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

Disclosures

Lab Med. 2018;49(2):123-129. 

In This Article

Results

During the 16-year study period, there were 127,932 measurements of 25(OH)D performed on specimens from 73,779 unique patients. We identified 1068 samples from 780 unique patients with 25(OH)D concentrations greater than 80 ng per mL. Thus, specimens with 25(OH)D levels greater than 80 ng per mL comprised 0.8% of total 25(OH)D measurements and 1.1% of patients tested.

The age range of those affected was 0.3 to 100.6 years, with a mean age of 49.0 years. Of these patients, 86 were younger than 18 years (11.0%). A total of 776 25(OH)D measurements were performed on specimens from 559 unique female patients (71.7% of unique patients tested), with a range from 81 to 480 ng per mL. A total of 290 25(OH)D measurements were performed in 221 unique male individuals (Table 1), with a range of 81 to 805 ng per mL. Among the patients with elevated levels, 89 (0.1% of unique patients tested) had 25(OH)D values greater than 120 ng per mL (Figure 1). Based on reported history, 17 patients were taking 50,000-IU tablets, 4 were taking 20,000-IU tablets, 6 were taking 10,000-IU tablets, 11 were taking 5000-IU tablets, and 6 were taking 1000-IU tablets (Figure 2). Also, 7 were taking liquid formulations with varying concentrations. The remaining patients were reportedly taking a combination of multivitamin and "other" supplements (Table 2). Eighteen patients had no vitamin D supplementation recorded in their medical record.

Figure 1.

Distribution of patients with and without symptoms at various vitamin D concentrations.

Figure 2.

Varying vitamin D supplementation concentrations and their frequency among patients with elevated 25(OH)D levels. MVI indicates multivitamin.

A total of 53 patients had concomitant serum/plasma total calcium drawn at the time of 25(OH)D testing. Only 7 of these patients had total calcium levels higher than the upper limit of the reference range (3 of whom were experiencing symptoms). In these 7 patients, total calcium values ranged from 10.8 to 19.8 mg per dL. The median was 13.3 mg per dL, and the mean was 13.8 mg per dL. For the remaining 47 patients, the total calcium concentrations ranged from 7.3 to 10.5 mg per dL (normal range, 8.5 to 10.5 mg/dL), with a median of 9.4 mg per dL. Based on linear regression statistical analysis, the correlation between vitamin D concentrations and total serum/plasma calcium concentrations was weak, with an r 2 value of 0.10 (Figure 3).

Figure 3.

Correlation between 25(OH)D levels and serum/plasma calcium concentrations. Linear regression statistics (95% confidence interval in parentheses): slope, 19.1 (3.5–34.7), y intercept, −0.14 (−157.1 to 156.9), r 2 = 0.10.

Among the patients with elevated 25(OH)D levels greater than 120 ng per mL, only 4 showed symptoms of vitamin D toxicity (Table 3). The first patient was a 4-month old boy with a 25(OH)D concentration of 496 ng per mL and a concomitant calcium value of 19.8 mg per dL. His symptoms included failure to thrive, constipation, weight loss, and nephrocalcinosis. He was receiving an incorrect dose of liquid vitamin D from a dropper, consisting of approximately 100,000 to 150,000 IU per day. The second patient was a 3-year-old girl with a 25(OH)D concentration of 480 ng per mL and total calcium level of 13.3 mg per dL at the time of diagnosis. Her symptoms included severe gastroenteritis, abdominal pain, vomiting, weight loss, polydipsia, polyuria, and nephrocalcinosis. In similar circumstances to the first patient, patient 2 was receiving an incorrect dose of liquid vitamin D from a dropper, of approximately 40,000 to 80,000 IU per day.

The third patient was a 62-year-old non-Hispanic white woman with a 25(OH)D concentration of 247 ng per mL. She had a normal total serum/plasma calcium concentration, at 9.6 mg per dL, but had abdominal pain, severe constipation, and nausea. She was taking 50,000 units of vitamin D per day, also in liquid form. Patient 4 was a 70-year-old non-Hispanic white woman with a 25(OH)D concentration of 194 ng per mL. She had an elevated calcium concentration of 11.4 mg per dL and had experienced renal failure, weakness, confusion, low mood, poor balance, and slurred speech. Her vitamin D supplementation reportedly consisted of only a single 1000 IU tablet per day; however, the reported history may be inaccurate.

The 2 patients with the most severe symptoms were pediatric patients receiving liquid vitamin D via "droppers." In both instances, the incorrect dosage was administered due to confusion between the words "dropperful" and "drop." As a result, the patients received an entire dropperful of liquid vitamin D and, on occasion, 2 to 3 entire droppersful, instead of the correct 1 to 3 drops.

The healthcare professionals treating those patients were able to obtain the original bottles of vitamin D and to determine that a dropper contained approximately 50 drops. There were 1000 IU per drop. Thus, patient 1 was receiving 100,000–150,000 IU per day. Also, based on the amount of vitamin D left in the bottle, it was estimated that he had received approximately 1.6 to 1.7 million units during an 8-week period. The parents of the second patient misinterpreted the instructions and also administered 1 dropperful instead of 1 drop. In this case, each drop contained 2000 IU. It was estimated that patient 2 received 3.5 to 5.5 million IU during a 6-month period, based on the amount of supplement left in the bottle.

Although we did not perform a detailed medical record review for patients with 25(OH)D less than 120 ng per mL, we did a search in the electronic medical records for patients with diagnostic codes related to "vitamin D poisoning," "vitamin D overdose," "vitamin D poisoning," or "vitamin D toxicity," to determine whether any hypervitaminosis D cases were missed. The results of this search identified many of the patients with serum/plasma 25(OH)D concentrations greater than 120 ng per mL whose cases were already reviewed in detail and also identified 7 patients assigned these diagnostic codes who did not have serum/plasma 25(OH)D concentrations exceeding 120 ng per mL. All 7 of these patients had at least a single 25(OH)D concentration greater than 80 ng per mL but none had values exceeding 120 ng per mL. None of these 7 case individuals had any symptoms suggestive of vitamin D toxicity. Further, 6 of the 7 patients had serum/plasma total calcium measurement(s) concurrent with the elevated 25(OH)D levels. For these 6 patients, total calcium concentrations were all within the reference range; the remaining patient did not have total calcium analysis performed.

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