eMedicine Specialties > Emergency Medicine > Endocrine & Metabolic
Hypercalcemia: Differential Diagnoses & Workup
Updated: Aug 5, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Differential Diagnoses
| HIV Infection and AIDS | Toxicity, Theophylline |
| Hyperparathyroidism | Toxicity, Thyroid Hormone |
| Malignancy | Toxicity, Vitamin |
| Sarcoidosis | Tuberculosis |
| Toxicity, Lithium | |
| Toxicity, Salicylate |
Other Problems to Be Considered
Pheochromocytoma
Immobilization
Addison disease
Inflammatory disorders
Rhabdomyolysis
Paget disease
Parenteral nutrition
Workup
Laboratory Studies
- Confirmatory tests: Changes in serum protein concentrations alter the total serum calcium level but do not affect the unbound fraction. Calcium level reported by the laboratory usually represents the bound and unbound calcium. When calcium levels are reported as high or low, the physician must be able to calculate the actual level of calcium. A common formula is as follows:
- Corrected total calcium (mg/dL) = (measured total calcium mg/dL) + 0.8 (4.4 - measured albumin g/dL)
- The corrected calcium value is useful in most situations, but individual variation can occur.
- If the corrected serum calcium level still is not accurate, it is possible to measure the free calcium ion activity (ie, ionized calcium level).
- Other nonspecific laboratory abnormalities commonly found in patients with hypercalcemia result from disordered renal function. Patients commonly have significant azotemia at presentation.
- Hypercalcemia may produce ECG abnormalities related to altered trans-membrane potentials that affect conduction time. QT interval shortening is common, and, in some cases, the PR interval is prolonged. At very high levels, the QRS interval may lengthen, T waves may flatten or invert, and a variable degree of heart block may develop. Digoxin effects are amplified.
- After a diagnosis of hypercalcemia is established, the next step is to determine the cause. Initial testing is directed at malignancy, hyperparathyroidism, and hyperthyroidism, the most common causes of hypercalcemia.
- The measurement of circulating PTH in the serum is the most direct and sensitive measure of parathyroid function. A reference range is 2-6 mol/L. A nonsuppressed PTH level in the presence of hypercalcemia suggests a diagnosis of primary hyperparathyroidism. If the PTH level is suppressed in the face of an elevated calcium level, hyperparathyroidism is unlikely.
- Parathyroid hormone-related peptide (PTHrP) is thought to mediate the hypercalcemia that develops with many malignancies. Assays to measure this peptide are available.6
- Measurement of calcitriol is difficult but can be accomplished. This laboratory value is useful in diagnosing hypercalcemia secondary to a granulomatous disease such as sarcoidosis.
- Other electrolytes also may be disturbed in hypercalcemia. Serum phosphate levels tend to be low or normal in primary hyperparathyroidism and hypercalcemia of malignancy. Phospate levels are elevated in hypercalcemia secondary to vitamin D–related disorders or thyrotoxicosis. Serum chloride levels usually are higher than 102 mEq/L in hyperparathyroidism and less than this value in other forms of hypercalcemia.
Imaging Studies
- No imaging studies definitively diagnose hypercalcemia.
- Consider hypercalcemia in patients with multiple nonspecific complaints and an associated lung mass.
- If laboratory evidence of primary hyperparathyroidism is present, CT scan of the head, MRI, ultrasound, or nuclear parathyroid scans may be helpful. Preoperative diagnostic imaging is essential in patients with previous neck surgery.
More on Hypercalcemia |
| Overview: Hypercalcemia |
 Differential Diagnoses & Workup: Hypercalcemia |
| Treatment & Medication: Hypercalcemia |
| Follow-up: Hypercalcemia |
| References |
| Further Reading |
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References
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Dent DM, Miller JL, Klaff L, Barron J. The incidence and causes of hypercalcaemia. Postgrad Med J. Sep 1987;63(743):745-50. [Medline].
Edelson GW, Kleerekoper M. Hypercalcemic crisis. Med Clin North Am. Jan 1995;79(1):79-92. [Medline].
Blomqvist CP. Malignant hypercalcemia--a hospital survey. Acta Med Scand. 1986;220(5):455-63. [Medline].
Mundy GR, Guise TA. Hypercalcemia of malignancy. Am J Med. Aug 1997;103(2):134-45. [Medline].
Grill V, Ho P, Body JJ, et al. Parathyroid hormone-related protein: elevated levels in both humoral hypercalcemia of malignancy and hypercalcemia complicating metastatic breast cancer. J Clin Endocrinol Metab. Dec 1991;73(6):1309-15. [Medline].
Diaz Guardiola P, Vega Pinero B, Alameda Hernando C, Pavon de Paz I, Iglesias Bolanos P, Guijarro de Armas G. [Primary hyperparathyroidism. An alternative to the surgery.]. Endocrinol Nutr. Mar 2009;56(3):132-5. [Medline].
Bilezikian JP. Clinical review 51: Management of hypercalcemia. J Clin Endocrinol Metab. Dec 1993;77(6):1445-9. [Medline].
Bilezikian JP. Management of acute hypercalcemia. N Engl J Med. Apr 30 1992;326(18):1196-203. [Medline].
Kiang DT, Loken MK, Kennedy BJ. Mechanism of the hypocalcemic effect of mithramycin. J Clin Endocrinol Metab. Feb 1979;48(2):341-4. [Medline].
Kinirons MT. Newer agents for the treatment of malignant hypercalcemia. Am J Med Sci. Jun 1993;305(6):403-6. [Medline].
Stewart AF. Clinical practice. Hypercalcemia associated with cancer. N Engl J Med. Jan 27 2005;352(4):373-9. [Medline].
Thirlwell C, Brock CS. Emergencies in oncology. Clin Med. Jul-Aug 2003;3(4):306-10. [Medline].
Keywords
elevated calcium level, elevated calcium, increased calcium level, high calcium, malignancy, hyperparathyroidism, primary hyperparathyroidism, parathyroid disease, calcium metabolism, excess calcium, vitamin D, bony metastases, serum calcium, plasma calcium, calcium regulation, calcitriol, 1, 25- dihydroxyvitamin D, calcitonin
parathyroid hormone, PTH, PTH-mediated hypercalcemia, non–PTH-mediated hypercalcemia, band keratopathy, sarcoidosis, granulomatous disease, multiple myeloma, hematologic malignancy, lymphoproliferative disease, multiple endocrine neoplasia, pheochromocytoma,hepatoma, adrenal insufficiency, hypophosphatasia, chronic hemodialysis, primary infantile hyperparathyroidism
