scholarly journals New Molecular, Biological, and Immunological Agents Inducing Hypophysitis

2017 ◽  
Vol 106 (1) ◽  
pp. 89-100 ◽  
Author(s):  
Anna Angelousi ◽  
Eleftherios Chatzellis ◽  
Gregory Kaltsas
Keyword(s):  
Anticancer Agents ◽  
Cytotoxic T Lymphocyte ◽  
Hormone Replacement ◽  
Interferon Α ◽  
Pituitary Hormone ◽  
Immunomodulatory Agents ◽  
Pituitary Antibodies ◽  
Available Information ◽  
Cell Death Protein ◽  
Sensitive Marker

Hypophysitis is a relatively rare disease that exerts a strong autoimmune component encompassing different etiologies. Immunomodulatory drugs, such as interferon-α, are known to rarely induce hypophysitis. In recent years, a large number of new biological and immunomodulatory agents have been introduced into clinical practice. Although immune-suppressing agents used for the treatment of autoimmune disorders only rarely are associated with hypophysitis, it is commonly encountered with immunomodulatory agents used for the treatment of cancer. Hypophysitis related to anti-cytotoxic T-lymphocyte-associated antigen-4 antibodies (anti-CTLA-4 Abs) occurs with a prevalence ranging from 0 to 18% and is considered a distinctive side effect of anti-CTLA-4 Abs treatment. Hypophysitis due to the programmed cell death protein-1 antibodies and their ligand is less common, its frequency ranging from 0 to 0.8%. No cases of hypophysitis have been described with molecular targeted agents. Diagnosis of hypophysitis still remains clinical since anti-pituitary antibodies are not a sensitive marker and thus its true prevalence is probably underestimated. The pathophysiology of hypophysitis induced by anticancer agents is not fully clarified. In most cases, treatment requires dose adjustment of the offending drug and pituitary hormone replacement. This mini-review aims to present currently available information regarding hypophysitis related to new molecular, biological, and immunological agents.

scholarly journals OP0287 IMMUNOMODULATORY THERAPIES FOR SEVERE FORMS OF COVID-19: A SYSTEMATIC LITERATURE REVIEW TO INFORM EULAR POINTS TO CONSIDER

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 175.1-175
Author(s):  
A. Alunno ◽  
A. Najm ◽  
X. Mariette ◽  
J. Emmel ◽  
L. Mason ◽  
...  
Keyword(s):  
Risk Of Bias ◽  
Respiratory Support ◽  
Disease Stage ◽  
Controlled Trials ◽  
Immunomodulatory Agents ◽  
Randomised Controlled ◽  
Available Information ◽  
Immunomodulatory Therapies ◽  
Global Health Problem

Background:The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) pandemic is a global health problem. Beside the specific pathogenic effect of SARS-CoV-2, a deleterious aberrant non-effective host immune response plays an important role especially in severe forms of COVID-19. There is intense investigation to explore the utility of immunomodulatory drugs commonly used in the Rheumatology arena as agents that may mitigate against COVID-19 to improve disease prognosis. Rheumatologists are used to the utilization of these immune targeted therapies.Objectives:To summarize the available information on the use of immunomodulatory agents in severe COVID-19.Methods:As part of a EULAR taskforce, a systematic literature search was conducted from January 2019 up to December 11, 2020. Two reviewers independently identified eligible studies according to the PICO framework P (population): patients with SARS-CoV-2 infection; I (intervention): any immunomodulator agent/strategy; C (comparator): any comparator; O (outcome) any clinical outcome including but not limited to mortality, admission to intensive care unit and clinical improvement. Data on efficacy and safety of immunomodulatory agents utilized therapeutically in SARS-CoV-2 infection at any stage were extracted. The risk of bias was assessed using validated tools.Results:Of 60372 records, 401 articles were eligible for inclusion. Studies were at variable risk of bias. Randomised controlled trials (RCTs) were available for the following drugs: hydroxychloroquine (N=12), glucocorticoids (N=6), tocilizumab (N= 4), convalescent plasma (N=4), interferon beta (N=2), IVIg (N=2) and N=1 each for anakinra, baricitinib, colchicine, leflunomide, ruxolitinib, interferon kappa, and vilobelimab. For glucocorticoids, dexamethasone reduced mortality only in patients requiring respiratory support; while methylprednisolone reduced mortality in patients aged 60 years or over. Data from RCTs on tocilizumab are conflicting and definite conclusions cannot be drawn at this point in time, but recent studies suggest possible benefit in patients requiring respiratory support. Hydroxychloroquine was not beneficial at any disease stage, one RCT with anakinra was negative, one RCT with baricitinib+remdesivir was positive, and individual trials testing some other compounds provided interesting, albeit preliminary, results.Conclusion:Although there is emerging evidence about immunomodulatory therapies for the management of COVID-19, conclusive data is scarce with some conflicting data. Since glucocorticoids seem to improve survival in some subsets of patients, RCTs comparing glucocorticoids alone versus glucocorticoids plus anti-cytokine/immunomodulatory treatment are warranted. This SLR informed the initiative to formulate EULAR points to consider on pathophysiology and use of immunomodulatory therapies in COVID-19.Figure 1.Forest plots showing the risk ratio (RR) and 95% confidence interval for mortality in randomized controlled trials divided by intervention. The latest follow-up available is reported in the timing column.Disclosure of Interests:None declared

