Thyroid Section

Thyroid

The thyroid gland is the largest endocrine gland in the body. It is a butterfly shaped structure that is present in the front of the neck. It secretes thyroid hormone – also called thyroxine(T4). It also secretes a small amount of triiodothyronine (T3). The thyroid gland requires iodine to synthesise thyroid hormones. The thyroid hormones regulate the metabolic rate of the body. All the tissues in the body require thyroid hormone to function optimally.

The amount of T4 and T3 secreted by the thyroid gland is regulated by the pituitary gland, which lies underneath your brain. The pituitary secretes thyroid stimulating hormone – TSH , which stimulates the thyroid gland to secrete T3 and T4. The pituitary senses the level of thyroid hormones in the blood, and maintains thyroid secretion in the normal range. If thyroid hormone level drops even a little the pituitary reacts by increasing the amount of TSH secreted.

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Problems due to increased or decreased functioning of the thyroid gland are diagnosed by performing blood tests called thyroid function tests.

TSH (thyroid stimulating hormone) is the test which is initially done. It is increased in patients with hypothyroidism and decreased in patients with hyperthyroidism. Normal ranges for adults are between 0.2 to 5 mU/L. In pregnancy the reference ranges are lower, with cutoffs depending on the stage of pregnancy.

Tests for total T4 levels, free T4 levels, and T3  may be done if TSH is lower than normal in order to look for hyperthyroidism.

Hypothyroidism is diagnosed on the basis of an increased TSH level. Unequivocally high levels indicate hypothyroidism and treatment is started directly.

Patients with borderline TSH levels are said to have subclinical hypothyroidism. Your doctor may ask for a thyroid antibody test and tests for levels of T4, T3 in order to determine the need for treatment.

A low TSH with high T4 and T3 suggest thyrotoxicosis (overactive thyroid). Your doctor will advise further tests in order to differentiate between different causes of thyrotoxicosis.

Antibody tests are done to conform a diagnosis of autoimmune thyroid disease. Thyroid peroxidase (TPO) is the usual antibody test done in patients with subclinical hypothyroidism. Thyroid stimulating hormone receptor antibodies (TSHR Ab, also known as TRAb) are checked in certain subgroups of patients with thyrotoxicosis.

Your doctor may repeat your tests 4 to 6 weeks after starting treatment. For hypothyroid patients , once the TSH is in the target range, tests need to be repeated only about once a year. Hyperthyroid patients require more frequent testing, and how often these will take place depend on the hormone level and treatment type.

Thyroid function tests can be influenced by medications and illnesses. Serious illness, liver disease and kidney disease can affect thyroid hormone levels. Certain medications such as contraceptive pills, steroids, drugs for epilepsy, anti TB drugs, lithium, amiodarone can also affect thyroid tests.

You should ask for a thyroid function test if you have symptoms of hypo or hyperthyroidism such as

  1. Swelling in front of the neck
  2. Dry skin, hair fall, puffiness of face
  3. Hoarseness of voice
  4. Weight gain or loss
  5. Irregular periods
  6. Heavy periods
  7. Tremors, palpitation
  8. Family history of thyroid disease
  9. Infertility

Hypothyroidism is condition in which the thyroid gland is underactive. This means that the gland is not producing sufficient thyroid hormone for the body’s needs.

own immune system becomes primed to damage his thyroid gland. Autoimmune disease may run in families.

Other rare causes of hypothyroidism are

  • Medicines such as lithium ( used for psychological problems) and amiodarone (used for heart problems)
  • Radiation for head and neck cancers
  • Congenital hypothyroidism – from birth due to defects in the formation of the thyroid gland

The thyroid hormones are necessary for optimum functioning of almost all the tissues of the body. A decrease in the level of thyroid hormones, therefore result in a general slowing down of the body. Some of the symptoms seen with hypothyroidism tiredness

