Diagnosis

Hyperparathyroidism

Etiology

Cause [wyr][vht]

• Primary hyperparathyroidism:

  • Solitary adenoma: 80%

    • Ectopic: thymus, thyroid, pericardium, retro-esophageal space, mediastinum

  • Four-gland hyperplasia: 15%

  • Cancer: < 1%

  • Parathyromatosis: multiple small functional nests of parathyroid tissue, usually after parathyroidectomy (seeding)

  • Normocalcemic primary hyperparathyroidism: elevated PTH despite normal serum calcium and no vitamin D deficiency

  • Lithium cause parathyroid calcium-sensing receptors resistance, requiring higher serum calcium levels to suppress PTH secretion

  • Other malignancy-related hypercalcemia: PTH-prodction in squamous cell carcinoma of the lung and renal cancers

  • Genetic Conditions Associated with Primary Hyperparathyroidism

    • Multiple endocrine neoplasia

    • Tumor-jaw syndrome

    • Familial hypocalciuric hypercalcemia

    • Severe neonatal hyperparathyroidism

    • Familial isolated hyperparathyroidism

• Secondary hyperparathyroidism (Four-gland hyperplasia):

  1. Initial hypocalcemia due to:

     • Chronic renal failure

     • GI malabsorption

     • Osteomalacia

     • Rickets

     • Lithium-related hyperparathyroidism

  2. Hypocalcemia --> Secondary PTH production:

  3. Characterized by elevated PTH and normal or low serum calcium concentration

• Tertiary hyperparathyroidism:

  • Develops from long-standing secondary hyperparathyroidism

  • Parathyroid glands become autonomously overactive after prolonged stimulation, leading to both high PTH and, eventually, high blood calcium

Pathophysiology [wyr]

1. Corrected calcium = Measured calcium + 0.8 x (4.0 - albumin)

2. Hypocalcemia and hyperphosphatemia stimulate PTH release

3. Hypercalcemia, vitamin D and hypermagnesemia inhibit PTH release

4. PTH increase calcium and reduce phosphorus by:

   1. Increases bone resorption --> releases calcium and phosphorus into the serum

   2. Increased absorption of calcium from intestines

   3. Increased vitamin D3 production

   4. Decreased renal calcium excretion

Complications [wyr]

• Nephrolithiasis caused by hypercalciuria

• Constipation and abdominal pain

• Hungry bone syndrome: Bone pain, osteoporosis, and fractures

• Neuropsychiatric symptoms: depression, anxiety, fatigue, cognitive dysfunction, memory loss

Epidemiology

Incidence per 100.000 [opm][zh4]

Approach

• Blood test: PTH, calcium (total, ionized), albumin, phosphorus, 25-hydroxyvitamin D, creatinine

• Urine: 24-hour urine calcium

• Ultrasound collum

• Sestamibi scan: parathyroid nuclear medicine

• CT collum

• MR collum

• Operative exploration

• Bone mineral density

• Genetic testing

Treatment

1. Primary hyperparathyroidism: [wyr]

   • Treat hypercalcemia:

     • Intravenous saline

     • Diuretics (furosemide, not thiazides)

     • Calcitonin

     • Bisphosphonates: antiresorptive agents

     • Denosumab: antiresorptive agents

     • Cinacalcet: activate the calcium-sensing receptor

     • Oral phosphates can reduce serum calcium levels up to 1 mg/dL

     • Dialysis

   • Parathyroidectomy is a permanent and curative treatment for symptomatic disease

   • Nonoperative surveillance: elderly with mild hypercalcemia and no complications

2. Secondary hyperparathyroidism:

   • Medical management is the mainstay of treatment.

   • Secondary hyperparathyroidism in chronic kidney disease:

     • Dietary phosphorus restriction

     • Phosphate binders

     • Vitamin D and its analogs

     • Calcimimetics

   • Parathyroidectomy only if unsuccessful medical therapy, calciphylaxis, refractory pruritus, severe hypercalcemia or hyperphosphatemia

3. Tertiary hyperparathyroidism:

   • Total parathyroidectomy with autotransplantation or subtotal parathyroidectomy

Differential diagnoses

Acute pancreatitis, Cancer, Cancer origo incerta, Chronic renal failure, Drug side effects, Familial hypocalciuric hypercalcemia, Hypercalcemia, Hyperthyroidism, MEN syndrome, Milk-alkali syndrome, Parathyroid adenoma, Sarcoidosis, Urolithiasis