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Pituitary Apr 2024To explore the potential role of focused radiotherapy in managing the lymphocytic hypophysitis (LH) refractory to medical therapy and surgery.
Successful treatment of medically and surgically refractory lymphocytic hypophysitis with fractionated stereotactic radiotherapy: a single-center experience and systematic literature review.
PURPOSE
To explore the potential role of focused radiotherapy in managing the lymphocytic hypophysitis (LH) refractory to medical therapy and surgery.
METHOD
A systematic literature review was conducted following PRISMA guidelines to identify the studies on radiation treatment for hypophysitis, along with the experience in our institution.
RESULTS
The study included eight patients, three from our institution and five from existing literature. The age at presentation ranged from 37 to 75 years old, with a median age of 58. The presenting symptoms involved headache in seven patients and diplopia in two patients. Pre-radiation visual field defects were noticed in four patients. All patients exhibited variable degrees of hypopituitarism before radiation, with oral corticosteroids being the initial medical treatment. Immunosuppressive therapy was attempted in two patients prior to radiation. Seven patients had a history of transsphenoidal surgery with a histologically confirmed LH. Three patients underwent stereotactic radiosurgery (SRS), while the remaining received FSRT, with a mean irradiation volume of 2.2 cm. A single-session total dose of 12 -15 Gy was administered in the SRS group. In the FSRT group, doses ranged from 24 to 30 Gy with a median dose of 25 Gy, delivered in 2 Gy fractions. Four patients achieved a resolution of visual field defects, while another two patients demonstrated improvement in their associated focal neurologic deficits. No change in pre-existing endocrine status was shown after radiation, except in one patient. Clinical response was achieved in seven patients after a single course of radiation, while one patient required the second course. Six patients remained stable on low-dose glucocorticoid during at least a 12-month follow-up period, and one discontinued it entirely without experiencing relapse. Three patients demonstrated a complete radiologic response, while the remaining showed a partial radiologic response.
CONCLUSIONS
Focused radiation, including FSRT, can play a role in symptomatic relief, effective mass shrinkage, and minimizing radiation exposure to critical surrounding structures in patients with refractory LH. However, further research efforts are necessary to better clarify its effects and optimal dose planning.
Topics: Humans; Adult; Middle Aged; Aged; Radiosurgery; Autoimmune Hypophysitis; Dose Fractionation, Radiation; Hypopituitarism; Treatment Outcome; Retrospective Studies
PubMed: 38270722
DOI: 10.1007/s11102-023-01367-8 -
Endocrine Connections Feb 2023High-dose glucocorticoids are associated with improved recovery of deficits in primary autoimmune hypophysitis (PAH), but optimal dosing, route, and duration are unclear.
OBJECTIVES
High-dose glucocorticoids are associated with improved recovery of deficits in primary autoimmune hypophysitis (PAH), but optimal dosing, route, and duration are unclear.
DESIGN
We reviewed literature for first-line glucocorticoid treatment in PAH until December 2021 and performed an individual patient data meta-analysis to analyze clinical, hormonal, and radiological outcomes with respect to route, dose, and duration (<6.5 vs 6.5-12 vs >12 weeks) of glucocorticoid treatment according to disease severity.
RESULTS
A total of 153 PAH patients from 83 publications were included. The median age at presentation was 41 (32.5-48) years with a female preponderance (70.3%). Visual field recovery was significantly better with i.v. (91.7%) as compared to oral (54.5%) route and high dose (100%) and very high dose (90.9%) as compared to medium dose (20%) of glucocorticoids. Corticotroph axis recovery was greater in i.v. (54.8% vs 28.1% oral, P = 0.033) route and increasing glucocorticoid dose group (0% vs 38.1% vs 57.1%), attaining statistical significance (P = 0.012) with very high-dose. A longer duration of treatment (>6.5 weeks) was associated with better corticotroph and thyrotroph recovery. The need for rescue therapy was lower with i.v. route (38% vs 17.5%, P = 0.012) and with increasing glucocorticoid doses (53.3% vs 34.3% vs 17.3%, P = 0.016). In severe disease, visual field and corticotroph axis recovery were significantly higher with i.v. route and very high-dose steroids. The adverse effects of glucocorticoids were independent of dose and duration of treatment.
CONCLUSIONS
Very high-dose glucocorticoids by i.v. route and cumulative longer duration (>6.5 weeks) lead to better outcomes and could be considered as first-line treatment of severe PAH cases.
PubMed: 36445257
DOI: 10.1530/EC-22-0311 -
Medicine Oct 2022Rheumatic diseases have been reported to sometimes involve the pituitary gland. This study aims to characterize the clinical features and outcomes of patients with...
