Thyroid Gland Physiology

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Full-Length Text

THYROID HORMONES

T3 (full name, triiodothyronine); T3 is more biologically active.

T4 (full name, thyroxine, aka, tetraiodonthyronine); the thyroid produces T4 in greater quantities; so, target tissues to need to use 5' iodinase convert T4 to T3.

THYROID HORMONE SYNTHESIS

Synthesis occurs both intra- and extracellularly.

Step 1:

Thyroglobulin is synthesized in the follicular epithelial cell and transported to the lumen; thyroglobulin is a tyrosine-rich protein.

Step 2:

The "i-trap," which is a sodium-iodine co-transporter, pulls iodiDe into the cell from the capillaries.

Iodide is a trace element that does not occur naturally in the body, so it must be consumed in the diet.

Step 3:

Oxidization of iodiDe to iodiNe by the enzyme thyroid peroxidase.

Step 4:

Organification, also driven by thyroid peroxidase, to combine iodine with the tyrosine of luminal thyroglobulin;

As a result of organification, two thyroid hormone precursors form and attach to thyrogobulin:
MIT (full name, monoiodotyrosine)
DIT (full name, diiodotyrosine)

Step 5:

Thyroid peroxidase drives coupling reactions:
Two DIT molecules combine to form T4.
One DIT molecule combines with one molecule of MIT to form T3.

Ultimately, some MIT and DIT will be "left over," and remain bound to thyroglobulin with T3 and T4 in the colloid.

Recall that, as we learned earlier, T4 is produced in larger quantities.

Step 6:

Thyroglobulin, along with thyroid hormone and its precursors, are endocytosed to the follicular cell.

Step 7:

Upon glandular stimulation, MIT and DIT are released from thyroglobulin; they remain within the cell to be recycled in the synthesis of new thyroglobulin.

Though omitted for simplicity, MIT and DIT are deiodinated.
IoDide returns to the pool of iodide within the cell.
Tyrosine molecules are recycled in the synthesis of new thyroglobulin molecules.

T3 and T4 are delivered to the systemic circulation to reach their target tissues.

Most T3 and T4 travels in the blood bound to thyroxine-binding globulin (a carrier protein); only free T3 and T4 are physiologically active.

THYROID HORMONE EFFECTS

Thyroid hormones trigger the synthesis of new proteins, which has widespread effects throughout the body:

Act synergistically with growth hormone to facilitate growth and maturation of the musculoskeletal system

Increase tissue oxygen consumption, basal metabolic rate, and body temperature.

Increase cardiac output and ventilation.

Crucial for CNS maturation and maintenance.

CLINICAL CORRELATIONS

Goiter is an enlargement of the thyroid gland that commonly occurs from:

• Iodine deficiency (globally)
• Hashimoto's thyroiditis (in the US)
• Grave's disease
• Multinodular goiter

Hepatic failure can cause decreased levels of TBG, which raises the concentration of free hormone, and, ultimately, inhibits further thyroid hormone production via negative feedback.

More on Hyperthyroidism

Over-secretion of thyroid hormone leads to weight loss and increased food intake, metabolic rate, temperature, sweating, and heart rate. Graves' disease, which is an immune disorder, is a common cause of hyperthyroidism.

More on Hypothyroidism

Disturbances in thyroid hormone production vary by age.

In newborns, too little thyroid hormone causes cretinism, which is characterized by growth and mental retardation.

In adults, hypothyroidism causes weight gain, physical and mental sluggishness, and menstrual defects.

A typical cause of hypothyroidism in many regions is an iodide-deficient diet, which is why the World Health Organization recommends salt iodization.

Full-Length Text

• Here we will learn about the synthesis and functions of thyroid hormones.

• To begin, start a table.

• Denote that the thyroid gland produces T3 (full name, triiodothyronine) and T4 (full name, thyroxine, aka, tetraiodonthyronine).
  • The two hormones differ by a single iodine atom.

