PHYSIOLOGY OF THE
THYROID GLAND
Dr. Amel Eassawi
OBJECTIVES
The student should be able to:
 Describe the distribution of iodine in the body, dietary
requirements for iodine and thyroid uptake of iodine.
 Identify the structure and formula for thyroxine (T4) and
triiodothyronine (T3).
 Know the basic steps involved in the biosynthesis of T3 and T4.
 Identify the bound forms and quantities of T3 and T4 in circulation.
 Relate the plasma half-life of thyroid hormones to their biological
effects.
 Describe the effects of TSH on thyroid activity.
 Describe the relationship of TSH, and TRH to T4 secretion.
 Know the physiological effects of thyroid hormone.
 Indicate the relative activities of T4 and T3.
 Describe the etiology, symptoms and treatment of thyrotoxicosis
and hypothyroidism.
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The largest endocrine gland, located in the anterior neck.
Consists of two lateral lobes connected by a median tissue mass called the isthmus
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THYROID GLAND
• The largest endocrine gland, located in the anterior neck
• Located just below the larynx
• Consists of two lobes of endocrine tissue joined in middle by narrow
portion of gland
• Consists of microscopic sacs known as thyroid follicles
• Interior filled with colloid, a protein-rich fluid (thyroglobulin)
• Between thyroid follicles are epithelial cells known as parafollicular
cells (C-cells) produce hormone called calcitonin.
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Thyroid Gland Histology
• The thyroid gland
consists of groups of
thyroid follicles
surrounded by
connective tissue
capsules
• Thyroid follicles are
composed of a space,
filled with the
glycoprotein colloid,
enclosed by a layer of
follicular cells
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THYROID GLAND
FETAL DEVELOPMENT
• Follicle cells able to synthesize thyroglobulin – 29th day
of gestation
• Ability to concentrate iodide and synthesize T4 – 11th week
• Follicles fill with colloid – 13-14 weeks
• Thyroid gland functional – 3rd month of fetal life
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THYROID HORMONES
 Thyroid hormone – the body’s major metabolic hormone
 Consists of two closely related iodine-containing compounds
T4 – thyroxine
T3 – triiodothyronine
 The parafollicular cells or “C” cells produce the hormone calcitonin.
 Calcitonin is a peptide hormone lowers blood calcium levels in
children. Antagonistic to parathyroid hormone (PTH).
 Calcitonin targets the skeleton, where it:
1. Inhibits osteoclast activity (and thus bone resorption) and
release of calcium from the bone matrix
2. Stimulates calcium uptake and incorporation into the bone
matrix.
 Regulated by calcium ion concentration in the blood (negative
feedback mechanism).
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THYROID HORMONES
The three thyroid hormones are:
1. Thyroxine (3,5,3’,5’- tetraiodothyronine) or T4:
Principal hormone secreted by the thyroid follicle cells. Normal
plasma levels of T4 range from 4.5 – 9.5 µg/mL. T4 has a circulating
half-life of 7 days.
2. Triiodothyronine (3,5,3’ – triiodothyronine) or T3:
Normal plasma concentrations of T3 range from 80-150 ng/100mL.
Most (2/3) of T3 is derived from peripheral deiodination of T4 by the
kidney and liver. T3 has a ½ life of about 1 day and it is at least 3
times more potent than T4 on an equal molar basis.
3. Reverse T3 (3,3’,5’ – triiodothyronine) or rT3:
Biologically inactive thyroidal product which circulates in the plasma
at a concentration of about 48 ng/100mL. Most of rT3 is derived
from peripheral conversion of T4.
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THYROID HORMONE
SYNTHESIS
Basic ingredients:
• Tyrosine
– Synthesized in sufficient amounts by body
• Iodine
– Obtained from dietary intake
Dietary Iodine Requirements:
• Approximately 100 µg/day of iodine are essential for the synthesis of
normal amounts of thyroid hormones. The major source of iodide
comes from the diet.
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THYROID HORMONE
SYNTHESIS
Steps in hormone synthesis and secretion:
Iodide Trapping
Organification Reaction
Coupling Reaction
Hormone Release
Iodide Trapping:
Transport of iodide is dependent on sodium gradient across basal
membrane of follicle cell
Sodium-iodide symporter (NIS) transports iodide atom against an
electrochemical gradient.
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THYROID HORMONE
SYNTHESIS
Organification Reaction:
Activated iodine incorporated into tyrosine residue of
thyroglobulin
Coupling Reaction:
• Iodinated tyrosine linked to form T4 and T3
Peripheral Deiodination:
• Type I and 2 deiodination
• Organ specific
• Inactivation of T4 and T3 (D3)
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TYHYROID HORMONES STORAGE
AND SECREATION
Storage:
Thyroglobulin and its attached residues of MIT, DIT, T3, and T4 are
stored in the colloid until secreted. The thyroid gland has a large
reservoir of hormone. In normal humans, about
250 µg of T4 per gram of wet weight can be stored in the gland.
Inhibition of hormone synthesis by antithyroidal substances for as
long as 2-weeks does not significantly reduce hormone levels in the
blood.
