I. Diagnosis

  1. Adjustment for error secondary to hypoalbuminemia: Add 0.8 to [Ca] for each 1.0 albumin below nl

II. Hypercalcemia becomes symptomatic when > 11.5:

  1. Decreased mental status
  2. Nausea and vomiting
  3. Hyperreflexia

II. Causes of elevated PTH with normal serum calcium (normocalcemic hyperparathyroidism)

  1. Calcium malabsorption
  2. Renal insufficiency
  3. Vitamin D deficiency
  4. Hypercalciuria of renal origin

III. Causes of hypercalcemia (1st two make up >95%)

  1. Malignancy, esp. bone mets from breast or SC lung Ca
  2. Hyperparathyroidism-May be associated with sx of fatigue, somnolence, muscle weakness and decreased libido in postmenopausal women (Surgery 124:980, 1998--AFP)
  3. Hypervitaminosis D
  4. Sarcoid (advanced)
  5. Severe renal disease
    1. Reduced GFR causes increased serum PO4 and consequently metastatic calcification and hypocalcemia; hypocalcemia also through decreased conversion of vit. D to 1,25-vit. D; consequently, high PTH, and consequently osteodystrophy; Tx: low-phosphate diet, as well phosphate binders, vitamin D, and Cinacalcet (the latter increases sensitivity of parathyroid calcium-sensing receptors, decreasing PTH secretion). 
  6. Hyperthyroidism
  7. Milk-alkali syndrome
  8. Thiazide diuretics (rarely the only factor but can exacerbate hypercalcemia e.g. from primary hyperparathyroidism)
  9. Vit. D/Ca supplement

V. Management

  1. Hypercalcemia of malignancy
    1. Fluid replacement with normal saline to correct the volume depletion that is typically present-Leads to enhanced renal calcium excretion
    2. Loop directics if patient is in danger of fluid overload
    3. Pamidronate IV can be used once patient is euvolemic
  2. Parathyroidectomy
    1. Common indications
      1. Serum Ca > 1mg/dl or more above normal
      2. History of life-threatening hypercalcemia
      3. Age < 50
      4. Kideny stones
      5. Reduced bone density
    2. Parathyroidectomy appeared to improve sx (e.g. fatigue) in pts with primary hyperparathyroidism, even those with only modest (< 10.9 mg/dL) elevations of serum calcium, in one uncontrolled study of 155 pts (Surgery 125:608, 1999--JW)
    3. Conservative tx (no surgery) ass'd with overall stable Ca levels and bone mineral density (though development of low BMD did occur in 6 pts) in an retrospective study of 60 pts with idiopathic hyperparathyroidism followed for for up to 10y (NEJM 341:1249, 1999--JW)
    4. Parathyroidectomy was ass'd with elimination of excess risk for fx in a cohort of 674 pts w/hyperparathyroidism c/w age- and and sex-matched controls (BMJ 321:598, 2000--JW)
    5. 53 pts with mild primary hyperparathyroidism (serum Ca 10.1-11.5 mg/dL) and no sx randomized to observation vs. parathyroidectomy; followed with SF-36 Health Survey for determination of overall well-being x 2y; mild but sig. higher scores in the surgery group on two of the domains on the SF-36 ("social functioning" and "role functioning-emotional") (Surgery 128:1013, 2000--JW)
    6. In a 6y retrospective study of 3213 pts with primary hyperparathyroidism, 60% of whom underwent surgery, surgery recipients had sig. lower incidence of fractures or gastric or duodenal ulcers (HR 0.69 and 0.59, respectively) but sig. higher incidence of kidney stones (HR 1.87).  Risk of death was sig. lower in surgery recipients (HR 0.65) after adjustment for potential confounders (BMJ 327:530, 2003--JW)
    7. Minimally invasive approach--Start with an imaging study of the neck, e..g u/s, and if a solitary adenoma is found, excision done under local cervical block anesthesia through small incision and parathyroid hormone level checked intra-operatively & if drops, surgery is concluded
  1. Gallium (inhibits osteoclasts)
  2. Saliuresis (gives lots saline, washes out Ca)
  3. Thyrocalcitonin (get tachphylaxis which can be delayed by giving corticosteroids too)
  4. Bisphosphonate, which causes metastatic calcification

VI. Sequelae

  1. Increases effect of digoxin
  2. Metastatic calcification (kidney, cornea, joints) if chronic
  3. Osteopenia if chronic