Hypophosphatasia with Coexisting Endocrinopathies: A Diagnostic Dilemma

Adult-onset hypophosphatasia presents a diagnostic challenge due to confounding clinical and analytical factors. Although rare, the consequence of missed diagnosis is significant, as it can potentiate skeletal mineralization defects. Despite the recent development of diagnostic criteria, integration into routine clinical practice remains limited, partly due to the variable course of disease progression. Effective management often requires a multidisciplinary team, including rheumatologists, orthopedic surgeons, endocrinologists, medical geneticists, dentists, physical and occupational therapists, pain specialists and clinical biochemists. Here, we present a case of adult-onset autosomal dominant hypophosphatasia, where diagnosis was complicated by coexisting endocrine disorders, Addison's disease and primary hypothyroidism. Persistently decreased alkaline phosphatase activity had been observed for over a decade and were initially attributed to hypothyroidism. However, an endocrinologist's clinical suspicion led to genetic testing, confirming hypophosphatasia. Although the patient exhibited no additional symptoms such as premature tooth loss, osteopenia, or osteoporosis, this incidental finding prompted a referral to medical genetics, carrier screening to support family planning, and cascade testing for family members.