Isolated Central Adrenal Insufficiency Due to Nivolumab: A Case Report
Bibliographic record
Abstract
Abstract Background: Immune checkpoint inhibitors are immunomodulatory antibodies directed against programmed cell death 1 (PD-1), Nivolumab, or cytotoxic T-lymphocyte antigen-4 (CTLA-4) Ipilimumab. They have improved outcomes in patients with advanced cancers including renal cell carcinoma, non-small cell lung cancer and melanoma. Several immune related adverse events (irAEs) have been recognized with use of immune checkpoint inhibitors, including those involving the endocrine system. We present a case of a patient presenting with isolated central adrenal insufficiency in the context of Nivolumab use. Clinical Case: Our patient is a 54-year old man with pre-existing primary hypothyroidism and metastatic renal cell carcinoma treated with Nivolumab. After receiving a total of 14 cycles of Nivolumab, he presented to the Emergency room with his sister, who found him confused and lethargic. On presentation, he was found to be hypoglycemic (random glucose was 2.2 mmol/L). On physical examination, his vital signs were stable and he appeared euvolemic. He was disoriented without focal neurological deficits. Initial blood work revealed sodium 134 mmol/L, (Normal 135-145mmol/L), potassium 4.5 mmol/L (Normal 3.5-5 mmol/L), and TSH being 12.6 mIU/L (Normal 0.4-4 mIU/L). He was resuscitated with IV Dextrose 50% bolus then admitted to hospital and kept on an IV dextrose infusion. While his glucose improved, he was found to have hyponatremia, and confusion persisted. His nadir sodium was 116 mmol/L without seizures or loss of consciousness and required treatment with hypertonic saline. Giving hypoglycemia and hyponatremia, morning cortisol and ACTH were checked and came back 4 nmol/L (Normal 133-537 nmol/L) and undetectable (< 0.7 pmol/L, Normal 1.6-13.9 pmol/L) respectively. The diagnosis of central adrenal insufficiency was made likely secondary to Nivolumab. He was started on Dexamethasone 8 mg daily. Sodium level normalized and glucose level improved with steroids. He was discharged home on prednisone 50 mg and then switched to hydrocortisone. Further work up confirmed preserved other anterior pituitary hormones. MRI of Sella did not show pituitary enlargement or inflammation. Conclusion: Our patient presented with hypoglycemia and hyponatremia; both could be the presenting manifestations of central adrenal insufficiency. Nivolumab has been commonly associated with thyroid dysfunction and thyroiditis. Given lack of expression of PD-1 in the pituitary, PD-1 inhibitors are less likely to be associated with hypopituitarism in general, or central adrenal insufficiency in particular. However, our report adds to the growing body of literature associating it with central adrenal insufficiency, which can be isolated. In so doing, it underscores the need for early recognition this association with Nivolumab, so as to avoid the potentially life threatening consequences of this condition.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".