New Molecular, Biological, and Immunological Agents Inducing Hypophysitis

Angelousi, Anna; Chatzellis, Eleftherios; Kaltsas, Gregory

doi:10.1159/000480086

Cited by 18 publications

(24 citation statements)

References 84 publications

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“…Recent studies in mouse and human pituitary glands have revealed that anti-CTLA-4 hypophysitis is characterized by the presence of circulating anti-pituitary antibodies and lymphocytic infiltration of the gland [43]. Ectopic expression of CTLA-4 has also been observed in the normal hypophysis in mice, particularly in prolactin- and TSH-secreting cells [43], as well as in hypophysitis and adenomas of the human pituitary gland [17, 44] (Fig. 3).…”

Section: Resultsmentioning

confidence: 99%

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Hypophysitis (Including IgG4 and Immunotherapy)

et al. 2020

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Hypophysitis is characterized by inflammation of the pituitary gland that can be primary (PH) or secondary (SH) to other diseases or following drug administration. It may also be classified according to anatomical and histopathological criteria, leading to variable degrees of hypopituitarism and/or compressive symptoms to nearby structures. There has recently been an increase in the number of hypophysitis cases, raising the interest on the spectrum of its pathogenesis, clinical, biochemical/endocrinological, and imaging features. However, the use of conventional biomarkers, including currently utilized pituitary autoantibodies, has relatively limited diagnostic accuracy. Lymphocytic hypophysitis (LH) is the commonest cause of PH, whereas IgG4-related hypophysitis is increasingly being recognized. Histiocytosis and granulomatous diseases are the most frequent causes of SH, although infections and lymphoma have also been reported. The increasing use of immune checkpoint inhibitors in oncology is associated with a high incidence of hypophysitis, providing further understanding of its pathogenesis. Hy-pophysitis can occur silently and be easily missed, potentially leading to substantial morbidity or mortality due to adrenal insufficiency, requiring a high index of clinical suspicion and timely initiation of appropriate treatment. In most cases of LH or drug-induced hypophysitis, active surveillance along with replacement of established hormonal deficiencies is needed. In the presence of compressive and/or evolving symptoms, treatment with glucocorticoids either alone or in combination with other immunosuppressive agents can be used. Surgical decompression is reserved for nonresponsive cases with threatened vital structures. Timely diagnosis and intervention are important to minimize disease-related morbidity and mortality. We aimed to review current concepts and recent developments in the pathogenesis, diagnosis, and management of hypophysitis.

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Section: Resultsmentioning

confidence: 99%

“…b A monoclonal antibody against PD-1 can block this pathway and result in upregulation of immune response and inhibition of tumor growth. Figure reproduced with permission of S. Karger AG, Basel from the original source [44].…”

Section: Resultsmentioning

confidence: 99%

Hypophysitis (Including IgG4 and Immunotherapy)

et al. 2020

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“…17,18 Other factors affecting the reported incidence of ipilimumab-induced hypophysitis are the lack of a precise and consistent definition of hypophysitis in different studies and the duration of follow-up that ranged from few months up to several years (Table 1). 16,20 Compared to patients who receive ipilimumab, those who receive treatment with anti-PD-1 or anti-PD-L1 agents are significantly less likely to develop hypophysitis. In a metaanalysis of 34 studies, it has been reported that the incidence of hypophysitis was 0.4% with anti-PD-1 and <0.1% with anti-PD-L1 therapy.…”

Section: Prevalence and Epidemiology Of Ipilimumab-induced Hypophysitismentioning

confidence: 99%

“…Recent in vitro and in vivo studies have suggested that immune and genetic factors are implicated and a combination of inflammatory and immune mechanisms result to tissue damage. 16,36,37 CTLA-4 acts as a negative regulator of the B7 and CD28 co-stimulation axis. In an immune response, activated T-cells upregulate the expression and the translocation of CTLA-4 in the plasma membrane.…”

