Why do we need calcium and phosphorus?
Calcium and phosphorus combine to make calcium phosphate in the body. This is the chief material that gives hardness and strength to bones and teeth. Calcium is also needed as part of the complex mechanism that helps blood to clot after an injury. It is also needed for muscles and nerves to work properly. Phosphorus works in conjunction with calcium for these functions. Phosphorus is also needed for the production of energy within the body.
What causes hyperparathyroidism?
Hyperparathyroidism can be classified as primary, secondary or tertiary.
Primary hyperparathyroidism
The term 'primary' hyperparathyroidism means that the disorder originates in the parathyroid glands. One or more of the parathyroid glands becomes enlarged and overactive. The gland or glands then release too much parathyroid hormone. This results in high levels of calcium in the blood. Causes are:
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Parathyroid adenoma: the most common cause of primary hyperparathyroidism, is a benign (non-cancerous) tumour of one or more of the parathyroid glands. This is known as a parathyroid adenoma.
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Parathyroid hyperplasia: most other cases of primary hyperparathyroidism are caused by hyperplasia. This is where one or more of the parathyroid glands become enlarged and, as a result of this, release more parathyroid hormone.
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Parathyroid carcinoma: rarely, primary hyperparathyroidism is caused by carcinoma (cancer) in one of the parathyroid glands.
Often, it is not clear why these conditions occur. Primary hyperparathyroidism does not usually run in families. However, in about 5 in 100 people with primary hyperparathyroidism, it can be linked to an inherited problem. It may be inherited alone as familial isolated hyperparathyroidism. It can also be inherited as part of a syndrome (a collection of problems) called multiple endocrine neoplasia which affects the parathyroids, the pancreas and the pituitary gland. Another rare inherited disorder called familial hypocalciuric hypercalcemia can give a picture of hyperparathyroidism.
If you have had radiotherapy to the head or neck, you are at increased risk of developing a parathyroid carcinoma (cancer). Parathyroid carcinoma is a rare cause of primary hyperparathyroidism.
Secondary hyperparathyroidism
The term 'secondary' hyperparathyroidism means that the disorder is caused by a problem elsewhere in the body. Causes include:
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Kidney disease: secondary hyperparathyroidism is usually seen in people with kidney disease. It occurs in nearly all people who are on long-term kidney dialysis because of kidney failure.
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Vitamin D deficiency (rickets/osteomalacia): this causes long-standing low levels of calcium in the blood.
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Intestinal malabsorption: there are various diseases that affect the gut and prevent the calcium that you eat from being absorbed (taken up) into your blood.
The long-standing low level of calcium in the blood, as a result of these diseases or deficiencies, means that the parathyroid glands are permanently being stimulated by the body to try to raise the calcium level. As a result, the parathyroid glands enlarge and their output of parathyroid hormone increases. The raised levels of parathyroid hormone are appropriate due to the low blood calcium levels.
If you have secondary hyperparathyroidism, your calcium levels do not generally become too high and so you do not tend to develop the symptoms related to this (see below). However, the increased levels of parathyroid hormone mean that calcium is released from bones to try to correct the low blood calcium levels. This means that you can suffer with bone pains, bone thinning (osteopenia), and your bones can become more fragile and break more easily. If you have secondary hyperparathyroidism due to kidney failure, the levels of phosphate in your blood will rise because your kidney cannot excrete it (get rid of) in your urine.
Tertiary hyperparathyroidism
This type of hyperparathyroidism occurs as a result of prolonged secondary hyperparathyroidism. In tertiary hyperparathyroidism, the original cause of secondary hyperparathyroidism, the low level of blood calcium, has gone. However, the parathyroid glands continue to produce large amounts of parathyroid hormone. The parathyroid glands start to act autonomously (by themselves) and are no longer sensitive to blood calcium levels. They are not 'switched off' when the blood calcium level rises. The result is high blood calcium levels.
Tertiary hyperparathyroidism is typically seen in people who have chronic kidney failure or in people who have had a kidney transplant.
Who gets hyperparathyroidism?
Primary hyperparathyroidism occurs in about one in 500 to one in 1000 people. It affects women twice as often as men. It is more likely to occur as you get older but can occur at any age. Rarely, primary hyperparathyroidism can run in families as part of the multiple endocrine neoplasia syndromes or as familial hyperparathyroidism.
What are the symptoms of hyperparathyroidism?
Often people with primary hyperparathyroidism either have no symptoms, or only have mild symptoms. You may only find out that you have hyperparathyroidism due to blood tests that are carried out for another reason, and which show high levels of calcium in the blood.
If you have primary or tertiary hyperparathyroidism and do develop symptoms, these tend to be due to hypercalcaemia (high levels of calcium in the blood). They include:
- Tiredness.
