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Heidi James, MD and Malcolm Thaler, MD

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Hypercalcemia is a relatively common electrolyte abnormality and is usually attributable to hyperparathyroidism. Be sure to order an albumin level to help caculate the ionized calcium and rule out a false positive.  If Calcium remains elevated on repeat testing, order a PTH level. If the PTH level is very high, that’s it, you’re done. The diagnosis is hyperparathyroidism. Continue to monitor that.  If the PTH is low-moderately elevated, your patient will need further work up to rule out malignancy and other conditions.



  • Hypercalcemia should be first corrected for albumin levels and confirmed with a repeat test.

  • Symptoms of hypercalcemia are diffuse but can be characterized by “stones (kidney), moans (bone pain), groans (constipation) and psychiatric overtones (confusion, cognitive deficits).” They will vary in severity based on the level of hypercalcemia.

  • Most cases (90%) of hypercalcemia are caused by hyperparathyroidism or malignancy. The first step is to order a parathyroid hormone level (PTH). Anything that is inappropriately elevated or normal in the setting of hypercalcemia is hyperparathyroidism or familial hypocalciuric hypercalcemia. If it is low, you should be thinking about malignancy, granulomatous disease, hyperthyroidism, hypervitaminosis D, prolonged immobilization and meds (thiazides, lithium).


  • Case: 53-year-old patient that you saw last week for a routine check up, and for some reason or other that escapes you as you're going through her lab tests, you felt compelled to order a calcium. It is high at 12.1 mg/dL (3.02 mmol/L, normal range: 8.5 to 10.2 mg/dL or 2.13 to 2.5 mmol/L).  What do we do with that value?

  • Pearl from Malcolm: We can say to our patients, "See how thorough I was? See how healthy you are? But, unfortunately what happens is sometimes things come back out of the normal range.”

  • Step 1: Remember ionized calcium is what counts not total calcium because much of it that is bound to albumin.

    • Anything that drives up albumin will also drive up total calcium such as dehydration or those people who just naturally have higher albumin levels. A high protein diet can also drive up albumin.

    • Corrected Ca = [0.8 x (normal albumin - patient's albumin)] + serum Ca level

    • Normal albumin level is 4 mg/dL Standard Units or 40 g/L if using SI Units

  • Step 2: Repeat the level within the next few days. You don’t have to wait weeks or months to do it. If it is normal, you can be done with it.

  • Step 3: If it is elevated  again, you can explore symptoms though they are somewhat vague and will can become more severe with increasing level of hypercalcemia or if there are acute changes. As with most other electrolyte disorders, the body can adapt to slower changes in time but not to acute changes.

    • Constitutional: fatigue

    • Cardiac: short QT interval associated with slight increased risk of supraventricular and ventricular tachyarrhythmias

    • GI: constipation

    • Renal: polyuria, polydipsia, renal stones (especially at higher levels over 14)

    • Neuro: Confusion, cognitive deficits (especially at higher levels over 14)

  • Step 4: You’ve confirmed it is real, you may initiate a work-up regardless of symptoms. They have smoldering hyperparathyroidism which can lead to bone problems later down the line like osteoporosis or osteitis fibrosis cystica.

    • Differential is broad but 90% are going to be caused by hyperparathyroidism or malignancy.

    • Other things to think about: Paget’s disease, hypervitaminosis D, hyperthyroidism, immobilization in the elderly, sarcoidosis and other granulomatous disease, meds (lithium, thiazides), familial hypocalciuric hypercalcemia (autosomal dominant)

    • Check a PTH

      • High = inappropriate = hyperparathyroidism

      • Normal or mildly elevated = inappropriate = likely familiar hypocalciuric hypercalcemia → check 24-hr urine sample and if <200mg per day you have your diagnosis

      • Low = think about the rest of the differential

        • TSH

        • 1,25 hydroxy vitamin D level

        • SPEP or urine electrophoresis

        • Parathyroid-hormone-related protein (most malignancies secrete)

  • What happened to the patient? She had hyperparathyroidism. Because she had no symptoms, she was monitored without immediate intervention. She gets her calcium and creatinine checked annually along with a DEXA scan every 2-3 years.

    • In someone who is younger with a calcium greater than 12, you don’t want them living such a long time with the effects of hypercalcemia so you can be thinking about a surgery consult.

Ian L., Dr -

Primary Hyperparathyroidism is common affecting 1% of the population and up to 3% of post - menopausal females .
Reference : Macfarlane et al Ann Endocrinology (Paris) May 76 (2) 120-7.
Ordering Calcium is therefore NOT wasteful .
Current belief is watchful surveillance is safe and Parathyroidectomy indication is not common but there is debate .

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