**4. Patient preparation for RAI therapy**

A close collaboration between, endocrinology and nuclear medicine, departments is required for the management of patients with thyroid disease who are candidates for RAI therapy. The determination of the activity, as well as the administration of radioiodine are responsibilities of the nuclear medicine physician. According to the EANM guidelines for the treatment of benign thyroid disease prior to any intervention a detailed medical history is needed including previous therapies for hyperthyroidism and especially any potential intake of iodine-containing medication (such as amiodarone and contrast media) or food [21]. The medical history should include medical conditions, surgeries, allergies and medications (especially those who may interfere with radioiodine uptake). Nuclear medicine physician should provide oral and written information about RAI therapy procedure, possible side effects, risk of recurrence and possible retreatment as well as radiation safety precautions post RAI therapy [14, 22] and rule out any possibility of pregnancy prior treatment. It is mandatory for female patients of childbearing age to undergo a pregnancy test 3 days prior to radioiodine administration and provide written signed declaration stating that they are not pregnant. Serum pregnancy test is preferable than urine test as it is more sensitive [23]. If previous hysterectomy has been reported or the patient is in postmenopausal state then the test can be omitted. Patients of both sexes should avoid conception 6 months post RAI therapy. RAI therapy is contraindicated in breastfeeding and it should be administrated 6 weeks to 3 months after lactation is disrupted [21]. To increase radioiodine uptake (RAIU), iodine restriction for 1 to 2 weeks and ATD withdrawal 3–7 days before RAI administration are also recommended.

Serum levels of TSH, FT3, FT4, TPO and TSI should be measured prior RAI therapy. Thyroid volume is assessed by ultrasonography (US) and in cases of a large goiter magnetic resonance imaging (MRI) is performed in order to estimate possible extension in the mediastinum. Computed Tomography (CT) is not preferred as the contrast media impair with the radioiodine uptake. Thyroid scintigraphy with 99mTc pertechnetate (99mTcO4) and radioiodine is also mandatory to provide metabolic information of the organ. Radioactive iodine thyroid uptake (RAIU) at 4-6 h and

24 h post administration must be measured. RAIU increases gradually over 24 h but in some patients it can be increased rapidly reaching maximum values at 4 to 12 h and return to normal after 24 h. In some nuclear medicine departments a fixed dose of radioiodine is used, therefore RAIU calculation is not needed.

For nodules >1–1,5 cm, with suspicious findings in US (hypoechoic nodules solid or cystic with hypoechoic solid component, with irregular shape, calcifications and presence of invasion in adjacent structures) which appear in scintigraphy as "cold' or with a decreased uptake, fine needle aspiration (FNA) biopsy is recommended [24].

Patients with GD may present with ophthalmopathy. An experienced ophthalmologist should estimate the severity of the disease as RAI therapy has been associated with exacerbation of the ophthalmopathy. Corticosteroid therapy should be considered [12]. Studies have shown a possible correlation between Grave's ophthalmopathy (GO) progression post RAI therapy in smokers. Cessation of smoking is recommended. RAI therapy in cases of active moderate-to-severe ophthalmopathy is contraindicated [25].

As transient elevation of thyroid hormones due to actinic thyroiditis may present, ATD therapy should be discontinued approximately one week before and be resumed 3–7 days post RAI therapy [18]. B-adrenergic blockade should be administered in cases of patients who are at a higher risk of complications due to hyperthyroidism.

#### **4.1 Patients' information for RAI therapy**

Patients should be properly and adequately educated concerning the procedures they will undergo, the precautions they should take, the outcomes and possible adverse events of RAI therapy. Fulfilling these needs requires a collaborative approach among patients and health care professionals. Patients should receive both written and verbal information. More modern approaches such as mobile health (mHealth) could also be helpful [26]. Except for the pre- and posttreatment use of thyroid specific medication, risk of recurrent disease and subsequent retreatment(s), early and late side effects, health care professionals should prepare the patients regarding radiation protection initiatives to reduce radiation doses to family members and general population, according to national rules. Unlike thyroid cancer patients, those who receive RAI therapy to treat benign thyroid diseases do not need hospitalization.