  • dry and coarse skin, hair fall
  • hoarse voice
  • constipation
  • muscle weakness, cramps and aches
  • Inability to tolerate cold
  • pins and needles in the fingers and hands (carpal tunnel syndrome)
  • heavier and longer periods
  • infertility
  • weight gain
  • swollen or puffy face
  • low mood or depression
  • memory problems
  • difficulty in concentration

It is diagnosed by clinical examination and blood test. An elevated TSH level is indicative of hypothyroidism. Thyroid antibody test may be done to confirm autoimmune disease

Subclinical hypothyroidism is a condition where the TSH level is slightly elevated (5 to 10 mU/L), with normal T4 levels. Most of these patients do not have any symptoms.These patients are treated in case of infertility, pregnancy or a planned pregnancy. Symptomatic patients and patients who test positive for TPO antibodies are also treated.

Patients are given levothyroxine tablets in order to compensate for the decreased hormone production by the thyroid. The dose of levothyroxine depends on the blood test reports and the age and weight of the patient. This tablet needs to be taken on an empty stomach . A gap of 30 to 45 minutes between the medication dose and your morning meal will ensure complete absorption.

The correct dose of levothyroxine is determined based on TSH readings in the normal range. The patient should not have symptoms of hypothyroidism with the correct dose of thyroid hormone. This frequently requires adjusting the thyroid hormone dose to obtain TSH level in the lower part of the reference range.

Thyroid function testing should ideally be repeated before planning pregnancy. A normal TSH prior to conception ensures lesser chances of infertility, miscarriages. The thyroid hormone dose is usually increased by 25 to 50 % after conception.

Any swelling in thyroid gland is called a goitre. Nodules are lumps in the thyroid gland. Around 80 to 90% of the nodules are harmless (benign), but have to evaluated by and endocrinologist/endocrine surgeon to confirm the same.

The main cause is unknown, but thyroid nodules and enlarged thyroid glands are more common in women and increase with age. The others causes like iodine deficiency, radiation to the neck, family history of thyroiditis or thyroid nodule, physiological etc.

If you have a nodule or swelling in your neck you should see your doctor at the earliest. Your doctor will assess the swelling by performing certain blood tests, ultrasound scan of the neck, fine needle aspiration cytology (if required) and taking a decision of further management. Most thyroid nodules are benign and don’t need surgery and can be kept on regular follow up.

Thyroid nodules can broadly be divided into

  • Benign (non-cancerous)
  • Cancerous

Some patients can have a

  • Single thyroid nodule (solitary)
  • Multiple nodules (multinodular goitre)
  • Diffuse goitre
  • Retrosternal goitre (nodule descending behind the collar bone)

The following tests are usually done for thyroid nodules or swellings

  • Blood tests – thyroid profile (T3, T4 and TSH) are the first test done to assess the function of the thyroid gland.
  • Ultrasound scan –It uses the sound waves to examine the structure of the thyroid nodule. It is a non-invasive painless tests helps in characterizing the nodule, whether it’s benign or malignant (cancerous).
  • Fine needle aspiration cytology –in this test a small needle is inserted into your nodule and few cells are removed. These cells are stained, looked under the microscope and graded as per BETHESDA 1 to 6. It helps in taking decisions whether the nodule needs surgery or can be followed up. Typically BETHESDA 1 & 2 can be followed up, 3 to 4 might need surgery and 5 & 6 will need surgery.
  • Other test that are selectively ordered are
    • CT Scan of the neck
    • Nuclear medicine scan

Most benign nodules don’t need surgery and can be followed up with physical and ultrasound examination. The following patients will benefit from surgery

  • Thyroid nodules > 4cm
  • Any compressive symptoms like difficulty in swallowing, sticking sensation in the throat, voice change, deviation of the windpipe etc.
  • Family history of thyroid cancer
  • Cosmetic
  • Any suspicion of cancer either on FNAC/ Ultrasound or physical examination

Surgery is required for several problems involving the thyroid gland. These include but are not limited to

  1. Enlarged thyroid – goitre causing difficulty in breathing or Solitary nodule thyroid adenoma (a benign tumour)
  2. Thyroid cancer
  3. Thyrotoxicosis – not responding to medical therapy
  4. Large thyroid nodule (>4cm) with indeterminate findings on FNAC
  5. Large nodule causing cosmetic concerns

The operation is performed under a general anaesthesia. You will usually be admitted on the morning of the surgery. You will asked to either take a light breakfast and come or come after an overnight fast , depending on the time fixed for the surgery.

