Abstract
Summary
Vitamin D is commonly recommended for daily intake as dietary sources are often insufficient. However, prolonged high-dose use can lead to serious complications. We present a rare case of a 2-month-old infant who developed severe hypercalcemia and hypertriglyceridemia due to an accidental overdose of 25-OH vitamin D, leading to hypertriglyceridemia and pancreatitis. The management challenges encountered while managing this case were the need for high glucose infusion rate fluids with insulin for hypertriglyceridemia, electrolyte imbalances secondary to forced diuresis, difficulties in providing fat-free formula, gradual introduction of maternal breastfeeding due to pancreatitis and rebound hypercalcemia requiring steroid treatment. These complications, rarely reported in hypervitaminosis D, highlight the need for careful vitamin D dosing in the pediatric population. Potential areas leading to vitamin D intoxication include improper formulation, lack of clarity in prescribing, concurrent use of other vitamin D-containing supplements, parental access to the internet for health supplements and easy availability.
Learning points
-
Children presenting with polyuria and failure to thrive should be screened for hypercalcemia as one of the causes.
-
Hypertriglyceridemia with pancreatitis can be managed with IV insulin infusion, high dextrose-containing fluids and gradual feed establishment as pancreatitis improves.
-
The case report underscores the serious and potentially life-threatening complications associated with vitamin D intoxication while emphasizing the importance of educating parents on safe dosage practices.
Background
Vitamin D supplementation is commonly recommended for infants at a dosage of 400 IU per day; however, an overdose can lead to life-threatening hypercalcemia. Vitamin D deficiency is defined as a blood level of 25-OH vitamin D below 20 ng/mL, insufficiency between 20 and 29 ng/mL, sufficiency above 30 ng/mL (1, 2) and toxicity at a level above 150 ng/mL. Intoxication from routinely recommended doses is extremely rare. Most cases of intoxication occur due to accidental overdoses related to prescribed regimens, formulation errors or self-initiated supplementation. Complications can be severe, including renal failure requiring hemodialysis (3).
Here, we report an unusual case of 25-OH vitamin D toxicity in a failure-to-thrive infant, who presented with hypercalcemia and hypertriglyceridemia leading to pancreatitis, which was resolved with treatment of vitamin D intoxication.
Case presentation
A 2-month-old female infant presented to our clinic due to persistent vomiting and decreased feeding for one month. There was no history of fever, loose stools, seizures, etc. Despite vomiting and decreased feeding, the infant was frequently passing urine during the day and night.
History
The baby was born at term to a primigravida mother with no comorbidities; there was no significant postnatal history. Her birth weight was 2.5 kg, and she was prescribed oral vitamin D 400 IU daily at the time of discharge. The infant was receiving both the mother’s breastfeeding and term formula milk. The family history was insignificant except that the parents belonged to a poor socioeconomic background and had no formal education.
Examination
On examination, she was severely malnourished, dehydrated, lethargic and hypotonic. There was no dysmorphism, subcutaneous nodules or xanthomas. Her systemic examination was unremarkable. Her weight was 1.6 kg and her length was 47 cm, and both were well below their respective third percentiles. We admitted the baby to the NICU for further management.
Investigations
During hospitalization, she underwent comprehensive evaluation, which showed a lipemic-appearing blood sample (Fig. 1), negative septic markers and severe hypercalcemia of 16.9 mg/dL with normal phosphorus, alkaline phosphatase, magnesium, creatinine and electrolytes. Parathyroid hormone levels were appropriately suppressed (Table 1). Due to the lipemic-appearing blood sample, her lipid profile was sent, which reported severe hypertriglyceridemia and hypercholesterolemia. Upon further inquiry, the mother mentioned giving a tablespoon of each of the two types of vitamin D drops (each containing 25-OH vitamin D, 400 IU per drop) daily, without proper dose measurement. Although the exact dose was unclear, we concluded that she was unknowingly administering a very high dose of 25-OH vitamin D, considering her method of administration. Subsequently, her vitamin D tests were sent, which reported 25-OH-vitamin D level >150 ng/mL and 1,25-dihydroxy vitamin D >200 pg/mL, confirming the diagnosis of hypervitaminosis D. Urine calcium-to-creatinine ratio was high and renal ultrasound revealed bilateral nephrocalcinosis. Due to persistent vomiting, her amylase and lipase were tested and it was found that they were markedly elevated.
Lipemic blood sample.
Citation: Endocrinology, Diabetes & Metabolism Case Reports 2025, 1; 10.1530/EDM-24-0132
Investigations at the presentation and last follow-up visit.
