Hypercalcemia in Emergency Medicine Clinical Presentation

Symptoms of hypercalcemia depend on the underlying cause of the disease, the time over which it develops (rapid increases in calcium cause more severe symptoms), and the overall physical health of the patient.

Mild elevations in calcium levels are usually asymptomatic and typically discovered on routine laboratory diagnostic testing (usually up to 11.5 mg/dL). ^[8]

As calcium levels increase, the following symptoms may occur:

• Nausea

• Vomiting

• Alterations of mental status

• Abdominal or flank pain (The workup of patients with a new kidney stone occasionally reveals an elevated calcium level.)

• Constipation

• Lethargy

• Depression

• Weakness and vague muscle/joint aches

• Polyuria, polydipsia, nocturia

• Headache

• Confusion

Severe elevations in calcium levels may cause coma.

Elderly patients are more likely to be symptomatic from only moderate elevations of calcium levels.

Hypercalcemia of malignancy may lack many of the features commonly associated with hypercalcemia caused by hyperparathyroidism. In addition, the symptoms of elevated calcium level may overlap with the symptoms of the patient's malignancy.

Hypercalcemia associated with renal calculi, joint complaints, and ulcer disease is more likely to be caused by hyperparathyroidism.

Hypercalcemia has few physical examination findings specific to its diagnosis. Often it is the symptoms or signs of underlying malignancy that bring the patient with hypercalcemia to seek medical attention. The primary malignancy may be suggested by lung findings, skin changes, lymphadenopathy, or liver or spleen enlargement.

Hypercalcemia can produce a number of nonspecific findings, as follows:

• Hypertension and bradycardia may be noted in patients with hypercalcemia, but this is nonspecific.

• Abdominal examination may suggest pancreatitis or the possibility of an ulcer.

• Patients with long-standing elevation of serum calcium may have proximal muscle weakness that is more prominent in the lower extremities; they also may have bony tenderness to palpation.

• Hyperreflexia and tongue fasciculations may be present.

• Anorexia or nausea may occur.

• Polyuria and dehydration are common.

• Lethargy, stupor, or even coma may be observed.

Long-standing hypercalcemia may cause band keratopathy, but this is rarely recognized in the ED.

If hypercalcemia is caused by sarcoidosis, vitamin D intoxication, or hyperthyroidism, patients may have physical examination findings suggestive of those diseases.

Hypercalcemia is divided into PTH-mediated hypercalcemia (primary hyperparathyroidism) and non–PTH-mediated hypercalcemia. ^{[17, 18, 19]}

PTH-mediated hypercalcemia is related to increased calcium absorption from the intestine.

Non–PTH-mediated hypercalcemia includes the following:

• Hypercalcemia associated with malignancy: Unlike PTH-mediated hypercalcemia, the elevation of calcium that results from malignancy generally worsens until therapy is provided. Hypercalcemia caused by malignancy is the result of increased osteoclastic activity within the bone. This results from one or both of the mechanisms that follow:

  • Extensive localized bone destruction may result from osteolytic metastasis of solid tumors. Evidence indicates that many malignant cells may release local osteoclastic activating factors.

  • Increased calcium levels resulting from malignancy caused by a PTH-related protein (PTH-rp) is a second mechanism. This protein is a humeral factor that acts on the skeleton to increase bone reabsorption; it acts on the kidney to decrease excretion of calcium. The gene that produces this protein is present in many malignant tissues.

• Granulomatous disorders: High levels of calcitriol may be found in patients with sarcoidosis and other granulomatous diseases. In these disorders, the increased level of calcitriol results from production within the macrophages, which constitute a large portion of some granulomas.

• Iatrogenic: In some cases, elevation of calcium is a known adverse effect of appropriate dosage. In other cases, large ingestions must be taken to induce the increase in calcium levels. Obtain a complete review of current medications for patients presenting with hypercalcemia. Record any vitamin use.

Other causes of hypercalcemia

These include the following:

• Neoplasms (nonparathyroid) - Metastasis to the bone from breast, multiple myeloma, and hematologic malignancies (Breast cancer is one of the most common malignancies responsible for hypercalcemia.)

• Nonmetastatic (humoral-induced) - Ovary, kidney, lung, head and neck, esophagus, cervix, lymphoproliferative disease, multiple endocrine neoplasia, pheochromocytoma, and hepatoma

• Pharmacologic agents - Thiazide, calcium carbonate (antacid), hypervitaminosis D, hypervitaminosis A, lithium, milk-alkali syndrome, and theophylline toxicity

• Endocrinopathies (nonparathyroid) - Hyperthyroidism, adrenal insufficiency, and pheochromocytoma

• Familial hypocalciuric hypercalcemia

• Tertiary hyperparathyroidism - Post–renal transplant and initiation of chronic hemodialysis

• Miscellaneous - Immobilization, hypophosphatasia, primary infantile hyperparathyroidism, AIDS, and advanced chronic liver disease

A study by Meehan et al found that 26.2% of patients with bipolar disorder undergoing lithium treatment had hypercalcemia. Out of a study population consisting of patients with bipolar disorder being treated with lithium, patients with bipolar disorder not being treated with lithium, and controls, hypercalcemia occurred in 87 individuals, including 82 (94.3%) of those undergoing lithium therapy. ^[20]

In a retrospective, observational study from Australia of emergency department patients, Taylor et al reported that risk variables for hypercalcemia included not only aforementioned factors—vomiting, polyuria, confusion, hyperparathyroidism, and cancer—but also female sex and type 1 diabetes mellitus. ^[21]

The aforementioned study by Lapointe et al, which looked at adult emergency department patients in two hospitals in Québec City, indicated that bone pain, the use of medications containing vitamin D, and hallucinations are risk factors for hypercalcemia. ^[14]