Goiter

A goiter is a chronic enlargement of the thyroid gland Thyroid gland The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland due to nonneoplastic growth occurring in the setting of hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto's disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism, hyperthyroidism Hyperthyroidism Thyrotoxicosis refers to the classic physiologic manifestations of excess thyroid hormones and is not synonymous with hyperthyroidism, which is caused by sustained overproduction and release of T3 and/or T4. Graves' disease is the most common cause of primary hyperthyroidism, followed by toxic multinodular goiter and toxic adenoma. Thyrotoxicosis and Hyperthyroidism, or euthyroidism. Morphologically, thyroid enlargement can be diffuse (smooth consistency) or nodular (uninodular or multinodular). Hashimoto’s thyroiditis Thyroiditis Thyroiditis is a catchall term used to describe a variety of conditions that have inflammation of the thyroid gland in common. It includes pathologies that cause an acute illness with severe thyroid pain (e.g., subacute thyroiditis and infectious thyroiditis) as well as conditions in which there is no clinically evident inflammation and the manifestations primarily reflect thyroid dysfunction or a goiter (e.g., painless thyroiditis and fibrous Riedel's thyroiditis). Thyroiditis is associated with a benign hypothyroid goiter, while Graves’ disease produces a toxic or hyperthyroid goiter. Nontoxic goiter is euthyroid and is usually due to iodine deficiency (the most common cause of goiter). Diagnostic tests Diagnostic tests Diagnostic tests are important aspects in making a diagnosis. Some of the most important epidemiological values of diagnostic tests include sensitivity and specificity, false positives and false negatives, positive and negative predictive values, likelihood ratios, and pre-test and post-test probabilities. Epidemiological Values of Diagnostic Tests include thyroid function tests and measurement of thyroid antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins. Ultrasound, CT, and/or MRI help if lab results are ambiguous and if worrisome features such as obstructive symptoms are present. Radioactive iodine uptake distinguishes hyperthyroid causes. Treatment depends on the underlying condition; options include observation, medication, surgery, and radioiodine ablation.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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Overview

Definition

  • Abnormal nonneoplastic enlargement of the thyroid, a highly vascular gland in the anterior neck region
  • Types according to morphology:
    • Uninodular or multinodular goiter: associated with 1 or more thyroid nodules Thyroid nodules A thyroid nodule is a disordered growth of thyroid cells that produces a mass in the thyroid gland. Most thyroid nodules are benign and detected either by the patient or by the clinician on examination. In other cases, a thyroid nodule is found in radiologic imaging incidentally. Ruling out of malignancy is important. Thyroid Nodules, causing thyroid enlargement
    • Diffuse goiter: smooth and symmetrically enlarged thyroid gland Thyroid gland The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland
  • Types according to thyroid function:
    • Toxic goiter: associated with hyperthyroidism Hyperthyroidism Thyrotoxicosis refers to the classic physiologic manifestations of excess thyroid hormones and is not synonymous with hyperthyroidism, which is caused by sustained overproduction and release of T3 and/or T4. Graves' disease is the most common cause of primary hyperthyroidism, followed by toxic multinodular goiter and toxic adenoma. Thyrotoxicosis and Hyperthyroidism (↑ thyroid hormones Thyroid hormones The 2 primary thyroid hormones are triiodothyronine (T3) and thyroxine (T4). These hormones are synthesized and secreted by the thyroid, and they are responsible for stimulating metabolism in most cells of the body. Their secretion is regulated primarily by thyroid-stimulating hormone (TSH), which is produced by the pituitary gland. Thyroid Hormones)
    • Nontoxic goiter: associated with euthyroidism or normal amount of thyroid hormones Thyroid hormones The 2 primary thyroid hormones are triiodothyronine (T3) and thyroxine (T4). These hormones are synthesized and secreted by the thyroid, and they are responsible for stimulating metabolism in most cells of the body. Their secretion is regulated primarily by thyroid-stimulating hormone (TSH), which is produced by the pituitary gland. Thyroid Hormones
  • Hypothyroid goiter: associated with hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto's disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism (↓ thyroid hormones Thyroid hormones The 2 primary thyroid hormones are triiodothyronine (T3) and thyroxine (T4). These hormones are synthesized and secreted by the thyroid, and they are responsible for stimulating metabolism in most cells of the body. Their secretion is regulated primarily by thyroid-stimulating hormone (TSH), which is produced by the pituitary gland. Thyroid Hormones)

