The diagnosis of HPT is made by the finding of an elevated calcium level with an elevated intact parathyroid hormone (iPTH) level. It is possible to have normocalcemic HPT if the calcium level is at the upper range of normal but the iPTH is elevated. Alternatively, patients sometimes have elevated calcium levels with the iPTH level being inappropriately in the high normal range. It is important when making the diagnosis of HPT to assess both calcium and iPTH levels so that the relative values of these tests can be compared. In a patient with normally functioning parathyroid glands, a high calcium should be associated with a low iPTH level.

In order to confirm the diagnosis of HPT and rule out familial benign hypocalciuric hypercalcemia (FBHH), a 24-hour urine calcium should be obtained. In FBHH, the urinary calcium is expected to be very low. A normal or elevated 24-hour urine calcium level effectively rules out FBHH. An elevated 24-hour urine calcium increases the risk of kidney stones.

The indications for surgery in HPT are well described in several National Institutes of Health (NIH) consensus conferences over the last few decades.⁴ Most surgeons and endocrinologists currently agree that patients with HPT who are symptomatic or have marked elevations in serum calcium should have surgery. A history of kidney stones and the presence of osteoporosis are widely accepted as indications for surgery. It is common for patients with HPT to have additional symptoms that may be associated with the disease, including low energy, bone pain, decreased proximal extremity muscle strength, decreased ability to concentrate, and reductions in short-term memory. Although all of these symptoms may be caused by conditions other than HPT, they are very common in patients with HPT and may influence the decision to recommend surgery.

The diagnosis of HPT in a young patient (<50 years old) also is a relative indication for parathyroidectomy because such patients will have more years to develop osteoporosis and other problems associated with HPT. In addition, for women of childbearing age, HPT also appears to increase the risks of spontaneous abortion.

There is currently no approved medical treatment for primary HPT. For this reason, the choice for patients and physicians is between parathyroidectomy and continued observation.

Once the decision is made to proceed to surgical treatment, localization studies to attempt to identify the location of the abnormal parathyroid gland are indicated. We recommend the routine use of technetium-99m (Tc-99m) sestamibi scan and ultrasound evaluation of the thyroid gland.⁵

Sestamibi scanning has high rates of sensitivity and specificity and is effective in localizing not only parathyroid adenomas in the neck but also in ectopic locations such as undescended glands in the neck or intrathoracic glands. Unfortunately, in cases of multigland disease, sestamibi scanning is least likely to identify the location of abnormal glands. Sestamibi is taken up by both thyroid and parathyroid cells. It is more rapidly cleared from thyroid cells than from abnormal parathyroid cells. For this reason, a comparison of early and delayed scans often reveals the presence of a persistent focus of increased activity in the abnormal parathyroid gland. With the use of fused sestamibi-computed tomography (CT) scanning or three-dimensional single photon emission computed tomography (SPECT) reconstructions, it is often possible to determine
whether the focus of uptake is anterior in the neck (at or near the level of the thyroid lobe) or more posterior. Because the superior parathyroid gland is located posterior to the recurrent laryngeal, posterior parathyroid glands on scans are most likely superior glands, whereas anterior glands are more likely to be inferior glands.

Ultrasonography is an effective noninvasive means of identifying abnormal parathyroid glands. The study can be performed in the radiology department or by surgeons in the clinic or operating room. Ultrasonography is effective in identifying enlarged parathyroid glands that are close to the thyroid gland. Abnormal parathyroid glands usually appear as hypoechoic lesions either posterior or inferior to the thyroid gland. Parathyroid glands that are located posterior to the esophagus and those in the mediastinum are less likely to be visualized on ultrasound.

Ultrasound is very effective at identifying thyroid nodules, which may be a source of increased uptake on sestamibi scans. We believe that thyroid nodules greater than 1 cm or with suspicious characteristics should be evaluated with fine needle aspiration cytology prior to planned parathyroidectomy. This strategy limits the chances of missing a nonpalpable thyroid malignancy and thus reduces the likelihood for reoperative neck surgery.

In cases of primary HPT when patients have negative preoperative localization studies, we recommend proceeding with surgery and planning on a four-gland exploration (see Part 5, Chapter 41). Some surgeons would obtain a four-dimensional CT scan of neck and chest prior to exploring the patient. However, we believe that additional evidence is required before this approach should be routinely adopted.

MIP can be performed either with local anesthesia and sedation or with general anesthesia, depending on surgeon and patient preference. We have found that because inferior parathyroid adenomas are located more anteriorly in the neck, these glands are more amenable to resection without using general anesthesia. Large posteriorly located superior parathyroid adenomas often are more challenging to remove without general anesthetic because of the need to rotate the thyroid lobe medially to gain access to the space posterior to the esophagus. Although it is possible to access these glands even when the patient is not asleep, surgeons should be cognizant of the challenge and choose the appropriate patient for such an approach.