Parathyroid Disease
Jul
31
The parathyroid glands are located at the front and base of the neck at the 4 corners of the thyroid gland (Figure 1). 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 (Figure 2). 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.
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| Fig 1 Thyroid Gland |
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| Fig 2 PTH Pathway |
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 (Figure 3). 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 (Figure 4). Treatment for all the mentioned conditions is surgery.
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| Fig 3 Parathyroid Adenoma | Fig 4 Parathyroid Hyperplasia |
| Table 1. | ||
| Types of Primary Hyperparathyroidism | Number of Glands Involved | % of Patients |
| Single Adenoma | 1 | 90-95% |
| Multiple Adenoma | 2-3 | 2-5% |
| Hyperplasia | All | 3-5% |
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
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.
| Table 2 |
Signs & Symptoms |
| System | |
| 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 |
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 1). 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.
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.
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:
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.
| Table 3. | ||||
| 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 |
| Secondary HPT | High | High | Low | - |
| Familial Hypercalciuric Hypercalcemia (FHH) | High | PTH | 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 (Figure 5). 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 (Figure 6).
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| Fig 5 Sestamibi Scan | 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.
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). Traditionally 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.
In primary hyperparathyroidism greater than 90% of cases are caused by an abnormality in one single gland (parathyroid adenoma). A parathyroid scan (Sestamibi scan) or other imaging (ultarsound or CT Scan) can often times find this one abnormal gland. This allows us to take a minimally invasive approach to this disease, by removing this one gland though a small incision, measuring between 1.5 to 2 cm or less then an inch (Figure 7). Despite the small size of incision, in expert hands finding the parathyroid gland is usually not challenging (Figure 8 & 9).
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| Fig 7 Parathyroidectomy Incision |
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| Fig 8 Parathyroid Gland & Recurrent Laryngeal Nere | Fig 9 Parathyroid Adenoma |
We also use intra-operative rapid PTH testing to confirm an appropriate decline in the level of PTH hormone. The PTH level is checked right before surgery and then again in the oprating room after the abnormal parathyroid gland is removed; when the PTH level falls, it shows us that the abnormal gland that was producing too much PTH has been removed. By doing this our surgeons can be certain that your surgery has been successful, immediately in the operating room.
Additionally, in cases of double adenoma or hyperplasia that was not recognized before the surgery, the PTH level does not fall, leading us to the other abnormal glands that need to be removed. This is as opposed to finding out after surgery that the calcium and PTH levels are persistently high, and that the patient needs a second surgery.
Due to the ease of surgery for the patient, it can be done under loco-regional anesthesia, with patient awake but sedated. This may be done in cases where the patient’s health condition precludes general anesthesia, or if the patient prefers not to have general anesthesia.
Parathyroid hyperplasia or four gland disease requires treatment of all four glands (total or subtotal parathyroidectomy), with possible re-implantation of part of one gland in the muscle, or leaving half of one gland (with its blood flow intact) to take over the function of maintaining the body’s calcium balance. Due to anatomic variation in the location and the number of parathyroid glands (three to six in 6% of people) Intra-operative rapid PTH testing, is crucial in making sure these patients are completely treated (Figure 10 & 11).
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| Fig 10 Superior Parathyroid Locations |
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| Fig 11 Inferior Parathyroid Locations |
Since only one gland is removed, the remaining glands take over the job of calcium balance within a short period of time. The patients:
Parathyroid hyperplasia - All parathyroid glands need to be identified and removed. Reimplantation of part of one gland or leaving ½ gland with its blood flow intact allows that gland to take over the job of calcium balance. This usually takes some time, as such although most patients are discharged home after surgery, some may need to be hospitalized until their calcium levels become normal. Otherwise the post-operative course is as outlined above.
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| Parathyroid pamphlet | Parathyroid post op |