Etiology

  • Iodine deficiency: most common cause worldwide
  • Biosynthetic defects
  • Autoimmune:
    • Hashimoto’s thyroiditis Thyroiditis Thyroiditis is a catchall term used to describe a variety of conditions that have inflammation of the thyroid gland in common. It includes pathologies that cause an acute illness with severe thyroid pain (e.g., subacute thyroiditis and infectious thyroiditis) as well as conditions in which there is no clinically evident inflammation and the manifestations primarily reflect thyroid dysfunction or a goiter (e.g., painless thyroiditis and fibrous Riedel's thyroiditis). Thyroiditis
    • Subacute lymphocytic thyroiditis Thyroiditis Thyroiditis is a catchall term used to describe a variety of conditions that have inflammation of the thyroid gland in common. It includes pathologies that cause an acute illness with severe thyroid pain (e.g., subacute thyroiditis and infectious thyroiditis) as well as conditions in which there is no clinically evident inflammation and the manifestations primarily reflect thyroid dysfunction or a goiter (e.g., painless thyroiditis and fibrous Riedel's thyroiditis). Thyroiditis
    • Postpartum thyroiditis Thyroiditis Thyroiditis is a catchall term used to describe a variety of conditions that have inflammation of the thyroid gland in common. It includes pathologies that cause an acute illness with severe thyroid pain (e.g., subacute thyroiditis and infectious thyroiditis) as well as conditions in which there is no clinically evident inflammation and the manifestations primarily reflect thyroid dysfunction or a goiter (e.g., painless thyroiditis and fibrous Riedel's thyroiditis). Thyroiditis
    • Granulomatous thyroiditis Thyroiditis Thyroiditis is a catchall term used to describe a variety of conditions that have inflammation of the thyroid gland in common. It includes pathologies that cause an acute illness with severe thyroid pain (e.g., subacute thyroiditis and infectious thyroiditis) as well as conditions in which there is no clinically evident inflammation and the manifestations primarily reflect thyroid dysfunction or a goiter (e.g., painless thyroiditis and fibrous Riedel's thyroiditis). Thyroiditis
    • Graves’ disease
  • Infiltrative disease:
    • Riedel’s thyroiditis Thyroiditis Thyroiditis is a catchall term used to describe a variety of conditions that have inflammation of the thyroid gland in common. It includes pathologies that cause an acute illness with severe thyroid pain (e.g., subacute thyroiditis and infectious thyroiditis) as well as conditions in which there is no clinically evident inflammation and the manifestations primarily reflect thyroid dysfunction or a goiter (e.g., painless thyroiditis and fibrous Riedel's thyroiditis). Thyroiditis
    • Sarcoidosis Sarcoidosis Sarcoidosis is a multisystem inflammatory disease that causes noncaseating granulomas. The exact etiology is unknown. Sarcoidosis usually affects the lungs and thoracic lymph nodes, but it can also affect almost every system in the body, including the skin, heart, and eyes, most commonly. Sarcoidosis
    • Histiocytosis
    • Cystinosis
    • Amyloid goiter
  • Radiation exposure
  • Goitrogen ingestion:
    • Lithium
    • Iodine
    • Food (cassava, millet)
  • Thyroid masses: cyst, adenoma, carcinoma

Epidemiology

  • About 200 million people affected in iodine-deficient areas
  • Women > men (4:1)
  • Incidence of goiter decreases with age.
  • Multinodular goiter:
    • More common in older adults
    • Carries up to 5% risk of thyroid cancer Thyroid cancer Thyroid cancer is a malignancy arising from the thyroid gland cells: thyroid follicular cells (papillary, follicular, and anaplastic carcinomas) and calcitonin-producing C cells (medullary carcinomas). Rare cancers are derived from the lymphocytes (lymphoma) and/or stromal and vascular elements (sarcoma). Thyroid Cancer

