Thyroid anatomy and physiology

What happens to thyroid hormone in distant cells?

• From around 3 days after birth thyroid levels in the blood remain fairly constant. Thyroid hormones are strongly bound to serum proteins, thyroid binding globulin (TBG) (&Thyroid-binding prealbumin), albumin and Transthyretin. Only a small amount of T4/T3 is free to enter cells. • T4 is converted in the peripheral tissues to T3. • Most T3 is generated by removing one iodine atom from the outer ring of T4 (de-iodination) and this occurs in the peripheral tissues. • T3 then enters the cell and can interact in two main ways. It can either bind to the thyroid hormone receptor which then enters the nucleus and alters gene expression OR it can bind to the thyroid hormone, then bind to RXR and then the T3-TR-RXR complex does its business in the nucleus. • Either way, the thyroid receptor has two units. The alpha and the beta subunits. The are different ratios of alpha and beta in the receptors throughout the body.

What are the physiological actions of thyroid hormones?

• Increased fat mobilisation leading to an increase in the Basal metabolic rate. • Decreases cholesterol blood levels • Increased gluconeogenesis and glycogenolysis to generate free glucose. • Growth, particularly in children. The effects work synergistically with Growth Hormone. • Increase HR, Cardiac contractility and Cardiac output. • Alterations in mental state. • Fertility: Hypothyroidism is associated with infertility.

What is the innervation like to the thyroid?

• Innervated by branches from the sympathetic trunk. Note that these nerves do not control the endocrine secretion - this is controlled by the pituitary gland. For interest: • Thyroid gland is bigger in women and in areas of iodine deficiency • It gets larger in puberty, pregnancy and lactation

Why is iodine important to the thyroid?

• Iodate in the diet is converted to iodide in the stomach • You need to eat iodine daily to maintain a normal iodine input (150mcg/day for men and women). Iodine is found in many different foods such as sea vegetables, cranberries, yogurt and potatoes. The thyroid is the major storage organ of iodine. However, there are other sites in the body that will take up iodide such as; Pregnancy, mammary glands in lactation the colon and the stomach (Capable of excreting back into gut). • Most of the iodine we lose from our body to maintain normal levels is through the urine.

Go through how iodine is synthesised?

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What is the blood supply like to the thyroid gland? Which arteries supply which bit of the thyroid?

• Remember the thyroid gland releases hormones directly into the blood - thus, it requires a high vascular supply. • Blood supply is through the superior and inferior thyroid arteries. These are paired arteries arising on the left and right • The superior thyroid artery is the first branch of the external carotid artery and supplies the superior and anterior portions of the gland • The inferior thyroid artery arises from the thyrocervical trunk which is a branch of the subclavian artery. It tends to supply the posterio-inferior aspect. • In 10% of the population there is an additional artery - the thyroid ima artery from the brachiocephalic trunk • Venous drainage is from the superior, middle and inferior thyroid veins - forming the vascular plexus which drain into the internal jugular vein and brachiocephalic vein.

How is thyroid hormone release regulated?

• The main stimulation of thyroid hormone release and synthesis is thyroid stimulating hormone (TSH) from the anterior pituitary which is in turn regulated by thyrotrophin-releasing hormone (TRH) from the hypothalamus. • TSH acts through a surface receptor (G-protein and cAMP) on the thyroid. • TSH is under negative feedback at the level of the hypothalamus and pituitary which sense the level of thyroid hormones in the plasma. Other non-thyroid related things can also effect levels such as Physical stress, pregnancy, drugs, foods. • Thyroid hormone (predominantly T3) completes the negative feedback loop by supressing the production of TSH and TRH. • Note that high levels of luteinizing hormone (LH) and HcG can also stimulate the TSH receptor and increase thyroid hormone levels. T3 receptors are also found in the pituitary gland and the hypothalamus, where they inhibit transcription of the gene for TRH prohormone and the release of TSH, respectively. Excess T3 inhibits TSH release while a deficiency of T3 stimulates TSH release. This feedback mechanism helps maintain T3 levels, and therefore stabilizes metabolic rate.

At what level does the thyroid gland sit? What connects the two lobes of the thyroid gland? What is superior and inferior to the thyroid?

• The normal thyroid gland consists of pear shaped left and right lobes • The thyroid gland is in the anterior neck, spanning between the C5 and T1 vertebrae • It is an endocrine gland, divided into two lobes which are connected by an isthmus. The isthmus joins the anterior parts of the lobes and crosses the 2nd to 4th tracheal rings. • Some thyroid glands have a superior extension off of the isthmus which forms the highly vascular pyramidal lobe (Not in all people) • The R&L lobes extend from the thyroid cartilage to the 6th tracheal ring • It lies behind the sternohyoid and sternothyroid muscles, wrapping around the cricoid cartilage and superior tracheal rings. INFERIOR to the thyroid cartilage of the larynx. • The cricoid cartilage is an easy landmark to identify - the tracheal rings extend beneath this cartilage. • The normal thyroid is not easily palpable or visible. By the time a goitre is palpable the thyroid gland has doubled in size. If it's visible - it has tripled.

How is thyroid tissue arranged? What is the functional unit of the thyroid tissue? What sits in the middle? What sits in between follicular cells? Where does the thyroid originate from? What happens to the microstructure of the thyroid when there's hypo/hyperthyroidism going on?

• Thyroid tissue is arranged into follicles, which are lined by a single layer of epithelial cells (follicular cells) and has a central lumen of colloid. The follicle is the functional unit of the thyroid gland. • The colloid is almost entirely made up of iodinated glycoprotein thyroglobulin. • The parafollicular or C-cells lie between the follicles. • There are many 1000's of follicles with interspersed blood vessels, lymphatics, connective tissue and parafollicular (c-cells) between them. • The thyroid develops from the 12th week of life and starts developing from just behind the tongue embryological.

What hormones does the thyroid produce?

• Thyroxine is from tyrosine. Tyrosine has 1 aromatic rings. Thyroxine has 2. • Major output of the thyroid gland is T4 (Despite T3 being the more biologically active one!) but it also produces T3. The difference is that T3 has 3 iodine molecules, not 4. • You can convert T4 to T3 and T3 to Reverse T3. To do this you use a De-iodinase enzyme which has lots of different types in different locations throughout the body. These enzymes remove iodine from T3 and T4 for use elsewhere.