Thyrotoxicosis: Diagnostic and Therapeutic Uses of Radioactive Iodine

​When general practitioners are presented with thyrotoxicosis in their practice, radioactive iodine can be a useful adjunct for imaging to aid in its diagnostic management, as well as for treatment. Singapore General Hospital shares more about the indications for referral and shared care with GPs post-treatment.

INTRODUCTION TO THYROTOXICOSIS

Thyroid diseases encompass a wide variety of problems seen at the primary healthcare setting, and experts estimate that up to 5 to 10 percent of the population suffer from a thyroid disorder. In particular, patients with thyrotoxicosis are commonly presented to the general practitioner (GP).

Causes of thyrotoxicosis

The causes of thyrotoxicosis may include:

• Graves’ disease
• Toxic adenomas
• Toxic multinodular goitre (+/- compressive symptoms)
• Thyroiditis
• Factitious hyperthyroidism

The goals of managing thyrotoxicosis would be to determine the aetiology as appropriate management depends on the underlying mechanism.

The most common cause of endogenous thyrotoxicosis (hyperthyroidism) would be Graves’ disease, also known as diffuse toxic goitre. Graves’ disease is an autoimmune condition affecting the thyroid that usually occurs in young to mid-adulthood, and in women more than men.

Up to 30% of patients with Graves’ disease suffer from Graves’ ophthalmopathy, and smokers are more prone to thyroid eye disease.

WHAT IS RADIOACTIVE IODINE (RAI)?

Iodine is a chemical element, and this trace mineral is found naturally in the environment and many foods. Its clinical significance lies in the fact that the body uses iodine to make thyroid hormones which control metabolism.

There are many radioisotopes of iodine, of which I-123 and I-131 are important for imaging and therapeutics respectively.

RAI IMAGING OF THE THYROID

How it works

Thyroid imaging and treatment capitalise on the process of hormone synthesis in the glands. This is dependent on the sodium-iodide symporter (NIS). Via the NIS, RAI gets trapped intracellularly. Radioiodine is then organified to form thyroid hormones (T3 and T4).

The images in Figure 1 show common causes of hyperthyroidism and their appearances.

Its role in thyrotoxicosis management

The role of thyroid nuclear imaging referred from the primary care setting will mainly be to relate the general structure of the gland to function. This will be particularly useful in differentiating the causes of thyrotoxicosis such as Graves’ disease from toxic nodular goitre or thyroiditis.

In Singapore, almost all healthcare institutions will usually use a different radiotracer, Tc-99m pertechnetate, as an imaging substitute for RAI thyroid scintigraphy as it is more easily accessible and has a shorter radiation half-life.

At Singapore General Hospital (SGH), our team will routinely pair thyroid nuclear imaging with a correlative ultrasound as an adjunct, and also for anatomical correlation.

WHO SHOULD BE REFERRED FOR RAI THERAPY OF THE THYROID

Indications for RAI therapy of hyperthyroidism

due to Graves’ disease, toxic multinodular goitre or adenoma

• Refractory to medical therapy
• Relapsed cases previously on medical therapy
• Allergy to antithyroid drugs
• Unsuitable for surgery

RAI is the most commonly used hyperthyroid treatment in the United States.

Contraindications to using RAI for therapy

• Hypersensitivity reaction to iodine
• Pregnancy or planning a pregnancy within 4 to 6 months
• Breastfeeding (patient will have to give up breastfeeding for that infant if RAI is given)
• Uncontrolled hyperthyroidism with FT4 > 30 (relative contraindication – will need better control before elective RAI therapy)
• Severe Graves’ ophthalmopathy

Do consider providing opportunistic smoking cessation advice to any patients referred for RAI therapy.

POSSIBLE SIDE EFFECTS AND COMPLICATIONS OF RAI THERAPY

• Nausea
• Metallic taste in mouth
• Salivary gland swelling and discomfort
• Transient discomfort of thyroid gland +/- rise in thyroid hormone levels
• Thyroid storm (rare)
• Aggravation of pre-existing Graves’ ophthalmopathy (rare)

On occasion, we may refer some patients for an ophthalmology assessment prior to RAI therapy should it be required.

Patients have to be counselled that they may develop hypothyroidism after RAI thyroid ablation necessitating lifelong thyroxine replacement, but this is the intended aim rather than a side effect.

EFFICACY OF RAI THERAPY

Treatment with RAI is efficacious and the majority of individuals have a successful clinical outcome, with most patients rendered hypothyroid within a few months after first-time RAI therapy.

A larger goiter size and thyroid stimulating hormone receptor antibody (TRAb) positivity at RAI may predict failure of first-time RAI therapy necessitating a second treatment.

Patients are discharged back to their primary care provider once they are hypothyroid and started on thyroxine replacement.

PREPARING FOR RAI THERAPY IN SGH

Patient preparation

After clinical consultation, our team of doctors and nurses will provide comprehensive counselling for RAI dose preparation with regard to medications and low iodine dietary advice.

Patients will be provided with a detailed pamphlet to help allay patient concerns regarding radiation exposure. They will also be given a set of instructions for what to do and what to avoid regarding radiation exposure to family and members of the public post-treatment as an outpatient.

No hospitalisation is needed with the low levels of RAI activity prescribed for hyperthyroidism.

RAI preparation

The RAI capsule or liquid is ordered by the laboratory and will require a three-week lead time (usually sourced from Europe). Upon its arrival, over the weekend, the relevant quality control and dose activity checks will be performed. It will then be placed securely in a lead-shielded area ready for outpatient administration on a weekday afternoon (Figure 3).

CONCLUSION

RAI is a useful adjunct for imaging to aid in the diagnostic management of patients presenting to the GP with thyrotoxicosis. In addition, RAI is one of the mainstays of treatment for hyperthyroidism with the preferred clinical outcome of lifelong thyroxine replacement rather than prolonged treatment with anti-thyroidal drugs.

After successful treatment with RAI, patients will be discharged back to their primary healthcare provider for further titration of thyroxine and long-term follow-up.

GPs can call the SGH Department of Nuclear Medicine and Molecular Imaging for appointments at 6321 4203 or 6321 3838.

REFERENCE

1. Tay WL, Chng CL, Tien CS, Loke KS, Lam WW, Fook-Chong SM, Tong AK. High Thyroid Stimulating Receptor Antibody Titre and Large Goitre Size at First-Time Radioactive Iodine Treatment are Associated with Treatment Failure in Graves’ Disease. Ann Acad Med Singap. 2019 Jun;48(6):181-187.

Dr Aaron Tong is a Senior Consultant and Director of Nuclear Medicine Operations at the Department of Nuclear Medicine and Molecular Imaging, Singapore General Hospital. He is also a Visiting Consultant and Clinical Governance Officer (Nuclear Medicine) at the Department of Radiology, Sengkang General Hospital. He received his specialist accreditation in nuclear medicine in 2015 and serves as the current Chairman in the Chapter of Nuclear Medicine Physicians, Academy of Medicine Singapore. He has a keen interest and takes an active role in various research and educational activities.

Dr Tham Wei Ying is a Consultant Nuclear Medicine Physician at Singapore General Hospital. She completed her nuclear medicine senior residency at SingHealth in 2018 and has been with the Department of Nuclear Medicine and Molecular Imaging since. She maintains a broad interest in both diagnostic and therapeutic nuclear medicine scans and procedures. She is also actively involved in education and is a core faculty member of the nuclear medicine senior residency programme.

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