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Endocrinology, Diabetes & Metabolism... Oct 2023IgG4-related disease is a multiorgan disorder in which nodules and hypertrophic lesions are observed simultaneously, or separately, in areas including the pancreas,...
SUMMARY
IgG4-related disease is a multiorgan disorder in which nodules and hypertrophic lesions are observed simultaneously, or separately, in areas including the pancreas, liver, lungs, salivary glands, thyroid glands, and pituitary glands. IgG4-related hypophysis is one of several IgG4-related diseases and is characterized by pituitary gland and pituitary stalk thickening, various degrees of hypopituitarism, and increased serum IgG4 levels. Steroid therapy is effective for patients with IgG4-related hypophysis, but the reported effectiveness of steroid therapy for restoring pituitary function differs between studies. Following an episode of autoimmune pancreatitis 10 years prior, enlargement of the pituitary gland and stalk along with panhypopituitarism and polyuria developed in a 73-year-old male. A high serum IgG4 level and biopsy of the submandibular gland showing infiltration of IgG4-positive plasma cells led to a clinical diagnosis of IgG4-related hypophysitis. Prednisolone treatment reduced the swelling of the pituitary gland and stalk and improved anterior pituitary function. Although arginine vasopressin secretion remained insufficient, polyuria was relieved and kept in remission even after prednisolone treatment was completed. This is the first reported case in which prednisolone was able to maintain both normal anterior pituitary function and remission of polyuria caused by IgG4-related hypophysitis. IgG4-related hypophysitis has previously been associated with a relapse of symptoms during treatment. However, the patient reported in this case study remained in remission for over 3 months after completion of steroid treatment and should be monitored closely for changes in pituitary function.
LEARNING POINTS
Steroid therapy is the first-line therapy for pituitary dysfunction and pituitary stalk swelling in IgG4-related hypophysitis. In this case, although posterior pituitary function remained insufficient, polyuria was relieved and kept in remission for over 3 months even after prednisolone treatment was completed. IgG4-related hypophysitis has been associated with the relapse of symptoms during steroid tapering, and changes in pituitary function and symptoms should be monitored closely. When we encounter cases of adrenal insufficiency and polyuria during observation of autoimmune pancreatitis or other IgG4-related disease, we should consider the possibility of IgG4-related hypophysitis in mind.
PubMed: 38131878
DOI: 10.1530/EDM-23-0007 -
Medicina 2023Hypophysitis is a pathology with low incidence and prevalence. Likewise, deep fungal infections in immunocompetent patients also represent a rare phenomenon. Even rarer...
Hypophysitis is a pathology with low incidence and prevalence. Likewise, deep fungal infections in immunocompetent patients also represent a rare phenomenon. Even rarer is the case described below, where these two mentioned elements are combined, namely: pituitary cryptococcoma or granulomatous hypophysitis caused by said pathogen in a host without altered immune response. After research in PubMed, there are limited cases in the medical literature of granulomatous hypophysitis caused by Cryptococcus spp., which simulated a pituitary macroadenoma by clinical and imaging manifestations. We did not find reports in which there is no evidence of involvement of the meningeal tissue. The fungal etiology is scarcely described in the reference guidelines for hypophysitis and we believe that Cryptococcus spp. it should be taken into account in the differential diagnosis of secondary granulomatous hypophysitis since it is a ubiquitous pathogen and the treatment is substantially different from other entities. It becomes more relevant given the current trend towards the use of high-dose systemic glucocorticoids for the treatment of hypophysitis, which could have generated greater damage if the correct diagnosis had not been made.
Topics: Humans; Autoimmune Hypophysitis; Pituitary Gland; Hypophysitis; Pituitary Neoplasms; Glucocorticoids
PubMed: 38117724
DOI: No ID Found -
Frontiers in Immunology 2023A recently discovered facet of paraneoplastic adrenocorticotropic hormone (ACTH) deficiency exists in two forms: a paraneoplastic spontaneous isolated ACTH deficiency...
