# Thyroid Scintigraphy and Radioactive Iodine Therapy

## Introduction

Thyroid scintigraphy is a cornerstone of nuclear medicine that leverages the thyroid gland's unique ability to **trap and organify iodine**. It plays a critical role in evaluating thyroid nodules, characterizing hyperthyroidism, and guiding radioactive iodine (RAI) therapy.

## Radiopharmaceuticals

### Technetium-99m Pertechnetate

Technetium-99m pertechnetate is **trapped but not organified** by thyroid follicular cells. It has a half-life of 6 hours and a gamma energy of 140 keV. Its advantages include low cost, rapid imaging (20 minutes post-injection), and a lower radiation dose. However, it cannot differentiate between true thyroid tissue and other trapping tissues, and it may produce **discordant nodules** that appear hot on pertechnetate but cold on iodine scans.

### Iodine-123 (I-123)

I-123 is **trapped and organified** by thyroid follicular cells, making it a physiologic tracer. It has a half-life of 13.2 hours and a gamma energy of 159 keV. It is preferred for diagnostic thyroid imaging and uptake calculations. Imaging is performed at **4-6 hours and/or 24 hours** post-administration. It offers better specificity than pertechnetate for characterizing nodules.

### Iodine-131 (I-131)

I-131 has a half-life of 8.02 days and emits beta particles (therapeutic) plus a 364 keV gamma ray (for imaging). It is used primarily for **therapy**, including thyroid ablation and thyroid cancer treatment, and for post-therapy whole-body scans. Its higher radiation dose limits diagnostic use. The **stunning effect** is an important consideration: diagnostic doses of I-131 may reduce subsequent therapeutic uptake.

## Thyroid Uptake and Scan Interpretation

### Normal Scan

A normal scan shows homogeneous tracer distribution throughout both thyroid lobes. **Normal I-123 uptake** is 10-30% at 24 hours, though this varies by institution and dietary iodine intake. The pyramidal lobe may be visualized as a normal variant.

### Patterns of Hyperthyroidism

| Condition | Uptake Pattern | 24-hr Uptake | Key Feature |
|-----------|---------------|-------------|-------------|
| Graves disease | Diffusely increased, homogeneous | >35% | Enlarged gland, TSI positive |
| Toxic multinodular goiter | Heterogeneous, multiple hot/cold nodules | Increased | Multiple nodules |
| Toxic adenoma | Single hot focus, suppressed background | Variable | Autonomous nodule |
| Subacute thyroiditis | Diffusely decreased | <5% | Thyrotoxicosis without hyperthyroidism |
| Factitious thyrotoxicosis | Very low | <1% | Exogenous hormone use |

**Graves disease** produces diffusely increased uptake (often greater than 35% at 24 hours) with homogeneous or mildly heterogeneous distribution in an often enlarged gland. **Toxic multinodular goiter** shows heterogeneous uptake with multiple hot and cold nodules and overall increased uptake. A **toxic adenoma** appears as a single focus of markedly increased uptake with **suppression of the remaining gland**. **Subacute thyroiditis (de Quervain)** is characterized by diffusely **decreased uptake** (less than 5%) despite elevated thyroid hormone levels, representing thyrotoxicosis without true hyperthyroidism. **Factitious thyrotoxicosis** shows very low uptake due to exogenous thyroid hormone administration.

### Nodule Characterization

A **hot (hyperfunctioning) nodule** shows increased uptake relative to surrounding tissue and carries a very low malignancy risk (less than 1%). A **warm nodule** has uptake similar to the surrounding tissue with low risk. A **cold (hypofunctioning) nodule** shows decreased or absent uptake and carries an approximately **5-15% malignancy risk**, requiring further evaluation with ultrasound and possible FNA biopsy. Scintigraphy is recommended for nodules with **low TSH** to identify autonomously functioning nodules.

## Radioactive Iodine Therapy

### Indications

RAI therapy is used for **Graves disease** refractory to or not suitable for antithyroid medications, for **toxic multinodular goiter** and **toxic adenoma**, and for **differentiated thyroid cancer** (papillary and follicular) post-thyroidectomy for remnant ablation and treatment of metastatic disease.

### Pre-Therapy Preparation for Thyroid Cancer

**TSH stimulation** is required to maximize iodine uptake, achieved either through thyroid hormone withdrawal for 3-4 weeks (targeting TSH greater than 30 mIU/L) or through **recombinant human TSH (Thyrogen)** injections. A **low-iodine diet** for 1-2 weeks prior to therapy depletes iodine stores. Serum **thyroglobulin** is checked as a tumor marker, and a negative **pregnancy test** must be confirmed in women of childbearing age.

### Therapy Administration

Typical doses for Graves disease are **10-15 mCi I-131**. Remnant ablation after thyroidectomy for thyroid cancer uses **30-100 mCi I-131**, while treatment of known metastatic disease requires **100-200 mCi I-131**. A post-therapy whole-body scan is obtained at **5-7 days** to identify functioning metastases.

### Radiation Safety Considerations

Patients receiving more than 33 mCi must follow **radiation safety precautions**, including maintaining distance from others, sleeping alone, and limiting time with children and pregnant women. Release criteria are based on measured dose rate or administered activity per NRC guidelines. Common side effects include **sialadenitis** (which sour candy and hydration can reduce), transient neck pain, and nausea. Rare complications include bone marrow suppression with cumulative doses and pulmonary fibrosis with diffuse lung metastases.

## Thyroglobulin and Follow-Up

**Thyroglobulin (Tg)** is the primary tumor marker for differentiated thyroid cancer. Detectable Tg after total thyroidectomy and ablation suggests **residual or recurrent disease**. **Anti-thyroglobulin antibodies** can cause falsely low Tg levels and must be monitored. Diagnostic I-123 or I-131 whole-body scans are used for surveillance. **FDG PET/CT** is valuable when Tg is rising but the radioiodine scan is negative, suggesting dedifferentiated disease.

## Clinical Pearls

A **hot nodule** on thyroid scintigraphy has a very low malignancy risk and generally does not require FNA biopsy. Low thyroid uptake in the setting of thyrotoxicosis suggests **thyroiditis or exogenous hormone use**, not Graves disease. The **stunning effect** of diagnostic I-131 can reduce therapeutic efficacy, which is why I-123 is preferred for diagnostic scans. Rising thyroglobulin with a negative radioiodine scan suggests **dedifferentiated disease** and warrants FDG PET/CT.

## References

1. Thyroid Scintigraphy: Current Concepts and Practice. *Radiographics*. 2018;38(7):2079-2098.
2. Haugen BR, et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer. *Thyroid*. 2016;26(1):1-133.
3. Radioactive Iodine Therapy for Differentiated Thyroid Cancer. *J Nucl Med*. 2019;60(10):1358-1367.
4. Silberstein EB, et al. SNM Practice Guideline for Therapy of Thyroid Disease with I-131. *J Nucl Med Technol*. 2012;40(4):287-293.