Thyroid gland

• Thyroid gland

  Located below the larynx on either sides and anterior to the trachea
• The first recognized endocrine gland
• Weight of thyroid gland in adult is 20g
• Thyroid hormones

  • T4 (tetraiodothyronine) (thyroxine) 90%
  • T3 (Triiodothyronine) 10%
  • Reverse T3
  • Calcitonin
• Thyroid gland

  • Contains a large amount of iodine
  • Synthesis is partially intracellular and partially extracellular
  • T4 is the major product
• Thyroid hormones [T3 - T4] biosynthesis

  1. Iodide pump

  2. Thyroglobulin synthesis

  3. Oxidation of iodide to iodine

  4. Iodination of tyrosine, to form mono-iodotyrosine (MIT) & di-iodotyrosine (DIT)

  5. Coupling; MIT + DIT = Tri-iodothyronine, (T3), DIT + DIT = Tetra-iodothyronine, (T4)/ Thyroxine

  6. Release
• Thyroglobulin formation and transport

  1. Glycoprotein

  2. Tyrosine

  3. Rough endoplasmic reticulum and Golgi apparatus
• Iodide pump or iodide trap

  1. Active transport

  2. Stimulated by TSH

  3. Wolff-Chaikoff effect

  4. Ratio of concentration from 30-250 times
• Oxidation of iodide to iodine

  1. Thyroid peroxidase

  2. Located in or attached to the apical membrane
• Organification of thyroglobulin

  1. Binding of iodine with thyroglobulin

  2. Catalyzed by thyroid peroxidase, to form MIT/DIT

  3. Remain attached to thyroglobulin until the gland stimulated to secret
• Coupling reaction

  1. DIT + DIT = T4 (faster)

  2. DIT + MIT = T3

  3. Catalyzed by thyroid peroxidase

  4. Stored as colloid

  5. Sufficient for 2-3 months
• Release of T4 and T3 to the tissues

  1. The release is slow because of the high affinity of the plasma binding proteins

  2. T4 & T3 readily diffuse through the cell membrane

  3. Stored in the targeted tissues (days to weeks)

  4. Most of T4 is deionized to T3 by iodinase enzyme

  5. In the nucleus, T3 mainly binds to "thyroid hormone receptor" and influence transcription of genes
• Basal Metabolic Rate (BMR)


  • The energy requirement under basal condition (mental and physical rest 12-18 hours after a meal)
  • Complete lack of thyroid hormones decreases BMR by 40-50%
  • Extreme increase of thyroid hormones increases BMR by 60-100%
• Effects of thyroid hormones on metabolism

  • Increase glucose uptake by the cells
  • Increase glycogenolysis
  • Increase gluconeogenesis
  • Increase absorption from the GIT
  • Increase lipolysis
  • Decrease plasma cholesterol by increase loss in feces
  • Increase oxidation of free fatty acids
  • Overall effect on protein metabolism is catabolic leading to decrease in muscle mass
• Metabolic enzymes induced by thyroid hormones

  • Cytochrome oxidase
  • NAPDH cytochrome C reductase
  • Alpha-glycerophosphate dehydrogenase
  • Malic enzymes
  • Several proteolytic enzymes
• Effects of thyroid hormones on the cardiovascular system

  • Increase heart rate
  • Increase stroke volume
  • Decrease peripheral resistance
  • Increase delivery of oxygenated blood to the tissues
• Mechanisms of cardiovascular effects of thyroid hormones

  • Thyroid hormones potentiate the effect of catecholamine in the circulation, activating β-adrenergic receptors
  • Direct induction of myocardial β-adrenergic receptors, sarcoplasmic reticulum, Ca+2 ATPase, and myosine
• Effects of thyroid hormones on the CNS in perinatal period

  • Thyroid hormones are essential for maturation of the CNS
  • Decrease of hormones secretion leads to irreversible mental retardation
• Effects of thyroid hormones on the CNS in adults

  • Increase in thyroid hormone secretion causes hyperexcitability and irritability
  • Decrease in thyroid hormones secretion causes slow movement, impaired memory, and decreased mental capacity
• Effects of thyroid hormones on bone

  Promote bone formation, ossification, fusion of bone plate, and bone maturation
• Effects of thyroid hormones on respiration

  • Increase ventilation rate
  • Increase dissociation of oxygen from Hb by increasing RBC 2,3-DPG (2,3 diphosphoglycerate)
• Effects of thyroid hormones on the GIT

  • Increase appetite and food intake
  • Increase of digestive juices secretion
  • Increase of G.I tract motility
  • Excess secretion causes diarrhea, lack of secretion causes constipation
• Effects of thyroid hormones on the autonomic nervous system

