Parathyroid (Hyperparathyroidism)

The primary function of the parathyroid glands is to regulate calcium within the blood. The parathyroid glands also control how much calcium is in the bones, and therefore how strong and dense the bones are. Calcium is the primary element which causes muscles to contract. Calcium levels are also very important to the normal conduction of electrical currents along nerves.

Knowing the major functions of calcium helps explain why people can get a tingling sensation in their fingers or cramps in the muscles of their hands when calcium levels drop too low. Additionally, too high a calcium level can cause a person to feel run down, sleep poorly, and cause irritability. Too high a calcium blood level can even cause a decrease in memory. More than half of patients with hyperparathyroidism (high blood calcium) state that they feel fine. However, after treatment, more than 85% of these patients say they feel "much better."

The parathyroid glands are sometimes confused with thyroid glands, but they have no related function. The thyroid gland regulates the body's metabolism and has no effect on calcium levels, while the parathyroid glands regulate calcium levels and have no effect on the metabolism.

An overactive parathyroid gland often mandates surgery, but as you will read in this protocol, some types of parathyroid disorders can be corrected with the proper use of dietary supplements.

Normal Parathyroid ActiviTY

The four to six parathyroid glands are quite small, and receive a large supply of blood. This assists them in monitoring the calcium level in the blood 24 hours a day. As the blood flow filters through the parathyroid glands, the glands detect the amount of calcium in the blood. Depending on calcium levels, they react by making more or less parathyroid hormone (PTH).

If calcium levels in the blood are too low, the cells of the parathyroids react and make more parathyroid hormone. Once the parathyroid hormone is released into the blood, it circulates to act in a number of places to increase the amount of calcium in the blood (such as removing calcium from bones). When the calcium level in the blood is too high, the parathyroids make less parathyroid hormone, allowing calcium levels to naturally decrease.

Producing Calcium in the BloOD

Parathyroid hormone (PTH) has a strong effect on bone cells, causing them to release calcium into the bloodstream. Under the presence of too much parathyroid hormone, however, the bones will continue to release their calcium into the blood at a rate which is too high, resulting in bones that have too little calcium and in serum calcium overload. This results in conditions medically defined as osteopenia and osteoporosis. When bones are subjected to high levels of parathyroid hormones over several years, they become brittle and prone to fractures.

Additionally, parathyroid hormones can act to increase blood levels of calcium by their influence on the intestines. The presence of the parathyroid hormone causes the lining of the intestine to become more efficient at absorbing calcium normally found in our diet.

Hyperparathyroidism: OveractiviTY

Too much PTH secretion is the primary disease of parathyroid glands. This condition is called hyperparathyroidism (excess hormone production). It occurs when one or more of the parathyroid glands function improperly, making excess hormones regardless of the level of calcium.

The most common cause of hyperparathyroidism is the development of a benign tumor in one or more of the parathyroid glands. Enlargement of one parathyroid gland is called a parathyroid adenoma and accounts for about 90% of all primary hyperparathyroid disease. Hyperparathyroidism inflicts damage to the body because it causes an abnormally high level of calcium in the blood, which slowly destroys the tissues by accelerating the calcification process.

Parathyroid adenomas are typically much bigger (about the size of a walnut) than the normal pea-sized parathyroid. Approximately 10% of all patients with primary hyperparathyroidism will have an enlargement of all parathyroid glands, called parathyroid hyperplasia. This condition is much less common than hyperparathyroidism, but the end results are identical on the tissues of the body.

Signs and Symptoms
Patients with persistently elevated calcium levels due to overproduction of parathyroid hormones can have complaints of bone pain. In the severe form, bones can give up so much of their calcium that they become brittle and break (osteoporosis and osteopenia). This problem is even more of a concern in older patients. Bones can also have small hemorrhages within their center that will cause "bone pain."

