Endocrine Abstracts

Background: Immune checkpoint inhibitors (ICIs) such as ipilimumab (CTLA-4 inhibitor) and nivolumab (PD-1 inhibitor) have revolutionised the management of advanced melanoma. However, they are increasingly associated with immune-related adverse events (irAEs), including endocrinopathies. Hypophysitis is a recognised but uncommon complication, particularly with CTLA-4 blockade, and can present with non-specific symptoms that may mimic disease progression or treatment toxicity. Prompt recognition and management are essential to prevent life-threatening complications such as adrenal crisis.

Case Presentation: We report a 58-year-old woman with metastatic melanoma and para-aortic lymphadenopathy, treated with combined ipilimumab and nivolumab. Following her third cycle of therapy, she was admitted with worsening morning headaches, nausea, and a single episode of vomiting. She also described paraesthesia and swelling of her hands and feet. On examination, she was haemodynamically stable with preserved visual fields. Initial investigations revealed hyponatraemia (Na 123 mmol/l) and a markedly low morning cortisol (34 nmol/l). Thyroid function tests showed low free thyroxine (FT4 7.2 pmol/l) with inappropriately low TSH (0.23 mU/l), consistent with secondary hypothyroidism. Her thyroid function had been normal one month earlier. The constellation of new endocrine abnormalities in the context of ICI therapy raised the suspicion of immune-mediated hypophysitis. MRI of the pituitary demonstrated diffuse enlargement of the anterior pituitary and infundibulum with homogeneous contrast enhancement, appearances in keeping with hypophysitis. Pituitary adenoma was considered in the differential but was less likely given the temporal relationship to immunotherapy. The patient was commenced on hydrocortisone replacement (20 mg three times daily, tapered to a maintenance regimen). Levothyroxine (50 μg daily) was initiated 48 hours later to avoid precipitating adrenal crisis. A complete pituitary hormonal profile (ACTH, prolactin, LH, FSH, IGF-1, GH) was arranged for further evaluation.

Discussion: This case highlights the importance of maintaining a high index of suspicion for ICI-induced hypophysitis in patients presenting with headache, hyponatraemia, or non-specific constitutional symptoms during immunotherapy. Early diagnosis with biochemical testing and MRI, followed by appropriate corticosteroid replacement, is crucial for preventing adrenal crisis. Thyroid hormone replacement should only be initiated after glucocorticoid therapy is established. Long-term endocrinology follow-up is essential, as many patients require lifelong hormone replacement.

Conclusion: Immune checkpoint inhibitors, while highly effective in advanced melanoma, can precipitate serious endocrine irAEs such as hypophysitis. Our case underscores the need for vigilant monitoring, multidisciplinary collaboration, and timely intervention to optimise both oncological and endocrine outcomes.