So you have primary hyperparathyroidism

You may feel fine — but you could need surgery.

If you've been told that you have primary hyperparathyroidism, chances are the diagnosis came as a complete surprise. Hyperparathyroidism is typically discovered in the course of blood testing for other reasons, and there are usually no symptoms — or only nonspecific ones, such as fatigue, constipation, aches and pains, trouble concentrating, or low mood. Primary hyperparathyroidism is often discovered postmenopausal women when bone health becomes an important issue.

At one time, hyperparathyroidism was recognized only when it had progressed to the point of causing serious problems such as bone disease, kidney stones, gastrointestinal disorders, and cognitive difficulties — classic signs and symptoms that clinicians have dubbed "the bones, stones, abdominal moans, and groans." These days, some people with primary hyperparathyroidism do have such symptoms. But since the introduction of automated blood chemistry screening in the 1970s, clinicians have been able to detect hyperparathyroidism, which causes elevated levels of calcium in the blood (hypercalcemia) before symptoms appear. This raises the question of what to do about asymptomatic (non-symptomatic) primary hyperparathyroidism, which now accounts for 80% of cases. Most people with asymptomatic primary hyperparathyroidism can have a fairly benign course for years, even a lifetime. But hyperparathyroidism does progress in some people, and they should undergo surgery, which is the only complete cure. The question is, who?

What causes hyperparathyroidism?

Primary hyperparathyroidism is a disorder of the parathyroids, four tiny pea-sized glands located behind the thyroid gland in the neck. Rarely, a parathyroid will be located elsewhere in the neck or upper chest region, and it's possible, though not common, to have more than four glands.

These glands produce parathyroid hormone (PTH), a hormone that helps regulate the balance of calcium and phosphorous in the body. Normally, the parathyroids pump out just enough PTH to counteract a drop in blood levels of calcium. PTH raises calcium levels by triggering the release of calcium from the bones and increasing calcium absorption in the kidneys and intestines. When calcium levels come back into line, PTH production drops off. Because calcium levels fluctuate throughout the day, the parathyroids are continually tweaking their PTH output to keep calcium at a normal level.

In primary hyperparathyroidism, one or more parathyroid glands produce more PTH than needed, raising calcium levels above the normal range. Usually, the cause is a benign (noncancerous) tumor, or adenoma, in a single parathyroid gland. Occasionally, adenomas grow on more than one parathyroid gland. In very rare instances (less than 0.5% of cases), a parathyroid tumor is cancerous.

Parathyroid glands may become overactive because of lithium therapy, past radiation to the neck, or certain gene defects. Roughly 3% to 5% of cases are linked to inherited syndromes. In some cases, the cause is simply unknown.

How is hyperparathyroidism diagnosed?

Some experts consider the term "asymptomatic" something of a misnomer because of the many nonspecific complaints associated with the disease. However, these aren't clear heralds of hyperparathyroidism, and people often discount them and don't seek medical attention for them.

Sometimes the diagnosis of hyperparathyroidism is made when doctors seek an explanation for low bone density noted on testing. Most often, it's made when routine blood screening detects hypercalcemia. The clinician will follow up with a repeat calcium measurement to confirm the elevated reading. PTH will also be tested. Inappropriately high levels of calcium and PTH on follow-up indicate primary hyperparathyroidism.

Thiazide diuretics and lithium can also cause hypercalcemia, so if PTH is high in people taking either drug, they should temporarily halt drug therapy, if possible, and have repeat PTH and calcium tests two or three months later.

Other diseases, including cancer, can raise calcium levels, but few cancers are also associated with excessive PTH.

An uncommon condition that can be confused with hyperparathyroidism is familial hypercalciuric hypercalcemia (FHH), a genetic disorder that resembles primary hyperparathyroidism but doesn't need to be treated. FHH is ruled out with urine tests in order to avoid unnecessary parathyroid surgery.

