9.1 Thyroid & Parathyroid Imaging & Uptake

The endocrine system, specifically the thyroid and parathyroid glands, has been the cornerstone of nuclear medicine since its inception. Endocrine imaging relies on the unique physiological properties of these glands to trap and organify specific radiopharmaceuticals, allowing for both precise functional assessment and targeted therapeutic interventions. For the ARRT Nuclear Medicine exam, mastering the nuances of radiopharmaceutical selection, uptake mathematics, and pathological imaging patterns is critical.

Thyroid Radiopharmaceuticals

Three primary radiopharmaceuticals are utilized for thyroid evaluation, each with distinct physical properties and clinical indications.

Iodine-123 (I-123) Sodium Iodide

I-123 is considered the ideal radiopharmaceutical for routine thyroid imaging and uptake studies. It decays by electron capture with a physical half-life of 13.2 hours and emits a 159 keV gamma ray, which is perfectly suited for gamma camera imaging. Because it does not emit beta particles, the radiation dose to the patient's thyroid is remarkably low compared to I-131. The standard administered dose for an adult uptake and scan is between 100 and 300 μCi (microcuries), given orally as a capsule or liquid. I-123 is both trapped and organified by the thyroid gland, providing a true representation of iodine metabolism.

Iodine-131 (I-131) Sodium Iodide

I-131 decays by beta emission and gamma emission (principal gamma at 364 keV) with a physical half-life of 8.04 days. The beta particles deliver a high local radiation dose, making I-131 the agent of choice for therapeutic ablation of hyperthyroidism and thyroid carcinoma, as well as for whole-body imaging to detect metastatic well-differentiated thyroid cancer. However, its high radiation dose and high-energy gamma emissions (which require high-energy collimators and degrade image resolution) make it unsuitable for routine diagnostic imaging. When used for whole-body scanning, typical doses range from 1 to 5 mCi.

Technetium-99m (Tc-99m) Pertechnetate

Tc-99m pertechnetate is an analog of iodine. It is trapped by the sodium-iodide symporter in the thyroid follicular cells but is not organified (not incorporated into thyroid hormone). It has a physical half-life of 6.02 hours and a 140 keV gamma emission. Administered intravenously (typically 2-10 mCi), imaging can commence just 15-20 minutes post-injection. This makes it ideal for patients who cannot swallow pills, those recently exposed to iodine-containing contrast, or when a rapid study is required. However, because it is only trapped, it cannot be used for true uptake calculations, and rarely, a nodule that appears 'hot' on a pertechnetate scan may actually be 'cold' on an iodine scan (discordant nodule).

Thyroid Uptake Calculation

The radioactive iodine uptake (RAIU) test measures the percentage of an administered dose of radioactive iodine that is accumulated by the thyroid gland over a specific time, usually 6 and 24 hours. This requires a standard (a dose identical to the one given to the patient, or a calculated fraction) and a non-imaging probe (thyroid uptake system).

The Mathematical Formula

The calculation for thyroid uptake must account for background radiation and the decay of the radiopharmaceutical. The standard formula is:

% Uptake = [ (Thyroid cpm - Patient Background cpm) / (Standard cpm - Room Background cpm) ] × 100

• Thyroid cpm (counts per minute): Counts obtained by placing the probe directly over the patient's neck.
• Patient Background cpm (Thigh cpm): Counts obtained over the patient's distal thigh. This represents circulating radiotracer in the blood pool that has not been taken up by the thyroid.
• Standard cpm: Counts from the standard capsule placed in a neck phantom (to simulate tissue attenuation).
• Room Background cpm: Counts obtained from the room without the patient or standard, representing ambient radiation.

Note: If the standard and patient are counted at the same time post-administration, physical decay cancels out in the equation. If the standard is counted at time zero and the patient at 24 hours, a decay factor must be applied to the standard counts.

