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Thyroid Disease, Evaluation and Treatment
The thyroid gland is located low in the central neck with lobes on either side running along the trachea. The primary function of the thyroid is to produce thyroid hormone which circulates throughout the blood stream to control cellular metabolism. Disorders of the thyroid gland are very common affecting women more often than men. Most thyroid problems are spontaneous but some are hereditary or may be caused by dietary deficiencies of iodine, radiation exposure or as a side effect of certain medications.
Inadequate production of thyroid hormone (hypothyroidism) is the most common problem, comes in many forms and can result in chronic fatigue, temperature intolerance, weight gain, heart dysfunction dementia and lower extremity edema. This problem is readily managed with hormone replacement with an oral form of the human hormone taken daily. This is typically managed by a primary care physician or endocrinologist.
Overproduction of thyroid hormone (hyperthyroidism) also occurs in several forms and may cause insomnia, weight loss, heart palpitations, high blood pressure, temperature intolerance, osteoporosis, and eye disorders among other problems. This often requires medical treatment to block or slow down the gland managed by an endocrinologist. Surgery to remove the gland is sometimes indicated.
Thyroid Nodules or Masses
Nodules or lumps within the thyroid gland are extremely common, occurring in 4% to 7% of people in the United States. These may be hereditary or spontaneous, single or multiple, hormone producing or not, and benign or malignant. Most nodules are benign (95%) and do not require treatment unless symptomatic with neck pressure, swallow difficulty or rarely breathing issues. The difficulty is determining whether a nodule is benign or malignant (cancerous).
Thyroid Nodule Evaluation
Appropriate evaluation of a thyroid nodule usually includes a thyroid ultrasound which is a non-invasive and relatively inexpensive procedure. Some ultrasound findings favoring benign nodules are smaller size, multiple nodules, cystic or fluid filled nodules, and absence of calcifications. Larger, solitary, solid nodules and those with calcifications and most nodules in persons with a family history of thyroid cancer or radiation exposure to the neck require a fine needle aspiration (FNA) biopsy for diagnosis. If the biopsy is malignant (5%) or suspicious (20%) surgical removal is recommended. If the biopsy favors a benign nodule (75%) usually a follow up ultrasound is recommended for observation. Evidence of growth of a nodule is an indication for either repeat biopsy or removal.
The most common indication for thyroid surgery is for a suspicion of cancer in a nodule. If the thyroid has no other nodules then a partial removal of the thyroid (lobectomy) removing the side of the gland with the nodule is an option. A frozen biopsy of the nodule is usually performed during surgery and if cancer is confirmed then the remainder of the gland is removed and removal of some lymph nodes may be indicated. If the frozen biopsy is indeterminate or suggests a benign lesion then the surgery is terminated. Occasionally the final pathology report will find a cancer that was not diagnosed at the time of surgery. If a partial removal had been performed then a second surgery is indicated for the complete removal of the cancer tissue and possibly lymph nodes.
Risks of Thyroid Surgery
The major risks of thyroid surgery are related to the structures in the neck closely approximated to the thyroid gland. These are the nerves to the vocal cord muscles (recurrent laryngeal nerve or RLN) and the parathyroid glands which produce parathyroid hormone to control calcium metabolism in the body (see below). The RLN runs on the underside of the thyroid gland en route from the chest to the voice box. The nerve enters the voice box at a point where the thyroid gland is firmly attached to the voice box. It is at this point where the nerve is at highest risk for injury during surgery. The overall risk of permanent nerve injury is very low with thyroid surgery (1-2%) The use of nerve monitoring with a specialized endotracheal tube during surgery (Nerve Integrity Monitor or NIM) may reduce the risk of injury to the nerve. Nerve injury may be temporary (2-5%) or permanent (1-2%) and results in hoarseness of the voice which can be improved with vocal cord injection or repositioning if necessary.
Most people have four parathyroid glands (range one to ten), two on each side which are located on the underside of the thyroid gland, share a blood supply with the gland and are often adherent to the gland or occasionally embedded within the gland. These glands may be bruised or inadvertently damaged during thyroid removal. One functioning parathyroid gland is adequate for hormone production, however if all remaining parathyroid glands are bruised during surgery then the patient may experience low blood calcium levels until the glands recover which may take weeks to months. This is managed with calcium and vitamin supplements in high doses until recovery occurs.
Thyroid Lobectomy verses Totyal Thyroidectomy
If thyroid surgery is performed for evaluation of a nodule as described previously, the preservation of the opposite side of the gland offers several advantages: 1) the remaining gland will produce enough hormone in 80% of people to prevent the need for thyroid medication after surgery; 2) the opposite RLN is not dissected and therefore not at risk of injury; 3) the opposite parathyroid glands are not at risk of injury. The disadvantages include: 1) The possible need for a second surgery if there is a delayed diagnosis of cancer; 2) the risk of developing a second nodule of concern requiring ultrasounds, FNA and possibly surgery in the future (this occurs in at least 25% of people with more than one nodule at the time of diagnosis); 3) the need for thyroid hormone replacement in 20% of people.