To confirm the hyperparathyroidism diagnosis, an endocrinologist may order additional tests for blood levels of phosphorus, vitamin D, creatinine, and biomarkers of bone turnover, as well as bone density testing using standard dual energy x-ray absorptiometry scanning. Bone loss in primary hyperparathyroidism is usually more pronounced at the forearm than at the spine or hip, but all three sites should be evaluated.

What about surgery?

When it causes kidney or bone disease or severe symptoms, primary hyperparathyroidism almost always calls for parathyroidectomy — removal of the enlarged parathyroid gland (or glands). In experienced hands, this operation has few complications, and it cures the condition 95% to 98% of the time.

Experts are less certain about what to do when hyperparathyroidism is asymptomatic. Asymptomatic primary hyperparathyroidism progresses to a more serious condition only about one-third of the time, so some experts favor simply monitoring most patients and, if necessary, managing the condition with lifestyle measures and medications. Others argue that the long-term cost of such medical management may exceed that of the relatively simple operation, which is increasingly performed as an outpatient procedure. Surgery eliminates the risk of disease progression altogether and may also get rid of many of the nonspecific complaints.

Experts acknowledge that medical management might be appropriate for people who don't meet the criteria for surgery (see "Decision factors for surgery in asymptomatic primary hyperparathyroidism") or who can't or won't undergo the surgery. But they also note that surgery might ultimately be recommended even for the most asymptomatic patients. Surgery is associated with a reduced lifetime risk of fractures.

Surgery: What's involved?

The standard surgery, called bilateral neck exploration, entails making a two- to five-inch incision across the front of the neck, examining all four parathyroid glands, and removing the enlarged ones. It's usually performed under general anesthesia, although local anesthesia is sometimes an option. A single abnormal parathyroid is usually at fault, but sometimes two or more must be removed.

Today, minimally invasive surgery is increasingly preferred. It involves a smaller, one- to two-inch incision, takes less time, and requires less anesthesia. This technique can be used whenever preoperative imaging indicates that there is a single abnormal parathyroid gland. The most common imaging method is sestamibi scanning, which uses a radioactive isotope called technetium sestamibi to identify the abnormal gland. (See the illustration "What is sestamibi scanning?") An ultrasound of the neck may be ordered as well.

PTH is tested in the operating room after the abnormal parathyroid gland is removed. The level should drop by more than 50% within a few minutes. If it does, surgery is over. If it doesn't, the surgeon will abandon the minimally invasive technique and look for other abnormal glands.

When skilled parathyroid surgeons perform these procedures, complication rates are very low (1% to 3%). Possible complications of both traditional and minimally invasive surgery include damage to the laryngeal nerve (which can cause hoarseness) and decreased parathyroid function. Work with your endocrinologist to find a surgeon with a lot of experience.

Nonsurgical measures for hyperparathyroidism

If you have asymptomatic primary hyperparathyroidism and aren't planning on surgery, you should have regular blood tests and bone density scanning (see "Monitoring primary hyperparathyroidism in nonsurgical patients"). You can also take the following steps to reduce the risk of bone loss and kidney problems:

• To lower the chances of kidney stones developing, drink at least six to eight glasses of water each day.
• Get adequate exercise, which helps protect your bones.
• Get calcium through food sources, not calcium supplements. If you take a vitamin D supplement, you should not need more than 800 IU per day.
• If possible, avoid thiazide diuretics and lithium therapy, which can contribute to hypercalcemia.

No currently available medication can cure primary hyperparathyroidism, but some may help reduce the complications. Alendronate (Fosamax), a bisphosphonate, decreases bone turnover and increases bone density at the spine and hip region, although it doesn't correct PTH or calcium levels in the blood. Cinacalcet (Sensipar) is a drug that helps normalize calcium levels by acting on the calcium-sensing receptors in the parathyroid glands to reduce PTH levels. So far, only small studies suggest the combination of the two drugs may have some benefit.