Milk-Alkali Syndrome and Evaluation of Hypercalcemia

1. Milk-Alkali Syndrome and Evaluation of Hypercalcemia Morning Report 8/18/2009 TJ O’Neill

2. Hypercalcemia • Occurs when entry of Calcium (from GI tract and bone) exceeds rate of loss (urine loss and bone deposition) • Should be confirmed with albumin level and preferable ionized Ca

3. Clinical Manifestations • Calcium 10.5-12- usually asymptomatic • 12-14- symptoms may depend on acuity • >14- usually symptomatic • Neurologic/Psychiatric- • Renal • GI • CV-

4. Diagnostic Approach • First determine real • Next check PTH

5. Diagnostic Approach • Step 1: • Assess clinical history, draw labs, do a PE, check medications • Repeat Ca, check albumin, intact PTH • Elevated Ca and PTH – Primary, Tertiary or FHH • Check urinary Ca or phos – urinary ca elevated (40%) or nl (rest) in primary. Low in FHH or primary with concomitant vit D deficiency so then do ca/cr clearance (discussed later). Phos is usually elevated in tertiary, but low in primary.

6. Diagnostic Approach • Step 2 • Check PTH –rp • If elevated, usually confirms dx of humoral hypercalcemia of malignancy • However, this assay is often not necessary for diagnosis since most patients have clinically apparent malignancy. The production of PTH (intact) and calcitriol is usually appropriately suppressed in these patients

7. Step 3 Analyze Vit D metabolites Calcidiol (25 OH) and calcitriol (1,25OH) should be measured if there is no obvious malignancy and neither PTH nor PTH-rp levels are elevated Elevated calcidiol is indicative of vitamin D intoxication due to the ingestion of either vitamin D or calcidiol itself Elevated calcitriol may be induced by direct intake of this metabolite, extrarenal production in granulomatous diseases or lymphoma, or increased renal production that can be induced by primary hyperparathyroidism but not by PTH-rp

8. Diagnostic Approach • Step 4 • Look for other causes • presence of low serum levels of PTH, PTHrp, and vitamin D metabolites suggests some other source for the hypercalcemia • absence of malignancy or increased PTH-rp, unsuspected stimulation of bone resorption (as with multiple myeloma, thyrotoxicosis, immobilization, Paget's disease, or vitamin A toxicity) and unrecognized calcium intake in the face of renal insufficiency (as in the milk-alkali syndrome) are the most likely candidates

9. PTH Nomogram

10. Milk-Akali Sydrome • Originally recognized in the 1920s during administration of the Sippy regimen, consisting of milk and bicarbonate, for treatment of peptic ulcer disease. • One study found that the milk-alkali syndrome accounted for two percent of hospitalized patients with hypercalcemia between 1985 and 1989, as compared with 12 percent between 1990 and 1993 • Calcium in large doses may lead to suppression of parathyroid hormone (PTH), which then produces enhanced bicarbonate retention by the kidney. Continuing ingestion of calcium carbonate and bicarbonate retention leads to alkalosis, which causes increased calcium resorption in the distal collecting system of the kidney. Also, hypercalcemia produces a renal concentrating defect that can be considered a form of nephrogenic diabetes insipidus.

11. Excessive Dietary Calcium • ¾ cup Total cereal, 1 cup milk = 1300mg Calcium

12. Treatment • Fluids • Calcitonin- Inhibits osteoclast formation • Furosemide?- inhibits Ca reabsorbtion in loop of Henle • Bisphosphonates