Parathyroid glands 

There are four parathyroid glands in our body. They are very small, about 1/ 5 of the inch and they are located on or behind the thyroid gland in the neck, or elsewhere around this area: usually two on the top and two on the bottom on each side of the neck. Parathyroid glands have sensors which detect amount of calcium in the bloodstream. They function normally to regulate calcium and phosphorus levels by secreting parathyroid hormone (PTH). PTH regulates the level of calcium in the blood, release of calcium from bone, absorption of calcium in the intestine, and excretion of calcium in the urine. When blood calcium levels falls, than parathyroid glands secrete PTH to stimulate calcium reabsorption from the kidneys and release it form the bone.

Calcium plays an important role in bone development and in maintaining bone strength. Calcium is also important in nerve transmission and muscle contraction. Hyperparathyroidism is a disorder of the parathyroid glands, which resulted form hyperfunctioning, or excessive secretion of parathyroid hormone (PTH). Primary hyperparathyroidism is a disorder of one (in 85% of the patients) or more than one (in 15% of the patients) parathyroid glands. This problem originates in the parathyroid glands in opposite to secondary or tertiary hyperparathyroidism that cause parathyroids to be overactive secondary to such a problem as kidney failure.

When parathyroid gland (or glands) became hyperfunctional and enlarged, it is ignoring our body needs and secretes too much parathyroid hormone (PTH) into blood causing calcium level to rises. Normal feedback mechanism that has to stop PTH overproduction is disrupted and one (or several) of the parathyroid glands loses their calcium sensor ability and starts functioning independently of the body needs. This condition of excessive accumulation of the calcium in the blood, called hypercalcemia. It is usually result of parathyroid adenoma, a benign overactive tumor of the parathyroid gland. Enlargements of all four glands called hyperplasia. In 85 percent of people with primary hyperparathyroidism there is only one adenoma and in 15 % of people more then one adenoma or hyperplasia. Rarely, less than 1 % of people may have cancer of the parathyroid gland.

This excess PTH release into the bloodstream may pole calcium out of the bones and cause osteopenia and then osteoporosis. Osteoporosis then may result in bone fractures.  The levels of calcium may increase in the urine, causing kidney stones. PTH also lowers blood phosphorus levels by increasing excretion of phosphorus in the urine. Excess of calcium in the blood stream may also result in excessive deposition of the calcium in other part of our body, including vessels.

The vast majority of primary hyperparathyroidism is idiopathic. It means that we do not know the reason for that.  Sometimes it is link to the exposure to radiation. In about 5 percent of cases can be linked to an inherited problem - syndromes. Familial multiple endocrine neoplasia type 1(MEN 1) syndrome is a rare, inherited syndrome that affects the parathyroids as well as the pancreas and the pituitary gland. Familial multiple endocrine neoplasia type 2 A (MEN 2A) syndrome is also affect thyroid gland (medullary thyroid carcinoma) and adrenal gland (pheochromocytoma). It is important to rule out familial hypocalciuric hypercalcemia (FHH) syndrome because this syndrome does not required treatment. This is why it is important to be evaluated by specialist (endocrinologist or endocrine surgeon) who is familiar with this syndromes and can determine if further testing needs to be perfomed.

How common is hyperparathyroidism?

In the United States, about 100,000 people develop the disorder each year. Women outnumber men two to one, and risk increases with age. In women 60 years and older, two out of 1,000 will develop hyperparathyroidism each year.

What are the symptoms of hyperparathyroidism?

Most commonly patient had no symptoms and she or he was found to have elevated blood calcium level on routine blood test.

When symptoms do appear, they are often mild and nonspecific, such as a feeling of weakness, tiredness, fatigue, depression, memory problems, muscle aches and bone pains, constipations, frequent urinations.

With more severe disease, increased calcium excretion in the urine may cause kidney stones. Increased bone resorption will result in bone fractures in situations that it would not normally happen. A person may have a loss of appetite, nausea, vomiting, severe constipation, impaired thinking, memory and confusion to the point that patient gets admitted to the hospital where blood would be routinely checked and found very high calcium level.

How to diagnose primary hyperparathyroidism?

Hyperparathyroidism is diagnosed by checking blood calcium and PTH levels and findings that both of them are elevated. Other diseases can cause high blood calcium levels and have to be ruled out as well, but only hyperparathyroidism it is resulted in the elevated calcium and  parathyroid hormone blood levels.

Once the diagnosis is established, other tests may be done to localize the disease, such as one gland versus several glands.

