MON-343 The Mystery of Recurrent PTH-Independent Hypercalcemia with Severe Hypophosphatemia

Abstract

BackgroundThe differential diagnoses for PTH independent hypercalcemia with hypophosphatemia are broad. Careful history with systematic evaluation for possible etiologies is necessary for accurate diagnosis and timely therapeutic intervention.Clinical CaseA 72-year old female was referred to our clinic for evaluation of hypercalcemia with low iPTH level. Review of lab workup over the past two years showed frequent occurrences of mild hypercalcemia, low iPTH and moderate to severe hypophosphatemia. She denied use of calcium, vitamin D, Vitamin A or herbal supplements and over the counter (OTC) medications. Age-appropriate cancer screening was up to date. She had no clinical evidence of granulomatous diseases or malabsorption syndrome. Labs revealed corrected calcium (cCa) 9.9 (8.5-10.5 mg/dL), iPTH 6.36 (12-88 pg/mL), phosphate 1.5 (2.5-4.5 mg/dl), magnesium 1.6 (1.8-2.7 mg/dl), 25-OH Vit D 30 (30-100 ng/mL), PTHrP 12 (14-27 pg/mL), 1,25 OH Vit D 32 (18-72 pg/ml), TSH 1.8 (03-5.6 uIU/mL), GFR 49 (>90 mL/min/1.73 m2) and bicarbonate 30 (23-31 mEq/L). FGF23, 1-mg ODST and SPEP were normal. 24-hour urine phosphate was 3 mg/24h, ruling out renal phosphate wasting.Two months later, she developed myalgia and generalized weakness. Labs showed cCa 11.3mg/dl, iPTH 3.79 pg/ml, phosphate <1 mg/dl, magnesium 1.2 mg/dl, bicarbonate 33 mEq/L. She was hospitalized for severe hypophosphatemia. Here, she revealed she was intermittently taking a “milky” antacid obtained from Mexico, for her GERD. She required IV phosphate and magnesium replacement and her mineral abnormalities normalized within 24 hours. She was advised to stop use of OTC antacids and provided daily phosphate and magnesium supplementation. 4 weeks later, she developed recurrent hypercalcemia 10.4 mg/dl, hypophosphatemia 1.1 mg/dl and alkalosis with bicarbonate 35 mEq/L, which corrected with supervised phosphate and magnesium supplementation and restricted access to home OTC medications.DiscussionMilk-alkali syndrome, characterized by the triad of hypercalcemia, metabolic alkalosis and renal failure, has been classically associated with ingestion of large amounts of milk and absorbable alkali. Once a common cause of hypercalcemia, its incidence declined rapidly with advent of new therapies for PUD. Recently, this syndrome, now described as calcium-alkali syndrome (CAS) has re-emerged due to use of high dose calcium carbonate supplements and OTC antacids, with a prevalence of 9-12% among hospitalized patients with hypercalcemia.We hypothesize our patient’s mineral abnormalities are explained by CAS. High doses of calcium from antacids can bind phosphate in the gut, leading to poor phosphate absorption and hypophosphatemia.ConclusionCAS is emerging as a frequent cause of hospital admissions for hypercalcemia. Severe hypophosphatemia can be a rare manifestation. Primary therapy is withdrawal of offending agent.