The thyroid is one of the larger endocrine glands in the body. It is located in the neck and produces hormones, principally thyroxine and triiodothyronine, that regulate the rate of metabolism and affect the growth and rate of function of many other systems in the body.

Gross anatomy

The thyroid is situated on the front side of the neck at the level of C5 to T1 vertebral bodies, just below the laryngeal prominence (Adam's apple), near the thyroid cartilage over the trachea but covered by layers of skin and muscle. The thyroid is one of the larger endocrine glands - 10-20 grams in adults- and butterfly-shaped: the wings correspond to the lobes and the body to the isthmus of the thyroid. It may enlarge substantially during pregnancy and when affected by a variety of diseases.

Blood supply

The thyroid gland is supplied by two pairs of arteries: the superior and inferior thyroid arteries of each side. The superior thyroid artery is the first branch of the external carotid, and supplies mostly the upper half of the thyroid gland, while the inferior thyroid artery is the major branch of the thyrocervical trunk, which comes off of the subclavian artery.

Histology of the thyroid

The thyroid is composed of spherical follicles that selectively absorb iodine (as iodide ions, I-) from the blood and for production of thyroid hormones. Twenty-five percent of all the body I- is in the thyroid gland. The follicles are made of a single layer of thyroid epithelial cells, which secrete T3 and T4. Inside the follicles is a colloid, which is rich in a protein called thyroglobulin. The colloidal material serves as a reservoir of materials for thyroid hormone production and, to a lesser extent, a reservoir of the hormones themselves. Scattered among follicular cells and in spaces between the spherical follicles are another type of thyroid cell, parafollicular cells or C cells, which secrete calcitonin.

Physiology

The primary function of the thyroid is production of the hormones thyroxine (T4), triiodothyronine (T3), and calcitonin. Up to 40% of the T4 is converted to T3 by peripheral organs such as the liver and spleen.

T3 & T4

Thyroxine is synthesized by the follicular cells from the tyrosine residues of the protein called thyroglobulin (TG). In the blood, T4 and T3 are partially bound to thyroxine-binding globulin, transthyretin and albumin. Only the free fraction (not bound to these proteins) has hormonal activity. The production of thyroxine is regulated by thyroid-stimulating hormone (TSH), released by the pituitary. The thyroid and thyrotropes form a negative feedback loop: TSH production is suppressed when the T4 levels are high, and vice versa. The TSH production itself is modulated by thyrotropin-releasing hormone, which is produced by the hypothalamus and secreted at an increased rate in situations such as cold (in which an accelerated metabolism would generate more heat). TSH production is blunted by somatostatin (SRIH).

Calcitonin

Parafollicular cells produce calcitonin in response to hypercalcemia (not TSH, which stimulates thyroxine production). Calcitonin plays a role in the calcium metabolism; it is the functional opposite of parathyroid hormone, but exerts its influence mainly on bone. Its relatively small role is signified by the fact that after removal of the thyroid, calcium levels typically remain stable.

The significance of iodine-In areas of the world where iodine - essential for the production of thyroxine, which contains four iodine atoms - is lacking in the diet, the thyroid gland can be considerably enlarged, resulting in the swollen necks of endemic goitre. Iodized salt is a cheap and easy way of adding iodine to the diet. This has eliminated endemic cretinism in most developed countries, and some governments have made the iodination of flour mandatory.

Diseases of the thyroid gland

Hyper- and hypofunction:

Hypothyroidism

· Hashimoto's thyroiditis / thyroiditis

· Ord's thyroiditis

· Postoperative hypothyroidism

· Postpartum thyroiditis

· Silent thyroiditis

· Acute thyroiditis

· Iatrogenic hypothyroidism

Hyperthyroidism

· Thyroid storm

· Graves-Basedow disease

· Toxic thyroid nodule

· Toxic nodular struma (Plummer's disease)

· Hashitoxicosis

· Iatrogenic hyperthyroidism

Anatomical problems:

· Goitre

· Endemic goitre

· Diffuse goitre

· Multinodular goitre

· Lingual thyroid

· Thyroglossal duct cyst

Tumors:

· Thyroid adenoma

· Thyroid cancer

· Papillary

· Follicular

· Medullary

· Anaplastic

· Lymphomas and metastasis from elsewhere (rare)

Hypothyroidism

Hypothyroidism is the disease state caused by insufficient production of thyroid hormone by the thyroid gland. There are several distinct causes for chronic hypothyroidism, the most common being Hashimoto's thyroiditis and hypothyroidism following radioiodine therapy for hyperthyroidism.

The severity of hypothyroidism varies widely. Patients are classified as "subclinical hypothyroid" if diagnostic findings show thyroid hormone abnormalities, but they do not exhibit any symptoms.

Signs and Symptoms

· Slowed speech and a hoarse, breaking voice

· Impaired memory

· Increased sensitivity to heat and cold

· A slow heart rate and sluggish reflexes

· Dry puffy skin, especially on the face, and hair loss, especially thinning of the outer 1/3 of the eyebrows

· Depression (especially in the elderly)

· Weight gain and obesity

· Anemia

· Slowed metabolism

· Constipation

· Fatigue

· Choking sensation or difficulty swallowing

· Shortness of breath

· Increased need for sleep

· Muscle cramps and joint pain

· Decreased sex drive

· Brittle fingernails

· Paleness

· Irritability

· Abnormal menstrual cycles

· Thin, fragile or absent cuticles

· Infertility or difficulty becoming pregnant

· Elevated serum cholesterol

Treatment

1. Substitution of thyroid hormones by taking thyroxine (T4) tablets, usually in the form of levothyroxine. Doses are started with smaller amounts of thyroxine and then slowly titrated under control of TSH levels. Usually the maintenance dose is about 1 to 2 micrograms (µg) per kilogram of body weight.

