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

Clin Endocrinol (Oxf). 2005 Nov;63(5):566-76. doi: 10.1111/j.1365-2265.2005.02383.x.


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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Calcium Carbonate / adverse effects
  • Diphosphonates / adverse effects
  • Diphosphonates / therapeutic use
  • Diuretics / therapeutic use
  • Female
  • Humans
  • Hypercalcemia / blood
  • Hypercalcemia / complications*
  • Hypercalcemia / diagnosis
  • Hypercalcemia / drug therapy
  • Hypercalcemia / etiology*
  • Kidney Diseases / blood
  • Kidney Diseases / complications*
  • Kidney Diseases / drug therapy
  • Magnesium / blood
  • Male
  • Middle Aged
  • Potassium / blood
  • Retrospective Studies
  • Sex Distribution
  • Sodium Bicarbonate / adverse effects


  • Diphosphonates
  • Diuretics
  • Sodium Bicarbonate
  • Calcium Carbonate
  • Magnesium
  • Potassium