Differences in checkpoint-inhibitor-induced hypophysitis: mono- versus combination therapy induced hypophysitis.

Objective: Immune checkpoint inhibitors (ICIs) are revolutionary in oncology but may cause immune-related (IR) side effects, such as hypophysitis. Treatment with anti-PD-(L)1, anti-CTLA-4 or anti-CLTA-4/PD-1 may induce hypophysitis, but little is known about the differences in clinical presentation or need for different treatment. We analyzed the differences of anti-PD-(L)1, anti-CTLA-4 and anti-CTLA-4/PD-1 induced hypophysitis. Methods: retrospective analysis of 67 patients (27 anti-PD-(L)1, 6 anti-CLTA-4 and 34 anti-CTLA-4/PD-1 induced hypophysitis). Results: The median time between starting ICIs and IR-hypophysitis was longer after anti-PD(L)-1) therapy (22 weeks versus 11 and 14 weeks after anti-CTLA-4 and anti-CTLA-4/PD-1 therapy, respectively). The majority of patients (>90%), presented with atypical complaints such as fatigue, nausea, and muscle complaints. Headache, TSH or LH/FSH deficiency were more common in anti-CTLA-4 and anti-CLTA-4/PD-1 versus anti-PD-(L)1 induced hypophysitis (83% and 58% versus 8%, 67% and 41% versus 11%, and 83% and 48% versus 7%, respectively). Pituitary abnormalities on MRI (hypophysitis or secondary empty sella syndrome) were only seen in patients receiving anti-CTLA-4 or anti-CTLA-4/PD-1 therapy. Recovery from TSH, LH/FSH and ACTH deficiency was described in 92%, 70% and 0% of patients after a mean period of 14 and 104 days, respectively, and did not differ between patients who did or did not receive high-dose steroids. Conclusion: The clinical presentation of IR-hypophysitis varies depending on the type of ICIs. MRI abnormalities were only seen in anti-CTLA-4 or anti-CTLA-4/PD-1 induced hypophysitis. Endocrine recovery is seen for LH/FSH and TSH deficiency but not for ACTH deficiency, irrespective of the corticosteroid dose.

A Toluene-induced Infundibulo-neurohypophysitis: A New Cause of Hypophysitis Secondary to Toxic Exposure.

BACKGROUND: Hypophysitis is a rare inflammatory disorder of the pituitary gland. Symptoms and signs of hypophysitis can be various, and its recognition may be challenging. Arginine vasopressin deficiency (AVP-D) due to exposure to a variety of drugs and toxic substances is rare, but some cases have been reported. Only 2 cases of AVP-D following toxic exposure to toluene, an aromatic hydrocarbon, have been reported in the literature. To our knowledge, our case represents the first description of an infundibulo neurohypophysitis (INH), manifested with AVP-D, secondary to inhalation of toluene. CASE REPORT: A 59-year-old man with an unremarkable medical history was referred to our department for headache, polyuria, and polydipsia after the inhalation of spray film containing toluene. The blood tests revealed a hyperosmolar plasma hypernatremia with normal kidney function. A desmopressin test was performed, with an improvement in water balances, blood electrolytes, and diuresis contraction. A pituitary MRI detected the absence of a normal hyperintense signal of the neuro-pituitary in the T1-weighted images. In consideration of the clinical signs and radiological imaging suggestive of INH, a therapy with desmopressin and corticosteroids was instituted, with gradual improvement of polyuria and resolution of the radiological features of INH. CONCLUSION: The exceptional finding of INH, manifested with AVP-D, following toluene inhalation could represent a new secondary cause of hypophysitis. The possibility that drugs or toxic substances never reported before could induce INH should not be excluded since the study on hypophysitis is relatively recent but emerging, predictably destined to increase exponentially in the coming years.

Immune checkpoint inhibitor-associated new-onset hypophysitis: a retrospective analysis using the FAERS.

