Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Milk-Alkali Syndrome Treatment & Management

  • Author: R Hal Scofield, MD; Chief Editor: George T Griffing, MD  more...
 
Updated: Aug 12, 2014
 

Approach Considerations

Mild hypercalcemia

The only care required is discontinuation of calcium carbonate or reduction of the dose to no more than 1200-1500mg of elemental calcium daily. In most patients, calcium supplementation should be changed to a form of calcium other than calcium carbonate. Thus, absorbable alkali is avoided.

Severe hypercalcemia

The patient should be admitted to the hospital. Saline diuresis, produced by infusion of large volumes of intravenous isotonic sodium chloride solution, is the treatment of choice. Further calciuresis can be induced by treatment with intravenous loop diuretics, although the utility of loop diuretics for hypercalcemia has been questioned.[34]

The typical patient is volume depleted; therefore, volume should be replaced with saline prior to institution of diuretic therapy. Care should be taken to not induce volume depletion with the diuretics, because this may worsen the hypercalcemia.

Calcium carbonate should be stopped to resolve the pathophysiology that produced the hypercalcemia. As stated previously, however, patients with milk-alkali syndrome may become transiently hypocalcemic during treatment with intravenous saline and intravenous diuretics.

Because laboratory studies such as PTH measurements will not have returned to normal when therapy is instituted, the serum calcium level must be monitored closely.

Pamidronate has been used successfully in the treatment of hypercalcemia secondary to milk-alkali syndrome. However, treatment of milk-alkali syndrome with bisphosphonates was associated with hypocalcemia in one series; 6 of 11 patients with milk-alkali syndrome developed treatment-induced hypocalcemia, with 5 of the 6 patients having received bisphosphonates,[7] while in the author’s series of 6 patients, none of whom received bisphosphonate, only 1 developed hypocalcemia.[6]

Treatment-related hypocalcemia

If hypocalcemia develops in the course of treatment, this usually can be treated with oral calcium supplementation. A calcium source without absorbable alkali, such as calcium citrate, is preferred. Rarely, intravenous calcium might be required to treat severe hypocalcemia.

Diet and activity

A low-calcium, low-phosphorus diet is required during hypercalcemia. No activity restrictions are necessary.

Consultations

Consultation with a nephrologist may be needed with severe renal disease and/or severe hypercalcemia, because dialysis sometimes is required. Consultation with an endocrinologist may be needed for interpretation of PTH and other laboratory studies.

Transfer

Occasionally, dialysis may be required with severe renal impairment. With elevated serum calcium and phosphorus levels, dialysis may be needed to urgently lower these parameters. This may prevent ectopic calcification.

 
 
Contributor Information and Disclosures
Author

R Hal Scofield, MD Professor, Department of Medicine, Section of Endocrinology, University of Oklahoma College of Medicine; Associate Member, Arthritis and Immunology Program, Oklahoma Medical Research Foundation; Staff Physician, Oklahoma City Department of Veterans Affairs Medical Center

R Hal Scofield, MD is a member of the following medical societies: American Association of Immunologists, American College of Physicians, American College of Rheumatology, American Federation for Medical Research

Disclosure: Nothing to disclose.

Coauthor(s)

Thuy-Trang Nguyen University of Louisville School of Medicine

Disclosure: Nothing to disclose.

Shabreen Abdul Sharief, MD Physician, Select Specialty Hospital

Shabreen Abdul Sharief, MD is a member of the following medical societies: American Medical Association, Indian Medical Association

Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD Professor Emeritus of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

Acknowledgements

Romesh Khardori, MD, PhD, FACP Former Professor, Department of Medicine, Former Chief, Division of Endocrinology, Metabolism, and Molecular Medicine, Southern Illinois University School of Medicine

Romesh Khardori, MD, PhD, FACP is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, and Endocrine Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

References
  1. Medarov BI. Milk-alkali syndrome. Mayo Clin Proc. 2009 Mar. 84(3):261-7. [Medline]. [Full Text].

  2. Kleinig TJ, Torpy DJ. Milk-Alkali syndrome: broadening the spectrum of causes to allow early recognition. Intern Med J. 2004 Jun. 34(6):366-7. [Medline].

  3. Irtiza-Ali A, Waldek S, Lamerton E, Pennell A, Kalra PA. Milk alkali syndrome associated with excessive ingestion of Rennie: case reports. J Ren Care. 2008 Jun. 34(2):64-7. [Medline].

  4. Jousten E, Guffens P. Milk-alkali syndrome caused by ingestion of antacid tablets. Acta Clin Belg. 2008 Mar-Apr. 63(2):103-6. [Medline].

  5. Addington S, Larson N, Scofield RH. Milk-alkali syndrome in pre-eclamptic pregnancy: report of a patient and evaluation of albumin-corrected calcium in pre-eclamptic pregnancies. J Okla State Med Assoc. 2006 Sep. 99(9):480-4. [Medline].