RAI capsule is administered on an outpatient basis, in authorized Nuclear Medicine Departments. After RAI administration the patient is advised to avoid eating or drinking anything for 2 h, to allow time for the iodine to be absorbed. After this time patients should eat as normal and drink plenty of fluids.

For a few weeks after the treatment patient's thyroid gland will be radioactive. The amount of radioactivity is gradually decreasing. During this period, which is estimated for each patient individually, they are advised to avoid or restrict to minimum radiation exposure to their environment. Patients are guided to reduce the radiation exposure to other people by limiting the amount of time they spend with them and by keeping more than three meters away from them. They must not share a bed with anyone or sleep within 2 meters of anyone, even if there is a wall between beds. For 1–1 ½ months after RAI treatment, patients should not spend more than a few minutes each day within arm's reach of any children or pregnant women. Of course, they also need to limit close and prolonged contact with any other people, and stay away from crowded places such as cinemas, theaters, public transport as well as their work place, where they may be close to the same person for a prolonged period of time.

#### *RAI Therapy for Graves' Hyperthyroidism DOI: http://dx.doi.org/10.5772/intechopen.96083*

Although, most of the radioactivity is concentrated in thyroid gland, for a few days after RAI treatment, some of the radioiodine is excreted by urine and sweat. Around 90% of administered radioiodine activity is excreted mainly through the kidneys. Thus, patients with renal insufficiency may retain radioiodine activity over a long period, thereby leading to more intense internal exposure to radiation than that observed in normal ones [27]. Drinking plenty of fluids and emptying bladder frequently can help minimize bladder and adjacent tissues' exposure. Patients are advised to take care with personal hygiene in the first few days after treatment. They are instructed to always flush the toilet after use and always wash their hands. They are also guided to use their own towels and face cloth. Their clothes do not need to be washed separately unless they experience any incontinence [28, 29].

### **5. Radiation dosimetry and dose calculation**

The aim of RAI therapy in GD is to cure hyperthyroidism. This is achieved by radiating and therefore destroying thyroid cells. The outcome is the patient to return to an euthyroid state or to become hypothyroid. RAI therapy is very effective, even in cases of possible retreatments, with a cure rate ~ 100%. Individualized dose of radioiodine for rendering a patient euthyroid is not feasible [30]. While several studies have been conducted, regarding the association between the optimal dose of radioiodine, thyroid's volume (based on ultrasound) and radioiodine turnover [31], there is lack of consensus for the proper dose regimen. The majority is in favor of rendering the patient hypothyroid [20] applying high radioiodine doses [32] to avoid the possibility of treatment's failure or relapse of the disease. Many nuclear departments apply fixed doses [33]. For rendering a patient euthyroid a target dose of ~150 Gy is needed. Higher doses (200–300 Gy) are applied for complete ablation.

The following equation recommended by the EANM, is used to estimate the appropriate radioiodine dose:

$$\mathbf{A} \mathbf{[MBq]} = \frac{F}{\ln 2} \times \frac{\mathbf{M} \mathbf{[g]} \times \mathbf{D} \mathbf{[Gy]}}{\int\_{0}^{\circ} \mathbf{R} U(t) dt} \tag{1}$$

A: radioiodine activity, F: conversion factor (between coulombs per kilogram and grays), M: mass of the target volume, D: the target dose.

Radioiodine uptake (RIU) is calculated as follows:

$$\text{RIU} = \frac{\text{Activity in thyroid Grad}}{\text{Administerend activity}} \times 100\% \tag{2}$$

As it has been mentioned above many nuclear medicine departments apply fixed doses, in a range of 200–800 MBq with the commonest applicable doses of 400–600 MBq. Estimation of the thyroid size is needed (based on ultrasound) [21].

