Primary hyperparathyroidism

Primary hyperparathyroidism is the release of too much parathyroid hormone from the parathyroid glands causing high levels of calcium in the bloodstream.

What is primary hyperparathyroidism?

Primary hyperparathyroidism is the inappropriate excess production and release (secretion) of too much parathyroid hormone from one or more of the four parathyroid glands.

Parathyroid hormone has two main actions: one is to stimulate the breakdown of bone so the calcium and phosphate crystals that make the bones rigid are broken down along with the bone structure. This releases calcium and phosphate into the bloodstream. Its other action is to increase calcium reabsorption in the kidney and to increase phosphate excretion by the kidney. By doing this, parathyroid hormone increases the levels of calcium in the blood when calcium levels are low. However, when excess parathyroid hormone is produced, calcium levels stay abnormally high.

It is the third most common endocrine disorder in men and women.

What causes primary hyperparathyroidism?

The most common cause of primary hyperparathyroidism is a single benign growth (adenoma) in one parathyroid gland and accounts for 75–85% of all cases. Growths in two parathyroid glands accounts for 2–12% of all cases, three parathyroid glands in less than 1–2% and four parathyroid glands in 1–15%. It is very rare to find cancer in the parathyroid glands and this accounts for less than 1% of all cases of primary hyperparathyroidism.

Usually the growths occur in one or both of the two parathyroid glands that are embedded in the lower section (pole), rather than the upper pole, of the two lobes of the thyroid gland. Hyperparathyroidism can also be caused by enlargement of all the parathyroid glands (hyperplasia).

What are the signs and symptoms of primary hyperparathyroidism?

In this condition, calcium levels in the bloodstream are raised above normal levels (hypercalcaemia). Seventy to eighty per cent of patients with this endocrine disorder have no obvious signs or symptoms of the disease. It is only discovered when a blood sample is taken (often for an entirely different purpose) and the test shows raised levels of calcium.

Where signs and symptoms related to hyperparathyroidism do become obvious, they are usually as a result of long-term significant hypercalcaemia.

The constantly high levels of calcium in the blood mean that more calcium is filtered by the kidney and some of this excess calcium will appear in the urine (hypercalciuria). At the same time, too much parathyroid hormone increases calcium reabsorption in the kidney. This can result in high levels of calcium in the kidney and the deposition of calcium in the kidney tissues (nephrocalcinosis) or even the formation of kidney stones. Kidney stones occur in about 20–35% patients with primary hyperparathyroidism.

Another consequence of primary hyperparathyroidism is reduced bone density or ‘brittle bones’ (osteoporosis) and an increased risk of a bone fracture.

Associated with bone disease is muscle weakness and joint and bone pains. Other symptoms of hyperparathyroidism can include frequent urination, loss of appetite, abdominal pain, constipation, malaise and fatigue. Mental health symptoms include depression, confusion and stupor.

How common is primary hyperparathyroidism?

It is difficult to estimate how many people have primary hyperparathyroidism because cases often go undetected, but it is about one to four in every 1,000 people or 30 cases in every 100,000 people per year. Postmenopausal women are more likely to develop primary hyperparathyroidism so that, by the age of 75, twice as many women are affected as men. In younger people the rate is similar in men and women.

Is primary hyperparathyroidism inherited?

For most patients, primary hyperparathyroidism is not an inherited condition. However, there are rare forms of hyperparathyroidism that can be inherited. These include multiple endocrine neoplasia types 1 and 2a, familial isolated primary hyperparathyroidism and the hyperparathyroidism-jaw tumour syndrome. Inherited causes of primary hyperparathyroidism account for less than 10% of all cases of primary hyperparathyroidism and so are very rare.

How is primary hyperparathyroidism diagnosed?

The diagnosis of hyperparathyroidism is made by measuring calcium levels in the blood on at least two occasions from a routine blood sample. This is followed by another blood sample to measure the concentration of parathyroid hormone. These tests are done in an outpatient clinic.

How is primary hyperparathyroidism treated?  

The only established treatment for hyperparathyroidism is surgical removal of the affected parathyroid glands. A surgical cure has been shown to ameliorate the ongoing bone density loss and may improve fatigue and impaired quality of life even in those thought to be asymptomatic.

The standard operation requires a full neck examination under general anaesthetic. This allows the surgeon to examine all four (or more) parathyroid glands. This is particularly critical in inherited causes of primary hyperparathyroidism where quite an extensive initial operation may be appropriate. In sporadic, typically single gland disease, minimally invasive surgery is the norm. Surgery under local anaesthetic is possible and this has particular advantages for elderly people who are at risk from a general anaesthetic and full neck surgery. Before surgery, the overactive gland is typically localised using a combination of ultrasound and Sestamibi (nuclear medicine scan) imaging. Computerised tomography (CT)/magnetic resonance imaging (MRI) scans are also sometimes used. Up to 90% of single adenomas can typically be localised pre-operatively but imaging techniques are less successful in identifying multiple adenomas or in patients with mild hyperparathyroidism.

There are some medical treatments available for patients who are unsuitable or not willing to have surgery but none offer a ‘cure’ for the condition. Specific drugs to treat osteoporosis may be indicated as may vitamin d therapy if deficiency is proven. Cinacalcet, is a drug that reduces parathyroid hormone secretion and is quite effective at reducing calcium levels in the blood. It may help in removing symptoms associated with hypercalcaemia in patients not undergoing surgery, or in patients with an inherited cause where further surgery is being delayed. Cinacalcet again does not deliver a ‘cure’ for the condition and long-term outcomes are still being assessed, as the agent is relatively new.

Are there any side-effects to the treatment?

Surgery for hyperparathyroidism is usually highly successful. However, about 1% of patients experience damage to the nerves controlling the vocal cords which may affect speech. A very small percentage of patients may lose all their parathyroid tissue if adenomas are present in all four glands. This will result in chronic low levels of calcium, which will require life-long treatment with vitamin D and possibly calcium supplements in addition.

What are the longer-term implications of primary hyperparathyroidism?  

Most patients have a single adenoma and after this abnormal gland is removed the other parathyroid glands recover and work normally. Therefore, after initial stabilisation, patients can be discharged as cured. Other patients with residual or recurrent disease, or where all parathyroid tissue has been removed, may require longer-term follow-up and regular monitoring to ensure that blood levels of calcium are within the normal range and that parathyroid hormone levels are just high enough to maintain the correct amount of calcium in the bloodstream.

Last reviewed: Mar 2015