scholarly journals Rheumatic immune-related adverse events from checkpoint inhibitor therapy: a case series

2021 ◽  
Vol 3 (2) ◽  
Author(s):  
Antonella Laria ◽  
Alfredomaria Lurati ◽  
Laura Castelnovo ◽  
Antonio Tamburello ◽  
Paola Maria Faggioli ◽  
...  
Keyword(s):  
Adverse Events ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Case Series ◽  
Hematologic Malignancies ◽  
Checkpoint Inhibitor Therapy ◽  
Cancer Immunotherapies ◽  
Cell Death Protein

Immune checkpoint inhibitors (ICIs) targeting cytotoxic T-lymphocyte associated protein-4 (CTLA-4), programmed cell death protein-1 (PD-1), and its ligand PD-L1 are established cancer immunotherapies for solid tumor and hematologic malignancies. These therapies are involved in immune-related adverse events (irAE), both general and rheumatic ones. In general, immune-related adverse events (irAE) management includes drug-holding, tapering doses of corticosteroids, and specific immunosuppression for clinically severe cases, such as infliximab or mycophenolate.

scholarly journals SAT-241 Pituitary Stalk Interruption Syndrome Presenting as Neonatal Hypotonia

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Nordie Anne Bilbao
Keyword(s):  
Pituitary Gland ◽  
Neonatal Period ◽  
Hormone Replacement ◽  
Brain Mri ◽  
Rare Condition ◽  
Pituitary Stalk ◽  
Pituitary Hormone ◽  
Thyroid Function Tests ◽  
Acth Stimulation ◽  
Central Hypothyroidism

Abstract Pituitary stalk interruption syndrome (PSIS) is a rare condition that include congenital anatomic abnormalities of the pituitary gland and hypopituitarism. There is a wide variety of clinical presentation, with the age at presentation encompassing from neonatal period to adulthood and including one or more pituitary hormone deficiencies. In recent literature there is increasing recognition of PSIS presenting in the neonatal period, mostly involving hypoglycemia. Our patient is a full-term male infant who presented in the newborn period with hypotonia and hypothermia. He also had hypoglycemia, which was initially thought to be associated to hyperinsulinism in the context of gestational diabetes. Micropenis was noted on physical exam. As part of the study for hypotonia, serial thyroid function tests were obtained revealing central hypothyroidism. A low dose ACTH stimulation test was performed which revealed adrenal insufficiency. The patient was started on cortisol and thyroid hormone replacement. Brain MRI showed an ectopic neurohypophysis located along the floor of the hypothalamus, a small anterior pituitary gland, and a partially absent infundibulum, findings consistent with pituitary stalk interruption syndrome. The patient received testosterone injections for micropenis and is being followed for development of other pituitary hormone deficiencies. PSIS is a rare congenital condition that is increasingly recognized in neonates manifesting with signs of hypopituitarism.

Growth hormone replacement for patients with adult onset growth hormone deficiency—what have we learned?