Other associated symptoms of hyperparathyroidism are the development of gastric ulcers and pancreatitis. High levels of calcium in the blood (hypercalcemia) can be dangerous to a number of organs, including the lining of the stomach and the pancreas, causing both of these organs to become inflamed and painful (ulcers and acute pancreatitis). The heart and vascular system may also be vulnerable to chronic calcium overload. Another common presentation for persistently elevated calcium levels is the development of kidney stones. Because the major function of the kidneys is to filter and clean the blood, they will be constantly exposed to high levels of calcium in patients with hyperparathyroidism.

The constant filtering of large amounts of calcium will cause the collection of calcium within the renal tubules, leading to kidney stones. In extreme cases the entire kidney can become calcified and even take on the characteristics of bone because of the deposition of so much calcium within the tissues. Not only is this painful because of the presence of kidney stones; in severe cases it can cause kidney failure.

The incidence of these problems depends primarily on the duration of the disease and its severity. Everybody will lose bone density, which is progressive. Pancreatitis and ulcers are much more rare. After diagnosis, almost 80% of patients claim to feel better (sleep better, etc.) 3 months after treatment.

Other Causes of Excess Calcium
There are several causes of hypercalcemia which should be considered in the initial diagnosis:

• Hypothyroidism causes increased bone turnover which results in mildly elevated serum calcium in about 20% of cases.
• Immobilization is a rare cause of hypercalcemia in adults.
• Benzothiadiazines (thiazides) cause a transient increase in blood calcium which reverts to normal after about a week. Thiazides can cause hypercalcemia in patients with high rates of bone turnover (i.e., hyperparathyroid patients).
• Vitamin A intoxication is a rare cause of hypercalcemia.

DiagnosIS

Hyperparathyroidism is relatively easy to detect because the parathyroid glands will be making an inappropriately large amount of PTH in the presence of elevated serum calcium. Another way to confirm the diagnosis is by measuring the amount of calcium in the urine over a 24-hour period of time. If the kidneys are functioning normally, they will filter much of this calcium in an attempt to rid the body of calcium, leading to an abnormally large amount of calcium in the urine. Measuring calcium in the urine, however, is an indirect measure of parathyroid activity and is only accurate 25-35% of the time.

The most accurate and definitive way to diagnose primary hyperparathyroidism is by testing for elevated PTH in the presence of elevated serum calcium. A standard blood-chemistry test can reveal elevated calcium levels caused by hyperparathyroid disease. If your blood test is high in calcium and parathyroid hormones, it may be an indication of hyperparathyroidism. People who do not have regular blood tests usually find out they have hyperparathyroidism when a bone suddenly breaks, a kidney stone develops, or when their kidneys fail altogether.

There are other diagnostic procedures (MRI, CT scans, sonography) to determine if excess parathyroid hormone is caused by a tumor or by a vitamin D3 or calcium deficiency.

Several additional lab tests may be ordered to examine some of the conditions associated with hypercalcemia. These would include:

• Thyroid and adrenal function tests that may include measurements of thyroid-stimulating hormone (TSH), and a.m. and p.m. cortisol levels
• Measurements of serum magnesium
• A comprehensive hormone profile, including measurements of estrogen and progesterone

Conventional Treatment OptiONS

Surgical Parathyroidectomy
Since the mid-1920s, the standard treatment for primary hyperparathyroidism has been to surgically remove the gland (or glands) overproducing hormones. Remember: this is a hormone problem, so the goal is to remove the source of the excess hormone. The patient is put to sleep under general anesthesia, an incision is made in the neck, and the thyroid gland is mobilized to allow the surgeon to identify the four to six parathyroid glands which reside moderately deep in the neck behind the thyroid. Patients are typically hospitalized overnight and occasionally as long as 1-2 days. The incision must be of sufficient length to allow the surgeon adequate exposure of the numerous important structures in the neck, and thus it is typically 3-4 inches long.

