RF30 | PSAT177 A Case of Hypercalcemia Related to Immune Checkpoint Inhibitor-Induced Sarcoidosis-like Granuloma
Bibliographic record
Abstract
Abstract Background Immune checkpoint inhibitor (ICI) is an essential part of the treatment of various advanced cancers, but its use can be associated with a number of side effects, including hypercalcemia. The mechanism through which hypercalcemia arises is not well established. One proposed mechanism is through sarcoidosis-like reactions. Here we present an illustrative case. Clinical Case A 75-year-old female with past medical history notable for stage IV endometrial adenocarcinoma treated with surgery plus adjuvant chemotherapy, presently on pembrolizumab for 9 months, hypertension, and diabetes was admitted with generalized fatigue, difficulty ambulating, slow movements, and slow speech. Stroke was ruled out with negative neurologic imaging. Blood work revealed elevated calcium 13.8 mg/dL (8.6-10.4 mg/dL) and ionized calcium 1.64 mmol/L (1.09-1.29 mmol/L). Additional workup showed suppressed PTH 7 pg/mL (11-51 pg/mL), 25-OH vitamin D 19 ng/mL (20-50 ng/mL), elevated 1,25(OH)2 vitamin D of 114 pg/mL (19.9-79.3 pg/mL), elevated angiotensin converting enzyme (ACE) level 90 U/L (12-69 U/L), and normal PTHrP, suggestive of PTH-independent hypercalcemia mediated by 1,25(OH)2D as seen in sarcoidosis. Two months prior to admission and seven months after starting pembrolizumab, surveillance CT found improvement in tumor burden but new intrathoracic lymphadenopathy. Lymph node biopsy via bronchoscopy identified non-caseating granulomas suggestive of a sarcoidosis-like reaction. The patient's moderate hypercalcemia was treated with intravenous fluids, calcitonin, and zoledronic acid 4 mg with normalization of calcium levels. Glucocorticoid therapy was initially deferred to avoid counteracting the effect of pembrolizumab, however prednisone 10 mg daily was started 1 month after discharge when calcium rose again to 11.1 mg/dL. Prednisone was tapered off over 8 weeks as her calcium and 1,25(OH)2D levels normalized. She then restarted pembrolizumb, but after the third month she had recurrence of hypercalcemia (calcium 10.8 mg/dL) with elevated 1,25(OH)2D (89.5 pg/mL). She was again treated with prednisone 10 mg daily which was tapered off over 6 weeks with resolution of hypercalcemia. Her calcium levels remained normal off pembrolizumab. The temporal correlation in our case strongly suggests that ICI administration caused sarcoidosis-like granulomas and hypercalcemia. Conclusion Immune checkpoint inhibitors are known to occasionally cause hypercalcemia, although the mechanisms are not well established. In our case, moderate hypercalcemia was likely caused by ICI-induced sarcoid-like granulomas that responded promptly to glucocorticoids and interruption of ICI-therapy. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 1:12 p.m. - 1:17 p.m.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.005 | 0.003 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".