Pathophysiology

Regulation of hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview

  • Hormones:
    • Thyrotropin-releasing hormone (TRH)
    • Thyroid-stimulating hormone (TSH)
    • Thyroid hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview (free and bound):
      • Thyroxine/tetraiodothyronine (T4): mostly a prohormone but with some hormonal activity
      • Triiodothyronine (T3): the more bioactive form, converted from T4
  • Hypothalamic–pituitary–thyroid axis:
    • Hypothalamus Hypothalamus The hypothalamus is a collection of various nuclei within the diencephalon in the center of the brain. The hypothalamus plays a vital role in endocrine regulation as the primary regulator of the pituitary gland, and it is the major point of integration between the central nervous and endocrine systems. Hypothalamus releases TRH → pituitary gland Pituitary gland The pituitary gland, also known as the hypophysis, is considered the "master endocrine gland" because it releases hormones that regulate the activity of multiple major endocrine organs in the body. The gland sits on the sella turcica, just below the hypothalamus, which is the primary regulator of the pituitary gland. Pituitary Gland releases TSH (prolactin release is also stimulated) → thyroid gland Thyroid gland The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland produces T3/T4:
      • When there is level of free T3/free T4 (FT3/FT4) → ↓ TSH and TRH
      • When there is ↓ level of FT3/FT4 → ↑ TSH and TRH
Hypothalamic–pituitary–thyroid axis feedback loop

Hypothalamic–pituitary–thyroid axis feedback loop:
When the thyroid hormones Thyroid hormones The 2 primary thyroid hormones are triiodothyronine (T3) and thyroxine (T4). These hormones are synthesized and secreted by the thyroid, and they are responsible for stimulating metabolism in most cells of the body. Their secretion is regulated primarily by thyroid-stimulating hormone (TSH), which is produced by the pituitary gland. Thyroid Hormones are low, the hypothalamus releases TRH, and this triggers the pituitary gland Pituitary gland The pituitary gland, also known as the hypophysis, is considered the "master endocrine gland" because it releases hormones that regulate the activity of multiple major endocrine organs in the body. The gland sits on the sella turcica, just below the hypothalamus, which is the primary regulator of the pituitary gland. Pituitary Gland to secrete TSH. This stimulates the thyroid gland Thyroid gland The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland to produce T4 and T3. Approximately ⅓ of the T4 produced is converted to the much more bioactive form T3.
Increase in free or unbound T3/T4 creates negative feedback, inhibiting the release of TRH and TSH.

Image by Lecturio.

Toxic goiter

  • ↓ TSH, ↑ FT3/FT4
  • Seen in Graves’ disease: TSH receptor antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins (TRAbs) stimulate the TSH receptor → thyroid growth + ↑ thyroid hormones Thyroid hormones The 2 primary thyroid hormones are triiodothyronine (T3) and thyroxine (T4). These hormones are synthesized and secreted by the thyroid, and they are responsible for stimulating metabolism in most cells of the body. Their secretion is regulated primarily by thyroid-stimulating hormone (TSH), which is produced by the pituitary gland. Thyroid Hormones
  • Also noted in multinodular goiter, where nodules become autonomous, leading to ↑ T3/T4

Nontoxic goiter

  • Normal thyroid function: 
    • The thyroid overcompensates to maintain the euthyroid state.
    • Small TSH elevation seen leading to growth of the thyroid:
      • Hyperplastic phase: ↑ follicle epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium
      • Involutional phase: when demand for thyroid hormone declines, follicle epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium involutes and colloid accumulates (“colloid goiter”)
    • May start as diffuse goiter → cycles of hyperplasia and involution → irregularity in growths (nodularities) → diffuse type turns into a multinodular goiter
  • Seen in:
    • Endemic goiter (in iodine-poor areas)
    • Sporadic goiter (in iodine-sufficient areas)
      • Exact mechanism unknown
      • Growth factors like TSH may affect follicular cells with unique growth potentials.
    • Biosynthetic defects of thyroid hormones Thyroid hormones The 2 primary thyroid hormones are triiodothyronine (T3) and thyroxine (T4). These hormones are synthesized and secreted by the thyroid, and they are responsible for stimulating metabolism in most cells of the body. Their secretion is regulated primarily by thyroid-stimulating hormone (TSH), which is produced by the pituitary gland. Thyroid Hormones
    • Goiter in pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-HCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care: ↑ hCG → thyroid stimulation
    • Physiologic goiter ( puberty Puberty Puberty is a complex series of physical, psychosocial, and cognitive transitions usually experienced by adolescents (11-19 years of age). Puberty is marked by a growth in stature and the development of secondary sexual characteristics, achievement of fertility, and changes in most body systems. Puberty: ↑ thyroid size as body grows and develops)
    • Goitrogens
    • Radiation exposure

