Ipilimumab-induced hypophysitis, a single academic center experience

Snyders, Travis; Chakos, Daniel; Swami, Umang; Latour, Emile; Chen, Yiyi; Fleseriu, Maria; Milhem, Mohammed; Zakharia, Yousef; Zahr, Roula

doi:10.1007/s11102-019-00978-4

Cited by 36 publications

(35 citation statements)

References 21 publications

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“…Several authors have reported high IH frequencies (11–13%) ( 15 , 16 ) and relative risk for all-grade IH as high as 22.03 ( 17 ). However, according to the latest reviews and meta-analyses IH incidences are lower but they notably depend on the type of ICI used and the treatment regimen ( 1 , 18 , 19 , 20 , 21 , 22 , 23 ).…”

Section: Immune Checkpoint Inhibitor-induced Hypophysitismentioning

confidence: 99%

“…The association between IH, gender and age needs to be further investigated because the data are not consistent. Some authors have reported higher frequencies of IH in older males (over the age of 60 years) ( 2 , 14 , 15 ). This is in contrast to primary hypophysitis, which is found mostly in younger females ( 12 ).…”

Section: Immune Checkpoint Inhibitor-induced Hypophysitismentioning

confidence: 99%

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Management of endocrine immune-related adverse events of immune checkpoint inhibitors: an updated review

Stelmachowska-Banaś

Czajka-Oraniec

2020

Endocrine Connections

114

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Immune checkpoint inhibitors (ICIs) belong to a new group of anticancer drugs targeting T-cell proteins involved in the activation of immune response toward malignancies. Their introduction into clinical practice was a milestone in modern cancer treatment. However, the significant advantage of ICIs over conventional chemotherapy in terms of therapeutic efficacy is accompanied by new challenges related to specific side effects. ICI-induced immune system activation could lead to the loss of self-tolerance, presenting as autoimmune inflammation and dysfunction of various tissues and organs. Thus, the typical side effects of ICIs include immune-related adverse events (irAEs), among which endocrine irAEs, affecting numerous endocrine glands, have been commonly recognized. This review aimed to outline the current knowledge regarding ICI-induced endocrine disorders from a clinical perspective. We present updated information on the incidence and clinical development of ICI-induced endocrinopathies, including the most frequent thyroiditis and hypophysitis, the rarely observed insulin-dependent diabetes mellitus and primary adrenal insufficiency, and the recently described cases of hypoparathyroidism and lipodystrophy. Practical guidelines for monitoring, diagnosis, and treatment of ICI-related endocrine toxicities are also offered. Rising awareness of endocrine irAEs among oncologists, endocrinologists, and other health professionals caring for patients receiving ICIs could contribute to better safety and efficacy. As immunotherapy becomes widespread and approved for new types of malignancies, increased incidences of endocrine irAEs are expected in the future.

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Section: Immune Checkpoint Inhibitor-induced Hypophysitismentioning

confidence: 99%

Section: Immune Checkpoint Inhibitor-induced Hypophysitismentioning

confidence: 99%

Management of endocrine immune-related adverse events of immune checkpoint inhibitors: an updated review

Stelmachowska-Banaś

Czajka-Oraniec

2020

Endocrine Connections

114

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“…Other studies also reported pituitary irAEs manifesting as isolated secondary adrenal insufficiency 11,22 . As reported by Snyders et al, 23 CTLA‐4 blockade therapy by ipilimumab can cause not only isolated secondary adrenal insufficiency but also composite hypopituitarism; all 15 of their cases with hypophysitis had adrenal deficiency, while 12 had concomitant central hypothyroidism and 8 had concomitant gonadal deficiency. Even though bias may be present because adrenal insufficiency is readily suspected and easily diagnosed due to its obvious symptoms, isolated secondary adrenal insufficiency seems to be a characteristic pituitary irAE during PD‐1 blockade therapy.…”

Section: Discussionmentioning

confidence: 73%

Clinical features and thyroid dysfunction in adverse events involving the pituitary gland during PD‐1 blockade therapy

Yamauchi

Taura

Hakata

et al. 2020

Clinical Endocrinology

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ObjectiveProgrammed cell death‐1 (PD‐1) blockade therapy, an immune checkpoint treatment, can induce hypophysitis or hypopituitarism as an immune‐related adverse event (pituitary irAE). We aimed to clarify the clinical features of pituitary irAEs during PD‐1 blockade therapy.Design, Patients and MeasurementsThis retrospective study investigated consecutive patients treated with nivolumab, an anti‐PD‐1 antibody, at Kyoto University Hospital between 1 September 2014 and 31 August 2019. We examined patients’ baseline characteristics and analysed the clinical data of those who developed pituitary irAEs.ResultsOf the 374 recruited patients, 7 (1.9%) developed pituitary irAEs, and each presented with isolated secondary adrenal insufficiency. In 4 patients, changes in ACTH were delayed relative to those in cortisol: when serum cortisol levels fell below the reference range, plasma ACTH levels were still normal. Pituitary irAEs were accompanied by elevated serum‐free T3 (fT3) levels, which resolved with glucocorticoid replacement. Serum TSH levels were not suppressed despite elevated serum fT3 levels and 1 patient even presented with high fT3 level above the reference range (fT3, 7.1 pmol/L; free T4 (fT4), 13.9 pmol/L; and TSH, 5.1 mIU/L).ConclusionsIsolated secondary adrenal insufficiency was a common pituitary irAE during PD‐1 blockade therapy. This condition was accompanied by thyroid dysfunction, including elevation of fT3 without TSH suppression.

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“…To date, most series have not reported recovery of ACTH function, although recovery of other pituitary axis is reported (9,37,38). As discussed previously, high dose steroids do not improve pituitary function recovery (24).…”

Section: Longer Term Prognosis Of Hypophysitismentioning

confidence: 88%

“…Currently, there are no reliable biomarkers for risk of hypophysitis, and given the protean presentation of hypopituitarism, adrenal insufficiency and hypophysitis, careful clinical assessment is required (9,23,37).…”

Section: Prediction Of Hypophysitismentioning

confidence: 99%

Endocrine toxicity of cancer immunotherapy: clinical challenges

Anderson

Morganstein

2021

Endocrine Connections

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Immune checkpoint inhibitors are now widely used in the treatment of multiple cancers. The major toxicities of these treatments are termed immune related adverse events and endocrine dysfunction is common. Thyroid disease, hypopituitarism and a form of diabetes resembling type 1 diabetes are now all well described, with different patterns emerging with different checkpoint inhibitors. We review the presentation and management of the common endocrine immune related adverse events, and discuss a number of recent advances in the understanding of these important, potentially life threatening toxicities. We also discuss some remaining dilemmas in management.

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Ipilimumab-induced hypophysitis, a single academic center experience

Cited by 36 publications

References 21 publications

Management of endocrine immune-related adverse events of immune checkpoint inhibitors: an updated review

Management of endocrine immune-related adverse events of immune checkpoint inhibitors: an updated review

Clinical features and thyroid dysfunction in adverse events involving the pituitary gland during PD‐1 blockade therapy

Endocrine toxicity of cancer immunotherapy: clinical challenges

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