Multifaceted physiological and therapeutical impact of curcumin on hormone-related endocrine dysfunctions: A comprehensive review.

Over the past five decades, Curcumin (Cur), derived from turmeric (Curcuma longa), has gained considerable attention for its potential therapeutic applications. Synthesizing insights from clinical trials conducted over the last 25 years, this review delves into diseases where Cur has demonstrated promise, offering a nuanced understanding of its pharmacokinetics, safety, and effectiveness. Focusing on specific examples, the impact of Cur on various human diseases is explored. Endocrine glands and associated signaling pathways are highlighted, elucidating how Cur influences cellular signaling. The article underscores molecular mechanisms such as hormone level alteration, receptor interaction, cytokine and adipokine expression inhibition, antioxidant enzyme activity, and modulation of transcription factors. Cur showcases diverse protective mechanisms against inflammation and oxidative damage by suppressing antiapoptotic genes and impeding tumor promotion. This comprehensive overview emphasizes the potential of Cur as a natural agent for countering aging and degenerative diseases, calling for further dedicated research in this realm.

Targeting Cell Senescence and Senolytics: Novel Interventions for Age-Related Endocrine Dysfunction.

Multiple changes occur in hormonal regulation with aging and across various endocrine organs. These changes are associated with multiple age-related disorders and diseases. A better understanding of responsible underling biological mechanisms could help in the management of multiple endocrine disorders over and above hormone replacement therapy (HRT). Cellular senescence is involved in multiple biological aging processes and pathologies common in elderly individuals. Cellular senescence, which occurs in many older individuals but also across the lifespan in association with tissue damage, acute and chronic diseases, certain drugs, and genetic syndromes, may contribute to such endocrine disorders as osteoporosis, metabolic syndrome, and type 2 diabetes mellitus. Drugs that selectively induce senescent cell removal, "senolytics,", and drugs that attenuate the tissue-destructive secretory state of certain senescent cells, "senomorphics," appear to delay the onset of or alleviate multiple diseases, including but not limited to endocrine disorders such as diabetes, complications of obesity, age-related osteoporosis, and cancers as well as atherosclerosis, chronic kidney disease, neurodegenerative disorders, and many others. More than 30 clinical trials of senolytic and senomorphic agents have already been completed, are underway, or are planned for a variety of indications. Targeting senescent cells is a novel strategy that is distinct from conventional therapies such as HRT, and thus might address unmet medical needs and can potentially amplify effects of established endocrine drug regimens, perhaps allowing for dose decreases and reducing side effects.

THERAPEUTIC USE OF RESVERATROL IN THE TREATMENT OF NEUROLOGICAL AND ENDOCRINOLOGICAL PATIENTS.

The article represents the data characterizing the use of resveratrol in the treatment of various diseases, including endocrinological and neurological. It was shown that resveratrol is widely used in the treatment of various diseases due to its ability to actively suppress the inflammatory process. At the same time, in autoimmune diseases resveratrol inhibits the function of the entire population of T-cells, but when it comes to the neoplastic process, it only inhibits the activity of a subpopulation of T-cells (Treg). Thus, resveratrol can be recommended in the treatment of any diseases associated with the activation of the T-cell immunity.

Growth and Growth Hormone through the Ages: Art and Science.

BACKGROUND: People have long been fascinated with the size and growth of living things, from the giants of classic mythology and art to the little people who also have appeared in classical art, as well as the courts of European monarchs, and were exploited in "shows." Serious medical evaluation began in the late 19th century with the description of acromegaly and its association with pituitary tumors. In the early 20th century, multiple investigators attempted to extract a growth-promoting factor from the anterior pituitary and then, over the decades, to purify it and distinguish it from other anterior pituitary hormones. With relatively pure growth hormone (GH), its biological activity in growth promotion and as a metabolic hormone were studied, and species specificity became apparent: primate GH was the only GH active in man. Human GH was prepared from cadaveric pituitaries and distributed by the NIH to treat children with GH deficiency, but there was never enough pituitary hGH for all of the children who required it. When Creutzfeldt-Jakob disease was found in some patients who received pituitary GH, the production and FDA approval of biosynthetic hGH dramatically accelerated. With a large supply, one could treat those who were GH deficient and test its efficacy in other causes of short stature; longer acting versions of hGH have now been developed, tested, and in a few instances received FDA approval. SUMMARY: It has been a long journey from the description of over- and underproduction of GH in animals to the production and clinical use of the biosynthetic hormones. KEY MESSAGES: The efforts of basic scientists led to the extraction and purification of GH. Clinical scientists have expanded the appropriate use of hGH for short children with conditions in addition to GH deficiency.

