Overview
Definition:
Hyperparathyroidism in children is characterized by excessive parathyroid hormone (PTH) secretion leading to hypercalcemia and secondary metabolic derangements
Primary hyperparathyroidism (PHPT) is rarer in children than in adults, often linked to genetic syndromes or adenomas
Secondary and tertiary hyperparathyroidism are more common, usually associated with chronic kidney disease (CKD) or vitamin D deficiency.
Epidemiology:
PHPT in children is estimated to occur at a rate of 1-5 per 100,000 population per year
Genetic predisposition, such as Multiple Endocrine Neoplasia (MEN) syndromes (MEN1, MEN2A) and familial isolated hyperparathyroidism, accounts for a significant proportion of pediatric cases, often presenting earlier than sporadic forms
Secondary hyperparathyroidism is prevalent in children with CKD on dialysis.
Clinical Significance:
Undiagnosed or untreated hyperparathyroidism in children can lead to significant morbidity, including bone demineralization (osteopenia, osteoporosis, fractures), nephrolithiasis, nephrocalcinosis, growth retardation, muscle weakness, pancreatitis, and neuropsychiatric symptoms
Early recognition and appropriate management, including timely surgical intervention when indicated, are crucial for optimizing long-term health outcomes and preventing irreversible damage.
Clinical Presentation
Symptoms:
Vague and nonspecific symptoms are common
These may include fatigue
Bone pain or fractures
Abdominal pain
Nausea and vomiting
Polyuria and polydipsia
Constipation
Muscle weakness
Cognitive impairment or mood changes
Short stature or failure to thrive.
Signs:
Physical examination may reveal signs of bone disease such as skeletal deformities
Palpable neck mass (rare)
Signs of renal dysfunction
Hypertension
Diminished reflexes
Short stature
Neurological deficits.
Diagnostic Criteria:
Diagnosis is based on biochemical evidence of elevated serum calcium levels, normal or elevated parathyroid hormone (PTH) levels, and exclusion of other causes of hypercalcemia
Key diagnostic criteria include: Persistent hypercalcemia (serum calcium >10.5 mg/dL or >2.62 mmol/L, corrected for albumin)
Elevated or inappropriately normal PTH levels
Biochemical evidence of bone resorption (elevated bone alkaline phosphatase) and/or renal calcium excretion (elevated urinary calcium).
Diagnostic Approach
History Taking:
Detailed family history for genetic syndromes (MEN1, MEN2A, familial hyperparathyroidism)
History of early onset osteoporosis or fractures
Chronic kidney disease or malabsorption
Vitamin D deficiency
Medication history (e.g., thiazide diuretics, lithium)
Symptoms suggestive of hypercalcemia: stones, bones, abdominal groans, and psychic moans.
Physical Examination:
Thorough assessment of skeletal development
Examination of the neck for any masses
Evaluation for signs of renal disease
Assessment of neurological and cognitive function
Measurement of height and weight for growth assessment.
Investigations:
Serum calcium (total and ionized) and albumin
Serum phosphorus
Serum PTH (intact PTH)
Serum alkaline phosphatase (total and bone-specific)
24-hour urinary calcium and creatinine
Renal function tests (serum creatinine, BUN)
Vitamin D levels (25-hydroxyvitamin D)
Imaging: Neck ultrasound or sestamibi scan for localization of parathyroid adenoma (especially in PHPT)
Bone densitometry (DXA scan) to assess bone mineral density
Genetic testing for MEN syndromes if suspected.
Differential Diagnosis:
Familial hypocalciuric hypercalcemia (FHH)
Tertiary hyperparathyroidism in CKD
Vitamin D intoxication
Malignancy-associated hypercalcemia
Sarcoidosis
Thiazide diuretic-induced hypercalcemia
Milk-alkali syndrome
Immobilization hypercalcemia.
Management
Initial Management:
For symptomatic hypercalcemia: aggressive hydration with intravenous normal saline
Loop diuretics (e.g., furosemide) to promote calcium excretion, only after adequate hydration
Treatment of underlying cause
Management of severe hypercalcemia with bisphosphonates or calcitonin in acute settings.
