THYROID HORMONE SECRETION

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THYROID HORMONE SECRETION

• CONTROL DIAGNOSIS

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THYROID STIMULATING HORMONE (TSH)

• Also called Thyrotropin.
• Secreted by the ANTERIOR PITUITARY.
• A glycoprotein with a m.w 28,000.
• Main function It increases the secretion of both
  Tri-Iodothyronine Thyroxine by the Thyroid
  Gland.

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THYROID STIMULATING HORMONE

• Mechanism of Action
• TSH TSH receptors (a typical G-protein coupled
  receptor) on the thyroid follicular cell membrane
  of the Thyroid Gland
• ?
• Adenylyl Cyclase stimulated
• ?
• ATP? cAMP
• ?
• Protein kinase A is activated
• ?
• Multiple phosphorylations throughout the cell
• ?
• Immediate increase in thyroid hormone secretion
• Stimulates growth of the thyroid glandular tissue
  

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THYROID STIMULATING HORMONE

• EFFECTS ON THE THYROID GLAND
• Increased secretion of TG and proteolysis of the
  TG already stored in the follicular cells.
• Increased activity of the NIS (SYMPORTER) so that
  Iodide Trapping is increased.
• Stimulates the step Organification.
• Increased number, size secretory activity of
  the thyroid cells (with change into columnar from
  cuboidal).

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THYROID STIMULATING HORMONE

• IN SUMMARY TSH increases all the known secretory
  activities of the thyroid gland!
• MOST IMPORTANT IS PROTEOLYSIS WHICH CAUSES
  RELEASE OF THE TH INTO THE BLOOD STREAM WITHIN 30
  MINUTES!

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• ANTERIOR PITUITARY SECRETION OF TSH IS REGULATED
  BY THYROTROPIN-RELEASING HORMONE FROM THE
  HYPOTHALAMUS

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THYROTROPIN RELEASING HORMONE (TRH)

• A tripeptide amide (pyroglutamyl-histidyl-proline-
  amide)
• Secreted by the nerve endings in the median
  eminence of hypothalamus
• Mechanism of secretion
• TRH TRH receptor in the pituitary cell membrane
  of the Pituitary Gland
• ?
• Phospholipase C second messenger system activated
  
• ?
• TSH released

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HYPOTHALAMIC-HYPOPHYSIAL PITUITARY AXIS

• Hypothalamus
• ?
• TRH
• ?
• Hypothalamic-Hypophysial portal system
• ?
• Anterior pituitary
• ?
• TSH
• ?
• Thyroid gland
• ?
• Tri-iodothyronine Thyroxine

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• IF TYROID HORMONE IS DEFICIENT, ITS SECRETION IS
  STIMULATED THROUGH THIS FEEDBACK SYSTEM!
• VICE VERSA!

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POINTS TO REMEMBER

• EXCITEMENT STRESS CAUSE A DECREASE IN THE TRH
  SECRETION therefore TSH secretion.
• Cold in infants increases the secretion of TRH by
  the hypothalamus thus causes an increase in the
  TSH secretion!
• BOTH THESE EFFECTS ARE NOT SEEN WHEN THE
  HYPOTHALAMIC- HYPOPHYSIAL TRACT HAS BEEN CUT
  SHOWING THAT THESE EFFECTS ARE MEDIATED THROUGH
  THE HYPOTHALAMUS

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REMEMBER

• When the rate of TH secretion increases by 1.75
  times normal, the rate of TSH secretion falls
  essentially to zero!
• This effect on the anterior pituitary is seen
  even when Anterior Pituitary has been separated
  from hypothalamus!

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THYROID FUNCTION TESTS
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THYROID FUNCTION TESTS

• 1. TESTS RELATED TO HORMONE CONCENTRATION IN
  BLOOD
• Serum total T4 conc. normal value is 5- 12 µg/
  dl
• Serum total T3 conc. normal value is 70-190 µg/
  dl
• Serum free T4 T3 conc. these values represent
  physiologically active forms of T4 T3
• ALL THE ABOVE VALUES ARE RAISED IN
  HYPERTHYROIDISM DECREASED IN HYPOTHYROIDISM

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THYROID FUNCTION TESTS

• 2. DIRECT TESTS OF THYROID FUNCTION
• - RADIOACTIVE IODINE UPTAKE TEST (RAIU) A
  small dose of 123I is given orally fraction
  taken up by the thyroid gland after 24 hours is
  found by taking pictures at 4 24 hours to
  measure its radioactivity.
• Normally this value is about 30.
• It is raised in Hyperthyroidism decreased in
  Hypothyroidism.
• Also used to assess residual thyroid tissue after
• thyroid gland removal.
• Determine recurrence of thyroid cancer

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THYROID FUNCTION TESTS

• 3. INDIRECT TESTS OF HOMEOSTATIC CONTROL
• Plasma conc. Of TSH normal level is 0.3- 3 mu/l.
• LOW in Hyperthyroidism
• Increased in Hypothyroidism of thyroid origin
• LOW or normal in pituitary or hypothalamic
  Hypothyroidism
• TSH is the Best single test to screen for thyroid
  disease.
• Levels of TSH reflect the amount of free,
  biologically active TH.
• TSH is the best test to monitor thyroid
  replacement therapy.
• TSH can remain misleadingly high with the
• initiation of thyroid replacement, pituitary
  reset.
• Wait 6-8 weeks before repeating TSH after
  starting the therapy.

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THYROID FUNCTION TESTS

• 4. MISCELLANEOUS TESTS
• Antithyroid antibodies Antithyroglobulin
  antibodies (TSI in Graves disease)
• Antibodies against TSH receptors
• Circulating antibodies against T3 T4
• Scanning images of thyroid gland (radio-iodine or
  Na) these techniques indicate areas of increased
  or decreased thyroid activity. Esp. useful with
  retrosternal goitre or ectopic thyroid tissue.
• Ultrasonic examination of thyroid gland measures
  the size of the thyroid gland helps
  differentiate b/w solid cystic thyroid nodules
  
• BMR raised in Hyper lowered in Hypothyroidism.