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Thyroid Hormones

Thyroid Hormones (T4/T3)

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Thyroid Gland –The Body's thermostat

Production of Thyroid Hormones T3/T4

Thyroid's T4/T3 production is controlled by hypothalamic control

T4-to-T3 Conversion

Result of Deficient Thyroid Hormones

Circulation and Transport of T3/T4

Neither TSH or blood Plasma T3/T4 Levels alone are a substantive evaluation of thyroid function


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Thyroid Disorders

The Thyroid gland –“The Body's Thermostat”

A butterfly-shaped gland wrapped around the windpipe -behind and below the Adam's apple. It is the largest endocrine gland in the body and the master gland of metabolism.

Produces thyroid hormones Thyroxine (T4) and Triiodothyronine (T3)

✔  T4 –Storage form

✔  T3 –Metabolically active form

T3 has three primary functions:

1. Enhance protein synthesis and growth

2. Help oxygen get into cells – determines how quickly the body uses energy (the basal metabolic rate (BMR)). Increasing cellular oxygen consumption increases production of cellular ATP (cell's energy currency)

3. Control body's sensitivity to other hormones

Thus, they basically influence all body functions, including:

✔ Nerve and bone formation

✔ Reproduction

✔  Condition of the skin, hair, nails and teeth

✔ Connective tissue strength and our speech/mental state

Most common problems of the thyroid gland are:

–   An overactive thyroid(called hyperthyroidism)

–   An underactive thyroid (called hypothyroidism).

–   Thyroid hormone Deficiency - can reduce BMR up to 50%;

–   Excessive thyroid hormone production - can increase BMR by 100%.

The functional units of the thyroid gland are spherical follicles -each follicle consists of:

-Thyroid follicular cells(aka. thyroid epithelial cells /follicular epithelial cells/ thyrocytes) (simple cuboidal type) forming the outside boundary . . .

–   Filled with a viscous material called colloid -which contains mostly glycoprotein thyroglobulin (Tg) molecules, that provide:

✔ The glycoprotein backbone for synthesis and storage of thyroid hormones

✔  A convenient depot for iodine storage and retrieval - when external iodine availability is scarce or erratic.

Production of Thyroid Hormones: Thyroxine (T4),Triiodothyronine (T3)

Iodine + Amino acid tyrosine → ( used to form) T3 and T4.

Thyroid production is a complex process taking place in thyroid follicles – its main steps are:

(1) TSH stimulation.

(2) Iodide Transport from the blood stream to the follicular lumen –iodide is concentrated to about 30 times blood concentration via the Sodium/iodide pump (NIS)

(3) Iodide is oxidized to iodine via the thyroperoxidase (TPO) enzyme mediated by H2O2, and then incorporated into tyrosine residues of colloid thyroglobulin (Tg) molecules and formed into thyroid hormones T3 and T4 –which can be stored as part of Tg for up to 3 months

(4) TSH stimulates formation and release of T3 and T4 -thyroid hormones are cleaved from thyroglobulin and released into circulation when needed

Importance of iodine supply for making thyroid hormones

–   Iodine supply, either too much or too little, impairs adequate synthesis -the main function of the thyroid gland is to make hormones, T4 and T3, which are essential for the regulation of metabolic processes throughout the body. As at any factory, effective production depends on three key components - adequate raw material, efficient machinery, and appropriate controls. Iodine is the critical raw material, because 65% of T4 weight is iodine.

For more detailed information on thyroid hormone production:

Thyroid Hormone Production - In detail

Thyroid feedback loop

Thyroid's T4/T3 production is controlled by hypothalamic control of the pituitary gland's production of thyroid stimulating hormone (TSH), by negative feedback of T3/T4 levels

The hypothalamus in the brain releases TRH (Thyrotropin-Releasing Hormone) - to modulate the pituitary gland's release of TSH (Thyroid Stimulating Hormone);

TSH circulating in the bloodstream tells the thyroid to make T3 and T4 thyroid hormones - and release them into the bloodstream, to be converted as needed to T3, mainly by the liver;

The pituitary gland's TSH production is sensitive to the T3/T4 levels in the blood

–   When the T3/T4 levels drop, the pituitary produces and releases more TSH -to stimulate the thyroid to release more T4 and T3 into the bloodstream;

–   As the thyroid hormone levels rise, the pituitary reduces or shuts off TSH - This negative feedback mechanism keeps the level of thyroid hormones in a fairly constant range with a normally-functioning thyroid.