Test | Reference range | At presentation | Last follow-up |
---|---|---|---|
Calcium, mg/dL | 8.6–10.2 | 16.9 | 10.1 |
Phosphorus, mg/dL | 4–7 | 2.6 | |
ALP, IU/L | 153 | ||
PTH, pg/mL | 16–87 | <3 | |
25-OH vitamin D, ng/mL | >30* | >150 | 47.6 |
1,25-OH vitamin D, pg/mL | 19–79 | >200 | |
Creatinine, mg/dL | 0.8 | ||
Urine calcium: creatinine | <0.2 | 1.1 | |
Triglycerides, mg/dL | <150 | 2,409 | 100 |
Cholesterol, mg/dL | <200 | 314 | |
LDL, mg/dL | <100 | 29 | |
VLDL, mg/dL | <30 | 481 | |
Lipase, U/L | 6–50 | 228 | 36 |
Albumin, g/L | 3.5–5.2 | 4 |
Value indicates sufficiency.
Key investigations at the presentation and recent follow-up visit are summarized in Table 1.
Serial trends of serum calcium and serum triglyceride and lipase are shown in Figs 2 and 3, respectively.
Trend of serum calcium.
Citation: Endocrinology, Diabetes & Metabolism Case Reports 2025, 1; 10.1530/EDM-24-0132
Trends of serum triglyceride and lipase.
Citation: Endocrinology, Diabetes & Metabolism Case Reports 2025, 1; 10.1530/EDM-24-0132
Treatment
The infant was kept nothing per os due to pancreatitis; hypercalcemic crises was managed with IV hyperhydration and IV furosemide. IV 0.45% dextrose saline was started at a rate of 1.5 times maintenance along with furosemide infusion at an initial dose of 0.3 mg/kg/h, which was increased up to 0.7 mg/kg/h.
Calcium levels were serially monitored and as the calcium levels decreased, IV furosemide and fluids were tapered, but the baby had rebound hypercalcemia, which required the resumption of furosemide and fluids. Bisphosphonates were considered but not given as first-line considering her age, instead oral prednisolone 2 mg/kg/day was started, which resulted in improvement in serum calcium levels. For hypertriglyceridemia, insulin infusion was started at 0.05 u/kg/h along with IV dextrose-containing fluids and the glucose infusion rate (GIR) was increased up to 15 mg/kg/min to maintain blood glucose within the normal range. After 48 h, fat-free formula was introduced and gradually progressed, which she tolerated well. Fluids and insulin infusion were tapered off accordingly. Her serial lipase and triglyceride values showed an improving trend (Fig. 3); hence, maternal breastfeeding was introduced. The parents’ lipid profile and the mother’s vitamin D and PTH levels were completely normal. Subsequently, the infant was discharged home with complete remission of symptoms, weight gain, serum calcium level of 10.9 mg/dL, triglyceride value of 148 mg/dL and lipase of 111 U/L on tapering doses of prednisolone.
Outcome and follow-up
As we tapered steroids on discharge, the infant had rebound hypercalcemia after 72 h; hence, we restarted 2 mg/kg/day prednisolone (Fig. 2). Prednisolone was given for a total duration of eight weeks and was tapered off slowly. She gained 1.5 kg weight in three months, her calcium levels remained stable within the normal range, and monitoring was discontinued after three months. Her vitamin D, triglycerides and lipase values remained normal. Mother’s breastfeeding was continued, and a follow-up ultrasound of the kidneys was planned to monitor nephrocalcinosis. Parents were educated in detail about the cautious administration of all medications and vitamin supplements.
Timeline of events is shown in Fig. 4.
Timeline of events.
Citation: Endocrinology, Diabetes & Metabolism Case Reports 2025, 1; 10.1530/EDM-24-0132
Discussion
Here, we report an unusual case of 25(OH)-vitamin D intoxication presenting with failure to thrive, hypercalcemia, hypertriglyceridemia and pancreatitis. All of the initial symptoms were resolved, following biochemical control of hypercalcemia and hypertriglyceridemia. In our review of the literature, 25(OH)-vitamin D intoxication has previously been reported in children presenting with hypercalcemia, hypercalciuria, nausea, vomiting, fatigue, dehydration, weight loss, confusion, lethargy and psychosis (4). The reported complications are failure to thrive (5, 10), nephrocalcinosis (6), hypertension (7), acute kidney injury, dyslipidemia (8) and pancreatitis (9, 10, 11).
