Predicting development of ipilimumab-induced hypophysitis: utility of T4 and TSH index but not TSH.
Date
2020-05-24Author
Siddiqui, MS
Lai, ZM
Spain, L
Greener, V
Turajlic, S
Larkin, J
Morganstein, DL
Type
Journal Article
Metadata
Show full item recordAbstract
PURPOSE: Ipilimumab, a monoclonal antibody inhibiting CLTA-4, is an established treatment in metastatic melanoma, either alone or in combination with nivolumab, and results in immune mediated adverse events, including endocrinopathy. Hypophysitis is one of the most common endocrine abnormalities. An early recognition of hypophysitis may prevent life threatening consequences of hypopituitarism; therefore, biomarkers to predict which patients will develop hypophysitis would have clinical utility. Recent studies suggested that a decline in TSH may serve as an early marker of IH. This study was aimed at assessing the utility of thyroid function tests in predicting development of hypophysitis. METHODS: A retrospective cohort study was performed for all patients (n = 308) treated with ipilimumab either as a monotherapy or in combination with nivolumab for advanced melanoma at the Royal Marsden Hospital from 2010 to 2016. Thyroid function tests, other pituitary function tests and Pituitary MRIs were used to identify those with hypophysitis. RESULTS AND CONCLUSIONS: Ipilimumab-induced hypophysitis (IH) was diagnosed in 25 patients (8.15%). A decline in TSH was observed in hypophysitis cohort during the first three cycles but it did not reach statistical significance (P = 0.053). A significant fall in FT4 (P < 0.001), TSH index (P < 0.001) and standardised TSH index (P < 0.001) prior to cycles 3 and 4 in hypophysitis cohort was observed. TSH is not useful in predicting development of IH. FT4, TSH index and standardised TSH index may be valuable but a high index of clinical suspicion remains paramount in early detection of hypophysitis.
Collections
Subject
Hypophysitis
Ipilimumab
Melanoma
TSH index
Adult
Aged
Antineoplastic Agents, Immunological
Biomarkers
Female
Follow-Up Studies
Humans
Hypophysitis
Ipilimumab
Male
Melanoma
Middle Aged
Prognosis
Retrospective Studies
Thyrotropin
Thyroxine
Language
eng
Date accepted
2020-05-13
License start date
2020-05-24
Citation
Journal of Endocrinological Investigation, 2020, 44 (1), pp. 195 - 203
Publisher
SPRINGER