Approach to hypercalcemia: Clinical sciences

Hypercalcemia refers to a serum calcium level above the upper limit of normal, which varies among different labs but is often considered greater than 10.5 mg/dL. Calcium plays a vital role in various body functions, such as myocardial contractility and nerve signaling. So, calcium imbalances, such as hypercalcemia, can result in cardiac and neurologic dysfunction. Some important causes of hypercalcemia that you should keep in mind include medications, malignancy, as well as different endocrine conditions like hyperparathyroidism or hyperthyroidism.

Now, if your patient presents with a chief concern suggesting hypercalcemia, you should first perform an ABCDE assessment to determine if your patient is unstable. If the patient is unstable, stabilize the airway, breathing, and circulation. Next, obtain IV access and put your patient on continuous vital sign monitoring, including blood pressure, heart rate, and pulse oximetry, as well as cardiac telemetry. Finally, if needed, provide supplemental oxygen.

Now, here’s a high-yield fact to keep in mind! Patients with severe or rapidly progressing hypercalcemia can present with lethargy, stupor, or even coma. Additionally, an ECG may reveal bradycardia, atrioventricular block, or a shortened QT interval. In this case, you should normalize calcium levels by starting intravenous hydration, as well as diuretics like furosemide or bisphosphonates like zoledronic acid.

Now that we're done with unstable patients, let’s go back to the ABCDE assessment and discuss the stable ones. First, obtain a focused history and physical examination, and obtain labs to check their serum calcium levels. Your patient may report personality and mood changes, as well as trouble concentrating, and even altered mental status. They might also experience gastrointestinal issues, such as abdominal pain, nausea, anorexia, and constipation. Additionally, history might reveal musculoskeletal pain; renal symptoms like polyuria; polydipsia; and nephrolithiasis. On the flip side, physical exam findings are typically nonspecific and might include weakness and signs of dehydration, like dry mucous membranes and poor skin turgor.

To remember the classic presentation of hypercalcemia, you can think of the mnemonic “groans, bones, stones, thrones, and psychiatric overtones.” Groans represent constipation and muscle weakness, which occur due to decreased muscle contractions. Bones is for bone pain resulting from chronic bone demineralization. Next, stones refer to a history of nephrolithiasis, since hypercalcemia will typically lead to hypercalciuria in an attempt to excrete the excess calcium; whereas thrones serve as a reminder of polyuria. Finally, psychiatric overtones include symptoms like mood changes or altered mental status.

Finally, labs will reveal a serum calcium level that’s above the upper limit of normal, so, at this point, you should consider, not diagnose yet, hypercalcemia. This is because approximately half of the calcium in the blood is bound to plasma proteins, mainly albumin, while the other half circulates as ionized calcium. Although ionized calcium reflects the body's calcium stores accurately, measuring it is more complex than measuring total serum calcium. Also, keep in mind that, when measuring total serum calcium in the setting of low serum albumin, there's a chance of getting false results, since the albumin-bound calcium is also affected.

So to avoid false results and truly diagnose hypercalcemia, you might need to calculate the corrected total serum calcium level. Do this by subtracting the patient's serum albumin level from 4 and multiplying the difference by 0.8. Next, add the product to the measured serum calcium, and you will obtain the corrected calcium level. If the corrected serum calcium level is above the reference range, you can confirm the diagnosis of hypercalcemia!