Thyroid function tests help to determine if your thyroid is not working correctly. If blood levels of thyroid hormone are high, the brain senses this and sends a message to stop producing TSH.

1. THYROID HORMONE:
• Gross and Microscopic Anatomy of the Thyroid Gland.
• Production of Thyroid Hormones.
• Transport of T3 and T4
• Actions of Thyroid Hormones.
• Regulation of Thyroid Hormones.
• Hyper- and Hypothyroidism

2. Histology of theThyroid Gland
• The thyroid gland contains numerous follicles, composed of
epithelial follicle cells and colloid.
 Also, between follicles are Para-follicular cells, which produce
Calcitonin.

3. TheThyroid Gland – Histology:

Squamous epithelial cells, cuboidal cells (follicle cells).
Gland is composed of hollow spheres, called colloid follicles.
Colloid fills the follicle cavities.

Follicle cells produce thyroglobulin.

4. Thyroid Hormones:
 There are two biologically active thyroid hormones:
- Tetraiodothyronine(T4; usually called thyroxine)
- Triiodothyronine (T3)
 Derived from modification of tyrosine(amino acid).

5. Differencesbetween T4 and T3:
• The thyroid secretes about 80mg of T4, but only 5mg of T3 per
day.
• However, T3 has a much greater biological activity about 10
folds than T4.
• An additional 25mg/day of T3 is produced by peripheral
monodeiodination of T4 by enzyme called 5’ Monodeiodenase.

6. Major sourcesof iodine:
• Thyroid hormones are unique biological molecules in that they
incorporate iodine in their structure.
• Thus, adequate iodine intake either through diet or water is
required for normal thyroid hormone production.
• Major sources of iodine are:
- iodized salt
- iodated bread
- dairy products
- shellfish
• Minimum requirement(RDA): 75 micrograms/day
• US intake: 200 - 500 micrograms/day

7. TheNext Step: Production of Thyroglobulin:
 Pituitary produces TSH, which binds to follicle cell receptors.
 The follicle cells of the thyroid produce thyroglobulin.
 Thyroglobulin is a very large glycoprotein.
 Thyroglobulin is released into the colloid space, where it’s
tyrosine residues are iodinated by I+
.
 This results in formation of monoiodotyrosine or diiodotyrosine.

8. Transport of Thyroid Hormones
• Thyroid hormones are lipid-soluble.
• Thus, they are found in the circulation associated with binding
proteins:
- Thyroid Hormone-Binding Globulin(TBG) (~70% of hormone)
- Pre-albumin(Transthyretin) (~15%)
- Albumin (~15%)
• Less than 1% of thyroid hormone is found free in the circulation.
• Only free and albumin-bound thyroid hormone is biologically
available to tissues.
• Among the amount of thyroid hormone production and release T4
is approximately 95% and T3 is 5%. But biological active is T3 so
T4 is converted to T3 in peripheral tissues by the enzyme
5’monodeiodinase and become active.

9. Conversion of T4 to T3
 T3 has much greater biological activity than T4.
 A large amount of T4 (25%) is converted to T3 in peripheral
tissues.
 This conversion takes place mainly in the liver and kidneys. The
T3 formed is then released to the blood stream.
 In addition to T3, an equal amount of “Reverse T3” may also be
formed. This has no biological activity.
T3 MIT + DIT
Reverse T3 DIT + MIT

10. Regulation of Thyroid HormoneLevels:
• Thyroid hormone synthesis and secretion is regulated by two
main mechanisms:
- An “auto regulation” mechanism, which reflects the
available levels of iodine.
- Regulation by the hypothalamus and anterior pituitary.

11. Auto regulation of Thyroid HormoneProduction
• The rate of iodine uptake and incorporation into thyroglobulin is
influenced by the amount of iodide available:
- Low iodide levels increase iodine transport into follicular cells
- High iodide levels decrease iodine transport into follicular cells
Thus, there is negative feedback regulation of iodide transport by
iodide.

12. Neuro endocrineRegulation of Thyroid Hormones: Roleof
TSH
• Thyroid-stimulating hormone (TSH) is produced by thyrotroph cells of
the anterior pituitary.
• TSH is a glycoprotein hormone composed of two subunits:
- alpha subunit (common to LH, FSH, TSH, hCG)
- TSH beta subunit, which gives specificity of receptor binding and
biological activity.

