Abstract Introduction Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycaemic state (HHS) are well-recognised acute complications of diabetes, but their presentation in patients with cancer—particularly as an initial manifestation—is poorly understood. ¹ Additionally, a small subset of rapidly progressive malignancies can present with metastatic disease in the absence of an identifiable primary tumour. These are classified as cancers of unknown primary origin (CUP), accounting for 3–5% of all cancers. ² Identifying CUP poses significant diagnostic and management challenges, especially in the acute care setting.²The European Society for Medical Oncology (ESMO) and the National Comprehensive Cancer Network (NCCN) recommend thorough physical examination, comprehensive laboratory testing, and whole-body imaging (CT and PET scans) for all patients with metastatic cancer of unknown primary (CUP).² Clinical Case We report a rare case of a 37-year-old woman with no known history of diabetes who presented to the emergency department with symptoms of vomiting, weight loss, and persistent headaches. Initial investigations revealed hyperglycaemia, ketonuria, and metabolic acidosis consistent with DKA. Neurological symptoms prompted an urgent CT head, which revealed multiple cerebral lesions with surrounding oedema. Subsequent MRI brain confirmed multiple ring-enhancing lesions suggestive of metastases. CT thorax/abdomen/pelvis and PET scan demonstrated widespread metastatic involvement including lungs, liver, and lymph nodes, but no identifiable primary tumour. Comprehensive infectious screening (including HIV, TB, and toxoplasmosis) and tumour markers (CEA, CA-125, CA 19-9, AFP, and beta-HCG) were unremarkable. An excisional biopsy of a cervical lymph node revealed poorly differentiated adenocarcinoma, consistent with a diagnosis of cancer of unknown primary (CUP). The patient’s DKA was promptly managed with insulin therapy and fluid resuscitation. Cerebral oedema was treated with high-dose dexamethasone. The case was discussed in a multidisciplinary team (MDT) meeting, and the patient was placed on CUP pathway. On follow-up, the malignancy remained of unknown origin, and the patient was referred for palliative oncological care. Conclusion This case highlights the rare presentation of diabetic ketoacidosis as the initial symptom of an occult malignancy, specifically cancer of unknown primary origin. It underscores the importance of a comprehensive and multidisciplinary approach when atypical features accompany common endocrine emergencies. Clinicians should maintain a high index of suspicion and consider broader differentials when metabolic disturbances coexist with unexplained neurological or systemic signs. References: 1. Shahid RK et al. Diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome in cancer patients. Clin Med. 2024;100262. 2. Stella GM et al. Cancer of unknown primary: perspectives and therapeutic strategies. J Transl Med. 2012;10:12.Table 1:Summary of Histopathological and Immunohistochemical Findings in Right Submandibular Lymph Node Biopsy Figure 1:MRI brain showing multiple brain metastases with associated perilesional vasogenic oedema causing mass effect (Coronal section)
Rahman et al. (Thu,) studied this question.