MON-745 - A Rare Coexistence of Bone Metabolism Disorders: Hypophosphatasia in the Setting of Primary Hyperparathyroidism

Introduction: Hypophosphatasia (HPP) is a rare genetic disorder of bone and mineral metabolism caused by mutations in the ALPL gene, leading to a deficiency in tissue-nonspecific alkaline phosphatase (TNALP).1 Symptoms can include early loss of teeth, musculoskeletal pain, fatigue, and fragility fractures; further, laboratory evaluation characteristically shows low alkaline phosphatase (ALP).1 On the other hand, primary hyperparathyroidism (PHPT) results in the overproduction of parathyroid hormone (PTH), usually caused by a parathyroid adenoma. PHPT results in increased bone turnover markers, including ALP.1 The coexistence of HPP and PHPT is extremely rare, and when present, can create a diagnostic challenge. In a patient with both disorders, ALP levels can be in the normal range, and the diagnosis of HPP can be missed.2

Case: We present a case of a 75-year-old woman with a history of osteopenia and osteoporosis referred to endocrinology for evaluation and management of hypercalcemia. During initial evaluation, the patient was noted to have mild hypercalcemia with a corrected serum calcium of 10.1 [reference 8.6-10.0 mg/dL] and an inappropriately normal PTH, raising concern for primary hyperparathyroidism. However, ALP was found to be consistently low to low-normal, with the lowest being 28 (reference 35-104 U/L), an atypical finding in the setting of primary hyperparathyroidism, which raised suspicion for HPP. A positive HPP panel confirmed the diagnosis, and enzyme replacement therapy with asfotase alfa was started. For PHPT evaluation, a parathyroid ultrasound revealed a possible left parathyroid adenoma; however, sestamibi scintigraphy revealed no convincing evidence of adenoma localization. Further, the decision was made to proceed with conservative management due to the patient’s lack of hypercalcemic symptoms and absence of risk factors such as chronic kidney disease and renal stones.

Conclusions: This case highlights the importance of maintaining clinical suspicion of HPP in patients who present with hyperparathyroidism and a low to normal ALP, as delaying diagnosis can lead to inappropriate management. Additionally, typical osteoporosis pharmacological agents such as bisphosphonates are contraindicated in HPP and may worsen skeletal outcomes if started.

References:

1. Mutlu, Ü., Sarıbeyliler, G., Hacişahinoğulları, H., Işcan, A. Y., Aksakal, N., Yalın, G. Y., Selçukbiricik, Ö. S., Üzüm, A. K., & Gül, N. (2022). A rare case of adult hypophosphatasia masked with primary hyperparathyroidism [Abstract ID: luac014.021]. Journal of the Endocrine Society, 6(Supplement_1).
2. Nachawi, N., Kodali, A., & Zhou, K. (2022). Adult hypophosphatasia: More than a skeletal problem [Abstract #1184925]. Endocrine Practice, 28(Supplement), S74–S98. https://doi.org/10.1016/j.eprac.2022.03.227

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