Revisitation of autoimmune hypophysitis: knowledge and uncertainties on pathophysiological and clinical aspects

Bellastella, Giuseppe; Maiorino, Maria Ida; Bizzarro, Antonio; Giugliano, Dario; Esposito, Katherine; Bellastella, Antonio; Bellis, Annamaria De

doi:10.1007/s11102-016-0736-z

Cited by 107 publications

(100 citation statements)

References 141 publications

(278 reference statements)

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“…As IgG4 cannot activate the complement pathway and is less effective for antibody-dependent cell-mediated cytotoxicity, the pathogenesis of the few anti-PD-1 or PD-L1-induced cases of hypophysitis is not clear. PD-1 could be expressed in pituitary cells or lymphocytes, as PD-L1 is expressed in pituitary adenomas (37) or as these antibodies are IgG4, they should share the same mechanism as IgG4-related hypophysitis (38).…”

Section: What Do We Know About the Mechanism Of Ici-induced Hypophysimentioning

confidence: 99%

MANAGEMENT OF ENDOCRINE DISEASE: Immune check point inhibitors-induced hypophysitis

Albarel

Castinetti

Brue

2019

European Journal of Endocrinology

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In recent years, the development of immunotherapy has constituted a revolution in the therapy for many cancers, with a specific toxicity profile including endocrine immune-related adverse events. Immune check point inhibitors (ICI)-induced hypophysitis is a common endocrine side effect, particularly with CTLA-4 antibodies and combination therapy, with frequent hormonal deficiencies at diagnosis. It can be difficult to evoke such diagnosis as the initial clinical symptoms are not specific (headache, asthenia…); thus, patients receiving such immunomodulatory therapies should be closely monitored by systematic hormone measurements, especially in the first weeks of treatment. Usually, hormonal deficiencies improve, except for corticotroph function. Despite a lack of large prospective studies on ICI-induced hypophysitis, some detailed longitudinal cohort studies have focused on such cases of hypophysitis and allow for optimal monitoring, follow-up and management of patients with this immune-related adverse event. In the case of ICI-induced hypophysitis, patients need long-term multidisciplinary follow-up, with specific education for those patients with corticotropin deficiency to allow them to be autonomous with their treatment. In this review, based on a clinical case, we detail the most relevant and novel aspects related to the incidence, diagnosis, treatment, evolution and management of hypophysitis induced by immunotherapy, with a focus on possible mechanisms and current recommendations and guidelines. Lastly, we emphasize several key points, such as the absence of indication to systematically treat with high-dose glucocorticoid and the pursuit of immunotherapy in such hypophysitis. These points should be kept in mind by oncologists and endocrinologists who treat and monitor patients treated by immunotherapy.

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Section: What Do We Know About the Mechanism Of Ici-induced Hypophysimentioning

confidence: 99%

MANAGEMENT OF ENDOCRINE DISEASE: Immune check point inhibitors-induced hypophysitis

Albarel

Castinetti

Brue

2019

European Journal of Endocrinology

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“…Hypophysitis secondary to IgG4-RD is one of the most recently described forms of hypophysitis and is defined by an inflammatory process of the pituitary gland that can involve contiguous structures [78]. As with AIP, patients with IgG4-related hypophysitis tend to be middle-aged and older men [14, 71, 79–81].…”

Section: Neurological Manifestations Of Igg4-rdmentioning

confidence: 99%

Neurological Manifestations of IgG4-Related Disease

Baptista

Casian

Gunawardena

et al. 2017

Curr Treat Options Neurol

106

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Opinion statementIgG4-related disease (IgG4-RD) is a multisystem inflammatory disorder. Early recognition of IgG4-RD is important to avoid permanent organ dysfunction and disability. Neurological involvement by IgG4-RD is relatively uncommon, but well recognised—hypertrophic pachymeningitis and hypophysitis are the most frequent manifestations. Although the nervous system may be involved in isolation, this more frequently occurs in conjunction with involvement of other systems. Elevated circulating levels of IgG4 are suggestive of the condition, but these are not pathognomonic and exclusion of other inflammatory disorders including vasculitis is required. Wherever possible, a tissue diagnosis should be established. The characteristic histopathological changes include a lymphoplasmacytoid infiltrate, storiform fibrosis and obliterative phlebitis. IgG4-RD typically responds well to treatment with glucocorticoids, although relapse is relatively common and treatment with a steroid-sparing agent or rituximab may be required. Improved understanding of the pathogenesis of IgG4-RD is likely to lead to the development of more specific disease treatments in the future.

