Editing Thyroid (section)

== Physiology ==

=== Thyroid hormone ===

** Synthesis
*** Occurs within the thyroid follicle unit, and is dependent on the presence of iodine
*** Follicular cells actively transport iodide anion across the cell membrane from the bloodstream into the cytoplasm via the Na/I symporter membrane protein, achieving a concentration within the follicular cells much higher than the systemic circulation
*** Iodide moves towards the follicular cell border with the colloid stores, and anions are oxidised to form the neutral I2 molecule, which can pass through the cell membrane into the colloid.
*** Colloid stores Tg, which contains a multitude of tyrosine residues. Colloid also contains the enzyme thyroid peroxidase (TPO), which catalyzes the next major step in thyroid hormone synthesis, which is the iodination of tyrosine residues on Tg, creating the molecule mono-iodotyrosine or di-iodotyrosine (DIT).
*** These two molecules form covalent bonds with one another to constitute the active forms of thyroid hormone tetra-iodothyronine or thyroxine (T4) (formed by two DITs and carrying four iodine molecules), or tri-iodothyronine (T3) (formed by a DIT and mono-iodotyrosine).
*** When stimulated by TSH, the follicular cells transport the activated thyroid hormones from the colloid centre into the bloodstream.
**
** Function
*** >99% of circulating thyroid hormones are bound to transport proteins such as albumin and T4-binding globulins; <1% exists in free form
*** T3 is the more potent form, but there is normally a higher concentration of T4 compared to T3
*** Many target organs can convert T4 to T3 through the deiodinase system
*** T4 and T3 bind to mitochondrial receptors leading to increased ATP production and energy consumption to produce heat - primary driver of basal metabolic rate
*** Critical for normal development, especially neurological
*** Increases cardiac output and vasodilation
*** Influences normal reproductive function
** Regulation
*** Low circulating T4 and T3 stimulate the hypothalamus to release thyrotropin-releasing hormone, which in turn stimulates the release of thyroid stimulating hormone from the anterior pituitary
*** TSH stimulates the formation of thyroid hormones by binding to its receptor on thyroid follicular cells - increased transport of iodine, as well as transport and release of T4 and T3 from the colloid into the bloodstream
*** Elevated T4 and T3 causes the reverse effect
** Iodine
*** Average daily requirement 0.1mg, all through diet
*** Thyroid uses almost all of it

=== Calcitonin ===

** Synthesis
*** Produces by parafollicular C cells
*** Not regulated by the same process as thyroid hormone
*** Release is stimulated by high serum calcium levels
** Function
*** Poorly understood
*** Decreases serum concentration of calcium through its end effect actions on bone (increasing osteoblast and decreasing osteoclast activity), gut (decreasing calcium absorption), and kidney (increasing calcium excretion)
*** Absence of calcitonin does not lead to a noticeable change in calcium homeostasis

=== Thyroid physiology in pregnancy ===

* Maternal thyroid hormone production rises significantly in first trimester, and declines steadily afterward
* Thyroid dysfunction causes congenital defects up until the fetal thyroid can produce its own hormone, which occurs about the mid-second trimester

=== Thyroid biomarkers ===

* TSH
** Secreted from anterior pituitary in pulsatile fashion, following circadian rhythm
** Normal range 0.4-4.12mIU/L
** Measurement can be affected by other illness (euthyroid sick syndrome) and medications such as glucocorticoids, frusemide, anticonvulsants and metformin
* T3 and T4
** Because high proportions of both hormones are bound in systemic circulation, measurement of free T4/T3 is more useful than total levels, which can be affected by fluctuations in levels of transporter proteins
* Thyroid autoantibodies
** TPOAb (anti-TPO)
*** Most accurate and most commonly used screening test for autoimmune thyroiditis (positive in >90% of patients, as well as 80% of patients with Graves disease; false positive rate 10-15%)
** TgAb (anti-Tg)
*** 80% sensitivity for autoimmune thyroiditis and 30% sensitivity for Graves disease
*** 10-15% false positive rate
*** Presence of TgAb interferes with the use of Tg measurement for the surveillance of differentiated thyroid cancer
** TRAb (anti-TSH receptor)
*** Reserved for diagnostic confirmation of Graves disease - positive in >90% of patients with the disease
*** Hypothesised to more closely correlate with severity of Graves
* Thyroglobulin (Tg)
** Precursor protein for the active iodinated forms of thyroid hormone
** Majority stored in colloid, but a small amount escapes into systemic circulation
** Particularly elevated in patients with differentiated thyroid cancer, but it's not helpful prior to surgery. Post-operative serum Tg measurement after total thyroidectomy is among the most sensitive cancer biomarkers in existence (as long as TgAb is absent - check it at the same time).
** Sensitivity can be augmented with TSH stimulation
* Calcitonin
** Serum calcitonin is the most useful biomarker for detection and surveillance of medullary thyroid cancer
** Can be performed in patients with or at risk of MTC (MEN2 syndrome)
** Controversial whether it is a good test in the workup of a thyroid nodule

[[Category:Anatomy]]