Real-World Experience of Monitoring Practice of Endocrinopathies Associated with the Use of Novel Targeted Therapies among Patients with Solid Tumors.

BACKGROUND: Cancer treatments have gradually evolved into targeted molecular therapies characterized by a unique mechanism of action instead of non-specific cytotoxic chemotherapies. However, they have unique safety concerns. For instance, endocrinopathies, which are defined as unfavorable metabolic alterations including thyroid disorders, hyperglycemia, dyslipidemia, and adrenal insufficiency necessitate additional monitoring. The aim of this study was to assess the prevalence of monitoring errors and develop strategies for monitoring cancer patients who receive targeted therapies. METHOD: A retrospective chart review was used to assess the prevalence of monitoring errors of endocrinopathies among cancer patients who received targeted therapies over one year. All of the adult cancer patients diagnosed with a solid tumor who received targeted therapies were included. The primary outcome was to determine the prevalence of monitoring errors of endocrinopathies. The secondary outcomes were to assess the incidences of endocrinopathies and referral practice to endocrinology services. RESULTS: A total of 128 adult patients with solid tumors were involved. The primary outcome revealed a total of 148 monitoring errors of endocrinopathies. Monitoring errors of the lipid profile and thyroid functions were the most common error types in 94% and 92.6% of the patients treated with novel targeted therapies, respectively. Subsequently, 57% of the monitoring errors in the blood glucose measures were identified. Targeted therapies caused 63 events of endocrinopathies, hyperglycemia in 32% of the patients, thyroid disorders in 15.6% of them and dyslipidemia in 1.5% of the patients. CONCLUSION: Our study showed a high prevalence of monitoring errors among the cancer patients who received targeted therapies which led to endocrinopathies. It emphasizes the importance of adhering to monitoring strategies and following up on the appropriate referral process.

Combined Therapy with Ixazomib, Lenalidomide, and Dexamethasone for Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal Gammopathy, and Skin Changes Syndrome.

Objective Immunomodulatory drugs and proteasome inhibitors are therapeutic options for polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. This study aimed to evaluate the efficacy and safety of the combination of ixazomib, lenalidomide, and dexamethasone (IRd) for POEMS syndrome. Methods Six consecutive patients with POEMS syndrome who were treated with the IRd regimen at Chiba University Hospital between April 2018 and August 2021 were included. Serum M-protein and serum vascular endothelial growth factor (sVEGF) levels, overall neuropathy limitation scales (ONLS), clinical symptoms, and adverse events were assessed. Results Of the six patients, five had received prior treatments. Patients received a median of 5 cycles (range, 3-28 cycles) of IRd. Following treatment, serum M-protein disappeared in two patients, sVEGF levels returned to normal in two patients, two patients showed a reduction in the ONLS of 1, and clinical symptoms improved in four patients. The median level of sVEGF decreased from 2,395 pg/mL (range, 802-6,120 pg/mL) to 1,428 pg/mL (range, 183-3,680 pg/mL) in three months. Adverse events, including rash, neutropenia, sensory peripheral neuropathy, and nausea, were observed in three patients, which necessitated dose reduction or discontinuation of treatment. Conclusion IRd can be a therapeutic option for POEMS syndrome, albeit with careful monitoring of adverse events.

Endocrine-related adverse conditions in patients receiving immune checkpoint inhibition: an ESE clinical practice guideline.

Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment but are associated with significant autoimmune endocrinopathies that pose both diagnostic and treatment challenges. The aim of this guideline is to provide clinicians with the best possible evidence-based recommendations for treatment and follow-up of patients with ICI-induced endocrine side-effects based on the Grading of Recommendations Assessment, Development, and Evaluation system. As these drugs have been used for a relatively short time, large systematic investigations are scarce. A systematic approach to diagnosis, treatment, and follow-up is needed, including baseline tests of endocrine function before each treatment cycle. We conclude that there is no clear evidence for the benefit of high-dose glucocorticoids to treat endocrine toxicities with the possible exceptions of severe thyroid eye disease and hypophysitis affecting the visual apparatus. With the exception of thyroiditis, most endocrine dysfunctions appear to be permanent regardless of ICI discontinuation. Thus, the development of endocrinopathies does not dictate a need to stop ICI treatment.