The two commonly performed types of thyroid surgery are total thyroidectomy , and hemithyroidectomy. The whole of the thyroid is removed during total thyroidectomy, whereas only one lobe of the thyroid is removed during hemithyroidectomy. Patients with thyroid cancer, multinodular goiter and Graves thyrotoxicosis require total thyroidectomy. Patients with a single benign nodule on one side can undergo hemithyroidectomy.

The surgery is usually performed through a 6 to 8 cm incision in the lower part of your neck.

 The surgeon carefully isolates and preserves important structures in the neck such as the nerves , blood vessels and the parathyroids. The thyroid is then carefully removed and the incision closed. A drainage tube is sometimes placed to drain extra fluid for 1 to 2 days. Patients with suspected thyroid cancer may need to have a more extensive surgery where the surgeon examines the lymph nodes in the neck for involvement with cancer.

Thyroid surgery is safe when performed by an experienced thyroid surgeon.  Rare complications that can occur are bleeding, hoarseness of voice and low calcium. Hoarseness of voice occurs due to inadvertent damage to the recurrent laryngeal nerve in the neck. It is usually transient and resolves in most cases. Low calcium occurs due to damage to the parathyroid glands or their blood supply.

You will need to stay in hospital for one or two days after surgery. A blood test for calcium will usually be done on the morning after the surgery. Calcium and vitamin D tablets will be prescribed in case of low calcium levels. Most patients will usually be discharged on the day after surgery. Patients who have had a total thyroidectomy will be asked to take thyroid hormone supplements.

Experienced surgeons usually place the scar along one of the creases in the neck. The scar may look slightly prominent for about 4 to 6 weeks after surgery, as healing occurs. The scan becomes much less noticeable by about 3 months after surgery.

Endoscopic surgery is performed in patients who are strongly motivated to avoid the surgical scar in the neck. It is performed for thyroid nodules less than 6 cm in size, which are not cancerous. It can be performed via a small incision in the floor of the mouth – transoral technique or via incisions in the armpit and the breast.

Cancer of the thyroid gland is rare, but is increasing in incidence. The term cancer is annoying, but most thyroid cancers have high cure rate and patients live a full and normal life.

Thyroid cancers can be broadly divided into

  • Well differentiated
    • Papillary thyroid cancer (most common, constitutes 80 to 85%)
    • Follicular cancers (5 to 10%)
  • Poorly differentiated cancer
  • Medullary thyroid cancer
  • Anaplastic (rare and most lethal)
  • Others (lymphoma etc)

We will be concentrating our discussion on well differentiated thyroid cancers as they are the common forms of cancer. Differentiated cancer respond well to the treatment and have good survival.

Thyroid cancers usually present with a nodule or swelling and most are asymptomatic. It can be detected on ultrasound or CT scan done for some other reasons. Some patients complain of sudden increase in the size of the swelling or voice change.

Not all nodules or swellings in the thyroid gland are cancerous – in fact most lumps and swellings in the thyroid gland are benign (non-cancerous).  It is most important, though, that any nodule should be investigated, even if it has been there a long time.

The following test are done when you have a thyroid nodule or a suspicion of cancer

  • Thyroid profile
  • Ultrasound of neck
  • Fine needle aspiration cytology (FNAC)
  • CT scan of neck ( in patients with advanced cancer or retrosternal nodules)

The specialist will usually arrange an ultrasound examination and in some cases a fine needle biopsy (fine needle aspiration cytology – FNAC) to remove cells from the lump or swelling for examination under a microscope. About 19 out of 20 thyroid lumps are benign. In some cases the biopsy will show thyroid cancer. Unfortunately sometimes the biopsy does not give a definitive answer. In such cases the biopsy may have to be repeated or additional tests may be requested. In some cases the only way of knowing whether a thyroid lump is cancerous is to remove a part of the thyroid gland by an operation.

