1- Where is the thyroid gland located in the human body?
The thyroid is a small gland, shaped like a butterfly, located in the neck, below the thyroid cartilage. This cartilage is also known as the Adam's apple, which is prominent in males. The gland is composed of two cone-like lobes or wings (left and right lobes) and they are connected via the thin thyroid tissue (isthmus). Lobes or wings are mainly located at the either side of larynx and trachea, and isthmus is located in front of trachea. The gland can move and change its position during swallowing. A normal thyroid gland usually weighs 2-3 grams in newborns and approximately 20-50 grams in adults.

2- What are the major structures neighboring the thyroid gland?
The thyroid is in close proximity to many vital structures in the neck. Three of them are important during thyroid surgery and they should be preserved. These are;
Lower laryngeal nerves, also known as recurrent laryngeal nerves (RLNs). There are 2 lower laryngeal nerves. One of them is on the right side the other is at the left side of the neck.  Both of the nerves generally run alongside the posterior surface of thyroid lobes and reach the vocal cords and innervate them. There are 2 vocal cords, right and left, which are located within the larynx at the top of the trachea. Vocal cords open during inhalation, close when holding one's breath, and vibrate for speech or singing. Nerve injury during the operation leads to the paralysis of the vocal cord. In the cases of right and left nerve damage, paralayzed cords may obstruct the airway and lead to breathing distress. On the other hand, damage to only one of these nerves causes hoarse and husky voice.
Upper laryngeal nerves or external branch of superior laryngeal nerves. Right and left nerves innervate the right and left cricothyroid muscles of larynx, which alter vocal cord tension and affect pitch of the voice. Injury to these nerve(s) results in difficulty in shouting or singing high notes.
Parathyroid glands: There are four parathyroid glands. 2 of these are located on the backside of the right thyroid lobe and the other 2 are located on the backside of the left thyroid lobe. A normal parathyroid gland usually weighs less than 50 miligrams. They produce parathyroid hormone (PTH), which regulates the calcium metabolism. Their damage during operation leads to drop blood calcium level.
3- What is the function of thyroid?
The main function of the thyroid gland is to release thyroid hormone (T3 and T4). 
These hormones are produced in follicular cells of thyroid gland. These cells also secrete thyroglobulin, a type of protein, to blood in tiny amounts. Blood thyroglobulin level is important in patients who have undergone total thyroid excision (total thyroidectomy) for differentiated thyroid carcinomas. The other hormone, which is produced by parafollicular cells is calcitonin. In some animals calcitonin is a significant regulator of calcium metabolism, but in human beings it has minimal physiologic effects.

4- What is structure and function of T3 and T4
Thyroid hormone is composed of thyrosine and iodine. Thyrosine is an aminoacid. If thyrosine has 3 iodine atoms it is called T3 (three iodothyronin), if it has 4 iodine atoms it is called T4 (tetra iodothyronin).
Through the release of T3 and T4, thyroid gland influences the metabolic rate of all tissues. Increased secretion and increased blood levels of these hormones increase the metabolic rate; on the other hand the metabolic rate decreases when their secretion or blood levels are decreased.
Thyroid hormone production is influenced by numerous factors. Most important factor is the thyroid stimulating hormone (TSH). TSH is produced and secreted by anterior pituitary gland which is situated at the bottom of the brain. When blood levels of T3 and T4 decrease, secretion of TSH increases; conversely TSH secretion decreases when blood levels of T3 and T4 increase.
5- How many types of thyroid diseases are there?
Thyroid diseases can be divided into 4 groups.
1. Goiter
Diffuse goiter
Nodular goiter

Any enlargement of the thyroid gland is referred to as a goiter. Enlargement may be diffuse (diffuse goiter) or nodular (nodular goiter). The term “thyroid nodule”refers to any abnormal growth of thyroid cells into a lump within the thyroid gland. Thyroid nodules may be single or multiple. A thyroid gland that contains multiple nodules is referred to as a multi-nodular goiter. If there is a single nodule, it is termed solitary thyroid nodule. If the nodule is filled with thyroid tissue, it is called solid nodule. If the nodule is filled with fluid or blood, it is called a thyroid cyst. If the nodule produces thyroid hormone in an uncontrolled manner, the nodule is referred to as autonomous. This type of nodule (toxic nodule) may cause hyperthyroidism, signs and symptoms of which are explained in detail below.
2. Functional thyroid disorders
The terms euthyroidism or euthyroid staterefer to normal thyroid function. Normal thyroid function means that the thyroid hormone production and secretion are normal and blood level of thyroid hormone is adequate. On the other hand abnormal levels of thyroid hormone in the bloodstream, regardless of the cause, can result in profound physiologic effects throughout all the systems of the body. This kind of abnormality is generally called functional thyroid disorders. There are 2 kinds of functional disorders: hyperthyroidism and hypothyroidism.

