A case of unexplained hypercalcemia

A variety of conditions can cause hypercalcemia, primary hyperparathyroidism (pHPT) and malignancy account for 80 to 90% of cases. The history, physical examination, chest X-rays, and laboratory assessment will provide the correct diagnosis with an accuracy of 95%. Adding measurement of intact parathyroid hormone (PTH) will increase the accuracy to 99%. In patients with underlying malignancy, elevation of serum calcium is most often caused by hypersecretion of PTH-related peptide (PTHrP). In the absence of malignancy or increased PTHrP and PTH in serum, stimulation of bone resorption (e.g. multiple myeloma) and unrecognized calcium intake in the face of renal insufficiency (as in milk-alkali-syndrome) or vitamin D intoxication are amongst the most common causes. We describe the case of a 44 year old iranian women, who first presented with acute renal failure. She reported generalized osseous pain. Calcium levels were decreased to 4.2 mmol/L (Phosphat 2.8 mmol/L). PTH was suppressed and PTHrP as well as Vitamine- D-metabolites were lowered. Parameters for stimulation of bone resorption were dramatically elevated. Bone x-ray and repeated bone scintigraphy showed diffuse signs of considerably activated bone metabolism without focal accentuation. Consecutive substitution of vitamine D and bisphosphonates resulted in a minimal reduction of bone metabolism, but significant improvement of pain. Subsequently three bone biopsies were obtained, that showed changes compatible with pHPT or secretion of PTHrP. Laboratory values could not confirm this suspected diagnosis. An activation of bone metabolism by PTHrP or aberrant PTH undetected by our assay, could not be excluded. Repeated laboratory and radiological examinations revealed no signs of tumor growth or systemical malignancy at any time. Other causes including sarcoidosis, hyperthyroidism, M. Paget, thiacides, famial hypocalciuric hypercalcemia, vitamine D intoxication, drugs or milk-alkali-syndrome could be excluded. Despite an extensive diagnostic work-up, the cause of hypercalcemia in this patient remained unclear.