[Endocrinopathies Associated with Immune Checkpoint Inhibitors]. / Endocrinopatias Associadas ao Tratamento com Inibidores do Checkpoint Imunológico.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that increase the efficiency of the immune system in the destruction of neoplastic cells. In recent years, these drugs have been increasingly used in the treatment of many neoplasms in advanced stages. However, the change in the regulation of the immune system induced by these drugs has the potential adverse effect of inducing autoimmunity in practically all organ systems. Endocrinopathies are one of the most common autoimmune adverse eventsof these drugs. MATERIAL AND METHODS: Non-systematic review of endocrinopathies reported in the context of treatment with ICIs. A search was carried out on PubMed until January 31st, 2020, and articles were selected based on their relevance and excluded in case of redundant content. The following search terms were used: "immune checkpoint inhibitor" and "endocrinopathy" / "endocrine system diseases" / "pituitary" / "thyroid" / "diabetes" / "adrenal" / "parathyroid". RESULTS: Endocrinopathies with all classes of ICIs (anti-CTLA-4, anti-PD-1, anti-PD-L1) have been reported. Thyroid dysfunction is the most frequently reported endocrinopathy, mainly with anti-PD-1 and anti-PD-L1. Hypophysitis is the most prevalent with anti-CTLA-4. The incidence of autoimmune diabetes in this context is increasing, mainly with anti-PD-1 and anti-PD-L1. Rare cases of primary adrenal insufficiency, Graves' disease and primary hypoparathyroidism have also been reported. CONCLUSION: Knowing the spectrum of endocrinopathies triggered by ICI, as well as their clinical features, diagnosis and treatment criteria is essential, given its high prevalence and the increasing number of cancer patients treated with these new drugs.

Introdução: Os inibidores do checkpoint imunológico (ICI) são anticorpos monoclonais que permitem aumentar a eficiência do sistema imunitário na destruição das células neoplásicas. Nos últimos anos, estes fármacos têm sido cada vez mais utilizados no tratamento de muitas neoplasias em estadios avançados. Contudo, a alteração da regulação do sistema imunitário induzida por estes fármacos tem como potencial efeito adverso o aparecimento de autoimunidade em praticamente todos os órgãos. As endocrinopatias são um dos eventos adversos autoimunes mais frequentes com estes fármacos.Material e Métodos: Revisão não sistemática sobre as endocrinopatias reportadas em contexto de tratamento com ICI. Foram pesquisados artigos publicados na PubMed até 31 de janeiro de 2020, selecionados com base na sua relevância e excluídos em caso de conteúdo redundante. Foram utilizados os seguintes termos de pesquisa: "immune checkpoint inhibitor" e "endocrinopathy" / "endocrine system diseases" / "pituitary" / "thyroid" / "diabetes" / "adrenal" / "parathyroid".Resultados: Foram já reportadas endocrinopatias com todas as classes de ICI (anti-CTLA-4, anti-PD-1, anti-PD-L1). A disfunção tiroideia é a endocrinopatia mais frequentemente reportada, principalmente sob anti-PD-1 e anti-PD-L1. A hipofisite é a mais prevalente sob anti-CTLA-4. É crescente a incidência de diabetes autoimune neste contexto, principalmente sob anti-PD-1 e anti-PD-L1. Foram reportados também casos raros de insuficiência suprarrenal primária, doença de Graves e hipoparatiroidismo primário.Conclusão: O conhecimento do espectro de endocrinopatias desencadeadas pela terapêutica com ICI, assim como as suas manifestações clínicas, critérios de diagnóstico e tratamento, é essencial, dada a sua elevada prevalência e o cada vez maior número de doentes oncológicos tratados com estes novos fármacos.

MANAGEMENT OF ENDOCRINE DISEASE: Papillary thyroid microcarcinoma: toward an active surveillance strategy.