Because of the numerous small nerves and other important structures within the neck, this operation can be technically challenging and is usually performed only by experienced endocrine surgeons or surgeons with extensive head and neck operative experience. During this operation, the surgeon identifies all four parathyroid glands and removes whichever ones are enlarged. Approximately 90% of the time, there is one large gland (an adenoma) and three normal glands. In this situation, the one large gland would be removed, leaving the three normal ones to function in a normal fashion indefinitely.

Interestingly, if the surgeon finds all four glands to be enlarged (hyperplasia), he or she typically takes out three or three and a half of these glands, leaving some parathyroid tissue behind to function normally in the future. Done successfully, this procedure has a cure rate of about 95%.

Although most people with hyperparathyroidism say they feel well when the diagnosis is made, the majority of these will actually say they feel better after the problem has been cured. This can only be known retrospectively when patients are allowed to comment on how they feel several months after the operation. Many patients who thought they were asymptomatic preoperatively will claim to sleep better at night, will be less irritable, and will find that they remember things much more easily than they could when their calcium levels were high. Some physicians elect not to refer their patients for a surgical procedure if they have a mild form of primary hyperparathyroidism.

Conventional Drug TreatmenTS

Bisphosphonates
Healthy bone tissue is constantly being broken down and then restored. This occurs so that old bone can be replaced by new bone. Bisphosphonates are analogues of pyrophosphate which concentrate in areas of increased bone turnover and inhibit bone resorption. As a result, the breakdown of bone tissue occurs more slowly than the laying down of new bone. This action helps to preserve the density and strength of the bone. Bisphosphonates include etidronate (Didronel), pamidronate (Aredia), and alendronate (Fosamax).

Some physicians have begun using bisphosphonates (especially Fosomax) to increase bone calcium rather than referring a patient for surgical hyperparathyroidectomy. Fosamax is an effective drug, but must be used appropriately. It is not a replacement for removal of an over-active parathyroid gland. The mechanism of action of bisphosonates does not cure the underlying problem of overproduced PTH. Experts in the field believe that after a parathyroid is surgically removed, Fosomax may have a role in trying to build bone density and replace the calcium that the parathyroid hormone removed.

Calcitonin
Calcitonin is a parathyroid hormone that acts to decrease the release of skeletal calcium, phosphorus, and hydroxyproline. Administration of glucocorticoids in combination with synthetic calcitonin (Calcimar, Cibacalcin, Miacalcin) may augment or prolong the action of calcitonin. Calcitonin therapy is of limited efficacy.

Plicamycin
Plicamycin (Mithramycin) is a natural substance isolated from Streptomyces plicatus that inhibits DNA synthesis. It's main use is to treat hypercalcemia of malignancy of the testes. The exact mechanism responsible for its effects on calcium is unknown. Because of plicamycin's extreme toxicity, it is considered only in cases of hypercalcemia in association with advanced neoplasms.

Gallium nitrate
Gallium nitrate (Ganite) inhibits bone resorption and alters the structure of bone crystals. It is prescribed for hypercalcemia in relation to certain cancers. Gallium nitrate is highly toxic to the kidneys (nephrotoxic).

Glucocorticoids
Glucocorticoids (cortisol, hydrocortisone) increase urinary calcium excretion and decrease intestinal calcium absorption when given in pharmacologic doses (e.g., 40-200 mg prednisone daily in divided doses). Glucocorticoids are mainly prescribed to inhibit inflammation in a variety of autoimmune disorders and also to treat deficiency of natural steroid hormones.

Phosphorus
Low phosphorus levels are associated with primary hyperparathyroidism. Hypophosphatemia decreases the rate of calcium uptake into bone, increases intestinal calcium absorption, and directly and indirectly stimulates bone breakdown.

Raising the serum inorganic phosphate concentration above the normal level does decrease serum calcium levels, sometimes strikingly. Intravenous phosphate is one of the most dramatically effective treatments available for severe hypercalcemia. However, its toxicity is so dangerous that it is used rarely and only in severely hypercalcemic patients with cardiac or renal failure.

