Guidelines for the Treatment of Asymptomatic Primary Hyperparathyroidism

The finding of hypercalcemia on routine biochemical testing or in the evaluation of postmenopausal women with osteoporosis is typically the initial clue to the diagnosis of primary hyperparathyroidism. The total serum calcium level, which combines both the free and albumin-bound components of circulating calcium, should be adjusted for the level of albumin. Measurement of ionized calcium may be useful in selected cases, such as in patients with hyperalbuminemia, thrombocytosis, Waldenström's macroglobulinemia, and myeloma; these patients may have elevated levels of total serum calcium, but normal levels of ionized serum calcium (artifactual hypercalcemia).

Measurement of serum PTH is the next step in the evaluation of hypercalcemia. An elevated level of PTH (or a level that is in an unexpected “normal” range) simultaneous with an elevated calcium level generally indicates a diagnosis of primary hyperparathyroidism. However, these laboratory findings may also occur with lithium or thiazide use, tertiary hyperparathyroidism associated with end-stage renal failure, and familial hypocalciuric hypercalcemia, and a medical and family history should be obtained to assess these possibilities. The finding of a normal level of albumin-adjusted or ionized serum calcium and an elevated level of PTH in patients with no other causes of secondary hyperparathyroidism is consistent with normocalcemic primary hyperparathyroidism. A low or undetectable PTH level rules out primary hyperparathyroidism and raises the possibility of cancer-associated hypercalcemia, often mediated by PTH-related protein, which does not cross-react with the PTH assay. If the PTH level is elevated in a person with a known malignant condition, the most likely diagnosis is concomitant primary hyperparathyroidism; ectopic production of PTH from a tumor is extremely rare.

Guidelines for the Treatment of Asymptomatic Primary Hyperparathyroidism

Variable	Criteria for Surgery*	Surveillance without Surgery
Serum calcium level	>1.0 mg/dl (0.25 mmol/liter) above upper limit of normal range	Annually
Creatinine clearance (calculated)†	Reduced to <60 ml/min	Not recommended
Bone mineral density	T score less than -2.5 at any site,‡ previous fragility fracture, or both	Every 1–2 yr (three sites)
Age	<50 yr	Not applicable

* Surgery should also be recommended for patients in whom surveillance is not feasible.
† The estimated glomerular filtration rate (milliliters per minute per 1.73 m² of body-surface area) should be calculated from the serum creatinine concentration, demographic characteristics (age, sex, and race or ethnic group), and other serum measurements (e.g., blood urea nitrogen and albumin concentrations) according to the following equation: 170×(serum creatinine in mg per deciliter) ^-0.999 ×(blood urea nitrogen in mg per deciliter) ^-0.170 ×(serum albumin in g per deciliter) ^0.318 ×(age in years) ^-0.176 ×(0.762 if patient is female)×(1.180 if patient is black).
‡ Sites were the lumbar spine, total hip, femoral neck, and distal third of the radius. According to the International Society for Clinical Densitometry, z scores instead of T scores should be used in evaluating bone mineral density in premenopausal women and men younger than 50 years of age.

References:

1. Marcocci C, Cetani F. Clinical practice. Primary hyperparathyroidism. N Engl J Med. 2011 Dec 22;365(25):2389-97. [Medline] 
2. Eastell R, Arnold A, Brandi ML, Brown EM, D'Amour P, Hanley DA, Rao DS, Rubin MR, Goltzman D, Silverberg SJ, Marx SJ, Peacock M, Mosekilde L, Bouillon R, Lewiecki EM. Diagnosis of asymptomatic primary hyperparathyroidism: proceedings of the third international workshop. J Clin Endocrinol Metab. 2009 Feb;94(2):340-50. [Medline]