Keith Forwith
Innovative Thyroid Surgeon
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Innovative Thyroid Surgeon
From the guidelines of the American Thyroid Association:
The American Thyroid Association recommends RAI therapy in anyone planning pregnancy for greater than six months from the time of diagnosis. Radioactive iodine is not safe for pregnant patients and so pregnancy should be avoided while Graves’ disease is present, and treatment is ongoing. Radioactive iodine is also a good option for poor surgical candidates. If there is significant heart and lung disease which puts a patient at high risk for surgical therapy, then radioactive iodine is a viable option. Likewise, if there has been previous operation on the neck or radiation for head and neck cancer, this increases thyroidectomy risk and radioactive iodine may be a good option for these patients.
One of the reasons to consider other options are the risks of radioactive iodine therapy. There is a small risk of thyroid storm with RAI treatment. Therefore, it is recommended that normal thyroid hormone levels be established with antithyroid medications prior to treatment with RAI. Response rates of RAI range from 60-86%. A typical dose of radioactive iodine therapy is 10-15 millicuries.
While some studies have found no increase in overall cancer risk after RAI treatment for hyperthyroidism, there is noted a trend towards increased risk of thyroid, stomach and kidney cancer and further research in this area is needed. Recent reports do show an increase in risk of death from breast cancer, kidney cancer and stomach cancer in patients who have prior treatment with RAI for Graves’ disease. Most people respond to RAI therapy with normalization of their thyroid function levels within four to eight weeks. In some patients this may take anywhere from two to six months. Sometimes the thyroid gland remains palpable or visible even after successful RAI therapy.
If hyperthyroidism persists after six months following radioactive iodine therapy, retreatment with more radioactive iodine or thyroidectomy is recommended. Radioactive iodine can shrink goiters by 20-50% over the course of one to two years. One of the reasons to potentially avoid radioactive iodine is there is a 20% incidence of permanent dry mouth. This is a very bothersome symptom to these patients and unfortunately there is not much help for that condition if it occurs. This is definitely a reason to consider other options, particularly if the patient has dry mouth tendencies prior to the onset of Graves’ disease. Radioactive iodine treatment also makes subsequent surgeries slightly higher risk and anyone who has had RAI in the past should make sure that their thyroid surgeon is experienced and high-volume to decrease these complication risks.
Since Graves’ disease will spontaneously resolve in about 30% of patients, it is important to monitor to determine when stopping antithyroid drugs would be safe. One of the best ways of following this is measurement of the TRAb antibody levels. The American Thyroid Association suggests that these labs be checked prior to the cessation of antithyroid drugs. When TRAb remains elevated despite treatment, relapse rates approach 80-100%. In these patients, it is not wise to discontinue the thyroid medications as hyperthyroidism will certainly recur. When TRAb levels are lower, relapse rates typically are in the 20-30% range so this makes stopping the medication much safer. Patients should be trialed for 12-18 months on antidrug therapy and if a patient becomes hyperthyroid after completing a course of methimazole, consideration should be given to definitive therapy. Options for definitive therapy include radioactive iodine and thyroidectomy. Read this to discover which may be the safest and best option for you.
Perhaps the main reason to avoid surgery in considering Graves’ treatment options is any comorbidity which puts the patient at high risk of having an operation. This would include cardiopulmonary disease, end stage cancer, or other debilitating disorders. The American Thyroid Association also recommended in their 2015 guidelines that lack of access to a high-volume thyroid surgeon would be a reason to not consider surgery.
Both methimazole and propylthiouracil (PTU) can present with risk to the fetus. Both methimazole and PTU given in the first trimester of pregnancy present an unacceptable risk for congenital malformations. With methimazole there is approximately a 10% rate of birth defects. This can include urinary system malformation and choanal atresia which is a narrowing of the back of the nose which results in difficulty breathing. Esophageal atresia or malformation of the esophagus can be present. Omphalocele is also a potential risk of methimazole.
Propylthiouracil presents birth defects in approximately 8% of patients. This includes malformations in the face and neck region. Typically, propylthiouracil is recommended before conception and it is recommended that this be switched to methimazole after the first trimester of pregnancy if antithyroid medications are required.
Patients should be rendered euthyroid, that is the TSH level should be in the normal range, and there should not be overactive thyroid function. This is typically achieved with antithyroid medications prior to surgery. It is a bad idea to operate on a patient while they are actively hyperthyroid. This dangerous situation increases the risk of thyroid storm -which can be a life-threatening situation. Thyroid storm can develop when the overactive thyroid gland is surgically manipulated, releasing sudden increased amounts of thyroid hormone. This can send the blood pressure and the heart rate skyrocketing. This is an extremely dangerous situation and can even result in intraoperative death.
