Endocrine Abstracts

Background: Hypocalcaemia is a common biochemical disorder; accurate distinction between inherited and acquired aetiologies is essential, as it directly influences treatment and long-term prognosis. This case highlights the diagnostic and therapeutic complexities inherent in hypocalcaemia in the presence of underlying genetic predisposition.

Case: A 57-year-old previously healthy gentleman presented with lethargy and non-specific paraesthesia. Routine blood tests indicated marked hypocalcaemia, adjusted calcium of 1.62mmol/l (Ref-2.2-2.6). He was admitted for intravenous calcium infusions, followed by oral alfacalcidol and calcium supplementation. However, hypocalcaemia persisted, necessitating further biochemical and clinical assessments. Investigations revealed suppressed parathyroid hormone (PTH), hyperphosphataemia, and hypercalciuria, raising suspicion of inherited calcium disorders, a calcium-sensing receptor (CASR)-related disorder. Family history uncovered his son had presented similarly in childhood, with persistent hypocalcaemia and suppressed PTH. Subsequent genetic evaluation confirmed autosomal dominant hypocalcaemia (ADH), a rare condition caused by activating mutations in CASR (ADH1). His alfacalcidol and calcium have been stopped, and he is managed with simple observation only, he remains well despite calcium of 1.6mmol/l. ADH is characterised biochemically by low serum calcium, inappropriately low or suppressed parathyroid hormone, hyperphosphataemia, and hypercalciuria. While approximately half of patients are asymptomatic or mildly symptomatic, others may present with paraesthesia, tetany, seizures, nephrocalcinosis, or basal ganglia calcifications. Notably, treatment with conventional calcium and vitamin D analogues can exacerbate hypercalciuria, predisposing to renal complications. This case highlights the significance of measuring urine calcium in the assessment of unexplained hypocalcaemia and considering genetic predisposition. The management of ADH should be symptom-driven, with maintaining serum calcium within the low-normal range while minimising the risk of renal impairment.

Conclusion: Not all cases of hypocalcaemia warrant aggressive treatment. The identification of ADH is paramount, as indiscriminate therapy could potentially result in greater harm than benefit. A personalised approach, incorporating genetic diagnosis and symptom evaluation, ensures optimal patient outcomes.