Rheumatic diseases have been reported to sometimes involve the pituitary gland. This study aims to characterize the clinical features and outcomes of patients with rheumatic disease-associated hypophysitis. We used the electronic medical record system in our hospital to identify nine patients with pituitary involvement in rheumatoid disease. We summarized the clinical characteristics, radiographic findings, treatments, and clinical outcomes of the 9 patients. We also performed a systematic literature review of systemic lupus erythematosus (SLE) cases with pituitary involvement published in PubMed and Wanfang databases from 1995 to 2021, and eight patients with complete information were selected. In the nine-patient cohort, the median age was 54 years, and the spectrum of rheumatic diseases included immunoglobulin G4-related disease (IgG4RD) (4/9), SLE (2/9), vasculitis (2/9), and Sjögren syndrome (SS) (1/9). All patients had pituitary abnormalities on radiological assessment, 6 developed diabetes insipidus (DI), and 8 presented with anterior pituitary hormone deficiencies in the disease duration. All the patients had multisystem involvement. As compared to hypophysitis with IgG4RD (IgG4-H), the age at onset of hypophysitis with SLE (SLE-H) patients was younger [(30.4 ± 16.4) years vs. (56.0 ± 0.8) years] and the disease duration was shorter [(14.0 ± 17.5) months vs. (71.0 ± 60.9) months] (P < .05). All patients were managed with glucocorticoids (GC) in combination with another immunosuppressant, and the majority of patients improved within 4 months. Six patients achieved disease remission while four required at least one hormone replacement therapy. Hypophysitis is a rare complication secondary to a variety of various rheumatic diseases that can occur at any stage. GC combined with additional immunosuppressants could improve patients' symptoms; however some patients also required long-term hormone replacement therapy in pituitary disorders.
Topics: Humans; Middle Aged; Adolescent; Young Adult; Adult; Hypophysitis; Pituitary Diseases; Hypopituitarism; Pituitary Gland; Glucocorticoids; Rheumatic Diseases; Immunosuppressive Agents; Collagen Diseases; Lupus Erythematosus, Systemic; Autoimmune Hypophysitis
PubMed: 36316923
DOI: 10.1097/MD.0000000000031338 -
The Journal of Clinical Endocrinology... Mar 2022Lymphocytic hypophysitis (LyHy) is characterized by inflammation of the pituitary and or neuroinfundibulum and is uncommon. Treatment options include observation,... (Meta-Analysis)
Meta-Analysis
CONTEXT
Lymphocytic hypophysitis (LyHy) is characterized by inflammation of the pituitary and or neuroinfundibulum and is uncommon. Treatment options include observation, high-dose glucocorticoids (HD-GCs) or surgery. Optimal first-line management strategy, however, remains unknown.
OBJECTIVE
This work aimed to assess response to first-line treatment options (observation, HD-GCs, or surgery) of clinically relevant outcomes (symptomatic, hormonal, and radiographic improvement) among patients with LyHy.
METHODS
A systematic review was conducted in 6 databases through 2020. Meta-analysis was conducted when feasible using a random-effects model.
RESULTS
We included 33 studies reporting on 591 patients (423 women, 72%) with LyHy. Improvement/resolution of anterior pituitary dysfunction was highest when HD-GCs was first-line treatment. Surgery was associated with the greatest proportion of patients who had regression on imaging. Subgroup analysis comparing HD-GCs to observation showed the odds of anterior pituitary hormone recovery (OR 3.41; 95% CI, 1.68-6.94) or radiographic regression (OR 3.13; 95% CI, 1.54-6.36) were higher with HD-GCs, but so was the need for additional forms of treatment (OR 4.37; 95% CI, 1.70-11.22). No statistically significant difference was seen in recovery of diabetes insipidus (OR 0.9; 95% CI, 0.26-3.10). Certainty in these estimates was very low.
CONCLUSION
Observation and use of HD-GCs both are successful first-line management strategies in LyHy. Although use of HD-GCs was associated with increased recovery of anterior pituitary hormone deficit, it also was associated with greater likelihood of additional treatment after withdrawal. Optimal dosing and duration of HD-GCs remains unknown.
Topics: Autoimmune Hypophysitis; Female; Glucocorticoids; Humans; Hypopituitarism; Male; Pituitary Diseases; Pituitary Hormones, Anterior
PubMed: 35137155
DOI: 10.1210/clinem/dgab839 -
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 -
Presse Medicale (Paris, France : 1983) Dec 2021Hypophysitis is defined as inflammation of the pituitary gland. It is a heterogeneous condition as it can originate from different parts of the pituitary gland, can be...
