Table 2. Summary of Reported IrAEs Involving Endocrine System: TSH, TPO Antibodies, TgAb, N/A, GAD, ACTH, DM, and DKA.
| References | Presentation | Number of cases | Age (mean) | Immune checkpoint inhibitors (number of cases) | Doses (mean) | Labs (number of cases) | Treatments (outcome) | ||
|---|---|---|---|---|---|---|---|---|---|
| Adrenal | |||||||||
| Cortisol | ACTH | ||||||||
| [53-63] | ACTH insufficiency | 12 | 39 - 83 (60) | Nivolumab-8, nivolumab/ipilimumab-4 | 2 - 13 (9) | Low-11 High-1 |
Low-11 High-1 |
Hydrocortisone, life long | |
| [64, 65] | Primary adrenal insufficiency | 2 | 43, 55 | Pembrolizumab-1, nivolumab-1 | 4, 10 | Low-2 | High-2 | Hydrocortisone with fludrocortisone, life long | |
| Thyroid | |||||||||
| Free T4 | TSH | Antibodies | |||||||
| [61, 65-69] | Thyroiditis followed by hypothyroidism | 7 | 46 - 73 (59) | Pembrolizumab-1, nivolumab-1, nivolumab/ipilimumab-5 | 1 - 8 (3) | Low-7 | High-7 | Negative-2, TPO/TgAb-2, TgAb-1, N/A-2 | Levothyroxine, life long |
| [70] | Hypophysitis with central hypothyroidism | 1 | 77 | Nivolumab/ipilimumab | 5 | Low | Low | N/A | Levothyroxine/steroids, life long |
| [53, 58, 59] | Hypophysitis with primary hypothyroidism | 3 | 54 - 83 (66) | Nivolumab-3 | 5 - 11 (7) | Low-3 | High-3 | TPO/TgAb-1, TPO-1, N/A-1 | Levothyroxine, life long |
| [71] | Myxedema crisis | 1 | 53 | Nivolumab | N/A | Low | High | N/A | Levothyroxine, life long |
| [72, 73] | Primary hypothyroidism | 2 | 62, 63 | Nivolumab-2 | 2, 1 | Low-1, N/A-1 | High-1, WNL-1 | TPO/TgAb-1, TPO-1 | Levothyroxine, life long |
| [74] | Thyroid storm | 1 | 24 | Nivolumab/ipilimumab | 2 | High | Low | Negative | Symptomatic treatment and hydrocortisone followed by prednisone |
| [62] | Thyroiditis followed by central hypothyroidism from hypophysitis | 1 | 53 | Nivolumab/ipilimumab | 3 | Low | Low | Negative | Levothyroxine, life long |
| [75] | Thyrotoxicosis from thyroiditis | 1 | 55 | Nivolumab | 2 | High | Low | TgAb | Symptomatic treatment |
| Pancreas | |||||||||
| HbA1c (mean) | Anti-GAD antibodies | ||||||||
| [66, 76-80] | Acute type 1 DM | 6 | 58 - 73 (79) | Pembrolizumab-2, pembrolizumab/ipilimumab-1, nivolumab-3 | 1 - 17 (8) | 6.3 - 9.7 (6.6) | Negative-3, positive-3 | Insulin injections, insulin dependent | |
| [69, 73, 81-94] | DKA | 16 | 34 - 80 (61) | Pembrolizumab-2, pembrolizumab/ipilimumab-2, nivolumab-8, nivolumab/ipilimumab-4 | 1 - 20 (6) | 6.5 - 10.7 (7.9) | Positive-8, negative-8 | Insulin drip followed by multiple insulin injections, insulin dependent | |
| Parathyroid | |||||||||
| Calcium | Parathyroid hormone | ||||||||
| [67] | Primary hypoparathyroidism | 1 | 73 | Nivolumab/ipilimumab | 2 | Low | Undetectable | Calcium and vitamin D, long-term calcium and vitamin D supplement | |
TSH: thyroid-stimulating hormone; TPO: thyroid peroxidase; TgAb: thyroglobulin antibodies; N/A: not available; GAD: glutamic acid decarboxylase; ACTH: adrenocorticotropic hormone; DM: diabetes mellitus; DKA: diabetic ketoacidosis.