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 secretion2. 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 hypothalamusMechanism of secretion: TRH + TRH receptor in the pituitary cell membrane of the

Pituitary Gland ↓

Phospholipase C second messenger system activated ↓

TSH released

HYPOTHALAMIC-HYPOPHYSIAL

PITUITARY AXISHypothalamus

↓TRH

↓Hypothalamic-

Hypophysial 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 afterthyroid gland removal.• Determine recurrence of thyroid cancer

THYROID FUNCTION TESTS3. 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 theinitiation 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.