TSH production is also reduced by:

–    Somatostatin – hormone that inhibits secretion of growth hormone

–    Rising levels of glucocorticoids and sex hormones (e.g. Estrogen, TESTOSTERONE)

–    Excessively high blood iodide concentration – as aself protecting mechanism.

TSH-T4 level conditions

T4-to-T3 Conversion

All the thyroid hormone metabolic activity comes from T3 - T4 is in the body just to be converted to T3 (Except during pregnancy, when T4 is needed for the fetus to develop properly). T4 essentially acts as a reservoir for T3;

Only ~20% of the body's T3 comes from the synthesis of T3 within the thyroid - the rest of the T3 is derived when the deiodinase enzyme removes one iodine molecule from T4. (the "3" and "4" refer to the number of iodine atoms in each thyroid hormone molecule).

Most T4 →T3 conversion(via deiodinase enzymes)takes place in the liver - but some also in other peripheral organs, including thyroid, kidneys, spleen and the brain's hypothalamus. The immediate effects of T3 last for 1-2 days.

Some people have a problem converting T4 to T3 not always indicated by lab tests.

Stress-activated hormones interfere with T4 to T3 conversion –stress hormones, such as CORTISOLand EPINEPHRINE (ADRENALINE) can divert the conversion of T4 hormones into inactive forms that do not activate metabolism.

Stress Affects TH production

Normal Blood levels of thyroid hormones

T4 - 8.0 - 23.0 pmo1/L

T3 - 0.9 - 2.8 nmo1/L

TSH - 0.40 - 5.00 mU/L.

Result of Deficient Thyroid Hormones

Without enough thyroid hormone in its active T3 state, the metabolism slows down - possibly resulting in:

Lowered pulse rate


Goiter (thyroid enlargement)

Weight gain / slow metabolism


Fluid retention

Dry/flaky skin

Cold hands or feet

Hair loss, dry/brittle hair

Brittle nails

Puffy face in morning


Swollen/droopy eyes

Low sex drive

Brain damage

Muscle aches/cramps

PMS, painful periods


Lower IQ

Heart palpitations


Yellow discoloration skin/palms

High cholesterol


Circulation and Transport of T3/T4

Plasma transport - Most of the circulating thyroid hormone is bound to transport proteins. Only a very small fraction is free (unbound) and biologically active.

When thyroid hormone is bound, it is not active, so the amount of free T3/T4 is what is important. Thus, measuring total T4 in the blood can be misleading.



Bound to thyroxine-binding globulin (TBG)


Bound to transthyretin or "thyroxine-binding prealbumin" (TTR or TBPA)




Unbound T4 (fT4)


Unbound T3 (fT3)


Membrane transport of T3/T4 -since they are lipophilic (“fat-loving”) molecules, T3 and T4 cross the cell membrane easily, and function via a well-studied set of thyroid hormone receptors (receptors in the nucleus of the cell);

Although they can even transverse the cell membrane in a passive manner, at least 10 different active, energy dependent and genetic regulated iodothyronine transporters have been identified in humans. They guarantee that intracellular levels of thyroid hormones are higher than extracellular blood plasma or interstitial fluids (tissue fluids).

Neither TSH or blood Plasma T3/T4 Levels alone are a substantive evaluation of thyroid function

The level of thyroid hormone (i.e. T3 and T4) production is determined by:

–   Levels of TSH released from the pituitary gland -producing a feedback loop so that TSH increases as thyroid hormones decrease, and TSH decreases when thyroid hormones increase;

–   AVAILABILITY of IODINE and TYROSINE(converted by the thyroid to the thyroid hormones) - Insufficient iodine causes thyroid cell enlargement (hypertrophy), leading to an enlarged thyroid (goiter).

Iodine Availability

–   The condition of the thyroid tissues themselves;

–    Further regulated by the hypothalamus, by other nutrient requirements, and no doubt other regulatory mechanisms;

–    TSH level is also not a reliable indicator of thyroid function for many people

(E.g. Low amounts of T4 in the blood, due to lack of dietary iodine to make them, gives rise to high levels of TSH);

A low TSH level should indicate optimum or high thyroid hormone levels

However, the TSH level simply indicates how much T4 the pituitary is getting, and. . . .

✔  The thyroid may be producing enough T4 (keeping TSH low), but the body isn't converting enough available T4 to T3

✔  The pituitary and the hypothalamus (which controls the pituitary) may not be functioning optimally


Book chapter on Thyroid hormone synthesis and secretion: http://www.thyroidmanager.org/Chapter2/2-frame.htm


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