A Diagnostic (Non)Dilemma

Introduction: Primary Hyperparathyroidism (pHPT) is a very common disease and should be thought of anytime persistent hypercalcemia is found. Having a normal range PTH level does not rule out pPHT and one should always obtain a 24hr urine Ca and evaluate end organ effects. A high bone turnover state is expected in pHPT with an elevated ALP. Case Description: 51 y/o M with PMHx of HIV on ART, CKD3, left knee avascular necrosis, and CHF presented for evaluation of hypercalcemia noted since 2017. Initially intermittent, serum calcium became persistently elevated to 11.2-11.8mg/dL (ionized Ca 5.8 mg/dL) over two years. He had no history of kidney stones or medications associated with hypercalcemia. Laboratory workup was notable for hypercalciuria (792mg/day), normal PTHrP, vitamin D 25 levels (35-68ng/mL), vitamin D 1,25 levels (48-69pg/mL) and persistently normal PTH (26-34pg/mL) and alkaline phosphatase (54 u/L) levels. Other workup included a DEXA scan with osteopenia, and a bone scan without focal uptake. Sestamibi parathyroid scan was negative, but neck ultrasound revealed a potential target lesion. Given the atypical presentation further validation was sought with undecalcified bone biopsy after double tetracycline labelling. Histology showed elevated bone turnover consistent with increased parathyroid activity, supporting the diagnosis of Normohormonal Primary Hyperparathyroidism (NHpHPT). Discussion: Classically, pHPT is recognized by the combination of hypercalcemia, with elevated or non-suppressed PTH levels. An absence of PTH elevation in our patient prompted a search for other causes of hypercalcemia including Familial Hypocalciuric Hypercalcemia (FHH), excessive dietary Ca intake, medications and Calcitriol mediated diseases, that were differentiated by elevated urinary calcium and normal vitamin D25 and vitamin D1, 25 levels. NHpHPT is defined by PTH level of 21-65pg/mL in patients with hypercalcemia. The most accepted hypotheses explaining the lower PTH levels is a lower physiological PTH setpoint. Accordingly, intraoperative PTH drop during parathyroidectomy (PTX) remains a 50% decrease to ensure sufficient resection of glandular tissue. Diagnosis can further be aided by assessing the end organ effects, specifically on the bones and kidneys. A lack of ALP elevation prompted a bone biopsy that showed high bone turnover consistent with pHPT. Ultimately, the patient underwent a parathyroidectomy.