PHYSIOLOGY – LECTURE

THYROID METABOLIC HORMONES

Dr. Kristine C. Israel-Zantua | 7 October 2022

OUTLINE
I. The Thyroid Gland
II. Synthesis & Secretion of the
Thyroid Hormones
A. Transport and
Metabolism of Thyroid
Hormones
III. Functions of the Thyroid
Hormones in the Tissues
A. Thyroid Hormones and
Transcription of Many
Genes
Synthesis of Thyroglobulin
- Thyroglobulin: synthesized by follicular cells
B. Physiologic effect of - secreted: into colloid via exocytosis of secretion granules that
Thyroid Hormones contain thyroid peroxidase
IV. Regulation of Thyroid - thyroglobulin molecule: contains 25-30 tyrosine molecules
- Includes production of the protein w/in the rough ER and
Hormone Secretion
shipping it to the golgi apparatus for addition of carbohydrates
V. Diseases of the Thyroid
VI. References

I. THE THYROID GLAND

- Located anterior to the cricoid cartilage in the anterior neck
- lined with cuboidal epithelial cells that secrete into the
interior of the follicles
- Composed of large number of follicles surrounded with
colloid (proteinacous
material)
- Thyroglobulin
o Large glycoprotein
o Contains the
thyroid hormones
- secretes 2 major metabolic
hormones: thyroxine (T4)
and triiodothyronine (T3), Iodination (Organification) and Coupling
which increase metabolic - takes place in the colloid
rate in the body - MIT and DIT formation
- Thyroid secretion: controlled o Iodine attached to tyrosine AA of thyroglobulin by
primarily by thyroid- peroxidase enzymes which facilitate removal of
stimulating hormone (TSH) electrons
secreted by the anterior o 1 iodine is added to form MIT or T1
Coupling
pituitary gland o 2 iodine are added to form DIT or T2
- T3 and T4 formation
II. SYNTHESIS & SECRETION OF THE THYROID HORMONES o Enzymes facilitate joining of MIT and DIT
- First three steps occur in the follicular cell o 1 MIT + 1 DIT = T3
o 1 MIT + 1 MIT = T4
Iodide Trapping (Iodide Pump) o Both T3 and T4 remain attached to the
- IODINE: essential to thyroid hormone synthesis Thyroglobulin
- ingested iodine → to iodide → absorbed from the gut - Endocytosis
o most iodide: excreted by kidneys o Thyroglobulin with T3 and T4 → follicular cell
o remainder iodide- taken up by thyroid gland
- thyroid follicular cells actively transport iodide from circulation
across their basal membrane into the cell (via Na+/ I- ions)