BACKGROUND: Our study aimed to investigate the prevalence and demographic characteristics of immune checkpoint inhibitor-associated hypophysitis (ICI-hypophysitis) using data from the FAERS, and the risk factors of prognosis were explored. METHODS: In this retrospective study, all cases of newly-diagnosed hypophysitis associated with FDA approved ICIs from 1st January 2007 to 31st December 2022 were accumulated using FAERS. Demographic data including age, sex, body weight, the prognosis of cases, and other co-occurred endocrinopathies induced by ICIs were analyzed and compared between different subgroups of immunotherapy. RESULTS: The reporting frequency of ICI-hypophysitis was 1.46% (2343/160089). Patients on the combination therapy had higher risk of hypophysitis reporting, followed by anti-CTLA-4 agent compared with other monotherapies (p < 0.001). Male subjects displayed higher reporting risk of ICI-hypophysitis (p = 0.015). Patients on anti-PD-1 therapy or the combination therapy showed higher occurrence rate of type 1 diabetes (anti-PD-1 vs. anti-PD-L1 vs. anti-CTLA-4 vs. combination therapy, 4.2% vs. 0.7% vs. 0.3% vs. 8.4%, p < 0.001). The occurrence rate of new-onset thyroid diseases in patients receiving combination therapy was higher than anti-PD-1 monotherapy (12.3% vs. 8.4%, p = 0.010). Elder age, lung cancer, and renal cancer emerged to be positively associated with severe clinical outcomes [>65 years, OR 1.042, 95%CI (1.022-1.063), p < 0.001; lung cancer, OR 1.400, 95%CI (1.019-1.923), p = 0.038; renal cancer, OR 1.667, 95%CI (1.153-2.412), p = 0.007]. Anti-CTLA-4 monotherapy was discovered to be a protective factor of severe outcomes [OR 0.433, 95%CI (0.335-0.558), p < 0.001]. Female sex and co-occurrence of ICI-related diabetes exhibited lower risk of death [female, OR 0.571, 95%CI (0.361-0.903), p = 0.017; diabetes, OR 0.090, 95%CI (0.016-0.524), p = 0.007]. CONCLUSIONS: ICI-induced hypophysitis is male-predominant irAE, most commonly seen in patients on anti-CTLA-4 mono- or combination therapy. Awareness among clinicians is critical when patients with elder age, lung or renal cancer develop hypophysitis, which indicates poor clinical outcomes. Female sex, anti-CTLA-4 monotherapy and co-occurrence of ICI-related diabetes are protective risk factors for poor prognosis.

Hypocortisolemic ASIA: a vaccine- and chronic infection-induced syndrome behind the origin of long COVID and myalgic encephalomyelitis.

Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), long COVID (LC) and post-COVID-19 vaccine syndrome show similarities in their pathophysiology and clinical manifestations. These disorders are related to viral or adjuvant persistence, immunological alterations, autoimmune diseases and hormonal imbalances. A developmental model is postulated that involves the interaction between immune hyperactivation, autoimmune hypophysitis or pituitary hypophysitis, and immune depletion. This process might begin with a deficient CD4 T-cell response to viral infections in genetically predisposed individuals (HLA-DRB1), followed by an uncontrolled immune response with CD8 T-cell hyperactivation and elevated antibody production, some of which may be directed against autoantigens, which can trigger autoimmune hypophysitis or direct damage to the pituitary, resulting in decreased production of pituitary hormones, such as ACTH. As the disease progresses, prolonged exposure to viral antigens can lead to exhaustion of the immune system, exacerbating symptoms and pathology. It is suggested that these disorders could be included in the autoimmune/adjuvant-induced inflammatory syndrome (ASIA) because of their similar clinical manifestations and possible relationship to genetic factors, such as polymorphisms in the HLA-DRB1 gene. In addition, it is proposed that treatment with antivirals, corticosteroids/ginseng, antioxidants, and metabolic precursors could improve symptoms by modulating the immune response, pituitary function, inflammation and oxidative stress. Therefore, the purpose of this review is to suggest a possible autoimmune origin against the adenohypophysis and a possible improvement of symptoms after treatment with corticosteroid replacement therapy.

Pituitary Complications of Checkpoint Inhibitor Use.

Immune checkpoint inhibitors have revolutionized cancer therapy but are associated with a risk of endocrine immune-related adverse events, including pituitary complications. Autoimmune hypophysitis, traditionally a rare diagnosis, has become a more frequently encountered clinical entity with the emergence of antitumor immunotherapy. This mini-review aims to consolidate current knowledge, encompassing the epidemiology, pathophysiology, clinical presentation, diagnosis, and management of pituitary complications of immune checkpoint inhibitor use.

Pregnancy in Autoimmune Hypophysitis: Management of a Rare Condition.

