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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 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 -
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 -
Endocrine Journal Apr 2020Hypophysitis, which is often accompanied by pituitary dysfunction, is classified into several subtypes based on the cause, histology, and the location of inflammation in...
Hypophysitis, which is often accompanied by pituitary dysfunction, is classified into several subtypes based on the cause, histology, and the location of inflammation in the pituitary gland. A definitive diagnosis requires pituitary biopsy, which is invasive, and the process is limited to specialized clinical settings. In this opinion paper, we review the literature associated with hypophysitis, and provide the guidelines of the Japan Endocrine Society for the diagnosis and treatment of autoimmune and IgG4-related hypophysitis.
Topics: Autoimmune Hypophysitis; Decompression, Surgical; Endocrinology; Glucocorticoids; Headache; Hormone Replacement Therapy; Humans; Hypopituitarism; Japan; Magnetic Resonance Imaging; Neurosurgical Procedures; Societies, Medical; Vision Disorders; Visual Fields
PubMed: 32037390
DOI: 10.1507/endocrj.EJ19-0569 -
Klinicka Onkologie : Casopis Ceske a... 2020Acute renal impairment is a relatively rare complication of anti-tumour immunotherapy. The incidence of renal toxicity due to immuno-oncological therapy is relatively... (Review)
Review
BACKGROUND
Acute renal impairment is a relatively rare complication of anti-tumour immunotherapy. The incidence of renal toxicity due to immuno-oncological therapy is relatively low, approximately 2% in patients treated with PD-1/PD-L1 inhibitors and 4.5% with combination treatments with PD-1/PD-L1 therapy and a CTLA-4 inhibitor. The most common underlying pathology is acute tubulointerstitial nephritis. Autoimmune nephropathy presenting as a electrolyte imbalance may also occur during immuno-oncological therapy. Discontinuation of immunotherapy and corticosteroid therapy are indicated in patients with moderate to severe renal toxicity.
CASE
A 61-year-old patient with metastatic renal cell carcinoma was admitted to hospital after 7 months of treatment with nivolumab for general deterioration, severe weakness, nausea, and anorexia. Laboratory examinations showed worsening of the glomerular filtration rate, severe hyperkalaemia, and metabolic acidosis. Thyroid hormone and cortisol levels were within normal ranges. Renal tubular acidosis resulting from immuno-oncological therapy was diagnosed, and treatment with methylprednisolone was initiated. Electrolyte abnormalities and symptoms improved rapidly, after which the dose of prednisone was gradually reduced; however, after a reduction to 5 mg daily, hyperkalaemia recurred and the patient was kept on a maintenance dose of 10 mg prednisone administered orally on a daily basis thereafter. Immunotherapy was not reintroduced.
CONCLUSION
Renal toxicity following immuno-oncological therapy usually presents initially as an increase in the serum creatinine level without any clinical signs or symptoms. Electrolyte disturbances, oliguria, anuria, and swelling may develop gradually. Endocrine and metabolic disorders such as new-onset type 1 diabetes mellitus, hypophysitis, adrenal insufficiency, and hypothyroidism should be excluded as possible causes of electrolyte abnormalities. Corticosteroids at the usual immunosuppressive dose are the treatment of choice. The prognosis is generally favourable because renal toxicity responds well to corticosteroid treatment regardless of the underlying pathology.
Topics: Antineoplastic Agents, Immunological; Humans; Immunotherapy; Kidney Diseases; Middle Aged; Prognosis
PubMed: 32075386
DOI: 10.14735/amko202029 -
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 -
Endocrine Aug 2021Primary autoimmune hypophysitis (PAHs) is a rare inflammatory disease of the pituitary gland. Although largely investigated, the pathogenesis of PAH is not completely...
INTRODUCTION
Primary autoimmune hypophysitis (PAHs) is a rare inflammatory disease of the pituitary gland. Although largely investigated, the pathogenesis of PAH is not completely clarified. We aimed to investigate the immune response in PAHs.
MATERIAL AND METHODS
Serum anti-pituitary and anti-hypothalamus antibodies (respectively APAs and AHAs) were investigated though an indirect immunofluorescence on monkey hypophysis and hypothalamus slides, serum cytokines though an array membrane and cell-mediated immunity though the white blood cells count.