Oxidation of Iodide
- occurs at the apical membrane of the follicular cells

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Proteolysis, Deiodinatoin, and Secretion
- release of T3 and T4 from thyroglobulin
o Vesicle fuses with lysosome
o Lysosomal enzyme cleave T3 and T4 from
thyroglobulin
- Release of T3 and T4 into the blood
o Move from the follicular cell into the blood by simple
diffusion
o More T4 is released
o T3 & T4 = Thyroxine
TO WATCH:
https://www.youtube.com/watch?v=uCjpGlnCjeA&t=27s
Effects of Thyroid Hormones Secondary to Increased
Metabolic Rate:
Essential To Normal Growth and Development
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A. Transport and metabolism of Thyroid Hormones
- Thyroid hormones: upon entering the blood, both T3 & T4
are highly bound to plasma proteins especially in the
thyroxine-binding globulin (TBG)
o Also bound to albumin and thyroxine-binding
prealbumin
o 99.9% of T4 bound to plasma proteins
o less than 0.1% is free hormone (taken up by the
tissues in which it exerts biological effects and is
metabolized)
o half-lives of T4 (7 days) and T3 (1 day) are very
long
- Alterations in plasma TBG levels do not influence free
thyroid hormone concentration
o decrease plasma TBG levels → decrease total
amount of thyroid hormones in plasma
e.g. during liver and kidney disease
o Increase plasma TBG levels → increase total
amount of thyroid hormones in plasma
e.g. during estrogen administration & pregnancy
o Transient change in the free hormone
concentration
- Most of the T4 secreted by the thyroid gland is
metabolized to T3
o Large amount of the hormone is deiodinated in
peripheral tissues → T3 and reverse T3
o T4 is a prohormone for T3
III. FUNCTIONS OF THE THYROID
HORMONES IN THE TISSUES
A. Thyroid Hormones and Transcription of Many Genes
- Stimulates or inhibits transcription of a large number of
genes
- Synthesis of numerous enzymes that later cell function
B. Physiologic effect of Thyroid Hormones
- Increase thermogenesis and sweating (because the skin
blood flow increases due to the need for heat elimination)
- Increase rate and depth of respiration (due to the need for
oxygen)
- Increased cardiac output (because the increased
metabolism and utilization of oxygen in tissues cause a
local vasodilation; associated with elevation in both stroke
volume and heart rate)
- Increased pulse pressure but not Mean Arterial Pressure
(because of the cardiac output and reduced peripheral
vascular resistance, the systolic arterial pressure is
elevated and diastolic arterial pressure is reduced)
- Increased utilization of substrates for energy (increased
metabolic rate is dependent on the oxygenation of
metabolic substrates)
- skeletal system: hypothyroid state → reduced growth
o babies are high risk in being hypothyroid if
mother has gestational diabetes mellitus
- teeth
- epidermis
- CNS
o In utero and first few years of postnatal life
o Deficient thyroid hormone → irreversible brain
damage (there will be mental retardation)
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Exitatory Effects on the Nervous System
- Wakefulness
- alertness, responsiveness
- increase speed and amplitude of peripheral nerve reflexes
- improve memory and learning capacity
‘Hypo’ means down, ‘hyper’ means up
IV. REGULATION OF THYROID HORMONE SECRETION
- To maintain a normal lvl of metabolic activity in the body, the
pre-plasma lvls of the thyroid hormone must be regulated
Thyroid Stimulating Hormone (TSH): primary controller of Thyroid
hormone secretion
- Promotes synthesis and secretion of thyroid hormones
- Has chronic effects to promote growth of the thyroid gland
o increased blood flow to thyroid gland
o induction of hypertrophy and hyperplasia
TO WATCH:
https://www.youtube.com/watch?v=PnT3Qj6mVXc
V. DISEASES OF THE THYROID GLAND
HYPERTHYROIDISM
- thyroid gland is increased to 2-3x its normal size, w/
tremendous hyperplasia and infolding of the follicular cell
lining into the follicles, so the number of cells is increased
greatly
- Grave’s Disease: most common form of hyperthyroidism; an
autoimmune disease in which antibodies called thyroid-
stimulating immunoglobulins (TSIs) form against the TSH
receptor in the thyroid gland.
- The antibodies that cause hyperthyroidism almost certainly
occur as the result of autoimmunity that has developed
against thyroid tissue
- Occasionally results from Thyroid Adenoma
Symptoms
1. a high state of excitability
2. intolerance to heat
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3. increased sweating
4. mild to extreme weight loss (sometimes as much as 100
pounds)
5. varying degrees of diarrhea
6. muscle weakness
7. nervousness or other psychic disorders
8. extreme fatigue but inability to sleep, and
9. tremor of the hands.
- Most people with hyperthyroidism exhibit some degree of
protrusion of the eyeballs called exophthalmos.
Treatment
- most direct treatment: surgical removal of most of the
thyroid gland.
HYPOTHYROIDISM
- often initiated by autoimmunity against the thyroid gland
(Hashimoto’s disease), but in this case the autoimmunity
destroys the gland rather than stimulates it
- thyroid glands of most of these patients first demonstrate
autoimmune thyroiditis (thyroid inflammation)
- Thyroid Goiter: type of hypothyroidism associated with
development of enlarged thyroid glands
o Endemic Colloid Goiter: results from Lack of
iodine which prevents production of both thyroxine
and triiodothyronine
o Idiopathic Colloid Goiter: exact cause is not
known; occurs in people who do not have iodine
deficiency— their goitrous glands may secrete
normal quantities of thyroid hormones, but more
frequently, the secretion of hormone is depressed
Physiological Characteristics of Hypothyroidism
- fatigue and extreme somnolence
- extreme muscular sluggishness
- a slowed heart rate
- decreased cardiac output
- decreased blood volume
- sometimes increased body weight
- constipation
- mental sluggishness
- failure of many trophic functions in the body as
evidenced by depressed growth of hair and scaliness of
the skin,
- development of a froglike, husky voice,
- in severe cases, development of an edematous
appearance throughout the body called myxedema
(develops in persons who have almost total lack of
thyroid hormone function)
Treatment
- a steady level of thyroid hormone activity is easily
maintained in the body via daily oral ingestion of one or
more tablets containing thyroxine.
CRETINISM
- caused by extreme hypothyroidism during fetal life, infancy,
or childhood
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 - characterized especially by failure of body growth and by
mental retardation
- results from congenital lack of a thyroid gland (congenital
cretinism), from failure of the thyroid gland to produce
thyroid hormone because of a genetic defect of the gland, or
from a lack of iodine in the diet (endemic cretinism)
- Treatment of the neonate with cretinism at any time with
adequate iodine or thyroxine usually causes normal return of
physical growth
o but unless the cretinism is treated within a few
weeks after birth, mental growth remains
permanently retarded.

VI. REFERENCES

Mostly from Dr. Queenie’s Lecture and Powerpoint Slides

Books:

Boron, W.F. and Boupaep, E.L. (2016) Medical Physiology. 3rd Edition,
Elsevier Publisher, Philadelphia.
Hall, J., Hall, M. (2021) Guyton and Hall Textbook of Medical
Physiology. 14th ed. Philadelphia: Elsevier.

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