Treatment  depends on the type of cancer and the stage at the time of treatment.

Surgery

A lobectomy (hemithyroidectomy) alone is sufficient treatment for benign conditions  while for thyroid cancer  it is better to remove the whole gland. The surgeon may also remove some of the lymph nodes in the neck to check whether any cancer cells have spread. There is a small risk that surgery may affect your parathyroid glands (which control the calcium in your body) or your voice. Usually this is temporary but in some cases the change may be permanent. Ask your surgeon to explain the risks to you beforehand. National guidelines recommend that your surgery is performed by an experienced endocrine or head-and-neck surgeon who regularly does thyroid and parathyroid surgery and who is working as part of a Multi-Disciplinary Team (MDT). (See: Your Guide to Thyroid Surgery.)

Radioactive iodine

After surgery you may be treated with radioactive iodine, known as radioactive iodine ablation (RAI ablation). You will not be treated with RAI ablation if you still have half your thyroid in your neck, or if your risk of the cancer recurring is very small. Normal thyroid cells and thyroid cancer cells are unique because they are the only cells in the body to store  iodine. This means radioactive iodine can be used to treat thyroid cancer. The radiation in the iodine destroys the thyroid cells. There are small risks associated with RAI ablation, such as dry mouth, altered taste and a minimal risk of other cancers which should be discussed with you before consent. After RAI ablation, patients can usually be monitored simply by an examination of the neck, blood tests and/or scans to see if the cancer is cured.

Currently there are two regimens used to prepare patients for RAI ablation: (1) recombinant TSH and (2) thyroid hormone withdrawal. Both approaches raise the level of TSH, which encourages the remaining thyroid cells, whether they are normal or cancerous, to take up the radioactive iodine very effectively.

  1. Thyroid hormone withdrawal – three to four weeks before RAI, your doctor will ask you to stop thyroid tablets. This will help any remaining thyroid tissue to take up radioactive iodine more efficiently. You may experience symptoms of hypothyroidism such as tiredness, lethargy, dry skin etc.
  1. Recombinant TSH (rhTSH) – two injections of recombinant TSH will be given on the two days before I 131 ablation. The advantage of this method is that you can continue levothyroxine treatment till ablation, and will not have to experience the discomfort sometimes associated with stopping levothyroxine.

Radioactive iodine treatment is usually given in the form of a capsule. You may need to stay in hospital for a few days to avoid exposing other people to radioactivity. Women need to avoid pregnancy for 1 year after radioiodine treatment.

Thyroxine (levothyroxine)

Levothyroxine is given after surgery to replace the thyroid hormone the thyroid gland normally produces. Thyroxine is required in all patients who undergo a total thyroidectomy. Occasionally levothyroxine is required after a lobectomy. You may be prescribed a higher than normal dose of thyroxine in order to suppress TSH. This is in order to suppress the blood TSH level, as a high TSH can cause any remaining thyroid cancer cells to grow.

You will need to have regular follow up visits. Blood tests to look for your thyroid hormone levels and to check for the presence of the thyroid tumour cells( thyroglobulin) will be done. A neck ultrasound may also be done. You may need a repeat  radioactive iodine scan.

Medullary thyroid cancer (MTC)

MTC is a rare form of thyroid cancer that arises from the C cells of the thyroid. MTC may be inherited as a genetic disorder, especially in younger patients. MTC is usually suspected based on the FNAC results and elevated levels of calcitonin in the blood.

MTC is treated surgically. Patients require a total thyroidectomy. The lymph nodes of the neck will be examined for cancer at the time of surgery and removed if necessary. Thyroxine will be prescribed after surgery. Radioactive iodine is not used in the treatment of MTC.

Anaplastic cancer

This is  a rare form of thyroid cancer, which usually affects older people. Patients usually present with a rapidly growing thyroid lump. This cancer tends to be very aggressive.Treatment may involve surgery, chemotherapy and radiotherapy.