Hypophysitis is defined as inflammation of the pituitary gland. It is a heterogeneous condition as it can originate from different parts of the pituitary gland, can be caused by different pathophysiological processes, and can be isolated or the manifestation of a underlying systemic disease. Hypophysitis usually presents with endocrine deficiencies, including diabetes insipidus, with varying patterns. A subset of patients presents with mass effects. The last decades major progress has been made in the understanding of this disease. New forms are now recognized, new diagnostics are being developed, and specific treatments are proposed. This review provides an overview of the current knowledge on hypophysitis using an aetiology-based approach and provides the clinician with a stepwise approach to the patient with (suspected) hypophysitis.
Topics: Autoimmune Hypophysitis; Diabetes Insipidus; Endocrine System Diseases; Erdheim-Chester Disease; Histiocytosis, Langerhans-Cell; Humans; Hypophysitis; Immune Checkpoint Inhibitors; Immunoglobulin G; Immunoglobulin G4-Related Disease; Pituitary Gland; Symptom Assessment; Xanthomatosis
PubMed: 34687912
DOI: 10.1016/j.lpm.2021.104076 -
Pituitary Aug 2021Immunotherapy with immune checkpoint inhibitor (ICI) monoclonal antibodies has shown to be an effective therapeutic alternative in several malignant tumors. However,... (Review)
Review
Immunotherapy with immune checkpoint inhibitor (ICI) monoclonal antibodies has shown to be an effective therapeutic alternative in several malignant tumors. However, adverse effects related to an activation of the immune system may accompany ICI therapy. Among the immune-related adverse events (irAEs) are autoimmune endocrine adverse effects, such as thyroiditis, and hypophysitis. Secondary adrenal insufficiency due to isolated ACTH deficiency (IAD) has also been recently reported to be associated with ICI antibodies. We carried out a systematic review of IAD cases induced by cancer immunotherapy published to date using PubMed's database. We selected 35 articles that reported 60 cancer patients diagnosed with IAD induced by ICI therapy. The prevalence was higher in men (ratio 1.6/1). Mean age at diagnosis was 63.2 ± 11.6 (range,30-87). Melanoma was the tumor most commonly reported (35%) followed by lung (28.3%) and kidney cancer (18.3%). The ICI monoclonal antibody most frequently associated was nivolumab in monotherapy (60%), followed by pembrolizumab (18.3%). Median (IQR) time to develop IAD after starting ICI therapy was 6 (4-8) months. The main symptoms at IAD diagnosis were fatigue (82.8%) and anorexia (67.2%). Hyponatremia (68%) and eosinophilia (31.8%) were the laboratory abnormalities most frequently associated with IAD. Pituitary magnetic resonance imaging (MRI) was normal in most patients (93%). Thyroiditis was the most prevalent (35%) endocrine irAE associated with IAD. In conclusion, ICI-induced IAD is a rare and potentially life-threatening condition that must be taken into account whenever treatment with immunotherapy in cancer patients is started due to their potential serious prognostic implications.
Topics: Adrenocorticotropic Hormone; Antineoplastic Agents, Immunological; Endocrine System Diseases; Genetic Diseases, Inborn; Humans; Hypoglycemia; Immunotherapy; Melanoma; Nivolumab; Thyroiditis
PubMed: 33761049
DOI: 10.1007/s11102-021-01141-8 -
Autoimmunity Reviews Aug 2020To evaluate prevalence and clinical features of immune-related adverse events (irAEs) to immune checkpoint inhibitors (ICIs) in accordance with the gender of treated...
OBJECTIVE
To evaluate prevalence and clinical features of immune-related adverse events (irAEs) to immune checkpoint inhibitors (ICIs) in accordance with the gender of treated cancer patients.
METHODS
A systematic review of the medical literature was conducted by searching all available clinical data up to December 2019 in several databases using a combination of MESH terms related to immune checkpoint inhibitors, autoimmunity, and gender. Analyzed data were related to all FDA approved ICIs and respective indications in cancer.
RESULTS
According to data from the literature, male display a slightly lower frequencies of ICIs-related endocrinopathies compared with females, specifically thyroid dysfunction. On the contrary, ICIs-hypophysitis has been reported at higher rates among males compared with females. ICI-induced Sicca/Sjogren's syndrome showed a more frequent occurrence in men than the idiopathic primary form. No differences in gender distribution seem to arise in hematologic and gastrointestinal-irAEs. Interestingly, the gender distribution of neurologic and vascular ICIs-irAEs appears male-dominant.
