Monte Minute‎ > ‎Monte Minute‎ > ‎

Untitled Post

posted Feb 9, 2015, 11:28 AM by Kevin Hauck

Today we have a post on the Milk-Alkali Syndrome from Firm 3's very own Julie Lorton:

Milk- Alkali Syndrome

In this week's Chief of Service noon conference, Dr. Fleischer from the Endocrinology Department precepted the case of a 67 year old woman presenting with altered mental status who was discovered to have an elevated calcium of 16.3, in the setting of taking up to 20 Tums tablets daily for reflux symptoms.

What is it?

The classic findings in Milk-Alkali syndrome are hypercalcemia, metabolic alkalosis, and AKI. The name is derived from the historic etiology of the disease, an antiacid regimen from the early 1900s involving hourly doses of milk plus sodium bicarbonate. Current cases usually involve large doses of calcium carbonate (or other calcium derivatives) rather than milk – often for bone health rather than ulcer disease these days. Following hyperparathyroidism and malignancy, it is the third most common cause of hypercalcemia.



Development of Milk-Alkali syndrome require intake of a large amount of calcium and absorbable alkali which overwhelms the normal calcium homeostasis system. Only a small percentage of those who consume a large amount of calcium/alkali will develop the syndrome however; in the majority, normal renal function and calcitriol suppression (leading to decreased intestinal calcium absorption) will maintain homeostasis.

The role of calcitriol in development of the syndrome remains unclear (some patients with the syndrome have appropriately suppressed calcitriol while others do not), however  with calcium intake >10 grams daily, large amounts of calcium can be absorbed despite calcitriol suppression.

The majority of mechanisms underlying the development of AKI and alkalosis occur in the kidney. Hypercalcemia leads to volume depletion in a variety of ways including renal vasoconstriction, blockade of ADH-dependent water reabsorption, and inactivation of the Na-K-2Cl channel in the thick ascending limb via a calcium-sensing receptor. Volume depletion subsequently contributes to metabolic alkalosis (in addition to the consumption of alkali via calcium carbonate, sodium bicarbonate, etc) by increasing bicarbonate absorption in the renal tubules. Metabolic alkalosis then actually contributes to ongoing hypercalcemia via activation of the TRPV5 renal calcium channel which increases calcium reabsorption at alkaline pH levels.

Volume depletion is the primary etiology of the AKI associated with Milk-Alkali syndrome, although chronic hypercalcemia/metabolic acidosis from the syndrome have also been associated with more chronic renal changes due to calcium preceiptation/deposition in the renal tubules/interstium.



Presentation depends on acuity/severity of hypercalcemia.

In acute hypercalcemia, patients may present with the classic “bones, stones, groans and psychiatric overtones” we all learned in medical school. More chronic cases may present with findings like polyuria/polydipsia, muscle aches and pruritus.

Milk-Alkali syndrome is often discovered incidentally on routine lab work in asymptomatic patients however. Common clinical scenarios include postmenopausal women on calcium supplements for osteoporosis prevention/treatment, patients taking OTC antiacids with calcium for gastritis/dyspepsia, and dialysis patients on calcium carbonate for secondary hyperparathyroidism. Patients at higher risk to develop Milk-Alkali include those with risk factors for renal insufficiency (elderly, on ACE-i/ARB/NSAIDs, CKD) or volume depletion (on diuretics, particularly thiazides which independently increase renal calcium reabsorption, pregnant women with hyperemesis, bulimic patients).



Clinical/medication history is key in making the diagnosis of Milk-Alkali syndrome; however there are also some findings on labs that can help differentiate the etiology of hypercalcemia.

PTH should be suppressed, differentiating Milk-Alkali from primary (or tertiary) hyperparathyroidism. Hypophosphatemia is a common finding since calcium carbonate binds phosphate (although not in the historic syndrome, since milk itself is high in phosphate and may cause hyperphosphatemia), whereas in Vitamin D intoxication (or granulomatous diseases which cause hypercalcemia via Vitamin D metabolism), hyperphosphatemia is common. Urine calcium, which can be evaluated with a spot Urine calcium:creatinine ration, will be low in Milk-Alkali syndrome unlike all other causes of hypercalcemia with the expception of Familial Hypocalciuric Hypercalcemia (in which degree of hypercalcemia would be expected to be mild and chronic). PTHrp obviously should not be elevated in Milk-Alkali unlike hypercalcemia  of malignancy.



Stopping/reducing the calcium intake is the most important step in management!

For more acute management of hypercalcemia, IV fluids are the most important treatment and will also improve AKI and alkalosis. Diuretics such as furosemide can also speed up calciuresis, however should be given only after adequate volume IV fluid administration as most patients wtih Milk-Alkali syndrome are already volume depleted.

Hypocalcemia can actually result transiently following treatment for Milk-Alkali because once the impetus for hypercalcemia (i.e. oral calcium) has been removed, serum calcium normalizes very quickly while PTH suppression is slower to recover. Bisphosphonate therapy is therefore not recommended for Milk-Alkali since it can contribute to more prolonged hypocalcemia once the initial hypercalcemia has resolved.


The patient in question had in fact received pamidronate in the ED prior to admission in addition to IV fluid and furosemide; her hypercalcemia resolved within 24 hours and currently, 4 days after admission, she is mildly hypocalcemic possibly due in part to bisphosphonate administation.




Morishita Y, Yoshizawa H, Kusano E. Renal injury in calcium-alkali syndrome. J Nephrol Therapeutics, S3:006 (2012), doi:10.4172/2161-0959.S3-006.

Patel AM, Goldfarb S. Got calcium? Welcome to the calcium–alkali syndrome. J Am Soc Nephrol, 21 (2010), pp. 1440–1443.