Overview
Definition:
Hypercalcemia in children is defined as a serum calcium concentration greater than 2 standard deviations above the mean for age and sex, typically exceeding 10.5 mg/dL (2.6 mmol/L)
It represents an imbalance between calcium absorption, bone resorption, renal excretion, and intestinal uptake, leading to elevated serum calcium levels
Prompt identification and management are crucial due to potential acute and chronic morbidities.
Epidemiology:
The prevalence of hypercalcemia in hospitalized children varies, with estimates ranging from 0.5% to 2%
In outpatient settings, it is less common
The incidence is higher in infants and neonates, often related to specific genetic conditions or iatrogenic causes
The etiologies differ significantly from adult hypercalcemia, with a higher proportion of PTH-dependent causes in younger children.
Clinical Significance:
Hypercalcemia in children can range from asymptomatic to life-threatening
It can lead to severe dehydration, renal failure, neurological symptoms, cardiovascular complications, and bone abnormalities
Understanding the distinction between PTH-dependent and independent causes is paramount for guiding appropriate diagnostic workup and therapeutic interventions, crucial for successful DNB and NEET SS examinations.
Clinical Presentation
Symptoms:
Symptoms are often nonspecific and may include lethargy
Irritability
Anorexia
Vomiting
Abdominal pain
Constipation
Polyuria
Polydipsia
Dehydration
Muscle weakness
Bone pain
In severe cases: confusion, coma, arrhythmias, pancreatitis, kidney stones.
Signs:
Physical examination may reveal signs of dehydration
Decreased deep tendon reflexes
Hypotonia
Shortening of the QT interval on ECG
Hypertension
Abdominal tenderness
Evidence of underlying cause (e.g., dysmorphic features, palpable masses).
Diagnostic Criteria:
Diagnosis is based on elevated serum calcium levels
Further confirmation requires ionized calcium measurement, which is the physiologically active form
Differentiating between PTH-dependent and independent causes is the cornerstone of the diagnostic workup, guiding the subsequent investigation pathway.
Diagnostic Approach
History Taking:
Key history points include duration of symptoms, dietary calcium intake, family history of hypercalcemia or related disorders, use of medications (e.g., vitamin D supplements, thiazide diuretics), recent immobilisation, and associated symptoms suggestive of underlying endocrine, genetic, or neoplastic disorders
Red flags include rapid onset, severe symptoms, and a family history of hypercalcemia.
Physical Examination:
A thorough physical examination should focus on assessing hydration status, vital signs, neurological function, cardiovascular system (for arrhythmias or murmurs), abdominal palpation for masses, and a detailed assessment for dysmorphic features suggestive of genetic syndromes.
Investigations:
Initial investigations include serum electrolytes, urea, creatinine, albumin, and ionized calcium
Serum phosphate, magnesium, and alkaline phosphatase levels are also important
For suspected PTH-dependent hypercalcemia, serum PTH levels are essential
PTH-related peptide (PTHrP) levels are measured if malignancy is suspected
Vitamin D levels (25-OH vitamin D, 1,25-OH vitamin D) are crucial
Urine calcium-creatinine ratio helps assess renal handling of calcium
Imaging may include renal ultrasound for stones and skeletal survey for fractures or osteolytic lesions
Genetic testing may be indicated for familial hypercalcemia syndromes.
Differential Diagnosis:
Differential diagnoses for hypercalcemia in children include: 1
PTH-dependent: Primary hyperparathyroidism, Familial Hypocalciuric Hypercalcemia (FHH), Tertiary hyperparathyroidism
2
PTH-independent: Vitamin D intoxication, Milk-alkali syndrome, Granulomatous diseases (e.g., sarcoidosis), Malignancy (rare in children, but consider neuroblastoma, leukemia, lymphoma), Medications (e.g., excessive vitamin D supplementation), Immobilization, Williams syndrome, Rhabdomyolysis, Thalassemia, Bartter syndrome, Pseudohyperparathyroidism (rare).
Etiology Classification
Pth Dependent:
This category involves elevated parathyroid hormone (PTH) levels or inappropriately normal PTH in the context of hypercalcemia
The most common causes in children are: Primary hyperparathyroidism (adenoma, hyperplasia, or carcinoma of parathyroid glands)
Familial Hypocalciuric Hypercalcemia (FHH), an autosomal dominant disorder
Tertiary hyperparathyroidism, often seen in chronic renal disease or vitamin D deficiency states leading to parathyroid hyperplasia.
