Goiter overview

# Overview
Goiter is the abnormal enlargement of the thyroid gland. Development of goiter doesn't imply the malfunction of the thyroid gland and Goiter occurs in a gland which is either in hypothyroid, euthyroid or hyperthyroid state. Lack of iodine in the diet is the most common cause of goiters worldwide. Goiter is usually painless but if large in size may lead to compression symptoms such as dysphagia, dyspnea and hoarseness of voice. Ancient documented texts with reference to goiter have been seen dating back to 2700 BC. In 1949, commercial synthesis of levothyroxine was done successfully. In 1974, an international committee of thyroid pathologists published the first WHO histological classification of thyroid tumors which had served as a basis for various clinical, pathological, and epidemiological studies. Goiter may also be classified according to various classification methods based on etiologic, epidemiological, anatomical, pathological, functional and morphological factors. When the TRH-TSH thyroid hormone axis is interfered, it results in the structural and functional changes of the thyroid gland. Increased TSH production is triggered by a deficiency in thyroid hormone synthesis or intake. In order to normalize thyroid hormone levels, the increase in TSH leads to increased cellularity and hyperplasia of the thyroid gland and when this process is continuous, it leads to goiter. Various factors have been associated with the cause of goiter such as hereditary, hormonal, dietary, pharmacological, physiological, environmental and pathological factors. The most common causes being, iodine deficiency, Grave's disease and Hashimoto's disease. Goiter may be caused by a mutation in the genes such as the thyroglobulin (Tg) gene, thyroid-stimulating hormone receptor (TSHR) gene and the sodium-iodide symporter (NIS) gene. As goiter manifests in a variety of clinical forms, differentiation must be established in accordance with the particular sub-type. The incidence of goiter is approximately 1400 - 1700 per 100,000 individuals in females and 900 per 100,000 individuals in males, worldwide. The prevalence of goiter is approximately 3000 per 100,000 individuals worldwide, for single thyroid nodules. The frequency of goiter increases in women over 45 years of age. The rate of occurrence of goiter in females is higher than that in males by a ratio of 4:1. There is no racial predilection to goiter. Screening for goiter initially involves physical examination followed by blood tests for free T4 and TSH and finally thyroid scan, ultrasound and biopsy to rule out malignancy. Slow growth of the nodules is observed in benign goiter. Rapid growth and large size of goiter causing compressive symptoms may be suggestive of thyroid cancer. Common complications of goiter include those related to the enlarged gland and to thyroidectomy. Prognosis is generally good for benign goiter. Although the prognosis is good and the risk is low, caution is advised for the possible development of malignancy. Careful monitoring of size, shape and consistency associated with pain is advised. Radiation exposure has been attributed to the possible development of malignancy. A history of low iodine intake, history of use of therapeutic drugs that hinder normal thyroid hormonal activity, radiation exposure and positive family history of thyroid diseases. Symptoms of goiter include, swelling at the base of the neck, dysphagia, hoarseness of voice and dyspnea. Physical examination of patients with Goiter is usually remarkable for swelling at the base of the neck. Patients with Goiter may be in a euthyroid, hypothyroid or hyperthyroid state. Patients should be evaluated for free T4, T3, TSH levels and TPO antibodies. Plain x-ray findings of the neck suggestive of goiter include tracheal deviation or compression and calcification within the goiter. Ultrasound may be helpful in determining the physical characteristics of the thyroid gland and also aids in ultrasound guided FNAC. Thyroid radioisotope scan may be helpful in the diagnosis of goiter. Barium swallow may be helpful in assessing compression of the esophagus due to goiter. Indirect laryngoscopy helps assess the mobility of the vocal cords. Pharmacologic therapy for goiter involves normalizing hormone levels and treating the inflammation. Treatment regimen involves Lugols iodine, antithyroid drugs and -adrenergic blockers. In some cases, radioactive iodine may be used to treat an overactive thyroid gland. Thyroid surgery may be advised in cases of goiter depending upon the symptoms and extent as well as type of gland pathology such as, compressive symptoms, thyroid hyper-functioning and thyroid cancer. Effective measures for the primary prevention of goiter include iodine supplementation and smoking cessation.

# Historical Perspective
Ancient documented texts with reference to goiter have been seen dating back to 2700 BC. In 1949, commercial synthesis of levothyroxine was done successfully.

# Classification
In 1974, an international committee of thyroid pathologists published the first WHO histological classification of thyroid tumors which had served as a basis for various clinical, pathological, and  epidemiological studies. Goiter may also be classified according to various classification methods based on etiological, epidemiological, anatomical, pathological, functional and morphological factors.

