The parathyroid glands are located at the front and base of the neck at the 4 corners of the thyroid gland (Fig. 1 Thyroid Gland). The glands produce parathyroid hormone (PTH), which regulates calcium balance in the body by increasing absorption of calcium in the intestines, re-absorption in the kidneys and release of calcium from our bones into the bloodstream (Fig. 2 PHT Pathway). It controls the production of the active form of Vitamin D (Vit D3) in the kidney, which is what helps absorption of calcium in the intestines.
As blood flows through the parathyroid glands, the amount of calcium and Vitamin D in the blood is checked by the parathyroid glands; if the amount of calcium or Vitamin D is low the gland produces PTH, and if the amount of calcium is high the gland stops producing PTH. Through this mechanism, there is minute-to-minute control of the level of calcium in the blood. The concentration of calcium in the blood is so important to normal functioning of the body, which is why there are four parathyroid glands, even though one gland would be enough to do the job. These glands are very active and are constantly working.
Hyperparathyroidism is a condition in which the parathyroid gland makes more of the PTH than it needs to, causing an imbalance in the amount of calcium in the body. This can lead to problems with the bones, muscles, nervous system, and kidneys.
In primary hyperparathyroidism, increased secretion of PTH occurs because one or more of the glands have become enlarged and since the parathyroid glands have only one function (to produce PTH), these enlarged glands continue to produce large amounts of PTH without regard to the amount of calcium in the blood. More then 90% of the cases are caused by enlargement of one gland, called a parathyroid Adenoma (Fig. 3 Parathyroid Adenoma). In approximately 5-10% of cases there are abnormalities in more then one gland. Sometimes this is because two or three glands are enlarged (Multiple Adenoma), and at others times it’s because all four glands are abnormal, called Parathyroid Hyperplasia (Fig. 4 Parathyroid Hyperplasia). Treatment for all the mentioned conditions is surgery.
Fig. 3 Parathyroid Adenoma
Fig. 4 Parathyroid Hyperplasia
|Types of Primary Hyperparathyroidism||Number of Glands Involved||% of Patients|
Secondary hyperparathyroidism happens as a consequence of low vitamin D levels, either due to kidney failure or dietary deficiency. All four glands increase their activity and secrete more PTH so as to increase the vitamin D levels. The treatment of secondary hyperparathyroidism is to correct the chemical imbalance. If untreated, over time all of the parathyroid glands start to work independently without being controlled by the level of calcium in the blood (this is called Tertiary hyperparathyroidism). The PTH levels continually rise and cause problems. Treatment for this condition is surgery.
Parathyroid cancer is very rare, and most parathyroid tumors are benign. Less than one percent of people with hyperparathyroidism are diagnosed with a malignant parathyroid tumor. Generally, on laboratory exam their PTH level is extremely high, and can be into the thousands
The Role of Vitamin D Deficiency
As the level of Vitamin D falls, the parathyroid glands produce more PTH to stimulate the kidney to produce more vitamin D. As a consequence the PTH causes calcium to be released from the bones, and over time thinning of bones and fractures occur.
Can Vitamin D deficiency happen at the same time as primary hyperparathyroidism? Yes, it is a common occurrence. Considering that in general, 40% of the population in the US has Vitamin D deficiency, it’s likely that these two conditions can happen at the same time. Studies show that when these patients are treated with Vitamin D replacement, their calcium levels did not get worse, and the bone density improved. This doesn’t cure the hyperparathyroidism, but it removes the effect of Vitamin D deficiency.
Signs & Symptoms
Every cell & organ in the body uses calcium to work properly; high calcium levels can cause a large number of problems and a variety of symptoms (Table 2). The severity of symptoms does not go hand in hand with the level of rise in calcium. Some patients with slight elevation in calcium may have severe osteoporosis, and others with high levels may have very few symptoms. Because the symptoms are so non-specific and the patients can have any combination of symptoms, they are not appropriately diagnosed as having a parathyroid disorder, and the patients go untreated. Interestingly, even the patients who are without symptoms find that they feel much better after surgery. In several medical studies it has been shown that 95% of patients state they feel better after surgery. As early as 72 hours after surgery, most patients feel an improvement in many of the symptoms.
