TABLE G-1 Case Studies of Vitamin D Toxicity
Study |
Patient/Population |
Preparation; Dose |
Duration |
Children |
|
|
|
Djamil and Tu-Tunji. 1931. Lancet letter to the editor |
2-yr-old male |
Vigantol (irradiated ergosterol); 3 tsp |
1 d |
1947. BMJ letter to editor |
Not specified |
Cod liver oil |
|
Ross. 1952. Journal of Pediatrics :815-822 |
4 infants ages 8-14 mo |
Irradited ergosterol containing an estimated 30,000–40,000 IU vitamin |
Daily for 8-12 mo |
Jacqz et al. 1985 |
Infants with hypercalcemia (2 cases with vitamin D toxicity) |
Vitamin D and calcium supplementation |
|
|
Case 1: 3 mo old |
|
|
|
Case 2: 7 mo old |
300 μg D3 |
|
Besbas et al. 1989. Turkish J Pediatrics 31:239-244 |
Case 1: 3 mo old |
Vitamin D: 45,000 IU/d |
45 d |
|
Case 2: 4 mo old |
Vitamin D: 60,000 IU/d |
30 d |
Dent. 1964. BMJ letter to editor |
6 yr old |
Vitamin D (Calciferol Tablets B.P.): 1.25 mg. (~50,000 IU)/d |
9 mo |
Counts et al. 1975. Ann Internal Med 82:196-200 |
4-yr-old male |
Vitamin D2 (Drisdol): 50,000 up to 100,000 IU/d |
2 mo following bilateral nephrectomy |
DeWind. 1960. Arch Dis Child 36:373-380 |
5.5 yr old |
Vitamin D: 100,000 IU + cod liver oil-2 T + multivitamin |
daily × 2–3 mo; and continued intake of tx vitamin D for 1 yr after hospitalization |
Barrueto et al. 2005. Pediatrics 116:e453-e456 |
2-yr-old male |
Vitamin D (ergocalciferol): 2,400,000 IU |
4 d |
Serum Calcium |
Serum 25(OH)D |
Symptoms/Health Effects |
|
|
Edema and albuminuria |
|
|
Response from editor: A toxic dose of more than 200,000 units would only be achieved with ingestion of 2.65 L cod liver oil/d |
18–19 mg/dL |
|
All presented with anorexia, weight loss, weakness; 2 infants recovered within 6–9 mo following removal of vitamin D; 2 infants died: autopsy showed fibrotic changes in vascular tissue, calcification of other tissues was noted, particularly lung |
|
|
Both cases presented with anorexia, diarrhea, and vomiting |
10.5 mg/dL |
129 ng/ml |
|
10.5 mg/dL |
126 ng/ml |
|
19.5 mg/dL |
|
Calcium phosphate crystals in urine; bilateral medullary nephrocalcinosis; vomiting and lethargy; both pts recovered without incident |
17.6 mg/dL |
|
|
|
|
Extreme thirst, hypercalcemia, symptoms of diabetes insipidus |
17.2 mg/dL |
635 ng/ml |
Leg pain, cessation of growth resulting from bone resorption; serum calcium, accompanied by nausea and vomiting. Tx with Ca-free dialysate failed to reduce serum Ca; prednisolone for 7 d; calcitonin tx stabilized serum Ca |
17 mg/dL |
|
Nausea and non-tender lumps over both tibias; X-rays showed alternating patterns of increased and decreased bone density. Loss of bone density and tissue calcification continued despite removal of vitamin D and the pt died |
14.4 mg/dL |
470 ng/ml |
Constipation and colic; persistent hypertension; no renal, cardiac, neurological symptoms noted. Acute toxicity treated with furosemide, calcitonin, and hydrocortisol |
Study |
Patient/Population |
Preparation; Dose |
Duration |
Adults |
|
|
|
Puig. 1998. Ann Internal Med 128(7):601-602 |
66-yr-old female |
Vitamin D: 200 IU + 1,000 mg calcium/twice daily |
3 yr |
Rizzoli et al. 1994. Bone 15:193-198 |
7 adults ages 55–84 |
Vitamin D3: 30,000–60,000 IU/d |
3 weeks to 7.5 yr |
Davies and Adams. 1976. The Lancet |
Case 1: 59-yr-old female post-thyroidectomy for 40 yr |
Vitamin D: 50,000–100,000 IU/d |
>30 yr |
|
Case 2: 71-yr-old female with Paget’s disease |
150,000 IU/d |
7 yr |
|
Case 3: 51-yr-old female |
100,000 IU/d |
10 yr |
1950. BMJ letter to editor |
|
Vitamin D2: 100,000 IU/d |
3 weeks |
Streck et al. 1979. Arch Intern Med 139:974-977 |
49-yr-old female post-thyroidectomy |
Vitamin D: 100,000 units/d; plus high calcium diet |
3.8 yr |
Sterling and Rupp. 1967. Acta Endocrinologica 54:380-384 |