• Denote that T3 is more biologically active.
  • And that the thyroid produces T4 in greater quantities.
  • This leads target tissues to need to convert T4 to T3.

• Denote that target tissues use 5' iodinase to convert T4 to T3, the biologically active form, as needed.

Let's sketch the anatomy of the thyroid gland, which sits anteriorly in the neck.

• First, show its gross anatomy as a gland with two lobes.

• Then, to show its histology, indicate that it comprises collections of follicular epithelial cells that surround colloid-filled lumens.

Now, let's show the steps of thyroid hormone synthesis.

• First, write that synthesis occurs both intra- and extracellularly.

• To illustrate this, draw a capillary, a follicular epithelial cell, and a lumen;

Next, show the key steps:

• Step 1: Thyroglobulin is synthesized in the follicular epithelial cell and transported to the lumen; thyroglobulin is a tyrosine-rich protein.

• Step 2: The "i-trap," which is a sodium-iodine co-transporter, pulls iodiDe into the cell from the capillaries.
  • Write that iodide is a trace element that does not occur naturally in the body, so it must be consumed in the diet.

• Step 3: Oxidization of iodiDe to iodiNe by the enzyme thyroid peroxidase;

• Step 4: Organification, also driven by thyroid peroxidase, to combine iodine with the tyrosine of luminal thyroglobulin;
  • As a result of organification, two thyroid hormone precursors form and attach to thyrogobulin:
  • MIT (full name, monoiodotyrosine) and DIT (full name, diiodotyrosine).

• Step 5: Thyroid peroxidase drives coupling reactions: two DIT molecules combine to form T4, and one DIT molecule combines with one molecule of MIT to form T3.
  • Ultimately, some MIT and DIT will be "left over," and remain bound to thyroglobulin with T3 and T4 in the colloid.
  • Recall that, as we learned earlier, T4 is produced in larger quantities.

• Step 6: Thyroglobulin, along with thyroid hormone and its precursors, are endocytosed to the follicular cell.

• Step 7: Upon glandular stimulation, MIT and DIT are released from thyroglobulin; they remain within the cell to be recycled in the synthesis of new thyroglobulin.
  • Though omitted for simplicity, MIT and DIT are deiodinated; ioDide returns to the pool of iodide within the cell, and tyrosine molecules are recycled in the synthesis of new thyroglobulin molecules.
  • T3 and T4 are delivered to the systemic circulation to reach their target tissues.

• Denote that most T3 and T4 travels in the blood bound to thyroxine-binding globulin (a carrier protein); only free T3 and T4 are physiologically active.

• As a clinical correlation, denote that hepatic failure can cause decreased levels of TBG, which raises the concentration of free hormone, and, ultimately, inhibits further thyroid hormone production via negative feedback.

Now, let's learn an overview of thyroid hormone effects.

• First, write that thyroid hormones trigger the synthesis of new proteins, which has widespread effects throughout the body.

• For example, thyroid hormones act synergistically with growth hormone to facilitate growth and maturation of the musculoskeletal system;
  • They increase tissue oxygen consumption, basal metabolic rate, and body temperature;
  • They increase cardiac output and ventilation.
  • They are crucial for CNS maturation and maintenance.

With these effects in mind, let's predict the clinical consequences of thyroid hormone disorders:

• In hyperthyroidism, over-secretion of thyroid hormone leads to weight loss and increased food intake, metabolic rate, temperature, sweating, and heart rate.
  • Graves' disease, which is an immune disorder, is a common cause of hyperthyroidism.
  • Hypothyroidism is the opposite; disturbances in thyroid hormone production vary by age:
  • In newborns, too little thyroid hormone causes cretinism, which is characterized by growth and mental retardation;
  • In adults, hypothyroidism causes weight gain, physical and mental sluggishness, and menstrual defects.
  • A typical cause of hypothyroidism in many regions is an iodide-deficient diet, which is why the World Health Organization recommends salt iodization.