Prior to surgery, calcium should be restored to normal levels and evaluation for overactive parathyroid glands (or hypercalcemia) should also be done. In Graves’ disease, a total thyroidectomy is the recommended operation. If a thyroid is removed completely, there is 0% risk of recurrence of the Graves’ disease. Sometimes a subtotal thyroidectomy is done by less experienced surgeons. This presents approximately an 8% risk of persistence of Graves’ disease or recurrence within the first five years following surgery. Therefore, subtotal thyroidectomy is not recommended.
The American Thyroid Association recommends that if surgery is chosen as a primary therapy for Graves’ disease, the patient should be referred to a high-volume thyroid surgeon. This is a strong recommendation by the ATA and is good advice. Specifically, average complication rates, lengths of hospital stay, and costs are reduced when the operation is performed by a surgeon who conducts many thyroidectomies. Complication rates in Graves’ disease are higher than in normal thyroidectomies, increasing the need for a high-volume, experienced surgeon. The American Thyroid Association sites a 51% higher complication rate in thyroidectomy done by low-volume surgeons in the setting of Graves’ disease. Following thyroidectomy for Graves’ disease in the hands of a high-volume thyroid surgeon, the rate of permanent hypoparathyroidism should be less than 2% and a permanent recurrent laryngeal nerve injury should occur in less than 1% of these operations. Higher complication rates are seen with less experienced surgeons. So, the advice to choose your surgeon wisely, is even more important in Grave’s disease.
Generally, pregnancy is a relative contraindication to surgery. It should be used only in the circumstance where rapid control of hyperthyroidism is required and antithyroid medications cannot be used. Thyroidectomy is best avoided in the first trimester to minimize the chances of birth defects. Third trimester surgery should also be avoided because of the risk of inducing preterm labor. When surgery cannot be avoided, optimal timing for thyroidectomy to be performed is in the second trimester. Certainly, there are surgical and anesthesia risks involved with this and a higher rate of complications is noted. Certainly, any consideration of surgery during pregnancy should be undertaken with a high-volume, very experienced thyroid surgeon. The length of time that a patient spends under anesthesia is also a risk factor and a high-volume surgeon that can more quickly complete the operation can lower those risks.
There are two basic medications that can be used to control Graves’ disease and bring thyroid levels into the normal range. The first and safest of those is propranolol. This beta blocker does an excellent job of controlling abnormal heart rates. Patients with Graves’ disease whose heart rate exceeds 90 beats per minute typically would benefit from beta blocker treatment. Propranolol is a very safe medication and has been used for quite a long time. This may not be appropriate for patients with coexistence cardiovascular disease and consultation with your physician on an individual case is always necessary. Patients with high heart rates typically see dramatic symptomatic improvement with the initiation of beta blocker treatment.
The other option is antithyroid medications. These come in two forms, either methimazole (Tapazole) or propylthiouracil (PTU). Of the two of these, methimazole is used most commonly because it is the safest of the two medications. Typically, methimazole is used in combination with beta blocker treatment. Patients taking beta blockers tend to have lower heart rates, less shortness of breath and less fatigue than patients who are on methimazole alone. In 2015, the American Thyroid Association issued new guidelines for hyperthyroidism and recommended an antithyroid medication such as methimazole be prescribed for a 12-18 month period. This allows for evaluation and identification of those patients who will spontaneously resolve and need no further treatment. In fact, there has been a dramatic increase in use of antithyroid medications for the treatment of Graves’ disease over the last decade.
While methimazole is frequently used, it does have some potential side effects which can limit its usage. Patients frequently have stomach upset with this medication; this will typically get better after they have been on it for a few weeks. The downside to methimazole therapy is that it can have some serious side effects. These do not happen very often but still should be considered. Minor side effects include a rash, itching, jaundice, change in color of the stools, joint pain, abdominal pain, nausea, fatigue, fever and sore throat.
Major or serious side effects can include a suppression of the immune system called agranulocytosis (aka aplastic anemia). This happens in 0.7% of patients but is a very serious complication. Any febrile illness with high fevers should be evaluated for this possibility for patients who are on these medications. Rarely a vasculitis or a drug-induced lupus-like syndrome can occur. Liver damage can occur in 3-4% of patients including a small risk of complete liver failure. Thankfully, this devastating complication is seen in 0.03% of the patients on methimazole. While most people can tolerate methimazole, 17-19% of patients discontinue this medication because of adverse side effects. Even less well tolerated is PTU where we see about a third of patients discontinue because of unwanted side effects.
When patients are started on methimazole or PTU, a baseline blood test is recommended. Low white blood cell counts are common in Graves’ disease, as are abnormal liver enzymes. So, it is important to establish a baseline to be used for comparison to make sure that the medication is not making these situations worse. Once on medications, free T4 and T3 should be checked about every six weeks after initiation of therapy. It is not uncommon that it takes more methimazole to bring a patient under control than it does to maintain once adequate control is achieved. Typically, we recommend testing every four to six weeks until a stable dose is established on these medications.
