The use of multichannel blood screening has increased the frequency of diagnosis of asymptomatic primary hyperparathyroidism. Previous expert panels have established standards of treatment with acknowledgment that a large number of patients with asymptomatic primary hyperparathyroidism and only vague symptoms could be followed safely without surgery. Biannual visits were recommended for this group of patients with determinations of blood pressure, serum calcium, serum creatinine, and creatinine clearance. Abdominal radiographs (or sonograms), a 24-hour urine collection for calcium, and bone mass measurements were recommended annually, with longer periods between evaluations when patients showed no changes. Important medical therapy included adequate mobility, and a diet with a normal calcium content. Bilezikian and associates reported on a workshop on asymptomatic primary hyperparathyroidism held at the National Institutes of Health in April 2002, at which questions about management of this disorder were considered.
The diagnosis of primary hyperparathyroidism was confirmed to be persistent elevated calcium in the presence of inappropriately normal elevated levels of parathyroid hormone (PTH). Drugs potentially causing hypercalcemia should be stopped when possible, and patients retested. Familial benign hypocalciuric hypercalcemia is a rare benign disorder with similar findings caused by a genetic mutation and diagnosed by a calcium-creatinine clearance ratio of less than 0.01, while the same measurement in primary hyperparathyroidism is usually greater than 0.02. The distinction between these two entities is important because surgery does not resolve familial benign hypocalciuric hypercalcemia. In addition, some patients have high normal calcium levels with elevated PTH, constituting normocalcemic primary hyperparathyroidism. This group should be evaluated for causes of secondary PTH elevation, including low calcium intake caused by malabsorption, renal insufficiency, vitamin D deficiency, or hypercalciuria of renal origin.
The initial evaluation for primary hyperparathyroidism should include evaluation of the target organs with bone densitometry, renal ultrasonography or abdominal radiographs, and determination of 24-hour urine calcium and urinary creatinine clearance. Tests for ongoing monitoring of patients who do not meet the criteria for surgical treatment include semiannual serum calcium determination, annual serum creatinine quantitation, and annual bone densitometry of the lumbar spine, hip, and forearm, along with a serum creatinine quantitation.
Surgery remains the only definitive treatment for primary hyperparathyroidism and is indicated under the circumstances noted in the accompanying table. Other considerations that have an uncertain impact on the decision for surgical treatment include neuropsychologic abnormalities, onset of menopause, cardiovascular abnormalities, gastrointestinal symptoms, and serum or urine markers of bone metabolism. There are no specific medical therapies for primary hyperparathyroidism. Currently, raloxifene, bisphosphonates, and calcimimetics are being evaluated. Optimal calcium intake of 1,000 to 1,200 mg per day is recommended, along with adequate vitamin D.
|Serum calcium level greater than 1 mg per dL (0.24 mmol per L) above the upper limit of normal|
|24-hour urinary calcium level greater than 400 mg (10 mmol per day)|
|Creatinine clearance reduced by more than 30 percent, compared with age-matched patients|
|Bone density at the lumbar spine, hip, or distal radius greater than 2.5 standard deviations below peak bone mass (t-score, < −2.5)|
|Patient younger than 50 years|
|Patient cannot be monitored reliably|
The authors conclude with an extensive research agenda about primary hyperparathyroidism and the need to recognize the disease early when the only manifestation may be an elevated PTH level. The natural history of these patients should be studied further before recommending PTH determinations as part of health surveillance programs. The role of vitamin deficiency in increasing the activity of disease in persons with primary hyperparathyroidism also needs more study.