Pth Independent:
In this category, PTH levels are suppressed (low or undetectable) in the presence of hypercalcemia, indicating that PTH is not the primary driver of elevated calcium
Common causes include: Vitamin D intoxication (excessive intake of vitamin D supplements or fortified foods)
Malignancy-associated hypercalcemia (due to PTHrP production, rare in children but consider neuroblastoma, lymphoma, leukemia)
Granulomatous diseases (e.g., sarcoidosis, tuberculosis, which produce calcitriol)
Medications (e.g., thiazide diuretics, lithium)
Severe dehydration
Immobilization
Genetic syndromes like Williams syndrome
Rhabdomyolysis
Milk-alkali syndrome.
Management
Initial Management:
Immediate management focuses on hydration and calcium lowering
Intravenous isotonic saline infusion is the cornerstone to promote renal calcium excretion and correct dehydration
Loop diuretics (e.g., furosemide) can be used once hydration is achieved to enhance urinary calcium loss, but only after adequate fluid resuscitation to avoid exacerbating dehydration and hypokalemia.
Medical Management:
If initial measures are insufficient, or for severe hypercalcemia, further medical management may be required
Bisphosphonates (e.g., pamidronate, zoledronic acid) are effective in reducing bone resorption and lowering calcium levels, particularly in cases of malignancy or severe hyperparathyroidism
Calcitonin can provide rapid but transient reduction in calcium
Glucocorticoids may be used for granulomatous diseases
Treatment of the underlying cause is paramount, whether it involves discontinuing offending agents, managing malignancy, or correcting vitamin D excess.
Surgical Management:
Surgical intervention, typically parathyroidectomy, is the definitive treatment for symptomatic primary hyperparathyroidism due to adenoma or hyperplasia
Indications include symptomatic hypercalcemia, evidence of end-organ damage (renal stones, bone disease), or significantly elevated PTH levels
Preoperative localization studies may be performed.
Supportive Care:
Supportive care involves meticulous monitoring of fluid balance, electrolytes, renal function, and cardiac rhythm
Nutritional support should be optimized, avoiding high-calcium or high-vitamin D intake unless indicated
Management of symptoms such as vomiting, constipation, and pain is essential.
Complications
Early Complications:
Acute complications include severe dehydration leading to pre-renal azotemia and acute kidney injury
Cardiac arrhythmias (e.g., QT prolongation, bradycardia)
Neurological symptoms ranging from confusion and lethargy to coma
Pancreatitis
Hypotonia and muscle weakness.
Late Complications:
Long-term complications can include nephrocalcinosis and chronic kidney disease
Osteopenia and fractures
Cardiovascular calcification
Growth retardation in chronic cases
Psychiatric disturbances.
Prevention Strategies:
Prevention strategies involve careful monitoring of calcium and vitamin D intake, especially in infants and children receiving supplementation
Prompt recognition and management of conditions predisposing to hypercalcemia (e.g., chronic renal disease, immobilization)
Genetic counseling for families with a history of hypercalcemic syndromes.
Key Points
Exam Focus:
Differentiate PTH-dependent from PTH-independent causes
Recognize common pediatric etiologies (primary hyperparathyroidism, FHH, vitamin D intoxication)
Understand the immediate management of acute hypercalcemia (saline and furosemide)
Know the role of bisphosphonates and parathyroidectomy
DNB and NEET SS questions often test the approach to diagnosis and management in specific pediatric scenarios.
Clinical Pearls:
Always measure ionized calcium
Assess hydration status before administering furosemide
Consider genetic causes in recurrent or familial cases
Remember that malignancy is a rare but serious cause of hypercalcemia in children, necessitating a thorough workup if suspected
A family history can be highly informative.
Common Mistakes:
Mistaking symptoms of dehydration for severity of hypercalcemia alone
Administering furosemide before adequate fluid resuscitation
Inadequate investigation of underlying cause
Failing to consider genetic causes of hypercalcemia in the pediatric population
Overlooking vitamin D intoxication as a common reversible cause.