INTRODUCTION: Hypophysitis is an inflammatory disorder of the pituitary gland. It can manifest variously, with endocrinological and neuro-ophthalmologic symptoms and signs, due to the compression of sellar and parasellar structures. CASE REPRESENTATION: Although hypophysitis is rare, this pituitary disease can occur during pregnancy or in the postpartum period. In this report, we describe the case of a woman with partial hypopituitarism secondary to autoimmune hypophysitis who, five years after the diagnosis and the immunosuppressive treatment, had an uneventful pregnancy and successfully delivered a healthy infant at term. CONCLUSION: We reported the clinical history of the patient and the evolution of the disease and also reviewed the management and treatment of autoimmune hypophysitis during pregnancy.

Acquired thyroid-stimulating hormone, luteinizing hormone, and follicle-stimulating hormone deficiencies with circulating anti-glycoprotein hormones alpha chain-positive cell antibodies.

BACKGROUND: A patient with systemic lupus erythematosus (SLE) suffered from acquired thyroid-stimulating hormone (TSH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) deficiencies. MRI findings revealed a slight atrophy of the pituitary gland. Further, the serum concentration of the covalent alpha subunit (glycoprotein hormones alpha chain [CGA]) in TSH-, LH-, and FSH-positive cells was below the detectable range. Because SLE is an autoimmune disorder, autoimmunity against the pituitary gland was suspected as the cause of pituitary deficiency. METHODS AND RESULTS: Immunofluorescence analysis showed that the patient's immunoglobulin G recognized CGA-positive cells in the pituitary gland; therefore, autoimmunity against CGA-positive cells may have caused TSH, LH, and FSH deficiencies in this patient. Moreover, cell-specific autoimmunity impairs pituitary hormone levels. Further research is required to clarify whether acquired TSH, LH, and FSH deficiencies are common in patients with SLE or other autoimmune diseases. CONCLUSION: Our findings highlight a unique case of acquired TSH, LH, and FSH deficiencies caused by circulating anti-CGA-positive cell antibodies, introducing a novel clinical concept of acquired hypopituitarism.

Immune Checkpoint Inhibitors-Induced Endocrinopathies: Assessment, Management and Monitoring in a Comprehensive Cancer Centre.

OBJECTIVES: To determine the incidence, presentation, frequency and management of immune checkpoint inhibitors (ICI)-related endocrinopathies in a comprehensive cancer centre in Oman, particularly with programme death 1/programme death-ligand 1 (PD-1/PD-L1) inhibitors. BACKGROUND: A high number of patients treated with PD-1/PD-L1 inhibitors for the management of solid tumours developed endocrinopathies. METHODS: This is a retrospective study of patients admitted to Sultan Qaboos Comprehensive Cancer Care and Research Centre (SQCCCRC) from August 2021 to December 2022. All adults diagnosed with solid cancers and have received at least one dose of ICIs were included. Patients with incomplete data were excluded from the analysis. Data regarding the ICI-induced endocrinopathy were collected. RESULTS: A total of 139 patients were included in the study of which 58% were females. The median age of the cohort was 56 years. The incidence of endocrine-related adverse events was 28%. The mean time for the development of endocrine adverse events after treatment initiation was 4.1 ± 2.8 months. Of the patients who developed toxicity, 90% had hypothyroidism. Ten patients developed hyperthyroidism, two patients were diagnosed with secondary adrenal insufficiency/hypophysitis and one patient developed Type 1 diabetes mellitus (DM). Using univariable logistic regression weight and body mass index (BMI) significantly impacted the development of endocrine immune-related adverse events (irAEs). CONCLUSIONS: This is the first study from the Sultanate of Oman to assess PD-1/PDL-1 ICI-induced endocrinopathies. The most common endocrine adverse event is thyroid dysfunction, mainly hypothyroidism followed by hyperthyroidism. Hypophysitis, primary adrenal insufficiency and CIADM occur less frequently, but have a more significant effect on the patient's health. The treating physician should be aware of ICI-induced endocrinopathies, screening and treatment. Furthermore, our study showed that patients with a higher BMI have a greater risk of developing irAES. Further studies are needed to establish the predictors of endocrine irAEs.

[Endocrine side effects of tumor treatment]. / Endokrine Nebenwirkungen von Tumortherapien.

