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Thyroid Cancer

Thyroid Thyroid 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: Anatomy cancer is a malignancy Malignancy Hemothorax arising from the thyroid Thyroid 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: Anatomy gland cells: thyroid follicular cells Thyroid follicular cells Epithelial cells of the thyroid gland that produce and secrete thyroxine and triiodothyronine. Thyroid Hormones (papillary, follicular, and anaplastic carcinomas) and calcitonin-producing C cells C cells Calcium Hemostasis and Bone Metabolism (medullary carcinomas). Rare cancers are derived from the 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: Histology ( lymphoma Lymphoma A general term for various neoplastic diseases of the lymphoid tissue. Imaging of the Mediastinum) and/or stromal and vascular elements (sarcoma). Driver mutations involving the receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors tyrosine Tyrosine A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine; thyroid hormones; and melanin. Synthesis of Nonessential Amino Acids kinase pathway (such as RET and BRAF) and a family history Family History Adult Health Maintenance of cancer or related syndromes increase the risk. Exposure to ionizing radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma and iodine Iodine A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126. 90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. Thyroid Hormones deficiency are also considered risk factors. The major types can present as 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 or enlarged cervical lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs nodes. The diagnostic approach includes thyroid-stimulating hormone Thyroid-stimulating hormone A glycoprotein hormone secreted by the adenohypophysis. Thyrotropin stimulates thyroid gland by increasing the iodide transport, synthesis and release of thyroid hormones (thyroxine and triiodothyronine). Thyroid Hormones, ultrasonography, and biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma. Treatment options are surgical removal of the thyroid Thyroid 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: Anatomy gland, with the addition of radioactive iodine Iodine A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126. 90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. Thyroid Hormones therapy and systemic therapy, depending on the type and extent of the thyroid Thyroid 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: Anatomy malignancy Malignancy Hemothorax.

Last updated: Oct 13, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Definition

Thyroid Thyroid 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: Anatomy cancer is a malignancy Malignancy Hemothorax arising from the cells of the thyroid Thyroid 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: Anatomy gland, including thyroid follicular cells Thyroid follicular cells Epithelial cells of the thyroid gland that produce and secrete thyroxine and triiodothyronine. Thyroid Hormones (thyrocytes), calcitonin-producing C cells C cells Calcium Hemostasis and Bone Metabolism, 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: Histology, and/or stromal and vascular elements.

Epidemiology

  • In the United States:
    • Thyroid Thyroid 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: Anatomy cancer accounts for 1% of new cancer diagnoses annually.
    • Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency has increased over 30 years, but mortality Mortality All deaths reported in a given population. Measures of Health Status has not changed.
  • Peak incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency dependent on type of cancer
  • Slight female predominance

Etiology

  • Genetic factors:
    • Driver mutations:
      • Set of genetic mutations Genetic Mutations Carcinogenesis found in different types of thyroid Thyroid 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: Anatomy cancer (e.g., papillary thyroid Thyroid 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: Anatomy carcinoma ( PTC PTC Acute Cholangitis): BRAF and RET mutations)
      • Most are involved in the receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors tyrosine Tyrosine A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine; thyroid hormones; and melanin. Synthesis of Nonessential Amino Acids kinase (RTK) pathway.
    • Family history Family History Adult Health Maintenance:
      • Family history Family History Adult Health Maintenance of thyroid Thyroid 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: Anatomy cancer (in 1st-degree relative)
      • Family history Family History Adult Health Maintenance of thyroid Thyroid 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: Anatomy cancer syndrome (familial polyposis, Cowden syndrome Cowden Syndrome Cowden syndrome, also known as multiple hamartoma syndrome, is an autosomal dominant inherited condition that presents with multiple, noncancerous growths on various parts of the body. The syndrome is classified as a phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome that is caused by mutations in the PTEN gene. Cowden Syndrome, MEN2)
  • Environmental factors:
    • Ionizing radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma:
      • Leads to DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure mutations, especially during first 2 decades of life
      • Noted in people exposed to radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma from the atomic bombs in Hiroshima and Nagasaki and from the nuclear plant accident in Chernobyl
    • Iodine Iodine A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126. 90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. Thyroid Hormones deficiency: higher frequency of follicular carcinoma