Fat-soluble vitamins are lifesaving at physiological levels but potentially dangerous at megadoses (12). For many people, the word ‘vitamin’ applies to something beneficial, not potentially harmful (13). Ultraviolet B waves (UVB) of sunlight stimulate the cutaneous synthesis of vitamin D3 or cholecalciferol, but its effect is dependent on the duration of exposure to sunlight and skin color. Cultural practices, insufficient UV light availability with climate changes, use of sunscreen and insufficient dietary intake may all contribute to the deficiency of vitamin D3. If the sunlight exposure is halved, the intake must be tripled and this can only be achieved by dietary supplementation (14). The injudicious use of 25(OH) vitamin D supplements with unrestricted availability of high doses has created serious potential for intoxication in all age groups, particularly in children due to the rapid distribution of 25(OH) vitamin D in adipose tissue because of their small body size. 25(OH) vitamin D has a high affinity for its transport-binding protein and has a half-life of 2–3 weeks; hence, it is more likely to cause intoxication compared to calcitriol, which has a very short half-life.
In our case, 25(OH) vitamin D intoxication was associated with hypercalcemia, hypertriglyceridemia and pancreatitis. The lipid-modulating effects of 25(OH) vitamin D have been previously reported in adults. In a meta-analysis of randomized-controlled trials, vitamin D supplementation provided a statistically significant increase in LDL-C (15). In an open-label prospective trial on adolescents to study the effects of treatment with 25(OH) vitamin D, there was an increase in the total cholesterol and serum triglyceride concentration from the baseline to follow-up (16). 25(OH) vitamin D affects body fat mass by inhibiting adipogenic transcription factors and lipid accumulation during adipocyte differentiation (17, 18). Moreover, it plays an important role in lipid metabolism by increasing the lipoprotein lipase activity, enhancing lipolysis and increasing the absorption of fat from the gut (18).
Hypercalcemia is an uncommon cause of pancreatitis; some studies suggest that hypercalcemia leads to calcium deposition in the pancreatic duct and accelerates the conversion of trypsinogen to trypsin causing autodigestion of the pancreas (19). In our case, 25(OH) vitamin D intoxication led to hypercalcemia, leading to pancreatitis.
Management largely revolves around hypercalcemia as 25(OH) vitamin D stores will take time to deplete. The recommendation is to discontinue all the sources of vitamin D and the reduction of dietary calcium, hyperhydration with isotonic fluids and diuretics to aid in renal calcium clearance after restoring volume with electrolyte correction, if required, as in our case. Therapy with glucocorticoids will decrease plasma calcium levels by reducing intestinal calcium absorption and promoting urinary excretion of calcium. Furthermore, it also changes the hepatic vitamin D metabolism to favor synthesizing the inactive metabolites. The treatment with glucocorticoids is effective, but long-term treatment is associated with significant adverse effects (20). Our patient responded well to glucocorticoids, and the dose was subsequently tapered off.
In severe toxicity, calcitonin and bisphosphonates are recommended, particularly in cases where hypercalcemia is the result of increased osteoclastic bone resorption due to the direct effect of 1,25(OH)2 vitamin D on bone tissue (3). In our patient, we opted not to use calcitonin because of the risk of tachyphylaxis, while the infant was too young to consider bisphosphonates as first-line management; hence, we decided to consider bisphosphonates after glucocorticoids.
In addition, we started insulin along with high GIR fluids for hypertriglyceridemia, which resulted in a drastic reduction in triglyceride levels. Insulin as a rapid activator of lipoprotein lipase accelerates triglyceride degradation and facilitates storage in adipocytes, decreasing pancreatitis. Bolus subcutaneous insulin is associated with a high risk of hypoglycemia; hence, IV insulin infusion along with dextrose infusion to aim euglycemia is an effective and safe treatment strategy for hypertriglyceridemia-associated pancreatitis (21).
This case represents an uncommon manifestation of 25(OH) vitamin D toxicity as hypertriglyceridemia and pancreatitis in infancy and was a challenging case to manage. The keynote is that 25(OH) vitamin D intoxication can typically be prevented by careful prescription and education of parents and the symptoms are completely reversible with timely diagnosis and management (20, 22).
Declaration of interest
The authors declare that no conflict of interest could be perceived as prejudicing the impartiality of the work reported.
Funding
This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.
Patient consent
Written informed consent for publication of their clinical details and/or clinical images was obtained from the parent of the patient.
Author contribution statement
All authors reviewed the revised manuscript and approved the final version of the manuscript. Bushra Rehman and Fozia Memon designed for this write-up, wrote the manuscript and managed the patient. Khadija Nuzhat Humayun and Muzna Arif managed the case thoroughly and provided expert advice and critical revision of the manuscript.
Patient’s perspective
Our daughter is currently well, and we had no idea that an overdose of vitamins led to her symptoms. We learned to be cautious in the future.