Hypothyroid goiter

  • ↑ TSH, ↓ FT3/FT4
  • Most commonly seen in Hashimoto’s thyroiditis Thyroiditis Thyroiditis is a catchall term used to describe a variety of conditions that have inflammation of the thyroid gland in common. It includes pathologies that cause an acute illness with severe thyroid pain (e.g., subacute thyroiditis and infectious thyroiditis) as well as conditions in which there is no clinically evident inflammation and the manifestations primarily reflect thyroid dysfunction or a goiter (e.g., painless thyroiditis and fibrous Riedel's thyroiditis). Thyroiditis
  • ↓ Thyroid hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview → ↑ TSH levels → ↑ cellularity and hyperplasia of the thyroid gland Thyroid gland The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland → goiter

Clinical Presentation

Signs and symptoms

  • Initially asymptomatic, as most goiters grow slowly
  • Presentation associated with thyroid dysfunction:
    • Hypothyroidism: fatigue, cold intolerance, swelling, constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation
    • Hyperthyroidism: weight loss, palpitations, dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea, tremors
  • Presentation associated with mass/obstructive effect:
    • Exertional dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea:
      • Most common obstructive symptom
      • Compression of trachea Trachea The trachea is a tubular structure that forms part of the lower respiratory tract. The trachea is continuous superiorly with the larynx and inferiorly becomes the bronchial tree within the lungs. The trachea consists of a support frame of semicircular, or C-shaped, rings made out of hyaline cartilage and reinforced by collagenous connective tissue. Trachea
      • Tracheal diameter of < 5 mm → stridor or wheezing Wheezing Wheezing is an abnormal breath sound characterized by a whistling noise that can be relatively high-pitched and shrill (more common) or coarse. Wheezing is produced by the movement of air through narrowed or compressed small (intrathoracic) airways. Wheezing occurs
    • Neck discomfort (from the enlarging mass)
    • Hoarse voice from recurrent laryngeal nerve compression
    • Dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming "stuck." Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia or difficulty swallowing from compression of the esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus
    • Phrenic nerve paralysis
    • Horner’s syndrome from compression of cervical sympathetic chain
    • Jugular vein compression
    • Superior vena cava Superior vena cava The venous trunk which returns blood from the head, neck, upper extremities and chest. Mediastinum and Great Vessels syndrome

Disease-specific manifestations

  • Tenderness/ pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain (granulomatous thyroiditis Thyroiditis Thyroiditis is a catchall term used to describe a variety of conditions that have inflammation of the thyroid gland in common. It includes pathologies that cause an acute illness with severe thyroid pain (e.g., subacute thyroiditis and infectious thyroiditis) as well as conditions in which there is no clinically evident inflammation and the manifestations primarily reflect thyroid dysfunction or a goiter (e.g., painless thyroiditis and fibrous Riedel's thyroiditis). Thyroiditis)
  • Accompanying orbitopathy, dermopathy (Graves’ disease)
  • Hard thyroid gland Thyroid gland The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland with extensive fibrosis beyond thyroid area (Riedel’s thyroiditis Thyroiditis Thyroiditis is a catchall term used to describe a variety of conditions that have inflammation of the thyroid gland in common. It includes pathologies that cause an acute illness with severe thyroid pain (e.g., subacute thyroiditis and infectious thyroiditis) as well as conditions in which there is no clinically evident inflammation and the manifestations primarily reflect thyroid dysfunction or a goiter (e.g., painless thyroiditis and fibrous Riedel's thyroiditis). Thyroiditis)
Patient from south sudan with a goiter

Patient from South Sudan with a goiter:
In rural areas of South Sudan, iodine deficiency is a major public health problem.

