Clinical Endocrinology

Milk–alkali syndrome is a major cause of hypercalcaemia among non-end-stage renal disease (non-ESRD) inpatients


Michalis K. Picolos, The University of Texas–Houston Medical School, 6431 Fannin Street, MSB 6·100, Houston, TX 77030, USA. Tel.: 713 500 6646; Fax: 713 500 6647; E-mail:


Objective  Milk–alkali syndrome, once a common cause of hypercalcaemia, is now considered rare. Our aim was to estimate the prevalence of milk–alkali syndrome among hypercalcaemic, non-end-stage renal disease (non-ESRD) inpatients of a University Hospital and identify patients’ and syndrome characteristics.

Design and patients  In this retrospective chart review study, we identified patients hospitalized with possible hypercalcaemia between November 1998 and October 2003 by a computer search of admission, discharge and consultation diagnoses. Patients with renal transplantation, stage 5 chronic kidney disease (CKD-5) and those admitted for parathyroidectomy were excluded. The remaining patients’ charts were reviewed for confirmation of hypercalcaemia and identification of the cause. In patients with milk–alkali syndrome, additional historical, clinical, laboratory and imaging data were collected.

Results  We identified 125 patients with hypercalcaemia, 11 (8·8%) of whom had milk–alkali syndrome, 42 (33·6%) had malignancy and 37 (29·6%) hyperparathyroidism. Thirty-five patients had severe hypercalcaemia, defined as corrected serum calcium  3·5 mmol/l. Malignancy accounted for 13 of those patients (37·1%) and milk–alkali for nine (25·7%). Conditions prevalent among the milk–alkali inpatients were female gender, hypertension, chronic kidney disease, osteoporosis, upper gastrointestinal diseases, diuretic treatment and vitamin D derivative supplementation. Five of the patients with milk–alkali syndrome were treated with bisphosphonates and all five developed hypocalcaemia, compared to one of the five who received conventional treatment (P = 0·047).

Conclusion  Milk–alkali was the third leading cause of hypercalcaemia of any degree and the second cause of severe hypercalcaemia among inpatients without ESRD. In milk–alkali syndrome, treatment with bisphosphonates contributes to post-treatment hypocalcaemia.