Hypophysitis Secondary to Cytotoxic T-Lymphocyte–Associated Protein 4 Blockade

Caturegli, Patrizio; Dalmazi, Giulia Di; Lombardi, Martina; Grosso, Federica; Larman, H. Benjamin; Larman, Tatianna; Taverna, G; Cosottini, Mirco; Lupi, Isabella

doi:10.1016/j.ajpath.2016.08.020

Cited by 330 publications

(318 citation statements)

References 33 publications

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“…Higher expression of CTLA-4 in the pituitary gland was reported to be related to hypophysitis, due to type II or type IV allergy by IgG1 or IgG2 type anti-CTLA-4 antibodies [18] . Yamauchi, et al reported that PD-L1 and PD-L2 expressions on thyroid gland might be related to nivolumab-induced thyroiditis [52] .…”

Section: Other Possible Mechanisms In Endocrine Iraesmentioning

confidence: 99%

“…Most of hypophysitis related to irAE is induced by anti-CTLA-4 antibody, and anti-PD-1 antibodyinduced hypophysitis is less common (<1.0%) [4,18] . Hypophysitis related to irAE occurs more often in men than women [15,16] .…”

Section: Hypophysitis Related To Iraementioning

confidence: 99%

“…In order to precisely diagnose, pituitary provocation tests is often recommended. ACTH insufficiency is usually permanent, on the other [18,19] . As predictive factors for hypophysitis related to irAE, eosinophilia, elevation of ESR/CRP/ LDH, and hyponatremia can be useful [9] .…”

Section: Hypophysitis Related To Iraementioning

confidence: 99%

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Endocrine dysfunctions during treatment of immune-checkpoint inhibitors

et al. 2018

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Immune-checkpoint inhibitors (ICIs) are novel agents directed to various malignant tumors. During ICI therapy, however, immune related adverse effects (irAEs) including endocrine dysfunctions have been reported. Dysfunctions in the pituitary gland and the thyroid gland by ICI are often observed, and those in the adrenal glands and the pancreas are less frequent. Positive correlation of the prevalence of endocrine irAEs to clinical antitumor effectiveness during ICI therapy has been reported. The mechanisms of endocrine irAEs by ICI, however, remain unclear, and optimal prevention, prediction, and treatment of the irAEs are still uncertain. This review describes possible mechanisms involved in ICI-related immunity, and discusses clinical management of endocrine irAEs during ICI therapy.

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Section: Other Possible Mechanisms In Endocrine Iraesmentioning

confidence: 99%

Section: Hypophysitis Related To Iraementioning

confidence: 99%

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Endocrine dysfunctions during treatment of immune-checkpoint inhibitors

et al. 2018

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“…AH can be fatal if the adrenal insufficiency is unrecognized23, so that some cases are still reported at autopsy4 (see Table 1 in ref. 4).…”

mentioning

confidence: 99%

In Situ Activation of Pituitary-Infiltrating T Lymphocytes in Autoimmune Hypophysitis

Lin

Gutenberg

Chen

et al. 2017

Sci Rep

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Autoimmune hypophysitis (AH) is a chronic inflammatory disease characterized by infiltration of T and B lymphocytes in the pituitary gland. The mechanisms through which infiltrating lymphocytes cause disease remain unknown. Using a mouse model of AH we assessed whether T lymphocytes undergo activation in the pituitary gland. Infiltrating T cells co-localized with dendritic cells in the pituitary and produced increased levels of interferon-γ and interleukin-17 upon stimulation in vitro. Assessing proliferation of CD3- and B220-postive lymphocytes by double immunohistochemistry (PCNA-staining) and flow cytometry (BrdU incorporation) revealed that a discrete proportion of infiltrating T cells and B cells underwent proliferation within the pituitary parenchyma. This proliferation persisted into the late disease stage (day 56 post-immunization), indicating the presence of a continuous generation of autoreactive T and B cells within the pituitary gland. T cell proliferation in the pituitary was confirmed in patients affected by autoimmune hypophysitis. In conclusion, we show that pituitary-infiltrating lymphocytes proliferate in situ during AH, providing a previously unknown pathogenic mechanism and new avenues for treatment.

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“…CTLA-4 antigen was expressed by pituitary endocrine cells with the highest levels found in patients with severe hypophysitis. In patients with severe hypophysitis, immune reactions induced aggressive necrotizing form with extensive destruction of the adenohypophyseal architecture (51). Pituitary autoantiboides against thyrotrophs, corticotrophs and gonadotrophs were identified in the sera of patients who developed hypophysitis (52).…”

Section: Secondary Hypophysitismentioning

confidence: 99%

DIAGNOSIS OF ENDOCRINE DISEASE: Expanding the cause of hypopituitarism

Pekić

Popović

2017

European Journal of Endocrinology

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Hypopituitarism is defined as one or more pituitary hormone deficits due to a lesion in the hypothalamic-pituitary region. By far, the most common cause of hypopituitarism associated with a sellar mass is a pituitary adenoma. A high index of suspicion is required for diagnosing hypopituitarism in several other conditions such as other massess in the sellar and parasellar region, brain damage caused by radiation and by traumatic brain injury, vascular lesions, infiltrative/immunological/inflammatory diseases (lymphocytic hypophysitis, sarcoidosis and hemochromatosis), infectious diseases and genetic disorders. Hypopituitarism may be permanent and progressive with sequential pattern of hormone deficiencies (radiation-induced hypopituitarism) or transient after traumatic brain injury with possible recovery occurring years from the initial event. In recent years, there is increased reporting of less common and less reported causes of hypopituitarism with its delayed diagnosis. The aim of this review is to summarize the published data and to allow earlier identification of populations at risk of hypopituitarism as optimal hormonal replacement may significantly improve their quality of life and life expectancy.Correspondence should be addressed to V Popovic

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Hypophysitis Secondary to Cytotoxic T-Lymphocyte–Associated Protein 4 Blockade

Cited by 330 publications

References 33 publications

Endocrine dysfunctions during treatment of immune-checkpoint inhibitors

Endocrine dysfunctions during treatment of immune-checkpoint inhibitors

In Situ Activation of Pituitary-Infiltrating T Lymphocytes in Autoimmune Hypophysitis

DIAGNOSIS OF ENDOCRINE DISEASE: Expanding the cause of hypopituitarism

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