Therapy for Hyperthyroidism

1. Hyperthyroidism is usually caused by the following situations
1. Graves' disease - the most common form of hyperthyroidism, resulting in an increase in thyroid hormone secretion
1. The gland maybe enlarged where a lump is actually seen on the patient's neck
2. Images may show a diffused homogenous gland with increased iodine uptake
3. Or the enlarged gland my have hetergenous uptake with hot, warm, and/or cold nodules
2. Plummer's disease is a toxic nodular goiter that occurs less often, but also results in the excretion of excess thyroid hormones
1. Gland usually has a single hot nodule
2. The term associated with this type of nodule is autonomous nodule because the nodule will not respond to decreased levels of TSH. Under normal physiological conditions the thyroid and its cells would "shut down" if high levels of TSH are secreted. However, since the nodule is autonomous, the nodule has no respond to decreased levels of TSH
3. Reduced TSH secretion, may even close down the production of T3 and T4 in normal thyroid tissue. From an imaging standpoint the only part visualized would be the hot nodule
3. Transient hyperthyroidism may also occur and is not a treatable condition because this condition is only temporary
1. Occurs when there is a sudden insult to the thyroid
2. Mild hyperthyroidism may result
3. Elevated hormone levels are noted
4. Radioiodine uptake is low (which is an indication of the transient situation)

2. Treatment for hyperthyroidism
1. Antithyroid medication therapy
1. This was the preferred method back in the 1940s when it was first introduced
2. Permanent remission varies considerably and may depend on environmental and/or dietary factors
1. Initially, permanent remission is seen in 60 to 80% of patients at 6 to 12 months post therapy
2. Cure rates changed in the US to 10 to 40%, over time, which maybe due to increased levels of iodine in the diet
3. This method is more effective in younger patients with small goiters
4. Methimazole (an antithyroid medication) inhibits TSH secretions resulting in decreased stimulation to the gland
5. Side effects
1. Toxic reaction such as skin rash and mid fever occur about 5-7% of the population
2. More severe toxic reaction, such as fever, chills, malaise, or pharyngitis can occur. In these cases medication should be discontinued
6. In general, antithyroid medication is consider unreliable, requires close medical supervision, and the patient must keep to a rigid therapeutic drug schedule
2. Surgical removal of part of the thyroid maybe suggested
1. Cure rate is around 85%
2. Relapse is about 5-20%
3. Hypothyroid occurs in 25-50% within 10 years post treatment
4. The question here is, if you remove too much tissue the patient may have an onset of early hypothyroidism
5. Advantage to this approach is that it quickly controls the disease and has a high cure rate
6. Radioiodine therapy is favored over the surgical approach
3. Radioiodine treatment is the method of choice
1. The response to this treatment depends on the amount of radioiodine give
2. Usually the patient is cured after his/her first dose
3. However, a second treatment of ¹³¹I maybe necessary in certain cases
4. The goal is to administer enough ¹³¹I to bring the patient back to a euthyroid state
1. Treatment usually results/causes early or late hypothyroidism
2. Usually the greater the dose, the sooner hypothyroidism will occur
3. Note - It is easier to treat hypothyroidism via the administration of supplement thyroid hormone, than it would be to treat hyperthyroidism with antithyroid medication
3. Treatment of the toxic nodular goiter (autonomous)
1. Treatment with ¹³¹I is idea when considering the following
1. ¹³¹I selectively goes to the hyper-functioning nodule
2. The remainder of the gland is being suppressed by low levels of TSH resulting in little damage to normal thyroid tissue (why is this a true statement)
3. Once treatment is over, the nodule has been radiated normal tissue will then be able to respond to increased levels of TSH, as T3 and T4 concentrations decrease
4. If tracheal compression from an enlarged gland is present then surgical intervention maybe required
5. Antithyroid medication generally does not have any permanent effects on toxic nodule(s)
6. Usually requires as much as 2 to 5 times the ¹³¹I therapy dose when compared with the treatment of Graves' disease
7. Complete disappearance of the nodule is uncommon
8. The result of hypothyroidism following treatment is uncommon, which relates to the undamaged thyroid tissue that was initially suppressed by the toxic nodule(s)