2004 ◽  
Vol 16 (4) ◽  
pp. 1-6
Author(s):  
Monique Piersanti
Keyword(s):  
Growth Hormone ◽  
Gh Deficiency ◽  
Hormone Replacement ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Adult Onset ◽  
Gh Replacement ◽  
Term Benefit

Growth hormone (GH) deficiency is a condition recognized to occur in individuals who have had multiple pituitary hormone deficiencies as a result of pathological processes or neurosurgical interventions. The indications, benefits, and risks of GH replacement therapy will be reviewed with an emphasis on those patients who were adults with the deficiency first emerged. The results of this analysis indicate that, although a measurable improvement can be detected in the patient's quality of life, body composition, and some cardiovascular parameters, the larger questions of long-term benefit and patient selection currently remain unanswered.

Hypohidrosis as an immune-related adverse event of checkpoint inhibitor therapy

Immunotherapy ◽  
2020 ◽  
Vol 12 (13) ◽  
pp. 951-956 ◽  
Author(s):  
Anna E Kersh ◽  
Lynn M Schuchter ◽  
Rosalie Elenitsas ◽  
Emily Y Chu
Keyword(s):  
T Lymphocyte ◽  
Adverse Reactions ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitor ◽  
Immune Checkpoint Blockade ◽  
Inhibitor Therapy ◽  
Lesional Skin ◽  
Checkpoint Inhibitor Therapy ◽  
Cutaneous Adverse Reactions ◽  
Cell Death Protein

Background: Immune checkpoint blockade therapies including cytotoxic-T-lymphocyte antigen 4 (CTLA-4) and programmed cell death protein-1 (PD-1) inhibitors have become indispensable tools for treating melanoma and other cancers. An increasing number of diverse cutaneous adverse reactions to immunotherapy have been documented in the literature and have been reported to affect up to 40% of patients treated with targeted therapies. Method & results: Herein, we report a case of a patient with metastatic melanoma treated with checkpoint inhibitor therapy who developed vitiligo, gastritis and hepatitis, all identified as adverse immune events and attributable to his immunotherapy regimen. He subsequently developed acquired idiopathic generalized hypohidrosis with biopsy of lesional skin demonstrating a peri-eccrine lymphocytic infiltrate. Conclusion: These findings suggest this acquired generalized hypohidrosis represents a lymphocyte-mediated adverse immune event related to this patient’s checkpoint inhibitor therapy.

scholarly journals MECHANISMS IN ENDOCRINOLOGY: Hypophysitis: diagnosis and treatment

2018 ◽  
Vol 179 (3) ◽  
pp. R151-R163 ◽  
Author(s):  
Mamta N Joshi ◽  
Benjamin C Whitelaw ◽  
Paul V Carroll
Keyword(s):  
Imaging Techniques ◽  
Immunosuppressive Agents ◽  
Treatment Strategies ◽  
Rare Condition ◽  
Diagnostic Value ◽  
Serum Markers ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Pituitary Mass ◽  
Pituitary Antibodies

Hypophysitis is a rare condition characterised by inflammation of the pituitary gland, usually resulting in hypopituitarism and pituitary enlargement. Pituitary inflammation can occur as a primary hypophysitis (most commonly lymphocytic, granulomatous or xanthomatous disease) or as secondary hypophysitis (as a result of systemic diseases, immunotherapy or alternative sella-based pathologies). Hypophysitis can be classified using anatomical, histopathological and aetiological criteria. Non-invasive diagnosis of hypophysitis remains elusive, and the use of currently available serum anti-pituitary antibodies are limited by low sensitivity and specificity. Newer serum markers such as anti-rabphilin 3A are yet to show consistent diagnostic value and are not yet commercially available. Traditionally considered a very rare condition, the recent recognition of IgG4-related disease and hypophysitis as a consequence of use of immune modulatory therapy has resulted in increased understanding of the pathophysiology of hypophysitis. Modern imaging techniques, histological classification and immune profiling are improving the accuracy of the diagnosis of the patient with hypophysitis. The objective of this review is to bring readers up-to-date with current understanding of conditions presenting as hypophysitis, focussing on recent advances and areas for future development. We describe the presenting features, investigation and diagnostic approach of the patient with likely hypophysitis, including existing conventional techniques and those in the research/development arena. Hypophysitis usually results in acute and persistent pituitary hormone deficiency requiring long-term replacement. Management of hypophysitis includes control of the inflammatory pituitary mass using a variety of treatment strategies including surgery and medical therapy. Glucocorticoids remain the mainstay of medical treatment but other immunosuppressive agents (e.g. azathioprine, rituximab) show benefit in some cases, but there is a need for controlled studies to inform practice.

