Thyroid Gland, Thyroid hormones, Disorders of Thyroid gland

 Thyroid gland 

The thyroid gland is butterfly shaped gland that overlaps the trachea in front of neck. It consists of the two lobes connected by bride of tissue called as the thyroid isthmus.



The normal thyroid is 12-20g in size and contains large amount of glycoprotein, thyroglobulin 

Function of Thyroid Gland 

  • The normal Thyroid is 12-20 in size and contains large amount of a glycoprotein, thyroglobulin. 
  •  The thyroid gland consists of many closely packed spherical follicles filled with colloid, a proteinaceous material composed mainly of thyroglobulin and stores thyroid hormone. 
  • Secrete thyroid hormones, which maintain metabolism in tissue 
  • Secrete calcitonin, a hormone that regulates circulating calcium levels. 
  • Absorb iodine 
  • Synthesize Thyroglobulin.

Thyroglobulin (Tg) 

  • Thyroglobulin (Tg) a glycoprotein, is synthesized by the thyroid cells and stored in the follicles 
  • Tg contain tyrosine residues, protein precursor of thyroid hormones 
  • Thyroid hormones are synthesized and stored in the Tg and regularly into blood 

Hypothalamus and Pituitary 

  • The hypothalamus is located in the brain and secrets hormones fir overall control of various physiologic process 
  • The pituitary gland rests at the base of the brain and is connected to the overlying hypothalamus
  • The pituitary gland responds to input from both the brain (via the hypothalamus) and the body (via the various peripheral endocrine glands) by secreting various hormones 

Regulation of thyroid hormone synthesis

 

  • Hypothalamus secretes TRH (Thyrotropin releasing hormone) which stimulates the synthesis and release of TSH (Thyroid stimulating hormone) from the pituitary gland 
  • TSH stimulates the thyroid gland to increase the synthesis and release of T4 (Tetra-iodothyronine) and T3 (Tri-iodothyronine) 
  • High thyroid levels rapidly and directly supress TSH and TRH levels while reduced level of thyroid hormones increase TSH and TRH production 
  • Hence thyroid hormones act in a negative feedback fashion.

Synthesis of Thyroid hormones

Iodine Absorption: Iodine is absorbed by thyroid gland from blood and transported to follicular cells 

Organification Iodine oxidation and tyrosyl Iodination: Iodine is oxidised to iodide and added to tyrosyl residues with in thyroglobulin (Tg) to form iodotyrosines 

Coupling of Iodotyrosine and storage of T4 and T3: Iodothyrosines are coupled in tg to form T4 and T3 that are stored within Tg 

Proteolysis of Tg and Release of T4 and T3:
Proteolysis of Tg release T4 and T3 into blood. T4 is secreted from the thyroid gland in about 20 folds excess over T3 

Function of Thyroid hormones

Calorigenic: Increase metabolic rate and oxygen consumption of almost all metabolically active tissues 

Growth and development: Essential for growth and skeleton maturation 

Central Nervous System: Plays critical role in development of nervous system 

Thermogenic: Necessary for thermogenesis (heat generation during vital process) 

Cardiovascular system: Increase heart rate, stroke volume and cardiac output, reduces peripheral vascular resistance etc. 

Metabolic: Regulation of lipid and carbohydrates

Tyroid peroxidase (TPO) 

  • TPO is an enzyme that catalyzes following reaction during thyroid hormones synthesis
  • Oxidation and organification 
  • Coupling of tyrosines 
Autoimmune hyperthyroidism
Can be detected by high levels of circulating antibodies against TPO(TPOAB), in most patients 

Thyroid Stimulating Hormone (TSH) 

  • Secreted by the anterior pituitary which binds to its receptors (TSH-R) present on thyroid cells 
  • Stimulates the thyroid gland for thyroid hormone synthesis and secretion 
  • Also Stimulates growth and vasculature of the thyroid gland 

Autoimmune hyperthyroidism

Can also be characterized by high levels of circulating antibodies directed against TSH receptors 

Transport, Protein Binding, Metabolism, Excretion

  • Approximately 99.98% of T4 and 99.7% of T3 are protein blunted to thyroxine-BindingGlobulin(TBG), Albumine and Pre-albumin or Transthyretin. 
  • Protein binding protects the hormones from metabolism and excretion, resulting in their long half lives 
  • Under normal conditions: 40% of T4 is converted to T3, 40%of T4 is converted to reverse T3 (rt3), 20% of T4 is metabolized in the liver and exerted in the bile. 

Half life 

T4 - About 7 days 
T3 - About 30 hours 

Peripheral conversation of Thyroid Hormones

  • Peripheral conversation of T4 to T3 takes place in the presence of Deiodinases (D1,D2,D3) enzymes in various organs 
  • It's take place in the presence of Deiodinases (D1 and D2) in the liver, kidneys, pituitary gland, brain, brown fat, heart, skeleton muscle and thyroid 
  • D3 deiodinase causes conversation of T4 into reverse T3(rT3) at placenta brain, and some sites of inflammation
  • About 87%of circulating T3 derives from peripheral conversation of T4 to T3 and only 13% from thyroid secretion.

Mode of action of Thyroid Hormones

  • Thyroid hormones enter cells and bonds to thyroid hormone receptor (TR) in the nuclei
  • The hormone- receptor complex then bind to DNA thereby modulating transcription of specific genes that regulates cells function 
  • T3 act more rapidly and 3-5 times more potent than T4 as T3 is less tightly bound to plasma proteins than T4 and binds more avidly to thyroid hormone receptor (TRs) with 10 fold greater affinity than T4 

Disorders of Thyroid gland 

Hyperthyroidism : An overactive Thyroid 

Hypothyroidism : An underactive Thyroid 

Thyroiditis : Inflammation of the Thyroid gland 

Goiter : An enlarged Thyroid 


Thyroid Nodule : Growth (lump) in Thyroid gland 


Thyroid Cancer : Malignant thyroid nodules or tissues 


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