The American Association of Endocrine Surgeons, Patient Education Site

Treatment of primary hyperparathyroidism

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Are there alternatives to an operation?

Observation

One alternative to have an operation is to observe closely. Blood calcium and parathyroid hormone (PTH) levels will be checked on a routine basis and routine follow-up visits to assess for development of symptoms will be scheduled. Studies have compared the outcomes of those patients who undergo parathyroidectomy versus those patients who do not undergo curative surgery. Many patients who are observed will go on to have increasing blood calcium and PTH levels or will develop one or more indications (i.e. reasons) for surgery.

In one of the best studies to date, researchers followed a group of patients with primary hyperparathyroidism who either did or did not have surgery for 10 years. Patients who did not have surgery had no change in calcium levels in the blood or urine, or bone mineral density. Ultimately, 27% of patients who initially did not meet the criteria for surgery, developed at least one new indication (i.e. reason) for parathyroidectomy over the next 10 years. Of the patients with kidney stones who had surgery, none developed new kidney stones. In contrast,of the patients with kidney stones at the beginning of the study period who did not have surgery, most did develop new kidney stones. After parathyroidectomy, bone mineral density in the spine increased about 8% after 1 year and 12% after 10 years.1 A later study from the same group followed patients choosing not to undergo surgery an additional five years (15 years total). After 15 years, over one third of initially asymptomatic patients developed at least one new indication for surgery. Bone density continued to decrease during the additional 5 years the study was carried out.45 Other studies have demonstrated that patients who are observed are at increased risk for fractures (73% versus 59% for those who have surgery) and other complications such as ulcers, kidney stones, heart rhythm disturbances, and life-threatenignly high calcium levels called hypercalcemic crisis (34% of patients who did not have surgery). 44, 46

Calcimimetics (Sensipar, Cinacalcet, etc)

Calcimimetics are medications that attach to a receptor on parathyroid cells and increases the ability of cells to respond to high blood calcium levels so that less PTH is produced. By causing less PTH to be made, calcimimetics decrease the amount of calcium in the bloodstream. Taking cinacalcet will NOT cure the disease process. It can only decrease parathyroid hormone secretion to a certain extent. On average it decreases calcium levels in the bloodstream by about 1 mg/dL. Currently, the use of calcimimetics is only FDA approved for patients with secondary hyperparathyroidism (see Special Cases: Secondary Hyperparathyroidism), not primary or tertiary hyperparathyroidism. Cinacalcet used in secondary hyperparathyroidism is generally for patients with renal failure who require dialysis.

Though not FDA approved, cinacalcet has been used to treat certain patients with primary hyperparathyroidism. 47, 48 One use has been in the rare instance that a patient has too many other severe medical problems and they cannot undergo surgery. This is an extremely rare situation as surgery for parathyroid disease can be performed under local anesthesia or general anesthesia, and the surgery is not associated with significant blood loss (usually less than 10cc) or significant stress on the body. Even patients well into their 80s and 90s tolerate parathyroid surgery without significant increases in complications (see Special Cases: Am I too old to have parathyroid surgery?). 49, 50

Another potential use for cinacalcet is in patients who have not been cured by parathyroidectomy. Usually, these patients have undergone several surgeries, including surgery performed by an experienced parathyroid surgeon. Oftentimes these patients will have more than one hyperactive parathyroid gland. Fortunately, this situation is also very rare, but for these patients who continue to have high calcium and parathyroid hormone levels, calcimimetics may be an option. Cinacalcet has also been used in the extremely rare patient with recurrent parathyroid cancer that cannot be cured. 51 These patients can experience extremely high and life-threatening calcium levels, and Cinacalcet has been found to be useful in these patients. (see Special Cases: Parathyroid Cancer)

As with any medication, calcimimetics can have serious side effects and can interact with other medications. Some of the side effects include calcium levels that are too low, nausea and vomiting, adynamic bone diseaseAdynamic bone disease - Normal bone cells are constantly reabsorbing old bone and creating new bone. Adynamic bone disease occurs when the bone does not undergo its normal cycle of breaking down and building up. This can lead to more fractures and blood vessel calcification., worsening heart function and liver function. Patients should seek further information about possible side effects associated with any medication they take. In addition, this medical therapy can be expensive. A recently published cost-effectiveness study estimated the yearly cost of Cinacalcet therapy (assuming 30mg twice daily) at just over $7,000.00 per year. For a patient with asymptomatic primary hyperparathyroidism, the estimated cost of Cinacalcet would have to decrease to less than $221 per year to be more cost-effective than surgery. 52

Osteoporosis Medications (i.e. bisphosphonates)

One of the main problems with primary hyperparathyroidism is that high PTH levels lead to lower bone density and potentially osteoporosis with an increased risk for fractures. Bisphosphonates are a type of medication that are used to treat decreased bone density. They inactivate or disable the the bone cell (i.e. the osteoclast) that causes bone breakdown in order to reduce bone turnover. Bisphosphonates do NOT treat the underlying disease but can help improve the decreased bone density caused by the disease.

