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Hyperparathyroidism

hyperparathyroidism


Hyperparathyroidism occurs when an excess of parathyroid hormone is released by the parathyroid glands in the neck. It generally leads to high levels of calcium in the blood. This can cause various symptoms, commonly tiredness, nausea (feeling sick), vomiting, kidney stones and bone pains. It can usually be treated with surgery.

What is hyperparathyroidism?

Your body has four parathyroid glands. They are small, pea-sized glands, located in your neck just behind your butterfly-shaped thyroid gland. Two parathyroid glands lie behind each 'wing' of your thyroid gland.

Your parathyroid glands release a hormone called parathyroid hormone. This hormone helps to control the levels of two chemicals in your body: calcium and phosphate.
Normally, parathyroid hormone release is triggered when the level of calcium in your blood is low. When the calcium level rises and is back to normal, the release of parathyroid hormone is suppressed.

Parathyroid hormone has a number of effects in your body:

  • It causes the release of calcium from your bones.
  • It causes calcium to be absorbed (taken up into your blood) from your intestine.
  • It stops your kidneys from excreting (getting rid of) calcium in your urine.
  • It causes your kidneys to excrete phosphate in your urine.
  • In hyperparathyroidism, your parathyroid glands make and release too much parathyroid hormone. Generally, this means that the calcium level in your blood becomes too high.

Why do we need calcium and phosphate?

Calcium and phosphate combine to make calcium phosphate in your body. This is the chief material that gives hardness and strength to your bones and teeth. Calcium is also needed as part of the complex mechanism that helps your blood to clot after an injury. As well, it is needed for your muscles and nerves to work properly. Phosphate works in conjunction with calcium for these functions. Phosphate is also needed for the production of energy within your body.

How is hyperparathyroidism caused?

Hyperparathyroidism is either primary, secondary or tertiary.

Primary hyperparathyroidism

In primary hyperparathyroidism, one or more of your parathyroid glands become enlarged and overactive. The gland, or glands, release too much parathyroid hormone. This results in a high level of calcium in your blood. Causes include:

A single parathyroid adenoma. This is the most common cause of primary hyperparathyroidism. There is a benign (non-cancerous) tumour of one of your parathyroid glands. This causes more parathyroid hormone to be released by the gland.

Hyperplasia affecting more than one parathyroid gland. This accounts for most other cases of primary hyperparathyroidism. Hyperplasia means that there is enlargement of a parathyroid gland. It usually affects more than one gland at the same time. As a result of the enlargement, more parathyroid hormone is released.

Parathyroid carcinoma. Very rarely, primary hyperparathyroidism is caused by carcinoma (cancer) in one of the parathyroid glands.

It is usually not clear why parathyroid adenoma or hyperplasia occurs. However, if you have had radiotherapy treatment to your head or neck in the past, you seem to have an increased risk of developing a parathyroid adenoma or carcinoma (cancer). Primary hyperparathyroidism seems to be more common in women than men and most commonly affects women after the menopause.

Primary hyperparathyroidism does not usually run in families. However, in a small number of people, it can be the result of an inherited condition called familial isolated hyperparathyroidism. Also, rarely, it may be inherited as part of a syndrome (a collection of problems) called multiple endocrine neoplasia (MEN) which affects the parathyroids, the pancreas and the pituitary gland.

Secondary hyperparathyroidism

Secondary hyperparathyroidism is caused by other diseases or deficiencies that are affecting your body. These other conditions cause a long-standing low level of calcium in your blood. This means that your parathyroid glands are permanently being stimulated to try to raise your blood calcium level. As a result, your parathyroid glands enlarge and their output of parathyroid hormone increases. The raised levels of parathyroid hormone are appropriate due to your low blood calcium level.

Some of the causes of secondary hyperparathyroidism include:

Kidney disease. This is the most common cause of secondary hyperparathyroidism. Secondary hyperparathyroidism occurs in nearly all people who are on long-term kidney dialysis because of kidney failure. Because you have kidney failure, your blood calcium level can become chronically low.

Vitamin D deficiency (rickets/osteomalacia). This is another common cause. Vitamin D deficiency causes a long-standing low level of calcium in your blood.
Intestinal malabsorption. There are various diseases that can affect your gut and prevent the calcium that you eat from being absorbed (taken up) into your blood. This can lead to a chronically low calcium level in your body.

Tertiary hyperparathyroidism

This type of hyperparathyroidism occurs as a result of prolonged secondary hyperparathyroidism. In tertiary hyperparathyroidism, the condition causing your low blood calcium level and the secondary hyperparathyroidism has been treated (or your blood calcium level has been corrected). However, your parathyroid glands continue to produce large amounts of parathyroid hormone. This is because they start to act autonomously (by themselves) and are no longer sensitive to your blood calcium level. They are not 'switched off' when your blood calcium level rises. This results in a high calcium level in your blood.