RESULTS
Nineteen PAH cases entered the study. APA or AHA were identified in all cases. APA were detected in 13 patients (68.4%) and AHA in 13 patients (68.4%). Ten patients (52.6%) were simultaneously positive for both APA and AHA. The prevalence of APAs and AHAs was higher as compared to those observed in 50 health controls (respectively 14% p < 0.001 and 24% p = 0.004) and in 100 not-secreting pituitary adenoma (NFPAs) (respectively 22% p = 0.002 and 8% p < 0.001). Similarly, the prevalence of simultaneous positivity for APA and AHA (52.9%) was higher as compared to the those detected in patients affected by NFPAs (0%; p < 0.001) and in health controls (16% p = 0.002). No differences were identified between PAHs and controls at qualitative and quantitative analysis of serum cytokines and white blood cells count.
CONCLUSIONS
This study suggest that APA and AHA may be detected in an high percentage of PAH cases and that their simultaneous identification may be useful for the differential diagnosis between PAH and NFPAs, in an appropriate clinical context.
Topics: Autoantibodies; Autoimmune Diseases; Autoimmune Hypophysitis; Humans; Hypopituitarism; Immunity, Cellular; Pilot Projects; Pituitary Gland
PubMed: 33484410
DOI: 10.1007/s12020-021-02612-5 -
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 -
EClinicalMedicine Apr 2024Immune-checkpoint inhibitors (ICI) have revolutionized cancer treatment by harnessing the immune system but ICI can induce life-threatening immune-related adverse events...
BACKGROUND
Immune-checkpoint inhibitors (ICI) have revolutionized cancer treatment by harnessing the immune system but ICI can induce life-threatening immune-related adverse events (irAE) affecting every organ.
METHODS
We extracted irAE from VigiBase, the international pharmacovigilance database, first reported in 2008 until 01/2023 to characterize irAE reporting trends, clinical features, risk factors and outcomes.
FINDINGS
We distinguished 25 types of irAE (n = 50,347cases, single irAE/case in 84.9%). Cases mainly involved anti-PD1 (programmed-death-1) monotherapy (62.4%) in male (61.7%) aged 64.3 ± 12.6 years. After 2020 vs. prior to 2016, proportion of anti-CTLA4 (Cytotoxic-T-Lymphocyte-Antigen-4) monotherapy prescription almost vanished (1.6% vs. 47%, respectively) contrasting with increased use of anti-PDL1 (PD1-ligand) monotherapy (18% vs. 0.9%) and anti-CTLA4+anti-PD(L)1 combination (20% vs. 8.9%). Anti-LAG3 (Lymphocyte-Activation-Gene-3) prescription was limited (<1%) in the studied timeframe. After 2020, over 14 different cancer types were treated vs. almost exclusively melanoma and lung cancers before 2016. Overall, the most reported irAE were skin reactions (22.9%), pneumonitis (18.5%), enterocolitis (14.4%) and thyroiditis (12.1%). ICI-myotoxicities (6.6%) included myositis, myocarditis and myasthenia-gravis like syndrome and were the most overlapping irAE (up to 30% overlap, vs. <3% in general for other inter-irAE overlap). The top factors associated with specific irAE (odds-ratio>5) were presence of thymic cancer for ICI-myotoxicities or hepatitis; presence of melanoma for vitiligo, uveitis or sarcoidosis; specific types of ICI regimen (anti-LAG3 for meningitis, anti-CTLA4 for hypophysitis); and specific reporting regions (eastern Asia for cholangitis). Median time-to-onset ranged from 31 to 273 days, being shortest for myotoxicities and most delayed for skin-bullous auto-immune reactions. Overall fatality was highest for myocarditis = 27.6%, myasthenia = 23.1%, severe cutaneous adverse reactions (SCAR) = 22.1%, myositis = 21.9%, pneumonitis = 21%, and encephalomyelitis = 18%; generally decreasing after 2020, except for myasthenia and SCAR. When reported, irAE recurrence rate after rechallenge was 28.9% (n = 275/951).
INTERPRETATION
This up-to-date comprehensive worldwide pharmacovigilance study defines the spectrum, characteristics, and evolution of irAE reporting summarizing over a decade of use. Multiple risk factors and clinical peculiarities for specific irAE have been identified as signals to guide clinical practice and future research.
FUNDING
Paul Gougis was supported by the academic program: "Contrats ED: Programme blanc Institut Curie PSL" for the conduct of his PhD. Baptiste Abbar was supported by "the Fondation ARC Pour le Rechercher Sur le Cancer". The RT2L research group (Institut Curie) was supported by the academic program "SHS INCa", Sanofi iTech award, and by Monoprix∗.
PubMed: 38560659
DOI: 10.1016/j.eclinm.2024.102536