Targeted and immune-based treatments represent significant innovations in oncology and impressively improve the prognosis of many tumor diseases. Their now widespread use as a standard treatment for several malignant diseases increasingly requires knowledge of how to deal with new adverse events (AE) induced by oncological agents in centers and routine practice [12, 13]. For example, the blockade of specific checkpoints of the inhibitory immune system by immune checkpoint inhibitors (ICI) causes the loss of immune tolerance to the body's own tissue with the occurrence of endocrine immune-related AE (irAE) in approximately 10% of patients treated with ICI [3, 11]. Targeted treatments, such as with tyrosine kinase inhibitors (TKI), mammalian target of rapamycin (mTOR) and phosphoinositide 3­kinase (PI3K) inhibitors often lead to disorders of glucose metabolism and thyroid gland dysfunction. The challenges of maintaining bone health during endocrine therapy in patients with prostate and hormone receptor-positive breast cancer and in the endocrine follow-up care of childhood cancer survivors are well-known and are becoming increasingly more important for the long-term prognosis and quality of life [5, 20]. However, although the recommendations for a systematic management of endocrine side effects of these relatively new tumor therapies can be found in guidelines, they are not yet established in routine clinical care [15, 19]. A close interdisciplinary cooperation is required for optimal care of people with cancer [7]. The development of such interdisciplinary cross-sectoral treatment structures is important as tumor treatment is primarily carried out by hematologists or oncologists, while the management of AE induced by oncological agents increasingly involves primary care physicians including internists and in the case of endocrine AE requires the specific expertise of endocrinologists and diabetologists.

Mikulicz's disease combined with IgG4-related hypophysitis: a case report.

BACKGROUND: IgG4-related diseases are very uncommon, and its diagnosis and treatment are complicated as it encompasses multiple disciplines. CASE PRESENTATION: A 77-year-old woman was admitted with a jaw mass and nausea and vomiting. Laboratory tests showed elevated serum IgG4, pituitary MRI suggested thickening of the pituitary stalk, and head and neck CT suggested orbital and mandibular masses. Patients with mandibular mass were diagnosed with Mikulicz's disease with IgG4-related hypophysitis. We found no other evidence of causing thickening of the pituitary stalk. She was given oral prednisolone 30 mg daily, and her nausea and vomiting improved significantly, and the mandibular and ocular masses decreased in size. CONCLUSION: Mikulicz's disease combined with IgG4-related hypophysitis is a rare case of IgG4-RD in elderly women. IgG4-RD is one of the causes of head and neck exocrine gland mass and pituitary stalk thickening in the elderly.

The co-occurrence of SAT, hypophysitis, and Schnitzler syndrome after COVID-19 vaccination: the first described case.

Subacute thyroiditis (also known as granulomatous thyroiditis, giant cell thyroiditis, de Quervain's disease, or SAT) is an inflammatory disease of the thyroid gland, usually spontaneously remitting, that lasts for weeks to months. However, recurrent forms sometimes occur which may have a genetic basis. In our paper, we have focused on the pathogenetics, symptoms, and treatment of SAT. We have described the 17-month disease course of a woman with persistent recurrent steroid-resistant SAT. SAT was well established and the patient's symptoms were not only recurrent neck pain with fever, but also recurrent chronic urticaria, which are symptoms that fulfil the criteria for the diagnosis of Schnitzler syndrome. Schnitzler syndrome occurred after vaccination with COVID-19 in the mechanism of ASIA syndrome. In our patient, Schnitzler syndrome involved the thyroid gland, causing persistent subacute thyroiditis, and the pituitary gland, causing transient swelling of the pituitary, which, to our knowledge, is the first reported case in the literature. Also unprecedented, as far as we know, is the fact that we performed thyroidectomy in the above patient, which reduced systemic inflammation and caused SAT to resolve, although only the inclusion of anakinra treatment resulted in resolution of the underlying condition.

A Rare Association of Autoimmune Hypophysitis With Seronegative Rheumatoid Arthritis: A Case Report.

Autoimmune hypophysitis (AH) is an uncommon condition where there is inflammation of the pituitary gland which leads to hormonal imbalances. It is often associated with autoimmune diseases; however, a case is yet to be reported with an association of AH with seronegative rheumatoid arthritis (RA). We present a case of a 45-year-old female who complained of polyuria/polydipsia and rapid weight gain. An MRI of the head revealed enlargement of the pituitary gland, concerning for AH. Although she was initially treated for diabetes insipidus, she began reporting new complaints of joint pains and morning stiffness. She was clinically diagnosed with seronegative RA and improved with a trial of hydroxychloroquine. A repeat MRI showed improvement in the abnormal pituitary findings, and the patient was closely monitored with a multidisciplinary approach. Diagnosing and managing patients with AH are topics that are still being explored and researched as it is a relatively rare pathology. Consequently, we found the need to discuss the relationship of AH with seronegative RA and delve into the various diagnostic and treatment approaches.