Image: “Iodine deficiency among goiter patients in rural South Sudan” by Chuot CC, Galukande M, Ibingira C, Kisa N, Fualal JO. License: CC BY 2.0

Diagnosis

Initial assessment

  • Determine history of:
    • Autoimmune disease
    • Iodine intake
    • Medications
    • Head and neck radiation
    • Thyroid disease and associated syndromes in family members
  • Palpation of the thyroid gland Thyroid gland The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland:
    • Determine morphology, consistency, size, and tenderness and search for signs of malignancy
    • Severity of goiter graded 0–2 by the World Health Organization (WHO)
  • Pemberton maneuver (worsens obstructive symptoms):
    • Have the patient hold the arms above the head for 1 minute.
    • This maneuver pushes the thyroid gland Thyroid gland The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland into the thoracic inlet.
    • The results are considered positive if the patient’s neck veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins distend or if facial plethora, cyanosis, or difficulty in swallowing occurs.
WHO classification of goiter
Grade Severity of goiter
0 No goiter
1
  • Palpable goiter but not visible when the neck is in the normal position (i.e., the thyroid gland Thyroid gland The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland is not visibly enlarged)
  • Nodules in a thyroid that is otherwise not enlarged
2 Clearly visible swelling in the neck when the neck is in a normal position and is consistent with an enlarged thyroid gland Thyroid gland The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland when the neck is palpated

Initial tests

Identify thyroid function and possible underlying cause:

  • Thyroid function tests:
    • TSH followed by FT3/FT4
    • Scenarios:
      • Toxic goiter: low TSH, ↑ T3/T4 
      • Nontoxic goiter: normal TSH
      • Hypothyroid goiter: Elevated TSH, ↓ FT3/FT4
  • Thyroid peroxidase Thyroid peroxidase A hemeprotein that catalyzes the oxidation of the iodide radical to iodine with the subsequent iodination of many organic compounds, particularly proteins. Thyroid Hormones (TPO) antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins:
    • For clear-cut hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto's disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism (in the United States), obtaining TPO antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins is not routine, since Hashimoto’s thyroiditis Thyroiditis Thyroiditis is a catchall term used to describe a variety of conditions that have inflammation of the thyroid gland in common. It includes pathologies that cause an acute illness with severe thyroid pain (e.g., subacute thyroiditis and infectious thyroiditis) as well as conditions in which there is no clinically evident inflammation and the manifestations primarily reflect thyroid dysfunction or a goiter (e.g., painless thyroiditis and fibrous Riedel's thyroiditis). Thyroiditis is the most common etiology.
    • In some cases with an unclear picture (e.g., normal TSH):
      •  TPO antibody measurements are obtained.
      • Presence of TPO antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins is suggestive of Hashimoto’s thyroiditis Thyroiditis Thyroiditis is a catchall term used to describe a variety of conditions that have inflammation of the thyroid gland in common. It includes pathologies that cause an acute illness with severe thyroid pain (e.g., subacute thyroiditis and infectious thyroiditis) as well as conditions in which there is no clinically evident inflammation and the manifestations primarily reflect thyroid dysfunction or a goiter (e.g., painless thyroiditis and fibrous Riedel's thyroiditis). Thyroiditis.
  • TRAbs: measured in hyperthyroidism Hyperthyroidism Thyrotoxicosis refers to the classic physiologic manifestations of excess thyroid hormones and is not synonymous with hyperthyroidism, which is caused by sustained overproduction and release of T3 and/or T4. Graves' disease is the most common cause of primary hyperthyroidism, followed by toxic multinodular goiter and toxic adenoma. Thyrotoxicosis and Hyperthyroidism

Subsequent tests

Identify goiter size and presence of nodule with its characteristics and obstructive effect:

  • Ultrasound (US):
    •  Indications: 
      • Thyroid asymmetry, firm consistency or tenderness
      • Rapid growth
      • Nodule(s)
      • Nondiagnostic exam and lab findings
    • An option to assess thyroid vascularity when radioactive iodine uptake (RAIU) scan is contraindicated
  • RAIU: 
    • Assessment of hyperthyroidism Hyperthyroidism Thyrotoxicosis refers to the classic physiologic manifestations of excess thyroid hormones and is not synonymous with hyperthyroidism, which is caused by sustained overproduction and release of T3 and/or T4. Graves' disease is the most common cause of primary hyperthyroidism, followed by toxic multinodular goiter and toxic adenoma. Thyrotoxicosis and Hyperthyroidism or subclinical hyperthyroidism Hyperthyroidism Thyrotoxicosis refers to the classic physiologic manifestations of excess thyroid hormones and is not synonymous with hyperthyroidism, which is caused by sustained overproduction and release of T3 and/or T4. Graves' disease is the most common cause of primary hyperthyroidism, followed by toxic multinodular goiter and toxic adenoma. Thyrotoxicosis and Hyperthyroidism
    • Can help differentiate hyperthyroid states (e.g., Graves’ disease versus multinodular goiter with autonomy)
  • CT or MRI:
    • In patients with obstructive or substernal goiter
    • In those with features suspicious for malignancy
    • Assessment of the thyroid gland Thyroid gland The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland, masses or nodules, and the surrounding structures