4. Treatment of Graves' disease
1. ¹³¹I treatment results in
1. Damage at the cellular level via beta radiation
2. Specifically at the cell colloid interface by damaging thyroid follicular cell function - essentially affecting the cell's ability to reproduce
3. There is a proportional relationship between the amount of radioiodine administered and the amount of damage that occurs
4. However, it is somewhat difficult to determine exactly how much ¹³¹I is needed to effectively destroy enough thyroid tissue to cause a euthyroid state
5. There are several factors that must be considered when ¹³¹I therapy is done
1. Size of the gland (which can only be estimated)
2. Percent uptake of the gland
6. At issue is that there is no known method of treatment with ¹³¹I that will prevent the patient from becoming hypothyroid
2. Treatment formulas and related material
1. Fixed millicurie dose
1. Just give a fixed amount/dose to all patients
2. Standard ¹³¹I dose is between 3-7 mCi
1. Approximately 60% of patients go into remission in 3-4 months
2. Other patients respond more slowly
3. 10-15% require a second dose
3. Disadvantages
1. Lacks a relationship between the mCi administered and the rad dose to the hyperactive gland
2. When therapy is administered: % uptake and gland size should be considered
3. Radiation dose should relate to the amount of radioactivity delivered per gram of thyroid tissue

2. Delivered uCi/gram formula (see above)
1. Most widely used method
2. Is an attempt to deliver a specific number of :Ci per gram of thyroid tissue
3. Percent uptake and estimation of gland size is required
4. Range of dose is between 55-80 μCi per gram of tissue
5. Should result in a 5000-7000 rads administered to the entire thyroid
6. Higher μCi/gram usually results in an accelerated treatment
7. Larger diffuse goiters (Graves') is thought to be more radio-resistant and may require a higher dose

3. Delivered rad formula (see above)
1. Attempts to deliver a specific amount of radiation to the thyroid
2. Has no apparent advantage to the delivered :Ci/gram formula

4. Delivered rad formula with utilization of effective half-life (see above)
1. This assumes the biological half-life of 24 days with an effective half-life of 6 days
2. Has no apparent advantage of the two other formulas
3. Most important: 5000-7000 rads appears to be key when treating the thyroid
5. Treatment is usually effective within 3 months following the ¹³¹I dose

6. Management of the hyperthyroid patient
1. Before therapy is give and after initial treatment
1. Antithyroid medication should be discontinued prior to radioiodine treatment
2. Antithyroid medication may be re-started as little as 3 days post ¹³¹I, but 1 week is preferred
3. Failure to stop antithyroid medication may void the ¹³¹I ability to treat the disease
2. End result - The issues surrounding hypothyroidism (post therapy treatment)
1. From 23-43% of treated patients become hypothyroid within a year
2. 11,000 Graves' patients treated with ¹³¹I where followed for mean period of 7.5 years
1. 59% percent became euthyroid within a year
2. 35% became hypothyroid
3. 6% had a recurrence of disease
4. Hypothyroidism occurred at a 2-3% per year following treatment
3. 5200 hyperthyroid patients were treated surgically
1. 62% where euthyroid at 12.7 years
2. 25% became hypothyroid
3. 14% had a recurrence of disease
4. Hypothyroidism occurred at a 0.7% per year following treatment
4. This is a high correlation between increasing amounts of ¹³¹I administered and the increased incidence of hypothyroid
5. If hypothyroidism is an outcome that can be expected, then following treatment, patients should be monitored. When hypothyroidism occurs, then supplemental hormone treatment is the course of action
3. Late complications
1. It does not appear to cause leukemia?
1. 18,000 radioiodinated treated patients where followed with 10,000 surgically treated patient for a total of 115,000 years
2. There was no difference between either group having a higher incidence of leukemia
2. It does not appear to cause any type of neoplasm
1. Risk of thyroid cancer seems to insignificant
2. However, x-ray therapy to the head and neck to children does have an increased incidence of thyroid cancer at 7-35 years post treatment
3. While no increased incidence of thyroid cancer has been seen in children that have ¹³¹I therapy treatment, it is not suggested and long term studies still need to be used to evaluated any possible effects on children
4. Regulatory issues
   1. If a patient is to be given special instructions on how to reduce the radiation exposure to other individuals if
      1. Receives more than 7 mCi or
      2. Emits more than 2 mr/hr

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Procedure for Treating Hyperthyroidism - Nodular
Procedure for Treating Hyperthyroidism - Diffuse Goiter

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