CONCLUSIONS
The present systematic review highlights for the first time that the distribution of patients experiencing irAEs associated with ICIs changes among the genders according to the specific drug used, the frequency of the cancer and of the autoimmune conditions in the general population.
Topics: Antineoplastic Agents; Autoimmune Diseases; Autoimmunity; Female; Humans; Male; Neoplasms; Sex Factors
PubMed: 32561463
DOI: 10.1016/j.autrev.2020.102590 -
Postgraduate Medicine Mar 2020Immune checkpoint inhibitors (ICPIs) are novel drugs in the field of oncology however carry the risk of immune-related dermatologic, gastrointestinal, and endocrine side...
Immune checkpoint inhibitors (ICPIs) are novel drugs in the field of oncology however carry the risk of immune-related dermatologic, gastrointestinal, and endocrine side effects which can be fatal. These new innovative immunoregulatory drugs have intertwined the fields of oncology and endocrinology. CTLA-4 and PD-1 are co-inhibitory receptors on T cells that turn the T cell 'off' when binding to receptors on APCs. Tumor cells can also carry receptors for CTLA- and PD-1. By rendering T cells inactive, tumor cells can evade immune attack. Antibodies that bind to CTLA-4 and PD-1 lead to T cell activation and destruction of both tumor and normal host cells. ICPIs have been used in a variety of malignancies including melanoma, kidney cancer, and non-small cell lung cancer. A unique underrecognized side effect of the autoimmune response is hypophysitis leading to central adrenal insufficiency which can be fatal. Additional immune-related adverse events (irAEs) include hypothyroidism, hyperthyroidism, diabetes, and hypoparathyroidism.
Topics: Adrenal Gland Diseases; Antineoplastic Agents, Immunological; CTLA-4 Antigen; Diabetes Mellitus, Type 1; Endocrine System Diseases; Humans; Hypophysitis; Immunotherapy; Neoplasms; Programmed Cell Death 1 Receptor; Severity of Illness Index; T-Lymphocytes; Thyroid Diseases
PubMed: 31876444
DOI: 10.1080/00325481.2019.1709344 -
European Journal of Cancer (Oxford,... Sep 2019New-onset pituitary gland lesions are observed in up to 18% of cancer patients undergoing treatment with immune checkpoint blockers (ICB). We aimed to develop and...
Machine learning defined diagnostic criteria for differentiating pituitary metastasis from autoimmune hypophysitis in patients undergoing immune checkpoint blockade therapy.
PURPOSE
New-onset pituitary gland lesions are observed in up to 18% of cancer patients undergoing treatment with immune checkpoint blockers (ICB). We aimed to develop and validate an imaging-based decision-making algorithm for use by the clinician that helps differentiate pituitary metastasis (PM) from ICB-induced autoimmune hypophysitis (HP).
MATERIALS AND METHODS
A systematic search was performed in the MEDLINE and EMBASE databases up to October 2018 to identify studies concerning PM and HP in patients treated with cytotoxic T-lymphocyte-associated protein 4 and programmed cell death (ligand) 1. The reference standard for diagnosis was confirmation by histology or response on follow-up imaging. Patients from included studies were randomly assigned to the training set or the validation set. Using machine learning (random forest tree algorithm) with the most-described six imaging and three clinical features, a multivariable prediction model (the signature) was developed and validated for diagnosing PM. Signature performance was evaluated using area under a receiver operating characteristic curves (AUCs).
RESULTS
Out of 3174 screened articles, 65 were included totalising 122 patients (HP: 60 pts, PM: 62 pts). Complete radiological data were available in 82 pts (Training: 62 pts, Validation: 20 pts). The signature reached an AUC = 0.91 (0.82, 1.00), P < 10 in the training set and AUC = 0.94 (0.80, 1.00), P = 0.001 in the validation set. The signature predicted PM in lesions either ≥ 2 cm in size or < 2 cm if associated with heterogeneous contrast enhancement and cavernous extension.
CONCLUSION
An image-based signature was developed with machine learning and validated for differentiating PM from HP. This tool could be used by clinicians for enhanced decision-making in cancer patients undergoing ICB treatment with new-onset, concerning lesions of the pituitary gland.
Topics: Algorithms; Autoimmune Hypophysitis; B7-H1 Antigen; CTLA-4 Antigen; Diagnosis, Differential; Humans; Machine Learning; Neoplasms; Pituitary Neoplasms; Programmed Cell Death 1 Receptor; ROC Curve; Radioimmunotherapy
PubMed: 31415986
DOI: 10.1016/j.ejca.2019.06.020