Evaluation and Management of Elevated Alkaline Phosphatase in Teenagers
In a teenager with elevated alkaline phosphatase, first obtain a comprehensive metabolic panel including serum calcium, phosphate, creatinine, liver transaminases, and bilirubin, then assess for symptoms of bone disease (pain, deformities, growth impairment, dental abnormalities) or liver disease (jaundice, hepatomegaly), as this will determine whether the elevation is physiologic (common during adolescent growth spurts) or pathologic. 1
Initial Clinical Assessment
Evaluate for specific clinical features that suggest pathologic causes:
- Bone-related symptoms: bone pain, skeletal deformities (varus/valgus deformities, intoeing/extoeing), growth impairment, delayed walking, waddling gait, dental abnormalities 2, 1
- Hepatobiliary symptoms: jaundice, hepatomegaly, recent illness, abdominal pain 1
- Growth parameters: measure height, weight, BMI, and assess growth velocity over time 1
Laboratory Workup Algorithm
First-tier testing (all asymptomatic patients):
- Comprehensive metabolic panel: calcium, phosphate, creatinine, liver transaminases (AST/ALT), bilirubin 1
- PTH and 25(OH) vitamin D levels to exclude metabolic bone disorders 1
Interpretation of initial results:
If phosphate is LOW with elevated ALP:
- Calculate TmP/GFR (tubular maximum reabsorption of phosphate per glomerular filtration rate) to assess for renal phosphate wasting 2
- Measure intact FGF23 levels (most informative in untreated patients) 2
- Consider X-linked hypophosphataemia (XLH), especially if family history present 2
If liver enzymes are elevated:
If all initial labs are normal:
- Consider transient hyperphosphatasemia (THP), a benign condition common in children and adolescents 3, 4
- Physiologic elevation is very common during adolescent growth spurts, with ALP levels naturally very high in early adolescence 5
Key Pathologic Diagnosis: X-linked Hypophosphataemia
Biochemical hallmarks of XLH:
- Hypophosphataemia with renal phosphate wasting (low TmP/GFR) 2
- Elevated ALP 2
- Elevated or inappropriately normal intact FGF23 levels 2
- Calcium usually in lower normal range 2
- PTH at upper limit of normal or slightly elevated 2
Important caveat: Serum phosphate levels might be in the normal range within the first 3-4 months of life, but teenagers should show clear hypophosphataemia 2
Management Based on Diagnosis
For confirmed XLH:
Treatment consists of oral phosphate supplements (20-60 mg/kg daily of elemental phosphorus) divided into 4-6 doses daily, combined with active vitamin D (calcitriol 20-30 ng/kg daily or alfacalcidol 30-50 ng/kg daily). 2
- Do NOT aim to normalize phosphate levels - fasting phosphate will not normalize with oral supplements alone 1
- Adjust dosing based on improvement of rickets, growth, ALP, and PTH levels 2
- Avoid doses >80 mg/kg daily to prevent gastrointestinal discomfort and hyperparathyroidism 2
- Monitor every 3-6 months with height, weight, BMI, blood pressure, ALP, calcium, phosphate, creatinine, PTH, and 25(OH) vitamin D 1
- Annual assessment of growth velocity and bone deformities 1
- Dental visits twice yearly after tooth eruption 1
For transient hyperphosphatasemia (THP):
- Adopt a "wait and see" approach with repeat ALP measurement in 4-8 weeks 3
- ALP levels typically normalize within 4 months without intervention 3, 4
- No further testing or referrals needed if clinical examination remains normal 3
Critical Pitfalls to Avoid
- Do not assume all elevated ALP in teenagers is physiologic - while growth-related elevation is common, pathologic causes must be excluded first 1
- Do not overlook XLH in patients with "mild" hypophosphataemia - inappropriately normal FGF23 in the setting of any degree of hypophosphataemia is diagnostic 2
- Do not attempt to normalize phosphate levels in XLH treatment - this is not achievable with conventional therapy and should not be the goal 1
- Do not order extensive imaging or specialty referrals before completing basic metabolic workup in asymptomatic patients 3