Hypothalamus-Pituitary-Thyroid Axis Quiz

Hypothalamus-Pituitary-Thyroid Axis

• The hypothalamus, pituitary, and thyroid gland work together in a feedback loop to regulate thyroid hormone production.
• TRH (Thyrotropin-releasing hormone) is released by the hypothalamus.
• TRH travels to the anterior pituitary.
• TSH (Thyroid-stimulating hormone) is released by the anterior pituitary.
• TSH travels to the thyroid gland.
• The thyroid gland releases T4 (thyroxine) and T3 (triiodothyronine).
• Thyroid hormones T3 & T4 stimulate metabolism.
• Thyroid hormones exert negative feedback on the hypothalamus and anterior pituitary.

Thyrotropin-Releasing Hormone (TRH)

• TRH is synthesized in the paraventricular nuclei of the hypothalamus.
• It travels to the anterior pituitary via the hypophyseal portal system.
• TRH stimulates the release of TSH from the anterior pituitary.
• TRH has a half-life of approximately 6 minutes in the blood.
• TRH is a tripeptide.
• TRH has anti-depressant and anti-suicidal properties.
• TRH receptor (TRHR) is a G protein-coupled receptor.
• TRH activates phospholipase C, leading to the formation of IP3 and DAG.
• This increases cytoplasmic calcium ion concentrations, stimulating the exocytosis of TSH into the blood.

Thyroid Stimulating Hormone (TSH)

• TSH is a glycoprotein hormone.
• TSH is produced by thyrotroph cells in the anterior pituitary.
• TSH stimulates the thyroid gland to produce T4 and T3.
• TSH levels are higher in children than adults.
• Normal range in adults is 0.4–2.5 µIU/mL.
• TSH stimulates the thyroid gland to produce thyroxine (T4), and then triiodothyronine (T3) which stimulates the metabolism.
• TSH is secreted throughout life but particularly reaches high levels during periods of rapid growth and development, as well as in response to stress.
• TSH regulates thyroid hormone synthesis.
• Increased TSH can lead to increased thyroid follicular cells (size and number), potentially resulting in goiter.
• TSH receptors are found mainly on thyroid follicular cells and are G protein-coupled receptors.

Thyroid Gland

• The thyroid gland is one of the largest endocrine glands in the body.
• It weighs approximately 20 grams.
• Thyroid gland size depends on age, sex, and physiological condition (e.g., pregnancy, lactation).
• The thyroid gland is located in the neck, just below the larynx, on either side of and anterior to the trachea.
• The thyroid gland has a rich blood supply.
• Blood supply is provided by various arteries and veins.
• The thyroid gland is made up of follicles, which are the functional units.
• Each follicle is spherical and filled with colloid.
• Follicular cells line the follicles.
• Follicular cells secrete into the interior of the follicles.
• Parafollicular cells (C cells) are located between follicles.
• Parafollicular cells (C cells) produce calcitonin.

Thyroid Hormones Secretion

• T3 and T4 are important thyroid hormones.
• T4 (thyroxine) accounts for 93% of the secretion.
• T3 (triiodothyronine) accounts for 7% of the secretion.
• Thyroid hormones are stored in follicles for 2 to 3 months.
• T3 is the active form of T4.
• T3 is more potent than T4 but present in smaller quantities in the blood.
• Almost all T4 is converted to T3 in tissues.
• Most T3 is produced by peripheral tissues (primarily the liver and kidneys) through the deiodination of T4.

Control of Thyroid Hormone Secretion

• Thyroid hormone (TH) secretion is tightly regulated by negative feedback loops involving TRH and TSH.
• THs negatively feedback on both the hypothalamus and anterior pituitary to inhibit further TRH and TSH release.
• The hypothalamus produces TRH, which stimulates the anterior pituitary to produce TSH.
• TSH stimulates the thyroid gland to produce T3 and T4.
• T3 and T4 then inhibit further production of TRH and TSH.

Mechanism of Action of Thyroid Hormones

• Thyroid hormones are lipophilic (fat-soluble).
• THs receptors are located within the target cells nuclei.
• T3 binds to nuclear receptors, triggering gene expression.

Thyroid Hormone Transport

• Most thyroid hormones (T3 and T4) are bound to transport proteins (e.g., thyroxine-binding globulin, albumin) in the blood.
• Only a small amount of T3 and T4 circulate freely in the blood.

Iodine Metabolism

• Iodine is an essential component of thyroid hormones.
• Dietary iodine is absorbed in the GI tract.
• The transport of iodide into the follicular cells is dependent on a Na+/I- cotransport system.
• Iodine is oxidized to iodine (I2).
• Iodine then attaches to tyrosine within thyroglobulin.
• Monoiodotyrosine (MIT) and diiodotyrosine (DIT) are formed.
• MIT and DIT combine to form T3 and T4.

Goiter/Swollen Neck

• Goiter means there is a swollen neck.
• Goiter commonly happens when there is a lack of iodine which the thyroid can no longer produce sufficient T3 & T4.
• This lack of production causes excessive stimulation from TSH that leads to the growth of the thyroid gland.

Hypothyroidism

• Hypothyroidism is a condition where the thyroid gland does not produce enough thyroid hormones.
• Causes include iodine deficiency, autoimmune diseases (like Hashimoto's thyroiditis), and certain medications.

Hyperthyroidism

• Hyperthyroidism is the opposite of hypothyroidism.
• Hyperthyroidism is an overproduction of Thyroid hormones T3 and T4.
• Hyperthyroidism can be caused by Graves' disease (autoimmune disease), toxic nodules, and certain types of thyroiditis.

Myxedema

• Myxedema is a life-threatening complication of untreated hypothyroidism.
• Symptoms include severe swelling of the face, slow breathing, a low body temperature etc

Hypothyroidism in Children (Cretinism)

• In children, hypothyroidism during postnatal development (Cretinism) can result in severe mental retardation and short stature.

Normal Thyroid Hormone Levels

• Normal ranges vary by age.
• Adults have a normal range of 0.4-4.0 mIU/L.

Diagnosis Hypo-/Hyperthyroidism

• Medical history and physical exam
• Thyroid function tests (TSH, T3, T4)
• Imaging tests (thyroid scan, ultrasound)
• Radioactive iodine uptake test

Treatments for Hypo-/Hyperthyroidism

• Hypothyroidism: hormone replacement therapy (e.g., levothyroxine)
• Hyperthyroidism: antithyroid medications, radioactive iodine, or surgery.