Vitamin D Toxicity: A 16-Year Retrospective Study at an Academic Medical Center

John P. Lee, DO; Michael Tansey, MD; Jennifer G. Jetton, MD; Matthew D. Krasowski, MD, PhD


Lab Med. 2018;49(2):123-129. 

In This Article

Materials and Methods

The study was conducted at the University of Iowa Hospitals and Clinics (UIHC), a 734-bed tertiary-/quaternary-care academic medical center located in Iowa City, Iowa. The data in the study were collected as part of a retrospective study approved by the University of Iowa Institutional Review Board (protocol #201612810), covering the time period from January 1, 2000, through December 31, 2016. This study was carried out in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki).

As described in a previous study coauthored by one of us, Epic Reporting Workbench (RWB) was used to retrieve past laboratory results and medication administration records.[11] In the retrospective timeframe, all serum/plasma 25(OH)D levels derived from testing performed for clinical purposes were retrieved from the electronic medical record. We did an additional search using RWB for patients in the retrospective time period with clinical encounter diagnostic codes related to "vitamin D poisoning" (ICD-9: 278.4; ICD-10, E67.3), "vitamin D overdose" or "vitamin D poisoning" (ICD-9: 963.5, E858.1, E962.0, E969, E980.4; ICD-10, T45.2X), and "vitamin D toxicity" (ICD-9: 278.4; ICD-10, T45.2X).

Multiple 25(OH)D assays were used during this time period, although none simultaneously. From January 2000 through mid-July 2005, the Nichols ADVANTAGE 25-OH Vitamin D immunoassay (Nichols Institute Diagnostics, Inc) was performed in-house. From late July 2005 through January 2012, specimens were tested at ARUP Laboratories using the DiaSorin immunoassay (DiaSorin). An in-house assay, the Abbott ARCHITECT 25-OH Vitamin D (Abbott Laboratories, Inc.) was used from mid-January 2012 through mid-October 2012. Starting in mid-October 2012, the laboratory moved to the Roche Elecsys Vitamin D assay (Roche Diagnostics for all products mentioned in this paragraph) on the in-house Modular E platform. Ultimately, in October of 2013, the laboratory switched to Roche cobas e602 analyzers. Total calcium assays were first performed on Roche Modular P analyzers. In October 2013, the laboratory switched to Roche cobas c702 analyzers. Both testing platforms used colorimetric methodologies.

Elevated 25(OH)D levels were defined as levels higher than 80 ng per mL based on a case report of a patient showing toxicity with a 25(OH)D serum/plasma concentration of only 80 ng per mL.[12] However, the published literature has shown that toxicity is unlikely unless 25(OH)D concentrations exceed 120 ng per mL.[12–14] Thus, our detailed medical record review focused on patients whose 25(OH)D exceeded 120 ng per mL. The medical record review included assessment for presence or absence of symptoms, total calcium levels (if performed), and type and concentration of vitamin D supplementation. Patients having symptoms were defined as those having 1 or more of the following symptoms in the absence of any other diagnosable cause: polydipsia, polyuria, decreased appetite, vomiting, constipation, abdominal pain, renal failure, nephrocalcinosis, and/or failure to thrive. These symptoms were required to be present at the time of the blood draw to test 25(OH)D levels. Normal total serum/plasma calcium concentrations are defined as 8.5 to 10.5 mg per dL.