Thyroid Gland - Anatomy & Physiology
The Thyroid Gland
thyroid gland products
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.
- 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)
- 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.
- 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.
- 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 regulation
- Thyrotropin-releasing hormone (TRH) is released from the hypothalamus and carried in the pituitary circulation.
- In the anterior pituitary gland, TRH stimulates thyrotrophs (aka, tyrotropes) to release thyroid-stimulating hormone (TSH).
- TSH travels in the systemic circulation to its target organ, the thyroid, where it triggers release of the thyroid hormones – T3 and T4.
- Thyroid hormones travel to the peripheral tissues, where some T4 is deiodinated to T3. Recall that T3 is more biologically active than T4.
- Via negative feedback at the hypothalamus and the anterior pituitary gland, thyroid hormones inhibit further secretion of TRH and TSH.
- Additionally, because iodine is essential for thyroid hormone production, low levels of the element also down-shift thyroid hormone production.
- In cases of excessive iodine exposure, the thyroid inhibits iodine organification, thereby avoiding over-production of thyroid hormone (the Wolff-Chaikoff effect). These regulatory details will return when we learn about treatments for thyroid disorders.
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.
Thyroid hormone effects
- 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
Clinical consequences of thyroid hormone disorders
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
- 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.