#### **6. RAI therapy outcome**

Initially the goal of RAI treatment was to render the patient euthyroid using low doses of I-131. Through the years it has become clear that hypothyroidism is an inevitable and unpredictable progressive outcome of RAI treatment. Nowadays,

hypothyroidism is the desired result of RAI treatment and it has been described by many authors as the elimination of hyperthyroidism [34]. RAI treatment fails when persistent hyperthyroidism occurs. In the majority of the patients thyroid hormones return to normal levels while clinical symptoms are reduced 4–8 weeks post therapy. More than 80% of the patients become hypothyroid 16 weeks post RAI therapy. Hypothyroidism, in rare cases can be transient and the patient may return to a euthyroid state or remainhyperthyroid. The latter is often associated with no decrease of thyroid size [12]. The desired outcome of RAI treatment is dependent on multivariable factors such as thyroid size, dose regimens, compensation of hyperthyroidism, iodine intake (diet or iodine containing medicine) and the timing of the withdrawal of ATDs.

When low dose regimes are preferred, then the possibilities of treatment failure increase and ATD continuance and/or RAI retreatment are needed. Unfortunately, the field of RAI dose regimen still remains vast and things become more complicated when a fixed dose is compared to an individualized one. Many authors suggest that a calculated dose of radioiodine has no advantage over a fixed dose, while others recommend individual dose showing correlation between the success of therapy and the radiation dose actually absorbed by the thyroid [35]. Other factors that influence treatment outcome have been studied as well. In their retrospective cohort study, Aung et al. found that RAI treatment failure was more frequent in patients with high levels, of thyroid hormone or TRABs and in those who received ATD after RAI treatment. There were no correlation found among RAI treatment failure and other parameters such as age, sex or smoking. Moreover approximately 7% of the patients developed GO and 13.3% of them required surgery. There seemed to be a correlation between high thyroid hormone levels and orbitopathy whereas high TRAB levels had no effect in the development of orbitopathy [36].

Despite more than 75 years' experience with RAI treatment of GD, it is not always feasible to predict the efficacy of the treatment or the factors that will eventually affect it. The "GREAT" score, a predictive model consisting of clinical and biochemical variables has been introduced as a clinical tool that predicts the success of antithyroid drug therapy for Graves' Disease. Calculation of the GREAT 6-point score is as follows: age (<40 or ≥ 40 years: 1 or 0 point, respectively), goiter (not visible to slightly visible or clearly visible: 0 or 2 points), FT4 (<3.1 or ≥ 3.1 ng/dl: 0 or 1 point), and TBII (<6; 6–19.9; >19.9 U/L: 0, 1, or 2 points) resulting in the GREAT score classes of I (0–1 point), II (2–3 points), and III (4–6 points). Higher recurrence rate at the end of follow up is observed in GREAT score class III when compared with class II or class I (16.4%) [37]. However, GREAT score has been suggested for predicting outcome before the start of ATD and to our knowledge there has not been developed yet a clinical tool that can estimate RAI results.

#### **7. Follow-up**

Regular review of thyroid function tests in patients who have undergone radioiodine treatment for thyroid disease is essential to assess the efficacy of the treatment and for timely detection of developing hypothyroidism or post treatment immunogenic hyperthyroidism. The first review of thyroid function post RAI therapy should be conducted 1–2 months later by assessing TSH, FT4 and total FT3 values and be repeated every 4–6 weeks for the first 6 months or until the patient becomes hypothyroid and is stable on LT4 treatment [13]. In patients at high risk for endocrine ophthalmopathy or who have received ATD, follow up is recommended at shorter intervals. In cases of RAI treatment for overt hyperthyroidism,

ATD should be initiated 3–5 days post RAI treatment. If RAI retreatment is deemed necessary, it can be conducted 6–12 months later. RAI retreatment is not necessary in cases of post therapy immunogenic hyperthyroidism; ATD administration for a few months is adequate. As it is mentioned above a lifelong testing of thyroid function is necessary, even in patients who have returned to an euthyroid state post RAI treatment.