2. Deficiencies of some dietary minerals and iodine can lead to hypothyroidism. Supplementation can be an effective treatment, but only if iodine deficiency has been documented.

3. Synthetic T3.

Hashimoto's thyroiditis

Hashimoto's thyroiditis, the most common form of thyroiditis, is an autoimmune disease where the body's own antibodies fight the cells of the thyroid. It is four times more common among women than men, and runs in families, with the HLADR5 gene most strongly implicated (conferring a relative risk of 3) in the UK. The genes implicated vary in different ethnic groups.

In many cases, Hashimoto's thyroiditis usually results in hypothyroidism, although in its acute phase, it can cause a transient hyperthyroid state. Treatment is by daily thyroxine, with the sodium salt of thyroxine liothyronine given when the need to raise levels of circulating thyroxine is urgent. Symptoms of Hashimoto's thyroiditis include symptoms of hypothyroidism and a goitre.

Hyperthyroidism

Hyperthyroidism (or "overactive thyroid gland") is the clinical syndrome caused by an excess of circulating free thyroxine (T4) or free triiodothyronine (T3), or both.

Major causes are:

· Graves' disease (the most common etiology with 70-80%)

· Toxic thyroid adenoma

· Toxic multinodular goitre

· Other causes of hyperthyroxinemia (high blood levels of thyroid hormones) are not to be confused with true hyperthyroidism and include subacute and other forms of thyroiditis (inflammation). Thyrotoxicosis (symptoms caused by hyperthyroxinemia) can occur in both hyperthyroidism and thyroiditis. When it causes acutely increased metabolism, it is sometimes called "thyroid storm".

Signs and symptoms

Major clinical features in humans are weight loss (often accompanied by a ravenous appetite), fatigue, weakness, hyperactivity, irritability, apathy, depression, polyuria, and sweating. Additionally, patients may present with a variety of symptoms such as palpitations and arrhythmias (notably atrial fibrillation), dyspnea, infertility, loss of libido, nausea, vomiting, and diarrhea.

Diagnosis

A diagnosis is suspected through blood tests, by measuring the level of TSH (thyroid stimulating hormone) in the blood. If TSH is low, there is likely to be increased production of T4 and/or T3. Measuring specific antibodies, such as anti-TSH-receptor antibodies in Graves' disease, may contribute to the diagnosis. In all patients with hyperthyroxinemia, scintigraphy is required in order to distinguish true hyperthyroidism from thyroiditis.

Treatment

Surgery-Surgery (to remove the whole thyroid or a part of it) is not extensively used because most common forms of hyperthyroidism are quite effectively treated by the radioactive iodine method.

Radioiodine-In Radioiodine (treatment) therapy, radioactive iodine is given orally (either by pill or liquid) on a one-time basis to ablate a hyperactive gland. The iodine given for ablative treatment is different from the iodine used in a scan. Radioactive iodine is given after a routine iodine scan, and uptake of the iodine is determined to confirm hyperthyroidism. The radioactive iodine is picked up by the active cells in the thyroid and destroys them. Since iodine is only picked up by thyroid cells, the destruction is local and there are no widespread side effects with this therapy.

Thyrostatics-are drugs that inhibit the production of thyroid hormones, such as methimazole (Tapazole®) or PTU (propylthiouracil).

Graves-Basedow disease or Graves’ disease

Graves-Basedow disease is a form of thyroiditis, an autoimmune disorder that stimulates the thyroid gland, being the most common cause of hyperthyroidism (overactivity of the thyroid). Also known in the English-speaking world simply as Graves' disease, it occurs most frequently in women (8:1 compared to men) of middle age. Symptoms include fatigue, weight loss and rapid heart beat. Because similar antibodies to those stimulating the thyroid also affect the eye, eye symptoms are also commonly reported. Treatment is with medication that reduces the production of thyroid hormone (thyroxin), surgery thyroidectomy or with radioactive iodine if refractory.

Goitre

A goitre is a swelling in the neck (just below Adam's apple or larynx) due to an enlarged thyroid gland. They are classified in different ways:

A "diffuse goitre" is a goitre that has spread through all of the thyroid (and is contrasted with a "simple goitre", "single thyroid nodule" and "multinodular goitre".

"Toxic goitre" refers to goitre deriving from inflammation, neoplasm, or malfunction of the thyroid, while "nontoxic goitre" refers to all other types (such as that caused by lithium or an autoimmune reaction.)

The most common cause for goitre in the world is iodine deficiency. Iodine is necessary for the synthesis of the thyroid hormones, triiodothyronine and thyroxine (T3 and T4). When iodine is not available, these hormones cannot be made. In response to low thyroid hormones, the pituitary gland releases thyroid stimulating hormone (TSH). Thyroid stimulating hormone acts to try and increase synthesis of T3 and T4, but it also causes the thyroid gland to grow in size as a type of compensation.

Goitre is more common among women. Treatment may not be necessary if the goitre is not caused by disease and is small. Removal of the goitre may be necessary if it causes difficulty with breathing or swallowing.

Thyroid cancer

Thyroid cancer is cancer of the thyroid gland. There are four forms: papillary, follicular, medullary and anaplastic. The most common forms (papillary and follicular) are fairly benign, and the medullary form also has a good prognosis; the anaplastic form is fast-growing and poorly responsive to therapy.

Masses of the thyroid are diagnosed by fine needle aspiration (FNA) or frequently by thyroidectomy (surgical removal and subsequent pathological examination). As the thyroid concentrates iodine, radioactive iodine is a commonly used modality in thyroid carcinomas.

Thyroid cancers can be classified according to their pathological characteristics. The following variants can be distinguished: