Hyperparathyroidism

Prevalence
1. Women: 2-3 cases per 1000 women over age 65 years
2. Men: 1 case per 1000 men over age 65 years
Ages
1. Range: 40-70 years old
2. Mean: 55 years old

Single Parathyroid Adenoma (82 to 85%)
Parathyroid Gland Hyperplasia or hypertrophy (15%)
Parathyroid Malignancy (rare, accounts for 0.5 to 3% of Primary Hyperparathyroidism)
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
Other Parathyroid related causes
1. Lithium Therapy
2. External neck radiation exposure
3. Neck surgery with Parathyroid injury or resection
Tertiary Hyperparathyroidism
1. Accelerated response to chronic Hypocalcemia (in advanced Renal Failure)
2. Parathyroid over-produces PTH causing Hypercalcemia

Vitamin D Deficiency
Decreased calcium intake
Renal Osteodystrophy
1. Chronic Kidney Disease stage 4 or stage 5 and
2. Decreased 1,25 dihydroxyvitamin D
3. Hyperphosphatemia
4. Hypocalcemia
Normocalcemic Hyperparathyroidism (associated with Osteoporosis)
1. Diagnosis of exclusion after ruling-out Vitamin D Deficiency and Chronic Kidney Disease

Mnemonic (classic presentation is uncommon)
1. Stones
2. Bones
3. Abdominal groans
4. Psychic moans
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

See Hypercalcemia
Familial Benign Hypocalciuric Hypercalcemia
1. Does not improve with surgery, unlike primary disease
2. Calcium to Creatinine ratio <0.01

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)
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
Encourage moderate Physical Activity
1. Minimize bone resorption
Encourage 64 ounces non-caffeinated fluid per day
1. Minimize risk of Nephrolithiasis
Encourage moderate calcium intake (1000 mg/day)
1. Low Calcium diet may surge Parathyroid Hormone
Medications
1. Calcium Lowering Therapy
  1. See Hypercalcemia
2. Pharmacologic Measures: Reduce bone resorption
  1. Estrogen Replacement Therapy (Postmenopausal)
  2. Bisphosphonates

Precautions
1. Re-evaluate on a periodic basis
2. Up to 15% of originally asymptomatic Hyperparathyroidism cases develop a surgical indication within 4.7 years
  1. Yu (2011) QJM 104(6): 513-21 [PubMed]
Indications in Primary Hyperparathyroidism
1. Serum Calcium >12 mg/dl (or >1 mg/dl above the upper limit of normal)
2. Hypercalcemic Crisis (Serum Calcium >14 mg/dl)
3. 24 hour Urine Calcium >400 mg/day
4. Osteoporosis (or T-Score <-2.5 at hip, spine or wrist)
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 <60 ml/min/1.73m2 or 30% below age-matched peers
11. Persistent Hypercalcemia symptoms (esp neuromuscular)
Efficacy
1. Successful in up to 95% of cases
2. Few complications
Single Parathyroid Adenoma
1. Surgery to locate and remove adenoma
2. Biopsy a second gland to rule out atrophy
Parathyroid hyperplasia or hypertrophy
1. Remove 3.5 glands
2. Autotransplant tissue into arm muscle