Because high PTH levels can cause bone loss, a measurement of bone density can help assess bone loss and the risk of fractures. Abdominal ultrasound may reveal the presence of kidney stones, a 24-hour urine collection for calcium needs to be performed to rule out familial hypocalciuric hypercalcemia (FHH) and provide information on increased urinary calcium excretion by kidney.

How is hyperparathyroidism treated? 

Recent Guidelines for the Management of Asymptomatic Primary Hyperparathyroidism: Summary Statement from the Third International Workshop guided the use of diagnostics and management for this condition in clinical practice.

All patients with biochemically confirmed primary hyperparathyroidism who have specific symptoms or signs of their disease should undergo surgical treatment. Because surgery is always considered to be definitive therapy in this disease, even in asymptomatic subjects, a decision to elect medical monitoring should follow guidelines regarding severity of the manifestations of disease, and patients should be appropriately monitored. New data on the natural history of asymptomatic primary hyperparathyroidism have favored surgery because bone density does not appear to be indefinitely stable. Moreover, up to one third of patients who are monitored long term develop signs of disease progression. It has also been demonstrated that bone density increases consistently after parathyroidectomy in association with decreases in bone turnover.

Guidelines for surgery

1) Serum calcium above at more than 1 mg/dl (>0.25 mM/liter) above the upper limits of normal.
2) Worsening of renal function (a GFR less than 60 ml/min)
3) Bone mineral density consistent with osteoporosis (T-score of –2.5 or less at the lumbar spine, femoral neck, total hip, or radius. In premenopausal women and in men younger than 50, the Z-score of –2.5 or less is recommended as the cut-point below which surgery is advised).
4) Age less then 50

Surgery to remove the enlarged gland (or glands) is cures it in 95 percent of operations.

Conservative medical therapy is consistent of Calcimimetics, a new class of drug that turns off secretion of PTH. They have been approved by the Food and Drug Administration for the treatment of hyperparathyroidism secondary to kidney failure with dialysis, and primary hyperparathyroidism caused by parathyroid cancer. They have not been approved for primary hyperparathyroidism.

Some patients who have mild disease, do not have surgical indications and do not need immediate treatment, long-term monitoring is performed. Periodic monitoring would consist of clinical evaluation, measurement of serum calcium levels, PTH level, evaluation for presence of kidney stones, and bone mass measurement. If the patient or physician choose long-term follow-up, the patient should try to drink lots of water, get plenty of exercise, and avoid certain diuretics, such as the thiazides. Immobilization (inability to move) and gastrointestinal illness with vomiting or diarrhea can cause calcium levels to rise. Patients with hyperparathyroidism should seek medical attention if they find themselves immobilized, vomiting, or having diarrhea.

Are there any complications associated with parathyroid surgery?

Surgery for hyperparathyroidism is highly successful with a low complication rate when performed by surgeons experienced with this condition. About 1 percent of patients undergoing surgery experience damage to the recurrent laryngeal nerve, which is controlling the vocal cords function, this can affect speech and result in hoarseness. One percent of patients loses all their parathyroid tissue and thus develops chronic low calcium levels, which may require treatment with multiple doses of the calcium with vitamin D a day. The complication rate is slightly higher for hyperplasia than it is for adenoma since more extensive surgery is needed. Rate of complications depend on surgeon experience in performing this procedures.

Are parathyroid imaging tests needed before surgery?

In order to perform minimally invasive procedure, localization tests are used to find parathyroid adenomas. They are including preoperative neck ultrasound and Sestamibi (parathyroid) scan.

References:

Bilezikian JP, Khan AA, Potts JT Jr; Third International Workshop on the Management of Asymptomatic Primary Hyperthyroidism. J Clin Endocrinol Metab. 2009 Feb;94(2):335-9.

The diagnosis and management of asymptomatic primary hyperparathyroidism revisited.
Khan AA, Bilezikian JP, Potts JT Jr; Guest Editors for the Third International Workshop on Asymptomatic Primary Hyperparathyroidism.

Presentation of asymptomatic primary hyperparathyroidism: proceedings of the third international workshop. Silverberg SJ, Lewiecki EM, Mosekilde L, Peacock M, Rubin MR. J Clin Endocrinol Metab. 2009 Feb;94(2):351-65.

Diagnosis of asymptomatic primary hyperparathyroidism: proceedings of the third international workshop. Eastell R, Arnold A, Brandi ML, Brown EM, D'Amour P, Hanley DA, Rao DS, Rubin MR, Goltzman D, Silverberg SJ, Marx SJ, Peacock M, Mosekilde L, Bouillon R, Lewiecki EM. J Clin Endocrinol Metab. 2009 Feb;94(2):340-50.