Primary Hyperparathyroidism

At a Glance

Primary hyperparathyroidism is a syndrome of excessive parathyroid hormone (PTH) secretion by the parathyroid glands. The most common cause (> 95%) is a sporadic, single parathyroid adenoma. Less common are parathyroid hyperplasia (~2.5%), parathyroid carcinoma, and multiple adenomas. Many patients are asymptomatic and present only with an incidental finding of elevated serum calcium on laboratory studies. Otherwise, patients present either with vague, nonspecific symptoms (e.g., fatigue, muscle weakness, mental disturbances) or with symptoms more obviously related to hypercalcemia, such as kidney stones.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

The initial biochemical work-up consists of serum calcium, PTH, albumin, thyroid function tests (e.g., TSH, free thyroxine), and measures of kidney function (e.g., blood urea nitrogen, creatinine). If PTH is high, then urine calcium is an appropriate follow-up test. 25-Hydroxyvitamin D should also be ordered as a follow-up to elevated PTH. High urine calcium in the setting of elevated serum PTH strongly supports primary hyperparathyroidism. High PTH and low urine calcium is consistent with familial hypocalciuric hypercalcemia.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications - OTC drugs or Herbals - that might affect the lab results?

Thiazide diuretics and lithium can complicate the interpretation of laboratory studies. Ideally, these drugs should be discontinued prior to laboratory work-up. Low serum albumin can complicate interpretation of serum calcium. In patients with hypoalbuminemia, corrected calcium should be calculated or, alternatively, an ionized calcium measured.

What Lab Results Are Absolutely Confirmatory?

There are no definitive laboratory tests, but the combination of elevated PTH and high urine calcium strongly supports primary hyperparathyroidism.

Additional Factors of Clinical Importance

Patients with low bone density and/or renal failure are at especially high risk of complications from primary hyperparathyroidism.

Errors in Test Selection and Interpretation

PTH should always be ordered together with serum calcium. The hallmark of primary hyperparathyroidism is inappropriately high PTH relative to serum calcium.

Secondary causes of high PTH (e.g., vitamin D deficiency) should also be ruled out. A common error is to misdiagnose primary hyperparathyroidism when, in fact, the patient has secondary hyperparathyroidism due to vitamin D deficiency or relative hypocalcemia, both of which are common disorders.

In primary hyperparathyroidism, PTH is not always dramatically elevated, although it is almost always in the top 50% of reference range. The key is inappropriately high PTH relative to serum calcium. Some physicians erroneously exclude primary hyperparathyroidism, because PTH is within reference range, even though it is inappropriately high relative to high serum calcium.

Clinicians should rule out familial hypocalciuric hypercalcemia by ordering urine calcium before diagnosing primary hyperparathyroidism.