|System||Signs & Symptoms|
|Neuro- Psychiatric||Depression Anxiety, Cognitive Dysfunction, “Fogginess” Headache, Fatigue, Forgetfulness, Poor Sleep|
|Musculo- Skeletal||Bone pain, Osteoporosis, Fractures, Muscle Weakness|
|Gastro- Intestinal||Constipation, Peptic ulcer disease, Anorexia, Acute pancreatitis, Abdominal pain|
|Renal||Kidney Stones Frequent urination, Night time urination|
|Cardiac||High Blood Pressure, Palpitations|
All patients with hyperparathyroidism will eventually develop osteoporosis. Taking medications such as Fosamax or Actonel will not help bones that are less dense due to parathyroid disease. Long-standing elevation in calcium places a heavy burden on the body and has been proven to lead to a decreased life expectancy. Parathyroid disease only gets worse with time in everyone. It will continually change, and will not get better on its own.
The disease can happen at any age but is most common in people over 60. The chance increases with age. Women are three times more likely to have hyperparathyroidism than men. Radiation to the head and neck increases risk of getting this problem. Hyperparathyroidism in childhood is extremely uncommon.
How to Diagnose Hyperparathyroidism
Physicians can make the diagnosis by recognizing a combination of signs and symptoms. However, in most cases, routine laboratory tests showing a high blood calcium level are what lead us to investigate this issue further. The following laboratory tests should be done confirm diagnosis:
- Calcium & PTHintact levels (done at least twice at different times)
- 25 Hydroxy Vitamin D level
- Creatinine levels
- 24 hour Urine Calcium level
A combination of an elevated calcium and PTH level confirms hyperparathyroidism. However, not all cases are as clear-cut as that. There are times when the calcium is high and the PTH level is in the upper range of normal, this can occur in the early stages of hyperparathyroidism. A fluctuation in the blood calcium level from high to normal range and high again is also a frequent occurrence in patients with parathyroid disease.
|Disease||Calcium||PTH||Vitamin D||Urine Calcium|
|Primary HPT||High||High||Normal||Normal or high|
|Early Primary HPT With Normal Calcium||Upper Normal||High||Normal||Normal or high|
|Early Primary HPT With Normal PTH||High||Upper Normal||Normal||Normal or High|
|Familial Hypercalciuric Hypercalcemia (FHH)||High||High||Normal||Low|
Imaging Studies Imaging studies (Sestamibi, Ultrasound, or CT Scan) help find the location of the abnormally enlarged gland (parathyroid Adenoma). Identifying the location of the abnormal parathyroid gland is very important in planning the surgery. However, these studies are not used to make the diagnosis, just for localization.
A sestamibi scan is the preferred method to find the location of the abnormal parathyroid gland (Fig. 5 Sestamibi Scan). This is a very technically challenging test, and in order to get accurate results it must be done by imaging centers with expertise. To precisely locate the gland with respect to the thyroid, trachea and other structures a CT scan or an ultrasound of the neck can be performed; when these tests are combined with sestamibi, they improve the chances of finding the parathyroid adenoma (Fig. 6 CT Scan).
The Dexa Scan or Bone Density Scan is important to document the impact of this disease on the bone density. This most important in women, elderly, and anyone who has been diagnosed with hyperparathyroidism and has had a bone fracture.
Next, learn more about Surgical Treatment of Hyperparathyroidsim.
Surgical Treatment of Hyperparathyroidism
The treatment of primary & tertiary hyperparathyroidism is surgery. There are no effective medical treatments for these conditions. Parathyroidectomy in general refers to removal of one or two abnormal parathyroid glands. Subtotal parathyroidectomy refers to removal of 3 and a half of the four glands. The half gland that remains is either left in its original place or cut into small pieces and left in a muscle, where it can reform blood vessels into itself and start working again (this usually takes one to two months). Traditional Parathyroidectomy is performed through a large incision where all four glands are identified and biopsied. Our team of expert surgeons utilizes the technique of minimally invasive parathyroidectomy via a small incision as well as intra-operative PTH hormonal testing to ensure a more effective and less invasive procedure. As a result, our patients’ recovery course is much simpler.
Next, learn more about Minimally Invasive Parathyroidectomy