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Phys Topicsrenal

Phys · renal

Electrolyte Disorders: Calcium, Magnesium and Phosphate

Also known as hypercalcaemia · hypocalcaemia · corrected calcium · ionised calcium · primary hyperparathyroidism · hypoparathyroidism · familial hypocalciuric hypercalcaemia · FHH · hypomagnesaemia · torsades de pointes · hyperphosphataemia · hypophosphataemia · CKD-MBD · tumor lysis syndrome · refeeding syndrome · hungry bone syndrome

Consultant-physician-depth guide to divalent ion disorders — corrected versus ionised calcium, the PTH-first hypercalcaemia workup and severe hypercalcaemia sequence, asymptomatic primary hyperparathyroidism decisions, post-surgical hypocalcaemia and acute tetany management, magnesium as the hidden blocker of potassium and calcium correction, torsades, CKD-MBD, tumor lysis and refeeding syndrome — structured for FRACP DWE and DCE preparation.

high28 referencesUpdated 17 July 202617 min readVerification in progress

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FRACP DWEFRACP DCEMRCP Part 2ABIM Internal Medicine

Red flags

  • Corrected calcium at or above 3.0 mmol/L with confusion, vomiting or ECG changes — hypercalcaemic crisis: saline first, same-hour senior review
  • Perioral tingling with carpopedal spasm or stridor after neck surgery — acute hypocalcaemia: IV calcium gluconate slowly, never push
  • Polymorphic ventricular tachycardia with a long QT — torsades de pointes: IV magnesium 2 g even when the magnesium level is normal
  • Refeeding a malnourished patient without thiamine and electrolyte monitoring — refeeding syndrome can kill within days
  • Rising phosphate and potassium with falling calcium and uric acid after chemotherapy — tumor lysis syndrome: prevention beats rescue
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FRACP DWEFRACP DCEMRCP Part 2ABIM Internal Medicine

Red flags

  • Corrected calcium at or above 3.0 mmol/L with confusion, vomiting or ECG changes — hypercalcaemic crisis: saline first, same-hour senior review
  • Perioral tingling with carpopedal spasm or stridor after neck surgery — acute hypocalcaemia: IV calcium gluconate slowly, never push
  • Polymorphic ventricular tachycardia with a long QT — torsades de pointes: IV magnesium 2 g even when the magnesium level is normal
  • Refeeding a malnourished patient without thiamine and electrolyte monitoring — refeeding syndrome can kill within days
  • Rising phosphate and potassium with falling calcium and uric acid after chemotherapy — tumor lysis syndrome: prevention beats rescue

Electrolyte Disorders: Calcium, Magnesium and Phosphate

The answer first

Calcium, magnesium and phosphate questions look like biochemistry and behave like physiology. Five rules carry you through almost every DWE vignette and every ward call [3]:

  1. Trust the right calcium. A total calcium without an albumin is half a result. Correct for albumin as a screen, but reach for ionised calcium whenever the correction assumptions break — critical illness, acid-base disturbance, paraproteinaemia, or when the story and the number disagree [1].
  2. PTH is the first test in hypercalcaemia. One number splits the differential in two: high or inappropriately normal PTH means parathyroid disease; suppressed PTH means malignancy, vitamin D or one of the rare mimics [2] [3].
  3. Severe hypercalcaemia is saline first. Volume repletion before any antiresorptive; calcitonin for speed within hours; a bisphosphonate — or denosumab in CKD — for durability over days [3] [7].
  4. Magnesium before potassium before calcium. Refractory hypokalaemia and refractory hypocalcaemia are both magnesium stories until proven otherwise — the kidney cannot hold potassium and the parathyroid cannot work without it [18] [19].
  5. Thiamine before calories. In the malnourished patient, feeding without thiamine and slow refeeding is how refeeding syndrome happens — phosphate, potassium and magnesium crash together [26].
The 30-second ward answer

"High calcium? Check the albumin and the PTH first — that splits parathyroid disease from malignancy. If it is severe, saline now, calcitonin for the next few hours, zoledronate or denosumab for the next few weeks. Low calcium with tetany? Calcium gluconate slowly through a monitored line, then fix the magnesium. Potassium that will not correct? Check the magnesium. Feeding someone malnourished? Thiamine first, slow calories, watch the phosphate. And when the numbers and the patient disagree, I order an ionised calcium." [3]