Thyroid Lymphoma

Lymphoma rarely affects the thyroid. It is diagnosed by a biopsy. Treatment usually involves chemotherapy.

The common forms of thyroid cancer – papillary and follicular, carry a very good prognosis. These tumours are curable even after they have spread to the lymph nodes. They are completely curable with surgery if diagnosed in the early stages. Even advanced cancer is cured/ controlled by radioiodine therapy and suppressive thyroxine.

It is a condition where there is an excess of thyroid hormones in the blood. If this excess is due to overproduction of thyroid hormones by the thyroid gland ,it is referred to as hyperthyroidism. The common causes of thyrotoxicosis are

  1. Graves disease
  2. Thyroiditis
  3. Toxic thyroid nodule
  4. Toxic multinodular goiter

Common symptoms are

  1. Weight loss
  2. Sweating, anxiety, decreased sleep
  3. Tremors, palpitation
  4. Breathlessness and easy fatiguability
  5. Diarrhoea
  6. Swelling in front of the neckpassing larger than usual amounts of urine

Graves’ disease is the most common cause of thyrotoxicosis. It is more common in women than in men. Graves disease is an autoimmune disease. Antibodies are produced by the body which bind to and stimulate the thyroid gland. The thyroid gland then becomes enlarged and produces an excess of thyroid hormones. The thyroid antibodies can also bind to the tissues of the eye socket and cause bulging , redness, pain and watering of the eyes.

Graves disease has a strong genetic component. It may affect people who have a family history of other autoimmune disorders. It is more common in smokers.

Graves’ disease is more common in people who smoke cigarettes. Smokers are also up to eight times more likely to develop thyroid eye disease than non-smokers.

Hyperthyroidism is initially suspected based on clinical symptoms, and findings seen on physical examination.

Blood tests are necessary to confirm a diagnosis of thyrotoxicosis. The TSH is low and Total T4, Total T3 and free T4 are high in patients with thyrotoxicosis. Once thyrotoxicosis is established, further tests may need to be done to confirm the cause of thyrotoxicosis.

A thyroid scan using either Technitium 99 or Iodine 131 may be necessary to make a diagnosis of Graves disease. Making the correct diagnosis is important, as different causes of thyrotoxicosis are treated differently. An ultrasound scan of the neck may also be needed to look for nodules in the gland.

Graves disease is the commonest cause of thyrotoxicosis. The available treatments for Graves disease are – antithyroid drugs to reduce the production of thyroid hormones; surgery to remove all or part of the thyroid gland; or radioactive iodine.

Antithyroid medications are often used as the first treatment and are the treatment of choice for children, and for women who are pregnant. The drugs available are carbimazole, methimazole and propylthiouracil. Carbimazole / methimazole are chemically similar and are commonly started first. Propylthiouracil is used in women planning pregnancy and in pregnant women.  Patients who respond well to antithyroid drug treatment may be continued on these medications for 18 to 24 months. 30-50% of patients may achieve lasting remission with drug treatment.

Radioactive iodine treatment is used as a treatment of choice in patients who do not respond to drug therapy. It is a reasonable first line treatment in patients who are not likely to be cured with drug therapy alone. It is safe and effective with few side effects. The radioactive I 131 is captured by the hyperactive thyroid gland. The radiation then emitted from within the thyroid shrinks the gland. Most patients would become hypothyroid after effective I 131 treatment. This will not be a major problem as thyroxine supplementation is a straightforward process which does not require much dose adjustment or monitoring. Radioactive iodine is usually not used in smokers and in patients with thyroid eye disease, as it may worsen eye disease.

Surgery is usually the treatment of choice for patients with very large goitres, for those with severe disease, and those with severe eye disease. After surgery you are likely to need to take levothyroxine for the rest of your life.

There is a very rare and unpredictable side-effect of antithyroid drugs due to a lowering of the number of white blood cells, which is called agranulocytosis. It affects 0.1 to 0.5 % of patients. Patients who develop symptoms of high fever, sore throat and ulcers in the mouth should stop the drug and promptly consult their doctor.