69-yr-old male with carcinoma of the larynx |
Vitamin D (Calciferol): 100,000 units/d |
3 weeks |
Aub. 1951. Amer Prac 2(11):976-981 |
59-yr-old female |
Vitamin D: 150,000 units/d |
6–8 weeks |
Vieth et al. 2002. Lancet 359:672 |
29- and 63-yr-old related males |
Vitamin D poisoning: 12.6 mg D3/g crystalline sugar (~1,700,000 IU/d) |
7 mo |
Serum Calcium |
Serum 25(OH)D |
Symptoms/Health Effects |
4.04 mmol/L (16.2 mg/dL) |
696 nmol/L (278.8 ng/ml) |
Anemia and dehydration; toxicity treated with milk-free diet |
3.30 mmol/L (mean) (13.2 mg/dL) (range = 2.52–4.59 mmol/L) (10.8–18.4 mg/dL) |
710 nmol/L (mean) (284.5 ng/ml) (range = 221–1692 nmol/L) (88.5–677.9 ng/ml) |
Asthenia, anorexia, nausea, polydipsia, polyuria; hypercalciuria; PTH levels were low normal. Discontinuation of vitamin D normalized calcemia in 3 d and calcidiol levels in 3 mo; bisphosphonate was used to inhibit bone resorption |
|
|
Pts reported nausea, vomiting; case 3 had extensive arterial and ligamentous calcification; tx with corticosteroids and withdrawal of vitamin D |
3.1 mmol/L (12.4 mg/dL |
|
|
4.5 mmol/L (18 mg/dL) |
450 nmol/L (180.3 ng/ml) |
|
3.75 mmol/L (15 mg/dL) |
400 nmol/L (160.3 ng/ml) |
|
|
|
Pt reported feeling well. Response from editor: Feeling well occurs early in toxicity. Toxic dose varies from 200,000–400,000 IU daily for 10 d. |
12.8 mg/dL; |
283 ng/mL |
Tx with prednisone resolved hypercalcemia via inhibition of bone resorption of calcium |
(Urinary calcium: 493–600 mg/24 hr) |
|
|
3.8–5.1 mEq/L (15.2–20.4 mg/dL) |
|
Nausea, anorexia, polyuria that progressed to dehydration and coma. Removal of vitamin D and tx with corticosteroids resolved elevated calcium and CV abnormality |
14.3 mg/dL |
|
Weight loss, memory loss; evidence of renal damage and corneal calcification. Tx not discussed |
3.82 mmol/L (15.3 mg/dL) |
1,555 nmol/L (623 ng/ml) |
Anorexia, fever, chills, vomiting, increased thirst; 5 kg weight loss; conjunctivitis, acute renal failure, PTH <1 pmol/L. Tx with IV hydrocortisone, sodium phosphate, and pamidronic acid; both patients survived. |
Study |
Patient/Population |
Preparation; Dose |
Duration |
Lilienfeld-Toal et al. 1978. Klin Wschr 56:715-717 |
70 yr old |
Vitamin D3: 15 mg/d |
3 weeks |
Selby et al. (1995) |
6 patients (most were hypoparathyroid) |
2.5–5.0 mg/d, (80,000 IU to 200,000 IU D2)/d |
2–13 yr |
Irnell (1969) Acta Med Scand. 185:147-152, 1969) |
34-yr old |
270,000 IU/d |
10 d |
|
45,000 IU/d |
6 yr |
|
Accidental or Industrial Poisoning |
|||
Scanlon et al. 1995. Am J Public Health 85:1418-1422 |
234 survey respondents |
Milk over-fortified with vitamin D at 70–600X concentration; (>50 IU/100 g) |
Intake range: (oz/d) < 5.5 5.5–11.0 11.1–19.6 ≥ 19.7 |
Blank et al. 1995. Am J Public Health 85:656-659 |
Hospital discharge, lab, and health dept data from cases of hypervitaminosis D |
Milk over-fortified with vitamin D + other risk factors, i.e., use supplements; sun sensitivity, history of cancer |
~3 yr |
Jacobus et al. 1992. New Engl J Med 326:1173-1177 |
8 individuals ages 8 mo to 82 yr consumed milk excessively fortified with vitamin D |
Milk over-fortified with cholecalciferol at concentrations of 396,400 and 376,800 IU/ml |
Variable exposure |
Thomson and Johnson. 1986. Postgrad Med J 62:1025-1028 |
7 family members; 3 adults and 4 children ages 1.5 to 14 yr |
Unknown food source containing excessively high vitamin D |
Single exposure |
Pettifor et al. 1995. Ann Intern Med 122:511-513 |
10 family members and 1 servant; age range 8-69 yr ingested oil containing a veterinary vitamin D concentrate |
Cholecalciferol concentrate in peanut oil = 2 million U/g |
Unknown exposure |
Serum Calcium |
Serum 25(OH)D |
Symptoms/Health Effects |
6.1 mval/L |
