Hyperparathyroidism

1. Pathophysiology
   1. Overactive Parathyroid Glands (>=1 of 4 glands)
   2. Produce excessive Parathyroid Hormone (PTH)
   3. Results in disorder of bone metabolism
2. Epidemiology
   1. Incidence
      1. Women: 2-3 cases per 1000 women over age 65 years
      2. Men: 1 case per 1000 men over age 65 years
   2. Ages
      1. Range: 40-70 years old
      2. Mean: 55 years old
3. Etiology
   1. Single Parathyroid Adenoma (82 to 85%)
   2. Parathyroid Gland Hyperplasia or hypertrophy (15%)
   3. Parathyroid Malignancy (0.5 to 3%)
   4. Familial Hyperparathyroidism (10-20%): Younger patients
      1. Multiple Endocrine Neoplasia Type I (MEN I)
      2. Multiple Endocrine Neoplasia Type I (MEN II)
      3. Familial Hypocalciuric Hypercalcemia
      4. Hyperparathyroidism-Jaw Tumor Syndrome
      5. Neonatal severe Primary Hyperparathyroidism
   5. Other Parathyroid related causes
      1. Lithium Therapy
      2. External neck radiation exposure
   6. Non-primary causes of Hyperparathyroidism
      1. Secondary Hyperparathyroidism in Hypocalcemia
         1. Vitamin D Deficiency (renal insufficiency)
         2. Decreased calcium intake
      2. Tertiary Hyperparathyroidism
         1. Accelerated response to chronic Hypocalcemia
         2. Parathyroid over-produces PTH causing Hypercalcemia
4. Symptoms and signs
   1. See Hypercalcemia
   2. Asymptomatic Hypercalcemia (up to 80% of cases)
5. Diagnosis
   1. Mnemonic (classic presentation is uncommon)
      1. Stones
      2. Bones
      3. Abdominal groans
      4. Psychic moans
   2. Constellation of findings
      1. See Hypercalcemia
      2. Calcium oxalate renal stones (Nephrolithiasis)
      3. Bony changes
         1. Osteitis fibrosa
         2. Salt and pepper skull
         3. Bone resorption
      4. Acute Pancreatitis
      5. Psychosis and depression
6. Labs
   1. Parathyroid Hormone (PTH) Level elevated
      1. Measure Intact PTH
      2. See Parathyroid Hormone for algorithm
   2. Serum Electrolyte abnormalities
      1. Hypercalcemia (Use Corrected Serum Calcium)
         1. Draw fasting with minimal Occlusion
         2. Discontinue Thiazide Diuretics for 2 weeks before
         3. Repeat serum testing in 2 weeks if normal
      2. Hyperchloremia
      3. Hypophosphatemia
      4. Hypokalemia
   3. Miscellaneous
      1. 1,25 Dihydroxyvitamin D3
         1. Indicated if Serum Calcium low
   4. Urine Calcium and Phosphate
      1. Hypercalciuria (24 hour Urine Calcium)
      2. Hyperphosphaturia
   5. Arterial Blood Gas
      1. Non-Anion Gap Metabolic Acidosis
   6. Renal Function
      1. Creatinine Clearance
7. Radiology
   1. Classic XRay Findings
      1. Skull XRay
         1. "Salt and pepper" skull
      2. Chest XRay
         1. Distal Clavicle resorption
      3. Hand XRay
         1. Second and third middle phalange bone resorption
      4. Dental XRay
         1. Bone resorption of Lamina dura around teeth
   2. Sestamibi Technetium Tc 99mParathyroid Scan
      1. Test Sensitivity for localizing adenoma: 95%
      2. Causes of non-localizing scan
         1. Ectopic PTH production
         2. Diagnostic error
         3. Four-gland hyperplasia
   3. End-organ evaluation
      1. Renal ultrasound
      2. Bone Densitometry (DEXA Scan)
         1. Lumbar spine
         2. Hip
         3. Forearm
8. Differential Diagnosis
   1. See Hypercalcemia
   2. Familial benign hypocalciuric Hypercalcemia
      1. Does not improve with surgery, unlike primary disease
      2. Calcium to Creatinine ratio <0.01
9. Management: Medical Monitoring
   1. Indications
      1. Asymptomatic patients without surgical indications
      2. Serum Calcium level only mildly increased
      3. No priot life-threatening Hypercalcemia
      4. Normal Renal Function
         1. Creatinine Clearance >70%
         2. No Nephrolithiasis
         3. No Nephrocalcinosis
      5. Normal Bone Mineral Density (Osteopenia or better)
   2. Avoid provocative factors
      1. Thiazide Diuretics and Lithium
      2. Avoid Volume depletion (maintain hydration)
      3. Avoid prolonged bedrest or inactivity
      4. Avoid High Calcium diet
      5. Avoid Vitamin D supplementation
   3. Encourage moderate Physical Activity
      1. Minimize bone resorption
   4. Encourage 64 ounces non-caffeinated fluid per day
      1. Minimize risk of Nephrolithiasis
   5. Encourage moderate calcium intake (1000 mg/day)
      1. Low Calcium diet may surge Parathyroid Hormone
   6. Medications
      1. Calcium Lowering Therapy
         1. See Hypercalcemia
      2. Pharmacologic Measures: Reduce bone resorption
         1. Estrogen Replacement Therapy (Postmenopausal)
         2. Bisphosphonates
10. Management: Surgery
    1. Indications in Primary Hyperparathyroidism
       1. Serum Calcium >12 mg/dl
       2. Hypercalcemic crisis (Serum Calcium >14 mg/dl)
       3. 24 hour Urine Calcium >400 mg/day
       4. Osteoporosis
       5. Osteitis fibrosa cystica
       6. Nephrolithiasis
       7. Nephrocalcinosis
       8. Young patient age (e.g. age <50 years)
       9. Exacerbating factors
          1. Dehydration
          2. Immobile patient
       10. Creatinine Clearance 30% below age-matched peers
       11. Persistent Hypercalcemia symptoms (esp neuromuscular)
    2. Efficacy
       1. Successful in up to 95% of cases
       2. Few complications
    3. Single Parathyroid Adenoma
       1. Surgery to locate and remove adenoma
       2. Biopsy a second gland to rule out atrophy
    4. Parathyroid hyperplasia or hypertrophy
       1. Remove 3.5 glands
       2. Autotransplant tissue into arm muscle
11. Monitoring of medically managed patients
    1. Every 6 month labs
       1. Serum Calcium
    2. Every 12 month labs
       1. Serum Creatinine
       2. Urinary Calcium Excretion
    3. Every 6-12 month labs for women
       1. Bone Density (DEXA Scan)
12. References
    1. Spiegel in Goldman (2000) Cecil Medicine, p. 1402-5
    2. (1991) Ann Intern Med 114:593-7
    3. Bilezikian (2002) J Clin Endocrinol Metab 87:5353-61
    4. Taniegra (2004) Am Fam Physician 69(2):333-40