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Updated: Sep 1 2021


  • Snapshot
    • 55-year-old woman presents to the clinic for an annual well exam. Routine laboratory tests demontrates elevated levels of hypercalcemia. The patient reports some mild diffuse abdominal pain over the past 2 weeks but otherwise denies any chest pain, palpitations, or fatigue. A follow up PTH level is high.
  • Introduction
    • Clinical definition
      • disorder characterized by the over secretion of parathyroid hormone (PTH) by one or more of the parathyroid glands
      • high levels of PTH leads to increase in serum calcium levels, causing hypercalcemia
      • can be of primary, secondary, or tertiary causes
    • Epidemiology
      • demographics
        • occurs in 0.1% of the population and 90% of cases result from a single adenoma
      • risk factors
        • severe, prolonged calcium or vitamin D deficiency
        • menopause
        • neck radiation
        • lithium use
    • Pathogenesis
      • PTH leads to
        • activation of osteoclasts leading to increased Ca2+ and phosphate reabsorption at the bone
          • stimulates osteoclasts by binding to its receptor on osteoblasts, inducing RANK-L and M-CSF synthesis
        • increased reabsorption of Ca2+ in the distal convoluted tubule at the kidney
        • stimulation of kidney 1α-hydroxylase in the proximal convoluted tubule to increase calcitriol production
  • Classification
    • Primary hyperparathyroidism
      • most commonly results from parathyroid adenoma or hyperplasia
      • associated conditions
        • osteitis fibrosa cystica
          • high osteoclast activity at bone resulting in cystic bone spaces with brown fibrous tissue
          • commonly occurs at the jaw
        • multiple endocrine dysplasia (MEN) 1 and 2A
    • Secondary hyperparathyroidism
      • secondary parathyroid hyperplasia as a result of low Ca2+ absorption and/or high phosphate levels
      • associated conditions
        • chronic renal disease
          • renal disease causes hypovitaminosis D
            • leads to ↓ Ca2+ absorption
        • renal osteodystrophy
          • bone lesions due to secondary hyperparathyroidism
    • Tertiary hyperparathyroidism
      • dysregulation of parathyroid glands following chronic renal disease
        • will secrete PTH regardless of Ca2+ levels
      • associated conditions
        • chronic renal disease
        • renal osteodystrophy
      • Hyperparathyroidism
      • Serum Ca
      • Serum Phos
      • Serum PTH
      • Primary
      • Secondary
      • normal or ↓
      • Tertiary
  • Presentation
    • Symptoms
      • asymptomatic (most common)
      • weakness
      • kidney stones (“stones”)
      • bone pain (“bones”)
      • constipation (“groans”)
      • abdominal/flank pain
      • depression (“psychiatric overtones”)
      • uncommon cause of secondary hypertension
    • Physical exam
      • hypertension
  • Imaging
    • Bone mineral density test
      • dual energy X-ray absorptiometry (DEXA) is the most common test to measure bone mineral density
      • allows for measurement of bone reabsorption
    • Computed tomography (CT)
      • abdominal CT may be indicated to determine if kidney stones or other abnormalities are present
    • Radiograph
      • cystic bone spaces (“salt and pepper”) most common at the skull
      • loss of phalange bone mass with increased concavity
      • subperiosteal thinning (cortical resorption)
    • Sestamibi parathyroid scan
      • allows for visualization of the parathyroid glands
      • indicated if surgery is expected
  • Studies
    • Serum calcium test
      • best initial test
      • primary hyperparathyroidism
        • hypercalcemia
      • secondary/tertiary hyperparathyroidism
        • hypocalcemia/normocalcemia
    • Serum PTH
      • best initial test
      • levels will be elevated in all forms of hyperparathyroidism
    • 24-hour urinary calcium
      • routinely measured in patients to assess risk of renal complications
      • helps to distinguish hyperparathyroidism from familial hypocaloric hypercalcemia (FHH)
      • hypercalciuria/normocalciuria
    • Serum 25-hydroxyvitamin D
      • helps in differentiating from FHH
      • guides management
    • Genetic testing
      • may be indicated in patients suspected of MEN 1 or MEN 2A
  • Differential
    • Paraneoplastic syndrome (e.g., squamous cell cancer of the lung)
      • distinguishing factors
        • serum PTH levels will be low due to negative feedback
    • Familial hypocalciuric hypercalcemia (FHH)
      • distinguishing factors
        • urine calcium will be low
  • Treatment
    • Acute hypercalcemia
      • IV fluids
      • loop diuretics
    • Asymptomatic patients
      • first-line
        • observation with follow-up
      • second-line
        • surgical intervention indicated in select patients with abnormal studies indicating skeletal and renal damage
    • Symptomatic patients (e.g., nephrolithiasis)
      • first-line
        • parathyroid surgery is the only definitive therapy
          • complications include post-op hypocalcemia (e.g., numbness, tingling, and muscle cramps)
          • treat with IV calcium gluconate
      • second-line
        • cinacalcet indicated in patients who are unable to have surgery
          • decreases PTH levels by sensitizing Ca2+ - sensing receptors at the parathyroid gland
  • Complications
    • Peptic ulcer disease
      • ↑ gastrin production stimulated by ↑ Ca2+
    • Acute pancreatitis
      • ↑ lipase activity stimulated by ↑ Ca2+
    • CNS dysfunction
      • anxiety, confusion, and coma
      • result of metastatic calcification of the brain
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