What is Parathyroid Adenoma?
The parathyroid glands were first discovered in animals in the mid-1800s, with the first removal of these glands done in Vienna by Felix Mandl in 1925. Since then, our understanding, ability to diagnose, and treatment of parathyroid issues have greatly improved.
The parathyroid glands are tiny, oval-shaped organs located near your thyroid, which is found in your neck. Most people have 4 of these glands, with 2 higher up (the superior glands) and 2 lower down (the inferior glands). The superior glands usually sit on the upper-middle part of the thyroid, while the inferior ones vary in their location as they develop and grow along the same path as the thymus, another gland in your body. Usually, the inferior glands are found in the lower third of the thyroid gland.
In terms of size, a healthy parathyroid gland is about the size of an apple seed and weighs around 0.5 g. Tiny tumors, or microadenomas, are those that weigh less than 0.1 g. Extremely large tumors, or giant adenomas, weigh more than 2 g. The average tumor weighs about 1 g.
What Causes Parathyroid Adenoma?
Parathyroid adenoma is a type of parathyroid disease, which also includes parathyroid hyperplasia (excessive growth) and parathyroid carcinoma (cancer).
The exact reason why parathyroid adenomas occur is still unknown for most patients. However, research shows that a common genetic mutation – the cyclin D1/PRAD1 gene – can often be associated with these adenomas. When this gene’s normal function is altered, it affects the secretion of the hormone PTH (parathyroid hormone), which is essential for controlling calcium levels in our bodies. About 20 to 40% of adenomas have an overexpression of cyclin D1, meaning it is produced in excessive amounts.
Environmental factors can also contribute to parathyroid disease. For example, people who have had radiation therapy may be at a higher risk of developing parathyroid disease later in their life. In addition, a long-term deficiency of calcium can lead to parathyroid disease as well, because this deficiency can cause the persistent stimulation of PTH.
Risk Factors and Frequency for Parathyroid Adenoma
Hyperparathyroidism is a condition largely caused by a single parathyroid adenoma, which is accountable for around 80% to 85% of cases. Other sources of the condition may include double adenomas, contributing to 4% to 5% of cases, or parathyroid hyperplasia, representing roughly 10% to 12% of instances. Rarely, less than 1% of hyperparathyroidism cases can be traced back to parathyroid carcinomas. Parathyroid adenomas are most frequently diagnosed in individuals between 50 and 70 years old, but they can appear at any age. The condition is more prevalent in women, as they are three times more likely to be affected than men.
- Hyperparathyroidism is primarily caused by a single parathyroid adenoma, accounting for 80% to 85% of cases.
- Double adenomas cause 4% to 5% of cases.
- Parathyroid hyperplasia is responsible for about 10% to 12% of cases.
- Parathyroid carcinomas are very rare and cause less than 1% of cases.
- Parathyroid adenomas most commonly occur in people aged 50 to 70, but can happen at any age.
- Women are three times more likely to be affected than men.
Signs and Symptoms of Parathyroid Adenoma
A parathyroid adenoma is a type of medical condition that may cause no symptoms for many patients, often only getting discovered during routine medical tests as it can lead to elevated calcium levels in the blood. However, if symptoms do occur, they’re often due to this high level of calcium, causing issues like bone pain, tiredness, increased urination, kidney stones, constipation, and changes in mental functions. Very high calcium levels can lead to more serious complications, like heart rhythm problems, coma, or even death. It’s rare for people with this issue to have visible physical signs, such as a lump in the neck – such symptoms could suggest other problems, like issues with the thyroid gland or a type of cancer called parathyroid carcinoma.
- Bone pain
- Tiredness
- Increased urination
- Kidney stones
- Constipation
- Changes in mental function
- Heart rhythm problems (in severe cases)
- Coma (in severe cases)
- Possible death (in severe cases)
Testing for Parathyroid Adenoma
If hypercalcemia, which is a higher than normal level of calcium in your blood, is seen on a routine blood test, this could be an early clue to hyperparathyroidism. In many cases, this excess calcium in the blood is mild, not always present, and usually not more than 1.0 mg/dL above the normal limit. If you repeatedly have unexplained high calcium levels, further tests may be needed. Your doctor could measure your parathyroid hormone (PTH) level – it might be high or it could be normal, but if it’s normal and you have hypercalcemia, it’s not an appropriate result. Another possible test could be a 24-hour urine calcium test, but this isn’t crucial for diagnosis.
Imaging tests are an essential next step. These tests not only help with surgical planning but also help in differentiating between whether you have a single abnormal parathyroid gland or multiple. Normal parathyroid glands are usually too small to be seen on an ultrasound, so if one is visible, it might mean there’s a problem. If an adenoma, which is a non-cancerous tumor, can be identified on the ultrasound, it should look like a uniformly gray-to-black oval shape outside of the thyroid gland itself. It should be separate from the normal thyroid tissue. There may also be an identifiable artery feeding into the adenoma. Ultrasounds aren’t always able to detect these adenomas and can miss them 20 to 40% of the time because the success of the test depends on the person doing the ultrasound. That’s why an ultrasound is often used alongside nuclear imaging tests.
