Thyroid Hormones: Synthesis, Functions and Clinical Scenario

Thyroid hormones are secreted by thyroid gland. It requires stimulation by TSH which is released by Pituitary gland. Thyroid hormones maintain the metabolic rate of the body by affecting the cardiovascular and Central nervous system of the body. The normal levels of Thyroid hormones are Total T3( 80-220 ng/dl) and Free T4 ( 0.8-1.8 ng/dl). There are some conditions in which the functioning of the thyroid gland is altered like Hypothyroidism , Hyperthyroidism and Thyroiditis , In these cases patient can feel signs and symptoms of the diseases due to abnormal levels of the thyroid hormones.

Thyroid gland

• The thyrocytes or follicular cells of the thyroid gland produce the thyroid hormones.
• C-cells/Parafollicular cells are other cells of thyroid gland that produces a hormone called as calcitonin.
• There is a colloid in the center of the gland which is surrounded by thyrocytes. The colloid material can store thyroid hormone for upto two or three months when the thyroid gland is inactive.
• There is an important protien called as thyroglobulin which is present inside the colloid which binds the hormones.

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Thyroid Hormone Synthesis

• The first step is Thyroglobulin secretion which is done by follicular cells.
• Iodine trapping- In this step the iodide enters the follicular cells. It is transported by Na+/I- symporter ( NIS) , a secondary active transporter. It is stimulated by TSH at most of the places. There is one Chloride iodide transporter called as Pendrin Transporter used to bring iodide molecule to colloid.
• Oxidation of Iodide- There is one enzyme called as Thyroid peroxidase enzyme (TPO) , which is attached to the membrane causes the conversion of iodide to iodine(I2).
• Organification of Iodine - The molecular iodine is organified by attaching to the tyrosine component of the thyroglobulin molecule. It leads to formation of compounds like Monoiodo Tyrosine (MIT) and Diiodotyrosine (DIT). TPO enhances this process.
• Coupling reaction - The Thyroglobulin molecule to which MIT and DIT are attached folds upon itself and that leads to coupling reaction. The reaction is:
  • MIT + DIT = T3
  • DIT + DIT = T4
  • DIT + MIT =rT3

• The TPO enzyme enhances the coupling step.
• There will be endocytosis of Colloid along with the thyroid hormone into the follicular cells and there is formation of an endocytic vesicle containing Tg molecule attached to the colloid.
• Then there will be the lysosomal digestion that will release the thyroid hormones T3,T4 and rT3. These are steroidal hence will easily enter the capillary. A carrier protien is required to transport the thyroid hormones called as binding protiens.
• Peripheral conversion- Most of the hormone secreted by Thyroid gland is in the form of T4 ( Less active form). But it can get converted into T3 which is the most active form of thyroid hormones in the peripheral organs. Deiodinase enzymes converts T4 to T3.

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Functions of Thyroid Hormones

• Thyroid hormones can increase the heart rate and contractility of the cardiovascular system. Hence it increases the systolic BP. It also reduces the Total Peripheral Resistance therefore reduces the Diastolic BP.
• It causes maturation of the CNS, this is the reason that deficiency of thyroid hormone in pregnant mother can lead to Cretinism in the baby.
• Increase in protien catabolism and muscle weakness ( Thyrotoxic myopathy).
• Promotes Bone formation and enhances the GH function.
• Increases the glucose absorption from GIT.
• Increases LDL receptors in liver, resulting in increased hepatic removal of cholesterol from the circulation .
• Increase in protien synthesis and degradation.

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Thyroid Hormones Clinical Scenario

• Conditions like Pregnancy , Hyperestrogenism increases the TBG concentration. Hence the patient with hypothyroidism needs to increase the dose of Thyroxine hormone Because an increase in the amount of bound hormone can lowers the level of free thyroid hormone.
• The Increase in the levels of thyroid hormone ( Hyperthyroidism) is seen in Graves disease, Toxic Multinodular Goitre and Toxic adenoma. The symptoms are weight loss, heat intolerance, sweating , fatigue and palpitations. There can be some other signs like Lid retraction and Exophthalmos.
• The decrease in the levels of thyroid hormone is seen in Hypothyroidism and its symptoms are Weight gain, dry skin and hairs, Menorrhagia, Periorbital edema, cold intolerance and bradycardia.

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