In the last decades, the incidence of thyroid cancer (TC) has more than doubled, but the disease-specific mortality rate was stable. To date, 30-40% of all TC is represented by papillary microcarcinomas (mPTC), an indolent tumor, that probably remained undiagnosed before routine ultrasound use. In 1993, Miyauchi was the first who hypothesized a conservative approach for low-risk mPTC and introduced the concept of active surveillance (AS) in its clinical management. The progression rate of mPTC during AS was low and delaying surgery did not impact the efficacy of treatment or outcome. Since then, several authors from all over the world have reported their experience of AS in mPTCs. As suggested by current guidelines, AS can be considered as an alternative to immediate surgery to avoid overtreatment in low-risk mPTC and may be the strategy to avoid complications from unnecessary surgery. In the last years, AS inclusion criteria have been extended to both bigger tumors and to younger/healthier patients. The adoption of AS should take into consideration not only tumor characteristics but also patient psychological profiles and medical team expertise. Its safety and efficacy have been demonstrated in long-term outcome studies and in other types of tumors; however, skepticism in patients, families and physicians should be overcome by strong recommendations coming from scientific guidelines. This review analyses the several and different experiences of AS and the potential obstacles in implementing it as a routine approach in mPTC patients.

Diagnosis and management of secondary causes of steatohepatitis.

The term non-alcoholic fatty liver disease (NAFLD) was originally coined to describe hepatic fat deposition as part of the metabolic syndrome. However, a variety of rare hereditary liver and metabolic diseases, intestinal diseases, endocrine disorders and drugs may underlie, mimic, or aggravate NAFLD. In contrast to primary NAFLD, therapeutic interventions are available for many secondary causes of NAFLD. Accordingly, secondary causes of fatty liver disease should be considered during the diagnostic workup of patients with fatty liver disease, and treatment of the underlying disease should be started to halt disease progression. Common genetic variants in several genes involved in lipid handling and metabolism modulate the risk of progression from steatosis to fibrosis, cirrhosis and hepatocellular carcinoma development in NAFLD, alcohol-related liver disease and viral hepatitis. Hence, we speculate that genotyping of common risk variants for liver disease progression may be equally useful to gauge the likelihood of developing advanced liver disease in patients with secondary fatty liver disease.

The side effects of immune checkpoint inhibitor therapy on the endocrine system.

Immune checkpoint inhibitors (ICIs) are a relatively newer class of drugs approved for the treatment of malignancies such as melanoma, renal, bladder and lung cancer. Immune-related adverse events (IrAEs) involving the endocrine system are a common side effect of these drugs. The spectrum of endocrine adverse events varies by the drug class. Cytotoxic T-lymphocyte-associated antigen-4 inhibitors commonly cause hypophysitis/hypopituitarism, whereas the incidence of thyroid disease is higher with programmed cell death (PD)-1/ ligand (PD-L) protein 1 inhibitors. The focus of this review is to describe the individual endocrinopathies with their possible mechanisms, signs and symptoms, clinical assessment and disease management. Multiple mechanisms of IrAEs have been described in literature including type II/IV hypersensitivity reactions and development of autoantibodies. Patients with pre-existing autoimmune endocrine diseases can have disease exacerbation following ICI therapy rather than de novo IrAEs. Most of the endocrinopathies are relatively mild, and timely hormone replacement therapy allows continuation of ICIs. However, involvement of the pituitary-adrenal axis could be life-threatening if not recognized. Corticosteroids are helpful when the pituitary-adrenal axis is involved. In cases of severe endocrine toxicity (grade 3/4), ICIs should be temporarily discontinued and can be restarted after adequate hormonal therapy. Endocrinologists and general internists need to be vigilant and maintain a high degree of awareness for these adverse events.

DIAGNOSIS OF ENDOCRINE DISEASE: Sex steroid action in adolescence: too much, too little; too early, too late.

ABSTRACT: This review aims to cover the subject of sex steroid action in adolescence. It will include situations with too little sex steroid action, as seen in for example, Turners syndrome and androgen insensitivity issues, too much sex steroid action as seen in adolescent PCOS, CAH and gynecomastia, too late sex steroid action as seen in constitutional delay of growth and puberty and too early sex steroid action as seen in precocious puberty. This review will cover the etiology, the signs and symptoms which the clinician should be attentive to, important differential diagnoses to know and be able to distinguish, long-term health and social consequences of these hormonal disorders and the course of action with regards to medical treatment in the pediatric endocrinological department and for the general practitioner. This review also covers situations with exogenous sex steroid application for therapeutic purposes in the adolescent and young adult. This includes gender-affirming therapy in the transgender child and hormone treatment of tall statured children. It gives some background information of the cause of treatment, the patient's motivation for medicating (or self-medicating), long-term consequences of exogenous sex steroid treatment and clinical outcome of this treatment.

