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Parathyroid/Bone Disorders

(20.05) Hypercalcemia with an Unusual Etiology

Saturday, May 11, 2024
12:10 PM – 12:25 PM CDT
Location: ePoster Showcase, Empire Ballroom Foyer, Level 2
Introduction : Calcium homeostasis is maintained by multiple hormones and organ systems. There are myriad differentials for hypercalcemia, but the most common cause is primary hyperparathyroidism. Of the remainder, most non-PTH mediated cases are due to malignancy or granulomatous disease. The following case presents a man with an unusual cause of hypercalcemia.

Case(s) Description :

A 59-year-old man with a history of hepatitis B cirrhosis status-post liver transplant, chronic kidney disease, heart failure with reduced ejection fraction, and type 2 diabetes was found to have elevated serum calcium and acute kidney injury on outpatient labs, prompting referral to the emergency department. Over the prior two months, he experienced fatigue, generalized weakness, nonproductive cough, and an unintentional weight loss of 30 lbs. 

Labs showed albumin-corrected calcium 15.8 mg/dL (8.7-10.5), phosphorus 3.6 mg/dL (2.7-4.5), and PTH 17.3 pg/mL (9.0-77). Vitamin D 78 ng/mL (30-96) and PTP-related protein < 0.4 pmol/L (< =4.2). Bone-specific alkaline phosphatase (ALP) was 466 U/L (55-135) with normal gamma-glutamyltransferase and mildly elevated liver enzymes. CEA, CA-19, AFP, and PSA were all unremarkable. SPEP revealed a polyclonal gammopathy. CT chest, abdomen, and pelvis was unremarkable. Liver biopsy was negative for rejection and malignancy. MRI brain findings correlated with CT scan, and revealed an abnormal marrow signal in the right frontal calvarium with periosteal thickening in the right frontal scalp. Bone scan showed increased metabolic activity in the right frontal calvarium and possibly in the right mid fibula.  X-ray of the right fibula was normal. Due to concern for osteomyelitis in the calvarium and immunosuppression, fungal serologies, HIV, Hep C, and RPR were ordered. Only RPR was positive (titer > 1:8192). Lumbar puncture with +VDRL in the CSF, confirming tertiary syphilis.

He received IV fluids and pamidronate for hypercalcemia. He was treated with IV penicillin for tertiary syphilis. Calcium gradually declined and normalized 6 weeks later. ALP gradually declined from a maximum of 804 U/L down to 143 U/L (mildly above ULN), 8 months later.

Discussion :

This patient’s high bone-specific ALP with normal GGT and increased metabolic activity on bone scan are suspicious for bony destruction as the cause of hypercalcemia. Reports of bone involvement in syphilis have been rarely reported, but none mention hypercalcemia. However, it appears to be the most likely etiology based on otherwise negative workup and long-term resolution of hypercalcemia after completing syphilis treatment.