INTRODUCTION
A recently discovered facet of paraneoplastic adrenocorticotropic hormone (ACTH) deficiency exists in two forms: a paraneoplastic spontaneous isolated ACTH deficiency (IAD) and an immune checkpoint inhibitor (ICI)-related hypophysitis. Autoantibodies against corticotrophs, such as circulating anti-proopiomelanocortin (POMC) antibodies are considered disease markers. However, the number of identified cases was limited, implying that the characteristics of these autoantibodies are not fully understood.
METHODS
We investigate circulating autoimmune autoantibodies in detail through a novel case of IAD that developed as a paraneoplastic autoimmune ACTH deficiency.
RESULTS
The patient developed IAD after 25 weeks of ICI therapy for metastasis of large-cell neuroendocrine carcinoma at 69 years of age. Ectopic ACTH expression and infiltration of CD3+, CD4+, CD8+, and CD20+ lymphocytes were observed in the tumor tissues and circulating anti-POMC antibodies were detected specifically in the patient's serum. Moreover, detailed analyses of immunofluorescence staining using patient serum revealed that the recognition site of the autoantibody was ACTH, which had not been identified in previous cases of paraneoplastic autoimmune ACTH deficiency.
CONCLUSION
This case involved a combination of paraneoplastic spontaneously acquired IAD and ICI-related hypophysitis occupying the middle ground. Moreover, our study reveals new aspects of anti-POMC antibodies in patients with paraneoplastic ACTH deficiency. This report expands our understanding of the immunological landscape and provides new insights for the identification of antibodies associated with paraneoplastic autoimmune ACTH deficiency.
Topics: Humans; Adrenocorticotropic Hormone; Autoantibodies; Corticotrophs; Hypophysitis; Immune Checkpoint Inhibitors; Pro-Opiomelanocortin
PubMed: 38035072
DOI: 10.3389/fimmu.2023.1284301 -
Archivos de La Sociedad Espanola de... Apr 2024Cancer therapy relies on new antitumoral drugs called immune checkpoint inhibitors (ICI), which produce long-lasting anti-tumor responses and lengthen survival, but... (Review)
Review
Cancer therapy relies on new antitumoral drugs called immune checkpoint inhibitors (ICI), which produce long-lasting anti-tumor responses and lengthen survival, but cause autoimmune-type toxicity. The clinical characteristics induced by ICI are not well characterized to date and careful collection of clinical data is required to accurately define its safety profile. We conducted a literature search in the main clinical search engines to identify pharmacological ocular iatrogenic events of ICIs related to ocular motility. Four systematic reviews were found that included this type of ocular iatrogenesis as well as numerous isolated case reports. Reported adverse effects include: oculomotor paresis, optic neuropathy, optic atrophy, myastheniform syndromes, thyroid pseudo-orbitopathy, orbital apex syndrome, and hypophysitis. Most were managed without interruption or with partial interruption of cancer treatment. Aggressive systemic treatments were required for adequate management of ocular iatrogenic events. It is essential that the ophthalmologist become familiar with the new ICI oncological treatments, capable of causing severe and disabling motilidad ocular iatrogenesis for the patient. The communication of adverse effects and the report of the treatments used can help the most appropriate management of these patients. Research should be oriented towards complex differential diagnosis and to optimize decisions on cancer treatments.
Topics: Humans; Immune Checkpoint Inhibitors; Eye Movements; Eye; Optic Atrophy; Optic Nerve Diseases; Graves Ophthalmopathy
PubMed: 38013131
DOI: 10.1016/j.oftale.2023.11.011 -
Seminars in Arthritis and Rheumatism Feb 2024IgG4-related disease (IgG4-RD) is a fibro-inflammatory disorder that can affect almost any organ. IgG4-related ophthalmic disease is a protean condition involving the... (Review)
Review
INTRODUCTION
IgG4-related disease (IgG4-RD) is a fibro-inflammatory disorder that can affect almost any organ. IgG4-related ophthalmic disease is a protean condition involving the orbit and ocular adnexa. Although a few cases of uveitis have been reported, the exact pattern of IgG4-related intraocular manifestations remains unclear. Here, we report on a nationwide French multicenter cohort of patients with IgG4-RD and uveitis and conducted a literature review.