Very rarely, live injury can occur in patients taking antithyroid drugs. It is more common with propylthiouracil.

Blood tests are carried out every 4 to 6 weeks initially. Later follow up requires tests , once in 2 to 3 months. Yearly evaluation is required for patients who are completely cured and off medication.

Hyperthyroidism can cause irregular periods, and difficulty conceiving. Fertility usually improves following treatment.

In women planning pregnancy, it is important to bring thyroid hormone levels down to normal before conception. This is usually done using antithyroid drugs like propylthiouracil.

Propylthiouracil is preferably used in pregnancy as less of it crosses the placenta than carbimazole/methimazole. There is a small risk of birth defects like cleft palate with the use of these drugs. The risk is smaller with propylthiouracil than carbimazole. The dose of medication may need to be frequently adjusted during the course of pregnancy as it is important to prevent both undertreatment and overtreatment. Requirement for medication usually decreases as the pregnancy progresses. However hyperthyroidism may worsen after deliver and requires follow up. Antithyroid drugs can be given during breast feeding  as only small amounts enter breast milk. However they are best taken in smaller divided doses, and following a feed.

Untreated hyperthyroidism in pregnancy can cause problems like miscarriage, poor weight gain, hypertension, and premature delivery. Rarely,women treated with surgery or radioactive iodine in the past can have increased levels of thyroid antibodies (TSH receptor antibodies) in the blood. These women require closer attention during pregnancy.

Thyroiditis is a common cause of thyrotoxicosis. Thyroiditis is caused due to inflammation and damage to the thyroid gland. Common causes of thyroiditis are

  1. Viral infection – subacute thyroiditis
  2. Drug related thyroiditis
  3. Postpartum thyroiditis
  4. Autoimmune thyroiditis

It is associated with symptoms of thyrotoxicosis like weight loss, sweating, palpitation, tremors and anxiety. A swelling in front of the neck and pain over the thyroid may be present. The patient may remember having an episode of viral infection in the recent past.

Blood tests show features of thyrotoxicosis such as decreased level of TSH , with increase in T4 and T3 levels. ESR may also be elevated. A diagnosis of thyroiditis is confirmed by seeing low uptake on a Tc 99 or I 131 radioactive uptake scan.

This is believed to be caused by a viral infection of the gland, usually associated with ‘flu-like’ symptoms. It is more common in women than men, most often affecting those aged 20-50.

In most patients thyroiditis subsides on its own in 2-3 months. Beta blockers may be given to control the symptoms of thyrotoxicosis. However some patients may require steroids or NSAIDs for relief of pain and symptoms. Some patients with thyroiditis may go on to become hypothyroid once thyroiditis resolves.

It is a condition usually associated with Graves disease. The eye muscles, eyelids, tear glands and fatty tissues behind the eye become inflamed. This can cause the eyes and eyelids to become red, swollen and uncomfortable and the eyes can be pushed forward (‘staring’ or ‘bulging’ eyes). In severe cases it can cause reduced vision due to pressure on the optic nerve. Damage to the cornea in the front of the eyes can occur if the bulging is severe. Eye disease can occasionally be seen even in the absence of thyrotoxicosis.

  About one fourth of people with Graves disease may develop eye disease. It is mild in most cases. It may be worse in smokers.

Bulging, redness, pain and watering of the eyes may be present. A feeling of grittiness may occur. Double vision or decrease in vision can occur in severe cases.

Mild cases improve with control of thyrotoxicosis. Selenium tablets or lubricating eye drops may be prescribed. More severe disease may require medications like steroids. Some patients may require radiation therapy or surgery

In most patients thyroiditis subsides on its own in 2-3 months. Beta blockers may be given to control the symptoms of thyrotoxicosis. However some patients may require steroids or NSAIDs for relief of pain and symptoms. Some patients with thyroiditis may go on to become hypothyroid once thyroiditis resolves.

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