Tertiary hyperparathyroidism is typically seen in people who have chronic kidney failure. It can also persist even after a kidney transplant.

What are the hyperparathyroidism symptoms?

Often people with primary hyperparathyroidism either have no symptoms, or only have mild symptoms. You may only find out that you have hyperparathyroidism because blood tests that are carried out for another reason show a high level of calcium in your blood.

If you have primary or tertiary hyperparathyroidism and do develop symptoms, these are due to hypercalcaemia (a high level of calcium in your blood). They can include:

  • Tiredness
  • Weak and easily tired muscles
  • Nausea (feeling sick), vomiting and feeling off your food
  • Constipation
  • Abdominal pain
  • Feeling very thirsty and passing urine frequently
  • Depression/low mood

In extreme cases, if left untreated, a high calcium level can lead to confusion, loss of consciousness, heart rhythm disturbances and, rarely, death. You may also have high blood pressure if you have hyperparathyroidism. It is unclear why this happens.

If you have secondary hyperparathyroidism, your calcium level is not high but low, so you do not develop all of the symptoms described above. However, you can develop bone complications (see below) and the symptoms related to that.

Are there any complications of hyperparathyroidism?

Not everyone with hyperparathyroidism gets complications. However, sometimes complications may develop. If you have primary or tertiary hyperparathyroidism, these complications are mostly due to a long-standing high level of calcium in your blood. They can include:

Kidney stones. Small stones may be passed in the urine without you noticing. Larger stones may get stuck, causing pain in your loin area that radiates to your groin. You may also notice blood in your urine.

Corneal calcification. Calcium can be deposited (collect) in the cornea of your eye. This doesn't usually cause any symptoms.

Pancreatitis. This is inflammation of your pancreas gland. Rarely, a high level of calcium due to hyperparathyroidism can cause pancreatitis. This can cause upper abdominal pain.

Peptic (stomach) ulceration. A high calcium level can stimulate the production of excess acid in your stomach and lead to stomach ulceration.

Kidney damage. A prolonged high calcium level in your blood can damage your kidneys and cause kidney failure.

In all types of hyperparathyroidism (including secondary hyperparathyroidism), the increased level of parathyroid hormone circulating in your blood causes high amounts of calcium to be released from your bones. This can cause weakness and thinning of your bones - a condition known as osteopenia. Your bones may become painful and more susceptible to breaks, or fractures.

How is hyperparathyroidism diagnosed?

Hyperparathyroidism is usually diagnosed after blood tests have shown a high level of calcium and a high level of parathyroid hormone. Usually, the level of phosphate in your blood is low.
If you have secondary hyperparathyroidism, your blood calcium level may be low or normal but you will still have a raised parathyroid hormone level. If you also have kidney disease, your blood phosphate level can be high because your kidney cannot excrete (get rid of) phosphate in your urine.

Your doctor may have suggested these blood tests because you have one of the complications of hyperparathyroidism, such as kidney stones or pancreatitis. They may also have suggested that your blood calcium level be tested for another reason. For example, if you have symptoms of low mood, tiredness, constipation or feeling thirsty. These may be possible symptoms of a high blood calcium level caused by hyperparathyroidism. However, these symptoms can also occur for a number of other reasons.

Will I need any further investigations?

Once blood tests have shown that you have hyperparathyroidism, you doctor will usually want to confirm which type of hyperparathyroidism you have and to look for any cause. They may also want to look for any complications that you may have. You will usually be referred to a specialist for further tests. Investigations may include:

Further blood tests. These can include blood tests to check your kidney function, your pancreas gland, and your bones.

  • Urine calcium level. You may be asked to collect your urine in a special container over a 24-hour period to measure the amount of calcium in your urine. You usually pass more calcium in your urine in hyperparathyroidism.
  • DEXA scan. Because hyperparathyroidism can cause thinning of your bones (osteopenia), your may be referred for a special scan to assess your bone thickness. This is called a DEXA scan.
  • X-rays. These can show changes in your bones due to the increased release of calcium from them.
  • Kidney ultrasound scan. This can show any kidney stones.
  • Ultrasound, CT or technetium scan of your neck. This can show if you have an enlarged parathyroid gland or glands. A scan may be suggested if surgery is being considered as a treatment option .
  • Biopsy of a parathyroid gland. A biopsy of one of your parathyroid glands may be suggested. This is a sample that is taken from the gland using a needle. It is usually carried out using scanning, such as ultrasound, to guide the doctor who is taking the biopsy. A biopsy may help to exclude parathyroid cancer.

What are the treatment options for hyperparathyroidism?

The treatment that you have depends on the type of hyperparathyroidism.

