Thyroid Cancer

Thyroid cancer was the eighth most common cancer in Hong Kong. In 2021, there were 1,140 new cases of thyroid cancer, accounting for 3.0% of all new cancer cases in Hong Kong, with 221 being males and 919 being females. Women have a much higher chance of getting the cancer than man, and the female to male ratio was about 5 to 1. The crude annual incidence rate of cancer per 100,000 Hong Kong population was 15.4.

Thyroid cancer is usually diagnosed at an early stage. With the advancement of treatments, they are highly curable, which causes its mortality rate to be relatively low in Hong Kong. However, as the cancer develops slowly, there is still chance of recurrence several years after the initial treatment. Therefore, regular follow-up is recommended.

What is thyroid cancer?

The thyroid is a gland in front of the neck beneath the voice box which shapes like a butterfly. It is an endocrine tissue which is responsible for the production of thyroxine.  Thyroxine is needed to keep the body functioning, which affects blood sugar level, heartbeat and kidney function. Situated behind the thyroid gland are parathyroid glands which secrete parathyroid hormone. Parathyroid hormone helps regulate calcium level in the body. 

Thyroid cancer is that cancer cells grow abnormally in the thyroid gland and it may spread to the regional lymph nodes or other sites, e.g. lung and bone.

The exact cause of thyroid cancer in most patients is unknown. The following are risk factors that can increase the chance of developing thyroid cancer:

• Exposure to high level of radiation: This may be due to radiotherapy given in childhood or exposure to high level of radiation in the environment, e.g. radiation leak from nuclear plant.
• Hereditary conditions: Familial medullary thyroid cancer, multiple endocrine neoplasia and familial adenomatous polyposis may increase the risk of thyroid cancer.
• Personal history: When you have history of goitre and benign thyroid nodules, you may have a higher chance of thyroid cancer. 
• Sex: Females are more prevalent.
• Diet: Lack of iodine in the diet may have a higher chance of thyroid cancer. 
• Age: Many patients with thyroid cancer are over 40 years old.

Commonly seen symptoms of thyroid cancer include:

• A painless lump in the neck with gradual increase in size.
• Persistent hoarseness
• Neck or throat pain, sometimes ear pain as well
• Difficulty in swallowing or breathing if the tumor abuts or causes compression on the esophagus or treachea
• Persistent coughing no symptoms of infection
• Swollen neck glands

Sometimes, thyroid cancer patients may not experience any of the symptoms. It can be found intentionally during physical examination by a doctor or during routine check up on imagings, e.g. CT or ultrasound scans.

The following may be used to diagnose thyroid cancer:

Ultrasound thyroid scan

• An ultrasound scan shows any nodules or masses in the thyroid gland. It can also scan for any lymph nodes involvement. The characteristics of the thyroid nodule, solid or cystic, can be seen clearly on ultrasound.

Biopsy

• If abnormal features are found in the thyroid gland or lymph nodes on ultrasound, a biopsy will be performed to get the definitive diagnosis.
• Biopsy can be done by fine needle aspiration or surgical biopsy:
  • Fine needle aspiration
    • Using a small needle, a sample of cells is taken out of a thyroid nodule and is examined under a microscope to check if cancer cells are present. The doctor may use an ultrasound scan to guide the position of needle.
  • Surgical biopsy
    • If a diagnosis cannot be made by fine-needle aspiration, the doctor will make a small cut close to thyroid and extract a sample of tissue. The tissue will be examined under microscopy to check for any cancer cells. 
    • If you are on anticoagulant or antiplatelet medications, you may need to stop or adjust the dose before biopsy.

Blood tests

• Several blood tests can help diagnosis and monitoring the patient’s condition during and after treatment. 
  • Thyroid-stimulating Hormone (TSH), Thyroxine (fT4)
    • TSH and fT4 are measured to check how well the thyroid is working. If you have total thyroidectomy, TSH and fT4 are used to check if you have any overdose or underdose of thyroxine replacement 
  • Thyroglobulin (Tg) and Thyroglobulin Antibody 
    • Thyroglobulin (Tg) is a protein made naturally by the thyroid as well as by differentiated thyroid cancer. In patients with differentiated thyroid cancer, Tg can be used to monitor for any recurrence. After total thyroidectomy, Tg should be low as surgery has removed all thyroid cells. If Tg is rising after surgery and/or radioactive iodine, it may be a sign of more cancer.  
    • Thyroglobulin antibodies (TgAb) are usually checked together with Tg. Thyroglobulin antibodies are proteins that attack Tg, interfering the results of Tg level. 
  • Calcitonin 
    • A tumor marker for medullary thyroid carcinoma
  • Carcinoembryonic antigen (CEA)
    • A tumor marker for medullary thyroid carcinoma

