Follow-up of Abnormal Metanephrine and Catecholamine Testing: Chasing Missed Neuroendocrine Tumors

From the Department of Medicine, Tufts Medical Center, Boston, MA.

Abstract

• Objective: To measure the frequency of missed pheochromocytoma test results and identify factors related to the risk of failed follow-up.
• Methods: We performed a retrospective review of the medical record to identify patients with abnormal urine or serum metanephrine or catecholamine test results over a 3-year period. We then searched the electronic medical record for documentation that the responsible physician was aware of the test results. We surveyed the physicians in cases where there were abnormal results and no documented follow-up to assess their awareness of the results and any follow-up actions they may have taken.
• Results: During the 3-year look-back period, 451 send-out tests for 332 patients were ordered for serum metanephrines, serum catecholamines, or urine catecholamines and/or metanephrines. Fifty-five tests affecting 46 patients returned with either moderately (n = 41) or critically elevated values (n = 5). Fifteen of these patients were inpatients when the tests were ordered, and 31 were outpatients. In 15 of 46 abnormal cases, there was no documentation in the electronic medical record that the responsible physician was aware of the result. Of the 15 cases without documentation, 6 of the responsible physicians in such cases were aware of the results.
• Conclusion: One-third of patients with abnormal lab testing for pheochromocytoma did not have clearly documented follow-up in the electronic medical record, and the majority of physicians in such cases were not aware of the results. Changes to the processes at health care institutions and reference laboratories are needed to improve follow-up of send-out lab results.

Delayed or missed follow-up of laboratory tests is a major source of medical harm [1–5]. Testing performed in both the inpatient and outpatient settings is susceptible to lost follow-up, in part because medical testing is a complex process that is vulnerable to multiple process-of-care failures [1,5–7]. In previous studies, the rate of missed follow-up of abnormal medical test results has ranged from 1% to 75% [6]. Laboratory test follow-up is a particularly challenging problem as patients transition between care settings [8,9]. In a study of 86 patients at one academic medical center, Moore and colleagues found that over a 1-year period, 41% of patients who had laboratory tests pending at the time of discharge had no documented follow-up for at least one of those tests [9]. More recently, Roy and colleagues reported that nearly half of 2644 patients discharged from general medicine hospitalist services at 2 academic tertiary care centers had pending laboratory or radiographic results. Nine percent of the pending results were potentially actionable, and a follow-up survey from the study revealed that 61% of physicians were unaware of pending results [10]. Similar findings have been reported in ambulatory care [5,8,11].

Among the universe of laboratory tests, tests performed at reference laboratories outside of the hospital or clinic where care is rendered (ie, “send-out” tests) are particularly susceptible to lost follow-up [12,13]. Because many of these tests are expensive and infrequently ordered, it is most feasible and economical for hospitals and clinics to transport these samples to regional or national laboratories for specialized testing [14,15]. Examples include the serotonin release assay, certain rheumatologic studies, cancer genetics, and advanced endocrine testing. Send-out testing poses several potential risks including accidental ordering of the wrong test, processing or transportation delays, failure of the outside laboratory to receive the specimen, failures of results reporting by the reference laboratory, incorrect result entry into the electronic medical record upon receipt, failure of the clinician to receive or note the result, or failure of clinician to interpret or act on the result [12,13,15]. Although previous studies have identified risk factors associated with missed abnormal test results [1], none to our knowledge have assessed the particular risks associated with samples processed at reference laboratories.

A critical event at our hospital involved a young woman who presented with respiratory failure attributed to a community-acquired pneumonia and systolic congestive heart failure that was thought to be related to her acute illness. Serum and urine metanephrines were ordered in the intensive care unit given the possibility that heart failure in a young patient could be attributed to an occult neuroendocrine tumor. The patient improved clinically and was discharged. Because the discharging service was unaware that the metanephrine tests had been ordered and were being processed at a national reference laboratory, they did not follow up on the test result or include it as pending in the discharge summary. Fortunately, the patient’s primary care physician discovered that the metanephrine levels were elevated and referred the patient for endocrine evaluation and definitive treatment.

Given the risk represented by pending send-out tests raised by this episode, we performed a retrospective study to identify other cases of missed abnormal send-out tests for metanephrines and catecholamines for in- and outpatients over the previous 3 years. We also sought to identify factors that increased the risk of failed follow-up.

Methods

Subjects and Setting

We studied adult in- and outpatients who received care at a 415-bed Boston-based academic medical center.

Project Design and Data Collection

We performed a retrospective record review of a cohort of patients with abnormal send-out laboratory tests for metanephrines and catecholamines. We collected laboratory reports of all results of urine and serum metanephrine and catecholamine tests performed from 1 January 2012 through 31 December 2014. All tests were performed at and reported by Quest Diagnostics in Chantilly, Virginia. The relevant tests were identified using a query of the online Quest Diagnostics system to extract all laboratory results for serum metanephrines, serum catecholamines, urine metanephrines, and urine catecholamines that resulted during this period. Reports were PDF files that were printed and reviewed manually. (Of note, providers typically view lab results directly in the electronic medical record. Reports were extracted from the Quest Diagnostics system for study purposes only.)

We used the reference ranges supplied by the laboratory to sort results into: normal levels, moderately elevated levels (1 to 4 times the upper limit of normal), and critically elevated levels (greater than 4 times the upper limit of normal). A physician (RZ) then reviewed the electronic medical record of each patient with moderately or critically elevated results for evidence that the responsible physician was aware of the results and had documented a follow-up plan. Documentation of physician awareness and follow-up was ascertained by notation and interpretation of the test result in either a discharge summary from the index admission or in an outpatient clinic note. The responsible physician was defined as the ordering physician for tests ordered in ambulatory care and the attending physician at time of discharge for inpatients. In cases where no documentation was identified in the medical record, the responsible physicians received an email questionnaire that asked (1) if they were aware of the abnormal result, (2) if aware of the result, did they notify the primary care physician or referring physician, and (3) if they were aware of any further follow-up or intervention.

Analysis

We stratified the cases into those with normal and abnormal labs values, and then further by those that did and did not have documentation of results and follow-up in the medical record. We then further stratified cases into those in which the responsible physician was aware and those in which they were unaware. If unaware, the patient was contacted directly by the risk management department, primarily for patient safety purposes. If we were unable to contact the patient, the patient’s listed primary care physician was contacted directly. We then performed qualitative analysis of the cases with abnormal results and no documented follow-up, with the goal of identifying common themes.