A number of studies have looked at using bisphosphonates in patients with primary hyperparathyroidism and osteoporosis to evaluate the ability of these medications to improve bone density. 53-58 Alendronate was the bisphosphonate used in most of these studies. In general, the studies have concluded that alendronate improved bone mineral density in the lumbar spine and hip, but did not improve bone mineral density to a significant extent in the radius (forearm). The studies did not follow patients longer than two years, so long term follow up is relatively short. Based on these small studies, the longer term effects of bisphosphonate therapy on bone density in patients with primary hyperparathyroidism are unclear, but bone density seems to reach a steady state, and did not decrease while on bisphosphonate therapy. These studies concluded that alendronate can be an effective agent to increase bone density in certain areas of the body. Its use should be considered in patients with primary hyperparathyroidism and decreased bone density, especially in those who are unable to undergo parathyroidectomy or decline surgery.

Bisphophonates are generally well tolerated, but as with any medications, they can have serious side effects and can interact with other medications. The most common side effects include gastrointestinal upset and possible ulcers. Bisphosphonate-associated osteonecrosisBisphosphonate-associated Osteonecrosis - Bisphosphonate-associated osteonecrosis (BON) of the jaw, although quite rare, can be a significant complication. As per the American Dental Association, the typical clinical presentation of BON includes pain, soft-tissue swelling and infection, loosening of teeth, drainage, and exposed bone.
These symptoms may occur spontaneously, or more commonly, at the site of previous tooth extraction. Patients may also present with feelings of numbness, heaviness and abnormal feelings of the jaw. However, BON may remain asymptomatic for weeks or months, and may only become evident after finding exposed bone in the jaw. The risk of developing BON in patients on oral bisphosphonate therapy appears to be very low. A comprehensive oral evaluation is recommended for all patients about to begin therapy with oral bisphosphonates (or as soon as possible after beginning therapy). It is important for dentists to be aware that while on treatment, invasive dental procedures should be avoided in patients receiving intravenous (IV) bisphosphonates, if possible.
(www.ADA.org)
(BON) of the jaw, although quite rare, can be a significant complication. As per the American Dental Association, the typical clinical presentation of BON includes pain, soft-tissue swelling and infection, loosening of teeth, drainage, and exposed bone. The risk of developing BON in patients on oral bisphosphonate therapy appears to be very low. Patients should seek further specific information about possible adverse side effects associated with any medication they take.

Hormone Replacement Therapy (i.e. Estrogens)

One of the main problems with primary hyperparathyroidism is that high PTH levels lead to lower bone density and potentially osteoporosis with an increased risk for fractures. Estrogen replacement is well known to have positive effects on bone density and heart disease in women who have gone through menopause. Several studies have looked at the potential role for estrogen replacement therapy in postmenopausal women with primary hyperparathyroidism. Estrogen increases bone density by inactivating or disabling the bone cell (i.e. the osteoclast) that causes bone breakdown. Estrogen does NOT treat the underlying disease but can help improve the decreased bone density caused by the disease.

Studies suggest that estrogen replacement therapy in postmenopausal patients with primary hyperparathyroidism leads to increases in bone mineral density on the average of 1.3 - 4.6% for the entire body. 59-61 Calcium and PTH levels in the blood do not seem to be affected to a significant extent by estrogen replacement, although this varies among the different studies. Overall, these studies suggest that in postmenopausal women with primary hyperparathyroidism and decreased bone density, estrogen replacement therapy is likely beneficial for at least several years with respect to bone density. The use of estrogens should be considered in patients with primary hyperparathyroidism and decreased bone density, especially in those who are unable to undergo parathyroidectomy or in those who decline surgery.

Although estrogen in general is tolerated well, as with any medication, estrogen can have serious side effects and can interact with other medications. While there are many positive effects gained from taking estrogens, patients should remember that estrogen replacement should not be used in patients with breast cancer or who are at high risk for breast cancer. Estrogens should be combined with progestins in those patients with a uterus. Patients should seek further specific information about possible adverse side effects associated with any medication they take.

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