After diagnosis, further tests will be done:

• CT scan/ PET-CT scan: 
  • To screen for any metastasis to other parts of the body

Thyroid cancer can be classified into 4 types:

• Papillary thyroid cancer
  • The most common type of thyroid cancer
  • Often occurs in young females
  • Generally found in just one lobe, with 10-20% of cases appearing in both lobes
• Follicular thyroid cancer
  • The second most common type of thyroid cancer
  • Occurs mostly in older people
  • Papillary thyroid cancer and follicular cancer are grouped as differentiated thyroid cancer, making up around 95% of all thyroid cancer cases.
• Medullary thyroid cancer (MTC)
  • Accounts for 3% of thyroid cancer cases
  • Sometimes the result of a genetic syndrome called MEN2 (Multiple Endocrine Neoplasia Type 2)
    • 25% of MTC is familial: MEN2 can potentially be inherited
    • The RET proto-oncogene test can confirm if MTC runs in a patient’s family
• Anaplastic thyroid cancer
  • A rare type but very aggressive type
  • Usually occurs in people aged above 60
  • Grows quickly and is difficult to cure
  • May be transformed by improperly treated papillary thyroid cancer 

Apart from the above types, non-Hodgkin lymphoma can rarely occur in thyroid.

Staging for differentiated thyroid cancer depends on the age of the person when diagnosed.

For those younger than 55 years of age

People younger than 55 years of age during diagnosis will have either stage I or stage II differentiated thyroid cancer.

• Stage I
  • The tumor may have grown into nearby tissues, or the cancer may have spread to nearby lymph nodes.
• Stage II
  • The cancer has spread to other parts of the body (distant metastasis), such as to the lungs, liver or bone. This is also called metastatic thyroid cancer.

Age 55 and older

People at or above 55 years of age during diagnosis will be given a stage from I to IV for differentiated thyroid cancer.

• Stage I
  • The tumor only exists in the thyroid and is no larger than 4 cm.
• Stage II
  • The tumor is larger than 4 cm and may have grown into nearby muscles in the neck.
  OR
  • The cancer has spread to nearby lymph nodes. The tumor is at any size and may have grown into nearby muscles in the neck.
• Stage III
  • The tumor has grown into any of the following areas:
    • soft tissue beneath the skin
    • voice box (larynx)
    • windpipe (trachea)
    • oesophagus
    • a nerve to the larynx (called the recurrent laryngeal nerve)
    • The cancer may also have spread to nearby lymph nodes.
• Stage IVA
  • The tumor has grown into the connective tissue in front of the spine (prevertebral fascia), into blood vessels in the space between the lungs (mediastinum), or around a carotid artery. The cancer may also have spread to nearby lymph nodes.
• Stage IVB
  • The cancer has spread to other parts of the body (called distant metastasis), such as to the lungs, liver or bone. This is also called metastatic thyroid cancer.

Depending on the thyroid nodule’s size, the main types of treatment are:

• Lobectomy
  • Removes one side, or lobe, of the thyroid. It may be done for low risk differentiated thyroid cancer (papillary or follicular carcinoma) or anaplastic carcinoma when the tumor is small and stays in the thyroid.
• Total thyroidectomy
  • Completely removes the thyroid. It is the most common type of surgery performed for thyroid cancer.
• Lymphadenectomy
  • Removes the lymph nodes from the neck
  • Usually done when cancer has spread to lymph nodes in the neck
• Common side effects include:
  • Bleeding or wound infection
  • Hoarseness
  • Fatigue
  • Removal of parathyroid glands may result in drastic fall of calcium level inside the body, which causes limb numbness, cramps and/or cardiac arrhythmia.  Patients can take calcium tablets or vitamin D as supplements.
  • Recurrent laryngeal nerve injury with aspiration, breathy voice in unilateral injury or airway obstruction in bilateral injury
  • A scar is left at lower part of neck after the operation, but it will gradually fade out.
• Other uncommon but serious side effects include: (<1% risk)
  • Pneumothorax 
  • Tracheomalacia causing airway problem 
  • Death due to serious surgical and anaesthetic complications