Medical Management:
For mild, asymptomatic PHPT, medical management may be considered, focusing on calcium and vitamin D intake, and regular monitoring
Vitamin D supplementation in secondary hyperparathyroidism is crucial, but careful titration is needed to avoid worsening hypercalcemia
Phosphate binders are used in renal hyperparathyroidism
Cinacalcet may be considered for severe hyperparathyroidism in CKD patients refractory to other treatments.
Surgical Management:
Surgery (parathyroidectomy) is indicated for: Symptomatic hyperparathyroidism (nephrolithiasis, fractures, significant bone pain, pancreatitis, neuropsychiatric symptoms)
Asymptomatic primary hyperparathyroidism with persistent hypercalcemia (serum calcium > 1 mg/dL above normal range), reduced bone mineral density (T-score < -2.0), or elevated 24-hour urinary calcium excretion (>400 mg/day)
Significant renal impairment or rapid progression of renal disease
Growth failure in pediatric patients with PHPT
Genetic syndromes associated with parathyroid hyperplasia or tumors.
Supportive Care:
Nutritional support to ensure adequate intake of calcium and vitamin D, tailored to the underlying cause
Regular monitoring of calcium, PTH, renal function, and bone mineral density
Management of complications such as pancreatitis, bone fractures, and renal stones.
Complications
Early Complications:
Hypocalcemia following parathyroidectomy (especially with extensive removal or hungry bone syndrome)
Persistent or recurrent hypercalcemia
Laryngeal nerve injury (hoarseness)
Wound infection or hematoma.
Late Complications:
Recurrent hyperparathyroidism due to residual or ectopic parathyroid tissue
Osteoporosis and fractures
Chronic kidney disease progression
Pancreatitis
Cardiovascular disease
Neurocognitive deficits.
Prevention Strategies:
Careful surgical technique with intraoperative PTH monitoring
Adequate preoperative correction of severe hypercalcemia and dehydration
Careful management of vitamin D and calcium intake post-surgery
Regular follow-up and monitoring of biochemical parameters and bone density.
Prognosis
Factors Affecting Prognosis:
The underlying cause of hyperparathyroidism (adenoma vs
hyperplasia vs
genetic syndrome)
The presence and severity of complications at diagnosis
Timeliness and appropriateness of surgical intervention
Adherence to medical management and follow-up.
Outcomes:
With timely and appropriate surgical management, the prognosis for children with hyperparathyroidism is generally good
Symptoms related to hypercalcemia often resolve
Bone density can improve over time
However, long-term complications can persist if not adequately managed
For secondary hyperparathyroidism in CKD, control of PTH is challenging and requires multifaceted management.
Follow Up:
Lifelong follow-up is recommended
Regular monitoring of serum calcium, PTH, phosphate, renal function, and bone mineral density
Periodic re-evaluation for recurrence or development of new complications
Genetic counseling for families with hereditary hyperparathyroidism syndromes.
Key Points
Exam Focus:
Hyperparathyroidism in children is rarer than in adults, with genetic syndromes playing a more prominent role
Surgical indications are generally more liberal in children due to potential for long-term skeletal and renal damage
Always consider MEN syndromes in pediatric PHPT
Hungry bone syndrome is a key postoperative complication.
Clinical Pearls:
Remember the "stones, bones, abdominal groans, and psychic moans" mnemonic for hypercalcemia symptoms
Ionized calcium is a more accurate measure of calcium status than total calcium, especially in patients with hypoalbuminemia
Intraoperative PTH monitoring significantly improves surgical success rates and reduces the risk of hypoparathyroidism.
Common Mistakes:
Delayed diagnosis due to nonspecific symptoms
Inadequate investigation of underlying causes
Over-reliance on medical management for severe or symptomatic disease in children
Failure to consider genetic syndromes
Inadequate postoperative monitoring for complications like hungry bone syndrome.