Case report and literature review: isolated ACTH deficiency induced by combined nivolumab and trastuzumab therapy in gastric adenocarcinoma.

Background: Isolated adrenocorticotropic hormone (ACTH) deficiency (IAD) is an uncommon endocrine disorder characterised by the selective reduction or absence of pituitary ACTH secretion, resulting in secondary adrenal insufficiency while other pituitary hormone axes remain functional. The clinical manifestations of this condition are frequently non-specific, and may include symptoms such as fatigue, decreased appetite, weight loss, hypotension, and hyponatremia. These symptoms can be easily confused with those of other diseases, resulting in either missed diagnoses or misdiagnoses. Glucocorticoid replacement therapy is generally considered to provide effective symptom relief and a favourable prognosis. In recent years, the widespread use of immune checkpoint inhibitors (ICIs) in cancer treatment has resulted in a significant increase in immune-related adverse events (irAEs). Isolated ACTH deficiency has been reported as a rare yet severe endocrine-type irAE, potentially arising from immune-mediated pituitary injury. In view of the nonspecific nature of its clinical presentation, early recognition and timely intervention are of critical importance. Case presentation: The present study reports the case of a patient diagnosed with gastric adenocarcinoma who underwent laparoscopic total gastrectomy, followed by combination therapy with oxaliplatin (OXA), nivolumab, and trastuzumab. Approximately eight months into the treatment regimen, the patient exhibited symptoms of isolated ACTH deficiency and hypothyroidism, indicative of a multi-endocrine system adverse reaction. Such multi-system endocrine dysfunction following this combination therapy is relatively uncommon. The present study analyses the patient's clinical presentation, laboratory findings, and imaging data, and discusses the differential diagnosis from post-gastrectomy dumping syndrome. Conclusion: This case demonstrates that in patients with malignant tumours receiving nivolumab and trastuzumab therapy, the presence of unexplained hypoglycaemia, persistent fatigue, anorexia, nausea, or vomiting - non-specific symptoms - should raise high suspicion for immune-related endocrine adverse reactions. It is imperative to emphasise the significance of preliminary testing for serum cortisol, ACTH, and thyroid function levels. Early recognition and prompt initiation of hormone replacement therapy can effectively prevent misdiagnosis, missed diagnosis, and delayed treatment.