Fellow Texas Tech University Odessa, Texas, United States
Introduction: Milk-Alkali Syndrome (MAS) is among the leading causes of hypercalcemia often following over-supplementation of exogenous calcium and may present with renal failure and metabolic alkalosis after onset of symptoms. We describe a patient with unusual precipitation of hypercalcemia, likely due to increased calcitriol (1,25 OH vitamin D) titration while on calcium supplements in the context of postoperative hypoparathyroidism.
Case Description: 64-year-old female with a history of parathyroidectomy treated with calcium citrate (675 mg daily), 25-OH vitamin D (4000 IU daily) and calcitriol 0.25 mcg BID for 20 years was found by PCP to have calcium of 7.2 (8.8-10.2 mg/dl) for which calcitriol was increased to 0.5 mcg BID. After one month of calcitriol titration, patient reported to the ED with fatigue, loss of balance and confusion for 15 days. Labs showed calcium 18.9 (8.8-10.2 mg/dl), 25-OH vitamin D 84 (>30 ng/ml), 1,25-OH vitamin D 31.2 (19.9-79.3 pg/ml), phosphorus 3 (1.6-2.4 mg/dl), PTH 6.5 (15-65 pg/ml), creatinine of 3 (0.5-1.0 mg/dl) and bicarbonate of 30 (22-29 mmol/L). There was no evidence of nephrocalcinosis on renal ultrasound. She was treated with calcitonin 400 units BID for four days, zoledronic acid 3 mg IV once and fluids. Serum calcium decreased to 9.2 mg/dl with improvement in symptoms and she was discharged on calcitriol 0.5 mcg am/0.25 mcg pm and calcium citrate/25-OH vitamin D (675 mg/4000 IU daily). She continued to experience intermittent paresthesias with serum calcium levels ranging from 6.5-9.5 mg/dl. Further workup revealed 24-hour urinary calcium 7390 mg ( <300 mg/24 hrs), serum creatinine 1.4 mg (0.5-1.0 mg/dl) and 25-OH vitamin D 77 ( >30 ng/ml). Treatment was adjusted with initiation of hydrochlorothiazide 12.5 mg BID, calcitriol lowered to 0.25 mcg BID, calcium citrate 516 mg/daily and 25-OH vitamin D was held. One month later, repeat 24-hour urinary calcium decreased to 280 mg ( <300 mg/24 hrs) along with stabilization of serum calcium and resolution of paresthesias.
Discussion: The pathogenesis of MAS from exogenous calcium in the setting of increased doses of calcitriol is not well known. The only factor that changed was the doubling of the calcitriol dose one month before hospitalization suggesting a robust response to calcitriol. 24hr urine calcium helped direct therapy, as the patient had hypercalciuria, denoting inadequate retention in the absence of PTH. Serum calcium stabilized at lower doses of calcium supplementation after adding HCTZ. A better understanding of calcitriol's pharmacokinetics could explain the appropriate, individualized supplementation and the need for close monitoring of calcium if adjusting the calcitriol dose.
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