Abstract
Background: The present recommendations, consensus, or guidelines for the replacement dosage for hypothyroidism induced by programmed cell death protein 1 (PD-1) therapy are not uniform, and there are very few special clinical trials that have examined the replacement dosage for it.
Objectives: This article illustrates the clinical characteristics of hypothyroidism induced by PD-1 antibodies (Abs) and reports the recommended replacement dosage for hypothyroidism.
Methods: Eighteen patients with overt primary hypothyroidism induced by PD-1 Abs (group 1) were selected from 655 patients with different tumor types. Retrospective analysis was performed on patients in group 1 and 18 patients with natural courses of overt primary hypothyroidism who were age- and sex-matched with the patients in group 1 (group 2). The replacement dosages required for the patients in the two groups were compared.
Results: Thyroid dysfunction occurred in group 1 after approximately 3.0 ± 1.4 cycles of PD-1 therapy (1-6 stages), with a median time of 61.5 days. The median time of onset of hypothyroidism among all patients was 87.5 days (30-240 days). Most of the patients with hypothyroidism were asymptomatic, and the onset of hypothyroidism was independent of age, sex, TPOAb, TgAb and TSH in group 1 (P>0.05). The average replacement dosage for patients in group 1 was 1.8 ± 0.6 μg/kg/d (0.6-3.2 μg/kg/d). Multiple linear regression analysis showed that sex, age, TPOAb, TgAb and TSH were not correlated with drug dosage.
Conclusion: It seemed that the average maintenance dosage of levothyroxine might need to be 1.8 μg/kg/day for patients with overt hypothyroidism induced by PD-1 Abs.
Graphical Abstract
[http://dx.doi.org/10.1001/jama.2016.4059] [PMID: 27092830]
[http://dx.doi.org/10.1056/NEJMoa1501824] [PMID: 25891174]
[http://dx.doi.org/10.1016/j.jaip.2020.06.028] [PMID: 32599218]
[http://dx.doi.org/10.1016/j.medcli.2015.02.010] [PMID: 25851909]
[http://dx.doi.org/10.1016/j.ejim.2017.08.019] [PMID: 28826822]
[http://dx.doi.org/10.1038/s41574-021-00484-3] [PMID: 33875857]
[http://dx.doi.org/10.1093/annonc/mdx225] [PMID: 28881921]
[http://dx.doi.org/10.1530/ERC-18-0320] [PMID: 30400055]
[http://dx.doi.org/10.1186/s40425-017-0300-z] [PMID: 29162153]
[http://dx.doi.org/10.1507/endocrj.EJ19-0163] [PMID: 31243183]
[http://dx.doi.org/10.1210/jc.2016-2118] [PMID: 27736313]
[http://dx.doi.org/10.1210/jc.2007-0297] [PMID: 17711927]
[http://dx.doi.org/10.1089/thy.2021.0685] [PMID: 35199588]
[http://dx.doi.org/10.7326/AITC202007070] [PMID: 32628881]
[http://dx.doi.org/10.1210/er.2011-0007] [PMID: 21791567]
[http://dx.doi.org/10.1002/cphy.c150017] [PMID: 27065175]
[http://dx.doi.org/10.1210/clinem/dgab263] [PMID: 33878162]
[http://dx.doi.org/10.1089/thy.2016.0229] [PMID: 27521067]
[http://dx.doi.org/10.1158/2326-6066.CIR-18-0613] [PMID: 31088848]
[http://dx.doi.org/10.1007/s11523-011-0197-2] [PMID: 22101606]
[http://dx.doi.org/10.1111/cen.13354] [PMID: 28423475]
[http://dx.doi.org/10.1111/cen.13063] [PMID: 26998595]
[http://dx.doi.org/10.1038/s41572-022-00357-7] [PMID: 35589725]
[http://dx.doi.org/10.4158/EP.7.1.16] [PMID: 11250763]
[http://dx.doi.org/10.1002/bjs.5157] [PMID: 16323163]
[http://dx.doi.org/10.4158/EP.5.5.233] [PMID: 15251659]
[http://dx.doi.org/10.1089/thy.2018.0116] [PMID: 30132401]
[http://dx.doi.org/10.1210/jc.2004-1306] [PMID: 15483074]
[http://dx.doi.org/10.1111/j.1532-5415.1984.tb02003.x] [PMID: 6699335]
[http://dx.doi.org/10.1001/archinte.165.15.1714] [PMID: 16087818]
[http://dx.doi.org/10.1089/thy.2020.0032] [PMID: 32264785]
[http://dx.doi.org/10.1210/jc.2017-00448] [PMID: 28609832]
[http://dx.doi.org/10.1007/s40618-019-01058-x] [PMID: 31093955]
[http://dx.doi.org/10.1530/EC-20-0342] [PMID: 33064663]