Radioactive iodine (RAI) 

• Only for patients with papillary thyroid cancer and follicular thyroid cancer who have complete thyroidectomy
• Radioactive iodine (RAI) is given to thyroid cancer patients after surgery as an adjuvant treatment, or given to patients with recurrent/ metastatic disease.  It is an odourless capsule taken orally.  After ingestion, the radioactive iodine is taken up by the remaining thyroid cells in the body, and the small dose of radiation is then concentrated in these cells, which disintegrates them.
• Before radioactive iodine therapy:
  • Avoid iodine-containing contrast agents used in X-ray or CT scans for 2-3 months 
  • Follow a low iodine diet 2 weeks before RAI. All seafood (e.g. fish, shrimps, crabs, shellfish, seaweed, oyster sauce), iodine-added salt, soya, eggs, cheese, milk, dietary supplements containing iodine, food addictive E127, as well as iodine-containing medications (e.g. iodine-containing cough medicine) should be avoided.
  • Stop Thyroxine, T4 4 weeks beforehand. Your doctor may prescribe T3, a short-term thyroxine replacement, for 2 weeks and ask you to stop 2 weeks before RAI. While stopping the thyroxine replacement, you may feel malaise.
  • If you cannot stop the thyroxine replacement, you may be given two doses of recombinant human thyroid stimulating hormone (rhTSH) starting two days before RAI.

• After RAI:
  • Precautions should be taken to minimize the possibility of radiation exposure to other people, especially pregnant women and children.
  • Residual radioactive substances will be excreted within a few days through urine, faeces, saliva and sweat.
  • High level of radiation can be detected in urine, blood, saliva and sweat within first 4 to 5 days after the therapy.

You will have high dose scan on Day 4-10 after RAI. This scan can detect any residual thyroid tissue or any distant spread of the thyroid cancer in your body.

Side effects of RAI and their management strategy include: 

• Usually these side effects are short-term, lasting for less than 2 weeks.
• In the long run, according to the published data, there will not be any significant increase in risk of second malignancy and infertility after thyroid remnant ablation.

External beam radiotherapy

• It is used as adjuvant treatment after surgery in differentiated thyroid cancer if there is residual disease. 
• It is also commonly used in patients with medullary thyroid cancer or anaplastic thyroid cancer as they are of high risk of recurrence. 
• It is often given 5 days a week for 5-6 weeks depending on the patient’s condition. You are not required to stay in hospital as you are not radioactive under external radiation therapy. It is safe to have close contact with others, including children.
• Common side effects include:
  • Tiredness, nausea and loss of appetite. Antiemetic may help reduce these effects.
  • Skin redness, dryness, irritation or darkening (like sunburn) in the treated area. Sore or blisters may develop in some area. 
  • Hair loss in the irradiated area and re-growth occurs after treatment. 
  • Inflammation of mucosa of mouth and throat may lead to sore throat, hoarseness, dry cough or difficulty in swallowing with easy choking and risk of aspiration chest infection. 
  • Dry mouth, thickening of saliva. 
  • Change or loss of taste. Food high in nutrients calories is recommended.
  • If the nose or paranasal sinuses are in the radiation field, patients may experience nasal stuffiness, discharge and sometimes bleeding, changes or temporary loss of smell sensation. 
  • Although external radiation therapy does not affect the reproductive capacity, pregnancy is recommended to take place one year after treatment.
•  Uncommon side effects include:
  • Severe pain and difficulty in swallowing: you may need admission or temporary tube feeding.
  • If the larynx (voice box) is within the radiation field, you may experience difficulties in breathing and even stridor in severe cases. 

Thyroxine replacement

• After total thyroidectomy, you need thyroxine replacement therapy. 
• Thyroxine is a pill taken every day.
• Thyroxine replacement therapy will reduce the serum TSH and slow the growth of any remaining thyroid cancer cells.

It depends on the type of thyroid cancer.