- Weak and easily tired muscles.
- Bone pains.
- 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, high calcium levels 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, as discussed above, you do not usually develop the symptoms of hypercalcaemia but of hypocalcaemia (low levels of calcium in the blood). You may however, develop bone pains, bone weakness and bone fractures.
Are there any complications of hyperparathyroidism?
Not everyone with hyperparathyroidism gets complications. However, sometimes one or more of the following may occur:
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Kidney stones: long-standing high calcium levels in the blood can lead to the formation of kidney stones. Small stones may be passed in the urine without you noticing. Larger stones may get stuck, causing pain in the loin area radiating to the groin. You may also notice blood in the urine. See separate leaflet on 'Kidney Stones' for further details.
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Corneal calcification: the high levels of calcium in the blood mean that calcium can be deposited (collect) in the cornea of the eye.
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Fractures (broken bones): the excess calcium that is released from the bones due to the high levels of parathyroid hormone can cause weakness and thinning of the bones, a condition known as osteopenia. The bones may become painful and more susceptible to breaks, or fractures.
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Pancreatitis: this is inflammation of the pancreas gland. Rarely, high levels of calcium due to hyperparathyroidism can cause pancreatitis. This can cause upper abdominal pain. See separate leaflet called 'Acute Pancreatitis' for details.
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Peptic (stomach) ulceration: high calcium levels can stimulate the production of a hormone in the stomach which may lead to increased production of gastric (stomach) juices and stomach ulceration.
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Kidney damage: prolonged high calcium levels in the blood can damage the kidneys and cause kidney failure.
How is hyperparathyroidism diagnosed?
Hyperparathyroidism is usually diagnosed after blood tests have shown high blood calcium levels along with raised parathyroid hormone levels. Usually, levels of phosphate in the blood are low. In secondary hyperparathyroidism, blood calcium levels may be low or normal and blood phosphate levels high.
Your doctor may have suggested these blood tests because you have had one of the complications of hyperparathyroidism such as kidney stones or pancreatitis. They may also have suggested that your blood calcium levels are tested for another reason. For example, if you have symptoms of low mood, tiredness, constipation or feeling thirsty. These may be possible symptoms of high blood calcium levels caused by hyperparathyroidism. However, these symptoms can also occur for a number of other reasons.
Will I need any investigations?
Once blood tests have shown high calcium and high parathyroid hormone levels, you doctor will usually want to discover the reason for this, and may also want to look for any complications. They may suggest:
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Further blood tests: these can include blood tests to check your kidney function, your pancreas gland, and your bones.
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Urine calcium levels: your doctor may ask you to collect your urine in a special container over a 24 hour period to measure the amount of calcium in your urine. You pass more calcium in your urine in hyperparathyroidism.
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DEXA scan: because hyperparathyroidism can cause thinning of the bones (osteopenia), your doctor may refer you for a special scan to assess your bone thickness. This is called a DEXA scan.
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X-ray pictures: these can show changes in your bones due to the increased release of calcium from them.
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Kidney ultrasound scan: if your doctor thinks that you may have kidney stones, they may suggest an ultrasound scan of your kidneys to look for these.
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Ultrasound, CT or technetium scan of your neck: this may show an enlarged parathyroid gland or glands. A technetium scan is a special radioactive scanning procedure.
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Biopsy of a parathyroid gland: if your doctor suspects that you may have carcinoma (cancer) of a parathyroid gland, they may suggest that a biopsy, or sample, of the gland is taken using a needle. This is usually carried out using scanning, such as ultrasound, to guide the doctor who is taking the biopsy.
What are the aims of treatment for hyperparathyroidism?
For primary hyperparathyroidism, the aims of treatment are to correct the levels of calcium in the blood, and to reduce the chance of any complications that can occur due to hypercalcaemia (high blood calcium levels). The aim of treatment in secondary hyperparathyroidism is to treat the underlying problem. This should then hopefully prevent tertiary hyperparathyroidism from developing.
What are the treatment options for hyperparathyroidism?
Primary hyperparathyroidism
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Monitoring: if you have mild primary hyperparathyroidism, with mildly raised calcium levels and little in the way of symptoms, your doctor may just suggest that you are regularly monitored. The monitoring procedure usually includes blood tests to check your blood calcium levels and kidney function, and regular blood pressure checks. It may also include DEXA bone scanning and kidney ultrasound scanning as described above. This monitoring approach is considered controversial by some. You should discuss the pros and cons with your doctor.
