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Hypercalcemia

Last updated: January 18, 2021

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Hypercalcemia is a condition of high calcium levels (total Ca2+> 10.5 mg/dL or ionized Ca2+> 5.25 mg/dL) in the blood serum. For information regarding the physiology and homeostasis of calcium, please see the hypocalcemia article. The most common causes of hypercalcemia are primary hyperparathyroidism and malignancy with paraneoplastic production of parathyroid hormone-related protein (PTHrP). Symptoms of hypercalcemia include nephrolithiasis, bone pain, abdominal pain, and polyuria. Management depends on the severity of calcium imbalance. Mild and asymptomatic moderate hypercalcemia is treated with oral rehydration and low calcium intake, while symptomatic moderate cases and severe cases require IV rehydration and calcitonin administration. Hypercalcemic crisis is a life-threatening complication that manifests with dehydration, oliguria, and altered consciousness and requires immediate forced diuresis.

Hypercalcemia = total serum calcium concentration > 10.5 mg/dL (> 2.62 mmol/L), or ionized (free) calcium concentration > 5.25 mg/dL (> 1.31 mmol/L) [1]

Types of hypercalcemia Etiology Pathophysiology
PTH-mediated Primary hyperparathyroidism
Secondary hyperparathyroidism
Tertiary hyperparathyroidism
Familial hypocalciuric hypercalcemia (FFH)
  • See FHH in subtypes and variants section below.
Non-PTH-mediated Hypercalcemia of malignancy
Granulomatous disorders (e.g., sarcoidosis)
Other Medications
Hyperthyroidism
Long periods of immobilization
  • Lack of weight-bearing activities → osteoclast activation → bone demineralization → hypercalcemia
Milk-alkali syndrome
Paget disease of the bone
Adrenal insufficiency

Primary hyperparathyroidism and hypercalcemia of malignancy account for > 90% of cases of hypercalcemia. Compared to primary hyperparathyroidism, serum calcium is typically higher in hypercalcemia of malignancy (> 13 mg/dL, or > 3.25 mmol/L), and patients, therefore, exhibit more severe symptoms.
References:[3][4]

The clinical presentation is variable and may be asymptomatic.

Hypercalcemia can cause pancreatitis. Hypocalcemia in patients with pancreatitis suggests pancreatic necrosis.

The presentation of hypercalcemia includes stones (nephrolithiasis), bones (bone pain, arthralgias), thrones (increased urinary frequency), groans (abdominal pain, nausea, vomiting), and psychiatric overtones (anxiety, depression, fatigue). Note that these are also the findings of vitamin D overdose!
References:[1]

Familial hypocalciuric hypercalcemia (FHH) [6]

Approach [7]

  1. Evaluate calcium imbalance
    • Initial test: serum calcium concentration
    • Confirm true hypercalcemia: measure ionized calcium or use serum albumin to calculate corrected calcium.
      • Corrected calcium (mg/dL) = measured total Ca2+ (mg/dL) + [0.8 x (4.0 - albumin concentration in g/dL)]
        • Increased ionized calcium, regardless of total calcium levels → true hypercalcemia (potentially symptomatic)
        • Increased total calcium with normal ionized (active) calcium → factitious hypercalcemia (asymptomatic finding)
  2. Differentiate between low PTH and high PTH: to determine the underlying cause of hypercalcemia
  3. Further tests

The corrected calcium concentration calculated using serum albumin may not be accurate when major pH changes have taken place in the body (e.g., following surgery). In these cases, it is better to measure ionized calcium directly.

PTH levels in hypercalcemia

Thiazide diuretics enhance Tubular calcium resorption → Discontinue them in hypercalcemia. Loop diuretics Lose calcium → Administer them in hypercalcemia.

References:[1][9][10]

  1. Agraharkar M. Hypercalcemia. In: Batuman V, Hypercalcemia. New York, NY: WebMD. http://emedicine.medscape.com/article/240681-overview. Updated: August 2, 2016. Accessed: February 10, 2017.
  2. Efremidou et al. Peptic Ulcer Perforation as the First Manifestation of Previously Unknown Primary Hyperparathyroidism. Case Reports in Gastroenterology. 2007; 1 (1): p.21-26. doi: 10.1159/000104224 . | Open in Read by QxMD
  3. Shane E. Diagnostic approach to hypercalcemia. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/diagnostic-approach-to-hypercalcemia.Last updated: November 1, 2016. Accessed: February 10, 2017.
  4. Renaghan AD, Rosner MH. Hypercalcemia: etiology and management. Nephrology Dialysis Transplantation. 2018; 33 (4): p.549-551. doi: 10.1093/ndt/gfy054 . | Open in Read by QxMD
  5. Nussbaum. Pathophysiology and management of severe hypercalcemia.. Endocrinol Metab Clin North Am. 1993; 22 (2): p.343-62.
  6. Shane E, Berenson JR. Treatment of hypercalcemia. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/treatment-of-hypercalcemia.Last updated: April 29, 2015. Accessed: February 10, 2017.
  7. Yoon HE, Kim TY, Lee S, et al. Adrenal insufficiency presenting as hypercalcemia and acute kidney injury. International Medical Case Reports Journal. 2016; Volume 9 : p.223-226. doi: 10.2147/imcrj.s109840 . | Open in Read by QxMD
  8. Le T, Bhushan V, Chen V, King M. First Aid for the USMLE Step 2 CK. McGraw-Hill Education ; 2015
  9. Shane E. Etiology of hypercalcemia. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/etiology-of-hypercalcemia?source=see_link#H17.Last updated: April 29, 2015. Accessed: February 10, 2017.
  10. Brown EM. Disorders of the calcium-sensing receptor: Familial hypocalciuric hypercalcemia and autosomal dominant hypocalcemia. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/disorders-of-the-calcium-sensing-receptor-familial-hypocalciuric-hypercalcemia-and-autosomal-dominant-hypocalcemia?source=machineLearning&search=Familial%20hypocalciuric%20hypercalcemia&selectedTitle=1~15§ionRank=1&anchor=H9#H9.Last updated: April 12, 2016. Accessed: February 10, 2017.
  11. Tao Le, Vikas Bhushan, Deol M, Reyes G. First Aid for the USMLE Step 2 CK, Tenth Edition. McGraw-Hill Education ; 2018