Minimally Invasive (Endoscopic Assisted) Thyroid Surgery
This newer technique of thyroid surgery builds off the experiences with other minimally invasive procedures including orthopedic surgery, gall bladder, prostate, kidney and stomach surgery. A much smaller incision is used (approximately one inch instead of the usual 4 inch incision) and endoscopes are introduced into the wound to allow portions of the surgery to be performed while watching a video monitor. Nodules measuring 3cm or less may be removed through this technique in most people. Lymph node dissection is typically not feasible through this technique. In addition to a smaller incision, significantly less dissection is required allowing for outpatient surgery (lobectomy only) and more rapid recovery.
Thyroid cancer afflicts over 20,000 people per year in the United States with the most common form being Well-differentiated Thyroid Carcinoma (WTC). Other less common forms include Medullary Thyroid Carcinoma and Anaplastic Thryoid Carcinoma.
Well-differentiated Thyroid Carcinoma
This form of thyroid cancer has an excellent prognosis, especially for people under 45 years of age. There are two types of WTC: papillary carcinoma (60-85% of thyroid cancers) and follicular carcinoma (5-20% of thyroid cancers). Papillary carcinoma has a high propensity of spread to the lymph nodes and other areas of the body while follicular carcinoma is more likely to be confined to the thyroid gland. The reason for the excellent prognosis for WTC, even with lymph node or other metastasis is the high affinity these cancer cells have for elemental iodine. The cells of thyroid gland produce Thyroid Hormone which is one of the few compounds in the body containing iodine. Treatment consists of surgery and radioactive iodine treatment followed by long term thyroid tissue suppression with thyroid hormone.
Surgery for WTC
Thyroid surgery for known WTC should strive to remove all normal thyroid tissue and as much known cancerous tissue as possible. Typically this consists of total thyroidectomy and at least a central compartment (or paratracheal) lymph node dissection. If there is any know neck lymph node spread a complete removal of lymph nodes from the anterior neck with preservation of all normal tissue structures (vessels, nerves and muscles) is indicated.
Radioactive Iodine Therapy for WTC
Elemental Iodine can be converted to a radioactive form (I131) and administered by mouth. The usual treatment dose of radioactive iodine for WTC is around 100 to 150 mCi. After circulating in the blood stream most of the radioactive iodine will be excreted in the urine and saliva. A small concentrated amount will remain in any remaining thyroid tissue including WTC cells. This provides a targeted lethal dose of radiation to the thyroid and cancer cells. Normal thyroid cells take up the iodine more than the WTC cells, therefore as much normal thyroid tissue should be surgically removed as possible prior to iodine treatment. Treatment is also preceded by consumption of a low iodine diet and thyroid tissue stimulation by either thyroid hormone withdrawal or artificial stimulation using injections of thyrogen hormone.
The body is imaged approximately one week after treatment with radioactive iodine to determine what tissues retained the iodine thus providing an indication of the amount of normal or WTC cells present. It is possible to retreat with radioactive iodine if necessary, usually at six or nine month intervals up to a total dose of 1000 mCi. Acute risks of I131 include nausea and vomiting and saliva gland inflammation. Long term risks include bone marrow suppression and dry mouth.
Medullary Thyroid Carcinoma
A less common form of thyroid carcinoma (3-10%) is Medullary Thyroid Carcinoma (MTC). This is hereditary in nature 30% of the time making up a portion of the Multiple Endocrine Neoplasm (MEN) syndromes. For high risk families (those with a history of MTC) genetic testing is available. Medullary carcinoma arises in the "C cells", a small subpopulation of neural crest cells found within the thyroid gland. These cells do not produce thyroid hormone and therefore do not take up iodine (I131). Rather the C cells produce the hormone calcitonin which is involved in calcium metabolism. Calcitonin levels can be measured in the blood stream and are elevated in the presence of MTC.
Treatment for MTC is primarily surgery. Complete removal of the thyroid gland and adjacent lymph nodes may be followed by external beam radiation as I131 is not effective. Post treatment monitoring relies heavily on watching for elevated calcitonin levels in the blood stream. There currently are several chemotherapeutic agents under investigation for the treatment of metastatic or non-operative MTC.
Anaplastic Thyroid Carcinoma
The least common (2-10%) and most aggressive form of thyroid carcinoma is called Anaplastic Carcinoma. The etiology of Anaplastic Carcinoma is unknown and is considered by most to be incurable. It often presents as a rapidly expanding neck mass with swallowing and breathing difficulties. Direct invasion of the voice box, trachea and esophagus is common. These cancers are often too large and invasive to be removed surgically. In these instances breathing is controlled with placement of a tracheotomy tube and treatment with chemotherapy and external beam radiation is undertaken.
Parathyroid Gland Disorders
Most people (80%) have four parathyroid glands (range one to ten), two on each side which are located on the underside of the thyroid gland, share a blood supply with the thyroid and are often adherent to the gland or occasionally embedded within the thyroid gland.