498 nmol/L (200 ng/ml) |
Fatigue and psychotic symptoms; no evidence of 2° osteoporosis was found. Tx with vitamin D was interrupted; the increased body pool of calcium returned to normal when serum vitamin D levels decreased to 200 ng/ml |
3.26 mmol/L (mean) (13.04 mg/dL) |
842 nmol/L (mean) (337.3 ng/ml) |
Admitted for hypercalcemia; renal failure |
6.6 mEq/L |
|
Patient exhibited symptoms of toxicity (tiredness, vomiting, diarrhrea, polyuria, weight loss, muscular weakness, headache) at 45,000 IU/d |
8.5–9.6 mEq/L |
|
|
|
|
Linear regression model showed a 1 oz increase in milk intake was associated with 1.39 ng/ml increase in serum 25(OH)D. No association was found between milk intake and elevated serum calcium; there was an association with elevated serum 25(OH) D and urinary calcium |
mean (mg/dL) |
mean (ng/ml) |
|
2.4 |
32.8 |
|
2.3 |
39.5 |
|
2.4 |
41.3 |
|
2.4 |
44.7 |
|
13.1 mg/dL (mean for 35 cases) |
224 ng/ml (mean for 35 cases) |
Consumption of milk from sources other than the over-fortified milk was not associated with hypervitaminosis D |
7 of 8 had hypercalcemia; 1 had hypercalcuria with normocalcemia |
Mean for all cases: 731 ± 434 nmol/L (293 ± 174 ng/ml) |
Vitamin D3 concentrate in milk that was up to 580 times in excess resulted in elevated serum vitamin D3, but not D2 in consumers. All consumers of the milk had elevated 25(OH)D levels and most had hypercalcemia |
2.72–4.08 nmol/L (10.9–16.3 mg/dL) |
832–1,287 nmol/L (333.0–515.6 ng/ml) |
Serum calcium levels returned to normal within 24 d but 25(OH)D levels remained elevated for 1 yr; 1,25 (OH)D was not significantly elevated in the adults |
3.46–4.61 nmol/L (13.8–18.4 mg/dL) |
847–1,652 nmol/L (339.3–661.9 ng/ml) |
Cholecalciferol poisoning did not elevate total 1-25 (OH)2D in 8 and only marginally in 3 of intoxicated patients; but did elevate free 1-25 (OH)2D in all |
Study |
Patient/Population |
Preparation; Dose |
Duration |
Hodges. 1985. British Med J 290:748-749. |
32-yr-old male working with crystalline vitamin D in a laboratory setting |
Unknown exposure |
Intermittent exposure: 32 d in 1981; 11 d in 1982; 22 d in 1983 |
Klontz. 2007. New Engl J Med 357:308-309 |
58-yr-old female diagnosed with diabetes and rheumatoid arthritis |
Vitamin D3 overdose in a supplement; 186,906 IU/6 capsules |
~2 mo |
Down et al. 1979. Postgrad Med J 55:897-902 |
3 family members; 2 adults ages 24 yr and 1 infant aged 11 mo |
Cholecalciferol concentrate in nut oil = 5 million IU/ml |
Single exposure |
Chiricone et al. 2003. J Nephrol 15:917-921 |
Case reports: |
Multivitamin preparation per injection; 100,000 IU vitamin D/vial |
|
62-yr-old male |
3 vials/d per 20 d/3 mo: total exposure estimate = 18,000,000 IU |
||
|
55-yr-old female |
|
3 vials/d per 20 d/1.5 mo total exposure estimate = 9,000,000 IU |
Serum Calcium |
Serum 25(OH)D |
Symptoms/Health Effects |
3.5–3.7 mmol/L (~14 mg/dL) |
496 ng/ml |
Polydypsia, polyuria, anorexia, nausea; tx with IV saline, furosemide; hydrocortisone |
3.75 mmol/L (15 mg/dL) |
1,171 nmol/L (469.2 ng/ml) |
Fatigue, constipation, back pain, forgetfulness, nausea, vomiting; tx with IV saline, furosemide, and pamidronate |
3.95 mmol/L (15.8 mg/dL) |
58–60 IU/ml (145–150 ng/ml) |
Both adults developed renal failure. The female aborted a 10-week fetus at 3 weeks post-diagnosis for hypervitaminosis D. Plasma vitamin D levels were 60 IU/ml 5 weeks post-diagnosis; nephrocalcinosis persisted in the adult male but neither had long-term renal impairment |
(mean for adults at 5 weeks post-exposure) |
(5 weeks post-exposure) |
|
Renal colic, confusion, lethargy, and weakness; reported passing small stones; tx with IV saline, furosemide, glucocorticoids |
||
15.3 mg/dL |
>150 ng/ml |
|
11.3 mg/dL |
>150 ng/ml |
|