Biopsy

Evaluate worrisome features (suspected malignancy) with fine-needle aspiration biopsy:

  • Suspicious nodule findings on US
  • Prominent nodules (≥ 1.5 cm)
  • Firm thyroid gland Thyroid gland The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland
  • Risk factors for malignancy:
    • Young age
    • History of radiation to the head or neck
    • Family history of thyroid cancer Thyroid cancer Thyroid cancer is a malignancy arising from the thyroid gland cells: thyroid follicular cells (papillary, follicular, and anaplastic carcinomas) and calcitonin-producing C cells (medullary carcinomas). Rare cancers are derived from the lymphocytes (lymphoma) and/or stromal and vascular elements (sarcoma). Thyroid Cancer
    • Familial adenomatous polyposis Familial Adenomatous Polyposis Familial adenomatous polyposis (FAP) is an autosomal dominant inherited genetic disorder that presents with numerous adenomatous polyps in the colon. Familial adenomatous polyposis is the most common of the polyposis syndromes, which is a group of inherited or acquired conditions characterized by the growth of polyps in the GI tract, associated with other extracolonic features. Familial Adenomatous Polyposis ( FAP FAP Familial adenomatous polyposis (FAP) is an autosomal dominant inherited genetic disorder that presents with numerous adenomatous polyps in the colon. Familial adenomatous polyposis is the most common of the polyposis syndromes, which is a group of inherited or acquired conditions characterized by the growth of polyps in the GI tract, associated with other extracolonic features. Familial Adenomatous Polyposis) or other associated syndromes
    • Firm, solid, and/or cold nodules

Management

Toxic goiter

  • Surgery or radioiodine ablation 
  • Thionamides are an option in those who decline radioiodine ablation or surgery.
  • Beta-blockers for symptomatic relief

Nontoxic goiter

  • Observation: 
    • Indicated for asymptomatic euthyroid nonobstructive goiters
    • Regular neck exam, with thyroid function tests and US
  • Suppression (levothyroxine) therapy for euthyroid goiter:
    • Controversial
    • Associated with angina, atrial fibrillation Atrial fibrillation Atrial fibrillation (AF or Afib) is a supraventricular tachyarrhythmia and the most common kind of arrhythmia. It is caused by rapid, uncontrolled atrial contractions and uncoordinated ventricular responses. Atrial Fibrillation, and ↓ bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones density
  • Iodine replacement if needed
  • Surgery (total or near-total thyroidectomy) for: 
    • Large (> 80–100 mL), growing goiters
    • Goiters causing obstruction
  • Radioiodine ablation: 
    • For those with growing goiters who are poor surgical candidates or who decline surgery
    • Goiter reduction by 50%

Hypothyroid goiter

  • Levothyroxine: 
    • For hypothyroid nonobstructive goiters
    • Goiter size may decrease, but with less efficacy.
  • Surgery if goiter causes obstruction