METHODS
Patients with uveitis and a concomitant definite diagnosis of IgG4-RD (Revised Comprehensive Diagnostic criteria, American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-RD, International Consensus Diagnostic Criteria for auto-immune pancreatitis, or diagnostic criteria for IgG4-related hypophysitis), were screened from our national IgG4-RD and systemic fibrosis database. Concomitantly, we conducted a PubMed literature review and selected cases of definite IgG4-RD with uveitis.
RESULTS
We reported on 16 patients (8 from our database and 8 from the literature) and a total of 30 episodes of uveitis. Uveitis cases represented 3 % of total IgG4-RD patients in the national database on IgG4-RD and systemic fibrosis. Uveitis was inaugural in IgG4-RD in 4/16 cases (25 %) (appearing before any other IgG4-related symptom, at a median of 9 months), occurred concurrently to other IgG4-related symptoms in 9/16 cases (56 %) (at a median of 15 months before IgG4-RD diagnosis), and appeared during follow up in 3/16 patients (19 %) (at a median of 57 months after first IgG4-related symptoms). When uveitis occurred during follow up, it was associated with IgG4-RD manifestations in other organs in 6/9 patients (67 %). Uveitis was bilateral in 8/16 cases (50 %) and granulomatous in 5/10 cases (50 %). It was anterior in 8/13 (62 %), intermediate in 3/13 (23 %), and global (panuveitis) in 4/13 patients (31 %). Median serum IgG4 at diagnosis was 3.2 g/L. Median follow up time was of 6 years, during which 8/16 patients (50 %) experienced at least one relapse of uveitis. Treatment data was available for 29/30 uveitis flares. Steroids were used in 28/29 episodes of uveitis (97 %), leading to remission of uveitis in 16/28 cases (57 %). Methotrexate and rituximab (in combination with systemic steroids) were administered as second- or third-line therapy in 6/29 (21 %) and 5/29 (17 %) episodes of uveitis, respectively, and led to remission of uveitis in 4/6 cases (67 %) and 4/5 cases (80 %), respectively. One third of uveitides required at least two different lines of treatment for remission induction (mainly a combination of both systemic steroids and methotrexate or rituximab).
DISCUSSION AND CONCLUSIONS
Uveitis may be one of the initial symptoms of IgG4-RD, and IgG4-RD should be considered in the diagnostic workup of uveitis. Its early onset in IgG4-RD may help with early diagnosis and treatment of the disease. Steroid monotherapy may be sufficient to treat IgG4-related uveitis, yet relapses were frequent (50 %) and ultimately a third of patients required at least two lines of treatment. Hence, steroid-sparing agents can be considered at early stages of the disease, particularly for patients with a high risk of relapse or steroid-related complications.
Topics: Humans; Immunoglobulin G; Immunoglobulin G4-Related Disease; Rituximab; Methotrexate; Uveitis; Fibrosis; Recurrence; Steroids; Multicenter Studies as Topic
PubMed: 38000318
DOI: 10.1016/j.semarthrit.2023.152278 -
Journal of Oncology Pharmacy Practice :... Mar 2024Autoimmune encephalitis is a rare immune-related adverse event of PD-1 inhibitors, nivolumab and pembrolizumab. Autoimmune hypophysitis can also be seen with the use of...
INTRODUCTION
Autoimmune encephalitis is a rare immune-related adverse event of PD-1 inhibitors, nivolumab and pembrolizumab. Autoimmune hypophysitis can also be seen with the use of these agents. The relationship between these two phenomena is currently unknown.