Hyperthyroidism (thyrotoxicosis or overactive thyroid):
In hyperthyroidism blood thyroid hormone levels are elevated. There are 3 main types of hyperthyroidism: Graves’s disease (toxic diffuse goiter), toxic multinodular goiter and single toxic nodular goiter (toxic adenoma). These are related to an excess production and secretion of active thyroid hormone from the thyroid. Other important causes of hyperthyroidism include painless and painful thyroiditis (due to excess hormone secretion from thyroid), Jod-Basedow disease (due to excess iodine intake), secondary hyperthyroidism (due to excess TSH secretion from the pituitary), and thyrotoxicosis factitia  (secondary to over-medication with thyroid hormone replacement medication).
Hypothyroidism (underactive thyroid)
In Hypothyroidism blood thyroid hormone levels are decreased due to the failure of thyroid gland to maintain an adequate blood level of thyroid hormone. Most common causes of hypothyroidism are Hashimoto’s thyroiditis (auto-immunity against the thyroid) and iodine deficiency goiter (predominantly seen in iodine deficient areas). Thyroidectomy (surgical removal of all or part of the thyroid gland) and radioactive iodine treatment for hyperthyroidism account for one-fourth of the cases. Other important causes of hypothyroidism include secondary hypothyroidism (due to lack of TSH production from pituitary), genetic thyroid enzyme defects and drug induced hypothyroidism (lithium, oral contraceptives, etc).
3. Inflammatory thyroid diseases (thyroiditis).
In medicine, the suffix -itis means inflammation; thyroiditis is the inflammation of the thyroid gland which may be associated with abnormal thyroid function.
There are five different kinds of thyroiditis.
Hashimoto's thyroiditis
This is the most common cause of thyroiditis and may run in families. It may also be referred to as chronic lymphocytic thyroiditis. Hashimoto’s thyroiditis is an autoimmune disease in which the thyroid gland is gradually destroyed by a variety of cell and antibody mediated immune processes. When most of the thyroid cells are damaged, they stop thyroid hormone production, which results in hypothyroidism.

Painful thyroiditis
This type of thyroiditis is also called subacute granulomatous thyroiditis.
Although the exact causes are not known, it usually starts out as a viral illness such as the flu or the common cold that invades the thyroid gland causing thyroiditis.
Painless thyroiditis
This type of thyroiditis is also referred to as subacute lymphocytic thyroiditis and and it is also considered to be autoimmune in origin.  If it occurs in women one to four months after delivery, it is called post partum thyroiditis.
Reidel’s thyroiditis
This very rare type of thyroiditis is called invasive fibrous thyroiditis and is also considered to be autoimmune in origin. As a result of inflammation, the thyroid gland itself becomes quite hard like a rock, and it may be very difficult to distinguish it from thyroid cancer. In the most severe forms of this disease, the thyroid gland may squeeze the trachea and may cause breathing difficulties. In these cases surgical intervention is necessary and wedge excision of thyroid isthmus is performed to decompress the trachea.
Acute suppurative thyroiditis
It is caused by a bacterial infection in the thyroid which causes pus to collect and form an abscess within the thyroid gland. This kind of thyroiditis is quite rare today, and antibiotics and surgery to drain the pus can result in complete cure.
4- Malignant tumors (cancers) of thyroid gland
Thyroid cancer is a thyroid neoplasm (tumor) that is malignant. There are four
main types of thyroid cancer, which are based on how the cancer cells look
under a microscope.

Papillary thyroid cancer (PTC)
Follicular thyroid cancer (FTC)
Medullary thyroid cancer (MTC)
Anaplastic thyroid cancer (ATC)
The follicular and papillary types can be classified together as "differentiated thyroid cancer (DTC)"

5- Which tests are utilized in the diagnosis of the diseases of the thyroid?
1. Thyroid Funtion Tests: Blood levels of TSH, T3, T4 (total or free).
TSH is the only test necessary in most patients with thyroid enlargement (nodular or diffuse). However, other tests should be done if TSH level is too high or too low.