Pathophysiology

Origins and precursor lesions

  • Most thyroid Thyroid 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: Anatomy cancers are derived from:
  • Rare types arise from:
    • Stroma or connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue: Histology (sarcoma)
  • Recognized precursor lesions:

Pathogenesis

  • Papillary thyroid Thyroid 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: Anatomy carcinoma:
    • Rearrangements involving RET and NTRK1 (seen in approximately 5%):
      • Form fusion genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure encoding constitutively active RTK
      • Lead to development of malignancy Malignancy Hemothorax
    • Gain-of-function mutations in BRAF:
      • BRAF encodes a serine Serine A non-essential amino acid occurring in natural form as the l-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines; pyrimidines; and other amino acids. Synthesis of Nonessential Amino Acids–threonine kinase
      • BRAF V600E: most common mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations
      • Noted in PTCs with recurrence, invasive growth, and extrathyroidal extension Extension Examination of the Upper Limbs
      • Not found in follicular thyroid Thyroid 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: Anatomy carcinoma
      • Also found in other cancers (e.g., melanoma Melanoma Melanoma is a malignant tumor arising from melanocytes, the melanin-producing cells of the epidermis. These tumors are most common in fair-skinned individuals with a history of excessive sun exposure and sunburns. Melanoma, colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy cancer)
  • Follicular thyroid Thyroid 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: Anatomy carcinoma:
    • Gain-of-function mutations in RAS RAS Renal artery stenosis (RAS) is the narrowing of one or both renal arteries, usually caused by atherosclerotic disease or by fibromuscular dysplasia. If the stenosis is severe enough, the stenosis causes decreased renal blood flow, which activates the renin-angiotensin-aldosterone system (RAAS) and leads to renovascular hypertension (RVH). Renal Artery Stenosis:
      • Thyroid Thyroid 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: Anatomy differentiation markers (such as thyroglobulin Thyroglobulin Thyroid Hormones and 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) are expressed, leading to follicular growth.
      •  Found in up to 40% of follicular adenomas and up to 50% of follicular carcinomas
    • Fusion gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics PAX8–PPARG:
      • Translocation results in fusion of PAX8 (a thyroid Thyroid 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: Anatomy transcription factor Transcription factor Generic term for proteins necessary for transcription Regulation of Transcription) and peroxisome proliferator–activated receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors gamma 1 (PPARG).
      • Effect: inhibition of cell differentiation and ↑ cell growth
    • Gain-of-function mutations of PIK3CA 
  • Anaplastic (undifferentiated) and poorly differentiated carcinoma:
    • Can arise from dedifferentiation of papillary or follicular thyroid Thyroid 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: Anatomy carcinoma (more mutational burden)
    • TP53 mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations → reduced apoptosis Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, I.e., DNA fragmentation. It is genetically-programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Ischemic Cell Damage of cells
    • TERT (encodes telomerase Telomerase An essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic chromosomes. DNA Replication) and CTNNB1 mutations appear to have aggressive cancer behavior.
  • Medullary thyroid Thyroid 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: Anatomy carcinoma:

Clinical Presentation

General features

  • Initially presents asymptomatically or as a painless thyroid Thyroid 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: Anatomy nodule Nodule Chalazion in the neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess:
    • May be on the thyroid Thyroid 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: Anatomy or a cervical lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs node
    • Progresses to a tender or painful lesion as disease advances
  • Usually euthyroid Euthyroid Thyroiditis, but 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 Hypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate. Thyrotoxicosis and Hyperthyroidism symptoms can occur.
  • Symptoms associated with local invasion: 
    • 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: Anatomy fixation
    • Recurrent laryngeal nerve damage → hoarseness Hoarseness An unnaturally deep or rough quality of voice. Parapharyngeal Abscess
    • Cervical sympathetic nerve invasion → Horner’s syndrome Horner’S Syndrome Pupil: Physiology and Abnormalities
    • Esophageal compression Compression Blunt Chest Trauma 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 and odynophagia Odynophagia Epiglottitis
  • Metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis:
    • Pulmonary metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis → cough, 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
    • Brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis neurologic deficits Neurologic Deficits High-Risk Headaches, seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures
    • 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. Bones: Structure and Types metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis 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. Bones: Structure and Types pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, pathologic fractures
    • Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy → abnormal liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes
Thyroid cancer

Thyroid Thyroid 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: Anatomy cancer:
Malignancy Malignancy Hemothorax presents as a solitary thyroid Thyroid 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: Anatomy nodule Nodule Chalazion.


Image by BioDigital, edited by Lecturio
Table: Specific features of major types of thyroid Thyroid 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: Anatomy cancers
Type Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency Clinical features
Differentiated (originating from thyrocytes)
Papillary carcinoma
  • Approximately 85% of cases
  • Most common in young women
  • Peak age: 30–50 years
  • Present as asymptomatic nodules or metastasis Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Grading, Staging, and Metastasis to cervical lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs nodes
  • Advanced disease: hoarseness Hoarseness An unnaturally deep or rough quality of voice. Parapharyngeal Abscess, cough, 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
  • Associated with 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, Cowden syndrome Cowden Syndrome Cowden syndrome, also known as multiple hamartoma syndrome, is an autosomal dominant inherited condition that presents with multiple, noncancerous growths on various parts of the body. The syndrome is classified as a phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome that is caused by mutations in the PTEN gene. Cowden Syndrome
  • Least aggressive; very good prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas if detected early
Follicular carcinoma
  • 5%–15% of cases
  • Women > men
  • Peak age: 40–60 years
  • Seen in areas of iodine Iodine A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126. 90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. Thyroid Hormones deficiency
  • Painless, slow-growing thyroid Thyroid 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: Anatomy nodule Nodule Chalazion
  • Cold nodules on scintigraphy Scintigraphy Sjögren’s Syndrome
  • Commonly spreads hematogenously to lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy or bones
  • Typically, regional lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs nodes are not involved.
  • Associated with Cowden syndrome Cowden Syndrome Cowden syndrome, also known as multiple hamartoma syndrome, is an autosomal dominant inherited condition that presents with multiple, noncancerous growths on various parts of the body. The syndrome is classified as a phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome that is caused by mutations in the PTEN gene. Cowden Syndrome
  • Good prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas if detected early
Undifferentiated (originating from thyrocytes)
Anaplastic carcinoma
  • < 5% of cases
  • Most common in women
  • Average age: 65 years
  • ¼ of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship have past history of or coexisting differentiated carcinoma.
  • Rapid growth → local compression Compression Blunt Chest Trauma
  • Most have spread beyond the thyroid Thyroid 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: Anatomy on presentation
  • Spreads via lymphatics and bloodstream
  • Poor prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas
Originating from parafollicular C cells C cells Calcium Hemostasis and Bone Metabolism
Medullary carcinoma
  • Can present as a neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess or lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs node mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast
  • Also can manifest with:
    • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea, flushing ( calcitonin Calcitonin A peptide hormone that lowers calcium concentration in the blood. In humans, it is released by thyroid cells and acts to decrease the formation and absorptive activity of osteoclasts. Its role in regulating plasma calcium is much greater in children and in certain diseases than in normal adults. Other Antiresorptive Drugs and from tumor-secreted vasoactive intestinal peptide Vasoactive intestinal peptide A highly basic, 28 amino acid neuropeptide released from intestinal mucosa. It has a wide range of biological actions affecting the cardiovascular, gastrointestinal, and respiratory systems and is neuroprotective. It binds special receptors. Gastrointestinal Neural and Hormonal Signaling ( VIP VIP A highly basic, 28 amino acid neuropeptide released from intestinal mucosa. It has a wide range of biological actions affecting the cardiovascular, gastrointestinal, and respiratory systems and is neuroprotective. It binds special receptors. Gastrointestinal Neural and Hormonal Signaling), prostaglandin and serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS)
    • Cushing’s syndrome due to adrenocorticotropic hormone Adrenocorticotropic hormone An anterior pituitary hormone that stimulates the adrenal cortex and its production of corticosteroids. Acth is a 39-amino acid polypeptide of which the n-terminal 24-amino acid segment is identical in all species and contains the adrenocorticotropic activity. Upon further tissue-specific processing, acth can yield alpha-msh and corticotropin-like intermediate lobe peptide (clip). Adrenal Hormones (ACTH)
  • Other biomarker: carcinoembryonic antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination ( CEA CEA A glycoprotein that is secreted into the luminal surface of the epithelia in the gastrointestinal tract. It is found in the feces and pancreaticobiliary secretions and is used to monitor the response to colon cancer treatment. Serum Tumor Markers)
  • Associated with MEN2 syndrome
  • Familial type: more aggressive

Rare malignancies

  • Hürthle cell carcinoma: 
    • Presentation similar that of follicular carcinoma ( thyroid Thyroid 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: Anatomy nodule Nodule Chalazion) but also differs in its tendency for lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs node spread
    • Histology: + oncocytes (eosinophilic cells with abundant cytoplasm)
  • Lymphoma Lymphoma A general term for various neoplastic diseases of the lymphoid tissue. Imaging of the Mediastinum
    • Most are B-cell lymphomas.
    • Associated with 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
  • Sarcoma: aggressive tumor Tumor Inflammation, with poor chemotherapy Chemotherapy Osteosarcoma response
  • Metastases from renal, breast, melanoma Melanoma Melanoma is a malignant tumor arising from melanocytes, the melanin-producing cells of the epidermis. These tumors are most common in fair-skinned individuals with a history of excessive sun exposure and sunburns. Melanoma, and colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy cancers

Diagnosis

Initial workup

  • Tests are directed by the presenting signs and symptoms.
  • Generally, the diagnostic approach follows the detailed workup for 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.
  • Thyroid-stimulating hormone Thyroid-stimulating hormone A glycoprotein hormone secreted by the adenohypophysis. Thyrotropin stimulates thyroid gland by increasing the iodide transport, synthesis and release of thyroid hormones (thyroxine and triiodothyronine). Thyroid Hormones (TSH): normal/↑ TSH or ↓ TSH
  • Thyroid Thyroid 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: Anatomy ultrasound (US):
    • Suspicious nodule Nodule Chalazion findings:
    • Other suspicious US findings:
      • Subcapsular location adjacent to recurrent laryngeal nerve or 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: Anatomy
      • Abnormal cervical lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs nodes
      • Central vascularity
      • Documented growth

Fine-needle aspiration biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma

  • ≥ 1 cm nodules and:
    • Elevated/normal TSH + suspicious US findings
    • Low TSH + suspicious US findings + cold or indeterminate nodules
  • Large nodules, ≥ 1.5 cm
  • Thyroid Thyroid 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: Anatomy nodule Nodule Chalazion of any size with risk factors:
    • Young age
    • Family history Family History Adult Health Maintenance of thyroid Thyroid 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: Anatomy 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
    • History of radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma
  • Suspicious lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs nodes on biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma
Thyroid nodules diagnostic algorithm

Schematic diagram of the diagnostic approach to 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

Image by Lecturio.
Table: Histopathology of thyroid Thyroid 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: Anatomy carcinomas
Type Histopathologic features
Papillary carcinoma
Follicular carcinoma
  • Often single nodules
  • Microscopic findings:
    • Uniform cells form small follicles with or without colloid Colloid Colloid solutions include large proteins or cells that do not readily cross capillary membranes. They remain in the ecf and do not distribute into the icf (similar to crystalloids). Intravenous Fluids.
    • Capsular invasion
    • Invasive carcinomas: + infiltration of thyroid Thyroid 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: Anatomy parenchyma and extrathyroidal tissues
  • Hürthle cell variant: with oncocytes (abundant granular eosinophilic cytoplasm)
Medullary carcinoma
  • May be a solitary lesion ( sporadic Sporadic Selective IgA Deficiency) or multiple, bilateral lesions (familial)
  • Microscopic findings:
    • Polygonal to spindle-shaped cells forming nests, trabeculae, or follicles
    • Stroma may contain amyloid deposits (from calcitonin Calcitonin A peptide hormone that lowers calcium concentration in the blood. In humans, it is released by thyroid cells and acts to decrease the formation and absorptive activity of osteoclasts. Its role in regulating plasma calcium is much greater in children and in certain diseases than in normal adults. Other Antiresorptive Drugs polypeptides).
Anaplastic carcinoma
  • Microscopic findings may have different patterns:
    • Large giant cells Giant cells Multinucleated masses produced by the fusion of many cells; often associated with viral infections. In aids, they are induced when the envelope glycoprotein of the HIV virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus. Giant Cell Arteritis
    • Sarcomatoid spindle cells Spindle Cells Acoustic Neuroma (resemble sarcomas)
    • Mix of giant and spindle cells Spindle Cells Acoustic Neuroma
  • When arising from well-differentiated cancers, foci of papillary or follicular differentiation can be seen.
  • Markers: (+) cytokeratin Cytokeratin Squamous Cell Carcinoma (SCC); usually (–) for thyroglobulin Thyroglobulin Thyroid Hormones (a marker for differentiation)

