Hypercalcemia - NEJM, liquids and electrolytes manual

Hypercalcemia

-Means a calcium level >10.4 mg/DL or a ionized calcium level >5.1 mg/DL. A mild to moderate hypercalcemia is from (10.4-13.5mg/DL) and a severe >13.5mg/DL.

-Every patient with hypercalcemia should has: albumin, PTH, [Urinary calcium], calcitriol, phosphorum and magnesium, Renal function

tests, ECG.

- The main treatment is liquid reposition with saline solution, and biphosphonates (specially in severe hypercalcemia) like Zolendronic and Alendronic Acid.

Ninety percent of cases of hypercalcemia overall are due to primary hyperparathyroidism or a malignant condition, but of those due to the latter, less than 1% are a consequence of Hodgkin's lymphoma.4 Similarly, among patients with Hodgkin's lymphoma, only 5% have hypercalcemia.5Hypercalcemia of malignancy typically occurs through the following mechanisms: a humoral effect mediated by PTHrP, osteolytic metastases, or ectopic 1-alpha-hydroxylation of 25-hydroxyvitamin D resulting in increased calcitriol levels.6 This last mechanism is characteristic of Hodgkin's lymphoma 7; the extrarenal production of calcitriol by the lymphoma or tumor-infiltrating macrophages substantially increases absorption of calcium from the intestine, raising the serum calcium level. In the normal state, 1-alpha-hydroxylase converts 25-hydroxyvitamin D to calcitriol under the control of PTH, in response to hypocalcemia. In contrast, the 1-alpha-hydroxylase in lymphoma cells or tumor-infiltrating macrophages is poorly sensitive to feedback from circulating PTH, leading to inappropriate calcitriol production.8

All patients with severe hypercalcemia require treatment to correct the serum calcium concentration, to restore euvolemia, and to address the underlying disease process. Volume resuscitation is central to recovery, followed by therapy to inhibit bone resorption, target the underlying cause of hypercalcemia, and induce calciuresis.9,10 In patients with calcitriol-mediated hypercalcemia, glucocorticoids are the therapy of choice, reducing calcitriol production by macrophages and typically correcting the serum calcium within 3 to 5 days after the initial dose.11For hypercalcemia of malignancy, bisphosphonates are the principal treatment — in particular, the potent agent zoledronic acid.

In this case, the elevated calcitriol level, with low levels of PTH and PTHrP, suggested lymphoma as the cause of the hypercalcemia and ultimately led to imaging, visualization of adenopathy not palpable on physical examination, definitive tissue diagnosis, and effective therapy. This case underscores the importance of measuring calcitriol levels while one searches for the underlying cause of hypercalcemia in cases unexplained by a high level of PTH or PTHrP