13. Other FactorsRegulating Thyroid HormoneLevels
• Diet: a high carbohydrate diet increases T3 levels, resulting
in increased metabolic rate (diet-induced thermo genesis).
• Low carbohydrate diets decrease T3 levels, resulting in
decreased metabolic rate.
• Cold Stress: increases T3 levels in other animals, but not in
humans.
• Any condition that increases body energy requirements (e.g.,
pregnancy, prolonged cold) stimulates hypothalamus 
TRH  TSH.

14. Actionsof Thyroid Hormones:
 Thyroid hormones are essential for normal growth of tissues,
including the nervous system.
 Lack of thyroid hormone during development results in short
stature and mental deficits (cretinism).
 Thyroid hormone stimulates or increase Basal Metabolic
Rate(BMR).

15. • Required for GH and prolactin production and secretion
• Required for GH action
• Increases intestinal glucose reabsorption (glucose
transporter)
• Increases mitochondrial oxidative phosphorylation (ATP
production)
• Increases activity of adrenal medulla (sympathetic; glucose
production)
• Induces enzyme synthesis
• Result: stimulation of growth of tissues and increased
metabolic rate. Increased heat production (calorigenic effect)

16. Effectsof Thyroid Hormoneon Nutrient Sources:
• Effects on protein synthesis and degradation:
-increased protein synthesis at low thyroid hormone levels
(low metabolic rate; growth)
-increased protein degradation at high thyroid hormone levels
(high metabolic rate; energy)
• Effects on carbohydrates:
-low doses of thyroid hormone increase glycogen synthesis
(low metabolic rate; storage of energy)
- high doses increase glycogen breakdown (high metabolic
rate; glucose production)

17. OneMajor Target Geneof T3: TheNa+
/K+
ATPasePump:
 Pumps sodium and potassium across cell membranes to
maintain resting membrane potential
 Activity of the Na+
/K+
pump uses up energy, in the form of ATP
 About 1/3rd of all ATP in the body is used by the Na+
/K+
ATPase
 T3 increases the synthesis of Na+
/K+
pumps, markedly
increasing ATP consumption(BMR increases).
 T3 also acts on mitochondria to increase ATP synthesis(size and
number of mitochondria will increase).
 The resulting increased metabolic rate increases thermo genesis
(heat production).

18. Thyroid HormoneActionswhich IncreaseOxygen
Consumption
• Increase mitochondrial size, number and key enzymes.
• Increase plasma membrane Na-K ATPase activity.
• Increase futile(ineffective) thermogenic energy cycles.
• Decrease super oxide dismutase activity.

19. Effectsof Thyroid Hormoneson theCardiovascular
System
• Increase heart rate
• Increase force of cardiac contractions
• Increase stroke volume
• Increase Cardiac output
• Up-regulate catecholamine receptors

20. Effectsof Thyroid Hormoneson theRespiratory System
• Increase resting respiratory rate
• Increase minute ventilation
• Increase ventilatory response to hypercapnia and hypoxia

21. EffectsThyroid Hormonesin Growth and Tissue
Development
 Increase growth and maturation of bone.
 Increase tooth development and eruption.
 Increase growth and maturation of epidermis, hair follicles and
nails.
 Increase rate and force of skeletal muscle contraction.

22. Effectsof Thyroid Hormoneson theNervousSystem
• Critical for normal CNS neuronal development
• Enhances wakefulness and alertness
• Enhances memory and learning capacity
• Required for normal emotional tone
• Increase speed and amplitude of peripheral nerve reflexes

23. Effectsof Thyroid Hormoneson theReproductiveSystem
• Required for normal follicular development and ovulation in the
female
• Required for the normal maintenance of pregnancy
• Required for normal spermatogenesis in the male

24. How isHypothyroidism Related to Goiter?
• During iodine deficiency, thyroid hormone production
decreases.
• This results in increased TSH release (less negative feedback).
• TSH acts on thyroid, increasing blood flow, and stimulating
follicular cells and increasing colloid production.

25. Midwest – theGoiter Belt
• If goiter is due to decreased I, then thyroid gland enlarges – called
endemic or colloidal goiter.
• Pituitary gland  TSH stimulate thyroid gland to produce TH, but
the only result is that the follicles accumulate more and more
unusable colloid.
• Cells eventually die from over activity and the gland atrophies.

26. Thyroid HormoneExcess: Hyperthyroidism
• Emotional symptoms (nervousness, irritability), fatigue, heat
intolerance, elevated metabolic rate, weight loss, tachycardia,
goiter, muscle wasting, apparent bulging of eyes, may develop
congestive heart failure.
• Causes:
(a) Excessive TSH release.
(b) Autoimmune disorders.

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