Warning! A differential white blood cell count (CBC) should be obtained any time there is a febrile illness or at the onset of a sore throat. Should a patient develop these types of illness and seek care at an urgent care center, it is important to let them know that you are on these medications and that there is a risk of immune suppression that needs to be evaluated during any of these types of illness. Liver function should be evaluated routinely to make sure there is hepatocellular integrity and no side effects from the medications. This should also be checked when there is an appearance of a rash, jaundice, light colored stool or dark urine. Joint pain, abdominal pain, bloating, anorexia, nausea or fatigue are also good reasons to check liver function for patients who are on antithyroid medications.
The duration of therapy with these medications should be discussed in light of antibody levels. Declining antibodies can be a good sign that Grave’s may resolve spontaneously. On the other hand, persistently high antibody levels typically mean that Grave’s is not going to resolve without definitive therapy. Options for definitive Grave’s therapy options are discussed here.
One of the first steps in evaluating hyperthyroidism is to obtain some routine laboratory workup. The most sensitive test for detecting excess thyroid hormone is the TSH (Thyroid stimulating hormone) exam. T4 should also be evaluated. T3 is the active form of thyroid hormone while T4 is the storage form of thyroid hormone. Neither T3 or T4 levels correlate directly with symptoms! Don’t let anyone tell you how bad your symptoms are based on lab tests! Typically, in Graves’ disease high levels of both T3 and T4 will be seen. There are several antibodies that contribute to hyperthyroidism, the most prevalent is thyrotropin receptor antibody, often abbreviated as TRAb. Ninety-six percent of patients with Graves’ disease are positive for the TRAb antibody. As part of the workup for Graves’ disease, your doctor will evaluate your pulse rate, blood pressure, respiratory rate.
Body weight changes are frequent with hyperthyroidism and while classically Graves’ disease can produce unintentional weight loss, there are many patients who experience weight gain with Graves’ disease. Many patients experience increased appetite – which can easily lead to weight gain, not loss. Graves disease can result in enlargement of the thyroid gland seen low in the neck. The thyroid gland can be tender and can be either symmetric or asymmetric. There may be nodules associated with Graves’ disease and an irregularity to the thyroid gland. In severe cases, the thyroid gland can cause compression of both the trachea and the esophagus. This would produce symptoms of exertional shortness of breath or difficulty swallowing.
Frequently, there are pulmonary symptoms associated with Graves’ disease. Rapid heart rate is often accompanied by a feeling of shortness of breath or a fast rate of breathing. Neuromuscular dysfunction is common in the setting of severe Graves’ disease. Swelling around the eyes is common, while swelling in the shins is an uncommon but well-known complication of Graves’ disease. Cardiac workup is frequently needed including EKG and possible echocardiogram, Holter monitor or myocardial perfusion studies. Typically, Graves’ disease gives an elevated heart rate and it is not unusual for heart rates to exceed 100 at rest in the Graves’ patient.
There are several options for imaging the thyroid in Graves’ disease.
In-office ultrasound is perhaps the easiest way to image the thyroid in Graves’ disease. Typically, what is seen is an overabundance of blood supply to the entire thyroid. The thyroid that is suffering from Graves’ disease has an increased blood supply. This is very evident during surgery as well. The high stimulation of the thyroid gland from the antibodies produces neovascularization, that is the thyroid has an abundant numbers of blood vessels and those blood vessels are dilated and high flow. This can easily be seen on a doppler imaging during a thyroid ultrasound examination.
Another option for evaluating the thyroid is the thyroid uptake scan, which is usually done at the hospital radiology department. In Graves’ disease, the entire gland is going to show an increased uptake of contrast material. This scan can be useful in distinguishing Graves’ disease from multinodular toxic goiter and toxic adenoma. Occasionally, hyperthyroidism is caused by thyroiditis in which case the uptake scan is going to show very little uptake. Perhaps the luckiest patients with hyperthyroidism are those that have a toxic adenoma. This is a single isolated area of the thyroid that is overproducing thyroid hormone, and this can be removed with a thyroid lobectomy. This not only cures the hyperthyroidism, but the remaining half functions normally. The result is that most patients would not require thyroid hormone supplementation after surgery. In multinodular toxic goiters, the entire thyroid would need to be removed in order to gain adequate control of the disease because the thyroid nodules tend to be on both sides of the thyroid. In some cases of Graves’ disease, particularly those with orbitopathy, imaging studies are not necessary as the diagnosis can be established clinically through either lab tests or through ultrasound. The need for thyroid uptake scans has diminished as the quality and the availability of ultrasound in the office setting has improved.
Innovative Thyroid Surgeon