Milk-Alkali Syndrome: Definition and Treatment
Milk-alkali syndrome (MAS) is a clinical triad of hypercalcemia, metabolic alkalosis, and acute kidney injury caused by excessive ingestion of calcium and absorbable alkali, most commonly calcium carbonate. 1, 2
Clinical Presentation
MAS presents with three defining features that must be present simultaneously:
- Hypercalcemia (elevated serum calcium levels) 2, 3
- Metabolic alkalosis (elevated serum bicarbonate and pH) 2, 3
- Acute renal failure (elevated creatinine with decreased GFR) 2, 3
Common symptoms include encephalopathy, confusion, nausea, vomiting, weakness, and in severe cases, seizures or posterior reversible encephalopathy syndrome. 1, 4
Diagnostic Criteria
The diagnosis requires:
- History of excessive calcium and alkali intake, particularly calcium carbonate (Tums, calcium supplements for osteoporosis prevention) 1, 2, 3
- Laboratory confirmation showing the classic triad of hypercalcemia, alkalosis, and renal impairment 2, 3
- Appropriately suppressed parathyroid hormone (PTH) in response to hypercalcemia (amino-terminal PTH should be low, though carboxy-terminal PTH may be falsely elevated due to renal failure) 1, 3
- Low or normal 1,25-dihydroxyvitamin D levels (appropriately suppressed by hypercalcemia) 1, 3
- Exclusion of other causes of hypercalcemia including malignancy, primary hyperparathyroidism, and granulomatous disease 2, 5
Treatment Algorithm
Step 1: Immediate Discontinuation
Stop all calcium and alkali-containing products immediately. This is the single most critical intervention. 2, 5, 3
Step 2: Volume Resuscitation
Administer aggressive intravenous fluid resuscitation with 0.9% normal saline to restore intravascular volume, enhance renal calcium excretion, and improve GFR. 1, 5, 3
Step 3: Calcitonin Administration
Initiate calcitonin therapy for rapid reduction of serum calcium levels in severe cases (typically 4 IU/kg subcutaneously or intramuscularly every 12 hours). 1
Step 4: Renal Replacement Therapy
Proceed to intermittent hemodialysis if the patient develops anuria, severe refractory hypercalcemia, or life-threatening complications despite conservative measures. 1, 3
Step 5: Supportive Care
Provide supportive management for encephalopathy, seizures, and other complications until metabolic abnormalities resolve. 1, 4
Prognosis and Reversibility
The acute and subacute forms of MAS are typically fully reversible with conservative treatment, including cessation of calcium/alkali intake and supportive measures. 2, 5, 3 However, chronic MAS may result in only partially reversible renal disease if diagnosis is delayed. 5 Early identification prevents progression to irreversible chronic renal failure. 5
Clinical Pitfalls
Physicians and patients are often unaware of the calcium and alkali content in over-the-counter medications, leading to missed diagnoses. 3 A detailed medication history, including all supplements and antacids, is essential. 3 The syndrome has resurged due to widespread use of calcium carbonate for osteoporosis prevention and self-treatment of dyspepsia. 5, 4, 3
Do not confuse elevated carboxy-terminal PTH (due to renal failure) with primary hyperparathyroidism—measure amino-terminal PTH, which should be appropriately suppressed in MAS. 1, 3