primary hyperparathyroidism

Introduction

Also see hyperparathyroidism.

Autonomous overproduction of parathyroid hormone with no evidence of secondary parathyroid stimulation.

Etiology

• parathyroid adenoma ~85%
• parathyroid hyperplasia ~15%
• parathyroid carcinoma ~1%

• 95% sporadic
• associated with MEN1 & MEN2/2A
• neonatal severe primary hyperparathyroidism (rare)

Epidemiology

• most common cause of hypercalcemia in outpatients
• higher incidence in women, age 50+ years

Pathology

• patients with normal serum PTH (intact) more likely to have multiple adenomas

Clinical manifestations

• often asymptomatic
• bone disease
  • osteoporosis
  • deformities, fractures
  • osteitis fibrosa cystica
  • Recklinghausen's disease (thin cortex, marrow fibrosis, hemorrhage, cysts esp jaw
• renal disease
  • calcium stones
  • hypertension
  • nephrocalcinosis
• gastrointestinal
  • nausea
  • peptic ulcer (associated with high serum gastrin)
  • constipation
  • gallstones
  • pancreatitis
• CNS disturbance
  • depression
  • lethargy
  • seizures
• other
  • weakness
  • fatigue
  • calcification of aortic valve & mitral valve, stomach, lungs, myocardium, blood vessels

Laboratory

• see hyperparathyroidism
  • serum calcium (high)
    • mean serum calcium prior to parathyroidectomy 10.9 mg/dL
    • serum ionized Ca+2 is not necessary if the serum albumin is normal [15[
  • a normocalcemic variant is described
    • other than serum calcium, other laboratory values similar
  • serum phosphate low
  • serum PTH high or inappropriately normal
    • 6% of patients have preoperative serum PTH (intact) <= 50 pg/mL (mean 40 pg/ml)*
    • 94% of patients have preoperative serum PTH (intact) > 60 pg/mL (mean 107 pg/ml)*
      • normal serum PTH (intact) is < 60 pg/mL
  • basic metabolic panel for eGFR
  • 24 hour urine calcium
    • high in 30% of primary hyperparathyroidism
    • low in hypocalciuric hypercalcemia, vitamin D toxicity, thiazide use
    • calcium/creatinine in 24 hour urine*
  • 25-OH vitamin D in serum* (50% with vitamin D deficiency)

* rule out familial hypocalciuric hypercalcemia before diagnosing primary hyperparathyroidism

* rule out vitamin D deficiency (all patients)

Radiology

• see hyperparathyroidism

Complications

• fractures, including hip fractures
  • vertebral fractures less common with normocalcemic variant

Differential diagnosis

• familial hypocalciuric hypercalcemia (FHH)
  • FHH with calcium/creatinine in 24 hour urine of < 0.01
• secondary hyperparathyroidism
  • normal serum calcium, elevated serum PTH
• celiac disease
  • autoimmune disease: diabetes type 1, autoimmune thyroiditis (hypothyroidism)
  • malabsorption: vitamin D deficiency, iron deficiency

Management

• serum calcium, skeletal complications & renal function determine choice between medical & surgical management
• parathyroidectomy generally treatment of choice
  • parathyroidectomy is associated with a lower risk of any fracture & hip fracture than non-operative mannagement among older adults
  • does not lower 8-year risk of symptomatic nephrolithiasis
  • no important outcome differences noted between parathyroidectomy & observation
  • does not prevent progression of chronic renal failure in adults > 60 years
• bisphosphonates increase bone mineral density, but increase risk of any fracture, including hip fracture relative to observation (RR=1.5)
• thiazides may reduce hypercalciuria & lower risk for calcium kidney stones
  • check serum calcium periodically
• cautious treatment of vitamin D deficiency (see hyperparathyroidism)
• also see hyperparathyroidism

More general terms

• hyperparathyroidism

More specific terms

• neonatal severe primary hyperparathyroidism

Patient information

primary hyperparathyroidism patient information