Postdiagnosis tests

Further tests should be obtained after diagnosis:

  • Laboratory tests:
    • Serum thyroglobulin Thyroglobulin Thyroid Hormones (differentiated thyroid Thyroid 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: Anatomy carcinoma)
    • Calcitonin Calcitonin A peptide hormone that lowers calcium concentration in the blood. In humans, it is released by thyroid cells and acts to decrease the formation and absorptive activity of osteoclasts. Its role in regulating plasma calcium is much greater in children and in certain diseases than in normal adults. Other Antiresorptive Drugs and carcinoembryonic antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination ( CEA CEA A glycoprotein that is secreted into the luminal surface of the epithelia in the gastrointestinal tract. It is found in the feces and pancreaticobiliary secretions and is used to monitor the response to colon cancer treatment. Serum Tumor Markers) (medullary thyroid Thyroid 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: Anatomy carcinoma)
  • DNA analysis DNA analysis Biochemical identification of mutational changes in a nucleotide sequence. Hyper-IgM Syndrome for RET germline mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations:
    • For medullary thyroid Thyroid 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: Anatomy carcinoma
    • RET + or unknown:
      • Serum calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes: workup for hyperparathyroidism Hyperparathyroidism Hyperparathyroidism is a condition associated with elevated blood levels of parathyroid hormone (PTH). Depending on the pathogenesis of this condition, hyperparathyroidism can be defined as primary, secondary or tertiary. Hyperparathyroidism (component of MEN2A)
      • Plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products fractionated metanephrines: workup for pheochromocytoma Pheochromocytoma Pheochromocytoma is a catecholamine-secreting tumor derived from chromaffin cells. The majority of tumors originate in the adrenal medulla, but they may also arise from sympathetic ganglia (also referred to as paraganglioma). Symptoms are associated with excessive catecholamine production and commonly include hypertension, tachycardia, headache, and sweating. Pheochromocytoma (component of MEN2A and B)
    • If index patient is positive, family screening Screening Preoperative Care and testing should be offered.
  • Imaging:

Management and Prognosis

Differentiated thyroid Thyroid 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: Anatomy carcinoma

  • Include papillary and follicular thyroid Thyroid 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: Anatomy carcinomas
  • Surgery:
  • Surgical complications Surgical complications Surgical complications are conditions, disorders, or adverse events that occur following surgical procedures. The most common general surgical complications include bleeding, infections, injury to the surrounding organs, venous thromboembolic events, and complications from anesthesia. Surgical Complications:
    • Hypoparathyroidism Hypoparathyroidism Hypoparathyroidism is defined as reduced parathyroid hormone (PTH) levels due to poor function of the parathyroid glands. The cause of hypoparathyroidism is most commonly iatrogenic following neck surgery, but it can also be associated with genetic or autoimmune disorders as well as infiltrative diseases causing destruction of the normal parathyroid tissue. Hypoparathyroidism ( parathyroid gland Parathyroid gland Two pairs of small oval-shaped glands located in the front and the base of the neck and adjacent to the two lobes of thyroid gland. They secrete parathyroid hormone that regulates the balance of calcium; phosphorus; and magnesium in the body. Hormones: Overview and Types removal) → ↓ calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes
    • Recurrent laryngeal nerve injury Nerve Injury Surgical Complications
    • Bleeding
  • Postsurgery assessment:
  • Radioactive iodine Iodine A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126. 90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. Thyroid Hormones therapy:
    • Ablation of remaining thyroid Thyroid 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: Anatomy tissue (residual and metastatic)
    • Given to patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with intermediate to high risk of persistent and recurrent disease
  • Levothyroxine Levothyroxine Thyroid Replacement Therapy:
    • Thyroid Thyroid 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: Anatomy replacement and thyroid Thyroid 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: Anatomy hormone–suppressive therapy
    • Suppression Suppression Defense Mechanisms of TSH:
      • Needed because TSH is a growth factor for thyroid Thyroid 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: Anatomy cells
      • TSH goal depends on disease extent and risk of recurrence.
      • If high-risk disease: TSH goal < 0.1 mU/L
  • Other treatments:
    • External radiotherapy: for inoperable tumors or painful 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. Bones: Structure and Types metastases
    • Kinase inhibitor therapy
    • Chemotherapy Chemotherapy Osteosarcoma (e.g., doxorubicin)
  • Surveillance Surveillance Developmental Milestones and Normal Growth (frequency dependent on findings/results):
    • Physical examination
    • Serum Tg Tg Thyroid Hormones
    • Serum TSH and thyroid Thyroid 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: Anatomy function tests
    • Neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess US and other radiologic tests (whole-body thyroid scan Thyroid Scan Nuclear Imaging, CT as indicated)