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Surgery: if your hyperparathyroidism is more severe, and/or you cannot tolerate your symptoms, or you have carcinoma of your parathyroid glands, your doctor may suggest surgery. If you have a single gland affected by an adenoma, hyperplasia or carcinoma, this is removed. The other three remaining glands should mean that your blood calcium levels return to normal. If you have more than one parathyroid gland affected, all abnormal glands need to be removed. This may mean that you would not have enough 'normal' parathyroid glands remaining. In this case, a small amount of one of the parathyroid glands may be removed and transplanted into one of your forearms. This means that, even if this gland tissue starts to over-function in the future, it can be more easily removed. Your calcium levels will need close monitoring after surgery to ensure that they return to normal and do not drop too low.
Secondary hyperparathyroidism
If you develop secondary hyperparathyroidism, it should be treated early to prevent problems from developing with your bones.
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Treatment to lower blood phosphate levels: this is needed first. You can reduce the intake of phosphate in your diet by restricting the amount of milk, cheese, eggs and dairy products that you eat. You are also likely to need some medication such as calcium carbonate. This binds to phosphate and helps to stop it from being absorbed from your gut after you have eaten.
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Treatment to raise calcium levels: you will then need to start supplements containing calcium and vitamin D in order to raise your blood calcium levels. Vitamin D in its special 'active' form may be given. This is because vitamin D is needed to allow calcium to be successfully absorbed in the gut from the food that we eat. Normally, vitamin D is converted to an 'active' form by the kidney to allow this action. In people with kidney disease, this conversion cannot happen. They need to be given the 'active' vitamin D to allow calcium absorption.
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Surgery: if secondary hyperparathyroidism is severe, surgery may be needed to totally, or partially, remove the parathyroid glands.
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Cinacalet: this is a drug that inhibits (reduces) the release of parathyroid hormone by the parathyroid glands. It is used in some people with secondary hyperparathyroidism who:
- have very high levels of parathyroid hormone in their blood that can't be lowered by other treatments, AND
- cannot have an operation to remove the parathyroid glands (a parathyroidectomy), because of the risks involved.
Tertiary hyperparathyroidism
The ideal is that tertiary hyperparathyroidism does not develop because secondary hyperparathyroidism is treated adequately. If it does develop, the treatment of tertiary hyperparathyroidism is usually surgery to remove the overactive glands. Again, a small amount of one of the glands can be transplanted into one of the forearms so that some remaining parathyroid gland tissue is left in the body to control calcium levels.
Complications from surgery
Complications from surgery to remove parathyroid glands are not very common. If complications do occur, they can include underactive parathyroid glands (hypoparathyroidism) and resulting low blood calcium levels. This may require long term treatment. Complications can also include damage to one of the nerves in the neck called the recurrent laryngeal nerve (this can cause cough and a hoarse voice), bleeding and infection. The surgery is sometimes unsuccessful and the hyperparathyroidism is not adequately treated.
What is the prognosis (outlook) of hyperparathyroidism?
Generally, after successful surgery to remove parathyroid glands , the outlook is very good. 95 to 98 people in 100 are cured after parathyroid surgery for primary hyperparathyroidism. Those people who have secondary or tertiary hyperparathyroidism tend to have a worse prognosis. This is because it is usually associated with underlying advanced chronic kidney failure.
Other advice
If you have hyperparathyroidism, make sure that you drink plenty of fluids and do not become dehydrated. You should also avoid taking certain drugs such as some diuretics (water tablets). If you are taking diuretics, you should discuss this with your doctor. If you are confined to your bed, for example, after an accident or illness, or if you have an illness causing vomiting or diarrhoea, this can cause your calcium levels to rise further. If you have hyperparathyroidism you should seek medical attention in these situations.
References
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American Association of Clinical Endocrinologists/American Association of Endocrine Surgeons; Position statement on the diagnosis and management of primary hyperparathyroidism. February 2005.
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Salen PN; Hyperparathyroidism; eMedicine November 2006
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Bollerslev J, Jansson S, Mollerup CL, et al; Medical observation, compared with parathyroidectomy, for asymptomatic primary hyperparathyroidism: a prospective, randomized trial. J Clin Endocrinol Metab. 2007 May;92(5):1687-92. Epub 2007 Feb 6. [abstract]
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Ambrogini E, Cetani F, Cianferotti L, et al; Surgery or surveillance for mild asymptomatic primary hyperparathyroidism: a prospective, randomized clinical trial. J Clin Endocrinol Metab. 2007 Aug;92(8):3114-21. Epub 2007 May 29. [abstract]
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Cinacalcet for the treatment of secondary hyperparathyroidism in patients with end-stage renal disease on maintenance dialysis therapy, NICE Technology Appraisal (2007)
© EMIS and PiP 2007 Updated: 12 Dec 2007 DocID: 8458 Version: 1