Difficulties in differentiating between checkpoint inhibitor pneumonitis and lung metastasis in a patient with melanoma

Immunotherapy ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 293-298 ◽  
Author(s):  
Houssein Safa ◽  
Priya Bhosale ◽  
Annika Weissferdt ◽  
Isabella C Glitza Oliva
Keyword(s):  
Clinical Presentation ◽  
Cytotoxic T Lymphocyte ◽  
Late Onset ◽  
Checkpoint Inhibitors ◽  
Lung Nodule ◽  
Complete Response ◽  
Lung Lesions ◽  
Discontinuation Of Treatment ◽  
Cell Death Protein ◽  
New Onset

The use of immune checkpoint inhibitors is associated with significant toxicities such as pneumonitis; the clinical presentation of the latter can be misleading and may mimic metastasis. We report the case of a melanoma patient who developed late-onset pneumonitis after discontinuation of treatment with anti-programmed cell death protein 1 (PD1) and anti-cytotoxic T lymphocyte antigen 4 (CTLA4) (patient had a complete response). The patient was asymptomatic, however, surveillance computed tomography (CT) scan showed a growing lung nodule and several new-onset, small lung lesions highly suspicious for recurrence. A biopsy of the lesions revealed organizing pneumonia with absence of malignant cells. The lung lesions completely resolved after 6 months without any intervention. The patient is still in complete remission 2 years after the initial diagnosis of melanoma.

scholarly journals PC3 - 142 Gamma Knife Radiosurgery in Patients with Persistent Acromegaly or Cushing’s Disease: Long-Term Risk of Hypopituitarism

2016 ◽  
Vol 43 (S4) ◽  
pp. S22-S22
Author(s):  
O. Cohen-Inbar
Keyword(s):  
Gamma Knife ◽  
Cavernous Sinus ◽  
Cushing’S Disease ◽  
Hormone Replacement ◽  
Gamma Knife Radiosurgery ◽  
Common Adverse Effect ◽  
Cushing's Disease ◽  
Pituitary Hormone

For patient with a recurrent or residual acromegaly or Cushing’s disease (CD) after resection, Gamma knife radiosurgery (GKRS) is often used. Hypopituitarism is the most common adverse effect after GKRS treatment. The paucity of studies with long-term follow up has hampered understanding of the latent risks of hypopituitarism in patients with a Acromegaly or CD. We report the long-term risks of hypopituitarism for patients treated with GKRS for Acromegaly or CD. Methods: From a prospectively created, IRB approved database, we identified all patients with a Acromegaly or CD treated with GKRS at the University of Virginia from 1989 to 2008. Only patients with a minimum endocrine follow up of 60 months were included. The median follow-up is 159.5 months (60.1-278). Thorough radiological and endocrine assessments were performed immediately before GKRS and at regular follow-up intervals. New onset of hypopituitarism was defined as pituitary hormone deficits after GKRS requiring corresponding hormone replacement. Results: 60 patients with either Acromegaly or CD were included. Median tumor volume at time of GKRS was 1.3 cm3 (0.3-13.4), median margin dose was 25 Gy (6-30). GKRS induced new pituitary deficiency occurred in 58.3% (n=35) of patients. Growth Hormone deficiency was most common (28.3%, n=17). The actuarial overall rates of hypopituitarism at 3, 5, and 10 years were 10%, 21.7%, and 53.3%, respectively. The median time to hypopituitarism was 61 months after GKRS (range, 12-160). Cavernous sinus invasion of the tumor was found to correlate with the occurrence of a new or progressive hypopituitarism after GKRS (p=0.018). Conclusions: Delayed hypopituitarism increases as a function of time after radiosurgery. Hormone axes appear to vary in terms of radiosensitivity. Patients with adenoma in the cavernous sinus are more prone to develop loss of pituitary function after GKRS.

scholarly journals SUN-279 A Rare Case of Atypical Rhaboid Teratoid Tumour with Germinoma Differentiation in a 59 Year Old Woman