Anaplastic thyroid Thyroid 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: Anatomy carcinoma

  • Surgery:
    • Often not performed, as disease is advanced at time of diagnosis
    • If with localized or locally advanced operable tumor Tumor Inflammation: total thyroidectomy Thyroidectomy Surgical removal of the thyroid gland. Goiter with neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess dissection and combine with other methods
  • Radiotherapy: adjuvant Adjuvant Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (freund’s adjuvant, bcg, corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity. Vaccination (postsurgery) or primary treatment for inoperable disease
  • Kinase inhibitors and/or chemotherapy Chemotherapy Osteosarcoma
  • Palliative care: important component, as disease progression is rapid
  • No role for radioactive iodine Iodine A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126. 90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. Thyroid Hormones therapy
  • Levothyroxine Levothyroxine Thyroid Replacement Therapy:
    • For thyroid Thyroid 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: Anatomy replacement (in those who have undergone thyroidectomy Thyroidectomy Surgical removal of the thyroid gland. Goiter)
    • TSH suppression Suppression Defense Mechanisms not required.
  • Surveillance Surveillance Developmental Milestones and Normal Growth:
    • Monitor with CT ( neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess, chest, abdomen, and pelvis Pelvis The pelvis consists of the bony pelvic girdle, the muscular and ligamentous pelvic floor, and the pelvic cavity, which contains viscera, vessels, and multiple nerves and muscles. The pelvic girdle, composed of 2 “hip” bones and the sacrum, is a ring-like bony structure of the axial skeleton that links the vertebral column with the lower extremities. Pelvis: Anatomy) every 3 months for the first 2 years (if there is initial response to treatment).
    • PET PET An imaging technique that combines a positron-emission tomography (PET) scanner and a ct X ray scanner. This establishes a precise anatomic localization in the same session. Nuclear Imaging detects disease not evident on CT.

Medullary thyroid Thyroid 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: Anatomy carcinoma

  • Surgery:
    • Total thyroidectomy Thyroidectomy Surgical removal of the thyroid gland. Goiter (with neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess dissection)
    • In MEN2 ( hyperparathyroidism Hyperparathyroidism Hyperparathyroidism is a condition associated with elevated blood levels of parathyroid hormone (PTH). Depending on the pathogenesis of this condition, hyperparathyroidism can be defined as primary, secondary or tertiary. Hyperparathyroidism and/or pheochromocytoma Pheochromocytoma Pheochromocytoma is a catecholamine-secreting tumor derived from chromaffin cells. The majority of tumors originate in the adrenal medulla, but they may also arise from sympathetic ganglia (also referred to as paraganglioma). Symptoms are associated with excessive catecholamine production and commonly include hypertension, tachycardia, headache, and sweating. Pheochromocytoma): Perform additional surgery (e.g., adrenalectomy Adrenalectomy Excision of one or both adrenal glands. Cushing Syndrome) as indicated.
  • Kinase inhibitors and/or chemotherapy Chemotherapy Osteosarcoma: for progressive, metastatic medullary thyroid Thyroid 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: Anatomy cancer
  • No role for radioactive iodine Iodine A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126. 90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. Thyroid Hormones therapy
  • Levothyroxine Levothyroxine Thyroid Replacement Therapy:
  • Postsurgery assessment:
    • Serum calcitonin Calcitonin A peptide hormone that lowers calcium concentration in the blood. In humans, it is released by thyroid cells and acts to decrease the formation and absorptive activity of osteoclasts. Its role in regulating plasma calcium is much greater in children and in certain diseases than in normal adults. Other Antiresorptive Drugs and CEA CEA A glycoprotein that is secreted into the luminal surface of the epithelia in the gastrointestinal tract. It is found in the feces and pancreaticobiliary secretions and is used to monitor the response to colon cancer treatment. Serum Tumor Markers: Normal results after surgery indicate very good prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas.
    • ↑ Levels: marker of residual or recurrent disease
  • Surveillance Surveillance Developmental Milestones and Normal Growth (frequency dependent on findings/results):
    • Physical examination
    • Serum calcitonin Calcitonin A peptide hormone that lowers calcium concentration in the blood. In humans, it is released by thyroid cells and acts to decrease the formation and absorptive activity of osteoclasts. Its role in regulating plasma calcium is much greater in children and in certain diseases than in normal adults. Other Antiresorptive Drugs and CEA CEA A glycoprotein that is secreted into the luminal surface of the epithelia in the gastrointestinal tract. It is found in the feces and pancreaticobiliary secretions and is used to monitor the response to colon cancer treatment. Serum Tumor Markers 
    • US of the neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess (other radiologic tests as indicated)