Normal and Abnormal Values

• Normal Range: The normal 24-hour RAIU typically ranges from 10% to 30%. The 6-hour uptake normally ranges from 5% to 15%.
• Hyperthyroidism: Values significantly above 30% indicate a hyperthyroid state (e.g., Graves' disease, toxic multinodular goiter).
• Hypothyroidism: Values below 10% may indicate hypothyroidism, thyroiditis, or iodine interference (e.g., recent CT with IV contrast, amiodarone, or excessive dietary iodine).

Clinical Pathologies and Imaging Patterns

Nodule Characterization

Thyroid nodules are common, and nuclear imaging plays a pivotal role in determining their functional status, which directly correlates with malignancy risk.

• Cold Nodule: A region of decreased or absent radiotracer uptake compared to normal thyroid tissue. This indicates non-functioning tissue. While most cold nodules are benign (e.g., cysts, adenomas, focal thyroiditis), approximately 15% to 20% are malignant. A cold nodule requires further evaluation, typically with fine-needle aspiration (FNA) ultrasound-guided biopsy.
• Hot Nodule: A region of intensely increased radiotracer uptake, often suppressing the rest of the gland. This represents an autonomously functioning adenoma (toxic nodule). Hot nodules are rarely malignant (less than 1% risk). They often cause hyperthyroidism and are treated with radioactive iodine or surgery.

Graves' Disease vs. Hashimoto's Thyroiditis

• Graves' Disease: An autoimmune disorder characterized by thyroid-stimulating immunoglobulins that mimic TSH, driving the gland to overproduce thyroid hormone. On a scan, Graves' disease presents as a diffusely enlarged gland (thyromegaly) with homogeneously increased radiotracer uptake. The 24-hour uptake is characteristically elevated, often exceeding 50-80%.
• Hashimoto's Thyroiditis: An autoimmune destruction of the thyroid gland, the most common cause of hypothyroidism in iodine-sufficient areas. While the 24-hour uptake may be normal, low, or even transiently elevated early in the disease, the imaging pattern is typically patchy, heterogeneous, and irregular, reflecting areas of glandular destruction intermixed with regenerating tissue.

Parathyroid Imaging

The parathyroid glands, typically four in number, are located on the posterior aspect of the thyroid gland and secrete parathyroid hormone (PTH) to regulate serum calcium. Hyperparathyroidism is most commonly caused by a single benign parathyroid adenoma. Localization of this adenoma prior to minimally invasive parathyroidectomy is a frequent indication for nuclear imaging.

Dual-Phase Single-Tracer Technique (Tc-99m Sestamibi)

Tc-99m sestamibi (Cardiolite), originally designed for myocardial perfusion, is sequestered by mitochondria. It is taken up by both normal thyroid tissue and parathyroid adenomas (which are rich in mitochondria).

• Early Phase (15-30 minutes): Images show uptake in both the thyroid gland and the parathyroid adenoma.
• Delayed Phase (2-3 hours): Tc-99m sestamibi washes out of normal thyroid tissue relatively quickly but is retained in the abnormal parathyroid adenoma. A focal area of retained activity on the delayed images is highly indicative of an adenoma.

Dual-Tracer Subtraction Technique

Some adenomas wash out rapidly, leading to false negatives on dual-phase imaging. The dual-tracer technique provides a functional subtraction.

• Tracer 1 (Thyroid Only): I-123 sodium iodide or Tc-99m pertechnetate is administered. These agents are taken up exclusively by the thyroid tissue, not the parathyroids.
• Tracer 2 (Thyroid + Parathyroid): Tc-99m sestamibi is administered, taken up by both glands.
• Subtraction: Using computer software, the "thyroid only" image is digitally subtracted from the "thyroid + parathyroid" image. Any remaining activity highlights the parathyroid adenoma. This technique is highly sensitive, particularly for ectopic adenomas hidden in the mediastinum or behind the thyroid.

Understanding these nuanced protocols, the physiological basis of radiotracer uptake, and the mathematical principles of quantification is essential for success on the ARRT examination and in clinical practice.