October 2013 Case 2

A 5 month old girl with hypercalcemia

Zoe Kinkade, M.D., Danyel Tacker, PhD.

Overview

A 5-month-old baby girl presented to the emergency department, intubated and with pulseless electrical activity. She was found apneic and pulseless, lying prone in a crib without blankets or other obstructive items. It was unknown how long she had been unresponsive. Parents reported that she had nasal congestion and sneezing for a few days prior, had decreased oral intake the prior evening, and seemed "more sleepy than usual".

The baby was the product of a 33-week gestation. It is unclear what precipitated the preterm labor, but there was mention in her medical record of chorioamnionitis at birth. She was intubated at birth for respiratory distress syndrome and received surfactant. She was treated with antibiotics and all cultures remained negative. After two weeks in the neonatal intensive care unit, she was released and had been developing appropriately since. All newborn screens were negative. The only current medical problem was gastric reflux for which she was taking Zantac and fed thickened formula. There was no significant family or social history. Two older healthy children also lived in the home.

Emergency medical technicians had inserted an intravenous catheter and administered 3 doses of epinephrine prior to arrival to the emergency department. Upon arrival, she received multiple doses of epinephrine, bicarbonate, calcium chloride, atropine, and normal saline and a pulse was returned. A CT scan of the head showed diffuse hypodensity of the brain parenchyma consistent with hypoxic ischemic injury. There was no evidence of trauma.

Physical exam revealed a pale, plump infant. Heart rhythm was regular with a systolic ejection murmur. She was sedated and intubated, so neurologic exam was mostly non-contributory. There were no identifiable injuries.

Gross Description

Initial labs were as follows (Key : Blue = decreased, Red = increased , Bold = critical):

Diagnosis

Question 1 : Regarding the elevated calcium level, what should be the next step ?

Answer

Please select an answer above.

Question 2 : What is this patient's corrected calcium concentration ?

Answer

Please select an answer above.

Question 3: What is the most likely source of an elevated calcium level in this case ?

Answer

Please select an answer above.

Discussion

This case illustrates the importance of checks and procedures in the laboratory regarding obviously spurious results. Before releasing a test value that is well outside the range of compatibility with life, a call should be made to the primary care team who is ordering the laboratory test. In this case, there was no critical value in place for calcium. Usually this will involve contacting the pathologist covering the clinical pathology service in order to communicate with the team. An identification check should be first, along with examination of the collection device to make sure it does not interfere with the results (i.e. a purple EDTA tube will chelate calcium, causing a falsely low result; the proper tube is a light green tube). Whether the specimen is hemolyzed or in some way looks abnormal should also be noted, as many serum/plasma analyte results are altered due to pre-analytic errors.

In this case, the initial ionized calcium was also elevated from the venous gas specimen. It is most likely that this was due to the administration of the CaCl2 solution, so it is possible that the baby experienced transient hypercalcemia. Given that the child was unresponsive prior to ED presentation and treatment, this was probably not the initial cause of the cardiorespiratory arrest.

Hypercalcemia is not as common in children as it is in adults. The most common causes of hypercalcemia in adults are hyperparathyroidism (90%), malignancy, renal failure, over-ingestion of vitamin D, milk-alkali syndrome, thyrotoxicosis, sarcoidosis, tuberculosis, lithium or thiazide diuretics, and prolonged immobilization(1). Children share the most common causes but also present unique heritable and acquired causes of hypercalcemia. The inherited causes include Jansen's disease, Williams-Beuren syndrome, hypophosphatasia, primary oxalosis, and congenital lactase deficiency. These generally have other anomalies that would likely have been detected in this 5 month old infant. Acquired caused include renal tubular acidosis, phosphate depletion from extreme maturity, subcutaneous fat necrosis of the newborn, and hypothyroidism.(2)

The patient's nutritional state is also important in the evaluation of calcium laboratory results, because approximately half of serum calcium is bound to protein (as seen by the corrected calcium equation above). This baby's serum albumin concentration was low, despite the infant appearing well-nourished. It is possible that the serum albumin was low because of dilution – it is established that the specimen was drawn from a line that was improperly flushed prior to collection. However, laboratory results suggesting hypercalcemia are generally seen in hyperalbuminemia. Subsequent specimens showed decreased albumin, but not to the degree seen in the initial specimen, suggesting that both an underproduction of albumin occurred in the patient, and dilution of the initial specimen.

Symptoms of hypercalcemia are predominantly neurologic, manifested by muscle weakness, depression, and coma. These symptoms may be difficult to detect in an infant, especially one that is already unresponsive. The faster the change in the serum calcium concentration, the more pronounced and severe the symptoms become. Treatment is individualized, based on the cause of the hypercalcemia and whether or not symptoms are present. Any patient with a serum calcium concentration greater than 14 mg/dL should be treated regardless of symptoms.(3)

In this case, if the calcium concentration reported in the initial specimen was accepted, the baby would have undergone aggressive therapy. However, the calcium concentration reported was beyond a level compatible with life, and was called into question. There were many other factors that provided evidence of a spurious test result, such as the chloride (elevated, likely due to the calcium salt administered in solution to the patient), albumin (decreased, likely due to dilution of the blood specimen by IV solution), etc. It is of primary importance to correlate different test results to each other, and in the context of patient presentation, and to remain vigilant in the laboratory to monitor for errors.

References

  1. http://www.uptodate.com/contents/etiology-of-hypercalcemia?detectedLanguage=en&source=search_result&search=hypercalcemia&selectedTitle=3%7E150&provider=noProvider. Accessed 27 Aug 2013.
  2. Jacobs TP and Bilezikian JP. 2005 CLINICAL REVIEW: Rare Causes of Hypercalcemia. J Clin Endocrinol Metab 90 (11): 6316-6322.
  3. Burtis CA, Ashwood ER, Bruns DE, Eds. Tietz textbook of clinical chemistry and molecular diagnostics. 5th Ed. Elsevier: St. Louis, 2012.