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Melissa-Rosina Pasqua ◽  
Huda Altoukhi ◽  
Valerie Panet-Raymond ◽  
Denis Sirhan ◽  
Jason Karamchandani ◽  
...  
Keyword(s):  
Diabetes Insipidus ◽  
Case Reports ◽  
Hormone Replacement ◽  
Sella Turcica ◽  
Proliferation Index ◽  
Pituitary Hormone ◽  
Malignant Tumours ◽  
Rhabdoid Tumour ◽  
Mixed Features ◽  
Atypical Teratoid

Abstract Atypical teratoid/rhabdoid tumours (ATRT) are a rare class of central nervous system malignant tumours which are comprised of elements of ectoderm and mesoderm germ-cell layers, but exhibit microscopic similarity to skeletal muscle. These tumours are more commonly seen in pediatric patients, with few case reports recently describing adult patients with this condition, in particular middle-aged women.1–3 We present the case of a previously healthy 59-year-old woman who was found incidentally to have a pituitary mass on CT head, with retrospective symptoms of headaches, polyuria, polydipsia, diplopia, and low blood pressure. At presentation, she was found biochemically to have pan-hypopituitarism with a left cranial nerve six deficit, with an MRI depicting a 19.5 x 22 x 11 mm suprasellar mass extending into the infundibulum and hypothalamus, with displacement of the optic chiasm; repeat imaging ruled out apoplexy. She was started on supplemental levothyroxine and hydrocortisone replacement therapy, and sent for urgent transsphenoidal resection, which was complicated afterwards by hypernatremia from diabetes insipidus. Preliminary reports were suggestive of germinoma given the diffuse presence of Oct 3/4 and C-kit, with a proliferation index of 99%; further cytology of lumbar puncture revealed no malignant cells. However, upon further pathological analysis, her tumour demonstrated loss of INI-1 expression, which is diagnostic of ATRT. Given the mixed features on immunohistochemistry, the final diagnosis was concluded as an atypical teratoid/rhabdoid tumour of the sella turcica with germinoma differentiation. A multi-disciplinary approach consisted of initial radiotherapy, with chemotherapy targeted towards a germinoma-type tumour, and pituitary hormone replacement including treatment for central diabetes insipidus. This represents a unique case of a rare tumour with germinoma differentiation in an older patient that has not been previously reported. References 1. Journal of Clinical Neuroscience 49 (2018) 16–21 2. Acta Neurochir (Wien) (2008) 150: 491–496 3. Surgical Neurology International 2014, 5:75

scholarly journals PD-1, TIM-3 and LAG-3 Expression in T Cells in a Patient with Recurrent Ossifying Fibroma. A Case Report.

2020 ◽  
Author(s):  
Alejandro García-Muñoz ◽  
Nayeli Goreti Nieto-Velázquez ◽  
Gabriela Damian-Morales ◽  
Carlos Liceaga-Escalera ◽  
Luis Alberto Montoya-Perez ◽  
...  
Keyword(s):  
T Cells ◽  
Case Report ◽  
T Cell ◽  
Peripheral Blood ◽  
Cytotoxic T Lymphocyte ◽  
Lymphocyte Activation ◽  
T Cell Response ◽  
Ossifying Fibroma ◽  
Slow Growing ◽  
Cell Death Protein

Abstract Background: Central ossifying fibroma is a benign, slow-growing tumor of mesenchymal origin with a predilection for the mandibular premolar and molar areas. The immunophenotype of T cells involved in the antitumor response against this benign tumor is unknown.Case presentation: In this case report, we described a case of a 48-year-old woman presenting with a very large recurrent ossifying fibroma in the mandible, which was successfully treated with hemimaxillectomy. In addition, we evaluated the expression of programmed cell death protein-1 (PD-1), lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin and mucin-domain containing-3 (TIM-3), cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), CD69 (activation inducer molecule) and CD25 (α chain of the high-affinity IL-2 receptor) in T cell populations from the tumor and peripheral blood of this uncommon lesion.Conclusions: The patient presented recurrent ossifying fibroma, and the tumor-infiltrating and peripheral blood T cells showed expression of PD-1, LAG-3, and TIM-3, suggesting an exhausted T cell response.

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