Table 5.
Cases that have T1D and hypophysitis due to ICI therapy.
| Case | Age | Sex | Primary disease | Therapy | A term to hypophysitis diagnosis from T1D* | Hormone disorder | Enlarged pituitary by MRI | HbA1c (mmol/mol) | CPR (nmol/L) | Autoantibody | HLA† |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Okahata S (2019)[3] | 52 | F | Breast cancer | Nivo | −1 mo | IAD | no | 62 | 0.10 | GAD-/IA-2-/IAA- | DRB1*14:05,14:06 DQB1*03:01,03:03 |
| Sum M (2018)[21] | 75 | M | Melanoma | Nivo +Ipi |
NA (T1D → hypophysitis) |
AD | enlarged | 60 | 0.10 | GAD+/islet- | NA |
| Khalid M (2019)[22] | 53 | M | Malignant melanoma | Nivo +Ipi |
−18 mo | IAD | no | NA | un- detectable |
GAD+ | NA |
| Lanzolla G (2019)[23] | 60 | M | Lung adeno-carcinoma | Atezo | 1 wk | AD | no | NA | un- detectable |
pituitary+ /21-hydroxylase+ /GAD-/IA-2- |
DRB1*04- DQB1*03 |
| Takata M (2022)[24] | 59 | M | Malignant melanoma | Nivo | −22 wk | IAD | NA | 58 | 0.18 | NA | NA |
| Hino C (2022)[25] | 45 | M | Sarcomatoid renal cell carcinoma | Nivo +Ipi |
73 d | AD | NA | 60 | 0.17 | GAD-/IAA- | NA |
| Ishiguro A (2022)[26] | 67 | M | Malignant melanoma | Nivo | 168 d | IAD | no | 54 | 0.86 | GAD+ | DRB1*08:02-DQB*03:02 |
| Luo J (2022)[27] | 76 | M | Non-small cell lung cancer | Pem | 4 mo | AD | NA | 27 | 0.01 | GAD-/IA-2- /islet- |
HLA-DQA1/DQB1 |
| Marchand L (2017)[28] | 55 | M | Pulmonary pleomorphic carcinoma | Nivo | 1 mo | IAD | no | 66 | un-detectable | GAD-/IA-2-/IAA-/islet- /Zinc 8- |
NA |
| Porntharukchareon T (2020)[29] | 70 | M | Non-small cell lung cancer | Nivo +Ipi |
simultaneous | IAD | no | 48 | un-detectable | GAD-/IA-2- | NA |
| Kikuchi F (2021)[30] | 62 | M | Renal cell carcinoma | Nivo | −3 mo | IAD | no | 65 | 0.07 | GAD- | NA |
| Boswell L (2021)[31] | 51 | M | Malignant melanoma | Nivo +Ipi |
−75 wk | IAD | no | 63 | 0.32 | GAD-/IA-2-/IAA- | DRB*01:01, DRB1*12:01 |
| Min Li (2022)[32] | 45 | M | Non-small-cell lung cancer | KN046‡ | −2 mo | AD | no | 77 | <0.03 | GAD-/IA-2- /islet- |
NA |
| This case | 81 | M | Renal cell carcinoma | Nivo +Ipi |
14 d | IAD | no | 46 | 0.01 | GAD-/IA-2-/IAA-/islet- /Zinc 8- |
DRB1*09:01- DQB1*03:03 |
CPR = serum C-peptide, GAD = anti-glutamic acid decarboxylase antibody, HbA1c = hemoglobin A1c, IA-2 = anti-insulinoma-associated antigen-2 antibody, IAA = insulin auto-antibody, ICI = immune checkpoint inhibitor, islet = islet cell antibody, NA = not assessed, Zinc 8 = zinc transporter 8 antibody.
*
Minus (−) means hypophysitis precedes T1D.
†
Bold letters are HLAs susceptible to T1D.
‡Recombinant humanized PD-L1/CTLA-4 bispecific single-domain antibody Fc fusion protein injection.