[A case of suspected IgG4-related hypophysitis presented with panhypopituitarism and central diabetes insipidus].

A 78-year-old man complained of subacute general fatigue and anorexia, following diplopia and gait disturbance. He demonstrated wide-based and small-stepped gait without objectively abnormal ocular movements. Brain |MRI showed enlargement of the pituitary stalk and gland with uniform contrast enhancement. PET-CT showed FDG |uptake in the pituitary gland, mediastinal lymph nodes, and left hilar lymph nodes. Blood investigations revealed panhypopituitarism and high serum IgG4 levels up to 265 |mg/dl. Histopathological examination revealed no IgG4-positive cell infiltration in the biopsied mediastinal lymph nodes. However, we suspected IgG4-associated hypophysitis based on the clinical symptoms and MRI findings, which were markedly resolved with steroid. Central masked diabetes insipidus was manifested, but was improved with oral desmopressin. We should pay close attention to the fact that IgG4-related hypophysitis may present with various symptoms regarded as indefinite complaints related to aging or underlying diseases, especially in elderly patients with multimorbidity.

Aberrant CD8+T cells drive reproductive dysfunction in female mice with elevated IFN-γ levels.

Introduction: Interferon-gamma (IFN-γ) is pivotal in orchestrating immune responses during healthy pregnancy. However, its dysregulation, often due to autoimmunity, infections, or chronic inflammatory conditions, is implicated in adverse reproductive outcomes such as pregnancy failure or infertility. Additionally, the underlying immunological mechanisms remain elusive. Methods: Here, we explore the impact of systemic IFN-γ elevation on cytotoxic T cell responses in female reproduction utilizing a systemic lupus-prone mouse model with impaired IFN-γ degradation. Results: Our findings reveal that heightened IFN-γ levels triggered the infiltration of CD8+T cells in the pituitary gland and female reproductive tract (FRT), resulting in prolactin deficiency and subsequent infertility. Furthermore, we demonstrate that chronic IFN-γ elevation increases effector memory CD8+T cells in the murine ovary and uterus. Discussion: These insights broaden our understanding of the role of elevated IFN-γ in female reproductive dysfunction and suggest CD8+T cells as potential immunotherapeutic targets in female reproductive disorders associated with chronic systemic IFN-γ elevation.

Pituitary and COVID-19 vaccination: a systematic review.

PURPOSE: This systematic review aims to examine the latest research findings and assess the impact of COVID-19 vaccination on the pituitary gland. METHOD: PubMed and Tripdatabase were searched from January 1st, 2020 to February 12th, 2024. Case reports, case series and reviews related to post COVID-19 vaccination pituitary disease were included. Eligible articles were tabulated and analysed in the attempt to provide an overview on the epidemiology, clinical presentation, imaging, treatment, outcomes and pathophysiological background of post COVID-19 vaccination pituitary disease. RESULTS: Among the 23 case reports included in this review, post COVID-19 vaccination hypophysitis was reported in 9 patients, pituitary apoplexy (PA) in 6 cases, SIADH in 5 cases and Isolated ACTH deficiency in 2 cases. Additionally, precipitating adrenal crisis was registered in 7 patients and pituitary tumor enlargement in 1 patient after receiving COVID-19 vaccination. CONCLUSION: Despite the rarity of these events, our research findings suggest an association between COVID-19 vaccination and the subsequent development of pituitary diseases. The most common manifestations include hypophysitis with ADH deficiency, PA and SIADH, with symptoms typically emerging shortly after vaccine administration. Potential pathogenetic mechanisms include molecular mimicry, vaccine adjuvants and vaccine-induced thrombotic thrombocytopenia (VITT), with the presence of ACE2 receptors in the hypothalamus-pituitary system contributing to the process. These findings can aid in diagnostic and treatment decisions for patients presenting with these syndromes. Nevertheless, given the rarity of these events, safety and efficacy of the currently available COVID-19 vaccines remain robust and we strongly advocate continuing pursuing vaccination efforts.

Postpartum Hypophysitis: A Case Report and a Literature Review.

Hypophysitis is a rare pituitary gland disease primarily seen in females of reproductive age. Patients can present with various non-specific symptoms, which makes diagnosis challenging. Appropriate endocrine workup supplemented with magnetic resonance imaging (MRI) helps establish a diagnosis. We present a case of a 22-year-old postpartum female who came with nausea, vomiting, and abdominal pain. Global endocrine insufficiency was seen in the laboratory workup, and an MRI confirmed the diagnosis of hypophysitis. She was treated with steroid and thyroid hormone supplementation.

