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Fall in thyroid stimulating hormone (TSH) may be an early marker of ipilimumab-induced hypophysitis


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.

Type Journal
ISBN 1573-7403 (Electronic) 1386-341X (Linking)
Authors De Sousa, S. M. C.; Sheriff, N.; Tran, C. H.; Menzies, A. M.; Tsang, V. H. M.; Long, G. V.; Tonks, K. T. T.
Responsible Garvan Author Dr Katherine Tonks
Publisher Name Pituitary
Published Date 2018-06-01
Published Volume 21
Published Issue 3
Published Pages 274-282
Status Published in-print
DOI 10.1007/s11102-018-0866-6
URL link to publisher's version
OpenAccess link to author's accepted manuscript version