SAT327 A Curious Case of Immune Checkpoint Inhibitor Induced Hypophysitis with Transient ACTH-dependent Hypercortisolism
Bibliographic record
Abstract
Abstract Disclosure: M. Shi: None. F. AlRubaish: None. N. Gupta: None. V. Larouche: None. S. Christopoulos: None. The use of immune checkpoint inhibitors (ICI) has increased exponentially over the last decade as these agents have shown to substantially improve the prognosis in multiple advanced malignancies. Despite these important clinical benefits, ICI are associated with many immune-related adverse events (irAE). Endocrinopathies are the most frequent irAE and include autoimmune thyroid disorders, hypophysitis and primary adrenal insufficiency. These endocrinopathies often require long-term surveillance and hormone supplementation. We report a relatively novel irAE case of transient central hypercortisolism that progressed to hypopituitarism. A 72-year-old woman with metastatic melanoma on combined ICI therapy of nivolumab-ipilimumab developed subclinical hyperthyroidism (TSH <0.02 mU/L [reference range (RR) 0.40-4.50 mU/L]; FT4 20.2 pmol/L [RR 9.0-26.0 pmol/L]) eight weeks following initiation of her immunotherapy. At week 11, she was found to have refractory hypokalemia (initial potassium at presentation 2.3 mmol/L RR 3.5-5.5 mmol/L) and metabolic alkalosis (pH 7.57 [RR 7.35-7.45]; bicarbonate 39 mmol/L [RR 22-31 mmol/L]). Physical exam was unremarkable for Cushingoid features. Subsequent investigations revealed central hypothyroidism (TSH 0.02 mU/L [RR 0.40-4.50 mU/L]; FT4 8.1 pmol/L [RR 9.0-26.0 pmol/L]) and levothyroxine replacement was started. She also had evidence of hypogonadotropic hypogonadism (FSH 4.2 U/L [postmenopausal RR 25.8-143.9 U/L]; LH 1.5 U/L [postmenopausal RR 13.2-45.7U/L]) and central hypercortisolism with a morning cortisol of 1082 nmol/L [RR 172-497 nmol/L] and an ACTH level of 18.3 pmol/L [RR 1.6-13.9 pmol/L]. The low dose dexamethasone suppression test was not suppressed (morning cortisol at 983 nmol/L). She underwent imaging studies of her abdomen and brain which revealed normal adrenal and pituitary glands, respectively. Close pituitary function monitoring during endocrinology follow-up revealed persistent elevation of cortisol and ACTH levels until week 15, then a subsequent decline in both cortisol and ACTH levels for which she started hydrocortisone replacement. Further follow-up blood work revealed morning cortisol levels below 50 nmol/L [RR 172-497 nmol/L] with undetectable ACTH levels from week 16 onwards. The hydrocortisone and levothyroxine replacement were continued, and the patient remained asymptomatic throughout her follow-ups. This case highlights that a transient episode of ACTH dependent hypercortisolism may be an early marker prior to the development of central adrenal insufficiency from ICI-related destructive immune hypophysitis. Furthermore, our report highlights that physicians and other healthcare professionals should remain vigilant in monitoring laboratory progression in these patients, as early recognition facilitated timely management in our patient and prevented complications. Presentation: Saturday, June 17, 2023
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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) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".