PL2 Thyroid Physiology

• Thyroxin/tetraiodothyronine (T4) & Triiodothyronine (T3)


  Synthesized by epithelial cells of the thyroid follicles and stored as colloids inside the follicles

  
• Colloid particles

  Components of thyroglobulin molecules
• Calcitonin


  Synthesized and secreted by Parafollicular cells, found in-between follicular cells
• Steps in the synthesis of thyroid hormones

  1. Iodide pump brings iodide from ECF into follicular cells

  2. Iodide oxidized to iodine by peroxidase enzyme

  3. Protein is synthesised by the epithelial cells

  4. Iodination of tyrosine to form monoiodotyrosine (MIT) and diiodotyrosine (DIT)

  5. Coupling of MIT and DIT give rise to T3 and T4 (stored in the thyroid follicles)
• Secretion

  1. Small droplets of colloids are taken by the epithelial cells through pinocytosis

  2. Proteolytic enzymes digest the thyroglobulin molecule and release T4 and T3 into the cytoplasm of the epithelial cells

  3. T4 and T3 diffuse through the basal border into the blood capillaries
• Circulating Hormones

  100% of T4 come from thyroid gland; 80% of T3 comes from conversion of T4 to T3 in target tissues<|>Only free hormones are metabolically active<|>Normal plasma T4 level = 8 mg/100 ml (99.98% in bound form)<|>Normal plasma T3 level = 0.15 mg/100 ml (99.8% in bound form)<|>Binding of the hormones with proteins (thyroid binding globulin(TBG), albumin, and pre-albumin) prevents the renal loss of these hormones<|>MIT and DIT are deiodinated to iodine and reused for T3 and T4 synthesis
• Regulation of thyroid hormone secretion

  1. The physiological levels of thyroid hormone is maintained by the hypothalamus-anterior pituitary-thyroid (HPT) gland axis along with negative feedback regulation

  2. When T3 and T4 increased, the hypothalamus & pituitary will inhibit the release of TRH and TSH

  3. With less TSH circulating to thyroid, less T3 and T4 will be released by thyroid
• Physiological actions of thyroid hormones

  • They do not have any specific target organ, their actions manifest in almost all the tissues of the body
  • There is a long delay in the onset of action and the action is prolonged
  • T3 acts about four times more rapidly than T4 and also about 4 times more potent than T4
• Causes of thyroid disorders

  • Too much production of thyroid hormone or hyperthyroidism
  • Too little thyroid hormone production or hypothyroidism
• Hyperthyroidism


  It occurs due to the presence of excess of TSH like substances in the blood<|>It occurs due to localized adenoma in the thyroid gland<|>As in Grave's disease (exophthalmic goiter), the thyroid stimulating auto antibodies produced by T lymphocytes stimulate the thyroid cells to grow larger and to produce excessive amount of thyroid hormones

  
• Hypothyroidism


  Decreased secretion of thyroid hormone due to genetic defect or lack of iodine in the diet or even due to congenital lack of thyroid gland<|>Leads to myxoedema in adults and cretinism in children
• Cretinism


  A new born baby with thyroid deficiency may appear to be normal at birth, because the thyroxin might have been supplied from mother. But few weeks after birth the baby starts developing the signs like sluggish movements and croaking sound while crying. Unless treated immediately the baby may become mentally retarded also<|>Skeletal growth is affected more than soft tissues. So, there is stunted growth and bloated body. Tongue becomes so big, that it hangs down with dripping saliva<|>A cretin is different from pituitary dwarf. In cretinism, there is mental retardation and the different parts of the body grow disproportionately. Whereas, in dwarfism, the development of nervous system is normal and different parts of the body grow proportionately
• Causes of cretinism

  • Maternal iodine deficiency
  • Inborn errors in thyroid hormone synthesis
  • Maternal antithyroid antibodies that cross the placenta and damage fetal thyroid
  • Fetal hypopituitary- hypothyroidism
• Mental deficiency is more severe, when the mother is hypothyroid and less responsive to replacement treatment with thyroxin
• Goiter