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas

  • Dependent on type of cancer and extent of disease
  • From 2010 to 2016 in the United States (5-year survival rate):

Clinical Relevance

  • 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: disordered growth of thyroid Thyroid 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: Anatomy cells, producing a mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast in the thyroid Thyroid 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: Anatomy gland: Nodules, the majority of which are benign Benign Fibroadenoma, are detected on examination or found incidentally in radiologic images. Workup includes TSH and US, followed by a radioactive iodine Iodine A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126. 90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. Thyroid Hormones uptake ( RAIU RAIU Thyrotoxicosis and Hyperthyroidism)/ thyroid scan Thyroid Scan Nuclear Imaging if hyperthyroidism Hyperthyroidism Hypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate. Thyrotoxicosis and Hyperthyroidism is present. Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma is recommended in those with suspicious US findings, cold nodules on thyroid scan Thyroid Scan Nuclear Imaging, large-sized nodules (generally, > 1.5 cm) and risk factors for malignancy Malignancy Hemothorax. Treatment is dictated by pathology findings.
  • 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 Autoimmune Disorder Septic Arthritis leading to destruction of the thyroid Thyroid 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: Anatomy cells and thyroid Thyroid 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: Anatomy failure. Presentation can be a painless goiter Goiter A goiter is a chronic enlargement of the thyroid gland due to nonneoplastic growth occurring in the setting of hypothyroidism, hyperthyroidism, or euthyroidism. Morphologically, thyroid enlargement can be diffuse (smooth consistency) or nodular (uninodular or multinodular). Goiter (in later stages, the gland is atrophic). Lab tests show elevated TSH, low free thyroxine Thyroxine The major hormone derived from the thyroid gland. Thyroxine is synthesized via the iodination of tyrosines (monoiodotyrosine) and the coupling of iodotyrosines (diiodotyrosine) in the thyroglobulin. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroid Hormones (T4), and positive 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: Types and Functions against thyroglobulin Thyroglobulin Thyroid Hormones and 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. Treatment is lifelong thyroid Thyroid 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: Anatomy replacement therapy.
  • 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: a condition characterized by a deficiency of thyroid Thyroid 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: Anatomy 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 and Types: Iodine Iodine A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126. 90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. Thyroid Hormones 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 a low free T4. Treatment is with levothyroxine Levothyroxine Thyroid Replacement Therapy.
  • Hyperthyroidism Hyperthyroidism Hypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate. Thyrotoxicosis and Hyperthyroidism: condition caused by sustained overproduction and release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology of the thyroid Thyroid 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: Anatomy 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 and Types T3 and T4. Graves’ disease Graves’ disease A common form of hyperthyroidism with a diffuse hyperplastic goiter. It is an autoimmune disorder that produces antibodies against the thyroid stimulating hormone receptor. These autoantibodies activate the TSH receptor, thereby stimulating the thyroid gland and hypersecretion of thyroid hormones. These autoantibodies can also affect the eyes (Graves ophthalmopathy) and the skin (Graves dermopathy). Thyrotoxicosis and Hyperthyroidism is the most common cause of hyperthyroidism Hyperthyroidism Hypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate. 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. Nervous System: Anatomy, Structure, and Classification. Lab tests show low TSH and elevated free T4. Treatment depends on the underlying condition.
  • Goiter Goiter A goiter is a chronic enlargement of the thyroid gland due to nonneoplastic growth occurring in the setting of hypothyroidism, hyperthyroidism, or euthyroidism. Morphologically, thyroid enlargement can be diffuse (smooth consistency) or nodular (uninodular or multinodular). Goiter: abnormal enlargement of the thyroid Thyroid 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: Anatomy gland that occurs in settings 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 Hypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate. Thyrotoxicosis and Hyperthyroidism, or euthyroidism: The presentation of goiter Goiter A goiter is a chronic enlargement of the thyroid gland due to nonneoplastic growth occurring in the setting of hypothyroidism, hyperthyroidism, or euthyroidism. Morphologically, thyroid enlargement can be diffuse (smooth consistency) or nodular (uninodular or multinodular). Goiter can be a diffusely enlarged or multinodular thyroid Thyroid 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: Anatomy gland. 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 Thyroid 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: Anatomy function tests and thyroid Thyroid 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: Anatomy 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: Types and Functions. Radiologic imaging helps if worrisome features are present. Treatment options are observation, medication, surgery, and radioiodine ablation Radioiodine Ablation Thyrotoxicosis and Hyperthyroidism, depending on findings.
  • MEN2 syndrome: MEN2 is an autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance condition involving the RET proto-oncogene. There are 2 syndromes: MEN2A consists of medullary thyroid Thyroid 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: Anatomy carcinoma, pheochromocytoma Pheochromocytoma Pheochromocytoma is a catecholamine-secreting tumor derived from chromaffin cells. The majority of tumors originate in the adrenal medulla, but they may also arise from sympathetic ganglia (also referred to as paraganglioma). Symptoms are associated with excessive catecholamine production and commonly include hypertension, tachycardia, headache, and sweating. Pheochromocytoma, and hyperparathyroidism Hyperparathyroidism Hyperparathyroidism is a condition associated with elevated blood levels of parathyroid hormone (PTH). Depending on the pathogenesis of this condition, hyperparathyroidism can be defined as primary, secondary or tertiary. Hyperparathyroidism; MEN2B consists of medullary thyroid Thyroid 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: Anatomy carcinoma, pheochromocytoma Pheochromocytoma Pheochromocytoma is a catecholamine-secreting tumor derived from chromaffin cells. The majority of tumors originate in the adrenal medulla, but they may also arise from sympathetic ganglia (also referred to as paraganglioma). Symptoms are associated with excessive catecholamine production and commonly include hypertension, tachycardia, headache, and sweating. Pheochromocytoma, Marfanoid body habitus, mucosal neuromas Mucosal Neuromas Multiple Endocrine Neoplasia, and ganglioneuromatosis of the bowel.

