Patients with papillary or follicular thyroid cancer (differentiated thyroid cancer) who had a total thyroidectomy. Appropriate in patients with tumor size more than 2 cm and has one or more risk factors, including obvious extrathyroidal extension, patients more than 45 years of age, lymph node metastases, and distant metastases. RAI therapy is recommended if the tumor is less than 2 cm and there are distant metastases.

MOA

Iodine is a natural precursor for thyroid hormones triiodothyronine (T3) and thyroxine (T4) and is uptaken from the blood into the thyroid follicular cell by the sodium and iodide transporter. Iodine-131 (I-131) exerts its effects once it is taken up by the follicular cells of the thyroid, emitting beta rays that further cause definitive local damage to the thyroid tissue. 

Since iodine is absorbed from the gastrointestinal tract and dispersed in the extracellular fluid, most of the absorbed iodine gets concentrated in the thyroid cells with functioning NIS. The thyroid follicular cells absorb iodine through the NIS.This lead to the ability of the well-differentiated thyroid cancer cells to absorb iodine through the sodium-iodide symporter makes RAI an effective treatment for them. If the cancer cells become undifferentiated, they lose the NIS expression, hence cannot take up RAI and do not respond to RAI treatment.

In patients with a low risk for recurrence, a dose of around 30 mCi can attain adequate ablation. In moderate and high-risk patients, the administered dose has to be escalated accordingly to a maximum of around 250 mCi.

Route of administration

Oral pill (common) or liquid or IV injection

Duration of action- Parameter to stop??
Only one treatment is needed.

Side effects of radioactive iodine treatment are uncommon, but can include:

The treatment does not affect fertility in women. Fertility can be reduced in men after treatment, but it should improve over time.

Why RAI given after surgery?

A course of RAI treatment is often recommended after 6 to 8 weeks of total thyroidectomy. This will help destroy any remaining thyroid cancer cell that is not removed by surgery or treat some types of thyroid cancer that have spread to lymph nodes and other parts of the body. This reduces the risk of the cancer coming back.

Pertinent physical findings suggesting possible malignancy include:

 

ii. Thyroglobulin 

increased thyroglobulin levels are found in the following conditions:

- Most commonly used, safe, painless, cost-effective.

- Depict internal structure of thyroid gland and its pathology. 

- Assess the comparative size of nodules, lymph nodes or goiters in patients.

- Identify the solid component of complex nodule.

- Guide and facilitate fine needle aspiration biopsy of nodule

However, it does not reliably differentiate benign lesions and cancer.

-        Altered protein and cell turnover rate leads to muscle atrophy

-        Increased lysosomal enzyme activity (cathepsin B and D) caused by thyroid hormone

·        cancer is found in the thyroid and the tumor is 4 centimeters or smaller; cancer has spread to nearby lymph nodes; or

·        cancer is found in the thyroid, the tumor is larger than 4 centimeters, and cancer may have spread to nearby lymph nodes; or

·        the tumor is any size and cancer has spread from the thyroid to nearby muscles in the neck and may have spread to nearby lymph nodes.

Increase of size of thyroid gland compresses the surrounding structure

-        Permanent hypothyroidism (RAI ‘destroys’ thyroid gland, minimising production of thyroid hormone)

-        Doesn’t affect other hormone as only thyroid gland uptake RAI

-        Well-differentiated thyroid cancer (papillary and follicular): Dosage is highly individualized as the degree of TSH suppression is initially based on the risk of disease recurrence using a staging system such as the American Thyroid Association (ATA) risk-of-recurrence stratification system . Long-term TSH suppression goals should account for response to therapy, risk of recurrent disease, age, and comorbid conditions .

-        Oral: Initial: 1.6 to 2 mcg/kg/day immediately postsurgery ; adjust dose as needed in 6 weeks based on TSH suppression goals :

-        Note: For patients with ATA low- and intermediate-risk disease whose initial surgery was a lobectomy, some experts initiate therapy at a later time when TSH concentrations or disease status dictate a need .

 

No drug for management of SE. Only symptomatic relief/treatment

 

-        Neck tenderness and swelling

-        Nausea and vomiting

-        Swelling and tenderness of the salivary glands

-        Dry mouth

-        Taste changes

Chewing gum or sucking on hard candy may help with salivary gland problems.

Sialagogue (agent that can increase saliva production) might help in managing dry mouth and taste change

Radioiodine treatment also reduces tear formation in some people, leading to dry eyes. If you wear contact lenses, ask your doctor how long you should keep them out.

Men who receive large total doses of radiation because of many treatments with RAI may have lower sperm counts or, rarely, become infertile. Radioactive iodine may also affect a woman’s ovaries, and some women may have irregular periods for up to a year after treatment. Many doctors recommend that women avoid becoming pregnant for 6 months to a year after treatment. No ill effects have been noted in the children born to parents who received radioactive iodine in the past.

People who have had RAI therapy may have a slightly increased risk of developing leukemia, stomach cancer, and salivary gland cancer in the future. Doctors disagree on exactly how much this risk is increased, but most of the largest studies have found that this is an extremely rare complication.

-       In the MAPK pathway, we have the RET gene

-       There will be chromosomal abnormalities (translocation/inversion)

-       If there is a point mutation ret goes towards the medullary carcinoma if there is translocation inversion of the chromosomes it goes towards the papillary carcinoma

-       2^nd gene which is mutated very frequently in papillary carcinoma is the BRAF gene

-       Pathogenesis due to the gain of function mutations involving the genes encoding the RET or BRAF 

-       RET GENE located on chromosome 10q11 (there is inversion and translocation)

-       This rearrangement will lead to production of a gene which will lead to increase in tyrosine kinase activity. 

-       BRAF gene gain of function mutation in this gene, most commonly a valine to glutamate change in codon 600 (brafv600e)

Risk Factors

History of radiation exposure (Ionizing radiation)

Childhood exposure (Low-dose radiation therapy to head and neck for benign diseases) 

Environmental exposure (Chernobyl) 

Genetics (Family Hx)

Female predominant with a F:M ratio of 3:1

Estrogen considered to be a potential risk factor for papillary thyroid cancer, this justifies the sex difference in the prevalence of thyroid nodules and thyroid cancer (https://pubmed.ncbi.nlm.nih.gov/25052473/) 

Commonly occurs around >50 yo (Median age)

White > Blacks

Signs and Symptoms

Presents as painless thyroid nodules

Mass in neck or cervical node

Cold nodules

Hoarseness and dysphagia (20%)

Complication

Extra thyroidal extension

Local or regional recurrences

Distant metastases

Levothyroxine 

Iodine restricted diet is recommended for 10 to 14 days prior.

Patient need to receive levothyroxine if total thyroidectomy is done. 

Used to keep TSH low or normal

Between treatments, suppressive doses of levothyroxine are given to maintain serum TSH levels <0.1 lIU/ml (unless there are specific contraindications)