Clinical Relevance

  • Thyroid nodule: disordered growth of thyroid cells, producing a mass in the thyroid gland Thyroid gland The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: The majority of nodules are detected on examination or found incidentally in radiologic images. Workup includes TSH and US, followed by a RAIU/thyroid scan if hyperthyroidism Hyperthyroidism Thyrotoxicosis refers to the classic physiologic manifestations of excess thyroid hormones and is not synonymous with hyperthyroidism, which is caused by sustained overproduction and release of T3 and/or T4. Graves' disease is the most common cause of primary hyperthyroidism, followed by toxic multinodular goiter and toxic adenoma. Thyrotoxicosis and Hyperthyroidism is present. Biopsy is recommended in those with suspicious US findings, cold nodules on thyroid scan, large-sized nodules (generally > 1.5 cm), and risk factors for malignancy. Treatment is dictated by pathology findings.
  • Hypothyroidism: condition characterized by the deficiency of thyroid hormones Thyroid hormones The 2 primary thyroid hormones are triiodothyronine (T3) and thyroxine (T4). These hormones are synthesized and secreted by the thyroid, and they are responsible for stimulating metabolism in most cells of the body. Their secretion is regulated primarily by thyroid-stimulating hormone (TSH), which is produced by the pituitary gland. Thyroid Hormones: Iodine deficiency and Hashimoto’s thyroiditis Thyroiditis Thyroiditis is a catchall term used to describe a variety of conditions that have inflammation of the thyroid gland in common. It includes pathologies that cause an acute illness with severe thyroid pain (e.g., subacute thyroiditis and infectious thyroiditis) as well as conditions in which there is no clinically evident inflammation and the manifestations primarily reflect thyroid dysfunction or a goiter (e.g., painless thyroiditis and fibrous Riedel's thyroiditis). Thyroiditis are the 2 leading etiologies Clinical features reflect the effects of slowed organ function/decreased metabolic rate. Lab tests show elevated TSH and low FT4. Treatment is with levothyroxine.
  • Hyperthyroidism: condition caused by sustained overproduction and release of the thyroid hormones Thyroid hormones The 2 primary thyroid hormones are triiodothyronine (T3) and thyroxine (T4). These hormones are synthesized and secreted by the thyroid, and they are responsible for stimulating metabolism in most cells of the body. Their secretion is regulated primarily by thyroid-stimulating hormone (TSH), which is produced by the pituitary gland. Thyroid Hormones T3 and T4: Graves’ disease is the most common cause of hyperthyroidism Hyperthyroidism Thyrotoxicosis refers to the classic physiologic manifestations of excess thyroid hormones and is not synonymous with hyperthyroidism, which is caused by sustained overproduction and release of T3 and/or T4. Graves' disease is the most common cause of primary hyperthyroidism, followed by toxic multinodular goiter and toxic adenoma. Thyrotoxicosis and Hyperthyroidism. Manifestations are mostly due to the increased metabolic rate and overactivity of the sympathetic nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. General Structure of the Nervous System. Lab tests show low TSH and elevated FT4. Treatment depends on the underlying condition.
  • Hashimoto’s thyroiditis Thyroiditis Thyroiditis is a catchall term used to describe a variety of conditions that have inflammation of the thyroid gland in common. It includes pathologies that cause an acute illness with severe thyroid pain (e.g., subacute thyroiditis and infectious thyroiditis) as well as conditions in which there is no clinically evident inflammation and the manifestations primarily reflect thyroid dysfunction or a goiter (e.g., painless thyroiditis and fibrous Riedel's thyroiditis). Thyroiditis: also called chronic lymphocytic thyroiditis Thyroiditis Thyroiditis is a catchall term used to describe a variety of conditions that have inflammation of the thyroid gland in common. It includes pathologies that cause an acute illness with severe thyroid pain (e.g., subacute thyroiditis and infectious thyroiditis) as well as conditions in which there is no clinically evident inflammation and the manifestations primarily reflect thyroid dysfunction or a goiter (e.g., painless thyroiditis and fibrous Riedel's thyroiditis). Thyroiditis: Hashimoto’s thyroiditis Thyroiditis Thyroiditis is a catchall term used to describe a variety of conditions that have inflammation of the thyroid gland in common. It includes pathologies that cause an acute illness with severe thyroid pain (e.g., subacute thyroiditis and infectious thyroiditis) as well as conditions in which there is no clinically evident inflammation and the manifestations primarily reflect thyroid dysfunction or a goiter (e.g., painless thyroiditis and fibrous Riedel's thyroiditis). Thyroiditis is the most common cause of hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto's disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism in iodine-sufficient regions. It is an autoimmune disorder that leads to destruction of the thyroid cells and thyroid failure. Presentation can be a painless goiter (in later/“burned-out” stages, the gland is atrophic). Lab tests show elevated TSH and low FT4 and are positive for antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins against thyroglobulin and thyroid peroxidase. Treatment is lifelong thyroid replacement therapy.
  • Graves’ disease: autoimmune disorder characterized by the presence of circulating antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins against the TSH receptors, causing the thyroid gland Thyroid gland The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland to hyperfunction: Clinical features include hyperthyroidism Hyperthyroidism Thyrotoxicosis refers to the classic physiologic manifestations of excess thyroid hormones and is not synonymous with hyperthyroidism, which is caused by sustained overproduction and release of T3 and/or T4. Graves' disease is the most common cause of primary hyperthyroidism, followed by toxic multinodular goiter and toxic adenoma. Thyrotoxicosis and Hyperthyroidism, orbitopathy, goiter, and dermopathy/pretibial myxedema. Laboratory tests show low TSH, elevated T4, and thyrotropin-receptor antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins (particularly the thyroid-stimulating immunoglobulins Immunoglobulins Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins). Treatment options include thionamides, radioiodine ablation, and surgery.
  • Thyroid cancer: most common endocrine system cancer: Malignancy arises from the cell types of the gland: thyroid follicular cells, calcitonin-producing C cells, lymphocytes Lymphocytes Lymphocytes are heterogeneous WBCs involved in immune response. Lymphocytes develop from the bone marrow, starting from hematopoietic stem cells (HSCs) and progressing to common lymphoid progenitors (CLPs). B and T lymphocytes and natural killer (NK) cells arise from the lineage. Lymphocytes, and stromal and vascular elements. Metastasis from other malignancies can occur in the thyroid gland Thyroid gland The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland. Patients can present with a growing thyroid mass, thyroid asymmetry, or gland enlargement/swelling. Diagnosis is by biopsy. Treatment varies by type and stage. Options include surgery, radioactive iodine, targeted therapy Targeted Therapy Targeted therapy exerts antineoplastic activity against cancer cells by interfering with unique properties found in tumors or malignancies. The types of drugs can be small molecules, which are able to enter cells, or monoclonal antibodies, which have targets outside of or on the surface of cells. Targeted Therapy and Other Nontraditional Antineoplastic Agents, and radiation therapy.
  • Metastases from other malignancies can occur in the thyroid gland Thyroid gland The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland. Patients can present with a growing thyroid mass, thyroid asymmetry, or gland enlargement/swelling. Diagnosis is by biopsy. Treatment varies by type and stage. Options include surgery, radioactive iodine, targeted therapy Targeted Therapy Targeted therapy exerts antineoplastic activity against cancer cells by interfering with unique properties found in tumors or malignancies. The types of drugs can be small molecules, which are able to enter cells, or monoclonal antibodies, which have targets outside of or on the surface of cells. Targeted Therapy and Other Nontraditional Antineoplastic Agents, and radiation therapy.

