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Hyperthyroidism II: Pathophysiology01:27

Hyperthyroidism II: Pathophysiology

Hyperthyroidism is a hypermetabolic state caused by elevated levels of thyroid hormones, triiodothyronine (T3) and thyroxine (T4). It results from dysregulation at the thyroid, pituitary, or immune system level and affects multiple organ systems.PathophysiologyThe most common cause of hyperthyroidism is Graves’ disease, an autoimmune disorder in which antibodies, specifically thyroid-stimulating antibodies (TSAb), a subtype of TSH receptor antibodies (TRAb), bind to and activate TSH receptors...
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Graves Disease II: Pathophysiology

Graves’ disease is an autoimmune disorder characterized by the production of thyroid-stimulating immunoglobulins (TSI) that activate TSH receptors, leading to excessive synthesis and release of thyroid hormones (T3 and T4) and resulting in hyperthyroidism.Among all causes of hyperthyroidism, Graves’ disease is the most common and can happen at any age, though it is more frequent in women. It produces a hypermetabolic state with features such as weight loss, tachycardia, tremor, and heat...
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Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
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Spontaneous Murine Model of Anaplastic Thyroid Cancer
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Papillary thyroid carcinoma tall cell variant.

Ronald Ghossein1, Virginia A Livolsi

  • 1Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. ghosseir@mskcc.org

Thyroid : Official Journal of the American Thyroid Association
|October 18, 2008
PubMed
Summary

Tall cell variant (TCV) of papillary thyroid carcinoma (PTC) is an aggressive subtype. TCV is underdiagnosed and linked to radioactive iodine-refractory disease, necessitating further research into targeted therapies.

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Area of Science:

  • Endocrinology
  • Oncology
  • Pathology

Background:

  • Tall cell variant (TCV) is the most common aggressive variant of papillary thyroid carcinoma (PTC).
  • TCV diagnosis has significant prognostic and management implications.
  • Understanding TCV's characteristics is crucial for clinicians.

Purpose of the Study:

  • To review the multifaceted aspects of TCV in papillary thyroid carcinoma.
  • To inform clinicians about the diagnostic criteria and clinical behavior of TCV.
  • To discuss the implications of TCV in radioactive iodine-refractory disease.

Main Methods:

  • Review of existing literature on TCV of PTC.
  • Analysis of diagnostic criteria, including cell height and proportion.
  • Comparison of TCV with classical PTC regarding prognosis and molecular features.

Main Results:

  • TCV is characterized by cells at least twice or thrice their width, with eosinophilic cytoplasm and PTC nuclear features.
  • There is ongoing debate regarding precise diagnostic criteria for TCV, leading to underdiagnosis.
  • TCV exhibits a higher recurrence and mortality rate than classical PTC, often associated with larger tumor size and extrathyroid extension (ETE).
  • TCV shows aggressive behavior independent of ETE and is linked to high Muc1 and matrix metalloproteinase expression, and B-RAF mutations.
  • TCV is overrepresented in radioactive iodine (RAI)-refractory, fluorodeoxyglucose-PET-positive thyroid cancers.

Conclusions:

  • TCV is a biologically and clinically aggressive PTC subtype that is frequently underdiagnosed.
  • TCV is disproportionately found in patients with RAI-refractory disease.
  • The high prevalence of B-RAF mutations in TCV suggests it as a potential therapeutic target for RAI-refractory cases.
  • Advanced imaging like FDG-PET is essential for detecting RAI-refractory disease, especially in cases with extensive ETE.
  • Further research is needed to identify TCVs prone to becoming RAI-refractory and to develop effective targeted therapies.