  • Produce the same action as catecholamines via β-adrenergic receptors, including increase in BMR, heat production, heart rate, and stroke volume
  • β-blocker (propranolol) is used in treatment of hyperthyroidism
• Regulation of thyroid hormones secretion is by the hypothalamic-pituitary axis
• Regulation of thyroid hormones secretion

  1. Thyrotropin-releasing hormone (TRH) from the hypothalamus acts on the thyrotrophs of the anterior pituitary to stimulate transcription and secretion of TSH

  2. Thyroid-stimulating hormone (TSH) from the anterior pituitary regulates metabolism, secretion, and growth of the thyroid gland

  3. TSH increases proteolysis of thyroglobulin, pump activity, iodination of tyrosine, coupling reaction, and has a trophic effect on the thyroid gland

  4. TSH secretion starts at 11-12 weeks of gestation

  5. TSH binding to its receptor activates adenylyl cyclase via Gs protein, increasing cAMP and activating protein kinase, leading to secretion and thyroid growth
• Hyperthyroidism


  • Over activity of the thyroid gland
  • Women to men ratio is 8:1
  • Thyroid gland activity is 5-10 times increase in secretion and 2-3 times increase in size
• Causes of hyperthyroidism

  • Graves' disease (an autoimmune disorder with increased circulating thyroid-stimulating immunoglobulins)
  • Thyroid gland tumor (95% benign, 5% malignant)
  • Exogenous T3 and T4
  • Excess TSH secretion from diseases of the hypothalamus or pituitary
• Symptoms of hyperthyroidism


  • Goiter in 95%
  • Smooth, warm and moist skin, heat intolerance, night sweating
  • Muscle atrophy
  • Tremor, enhanced reflexes, irritability
  • Increase heart rate, increase stroke volume, arrhythmias, hypertension
  • Weight loss, diarrhea
  • Increase glomerular filtration rate
  • Anxious staring expression, protrusion of eye balls
  • Menstrual cycle disturbance
• Diagnosis of hyperthyroidism

  Serum T3, T4 measurement: high T3, T4 and low TSH in primary hyperthyroidism, high T3, T4 and high TSH in secondary hyperthyroidism
• Treatments for hyperthyroidism

  • Medical therapy with propylthiouracil for 12-18 months
  • Surgery: subtotal thyroidectomy, indicated for relapse after medical treatment, drug intolerance, cosmetic reasons, or suspected malignancy
• Hypothyroidism

  Under activity of the thyroid gland, more common in women aged 30-60 years
• Causes of hypothyroidism


  • Inherited abnormalities of thyroid hormone synthesis
  • Endemic colloid goiter due to iodine deficiency
  • Idiopathic nontoxic colloid goiter
  • Gland destruction (surgery)
  • Pituitary diseases or tumor
  • Hypothalamus diseases or tumor
• Symptoms of hypothyroidism

  • Dry skin, cold intolerance
  • Decreased muscle bulk, skeletal growth, muscle sluggishness, slow relaxation after contraction
  • Slow movement, impaired memory, decreased mental capacity
  • Decreased blood volume, heart rate, and stroke volume
  • Constipation, increased weight
  • Decreased glomerular filtration rate
  • Edematous appearance throughout the body (myxedema)
  • Loss of libido, menstrual cycle disturbance
• Diagnosis of hypothyroidism

  Serum T3, T4 are low, TSH is elevated in primary hypothyroidism, TSH is low in secondary hypothyroidism
• Treatment of hypothyroidism

  1. L-thyroxine, starting dose 25-50 μg, increased to 200 μg over 2-4 weeks, first response seen is weight loss
• Cretinism


  Extreme hypothyroidism during infancy and childhood, leading to failure of growth
• Causes of cretinism

  • Congenital lack of thyroid gland
  • Genetic deficiency leading to failure to produce hormone
  • Iodine deficiency in the diet (endemic cretinism)
• Symptoms of cretinism

  • Infant is normal at birth but abnormality appears within weeks
  • Protruding tongue
  • Dwarf with short limbs
  • Mental retardation
  • Often umbilical hernia
  • Delayed teeth development
• Changes in cretinism are irreversible unless treatment is given early
• Basal Metabolic Rate (BMR) calculation

  For men: BMR = 66 + (13.7 x weight in kg) + (5 x height in cm) - (6.8 x age in years)

  For women: BMR = 65 + (9.6 x weight in kg) + (1.8 x height in cm) - (4.7 x age in years)