References

  1. Alkabban F, Patel B. (2020). Nontoxic goiter. StatPearls. Retrieved February 13, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK482274/
  2. Fitzgerald PA. (2021). Thyroid nodules & multinodular goiter. In Papadakis MA, McPhee SJ, Rabow MW (Eds.). Current Medical Diagnosis & Treatment 2021. New York: McGraw-Hill.
  3. Jameson J, Mandel SJ, Weetman AP. (2018). Thyroid nodular disease and thyroid cancer. In Jameson JL, et al. (Eds.) Harrison’s Principles of Internal Medicine, 20th ed., vol. 2, pp 2710–2714.
  4. Kuo LE, Cho NL. (2020). Thyroid & parathyroid. In: Doherty GM (Ed.), Current Diagnosis & Treatment: Surgery, 15th ed. New York: McGraw-Hill.
  5. Mulinda J, Khardori R. (2020). Goiter. Medscape. Retrieved February 12, 2021, from https://emedicine.medscape.com/article/120034-overview#a6
  6. Ross D. (2020). Clinical presentation and evaluation of goiter in adults. UpToDate. Retrieved February 14, 2021, from https://www.uptodate.com/contents/clinical-presentation-and-evaluation-of-goiter-in-adults
  7. Ross, D. (2019). Treatment of nontoxic, nonobstructive goiter. UpToDate. Retrieved February 14, 2021, from https://www.uptodate.com/contents/treatment-of-nontoxic-nonobstructive-goiter
  8. Peeters RP, Visser TJ. (2000). Metabolism of thyroid hormone. In Feingold KR, Anawalt B, Boyce A, et al. (Eds.), Endotext. MDText.com, Inc. http://www.ncbi.nlm.nih.gov/books/NBK285545/

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