Section: Pathophysiologymentioning

confidence: 99%

<p>Managing Ipilimumab-Induced Hypophysitis: Challenges and Current Therapeutic Strategies</p>

Tsoli¹,

Kaltsas²,

Angelousi³

et al. 2020

CMAR

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Over the past years, progress has been made in cancer immunotherapy following the development of immune checkpoint inhibitors (ICI) that have been proved effective in the management of many malignancies. Ipilimumab, a monoclonal antibody against cytotoxic T-lymphocyte antigen-4 (CTLA-4), has been approved for the treatment of advanced melanoma but has been associated with the development of several endocrine immunerelated adverse events (irAEs). Hypophysitis is the most common endocrine irAE related to ipilimumab with a reported incidence ranging from 1.8% to 17%. The mechanism underlying ipilimumab-induced hypophysitis implicates immune, inflammatory and genetic factors, but there are still some points that are not well understood and remain to be elucidated. The diagnosis is based mainly on clinical, biochemical and imaging data. The majority of patients display multiple hormone deficiencies that may recover or persist for a prolonged period of time with corticotroph deficiency usually being permanent. Immune-related hypopituitarism is treated with replacement of deficient hormones while in severe forms of hypophysitis treatment with high-dose glucocorticoids may be required. Proper evaluation and registration of patients in clinical trials and further investigation are needed to precisely clarify the pathophysiology of the ICI-related hypophysitis, define predictive factors and ameliorate the management and outcome of the disease.

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“…As for the underlying pathophysiology of ICP inhibitor-induced hypophysitis, it has been postulated that pituitary immunogenicity is mediated by CTLA-4 antigen expression by pituitary endocrine cells. This leads to complement activation and infiltration of macrophages (type II hypersensitivity reaction) and autoreactive T lymphocytes (type IV hypersensitivity reaction) (28,29,30,31). The susceptibility of pituitary cells to ICP inhibitors has been recently nicely demonstrated in a patient with pituitary carcinoma resistant to all available treatments including temozolomide but responding robustly to combination ICP inhibitor therapy (32).…”

Section: Autoimmune Hypophysitis Related To Immune Checkpoint (Icp) Imentioning

confidence: 99%

DIAGNOSIS OF ENDOCRINE DISEASE: Drug-induced endocrinopathies and diabetes: a combo-endocrinology overview

Diamanti-Kandarakis

Duntas

Kanakis

et al. 2019

European Journal of Endocrinology

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In the currently overwhelming era of polypharmacy, the balance of the dynamic and delicate endocrine system can easily be disturbed by interfering pharmaceutical agents like medications. Drugs can cause endocrine abnormalities via different mechanisms, including direct alteration of hormone production, changes in the regulation of the feedback axis, on hormonal transport, binding and signaling, as well as similar changes to counter-regulatory hormone systems. Furthermore, drugs can interfere with the hormonal assays, leading to erroneous laboratory results that disorientate clinicians from the right diagnosis. The purpose of this review is to cover a contemporary topic, the drug-induced endocrinopathies, which was presented in the monothematic annual Combo Endo Course 2018. This challenging part of endocrinology is constantly expanding particularly during the last decade, with the new oncological therapeutic agents, targeting novel molecular pathways in the process of malignancies. In this new context of drug-induced endocrine disease, clinicians should be aware that drugs can cause endocrine abnormalities via different mechanisms and mimic a variety of clinical scenarios. Therefore, it is extremely important for clinicians not only to promptly recognize drug-induced hormonal and metabolic abnormalities, but also to address the therapeutic issues for timely intervention.

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New Molecular, Biological, and Immunological Agents Inducing Hypophysitis

Cited by 18 publications

References 84 publications

Hypophysitis (Including IgG4 and Immunotherapy)

Hypophysitis (Including IgG4 and Immunotherapy)

<p>Managing Ipilimumab-Induced Hypophysitis: Challenges and Current Therapeutic Strategies</p>

DIAGNOSIS OF ENDOCRINE DISEASE: Drug-induced endocrinopathies and diabetes: a combo-endocrinology overview

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