Primary hyperparathyroidism

There are some different options for treating primary hyperparathyroidism. These include:

Regular monitoring of your symptoms. If you have mild primary hyperparathyroidism, with a mildly raised calcium level and little in the way of symptoms, your doctor may just suggest that you be regularly monitored. The monitoring procedure usually includes blood tests to check your blood calcium level and kidney function, regular blood pressure checks and monitoring for any symptoms that you may have. It may also include DEXA bone scanning as described above. This monitoring approach is considered controversial by some. You should discuss the pros and cons with your doctor.

Surgery (parathyroidectomy). There are consensus guidelines that have been drawn up to determine when someone with hyperparathyroidism should have surgery to remove the abnormal parathyroid gland or glands (parathyroidectomy).

Drug treatment. This is used in people with more severe hyperparathyroidism who choose not to have surgery, or who do not meet the guidelines for surgery. Treatment aims to improve bone density (thickness) and correct your high calcium level. Various drugs may be used. These include a group of drugs called bisphosphonates. Another drug called cinacalcet can help to reduce calcium and parathyroid hormone levels and increase the phosphate level in your blood but it does not seem to improve bone density. Sometimes hormone replacement therapy may be suggested in postmenopausal women who also have menopausal symptoms that they wish treatment for.

Secondary hyperparathyroidism

If you develop secondary hyperparathyroidism, it should be treated early to prevent bone complications from developing and also to reduce the chance of tertiary hyperparathyroidism. The underlying condition that is causing secondary hyperparathyroidism needs to be treated; for example, treating vitamin D deficiency with vitamin D supplements.

Chronic kidney disease is the most common cause of secondary hyperparathyroidism. Treatment in chronic kidney disease includes:

  • Treatment to lower your blood phosphate level. You can reduce your intake of phosphate by restricting the amount of milk, cheese, eggs and dairy products that you eat. You may also need some medication such as calcium carbonate. This binds to phosphate and helps to stop it being absorbed from your gut after you have eaten.
  • Treatment to raise your calcium level. You will need to start supplements containing calcium and vitamin D in order to raise your blood calcium level. You need to take an 'active' form of vitamin D to allow calcium to be absorbed successfully from the food that you eat. Normally, vitamin D is converted to this 'active' form by the kidney. However, if you have kidney disease, this conversion cannot happen.
  • Cinacalet. This drug reduces the release of parathyroid hormone by the parathyroid glands. It is sometimes used if you have secondary hyperparathyroidism due to chronic kidney disease and other treatments have not been effective, and surgery is not an option for some reason.Surgery to remove abnormal parathyroid glands may be considered if secondary hyperparathyroidism is severe and does not respond to medical treatment.

Tertiary hyperparathyroidism

The ideal situation is that tertiary hyperparathyroidism does not develop because secondary hyperparathyroidism is successfully treated. However, if it does develop, the treatment of tertiary hyperparathyroidism is usually surgery to remove the overactive parathyroid glands. Often, a small amount of one of the glands is transplanted into one of your forearms. This means that some remaining parathyroid gland tissue is left in your body to control calcium levels but it is easily accessible if further surgery is needed.

Possible complications after surgery

Complications after surgery to remove parathyroid glands are not very common. However, in some people, complications may occur. They include:

  • Hypocalcaemia (low calcium level). Sometimes after surgery, because your bones are 'hungry', calcium and phosphate can be rapidly taken up from your blood and deposited in your bones. This can lead to hypoparathyroidism (underactive parathyroid glands) and a low blood calcium level. This is usually transient and goes when your remaining normal parathyroid glands become sensitive again and can control your blood calcium level. However, sometimes hypoparathyroidism can persist and some people need long-term drug treatment with calcium and vitamin D supplements.
  • Nerve damage in the neck. Damage to one of the nerves in your neck, called the recurrent laryngeal nerve, can sometimes occur during the operation. This can cause a cough and a hoarse voice.
  • Bleeding. This can sometimes occur after surgery. Rarely, the blood can collect in your neck and put pressure on your airway, causing breathing difficulties. This needs quick treatment to remove the blood clot.
  • Infection. After any type of surgery this is a possible complication.
  • Persisting hyperparathyroidism. Occasionally, surgery is unsuccessful and hyperparathyroidism is not adequately treated.

What is the prognosis (outlook) of hyperparathyroidism?

In primary hyperparathyroidism, after successful parathyroidectomy (surgery to remove the parathyroid glands), the outlook is usually excellent and most people are cured. If you do not have symptoms and are followed up without surgery, there is also generally a good prognosis. Significant bone loss and other symptoms may be absent for many years when you are followed up.

However, if you have secondary or tertiary hyperparathyroidism, the prognosis tends to be worse. This is because it is usually caused by underlying advanced chronic kidney failure.


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