References

  1. American Cancer Society. (2021). Survival rates of thyroid cancer. Retrieved February 25, 2021, from https://www.cancer.org/cancer/thyroid-cancer/detection-diagnosis-staging/survival-rates.html 
  2. Jameson J, Mandel SJ, Weetman AP. (2018). Thyroid nodular disease and thyroid cancer. In: Jameson J, et al. (Eds.), Harrison’s Principles of Internal Medicine, 20th ed. McGraw-Hill.
  3. Maitra A. (2021). The endocrine system. In Kumar V, Abbas A, Aster J (Eds.), Robbins & Cotran Pathologic Basis of Disease, 10th ed. Elsevier.
  4. Malchoff C. (2019). Oncogenes and tumor suppressor genes in thyroid nodules and nonmedullary thyroid cancer. UpToDate. Retrieved February 21, 2021, from https://www.uptodate.com/contents/oncogenes-and-tumor-suppressor-genes-in-thyroid-nodules-and-nonmedullary-thyroid-cancer
  5. Sharma P. (2020). Thyroid cancer. Medscape. Retrieved February 23, 2021, from https://emedicine.medscape.com/article/851968-overview
  6. Tuttle R. (2020). Papillary thyroid cancer: clinical features and prognosis. UpToDate. Retrieved February 23, 2021, from https://www.uptodate.com/contents/papillary-thyroid-cancer-clinical-features-and-prognosis
  7. Tuttle R. (2020). Medullary thyroid cancer: Surgical treatment and prognosis. UpToDate. Retrieved February 24, 2021, from https://www.uptodate.com/contents/medullary-thyroid-cancer-surgical-treatment-and-prognosis
  8. Tuttle R. (2020). Differentiated thyroid cancer: overview of management. UpToDate. Retrieved February 24, 2021, from https://www.uptodate.com/contents/differentiated-thyroid-cancer-overview-of-management

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