2. Thyroid autoantibodies
The body normally produces antibodies to foreign substances such as bacteria; however, some people are found to have antibodies against their own thyroid tissue. The most important thyroid antibodies are Anti TPO antibody, Anti Tg antibody and Anti TSH-R antibody. Blood levels of these antibodies do not determine thyroid function. They indicate the underlying disorder. Anti TPO antibody and Anti Tg antibody level is high in Hashimoto’s thyroiditis. Anti TSH-R antibody test is diagnostic of Graves’ disease (A type of hyperthyroidism) and is found to be increased in 90% of these patients.

3. Thyroid imaging tests
Thyroid Ultrasonography (USG):
USG is an noninvasive and inexpensive method for the evaluation of the thyroid gland. It is helpful for detecting the dimensions of the thyroid and the nodules and for differentiating solid nodules from cystic nodules. Combining high-resolution USG with Doppler and analysis of the vascular characteristics of a thyroid nodule is a useful tool in screening thyroid nodules for malignancy. Studies have shown that the risk of malignancy is higher in nodules with an increased central vascular pattern. USG can also be used to assess the cervical lymph nodes and to guide fine-needle aspiration biopsy (FNAB) of nodules and lymph nodes.

  1. Radionuclide imaging (Thyroid scanning)

Radioactive atoms (iodine-123, iodine-131 or Technetium-99m) are used to image the thyroid glands. Technetium-99 is widely used because it has a shorter half-life and minimizes radiation exposure. The images provide information about size, shape and functional activity of the gland. The nodule that traps less radioactivity than the surrounding gland are termed cold nodule(s), whereas nodule(s) that demonstrates increased activity are termed hot nodule(s). The disadvantage of a thyroid scan is that it can't distinguish between benign and malignant cold nodules.

Others
CT and MRI are particularly useful in evaluating the extent of the large goiters and substernal goiter (goiter which grows into the chest) and their relationship to the airway and the vascular structures.
In cases where other imaging studies are negative, PET can be used to screen for thyroid cancer metastases.

4. Thyroid fine needle aspiration biopsy (FNAB)
FNAB is the most important test in the evaluation of patients with thyroid nodules or masses. The test is fast, is minimally invasive, has few risks, and causes little discomfort to the patients. In this technique, a fine needle is inserted directly into the thyroid nodule(s), which can be felt manually (palpable nodule), and several passes are made while aspirating the syringe. After an adequate amount of tissue (or cells) has been collected, suction on the syringe is released and the needle is withdrawn. If the nodule can not be felt manually (non-palpable nodule) or if the nodule has areas within it that are specifically important, an ultrasound may be needed to help guide the insertion of needle. It should be noted that the data have suggested that ultrasonography-guided FNAB may be preferable to palpation-guided FNAB. Material in the needle and/or syringe is immediately placed on dry glass slides and stained with special stains and examined under microscope. Skilled pathologists can accurately diagnose the majority of thyroid diseases.
Most of the biopsy results are diagnostic (65% benign, 5% malign), the others can be suspicious (20%) and non-diagnostic (10%). If a biopsy is reported as non-diagnostic, it should be repeated.

5. Genetic tests
Approximately 25% of medullar thyroid cancers (MTC) are caused by an inherited cancer risk. This type of MTC is called hereditary MTC and is caused by mutations in the RET gene. Genetic testing for mutations in the RET gene is available.

6. Tumor markers
There are 3 important tumor markers. These are thyroglobulin, calcitonin and CEA. Thyroglobulin is used to follow up papillary and follicular thyroid cancer, which are treated with surgery. Calcitonin and CEA are used to follow up medullary cancer, which is treated with surgery. Calcitonin is also used to diagnose medullary cancer. 

 

7- What is the treatment of goiters and nodules?

  1. Diffuse goiter

Most patients with diffuse goiters and normal thyroid functions do not have any complaints, and these patients do not require treatment.  Some patients complain of a pressure sensation in the neck. As goiters become very large, compressive symptoms such as swallowing and/or breathing difficulties, ensue. Some patients also describe having to clear their throats frequently. Thyroid hormone may be given to these patients and to patients who have elevated TSH levels to reduce the TSH stimulation of gland growth (thyroid suppression treatment). Surgical treatment is reserved for goiters that continue to increase in size despite thyroid suppression treatment, and for goiters which grow into the chest and cause obstructive symptoms. Another reason to remove a goiter is for cosmetic reasons.

