SAT-004 - Diagnosis of Central Diabetes Insipidus and Hypophysitis Secondary to Immune Checkpoint Inhibitor Therapy

Introduction

Immune checkpoint inhibitors (ICIs) like atezolizumab are effective for treating malignancies such as small cell lung cancer (SCLC), but with increased use in clinical practice, side effects such as endocrinopathies have been noted. We report a rare case of central diabetes insipidus (CDI) and hypophysitis presumed secondary to atezolizumab, highlighting a unique presentation of hypothalamic-pituitary axis dysfunction.

Case Description

A 69-year-old male with SCLC, treated with atezolizumab since 2023, presented with generalized weakness, altered mental status, polydipsia, and polyuria for two weeks. His medical history included central hypothyroidism and secondary adrenal insufficiency managed with levothyroxine and corticosteroids stemming from prior immune checkpoint inhibitor use. On admission, he was hypothermic (94.3°F) and hypotensive. Laboratory findings revealed hypertonic hypernatremia (Na 155 mmol/L, serum osmolality 333 mOsm/kg) and polyuria (>250 cc/hr), suggestive of diabetes insipidus. No copeptin was collected. MRI Sella turcica showed new expansile T2 signal hypersensitivity in the pituitary infundibulum compared to imaging five months prior, consistent with hypophysitis. Desmopressin was initiated, resolving polyuria and hypernatremia, indirectly confirming CDI.
The patient’s hospitalization was complicated by persistent hypothermia, initially attributed to adrenal crisis. High-dose steroids were trialed to address suspected ICI-induced hypophysitis but hypothermia persisted despite treatment. Steroid taper was initiated, and due to ongoing hypothermia precluding safe discharge, the patient was transitioned to hospice care and died shortly after.

Discussion/Conclusion

This case describes a rare presentation of CDI and hypophysitis secondary to atezolizumab, with < 1% incidence of hypophysitis per manufacturer data. Beyond posterior pituitary involvement, hypothermia due to hypothalamic involvement from ICI toxicity contributed to the patient’s demise. This suggests that ICI-induced inflammation may disrupt the hypothalamic-pituitary axis, impairing ADH secretion and thermoregulation in the absence of adrenal crisis, myxedema coma, or other contributing syndromes given adequately repleted thyroid and glucocorticoids during hospitalization. Clinicians should maintain a high index of suspicion for such complications in ICI-treated patients, as early recognition and management are critical. This case underscores the need for vigilant monitoring as ICI use expands in oncology.

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