Abstract
Purpose
Hypophysitis develops in up to 19% of melanoma patients treated with ipilimumab, a cytotoxic T-lymphocyte antigen-4 antibody. Early detection may avert life-threatening hypopituitarism. We aimed to assess the incidence of ipilimumab-induced hypophysitis (IH) at a quaternary melanoma referral centre, and to determine whether cortisol or thyroid stimulating hormone (TSH) monitoring could predict IH onset.
Methods
We performed a retrospective cohort study of ipilimumab-treated patients at a quaternary melanoma referral centre in Australia. The inclusion criteria were patients with metastatic or unresectable melanoma treated with ipilimumab monotherapy, and cortisol and TSH measurements prior to ≥ 2 infusions. The main outcomes were IH incidence and TSH and cortisol patterns in patients who did and did not develop IH.
Results
Of 78 ipilimumab-treated patients, 46 met the study criteria and 9/46 (20%) developed IH at a median duration of 13.0 weeks (range 7.7–18.1) following ipilimumab initiation. All patients whose TSH fell ≥ 80% compared to baseline developed IH, and, in 5/9 patients with IH, TSH fell prior to cortisol fall and IH diagnosis. Pre-cycle-4 TSH was significantly lower in those who developed IH (0.31 vs. 1.73 mIU/L, P = 0.006). TSH fall was detected at a median time of 9.2 (range 7.7–16.4) weeks after commencing ipilimumab, and a median of 3.6 (range of − 1.4 to 9.7) weeks before IH diagnosis. There was no difference in TSH between the groups before cycles 1–3 or in cortisol before cycles 1–4.
Conclusions
TSH fall ≥ 80% may be an early marker of IH. Serial TSH measurement during ipilimumab therapy may be an inexpensive tool to expedite IH diagnosis.
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Acknowledgements
The authors thank Dr Alexander Guminski, Dr Yael Barnett, Georgia Cairns CNC and Anna Hoadley CNC for assisting with this study.
Funding
SMCD is supported by a Royal Adelaide Hospital AR Clarkson Fellowship. NS is supported by a University of New South Wales Research Training Program Scholarship. AMM is supported by a Cancer Institute NSW Fellowship. GVL is supported by an NHMRC Fellowship and by the University of Sydney Medical Foundation.
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AMM: Advisory board MSD, Novartis, Chugai, Pierre Fabre, honoraria BMS, Roche. GVL: Consultant advisor to Amgen, BMS, Merck, Array, Novartis, Pierre-Fabre and Roche.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Formal consent was not required for this type of study.
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De Sousa, S.M.C., Sheriff, N., Tran, C.H. et al. Fall in thyroid stimulating hormone (TSH) may be an early marker of ipilimumab-induced hypophysitis. Pituitary 21, 274–282 (2018). https://doi.org/10.1007/s11102-018-0866-6
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DOI: https://doi.org/10.1007/s11102-018-0866-6