BASICS
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 for indigestion or "heart burn "
- Also seen with treatment/prevention of postmenopausal osteoporosis, consumption of carbonated beverages and calcium salts
- Characterized by the following:
- Hypercalcemia
- Metabolic alkalosis
- System(s) affected: endocrine/metabolic; gastrointestinal; renal/urologic
- Synonym(s): Burnett syndrome; milk poisoning; milk drinker 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.
GENERAL PREVENTION
- Avoid excess milk and/or absorbable antacids.
- Use noncarbonate salts for calcium supplementation.
ETIOLOGY AND PATHOPHYSIOLOGY
- Cyclic process: hypercalcemia from high-calcium intake (usually >4 g/day) coupled with increased renal calcium reabsorption due to metabolic alkalosis (by sensitizing calcium-sensing receptor in the kidney)
- Hypercalcemia leads to suppression of parathyroid hormone " reduced urinary calcium excretion (by inducing volume depletion). An increase in the reabsorption of bicarbonate also maintains the metabolic alkalosis.
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 woman
COMMONLY ASSOCIATED CONDITIONS
- Peptic ulcer disease
- Hiatal hernia
- Gastroesophageal reflux
- Osteoporosis
- Hypertension
- Hyperparathyroidism
- Hypercalcemia of malignancy
DIAGNOSIS
HISTORY
- Calcium-containing supplement use
- Symptoms of hypercalcemia ( "stones, bones, moans and groans " ):
- Nausea, vomiting, constipation
- Polyuria
- Mental status changes including lethargy, irritability, or depression
- Myalgias, muscle weakness, bone pain
- Headache
- Dry mouth
PHYSICAL EXAM
- Signs of hypovolemia:
- Tachycardia
- Dry mucous membrane
- Flat jugular vein
- Band keratopathy
- Periarticular calcinosis
DIFFERENTIAL DIAGNOSIS
Other causes of hypercalcemia:
- Primary hyperparathyroidism
- Malignancy-induced hypercalcemia
- Medication-induced hypercalcemia (lithium, vitamin D)
- Familial hypocalciuric hypercalcemia
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
- Serum calcium, phosphorus
- Ionized calcium (or corrected calcium with albumin)
- PTH
- 25-OH vitamin D
- Serum electrolytes (sodium, potassium, bicarbonate, BUN)
- Serum creatinine
- Arterial or venous blood gas
- TSH
Test Interpretation
- Hypercalcemia
- Mild metabolic alkalosis
- Increased BUN and creatinine levels
- Hypophosphatemia
TREATMENT
GENERAL MEASURES
- Stop calcium and alkali (carbonate salts):
- Supplements
- Over-the-counter antacids
- Volume expansion
- To maintain urine output of 3 L/day
MEDICATION
First Line
- Treat hypercalcemia:
- Hydration first: isotonic sodium chloride (0.9%) IV when serum calcium >15 mg/dL (3.75 mmol/L)
- Calciuresis: IV furosemide (1)[B]
- Precautions: Avoid volume depletion and replace electrolyte losses due to furosemide use.
Second Line
- Bisphosphonates inhibit bone resorption and have been used; however, associated with hypocalcemia (2)[C]
- Dialysis is rarely indicated (3)[B].
ISSUES FOR REFERRAL
- Persistent renal insufficiency
- Marked or symptomatic hypercalcemia
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
- Symptomatic hypercalcemia
- Correct volume depletion with IV hydration.
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
- Kidney function
- Fluid intake and output
- Correction of calcium after treatment
PATIENT EDUCATION
Daily calcium should not exceed 1.2 to 1.5 g.
PROGNOSIS
Favorable with appropriate therapy
COMPLICATIONS
Renal damage can be permanent.
REFERENCES
11 Suki WN, Yium JJ, Von Minden M, et al. Acute treatment of hypercalcemia with furosemide. N Engl J Med. 1970;283(16):836 " 840.22 Arroyo M, Fenves AZ, Emmett M. The calcium-alkali syndrome. Proc (Bayl Univ Med Cent). 2013;26(2):179 " 181.33 Gradwohl-Matis I, Franzen M, Seelmaier C, et al. Renal replacement therapy with regional citrate anticoagulation as an effective method to treat hypercalcemic crisis. ASAIO J. 2015;61(2):219 " 223.
ADDITIONAL READING
- Malcolm OT. Identification, treatment, and prevention of calcium-alkali syndrome in elderly patients. Consult Pharm. 2015;30(8):444 " 454.
- Medarov BI. Milk-alkali syndrome. Mayo Clin Proc. 2009;84(3):261 " 267.
- Patel AM, Goldfarb S. Got calcium? Welcome to the calcium-alkali syndrome. J Am Soc Nephrol. 2010;21(9):1440 " 1443.
- Swanson CM, Mackey PA, Westphal SA, et al. Nicotine-substitute gum-induced milk alkali syndrome: a look at unexpected sources of calcium. Endocr Pract. 2013;19(6):142 " 144.
CODES
ICD10
E83.52 Hypercalcemia
ICD9
275.42 Hypercalcemia
SNOMED
Milk alkali syndrome (disorder)
CLINICAL PEARLS
- Over-the-counter antacid or calcium supplement use can lead to hypercalcemia.
- Daily calcium supplementation should not exceed 1.2 to 1.5 g.
- Treatment is based on stopping excess consumption and ensuring adequate hydration.