CASE REPORT
We describe a 79-year-old man with anterior scalp melanoma who received adjuvant nivolumab therapy. Sixteen weeks after the completion of nivolumab therapy, the patient presented to the hospital with altered mental status, anterograde amnesia, and symptoms of nausea and vomiting. The patient's encephalopathy was associated with confabulations. Workup identified increased CSF protein without increased cellularity, along with decreased serum cortisol and ACTH levels. This was consistent with encephalitis and central adrenal insufficiency.
MANAGEMENT AND OUTCOME
The patient had a robust clinical response to steroids, with resolution of mental status changes and normalization of blood pressure. He continues to receive maintenance steroid therapy without any further symptoms six months later.
CONCLUSIONS
We report herein a unique case of encephalopathy in the setting of nivolumab use for the treatment of melanoma. The condition resembled Korsakoff psychosis seen in the setting of alcoholism and was associated with central adrenal insufficiency. A prompt response to steroids was both diagnostic and therapeutic in our case, suggesting the resolution of autoimmune phenomena related to nivolumab.
Topics: Male; Humans; Aged; Nivolumab; Melanoma; Encephalitis; Adrenal Insufficiency; Korsakoff Syndrome; Steroids
PubMed: 37981786
DOI: 10.1177/10781552231215088 -
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 -
JCEM Case Reports Mar 2023Lymphocytic infundibulo-neurohypophysitis (LINH) is a rare autoimmune inflammatory process that selectively affects the neurohypophysis and the pituitary stalk,...
Lymphocytic infundibulo-neurohypophysitis (LINH) is a rare autoimmune inflammatory process that selectively affects the neurohypophysis and the pituitary stalk, typically presenting with central diabetes insipidus (CDI). LINH is considered underdiagnosed because the definitive diagnosis requires invasive pituitary surgery with a high risk of complications. We present a case of CDI resulting from LINH, which was treated with conservative management, eschewing both glucocorticoid treatment and pituitary surgery. At presentation, the hormonal assessment indicated the presence of CDI without anterior pituitary dysfunction. Magnetic resonance imaging revealed stalk thickening without a posterior pituitary bright spot, and anti-rabphilin-3A antibodies were positive in serum. Collectively, we made a diagnosis of LINH. Considering that the patient did not exhibit any symptoms of mass effect, we chose conservative treatment with desmopressin acetate. One year later, the stalk thickening regressed spontaneously without surgical or glucocorticoid treatment, although the posterior pituitary bright spot remained absent, and CDI did not improve. The inflammatory process of LINH is mostly self-limited and recovers spontaneously, whereas life-long desmopressin treatment may be required because of pituitary stalk fibrosis and atrophy. Our case highlights the importance of noninvasive diagnosis and careful follow-up in preventing unnecessary interventions for patients with LINH.
PubMed: 37908468
DOI: 10.1210/jcemcr/luad020 -
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 -
Internal Medicine (Tokyo, Japan) Jun 2024A 75-year-old woman presented with nausea and vomiting. Magnetic resonance imaging (MRI) revealed that she had a pituitary mass. A biopsy revealed lymphocytic...
A 75-year-old woman presented with nausea and vomiting. Magnetic resonance imaging (MRI) revealed that she had a pituitary mass. A biopsy revealed lymphocytic hypophysitis (LYH). Symptoms were improved by hormone replacement therapy. Although she was asymptomatic, follow-up MRI revealed an increase in the size of the mass. Intravenous methylprednisolone (IVMP) reduced the size of the mass; however, right ophthalmalgia and oculomotor nerve palsy developed. MRI showed that the pituitary mass had enlarged to the right oculomotor nerve in the cavernous sinus and to the right internal carotid artery (ICA), causing stenosis of the ICA. After IVMP administration, the symptoms dramatically improved, but ICA stenosis persisted.
Topics: Humans; Female; Aged; Oculomotor Nerve Diseases; Carotid Stenosis; Methylprednisolone; Autoimmune Hypophysitis; Recurrence; Magnetic Resonance Imaging; Carotid Artery, Internal; Diagnosis, Differential
PubMed: 37813605
DOI: 10.2169/internalmedicine.2674-23