Hyperparathyroidism in Children

Introduction to Hyperparathyroidism in Children

Hyperparathyroidism is a disorder characterized by excessive production of parathyroid hormone (PTH) from the parathyroid glands. While more common in adults, it can occur in children and adolescents, presenting unique diagnostic and management challenges.

In pediatric populations, hyperparathyroidism can be classified into:

  • Primary Hyperparathyroidism (PHPT): Caused by autonomous overproduction of PTH
  • Secondary Hyperparathyroidism: Resulting from chronic hypocalcemia, often due to renal disease or vitamin D deficiency
  • Tertiary Hyperparathyroidism: Autonomous PTH secretion following longstanding secondary hyperparathyroidism

The incidence of PHPT in children is estimated to be 2-5 cases per 100,000 person-years, making it a rare but significant endocrine disorder in this age group.

Etiology of Pediatric Hyperparathyroidism

The causes of hyperparathyroidism in children can be diverse:

1. Primary Hyperparathyroidism:

  • Sporadic adenoma (most common cause)
  • Genetic disorders:
    • Multiple Endocrine Neoplasia (MEN) syndromes (MEN1, MEN2A)
    • Familial Hypocalciuric Hypercalcemia (FHH)
    • Hyperparathyroidism-Jaw Tumor Syndrome
  • Parathyroid hyperplasia
  • Rarely, parathyroid carcinoma

2. Secondary Hyperparathyroidism:

  • Chronic kidney disease
  • Vitamin D deficiency or resistance
  • Malabsorption syndromes
  • Pseudohypoparathyroidism

3. Tertiary Hyperparathyroidism:

Usually a consequence of longstanding secondary hyperparathyroidism, particularly in children with end-stage renal disease.

Clinical Presentation

The clinical presentation of hyperparathyroidism in children can be subtle and nonspecific, often leading to delays in diagnosis. Symptoms may include:

  • Fatigue and weakness
  • Bone pain and fractures
  • Growth retardation
  • Abdominal pain
  • Nausea and vomiting
  • Polyuria and polydipsia
  • Neuropsychiatric symptoms (irritability, depression, cognitive changes)
  • Nephrolithiasis (kidney stones)

Physical examination findings may include:

  • Short stature
  • Skeletal deformities (in severe cases)
  • Palpable neck mass (rare)
  • Signs of associated syndromes (e.g., mucosal neuromas in MEN2A)

It's important to note that many children with hyperparathyroidism may be asymptomatic, with the condition discovered incidentally during routine blood tests.

Diagnosis of Pediatric Hyperparathyroidism

Diagnosis of hyperparathyroidism in children involves a combination of biochemical testing, imaging studies, and sometimes genetic analysis:

1. Laboratory Tests:

  • Serum calcium and ionized calcium (elevated)
  • Parathyroid hormone (PTH) levels (inappropriately normal or elevated)
  • Phosphorus (usually low)
  • 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D
  • Alkaline phosphatase (may be elevated)
  • 24-hour urinary calcium excretion
  • Renal function tests

2. Imaging Studies:

  • Neck ultrasound (first-line imaging modality)
  • 99mTc-sestamibi scintigraphy
  • 4D-CT scan
  • MRI (in select cases)

3. Bone Density Assessment:

  • Dual-energy X-ray absorptiometry (DXA) scan

4. Genetic Testing:

Consider genetic testing for:

  • MEN1 gene mutations
  • RET proto-oncogene mutations (for MEN2A)
  • CASR gene mutations (for FHH)
  • CDC73/HRPT2 gene mutations (for Hyperparathyroidism-Jaw Tumor Syndrome)

Differential diagnosis should include other causes of hypercalcemia in children, such as malignancy, granulomatous diseases, and medication effects.

Treatment of Pediatric Hyperparathyroidism

The treatment approach for hyperparathyroidism in children depends on the underlying cause, severity of symptoms, and associated complications:

1. Primary Hyperparathyroidism:

  • Surgical Management:
    • Parathyroidectomy is the definitive treatment
    • Minimally invasive parathyroidectomy for single adenomas
    • Bilateral neck exploration for multigland disease or genetic syndromes
    • Intraoperative PTH monitoring to confirm adequate resection
  • Medical Management (for non-surgical candidates or temporary control):
    • Cinacalcet (calcimimetic agent)
    • Bisphosphonates (for severe hypercalcemia or significant bone involvement)
    • Adequate hydration
    • Dietary calcium restriction

2. Secondary Hyperparathyroidism:

  • Treatment of underlying cause (e.g., vitamin D supplementation, management of chronic kidney disease)
  • Phosphate binders in renal disease
  • Vitamin D analogs (calcitriol, paricalcitol)
  • Calcimimetics (cinacalcet) in select cases

3. Tertiary Hyperparathyroidism:

  • Often requires parathyroidectomy
  • Medical management similar to secondary hyperparathyroidism may be attempted initially

Post-treatment monitoring is crucial, including regular assessment of serum calcium, PTH, and vitamin D levels. Long-term follow-up is essential, particularly for children with genetic syndromes.

Complications of Pediatric Hyperparathyroidism

Untreated or poorly managed hyperparathyroidism in children can lead to several complications:

  • Skeletal complications:
    • Osteoporosis and increased fracture risk
    • Osteitis fibrosa cystica (in severe cases)
    • Growth retardation and short stature
  • Renal complications:
    • Nephrolithiasis (kidney stones)
    • Nephrocalcinosis
    • Renal insufficiency
  • Neuropsychiatric complications:
    • Cognitive impairment
    • Depression and anxiety
    • Fatigue and sleep disturbances
  • Cardiovascular complications:
    • Hypertension
    • Left ventricular hypertrophy
    • Vascular calcifications (especially in chronic kidney disease)
  • Gastrointestinal complications:
    • Peptic ulcer disease
    • Pancreatitis (rare)
  • Endocrine complications:
    • Impaired glucose tolerance
    • Growth hormone resistance

Early diagnosis and appropriate management are crucial to prevent these complications and ensure optimal growth and development in affected children.

Prognosis of Pediatric Hyperparathyroidism

The prognosis for children with hyperparathyroidism largely depends on the underlying cause, timely diagnosis, and appropriate management:

  • Primary Hyperparathyroidism:
    • Excellent prognosis with successful surgical treatment
    • Most symptoms and metabolic abnormalities resolve post-surgery
    • Bone mineral density typically improves over time
    • Growth velocity may increase, but final height can be affected if diagnosis is delayed
  • Secondary Hyperparathyroidism:
    • Prognosis varies depending on the underlying cause and its management
    • Improvement in renal osteodystrophy with proper treatment of renal disease
    • Reversibility of skeletal changes with vitamin D repletion in nutritional deficiency cases
  • Tertiary Hyperparathyroidism:
    • Generally good outcomes with parathyroidectomy
    • Ongoing management of underlying renal disease is crucial

Long-term follow-up is essential, particularly for children with genetic syndromes who may be at risk for recurrence or development of other endocrine tumors. Regular monitoring of growth, bone health, and endocrine function is recommended throughout childhood and adolescence.

Early diagnosis and treatment are key to optimizing outcomes and minimizing long-term complications in pediatric hyperparathyroidism.



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