using a mouse model of AH (experimental autoimmune hypophysitis, EAH), we show that interleukin-1 receptor-associated kinase 1 (IRAK1) is upregulated in the pituitaries of mice that developed EAH. We identified rosoxacin as a specific inhibitor for IRAK1 and found it could treat EAH. Rosoxacin treatment at an early stage (day 0-13) slightly reduced disease severity, whereas treatment at a later stage (day 14-27) significantly suppressed EAH. Further investigation indicated rosoxacin reduced production of autoantigen-specific antibodies. Rosoxacin downregulated production of cytokines and chemokines that may dampen T cell differentiation or recruitment to the pituitary. Finally, rosoxacin downregulated class II major histocompatibility complex expression on antigen-presenting cells that may lead to impaired activation of autoantigen-specific T cells. These data suggest that IRAK1 may play a pathogenic role in AH and that rosoxacin may be an effective drug for AH and other inflammatory diseases involving IRAK1 dysregulation.
Topics: Autoantigens; Autoimmune Hypophysitis; Interleukin-1 Receptor-Associated Kinases; Animals; Mice
PubMed: 36499283
DOI: 10.3390/ijms232314958