Management of endocrine conditions at the end of life.

An important facet to end-of-life care is deprescribing. This can be challenging when reviewing life-sustaining endocrine medications but, unlike for diabetes, there is no national guidance to support patients and clinicians faced with care planning. This article reviews the limited current evidence to highlight areas for further discussion and research with the aim of moving towards consensus opinion. Discontinuation of certain endocrine medications, including corticosteroids, desmopressin and levothyroxine, is likely to precipitate an 'endocrine-driven mechanism of death', while it may be reasonable to discontinue other endocrine medications without the risk of hastening death or causing unnecessary symptoms. However, the over-arching theme should be that early discussion with patients regarding conversion or discontinuation of endocrine medications or monitoring is central to care planning.

Health Outcomes Among Long-term Opioid Users With Testosterone Prescription in the Veterans Health Administration.

Importance: Androgen deficiency is common among male opioid users, and opioid use has emerged as a common antecedent of testosterone treatment. The long-term health outcomes associated with testosterone therapy remain unknown, however. Objective: To compare health outcomes between long-term opioid users with testosterone deficiency who filled testosterone prescriptions and those with the same condition but who did not receive testosterone treatment. Design, Setting, and Participants: This cohort study focused on men in the care of the Veterans Health Administration (VHA) facilities throughout the United States from October 1, 2008, to September 30, 2014. It included male veterans who were long-term opioid users, had low testosterone levels (<300 ng/dL), and received either a testosterone prescription or any other prescription. It excluded male patients with HIV infection, gender dysphoria, or prostate cancer and those who received testosterone in fiscal year 2008. Data were analyzed from April 1, 2017, to April 30, 2019. Exposure: Prescription for testosterone. Main Outcomes and Measures: All-cause mortality and incidence of major adverse cardiovascular events (MACE), vertebral or femoral fractures, and anemia during the 6-year follow-up through September 30, 2015. Results: After exclusions, 21 272 long-term opioid users (mean [SD] age, 53 [10] years; n = 16 689 [78.5%] white) with low total or free testosterone levels were included for analysis, of whom 14 121 (66.4%) received testosterone and 7151 (33.6%) did not. At baseline, compared with opioid users who did not receive testosterone, long-term opioid users who received testosterone treatment were more likely to have obesity (43.7% vs 49.0%; P < .001), hyperlipidemia (43.0% vs 48.8%; P < .001), and hypertension (53.9% vs 55.2%; P = .07) but had lower prevalence of coronary artery disease (15.9% vs 12.9%; P < .001) and stroke (2.4% vs 1.3%; P < .001). After adjusting for covariates, opioid users who received testosterone had significantly lower all-cause mortality (hazard ratio [HR] = 0.51; 95% CI, 0.42-0.61) and lower incidence of MACE (HR = 0.58; 95% CI, 0.51-0.67), femoral or hip fractures (HR = 0.68; 95% CI, 0.48-0.96), and anemia (HR = 0.73; 95% CI, 0.68-0.79) during the follow-up period of up to 6 years, compared with their counterparts without a testosterone prescription. In covariate-adjusted models, men who received opioids plus testosterone were more likely to have resolved anemia compared with those who received opioids only during the 6-year follow-up (HR = 1.16; 95% CI, 1.02-1.31). Similar results were obtained in propensity score-matched models and when analyses were restricted to opioid users with noncancer pain or those who did not receive glucocorticoids. Conclusions and Relevance: This study found that, in the VHA system, male long-term opioid users with testosterone deficiency who were treated with opioid and testosterone medications had significantly lower all-cause mortality and significantly lower incidence of MACE, femoral or hip fractures, and anemia after a multiyear follow-up. These results warrant confirmation through a randomized clinical trial to ascertain the efficacy of testosterone in improving health outcomes for opioid users with androgen deficiency.