Thyroid nodule(s)
In general, nodular goiter is a common disease, and 5% of thyroid nodules are malignant. A rational approach to the management of a thyroid nodule is based on the ability to distinguish between benign and malignant nodules.
Factors suggesting a malignant diagnosis include the following: Patients younger than 20 years or older than 70 years, male sex, associated symptoms of dysphagia (difficulty in swallowing) or dysphonia (changes in the patients’ voice), history of neck irradiation, firm, hard, or immobile nodule and presence of cervical lymph node enlargement. It should be remembered that these factors do not provide absolute diagnostic information. As mentioned above, ultrasound examination is necessary to determine the characteristics of a thyroid nodule. The ultrasonographic appearance and size of a thyroid nodule may have some diagnostic importance as solid nodules larger than 3 cm and cystic nodules larger than 4 cm are thought to have an increased risk of malignancy. However, findings suggest that non-palpable nodules (incidentally found on high-resolution ultrasonography) may have a risk of malignancy. As a general rule, if a nodule is cold, solid, single and greater than 1cm FNAB should be done. If this kind of nodule is smaller than 1 cm, FNAB may be performed according to the clinical findings and USG appearance. If there are multiple nodules (multi-nodular goiter), FNAB can be done on one or more of these nodules.
Patients who need surgery

1- In patients with nodule(s) and radiation history or FNAB confirmed cancer diagnosis, surgery is necessary.
2- In patients where FNAB results of nodule(s) are suspicious or indeterminate, surgery should be considered as the primary treatment option.
3- Surgery may be considered in following patients: Those with no cancer diagnosis but with pressure symtoms (difficulties in swallowing and breathing and compress the blood vessels of the neck), those with multiple clinical and/or ultrasound cancer risk factors.
4- Since cystic nodules larger than 4cm in diameter carry cancer risk, surgery is recommended in such cases.

  1. 5-Toxic nodules also may reguire surgery
  2. 6- Another reason to remove a nodular goiter is for cosmetic reasons.

8- What is the clinical signs and treatment of thyroiditis
Hashimoto's thyroiditis
Many people who have Hashimoto's disease have no symptoms at all. In some patients, thyroid enlarges slightly or moderately, and the thyroid may appear as a painless anterior neck mass. Nearly 80% of the patients with thyroiditis are euthyroid and 15% of the patients are hypothyroid when disease is diagnosed. Occasionally (5% of the cases), Hashimoto's thyroiditis may cause short-lived hyperthyroidism, as high levels of thyroid hormone is released into the blood stream while thyroid cells are destroyed. Clinical signs of hypothyroidism and hyperthyroidism will be discussed later.
Hashimoto's thyroiditis is simply diagnosed by thyroid antibody tests (anti TPO and anti Tg antibody). The anti TPO antibody test is much more sensitive than anti Tg antibody test; therefore, some doctors use only the anti TPO antibody test. In these patients, thyroid function tests should also be done to confirm whether a patient has hypothyroidism or not.
Hashimoto's thyroiditis does not form discrete nodule(s) in the thyroid. If there is a nodule or a rapidly enlarging thyroid, it must be examined.
In the absence of goiter and if the patient is in euthyroid state no therapy is necessary. But, If there is a goiter, thyroid hormone may be given for shrinkage of the thyroid. Thyroid hormone replacement therapy is indicated in overt hypothyroidism.
Painful thyroiditis
This type of inflammation is quite painful. Pain at the thyroid area may extend to the jaw or ear. Sometimes only one lobe of the thyroid is affected. Painful thyroiditis typically progresses through four stages. First stage is hyperthyroid state, which is caused by the release of surplus thyroid hormone to the bloodstream. Thus, level of thyroid hormone in the bloodstream and blood red cell sedimentation rate are increased. Sometimes levels of antibodies (anti Tg and anti TPO) are also increased. This stage is generally followed by euthyroidism, hypothyroidism and again euthyroidism phases. Occasionally, however, the thyroid is damaged in the process and can never produce normal quantities of thyroid hormone, which results in permanent hypothyroidism.
Painful thyroiditis is a self-limited disease; therefore, treatment is primarily symptomatic. For example, pain killer for neck pain. If hypotyhroid state persists, thyroid hormone replacement therapy should be started.
Painless thyroiditis
The clinical findings and the results of the laboratory tests for painless thyroiditis, except pain and sedimentation rate, are similar with painful thyroiditis. The clinical course also parallels painful thyroiditis. Treatment of painless thyroiditis is also symptomatic.