High Calcium Levels, Bone Marrow Sarcoidosis May Be Associated

Elevated levels of calcium in blood and urine can be associated with the development of bone marrow sarcoidosis, according to a report published in the journal Biomarker Research.

The study, “Hypercalcemia Associated With Isolated Bone Marrow Sarcoidosis In A Patient With Underlying Monoclonal Gammopathy Of Undetermined Significance: Case Report And Review Of Literature,” reported the rare case of bone marrow sarcoidosis in a 57-year-old Caucasian woman. The patient had a history of monoclonal gammopathy of undetermined significance (MGUS, a disease similar to multiple myeloma, but less aggressive) who developed hypercalcemia (excessive calcium levels in the blood).

Previously reported cases of bone marrow sarcoidosis were mostly detected in patients with severe, chronic, and widespread sarcoidosis. The clinical manifestation of bone marrow sarcoidosis includes non-specific and variable symptoms such as fever, fatigue, melancholy, weight loss, and night sweats. The symptoms can overlap with systemic sarcoidosis.

Previous studies have suggested an association between sarcoidosis and immunosuppressive drugs against blood cancers, although the diagnosis of sarcoidosis usually preceded the cancer.

The team of researchers followed a patient they diagnosed with sarcoidosis four years after she had been diagnosed with MGUS. The patient complained that she had several weeks of dry mouth, excessive thirst, and episodes of confusion. Blood analyses revealed that her calcium levels were very high, 14.4 mg/dL, and she was sent to the hospital.

The doctors thought she was taking too much calcium so her calcium supplements were stopped, which decreased her calcium levels to 10 mg/dL. But because of her history of MGUS, doctors worried that she could develop myeloma, so the patient underwent a bone marrow biopsy. The team found the presence of granulomas, but they did not suggest cancer.

After two weeks, a new analysis of calcium levels indicated an increase (12.7 mg/dL) despite adequate fluid intake. A new battery of exams was performed to understand the origin of the patient’s hypercalcemia, but doctors ended up correlating this to the granulomas, for lack of another cause.

The patient then underwent sarcoidosis tests, which revealed elevated ACE serum level (a measure of blood pressure control) and hypercalciuria (elevated calcium levels in the urine), which together with hypercalcemia have been associated with sarcoidosis.

The doctors prescribed prednisone treatment for nine days, but when the patient stopped the treatment, calcium levels rose again. She then received a slow prednisone treatment for four months — one month after the end of the therapy, a follow-up bone marrow biopsy showed partial resolution of the granulomas. Two years later, the patient had no symptoms and normal calcium levels.

“Aside from her known MGUS, our patient has never had any malignant disease and was never treated with chemotherapy or immunosuppressives,” the authors wrote in their report. “This raises the possibility that MGUS, in addition to hematologic malignancies, may also be a risk factor in the development of sarcoidosis.”

The researchers concluded: “The clinical suspicion for sarcoidosis should be raised in patients with underlying hematologic disorders or malignancies. Due to the rarity of the condition, long terms outcomes in such patients are unclear. Surveillance and regular follow-up is planned in view of the possibility of progression to multiple myeloma or another lymphoproliferative disorder.”