Papillary thyroid cancer and follicular thyroid cancer

• Papillary thyroid cancer and follicular thyroid cancer are called differentiated thyroid cancer. If the cancer has spread to other parts of the body (main sites are bone and lung), surgery will be performed to remove the whole thyroid gland followed by prescriptions of radioactive iodine.
• Radioactive iodine can be given every 9 to 12 months if the cancer cells are responsive to RAI.
• If the disease does not uptake RAI or the disease progresses after RAI therapy, it is called an “RAI refractory differentiated thyroid cancer”. 
• You may not need any active treatment even the thyroid cancer becomes RAI refractory. Active surveillance and watchful waiting can be done if the disease is not causing any symptom and is slow growing. 
• However, if the disease progresses rapidly or becomes symptomatic, your doctor may discuss with you about targeted therapies. There are two targeted agents used for RAI refractory differentiated thyroid cancer:
  • Lenvatinib
    • Administration: taken orally, once every day
    • Side effects: high blood pressure, diarrhoea, decreased appetite, decreased weight, proteinuria, and nausea.
  • Sorafenib
    • Administration: taken orally, once every day
    • Side effects: hand-foot skin reactions or other skin problems, diarrhoea, fatigue, weight loss, and high blood pressure.
• Other targeted agents for differentiated thyroid cancers may be considered if specific gene mutations are found:
  • Larotrectinib/ Entrectinib: 
    • For thyroid cancers that have an NTRK gene fusion
    • Administration: taken orally
    • Larotrectinib: twice a day (Side effects: deranged liver function, anemia, fatigue, low serum albumin level, low neutrophil, diarrhea, constipation)
    • Entrectinib: daily (Side effects: mood disorders, lung infection, anemia, neutropenia)
  • Pralsetinib/ Selpercantinib:
    • For thyroid cancers with RET fusion-positive
    • Administration: taken orally

Medullary thyroid cancer

• Targeted therapies that can be used in patients with metastatic medullary thyroid cancer include: 
  • Vandetanib 
    • Administration: taken orally, once every day
    • Side effects: diarrhoea, skin rash, nausea, high blood pressure, headache, fatigue, loss of appetite, and stomach pain. More serious side effects such as respiratory and heart problems can occur.
  • Cabozantanib
    • Administration: taken orally, once every day
    • Side effects: constipation, stomach pain, high blood pressure, hair colour changes, fatigue, nausea, swelling, and colon problems.
  • Pralsetinib/ Selpercantinib:
    • For thyroid cancers with RET fusion-positive
    • Administration: talken orally

Anaplastic thyroid cancer

• Anaplastic thyroid cancer usually progresses very rapidly and easily spreads to other parts of the body. Systemic anti-cancer treatment includes chemotherapy and sometimes targeted therapy.
• Chemotherapy can be used alone or in combination to treat thyroid cancer. Common chemotherapy agents for anaplastic thyroid cancer include:
  • Doxorubicin 
  • Cisplatin 
  • Paclitaxel 
  • Docetaxel 
  • Dacarbazine 
• However the response rate of chemotherapy in anaplastic thyroid cancer is low, around 10-20%. Side effects include hair loss, diarrhoea, sore mouth and throat, nausea and vomiting, low white cell count/ platelet count and skin problems such as dry, itchy skin.
• Targeted agent
  • The doctor may check for any gene mutation to decide if any suitable targeted agents.
  • The combination of 2 targeted therapies, dabrafenib, a BRAF inhibitor, and trametinib, a MEK inhibitor, is an option for people with anaplastic thyroid cancer with BRAF gene mutation.
  • Administration: both drugs are oral medications.
  • Side effects include fever, rash, headache, joint pain, cough, nausea, vomiting, diarrhoea, muscle pain, dry skin, decreased appetite, high blood pressure, and difficulty in breathing.

As the cause of thyroid cancer is mostly unknown, there is no definite preventive measure. One should be alert if a family member has been diagnosed with thyroid cancer or a thyroid problem. It is best to take a self-check on the neck semi-annually and to have regular ultrasound scans.

Hong Kong Cancer Registry, 2020, Thyroid cancer

The Hong Kong Anti-Cancer Society: Thyroid cancer (Chinese only)

Smart Patient (by Hospital Authority): Thyroid cancer

American Society of Clinical Oncology (ASCO): Thyroid cancer

Special thanks to Mr. Joshua Tang, Ms. Sonia Yee-Sheung Chan (Class M23), medical student of Li Ka Shing Faculty of Medicine, the University of Hong Kong, and Dr. Wendy Wing-Lok Chan, Department of Clinical Oncology, the University of Hong Kong for authoring and editing this article.

Last updated on 18th Dec, 2023.