Endocrine Abstracts

Introduction and Objectives: Vitamin D deficiency is highly prevalent. Both physicians and the population are increasingly aware of this fact, and the demand for determinations of vitamin D has escalated. The vitamin D status of the patients is most commonly assessed by the measurement of 25-hydroxycholecalciferol using an automated immunoassay. However, immunoassays are prone to interferences by circulating immunoglobulins such as rheumatoid factor, or more rarely by paraproteins in patients with multiple myeloma or monoclonal gammopathy. We hereby present the novel case of a patient with Waldenström macroglobulinemia who presented artifactually high levels of 25-hydroxycholecalciferol in successive routine clinical measurements, in order to raise awareness of this potentially dangerous laboratory error.

Methods: Review of the patient’s clinical records and of the relevant literature

Results: A 66-year-old had been diagnosed with Waldenström macroglobulinemia in 2013 and was treated with rituximab. He was referred to our Endocrinology Clinic in October 2023 because in all five routine measurements of 25-hydroxycholecalciferol performed by immunoassay since April 2021 up to October 2023 the result was >154.2 ng/mL (normal range 30.0 - 84.2 ng/mL) over the maximum measurable range and potentially toxic. The patient denied taking any supplement of vitamin D or multivitamins, had little solar exposure and did not consume cod liver. The measurements of calcium (over 20 determinations in a10-year follow-up), phosphate and intact PTH were repeatedly normal. The patient had no history of renal lithiasis, but an abdominal CT scan from 2018 showed cholelithiasis, which had caused no symptoms. There were no symptoms of hypercalcemia or vitamin D toxicity, consistently with the normocalcemia of the subject. The proteinogram showed a monoclonal paraprotein (IgM kappa light chain), 16.4 g/l. Rheumatoid factor was negative. We suspected paraprotein interference in the 25-hydroxycholecalciferol immunoassay and in November 2023 ordered a liquid chromatography- tandem mass spectrography (LC-MS/MS, reference method) yielding a result of 23.0 ng/mL of 25-hydroxycholecalciferol (low-normal) while our routine immunoassay again returned >154.2 ng/mL from the same venous sample.

Conclusion: The reference method confirmed an artifactual elevation of 25-hydroxycholecalciferol and discarded toxic levels, with the Waldenström paraprotein as the most likely culprit. While there are a few reports of similar interferences in patients with multiple myeloma or monoclonal gammopathy, or high levels of rheumatoid factor, this is a novel result in Waldenström macroglobulinemia. Physicians, especially endocrinologists, should be aware of this fact In order to avoid unnecessary diagnostic and therapeutic procedures.