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“…Magnetic resonance remains the gold standard for imaging. The homogenous enhancement of the pituitary gland, thickening of a non-deviated stalk, and a missing posterior lobe signal in a T1 modality are the most characteristic radiological changes [3]. Hormonal substitution is the cornerstone of therapy.…”

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confidence: 99%

Radiological and hormonal improvements in a 22-year-old patient with lymphocytic hypophysitis — the watchful waiting approach

Gilis‐Januszewska

Rogoziński

Hubalewska‐Dydejczyk

2020

Endokrynologia Polska

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Hypophysitis is a rare condition describing inflammation of the pituitary gland. The disorder may be primary, involving the pituitary gland itself, or secondary, due to other diseases or drugs. The incidence of primary hypophysitis is one case per 9 million [1]; however, new forms of the condition are increasingly diagnosed and the actual occurrence appears to be higher. Symptoms are connected with the presence of a pathological mass in the pituitary area and hormonal abnormalities. The diagnosis is based on clinical presentation, laboratory tests, and imaging. Deficiency of ACTH is found in 60% of cases, followed by deficits of LH/FSH in 52%, TSH in 52%, ADH in 39%, GH in 38%, and a high PRL level in 37% of cases [2]. Magnetic resonance remains the gold standard for imaging. The homogenous enhancement of the pituitary gland, thickening of a non-deviated stalk, and a missing posterior lobe signal in a T1 modality are the most characteristic radiological changes [3]. Hormonal substitution is the cornerstone of therapy. In cases with severe neurological symptoms, high-dose steroids or other immunosuppressant drugs are used. Surgery and radiotherapy are options for patients with significant consequences of mass-effect and those resistant to pharmacological treatment. Hypophysitis often leads to atrophy of the pituitary gland. More than 70% of patients require long-term hormonal substitution [4].A 22-year-old patient without a significant past medical history was admitted to a regional hospital with a four-month history of excessive thirst and frequent urination. The occurrence of polydipsia and polyuria was associated with respiratory tract infection. The patient's hobbies included amateur kickboxing, but he denied any head trauma. Based on a water deprivation test, diabetes insipidus was diagnosed, with substantial improvement in symptom control after administration of desmopressin. MR of the pituitary area revealed a thickened non-deviated stalk of 4.5 mm and a missing posterior pituitary lobe signal. During several hospitalisations in the Endocrinology Department, gonadal and somatotropic axis insufficiencies as well as mild hyperprolactinaemia were discovered. Adequate control of diabetes insipidus was confirmed. Thyroid and adrenal gland function were unaffected. To exclude secondary causes of the observed symptoms, multiple imaging and biochemical studies were performed with unremarkable findings. The patient was diagnosed with lymphocytic hypophysitis. In a control MR the pituitary stalk was enlarged to 5 × 5 × 5 mm and the pituitary lobes did not show any deviations. Due to the lack of severe neurological symptoms, treatment was continued with desmopressin only. During a follow-up assessment, the stalk size normalised to 2.5 × 3 × 3 mm on MR (Fig. 1). Prolactin and testosterone values were within normal limits. Unfortunately, the diabetes insipidus was persistent, and only a transient improvement in IGF-1 levels was observed (Tab. 1).This case report shows that diabetes insipidus may be the first manifestati...

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Revisitation of autoimmune hypophysitis: knowledge and uncertainties on pathophysiological and clinical aspects

Cited by 107 publications

References 141 publications

MANAGEMENT OF ENDOCRINE DISEASE: Immune check point inhibitors-induced hypophysitis

MANAGEMENT OF ENDOCRINE DISEASE: Immune check point inhibitors-induced hypophysitis

Neurological Manifestations of IgG4-Related Disease

Radiological and hormonal improvements in a 22-year-old patient with lymphocytic hypophysitis — the watchful waiting approach

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