Hypercalcemia

Corrected Ca2+ = Measured Ca2++ 0.8 (4 – Albumin)

Signs & Symptoms

  • Typically seen when Calcium levels are > 12.0 mg/dL
  • Stones, bones, groans, psychiatric overtones
    • Nephrolithiasis
    • Bone pain
    • Abdominal pain
    • Psychosis/altered mental status
  • Increased urination and thirst
  • EKG: Shortened QT interval (1)

Hormonal Control

Calcitonin: Decreases serum Ca2+ and PO43-

  • Synthesized by thyroid parafollicular cells (“C-cells”)
  • Activates osteoblasts -> moves Ca2+ from blood to the bone

Parathyroid Hormone: Increases serum Ca2+ and lowers serum PO43-

  • Synthesized by parathyroid chief cells
  • Activates osteoclasts -> moves Ca2+ from bone to the blood
  • Increases renal reabsorption of Ca2+
  • Decreases renal reabsorption of PO43-
  • Activates 1-α-hydroxylase (increases levels of 1,25-(OH)-Vitamin D)

Vitamin D: Increases serum Ca2+ and serum PO43-

  • Absorbed through diet or via sunlight exposure
    • Converted to 25-(OH)-Vitamin D (Calcidiol) by liver
      • Converted to 1,25-(OH)-Vitamin D (Calcitriol) by kidneys
  • Increases GI absorption of Ca2+
  • Activates osteoclasts -> moves Ca2+ and PO43- from bone to the blood

Approach

*: If PTH is normal, this is inappropriate – in hypercalcemia, the PTH should be low because of calcium-mediated feedback inhibition of the parathyroid gland.
**: Granulomas contain the enzyme 1-α-hydroxylase, which converts 25-(OH)-Vitamin D to 1,25-(OH)-Vitamin D, which in turn leads to increased calcium levels

Management

  1. Treat Underlying Condition (i.e. parathyroidectomy, immunosuppression, stop thiazides, etc.)
    • Parathyroidectomy indications in hyperparathyroidism
      • Age < 50
      • Calcium level > 1 mg/dL above UNL
      • Creatinine clearance < 60 mL/min
      • Urinary calcium > 400 mg/day
      • Nephrolithiasis
      • Osteoporosis
  2. IV Fluids
    • Hypercalcemia causes decreased reabsorption of Na+ in the kidneys, therefore producing a natriuresis leading to volume depletion
    • Normal Saline preferred instead of Lactated Ringer’s because of calcium component of Lactated Ringer’s
    • 200-300 mL/hr, with a goal urine output of 100-150 mL/hr (2)
  3. Bisphosphonates (Effect in few days)
    • Inactivates osteoclasts, leading to reduction of bone resorption
    • Pamidronate
    • Zoledronic acid (more potent)
  4. Calcitonin (Effect in hours)
    • Activates osteoblasts
  5. Denosumab
    • RANKL-inhibitor, decreasing osteoclastic activity, leading to reduction of bone resorption
    • Indicated if hypercalcemia is refractory to bisphosphonates or if bisphosphonates are contraindicated due to renal impairment (3)
  6. Calcimimetics
    • Cinacalcet
    • Increases sensitivity of the calcium-sensing receptor, decreasing PTH secretion
    • Indicated in hypercalcemia secondary to parathyroid carcinoma (4)
    • Also hold promise in the treatment of FHH
  7. Dialysis
    • Indicated if severe hypercalcemia, life-threatening findings (neurologic changes or EKG changes), or if refractory and associated with renal failure (5)

References

  1. Kelwade, J., Modi, K., Kumar, N., & Parekh, H. (2016). Hypercalcemia and electrocardiogram changes. Retrieved February 17, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5105587/
  2. Holliman, K. (2012, May 15). Too much of a good thing. Retrieved February 19, 2021, from https://acphospitalist.org/archives/2012/05/hypercalcemia.htm
  3. Thosani, S., & Hu, M. (2015). Denosumab: A new agent in the management of hypercalcemia of malignancy. Retrieved February 19, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4976858/
  4. Loh, H., & Mohd Noor, N. (2014). The use of hemodialysis in refractory hypercalcemia secondary to parathyroid carcinoma. Retrieved February 19, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010034/
  5. Basok, A., Rogachev, B., Haviv, Y., & Vorobiov, M. (2018, May 31). Treatment of extreme hypercalcaemia: The role of haemodialysis. Retrieved February 19, 2021, from https://casereports.bmj.com/content/2018/bcr-2017-223772

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