Estrogen-Replacement Therapy
Synthetic estrogens may be indicated in postmenopausal women with hyperparathyroidism. Estrogen-replacement therapy may potentially be an alternative form of therapy to surgery in elderly women with primary hyperparathyroidism. In one study, estrogen-replacement therapy (ERT) appeared as effective as parathyroidectomy (combined with either calcitriol or calcium supplements) for the treatment of osteoporosis in elderly postmenopausal women showing primary hyperparathyroidism symptoms. According to the researchers: "Although hormone replacement therapy has little effect on serum calcium levels, it suppresses bone turnover, reduces urinary calcium excretion, and increases bone mineral density throughout the skeleton in postmenopausal women with mild primary hyperparathyroidism. This therapy is thus an important management option for these patients" (Grey et al. 1996).

Later that same year, the Department of Endocrinology at St. George Hospital (Sydney, Australia) reported ERT appeared to be as effective as parathyroidectomy (combined with either calcitriol or calcium supplements) for the treatment of osteoporosis in elderly postmenopausal women presenting with primary hyperparathyroidism (PHPT) (Diamond et al. 1996).

The concern with using estrogen drugs is that several well-controlled human studies show that they increased the risk of breast cancer and cardiovascular disease. Therefore, the use of estrogen drugs to mitigate the effects of primary hyperparathyroidism should be limited to elderly women who are too debilitated to tolerate surgical removal of the affected parathyroid glands.

An alternative to synthetic estrogen to combat bone loss may lie in soy-derived natural estrogens. The main ingredients in soy, the isoflavones genestein and daidzin, bind loosely with estrogen receptors and may positively affect bone health.

A 6-month study on 66 postmenopausal women was conducted at the University of Illinois at Urbana-Champaign to investigate bone density and bone mineral content in response to soy therapy (Potter et al. 1998). In this study, postmenopausal women received on a daily basis either phytoestrogens derived from soy protein or milk-derived protein (that contained no phytoestrogens). The results showed significant increases in bone density and bone mineral content for the lumbar spine in the women receiving the phytoestrogens derived from soy protein diets compared to the control diet. Increases in other skeletal areas also were noted in the women on the soy diets. Dr. J. W. Erdman, Jr., the lead scientist, concluded that soy isoflavones show real potential for maintaining bone health.

Kenneth D. Setchell, Ph.D., of Children's Hospital and Medical Center (Cincinnati, OH), confirmed the estrogenic activity of the principal soy isoflavones daidzin, genistein, and glycitein. Setchell (1997) conducted research on the chemical structure and metabolism of soy phytoestrogens and concluded that consuming modest amounts of soy protein results in relatively high blood concentrations of phytoestrogens and that this could have a significant hormonal effect in many individuals. Theoretically, there are enough phytoestrogens in the newer soy extracts for many women to derive effective estrogen replacement therapy.

When Surgery Can Be AvoidED

Although primary hyperparathyroidism normally mandates surgery to remove one or more parathyroid glands that have developed benign tumors, secondary hyperparathyroidism can be caused by a dietary calcium or vitamin D deficiency. To rule out secondary hyperparathyroidism, a good first step is to supplement with 1000 IU of vitamin D3 every day, along with 2000 mg of elemental calcium. This much calcium and vitamin D3 will act as a signal to your parathyroid glands to stop producing so much parathyroid hormone. When your bloodstream is loaded with calcium, your parathyroid glands will no longer have to pull it from your bones to guarantee proper calcium metabolism. Many people undergo surgery to remove one or more parathyroid glands when, in fact, all they may need to do is take calcium and vitamin D3. This amount of daily vitamin D3 supplementation was confirmed to be safe in the American Journal of Clinical Nutrition in May 1999 (Vieth 1999).

Numerous studies demonstrate and report that glucocorticoid-induced osteoporosis is associated with the development of secondary hyperparathyroidism. Supplementation of calcium and vitamin D has been shown to be an effective method for prevention and treatment.

