Endocrine Abstracts

Background: Immune checkpoint inhibitors such as pembrolizumab can cause immune-related adverse events (irAEs), including endocrine dysfunctions. While thyroiditis and adrenal insufficiency are more common, hypophysitis is rare with PD-1 inhibitors. Central diabetes insipidus (DI) is even more unusual.

Case: We report a 67-year-old female with metastatic lung adenocarcinoma (T4 N0 M1 c) on pembrolizumab who developed dual endocrine toxicities—ACTH deficiency (secondary adrenal insufficiency) and central diabetes insipidus. She presented with polyuria and polydipsia during ongoing immunotherapy (Cycle 12), and was diagnosed via hormonal testing and osmolality studies. Treatment with prednisolone and desmopressin resulted in rapid symptomatic improvement.

Conclusion: This case highlights the importance of vigilance for rare endocrine irAEs such as diabetes insipidus in patients receiving PD-1 inhibitors. Early recognition and hormone replacement allowed continuation of pembrolizumab with maintained disease control. A 67-year-old female with stage T4 N0 M1 c right lung adenocarcinoma was initiated on palliative pembrolizumab following initial chemoradiotherapy. She had no prior history of endocrine or autoimmune disorders.

Disease Status: - She was approaching Cycle 13 of pembrolizumab.

- A recent CT chest/abdomen/pelvis (May 2025) demonstrated a partial response with no evidence of progression.

Presenting Symptoms: - The patient developed polyuria, polydipsia, and mild fatigue over several weeks.

- She remained weight stable and was wheelchair-dependent due to prior cancer-related deconditioning.

Endocrine Workup: - Morning cortisol: Low

- ACTH: Low-normal → consistent with secondary adrenal insufficiency

- Plasma osmolality: High

- Urine osmolality: Inappropriately low

- Response to desmopressin: Immediate clinical and biochemical improvement, confirming central diabetes insipidus

Diagnosis: - Pembrolizumab-induced hypophysitis, presenting with:

- ACTH deficiency (Addison’s disease)

- Central diabetes insipidus

Management: - Initiated on prednisolone 5 mg once daily (maintenance glucocorticoid)

- Desmopressin 100 mg twice daily (oral)

- Provided with hydrocortisone emergency kit for intercurrent illness

Outcome: - Rapid symptom relief

- Stable biochemical parameters

- Continued pembrolizumab without interruption

- Imaging follow-up confirmed ongoing tumor control without new lesions

Discussion: Immune-related endocrine toxicities are increasingly recognized with checkpoint inhibitor therapy. While thyroiditis and primary adrenalitis are common, hypophysitis is less frequently seen with PD-1 inhibitors and more classically associated with CTLA-4 blockade. Central diabetes insipidus is exceedingly rare as an irAE. The posterior pituitary is less susceptible to autoimmune inflammation, making isolated or combined anterior/posterior involvement unusual. Only a handful of cases combining ACTH deficiency and DI have been reported with anti–PD-1 therapy. In this patient, early recognition of symptoms and prompt hormonal evaluation were key. The dual endocrine dysfunction was effectively managed with steroid and desmopressin replacement, allowing continuation of pembrolizumab and preservation of quality of life.