Vitamin D Intoxication in childen

1. BILATERAL NEPHROCALCINOSIS IN AN
INFANT-AN AVOIDABLE MENACE
Dr Jishnu.K.R(PG II Year)
Department of Pediatrics
KIMS

2. CASE SCENARIO
• 10 mo old male child admitted to KIMS in March 2020
 Fever - 7days
 Vomiting- 5 days
 Excessive cry- 3days
• H/O Past Illness- H/o poor weight gain and non erupted teeth(+),No h/o
admission in hospital with diarrhoea,pneumonia or any other illness

3. • Antenatal History- Normal,Non consanguineous marraige,No H/o fever in
mother,Antenatal USG of mother - Normal
• Natal History- First order child,Term,NVD,Birth weight-2.7KG
• Post Natal History- No h/o admission to NICU
• Immunization History- Immunised till age
• Devolopment History- Attained devolopmental milestones as per age

4. • Dietary History- Exclusive breast feeding till 3 months of age followed by
which formula feeding was given.
• Weaning started at the age of 6months with semi-solid home made
foods(cereal based)
 Calorie Gap- 400Kcal/kg/day
 Protein Gap- 1.5g/kg/day
• Family History- Non consanguineous marraige,No h/o of any chronic or
genetic diseases in family members
• Socioeconomic History- Lower socioeconomic class

5. • General Examination:-
- Child was consious but lethargic.
-Pallor(+)
- Vitals:- Temp-101F, HR-120/min, BP-112/70 mm Hg(>95th centile,95th
percentile- 102/54 mmHg),RR-27/min
- Anthropometry- Length-67cm(Less than 3rd percentile)
Weight- 5.2kg(Less than 3rd percentile)
HC- 42cm(Btw 3rd and 5th percentile)
Wt/L- below -3z score
MUAC-10cm(MUAC<11.5cm- Severe Acute Malnutrition)

6. -Head to Toe Examination-
Teeth - not erupted,
Head,hair,face,eyes,mouth,tongue,ears,nose,limbs,chest,abdomen,genitalia,spine,
skin and nails- Normal
- Systemic Examination-
CNS-
Higher mental function- Normal
Sensory system- Normal
Motor system- Muscle wasting(+) in bilateral upper and lower limbs
Reflexes- Normal
No Meningeal Signs

7. -Cardiovascular,Respiratory and Gastrointestinal system Examination- Normal
- Provisional Diagnosis- Severe Acute Malnutrition with Urinary Tract Infection
-Differential Diagnosis- Severe Acute Malnutrition with Enteric Fever,Malaria,Sepsis

8. On Investigations
• CBC: TLC- 15000/cumm (N78, L21, E1), TPC-270000/cumm,
Hb-10 gm%
• CPS- Microcytic Hypochromic Anemia
• Urine: PH-7.0, Protein- Absent, Sugar- Absent,Pus cell- 4 – 6/hpf
• CRP: 5mg/dl
• LFT- SGOT- 36U/L
SGPT- 35U/L
ALP- 95U/L
S.Bilirubin- 0.28mg/dl
• RFT- S.Urea-39.4mg/ml
S.Creatinine- 0.59mg/dl
• Electrolytes- S.Sodium- 135mmol/L
S.Potassium-5mmol/L
S.Chloride - 98mmol/L

9. Investigations ctd
• MP-ICT- Negative
• Typhidot IgM- Negative
• TSH- 2.5mg/dL , FT4- 1.5mg/dL
• RBS- 94mg/dl
• Blood Culture and Urine Culture was sent.

10. Day 1
• Child was treated with IV Fluids and IV Ceftriaxone
• USG kidney, ureter and bladder(KUB) showed Bilateral Medullary
Nephrocalcinosis(NC)
• On detailed enquiry,documentation of Mega dose of Vitamin D, total amont
of vitamin D 8400,000 IU over 3 months (injection Vitamin D 600,000 I.M
weekly, 14doses) was seen.

11. On further Investigation
ABG- Normal(HCO3- 22meq/L)
Serum calcium -14.8 mg/dl(N =8.5-10.5)
Phosphorus- 4.5mg/dl(N=3.5-5.5 )
Magnesium- 2.5 mg/dl(N=1.6-2.6)
Alkaline phosphatase-95 IU/L(N= 44-147 IU/L)
Parathormone(PTH)- 4.84 pg/ml(N=15-65)
25(OH)D level - >150 ng/ml(N= 20-80)
ECG- Normal

12. • Morning urine calcium/creatinine(Ca/cr) ratio- 2.33, suggestive of
hypercalciuria (N<0.8 in 6-12 months).
• X-ray wrist with elbow and Echocardiography- Normal
• Child was diagnosed as a case of Severe Acute Malnutrition with Urinary
Tract Infection with Vitamin D Intoxication with Medullary
Nephrocalcinosis

13. Treatment
• All medicine containing vitamin D and calcium was stopped
• Breast feeding was witheld temporarily with continuing oral feeding on
demand
• Intravenous Normal Saline(150 ml/kg/day)
• Oral furosemide(1 mg/kg/day) in 3 divided doses
• Oral nifedipine(0.25 mg/kg/day)
• During this treatment he was monitored regularly for improvements of
symptoms, intake/output chart and serum calcium level.