References
- 1↑
Holick MF . Vitamin D deficiency. New Engl J Med 2007 357 266–281. (https://doi.org/10.1056/nejmra070553)
- 2↑
Holick MF , Binkley NC , Bischoff-Ferrari HA , et al. Evaluation, treatment, and prevention of vitamin D deficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2011 96 1911–1930. (https://doi.org/10.1210/jc.2011-0385)
- 3↑
Asif A & Farooq N . Vitamin D toxicity. In InStatPearls. StatPearls Publishing, Treasure Island, FL, USA, 2023.
- 4↑
Levita J , Wilar G , Wahyuni I , et al. Clinical toxicology of vitamin D in pediatrics: a review and case reports. Toxics 2023 11 642. (https://doi.org/10.3390/toxics11070642)
- 5↑
Bilbao NA . Vitamin D toxicity in young breastfed infants: report of 2 cases. Glob Pediatr Health 2017 4 2333794X17731695. (https://doi.org/10.1177/2333794x17731695)
- 6↑
Atabek ME , Pirgon O & Sert A . Oral alendronate therapy for severe vitamin D intoxication of the infant with nephrocalcinosis. J Pediatr Endocrinol Metab 2006 19 169–172. (https://doi.org/10.1515/jpem.2006.19.2.169)
- 7↑
Singh P , Nimesh M , Jhamb U , et al. An unsuspected pharmacological vitamin D toxicity in a child and its brief review of literature. Toxicol Int 2015 22 167. (https://doi.org/10.4103/0971-6580.172284)
- 8↑
Sharawat IK . Hypervitaminosis D with Dyslipidemia: An Unusual Scenario. Indian Pediatr 2016 53 174–175.
- 9↑
De Waele B , Smitz J & Willems G . Recurrent pancreatitis secondary to hypercalcemia following vitamin D poisoning. Pancreas 1989 4 378–380. (https://doi.org/10.1097/00006676-198906000-00017)
- 10↑
Zhou L , Taylor-Miller T , Zacharin M , et al. Extreme hypercalcaemia due to accidental vitamin D intoxication. J Paediatrics Child Health 2018 55 104–106. (https://doi.org/10.1111/jpc.14127)
- 11↑
Stokes VJ , Nielsen MF , Hannan FM , et al. Hypercalcemic disorders in children. J Bone Mineral Res 2017 32 2157–2170. (https://doi.org/10.1002/jbmr.3296)
- 12↑
Scharfman WB & Propp S . Anemia associated with vitamin D intoxication. New Engl J Med 1956 255 1207–1212. (https://doi.org/10.1056/nejm195612272552601)
- 13↑
Hoff W . Vitamin-D poisoning. The Lancet 1980 315 1308. (https://doi.org/10.1016/s0140-6736(80)91770-5)
- 14↑
Allgrove J . Physiology of calcium, phosphate, magnesium and vitamin D. Endocr Dev 2015 28 7–32. (https://doi.org/10.1159/000380990)
- 15↑
Wang H , Xia N , Yang Y , et al. Influence of vitamin D supplementation on plasma lipid profiles: a meta-analysis of randomized controlled trials. Lipids Health Dis 2012 11 42–49. (https://doi.org/10.1186/1476-511x-11-42)
- 16↑
Javed A , Kullo IJ , Balagopal PB , et al. Effect of vitamin D3 treatment on endothelial function in obese adolescents. Pediatr Obes 2016 11 279–284. (https://doi.org/10.1111/ijpo.12059)
- 17↑
Ding C , Gao D , Wilding J , et al. Vitamin D signalling in adipose tissue. Br J Nutr 2012 108 1915–1923. (https://doi.org/10.1017/s0007114512003285)
- 18↑
Park CY & Han SN . The role of vitamin D in adipose tissue biology: adipocyte differentiation, energy metabolism, and inflammation. J Lipid Atheroscler 2021 10 130. (https://doi.org/10.12997/jla.2021.10.2.130)
- 19↑
Chen KC , Liao CY & Huang WC . The case| pancreatitis with hypercalcemia. Kidney Int 2019 95 1521–1522. (https://doi.org/10.1016/j.kint.2018.12.011)
- 20↑
Marcinowska-Suchowierska E , Kupisz-Urbańska M , Łukaszkiewicz J , et al. Vitamin D toxicity–a clinical perspective. Front Endocrinol 2018 9 550. (https://doi.org/10.3389/fendo.2018.00550)
- 21↑
Poon SW , Leung KK & Tung JY . Management of severe hypertriglyceridemia due to lipoprotein lipase deficiency in children. Endocrinol Diabetes Metab Case Rep 2019 2019 1–5. (https://doi.org/10.1530/edm-19-0052)
- 22↑
Gérard AO , Fresse A , Gast M , et al. Case report: severe hypercalcemia following vitamin d intoxication in an infant, the underestimated danger of dietary supplements. Front Pediatr 2022 10 816965. (https://doi.org/10.3389/fped.2022.816965)