Transcript ABNORMALITIES OF THYROID HORMONE

THYROID HORMONE
SECRETION
CONTROL & DIAGNOSIS
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.
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
↓
1. Immediate increase in thyroid hormone secretion
2. Stimulates growth of the thyroid glandular tissue
THYROID STIMULATING HORMONE
EFFECTS ON THE THYROID GLAND:
1. Increased secretion of TG and proteolysis of
the TG already stored in the follicular cells.
2. Increased activity of the NIS (SYMPORTER)
so that Iodide Trapping is increased.
3. Stimulates the step Organification.
4. Increased number, size & secretory activity of
the thyroid cells (with change into columnar
from cuboidal).
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!
• ANTERIOR PITUITARY SECRETION OF
TSH IS REGULATED BY
THYROTROPIN-RELEASING HORMONE
FROM THE HYPOTHALAMUS
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
HYPOTHALAMICHYPOPHYSIAL
PITUITARY AXIS
Hypothalamus
↓
TRH
↓
HypothalamicHypophysial portal
system
↓
Anterior pituitary
↓
TSH
↓
Thyroid gland
↓
Tri-iodothyronine &
Thyroxine
IF TYROID HORMONE IS DEFICIENT, ITS
SECRETION IS STIMULATED
THROUGH THIS FEEDBACK SYSTEM!
&
VICE VERSA!
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
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!
THYROID FUNCTION TESTS
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
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
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.
THYROID FUNCTION TESTS
4. MISCELLANEOUS TESTS:
• Antithyroid antibodies & Antithyroglobulin antibodies (TSI in Grave’s
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.