Bilateral Sixth Nerve Palsy: A Rare Presentation of Primary Hypophysitis.

Cranial nerve palsy is common in pituitary disease and depends on the extension of the lesion into the cavernous sinuses. Bilateral cranial nerve palsy was described in pituitary adenomas with apoplexy and in only one case in hypophysitis. We present a case of a 32-year-old female manifesting with headache, diplopia, bilateral sixth nerve palsy, and hypopituitarism. Magnetic resonance imaging (MRI) revealed symmetric expansion of the pituitary gland, with bilateral cavernous sinus invasion and thickening of the pituitary stalk. Hypophysitis was suspected, and after treatment with IV methylprednisolone boluses, a decrease in the pituitary lesion was observed, with complete remission of sixth nerve palsy in the right eye and partial improvement in the left eye. In this case, we report an infrequent form of presentation of hypophysitis, and highlight that steroids are the first line of treatment.

A case of hypophysitis after COVID-19 vaccination with a detection of anti-pituitary antibody, with review of literature.

COVID-19 vaccines have resulted in a remarkable reduction in both the morbidity and mortality associated with COVID-19. However, there are reports of endocrine rare clinical conditions linked to COVID-19 vaccination. In this report, we present a case of hypophysitis following COVID-19 vaccination and review the literature on this condition. This case involved a 72-year-old male with type 1 diabetes who experienced symptoms such as vomiting, appetite loss, and headaches following his fifth COVID-19 vaccine dose. He was diagnosed with secondary adrenal insufficiency; subsequent assessment revealed an enlarged pituitary gland. Unlike previous cases, our patient has partial recovery from pituitary insufficiency, and his pituitary function gradually improved over time. Anti-pituitary antibodies (APAs) against corticotrophs, thyrotrophs, gonadotrophs, and folliculo stellate cells (FSCs) were detected in serum samples taken 3 months after onset. Hypophysitis after COVID-19 vaccination is a rare clinical condition, with only eight cases reported by the end of 2023, most occurring after the initial or second vaccination. Symptoms of hypophysitis after COVID-19 vaccination are similar to those of classic pituitary dysfunction. Pituitary insufficiency is persistent, with five of the above eight patients presenting posterior pituitary dysfunction and three patients presenting only anterior pituitary dysfunction. Two of those eight patients had autoimmune diseases. Our case suggests a potential link between acquired immunity, APA production, and pituitary damage. To elucidate the etiology of hypophysitis associated with COVID-19 vaccination, detailed investigation of patients with nonspecific symptoms after vaccination against COVID-19 is necessary.

Pituitary-related immune adverse events induced by programmed death Protein-1 inhibitors differ clinically from hypophysitis.

OBJECTIVE: We aimed to elucidate the clinical features of pituitary immune-related adverse events (irAEs) induced by PD-1 inhibitors in a Chinese cohort and the previous literatures. PATIENTS AND DESIGN AND MEASUREMENTS: We retrospectively analysed the clinical manifestations, laboratory examination findings, imaging features and treatments of 14 patients with pituitary irAEs caused by PD-1 inhibitors in our cohort. In addition, we searched PubMed for all English articles on pituitary irAEs induced by PD-1 inhibitors published from 1950 to 2023. A total of 47 articles were included, and the clinical characteristics of 94 patients with pituitary irAEs induced by PD-1 inhibitors in these literatures were compared to the characteristics of our cohort. RESULTS: Among the 14 patients in our cohort with pituitary irAEs induced by PD-1 inhibitors, 12 patients (85.71%, 12/14) exhibited isolated ACTH deficiency (IAD), 100.0% (14/14) of the central adrenocortical insufficiency, and 2 patients showed more than one hypothalamic-pituitary axis injury (14.29%, 2/14). Pituitary magnetic resonance imaging in all the 14 patients showed no pituitary enlargement. In previous studies we reviewed, 82.98% of the total (78/94) presented with pituitary irAEs as IAD, 100.0% (94/94) of the central adrenocortical insufficiency, and 78.33% of the patients showed no abnormality of the pituitary gland (47/60). The pituitary irAEs caused by PD-1 inhibitors did not involve typical manifestations of hypophysitis, such as pituitary enlargement, headache, visual field defects, and multiple pituitary function impairments in our cohort and the previous literatures. CONCLUSION: In our study, pituitary immune-related adverse reactions induced by PD-1 inhibitors mainly manifested isolated ACTH deficiency rather than hypophysitis.