Background: Hypercalcaemia is a common biochemical abnormality with a broad differential diagnosis. In patients with chronic kidney disease (CKD) and malignancy, interpretation of calcium homeostasis can be particularly challenging, increasing the risk of diagnostic anchoring and inappropriate management. Familial hypocalciuric hypercalcaemia (FHH) is a rare inherited disorder that should be considered in cases of persistent PTH-dependent hypercalcaemia, although diagnosis may be confounded by CKD.

Case: We present the case of a 72-year-old woman with stage 4 CKD and a history of multiple myeloma in sustained remission who developed progressive hypercalcaemia and worsening renal function. Initial concern centred on malignancy-related hypercalcaemia or CKD-associated mineral and bone disorder. However, review of her longitudinal biochemical profile demonstrated persistent hypercalcaemia with an inappropriately elevated parathyroid hormone dating back more than five decades. Interpretation of urinary calcium excretion was limited by advanced CKD, prompting careful integration of the patient's clinical history, family history and biochemical findings. Genetic testing ultimately confirmed a heterozygous pathogenic calcium-sensing receptor (CASR) variant, establishing the diagnosis of familial hypocalciuric hypercalcaemia. Recognition of the underlying diagnosis avoided unnecessary parathyroid surgery and enabled successful medical management with cinacalcet.

Conclusion: This case highlights the diagnostic complexity of PTH-dependent hypercalcaemia in the presence of CKD and previous malignancy. It demonstrates the importance of avoiding premature diagnostic closure, particularly when common conditions may obscure rarer endocrine disorders. A thorough longitudinal review of biochemical data, careful family history and appropriate use of genetic testing are essential in establishing the correct diagnosis. Recognition of FHH has significant implications for patient management, preventing unnecessary intervention while facilitating appropriate long-term treatment and genetic counselling.