  Enlargement of thyroid gland

  
• Toxic goiter

  Goiter in hyperthyroidism, due to tumor of the thyroid gland, the size of the gland is increased due to increased number of hormone secreting cells and the hormone level also is increased to a great extent
• Nontoxic goiter


  Goiter in hypothyroidism, there is enlargement gland, but secretion of hormone is less
• Types of nontoxic goiter

  • Endemic colloid goiter (iodine deficient goiter)
  • Idiopathic nontoxic goiter
• Endemic colloid goiter

  It occurs when iodine uptake is less than 50 micro gram/day. Because of lack of iodine there is no formation of hormones. By feed back mechanism hypothalamus and pituitary are stimulated and are released more of TRH and TSH which in turn cause the growth of the thyroid follicles and increase its size causing goiter
• Idiopathic nontoxic goiter


  The exact cause is not known. Patients are first affected by thyroiditis, which reduces the synthesis of thyroid hormones, which in turn causes increased secretion of TSH causing increase in the size of the gland. Some food stuff (vegetables like turnips,cabbage soybeans) contains goiterogenic substances can produce goiter during low iodine intake
• Thyroid function tests

  • Direct measurement of free T3 and T4 in the plasma
  • Measurement of basal metabolic rate (BMR)
  • Measurement of TRH and TSH in the plasma

  
• Calcitonin


  It is a polypeptide consists of 32 amino acids secreted by the Parafollicular or "C"- cells of the thyroid glands<|>Plays an important role in the maintenance of calcium level in the blood along with parathyroid hormone<|>Calcitonin reduces the blood calcium level by acting on bones, kidneys and intestine
• Hormone for thyroid gland

  1. T3, T4
  2. calcitonin
• Effect of thyroid hormone deficiency on growth and development

  1. Congenital deficiency of thyroxin results in growth retardation
  2. Long bones remain in the infantile stage due to delay in the appearance of epiphyseal centers and bone age lags behind the chronological age.
  3. bones of the skull are affected and hence eruption of teeth is delayed
• Effect of thyroid hormone on metabolic rate

  1. stimulate the basal metabolic rate, oxygen consumption, and heat production in most tissues (except adult brain, testis, uterus and anterior pituitary)
• effect of thyroid hormone on CNS

  1. decrease = impairment of memory, somnolence and slowness of speech
  2. increase = hyper excitability, irritability, restlessness, and insomnia
• Effect of thyroid hormone on cardiovascular system

  Hyperthyroid state is characterized by tachycardia, increased cardiac output, increased pulse pressure and cutaneous vasodilatation.
• Effect of TH on carbohydrate & fat metabolism

  1. Increases cellular metabolism.
  2. Increases the rate of absorption of glucose.
  3. Increases gluconeogenesis & glycolysis.
  4. Increases insulin secretion.
  5. Causes depletion of fat from the adipose tissues leading to increased free fatty acid level.
  6. Lowers blood cholesterol level
• Effect of TH on protein metabolism

  Excessive doses of thyroxin, produces greater protein catabolism and negative nitrogen balance.

  Muscle weakness and creatinuria are characteristic features of a hyperthyroid patient
• Effect of TH on muscles

  • Slight increase in thyroid hormone makes the muscles react with vigor
  • excess causes weakening of muscles due to excess protein catabolism
  • hyperthyroid = muscle tremor
  • hypo = muscle become sluggish & relax slowly after contraction
• Effect on GIT

  Thyroid hormone increases the rate of gastrointestinal juices secretion and rate of absorption of food stuff in the intestine.
• Effect on reproduction

  1. Hypo in men = complete loss of libido
  2. hyper in men = impotence
  3. normal in women = the normal rhythmicity of ovarian cycles or lactation
• Hyperthyroidism due to Graves disease


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• Symptoms of hyperthyroidism

  1. Intolerance to heat
  2. Increased sweating due to vasodilatation.
  3. Decrease in body weight due to fat mobilization
  4. Diarrhea due to increased motility of GIT.
• General symptoms of myxoedema

  • Fatigue and muscular sluggishness
  • Extreme somnolence with sleeping
  • menorrhagia
  • decreased CVS function