14. Day 2
• Repeat Investigation:-
-Repeat calcium level was 14.5 mg/dL
- Prednisolone @1mg/kg/day was added

15. Day 3
• Urine culture grown Citrobacter Freundi which was senstive to Amikacin
• Since the child was afebrile after staring IV Ceftriaxone,it was continued.

16. Day 4
• In view of persisting hypercalcemia(S.Calcium- 14.3mg/dl) ,Oral
alendronate was added in a dose of 5 mg/day
• Prednisolone was stopped
• Calcitonin was not given because of the parents refusal and risk of
tachyphylaxis.

17. Day 7
• Serum calcium dropped rapidly to 12 mg/dl and I.V Normal Saline
was discontinued.
• Feeding was started with proper dietary advice for Severe Acute
Malnutrition with calorie of 900Kcal/day and 16g/day protein.
• He required total 3 doses of oral alendronate

18. At the time of discharge:-
• Child was afebrile
• S. Calcium- 10.5mg/dl
• Child was on energy rich diet with total calorie intake of 900Kcal/day and
protein intake of 16g/day
• Oral Nifedipine was advised to continue till the follow up after 1 week.
• Parents were counselled regarding regular follow up, but due to pandemic
situation in region, they failed.

19. Metabolism Of Vitamin D

20. VITAMIN D INTOXICATION
• First reported in India in 2004 in AIIMS New Delhi
(Ref:- Acute Vitamin D Toxicity in an infant,The Japanese society for Pediatric
Endocrinology, 2004)
• Follow up of this case after 14 years showed persistent medullay
nephrocalcinosis.
• In a retrospective study of 152 children and adolescents,prophylactic bolus
administration of Vitamin D was the cause of nephrocalcinosis in 9% cases.
(Ref:- Nephrocalcinosis in children:a retrospective multi centre study, Acta
Pediatrica 2009)

21. - Etiology:-
 High doses of vitamin D given by health care providers
 Inappropriate administration of high doses in infants for complaints
such as delayed teething, ‘late walking’, and ‘knock-kneed gait’.
-According to the AAP:-
 Serum levels above 100 ng/ml -Hypervitaminosis D
 Serum levels above 150 ng/ml- Vit D Intoxication(VDI)

22. Mechanism of Vitamin D Intoxication(VDI)
• Serious consequences due to the degree of hypercalcemia and subsequent
hypercalcuria/nephrocalcinosis.
• Active vitamin D is a potent stimulator of osteoclastogenesis resulting in
bone resorption
• Hypercalcemia predominantly results from bone resorption.

23. Hypercalcemia

25. LABORATORY DIAGNOSIS
In patients with VDI:-
Hypercalcemia,
Normal or high serum phosphorus levels,
Normal or low levels of alkaline phosphatase,
High levels of serum 25OHD,
Low serum parathyroid hormone,
High urine calcium/creatinine ratio
Medullary nephrocalcinosis can be detected better in ultrasound scanning

26. Treatment
• Discontinuing intake
• Diet with low calcium and phosphorus content
• Intravenous (IV) hydration with Normal Saline
• Loop diuretics
• Glucocorticoids
• Calcitonin
• Bisphosphonates
• Hemodialysis

28. Nephrocalcinosis
• Well known but rare complication of VDI which is usually irreversible
• Defined as generalized deposition of calcium salts(Calcium oxalate or
phosphate) in the kidney,predominantly in the interstitium.
• Usually involves renal medulla(>97%cases) and less commonly cortex.

29. • Grading-
- I - Mild increase in echogenecity of medullary pyramids
-II - Mild diffuse increase in echogenecity of medullary pyramids without
accoustic shadowing
-III - Homogenous increase in echogenecity of medullary pyramids with
accoustic shadowing.

30. Causes
• Primary hyperparathyroidism
• Distal renal tubular acidosis
• Primary hyperoxaluria
• Barter's syndrome
• Hereditary hypophosphatemic rickets with hypercalciuria
• Idiopathic hypercalciuria
• Vitamin D Intoxication

31. In a pediatric series of 40 patients from North India with NC:-
RTA (50%),
Idiopathic hypercalciuria (7.5%),
Primary hyperoxaluria (7.5%)
Vitamin D Intoxication (5%)
•In a series of 41 patients from Italy with NC :-,
Renal tubulopathies (41%)
Vitamin D Intoxication (10%)
Ref:Etiology of ephrocalcinosis in northern Indian Children, Pediatric Nephrol 2007

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