The glands are normally pea sized and appear very similar to normal lymph nodes. Parathyroid glands produce Parathyroid Hormone (PTH) which can be measured in the blood stream. PTH participates in control of calcium metabolism with in the body helping to maintain the calcium levels in the blood stream by directing uptake of calcium from the food during digestion or by pulling calcium out of the bones.
This uncommon condition results from the overproduction of parathyroid hormone (PTH) by the parathyroid gland(s). This can occur due to kidney problems altering the parathyroid glands (secondary and tertiary hyperparathyroidism) or due to a specific problem with the parathyroid gland(s) (primary hyperparathyroidism). The most common form of primary hyperparathyroidism results from a benign tumor (adenoma) on one gland (96%). Rarely there is an adenoma of more than one gland (1%) or there is enlargement of all four glands (3-4%) called hyperplasia.
Symptoms of hyperparathyroidism are known as "moans, groans, stones and bones". In cases of mild hyperparathyroidism there are few symptoms but patients may complain of fatigue, depression, aches and pains. The elevated PTH pulls calcium out of the bones causing osteoporosis or osteopenia, bone weakness and bone pain. There is also an elevation of calcium secreted in the urine which may cause calcification in the kidney and kidney stones. This may cause pain and kidney dysfunction. Very high levels of calcium in the blood stream may cause stomach ulcers, pancreatitis and nervous system issues. Many of these symptoms are reversible within months of treating the underlying problem.
Diagnosis of Hyperparathyroidism
When a patient has chronically elevated blood calcium levels or kidney stones an evaluation for hyperparathyroidism is appropriate. Blood testing including a regular and ionized calcium, PTH and Vitamin D levels are combined with a 24-hour urine collection for calcium. If hyperparathyroidism is suspected the degree of severity should be evaluated with bone density testing and possibly kidney imaging for stones.
When laboratory testing suggests hyperparathyroidism it is appropriate to try to localize the enlarged parathyroid with imaging studies. Neck ultrasonography is non-invasive and gives critical information about the overlying thyroid gland and will often show an enlarged mass behind the thyroid consistent with an enlarged parathyroid gland. Nuclear medicine imaging (sestamibi scan) uses a radiotracer which is taken up by the parathyroid cells more actively than the surrounding tissues (thyroid) and stays in the parathyroid glands longer. Thus scanning immediately and in a delayed fashion can help distinguish parathyroid from thyroid uptake. Normal parathyroid glands do not take up enough tracer to be imaged, enlarged glands will often show uptake (75-95% of the time). There are other methods to localize the abnormal gland but these are currently the most reliable.
Treatment of Hyperparathyroidism
Very early forms of hyperparathyroidism may have few or no associated symptoms. The process may not have persisted long enough to cause bone or kidney changes as the PTH level is not yet profoundly elevated. These cases are usually associated with smaller adenomas where the gland is too small to image. In some instances it may be appropriate to consider observation in this setting to allow the disease to progress until the gland is large enough be imaged. Typically, however, treatment is indicated once the problem is identified.
Treatment of primary hyperparathyroidism is the surgical removal of the offending parathyroid gland(s). A person needs at least one functioning parathyroid gland to meet hormonal requirements post removal. Thus the removal of glands should be minimized to include only disease glands. Recent advancements include the gland localization by imaging as described above, the development of the ability to measure PTH blood levels during surgery and of newer minimally invasive surgical techniques. Some also find the use of radioactive tracers and intraoperative probes beneficial.
Minimally Invasive Parathyroid Surgery
If the offending parathyroid has been localized with imaging prior to surgery a limited surgical procedure is often appropriate. The use of intraoperative ultrasonography confirms the enlarged gland location for the surgeon. A small incision is performed and the use of endoscopes can help to minimize the dissection of tissues. The gland is carefully identified and removed. Blood levels of PTH are checked prior to gland removal and 5 and 10 minutes after removal. An appropriate drop in PTH level combined with frozen biopsy of the removed gland confirms the successful treatment of the problem in most cases. This procedure can be performed under local anesthesia if desired and is usually an outpatient procedure.
If the intraoperative PTH level does not drop as much as expected then more than one gland is involved and a full exploration is indicated (see below). Very occasionally (<5%) the PTH level does drop appropriately but then elevates again in the months after surgery. This suggests a second gland is involved but was much smaller than the original enlarged gland.
Four Gland Exploration
In the setting where the offending gland may not be identified or more than one offending gland is suspected, a larger surgery is indicated. This involves a full exploration of both sides of the neck to identify all four glands. A comparison is then made visually to determine which appear abnormal and PTH levels are monitored after removal to confirm adequate treatment. Again, one gland (or a portion of one in the setting of hyperplasia) must remain to provide enough hormone production. Challenges to this surgery may include an abnormal number of glands (one to ten), abnormal location of the glands (high in the neck to low in the chest) and scar tissue from prior surgery.
Fortunately complications from parathyroid surgery are infrequent (<1%) particularly with the minimally invasive approach. Possible problems include injury to the nerve to the vocal cord causing hoarseness, trauma to the remaining parathyroid glands causing hypoparathyroidism (low PTH and blood calcium levels) which may be temporary or permanent and missing an abnormal gland which could require repeat surgery.