Therapeutic Targeting of the IGF Axis.

The insulin like growth factor (IGF) axis plays a fundamental role in normal growth and development, and when deregulated makes an important contribution to disease. Here, we review the functions mediated by ligand-induced IGF axis activation, and discuss the evidence for the involvement of IGF signaling in the pathogenesis of cancer, endocrine disorders including acromegaly, diabetes and thyroid eye disease, skin diseases such as acne and psoriasis, and the frailty that accompanies aging. We discuss the use of IGF axis inhibitors, focusing on the different approaches that have been taken to develop effective and tolerable ways to block this important signaling pathway. We outline the advantages and disadvantages of each approach, and discuss progress in evaluating these agents, including factors that contributed to the failure of many of these novel therapeutics in early phase cancer trials. Finally, we summarize grounds for cautious optimism for ongoing and future studies of IGF blockade in cancer and non-malignant disorders including thyroid eye disease and aging.

Guideline of guidelines: testosterone therapy for testosterone deficiency.

We analysed the guidelines for testosterone therapy (TTh) produced by major international medical societies including: the American Urological Association, European Association of Urology, American Association of Clinical Endocrinologists, British Society for Sexual Medicine, Endocrine Society, International Society for Sexual Medicine, and the International Society for the Study of the Aging Male, and compared their recommendations. All the organisations were in general agreement concerning the following key points: Only men meeting the criteria for testosterone deficiency (TD) should be treated. Consider screening asymptomatic men with certain conditions that increase the risk of TD. Exogenous TTh causes impairment of spermatogenesis. There is no evidence that TTh causes prostate cancer. Men on TTh require careful laboratory monitoring.

The Hydrocarbon Staple & Beyond: Recent Advances Towards Stapled Peptide Therapeutics that Target Protein-Protein Interactions.

Anomalous protein-protein interactions (PPIs) have been correlated to a variety of disease states, such as cancer, infectious disease, neurological disorders, diabetes, endocrine disorders and cardiovascular disease. Stapled peptides are an emerging intervention for these PPIs due to their improved structural rigidity and pharmacokinetic properties relative to unstapled peptides. This review details the most recent advances in the field of stapled peptide therapeutics, including the increasing variety of PPIs being targeted and types of peptide staples being employed.

Iron Chelation Therapy as a Modality of Management.

Introduction of MRI techniques for identifying and monitoring tissue iron overload and the current understanding of iron homeostasis in transfusion-dependent (TDT) and non-transfusion-dependent thalassemia have allowed for a more robust administration of iron chelation therapies. The development of safe and efficient oral iron chelators and the insights gained from large-scale prospective studies using these agents have improved iron overload management. A significant reduction in iron toxicity-induced morbidity and mortality and improvements in quality of life were observed in TDT. The appropriate management of tissue-specific iron loading in TDT has been portrayed using evidence-based data obtained from investigational studies.

Endocrinopathies with use of cancer immunotherapies.

BACKGROUND: Immunomodulatory therapies, including CTLA-4 and PD-1 inhibitors, provide a directed attack against cancer cells by preventing T cell deactivation. However, these drugs also prevent the downregulation of auto-reactive T cells, resulting in immune-related adverse events (IRAEs). Reports show a varied incidence of endocrine IRAEs, ranging from 0% to 63%. OBJECTIVE: To describe the frequency and clinical characteristics of endocrine IRAEs in patients taking cancer immunomodulatory therapies. DESIGN: Retrospective cohort study. PATIENTS: A total of 388 patients aged ≥18 years who were prescribed ipilimumab, nivolumab and/or pembrolizumab between 2009 and 2016 at our institution. MEASUREMENTS: Biochemical criteria were used to define endocrine IRAEs, including thyroid, pituitary, pancreas and adrenal dysfunction, following use of immunomodulatory therapies. RESULTS: Fifty endocrine IRAEs occurred in our cohort, corresponding to a rate of 12.9%. The most common endocrine IRAEs were thyroid dysfunction (11.1%), with a lower incidence of pituitary dysfunction (1.8% of patients). CONCLUSIONS: Over 12% of patients receiving ipilimumab, nivolumab and/or pembrolizumab in our study sample developed an endocrine IRAE. Patients who undergo treatment with immunomodulatory therapies should be monitored for the development of endocrine IRAEs.