Milk-Alkali Syndrome

Description

• Milk-alkali syndrome results from ingestion of excessive amounts of calcium and absorbable alkali (e.g., bicarbonate and citrate salts).
• Historically seen during self-treatment of indigestion or reflux (heartburn)
• Also seen with treatment/prevention of postmenopausal osteoporosis, consumption of carbonated beverages and calcium salts
• Characterized by:
  • Hypercalcemia
  • Metabolic alkalosis
    • ± Renal insufficiency
• System(s) affected: endocrine/metabolic; gastrointestinal (GI); renal/urologic
• Synonym(s): Burnett syndrome; Cope syndrome; milk poisoning; milk drinker syndrome; calcium alkali syndrome

Epidemiology

Incidence

• Third most common cause of hypercalcemia
• Recent increase associated with treatment for prevention of osteoporosis

Prevalence
Infrequent in the outpatient setting but 9–12% among hospitalized patients who have hypercalcemia

Etiology and Pathophysiology

• Cyclic process between intestines and kidneys: hypercalcemia from high-calcium intake (usually >4 g/day) believed secondary to inadequate response to calcitriol
• Hypercalcemia leads to vasoconstriction ultimately decreasing glomerular filtration.
• Activation of calcium-sensing receptors increases calcium reabsorption, absorption of bicarbonate, and natriuresis (maintaining alkalotic state).
• Blockade of antidiuretic hormone leads to increased diuresis.

Risk Factors

• Use of calcium-containing antacids or supplements
• Chronic kidney disease
• Simultaneous vitamin D supplementation
• Thiazide diuretic therapy
• Pregnancy (increased GI calcium absorption)
• Elderly
• Postmenopausal women (more common overall in women)
• Nicotine substitute chewing gum in large quantities

General Prevention

• Avoid excess milk and/or absorbable antacids.
• Use noncarbonate salts for calcium supplementation.
• Caution in elderly treated with ACE-I/ARB, NSAIDs, and diuretic

Commonly Associated Conditions

• Peptic ulcer disease
• Hiatal hernia
• Gastroesophageal reflux
• Osteoporosis
• Hypertension
• Hyperparathyroidism
• Hypercalcemia of malignancy