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References28ShowHide
  1. [1]Payne RB, Little AJ, Williams RB, et al. Interpretation of serum calcium in patients with abnormal serum proteins Br Med J, 1973.PMID 4758544
  2. [2]Carroll MF, Schade DS. A practical approach to hypercalcemia Am Fam Physician, 2003.PMID 12751658
  3. [3]Minisola S, Pepe J, Piemonte S, et al. The diagnosis and management of hypercalcaemia BMJ, 2015.PMID 26037642
  4. [4]Bilezikian JP, Brandi ML, Eastell R, et al. Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the Fourth International Workshop J Clin Endocrinol Metab, 2014.PMID 25162665
  5. [5]Christensen SE, Nissen PH, Vestergaard P, et al. Familial hypocalciuric hypercalcaemia: a review Curr Opin Endocrinol Diabetes Obes, 2011.PMID 21986511
  6. [6]Marx SJ. Familial Hypocalciuric Hypercalcemia as an Atypical Form of Primary Hyperparathyroidism J Bone Miner Res, 2018.PMID 29115694
  7. [7]Major P, Lortholary A, Hon J, et al. Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials J Clin Oncol, 2001.PMID 11208851
  8. [8]Hu MI, Glezerman IG, Leboulleux S, et al. Denosumab for treatment of hypercalcemia of malignancy J Clin Endocrinol Metab, 2014.PMID 24915117
  9. [9]Hu MI, Glezerman I, Leboulleux S, et al. Denosumab for patients with persistent or relapsed hypercalcemia of malignancy despite recent bisphosphonate treatment J Natl Cancer Inst, 2013.PMID 23990665
  10. [10]Donovan PJ, Sundac L, Pretorius CJ, et al. Calcitriol-mediated hypercalcemia: causes and course in 101 patients J Clin Endocrinol Metab, 2013.PMID 23979953
  11. [11]Beall DP, Henslee HB, Webb HR, et al. Milk-alkali syndrome: a historical review and description of the modern version of the syndrome Am J Med Sci, 2006.PMID 16702792
  12. [12]Holick MF. Vitamin D deficiency N Engl J Med, 2007.PMID 17634462
  13. [13]Brandi ML, Bilezikian JP, Shoback D, et al. Management of Hypoparathyroidism: Summary Statement and Guidelines J Clin Endocrinol Metab, 2016.PMID 26943719
  14. [14]Bollerslev J, Rejnmark L, Marcocci C, et al. European Society of Endocrinology Clinical Guideline: Treatment of chronic hypoparathyroidism in adults Eur J Endocrinol, 2015.PMID 26160136
  15. [15]Mantovani G. Clinical review: Pseudohypoparathyroidism: diagnosis and treatment J Clin Endocrinol Metab, 2011.PMID 21816789
  16. [16]Mantovani G, Bastepe M, Monk D, et al. Diagnosis and management of pseudohypoparathyroidism and related disorders: first international Consensus Statement Nat Rev Endocrinol, 2018.PMID 29959430
  17. [17]Hoffman E. The Chvostek sign; a clinical study Am J Surg, 1958.PMID 13545482
  18. [18]Huang CL, Kuo E. Mechanism of hypokalemia in magnesium deficiency J Am Soc Nephrol, 2007.PMID 17804670
  19. [19]Ayuk J, Gittoes NJ. How should hypomagnesaemia be investigated and treated? Clin Endocrinol (Oxf), 2011.PMID 21569071
  20. [20]Ayuk J, Gittoes NJ. Treatment of hypomagnesemia Am J Kidney Dis, 2014.PMID 24100128
  21. [21]Danziger J, William JH, Scott DJ, et al. Proton-pump inhibitor use is associated with low serum magnesium concentrations Kidney Int, 2013.PMID 23325090
  22. [22]Blanchard A, Bockenhauer D, Bolignano D, et al. Gitelman syndrome: consensus and guidance from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference Kidney Int, 2017.PMID 28003083
  23. [23]Panchal AR, Bartos JA, Cabañas JG, et al. Part 3: Adult Basic and Advanced Life Support: 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Circulation, 2020.PMID 33081529
  24. [24]Ketteler M, Block GA, Evenepoel P, et al. Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder: Synopsis of the Kidney Disease: Improving Global Outcomes 2017 Clinical Practice Guideline Update Ann Intern Med, 2018.PMID 29459980
  25. [25]Howard SC, Jones DP, Pui CH. The tumor lysis syndrome N Engl J Med, 2011.PMID 21561350
  26. [26]Mehanna HM, Moledina J, Travis J. Refeeding syndrome: what it is, and how to prevent and treat it BMJ, 2008.PMID 18583681
  27. [27]Cortes J, Moore JO, Maziarz RT, et al. Control of plasma uric acid in adults at risk for tumor Lysis syndrome: efficacy and safety of rasburicase alone and rasburicase followed by allopurinol compared with allopurinol alone--results of a multicenter phase III study J Clin Oncol, 2010.PMID 20713865
  28. [28]Brasier AR, Nussbaum SR. Hungry bone syndrome: clinical and biochemical predictors of its occurrence after parathyroid surgery Am J Med, 1988.PMID 3400660

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