The best test to find these adenomas is a scintigraphy scan. This is a special type of imaging test which is done after a small amount of a radioactive substance called technetium-99m is injected into your vein. Combined with a test called a single-photon emission computed tomography (SPECT) scan, this technique has a success rate of 91 to 98% in detecting parathyroid adenomas.
Another option is a type of imaging where two radioactive substances are used – technetium-99m pertechnetate and thallium-201. Both the thyroid and parathyroid take up thallium, while only the thyroid takes up pertechnetate. The images are then compared to visualize the glands. Drawbacks to this method include the need for special software, long scanning times, and limited views.
Other imaging such as 4D CT and MRI scan can be used to find parathyroid adenomas, but they are less successful, detecting them in around 75% and 40%-85% of cases respectively. These methods are most useful for finding abnormal glands that are not in the usual place following failed parathyroid surgery.
Treatment Options for Parathyroid Adenoma
In the past, treatment for hyperparathyroidism typically involved exploration of all four parathyroid glands. However, as 85% of hyperparathyroidism cases are caused by a single abnormal gland called an adenoma, a less invasive surgery called minimally invasive parathyroidectomy is being recognized as the best approach.
Hyperparathyroidism is a condition where the parathyroid glands produce too much parathyroid hormone (PTH). PTH regulates the body’s calcium levels. An adenoma is a non-cancerous tumor that can form on the parathyroid glands and cause them to overproduce PTH, which then can cause a number of health problems.
After removing the adenoma, doctors use a test known as the Miami criteria to measure PTH levels in the blood. This test is based on the fact that PTH has a short ‘half-life’, which means it breaks down quickly in the body. According to this criteria, PTH levels should drop by at least 50% within 10 minutes of removing the adenoma. If this does not occur, it may mean not all of the abnormal gland tissue has been removed, and further exploration may be needed.
Occasionally, gland tissue can be found in unexpected places like behind the throat (retropharyngeal plane), behind the esophagus (retro-esophageal plane), in the posterior mediastinum (a space in the chest between the lungs), the thymus (a small organ behind the breastbone), inside the thyroid capsule or gland, in the space containing the carotids (major arteries in the neck), or within the chest cavity (mediastinum).
What else can Parathyroid Adenoma be?
When a patient has high levels of calcium in their blood, also known as hypercalcemia, the two most common causes that doctors generally consider are malignancy (cancer) and hyperparathyroid. Together, these two conditions make up 90% of hypercalcemia cases. Cancer usually leads to much higher levels of calcium than a non-cancerous parathyroid disease.
Another disease that can cause hypercalcemia is Familial Hypocalciuric Hypercalcemia (FHH). Roughly 20% of patients with FHH may also have high levels of parathyroid hormone (PTH), which can make it difficult to tell the difference between FHH and parathyroid diseases. However, people with FHH typically have a low level of calcium in their urine and a certain level of calcium to creatinine (a waste product generated by muscles) ratio. But, these characteristics are not seen in individuals with parathyroid adenomas.
The doctor should also check whether the patient has been taking certain medications like thiazide diuretics and lithium, which could increase calcium levels. So, when patients have high levels of calcium, their medication history should be checked for these drugs.
Possible Complications When Diagnosed with Parathyroid Adenoma
: If a parathyroid adenoma isn’t treated, it can cause complications linked to high calcium levels. One unusual health crisis that it can lead to involves extremely high calcium levels (often higher than 15 mg/dL) causing changes in mental state that can eventually lead to a nervous system breakdown and coma.
There may also be complications that result from surgically removing the parathyroid adenoma. One significant concern is potential injury to the laryngeal nerve, which can occur during any surgical procedure targeting the endocrine system. Damage to this nerve can lead to voice hoarseness (if only one side is damaged) or blockage of the airways (if damage is on both sides). This damage can be caused by direct harm to the nerve from surgical clips, forcible handling, or over-stretching, or alternatively from indirect effects like thermal injury, compression, or excessive exposure of the nerve. If the damage is due to compression or stretching, it could potentially recover in about 4 to 6 weeks time. However, if no improvement is seen after 6 to 12 months, the damage should be assumed to be permanent. If the nerve injury is identified during the surgery, immediate repair or graft should be undertaken.
Common Complications to aware of:
- High calcium levels leading to changes in mental state
- Breakdown of the nervous system
- Coma
- Damage to the laryngeal nerve during surgery
- Hoarseness of voice
- Airway blockage
- Potential permanent damage to the nerve
Recovery from Parathyroid Adenoma
Following a parathyroidectomy, which is a surgical procedure to remove the parathyroid glands, your calcium levels might decrease for a few days (2-4 days). Most people don’t experience any symptoms from this, but if you do, you may need treatment with a substance called calcium gluconate. In case the low calcium condition continues, you might need to take oral calcium supplements.