Magnesium
A decrease in plasma magnesium stimulates parathyroid secretion, and magnesium may exert a direct inhibitory effect on the gland (Ganong 1995).

Magnesium is a mineral that is commonly paired with calcium due to their opposing effects. While calcium serves to contract muscles, magnesium loosens. Thus, excess calcium causes constipation and muscle cramping, while excess magnesium causes diarrhea. The appropriate daily dose of magnesium can be determined by increasing the amount until loose stools occur, and then reducing to maintain normal consistency of stools.

Hemodialysis Considerations
In treating hemodialysis patients who have uremic hyperparathyroidism, the addition of the drug calcitonin to vitamin D3 therapy may inhibit bone resorption and increase bone mineral density. Dialysis patients often suffer from uncontrolled serum phosphate levels that preclude successful treatment with vitamin D3. Blood phosphate levels should be carefully monitored in dialysis patients.

Calcium-alpha-ketoglutarate is known as a highly effective phosphate binder in hemodialysis patients. Also, alpha-ketoglutarate has been shown to improve metabolic alterations. A study investigated the effect of long-term phosphate-binding therapy with calcium-alpha-ketoglutarate to determine whether phosphate accumulation is the main reason for secondary hyperparathyroidism in kidney dialysis patients. Calcium ketoglutarate was prescribed to 14 patients in a mean dosage of 4.5 grams a day (which provided 975 mg of elemental calcium) for a period of 36 months. Serum phosphate levels continuously dropped, whereas serum calcium levels increased to normal levels. Intact parathyroid hormone levels continuously normalized in all patients. The present data show that long-term treatment with calcium-alpha-ketoglutarate normalizes secondary hyperparathyroidism by simultaneously binding phosphate and correcting the calcium/phosphate ratio in serum without vitamin D treatment (Zimmerman et al. 1996).

SUMMARY

Too much parathyroid hormone is clinically defined as hyperparathyroidism. The excess parathyroid hormone pulls calcium from the bones which overloads the blood system with excessive amounts of calcium. Many long-term degenerative diseases have been linked to this type of calcium imbalance.

A standard blood-chemistry test can reveal elevated calcium levels caused by hyperparathyroid disease. Only a PTH (parathyroid hormone) blood test can effectively diagnose hyperparathyroidism. If your blood test is high in calcium and parathyroid hormone, it may be an indication of hyperparathyroidism.

Surgery is necessary when there is a parathyroid tumor that causes the overproduction of PTH. This is called primary hyperparathyroidism. Surgery is the often the only option in treating this condition.

When overproduction of PTH is caused by a calcium deficiency, this is classified as secondary hyperparathyroidism. The first step in countering secondary parathyroidism is to take 1000 IU of vitamin D3 every day, along with 2000 mg of elemental calcium. This much calcium and vitamin D3 will act as a signal to your parathyroid glands to stop producing so much parathyroid hormone.

A serum magnesium deficiency can stimulate the parathyroid glands to secrete more PTH, thus removing too much calcium from the bones. Consuming 500-1500 elemental mg of magnesium a day can help maintain optimal serum magnesium status.

Soy phytoestrogens have been shown to increase bone density and bone mineral content in postmenopausal women. One caplet morning and night of Mega Soy Extract (135 mg) is recommended.

Elderly postmenopausal women with primary hyperparathyroidism who are not candidates for surgery may consider estrogen-replacement therapy combined with either calcitriol or calcium supplements for the treatment of osteoporosis. The use of a bisphosphonate drug would also mitigate against calcium depletion from the bones.

Product availabiliTY

Calcium Citrate w/D3 capsules, Magnesium Citrate capsules, Bone Assure (encapsulated calcium-magnesium-vitamin D3 and bone protecting nutrients), and Mega Soy Extract can be ordered by telephoning (800) 544-4440 or by ordering online.