# Pathophysiology
When the TRH-TSH thyroid hormone axis is interfered, it results in the structural and functional changes of the thyroid gland. Increased TSH production is triggered by a deficiency in thyroid hormone synthesis or intake. In order to normalize thyroid hormone levels, the increase in TSH leads to increased cellularity and hyperplasia of the thyroid gland and when this process is continuous, it leads to goiter.

# Causes
Various factors have been associated with the cause of goiter such as hereditary, hormonal, dietary, pharmacological, physiological, environmental and pathological factors. The most common causes being, iodine deficiency, Grave's disease and hashimoto's disease. Goiter may be caused by a mutation in the genes such as the thyroglobulin (Tg) gene, thyroid-stimulating hormone receptor (TSHR) gene and the Na+/I- symporter (NIS) gene.

# Differentiating Goiter from other Diseases
As goiter manifests in a variety of clinical forms, differentiation must be established in accordance with the particular subtype.

# Epidemiology and Demographics
The incidence of goiter is approximately 1400 to 1700 per 100,000 individuals in females and 900 per 100,000 individuals in males, worldwide. The prevalence of goiter is approximately 3000 per 100,000 individuals worldwide, for single thyroid nodules. The frequency of goiter increases in women over 45 years of age. The rate of occurrence of goiter in females is higher than that in males by a ratio of 4:1. There is no racial predilection to goiter.

# Risk Factors
Common risk factors in the development of goiter include non-iodized salt, age over 45 years, female gender, drugs and radiation therapies.

# Screening
Screening for goiter initially involves physical examination followed by blood tests for free T4 and TSH and finally thyroid scan, ultrasound and biopsy to rule out malignanacy.

# Natural History, Complications and Prognosis
Slow growth of the nodules is observed in benign goiter. Rapid growth and large size of goiter causing compressive symptoms may be suggestive of thyroid cancer. Common complications of goiter include those related to the enlarged gland and those related to thyroidectomy. Prognosis is generally good for benign goiter. Although the prognosis is good and the risk is low, caution is advised to prevent the possible development of malignancy. Careful monitoring of size, shape and consistency associated with pain is recommended. Radiation exposure has been attributed to the possible development of malignancy.

# Diagnosis

## History and Symptoms
A history of low iodine intake, history of use of therapeutic drugs that hinder normal thyroid hormonal activity, radiation exposure and positive family history of thyroid diseases. Symptoms of goiter include, swelling at the base of the neck, difficulty swallowing, hoarseness of voice and difficulty in breathing.

## Physical Examination
Physical examination of patients with goiter is usually remarkable for swelling at the base of the neck.

## Laboratory Findings
Patients with goiter may be in a euthyroid, hypothyroid or hyperthyroid state. Patients should be evaluated for free T4, T3, TSH levels and thyroid peroxidase (TPO) antibodies.

## Electrocardiogram
There are no ECG findings associated with goiter.

## Chest X Ray
Plain x-ray radiography findings of the neck suggestive of goiter may include tracheal deviation or compression and calcification within the goiter.

## CT
Although CT scan gives an excellent anatomical detail of thyroid swelling but has no role as the first line of investigation. CT scan also helps to assess recurrence and intrathoracic or retrosternal goiter.

## MRI
Although MRI gives an excellent anatomical detail of thyroid swelling but has no role as the first line of investigation. MRI also helps to assess recurrence and intrathoracic or retrosternal goiter.

## Echocardiography or Ultrasound
Ultrasound may be helpful in determining the physical characteristics of the goiter. Ultrasound also aids in guided FNA.

## Other Imaging Findings
Thyroid radioisotope scan may be helpful in the diagnosis of goiter. It is helpful in determining the functional activity by distinguishing a nodule as hot, warm, or cold, based on the relative amount of uptake of radioactive isotope. The radioactive isotopes that are most commonly used include Iodine-123, Technetium-99m and Iodine-131

## Other Diagnostic Studies
Barium swallow may be helpful in assessing compression of the esophagus due to goiter. Indirect laryngoscopy helps assess the mobility of the vocal cord.

# Treatment

## Medical Therapy
Pharmacologic medical therapy for goiter involves normalizing hormone levels and treating the inflammation. Treatment regimen involves Lugol's iodine, antithyroid drugs and -adrenergic blockers. In some cases, radioactive iodine may be used to treat an overactive thyroid gland.

## Surgery
Thyroid surgery may be advised in cases of goiter depending upon the symptoms and adverse effects associated with the development of goiter such as, compression related symptoms, thyroid hyper-function and thyroid cancer.

## Primary Prevention
Effective measures for the primary prevention of goiter include iodine supplementation and smoking cessation.

## Secondary Prevention
Secondary prevention measures for goiter are similar to the primary prevention for goiter.

## Cost-Effectiveness of Therapy

## Future or Investigational Therapies