  6. Beall DP, Scofield RH. Milk-alkali syndrome associated with calcium carbonate consumption. Report of 7 patients with parathyroid hormone levels and an estimate of prevalence among patients hospitalized with hypercalcemia. Medicine (Baltimore). 1995. 74(2):89-96. [Medline].

  7. Picolos MK, Lavis VR, Orlander PR. 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. [Medline].

  8. Wu KD, Chuang RB, Wu FL, Hsu WA, Jan IS, Tsai KS. The milk-alkali syndrome caused by betelnuts in oyster shell paste. J Toxicol Clin Toxicol. 1996. 34(6):741-5. [Medline].

  9. Gibbs CJ, Lee HA. Milk-alkali syndrome due to Caved-S. J R Soc Med. 1992 Aug. 85(8):498-9. [Medline]. [Full Text].

  10. Nakanishi T, Uyama O, Yamada T, Sugita M. Sustained metabolic alkalosis associated with development of the milk-alkali syndrome. Nephron. 1992. 60(2):251. [Medline].

  11. Brandwein SL, Sigman KM. Case report: milk-alkali syndrome and pancreatitis. Am J Med Sci. 1994 Sep. 308(3):173-6. [Medline].

  12. Campbell SB, Macfarlane DJ, Fleming SJ, Khafagi FA. Increased skeletal uptake of Tc-99m methylene diphosphonate in milk-alkali syndrome. Clin Nucl Med. 1994 Mar. 19(3):207-11. [Medline].

  13. Duthie JS, Solanki HP, Krishnamurthy M, Chertow BS. Milk-alkali syndrome with metastatic calcification. Am J Med. 1995 Jul. 99(1):102-3. [Medline].

  14. Spital A, Freedman Z. Severe hypercalcemia in a woman with renal failure. Am J Kidney Dis. 1995 Oct. 26(4):674-7. [Medline].

  15. Fiorino AS. Hypercalcemia and alkalosis due to the milk-alkali syndrome: a case report and review. Yale J Biol Med. 1996 Nov-Dec. 69(6):517-23. [Medline]. [Full Text].

  16. Lin SH, Lin YF, Shieh SD. Milk-alkali syndrome in an aged patient with osteoporosis and fractures. Nephron. 1996. 73(3):496-7. [Medline].

  17. Muldowney WP, Mazbar SA. Rolaids-yogurt syndrome: a 1990s version of milk-alkali syndrome. Am J Kidney Dis. 1996 Feb. 27(2):270-2. [Medline].

  18. Sulkin T, Krentz AJ. Iatrogenic recurrent severe hypercalcaemia and renal impairment. Postgrad Med J. 2000 Dec. 76(902):800, 807. [Medline]. [Full Text].

  19. Camidge R, Peaston R. Recommended dose antacids and severe hypercalcaemia. Br J Clin Pharmacol. 2001 Sep. 52(3):341-2. [Medline]. [Full Text].

  20. George S, Clark JD. Milk alkali syndrome-an unusual syndrome causing an unusual complication. Postgrad Med J. 2000 Jul. 76(897):422-3. [Medline]. [Full Text].

  21. Vanpee D, Delgrange E, Gillet JB, Donckier J. Ingestion of antacid tablets (Rennie) and acute confusion. J Emerg Med. 2000 Aug. 19(2):169-71. [Medline].

  22. Liu SW, Kumar AM, Nadel ES, Brown DF. A young woman with altered mental status. J Emerg Med. 2002 May. 22(4):405-8. [Medline].

  23. Robertson WC Jr. Calcium carbonate consumption during pregnancy: an unusual cause of neonatal hypocalcemia. J Child Neurol. 2002 Nov. 17(11):853-5. [Medline].

  24. Morton A. Milk-alkali syndrome in pregnancy, associated with elevated levels of parathyroid hormone-related protein. Intern Med J. 2002 Sep-Oct. 32(9-10):492-3. [Medline].

  25. Gordon MV, McMahon LP, Hamblin PS. Life-threatening milk-alkali syndrome resulting from antacid ingestion during pregnancy. Med J Aust. 2005 Apr 4. 182(7):350-1. [Medline].

  26. Verburg FA, van Zanten RA, Brouwer RM, Woittiez AJ, Veneman TF. [A man with a classic serious milk-alkali syndrome and a carcinoma of the stomach]. Ned Tijdschr Geneeskd. 2006 Jul 22. 150(29):1624-7. [Medline].

  27. Ennen CS, Magann EF. Milk-alkali syndrome presenting as acute renal insufficiency during pregnancy. Obstet Gynecol. 2006 Sep. 108(3 Pt 2):785-6. [Medline].

  28. Caruso JB, Patel RM, Julka K, Parish DC. Health-behavior induced disease: return of the milk-alkali syndrome. J Gen Intern Med. 2007 Jul. 22(7):1053-5. [Medline]. [Full Text].

  29. Dinnerstein E, McDonald BC, Cleavinger HB, Thadani VM, Jobst BC. Mesial temporal sclerosis after status epilepticus due to milk alkali syndrome. Seizure. 2008 Apr. 17(3):292-5. [Medline].

  30. Kaklamanos M, Perros P. Milk alkali syndrome without the milk. BMJ. 2007 Aug 25. 335(7616):397-8. [Medline]. [Full Text].

  31. Shah BK, Gowda S, Prabhu H, Vieira J, Mahaseth HC. Modern milk alkali syndrome--a preventable serious condition. N Z Med J. 2007 Sep 21. 120(1262):U2734. [Medline].

  32. Miller PD. Vitamin D, calcium, and cardiovascular mortality: a perspective from a plenary lecture given at the annual meeting of the American Association of Clinical Endocrinologists. Endocr Pract. 2011 Sep 1. 17(5):798-806. [Medline].

  33. Papworth K, Grankvist K, Ljungberg B, Rasmuson T. Parathyroid hormone-related protein and serum calcium in patients with renal cell carcinoma. Tumour Biol. 2005 Jul-Aug. 26(4):201-6. [Medline].

  34. LeGrand SB, Leskuski D, Zama I. Narrative review: furosemide for hypercalcemia: an unproven yet common practice. Ann Intern Med. 2008 Aug 19. 149(4):259-63. [Medline].

  35. Patel AM, Goldfarb S. Got calcium? Welcome to the calcium-alkali syndrome. J Am Soc Nephrol. 2010 Sep. 21(9):1440-3. [Medline].

  36. Swanson CM, Mackey PA, Westphal SA, Argueta R. Nicotine-substitute gum-induced milk alkali syndrome: a look at unexpected sources of calcium. Endocr Pract. 2013 Nov-Dec. 19(6):142-4. [Medline].

  37. Patel AM, Adeseun GA, Goldfarb S. Calcium-alkali syndrome in the modern era. Nutrients. 2013 Nov 27. 5(12):4880-93. [Medline]. [Full Text].

  38. Chhabra L, Spodick DH. Milk Alkali syndrome: an electrocardiographic masquerader for non-hypothermic Osborn phenomenon. Heart. 2013 Sep. 99(17):1302-3. [Medline].

  39. Neupane S. Incidence of milk alkali syndrome in the Women's Health Initiative clinical trial and cohort study. Osteoporos Int. 2014 Mar. 25(3):1193. [Medline].

  40. Soyfoo MS, Brenner K, Paesmans M, Body JJ. Non-malignant causes of hypercalcemia in cancer patients: a frequent and neglected occurrence. Support Care Cancer. 2013 May. 21(5):1415-9. [Medline].

 
Previous
Next
 
The hospital course of a patient with milk-alkali syndrome who, during treatment, developed symptomatic hypocalcemia with a markedly elevated serum parathyroid hormone level (PTH). Thirty days after discharge, the calcium and PTH levels were normal.
Table. Summary of 65 Consecutively Reported Adult Patients With Milk-Alkali Syndrome*
Mean Age 51 Years (Range, 24-95 y)
Sex 35 men and 43 women
Calcium source Calcium carbonate in all but 1
Ingestion of bicarbonate In 7 patients
Ingestion of milk In 20 patients (plus one who ate yogurt)
Mean serum calcium 15.1mg/dL (3.75mmol/L) (range, 11.1-27.5mg/dL)
High serum phosphorus In 12 patients
Permanent renal insufficiency In 20 of 57 patients eligible for evaluation
Parathyroid exploration In 3 patients
Hypocalcemia with treatment In 16 patients
*These data are derived from the 7 patients reported, plus the 28 reviewed in Beall and Scofield, 1995,[6] as well as additional patients reported by Gibbs and Lee, 1992;[9] Nakanishi et al, 1992[10] ; Brandwein and Sigman, 1994[11] ; Campbell et al, 1994[12] ; Duthie et al, 1995[13] ; Spital and Freedman, 1995[14] ; Fiorino, 1996[15] ; Lin et al, 1996[16] ; Muldowney and Mazbar, 1996[17] ; Sulkin and Krentz, 1999[18] ;



Camidge and Peaston, 2000[19] ; George and Clark, 2000[20] ; Vanpee et al, 2000[21] ; Liu et al, 2002[22] ; Robertson, 2002[23] ; Morton, 2002[24] ; Kleinig and Torpy, 2004[2] ; Picolos et al, 2005[7] ; Gordon et al, 2005[25] ; Addington et al, 2006[5] ; Verburg et al, 2006[26] ; Ennen and Magann, 2006[27] ; Caruso et al, 2007[28] ; Dinnerstein et al, 2007[29] ; Javid et al, 2007; Kaklamanos and Perros, 2007[30] ; Shah et al, 2007[31] ; Irtiza-Ali et al, 2008[3] ; and Jousten and Guffens, 2008.[4]



Two of the patients were pregnant.



Previous
Next
 
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.