Secretion:
Secretion of thyroid hormone involves endocytosis, specifically
macropinocytosis and micropinocytosis of the colloid by the follicle
cells and subsequent formation of vesicles containing the
thyroglobulin molecule and its residues. The vesicles merge with
lysosomes containing active proteases which hydrolyze the
thyroglobulin molecule and release MIT, DIT, T4 and T3 into the
cytoplasm. Subsequently, T4 and T3 diffuse into the plasma.
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TYHYROID HORMONES
STORAGE AND SECREATION
Deiodination:
MIT and DIT are deiodinated in the cytoplasm by a microsomal
NADPH-dependent deiodinase. The liberated iodide is either
immediately used for the synthesis of new hormones in the colloid or
lost into the circulation as an “iodide leak”. Deiodination of T4 to T3
occurs by thyroidal type 1 and 2 deiodinases.
Excessive Thyroidal Iodide:
Organification of iodine decreases in response to increasing thyroidal
iodide. This phenomenon is called the “Wolff-Chaikoff effect”. As iodide
levels remain high, the gland adapts and begins to make normal
amounts of thyroid hormone.
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Synthesis of Thyroid Hormone
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Synthesis, Storage and Secretion of Thyroid Hormones
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PATHWAY OF THYROID HORMONE
SYNTHESIS
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THYROID HORMONES
TRANSPORT
T4 and T3 poorly soluble in water.
Transported in plasma by binding proteins:
1. Thyroxine-binding globulin (TBG)
2. Transthyretin (TTR)
3. Albumin
70-80% of T3 bound to (TBGs)
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THYROID HORMONE REGULATION
• Hypothalamic-Pituitary-Thyroid Axis
• Thyroid Gland Autoregulation
• Peripheral Regulation
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THYROID HORMONE REGULATION
Hypothalamic-Pituitary-Thyroid Axis
Thyrotropin-releasing hormone (TRH)
• Tripeptide
• Released from hypothalamus/episodic secretory pattern
• Stimulates thyrotroph cells
Thyroid-stimulating hormone (TSH)
•
•
•
•
Glycoprotein secreted by thyrotrophs
Regulates thyroid gland growth, secretion, and metabolism
Thyrotrophs stimulated by TRH
Present in fetal plasma – (18-26 weeks of gestation)
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THYROID CELL FUNCTIONS
STIMULATED BY TSH
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THYROID HORMONE REGULATION
Thyroid-stimulating hormone (TSH) stimulates:
• Trapping mechanism
• Organification and coupling reactions
• Increase in follicle cell size
• Enlargement of Golgi apparatus
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HYPOTHALAMIC-PITUITARY-THYROID AXIS
•
•
•
•
Negative feedback regulation
Anterior pituitary: primary feedback effect
Free fraction of T4 and T3 participate
T4 and T3 inhibit TRH and TSH
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REGULATION BY ENERGY
INTAKE/ADIPOSE STORES
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ENVIRONMENTAL REGULATION OF
THYROID HORMONE SECRETION
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THYROID GLAND
AUTOREGULATION
Thyroid Gland Autoregulation:
Thyroid gland function is controlled by an autoregulation mechanism
that maintains adequate thyroidal stores of T4 and T3 when plasma
iodide levels vary outside normal limits.
Peripheral Regulation of Thyroid Hormone
Increases in thyroid hormone results in increased formation of the
biologically inactive thyroidal product rT3.
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EFFECTS OF THYROID HORMONE
• Thyroid hormones bind to nuclear thyroid
hormone receptor
• T3 is ten times more potent than T4
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THYROID HORMONE EFFECTS
All body cells affected either directly or indirectly by thyroid
hormone:
1. Main determinant of basal metabolic rate (BMR). BMR regulator of
body's rate of O2 consumption & energy expenditure under resting
conditions.
2. Influences synthesis and degradation of carbohydrate, fat, and
protein.
3. Increases target-cell responsiveness to catecholamines by causing
a proliferation of specific catecholamine target-cell receptors
4. Increases heart rate and force of contraction.
5. Essential for normal growth. Stimulates GH secretion and
increases production of IGF-I by liver. Promotes effects of GH & IGFI on synthesis of new structural proteins on skeletal growth.
6. Plays crucial role in normal development of nervous system.
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THYROID REGULATION OF CARDIOVASCULAR
FUNCTION
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THYROID HORMONES
ABNORMALITIES
• Goiter - enlargement of the thyroid gland,
causing a swelling in the front part of the
neck.
• Hyperthyroidism
• Hypothyroidism
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THYROID HORMONES
ABNORMALITIES
Hypothyroidism
–Primary: failure of thyroid gland (↓T3 & T4; ↑TSH); Goiter
–Secondary: deficiency of TRH, TSH, or both (↓T3 & T4; ↓TSH and/or ↓
TRH); no Goiter (because thyroid gland is not being adequately stimulated)
–Inadequate dietary supply of iodine (↓T3 & T4; ↑TSH), Goiter
Symptoms of hypothyroidism:
1. Reduced BMR.
2. Poor tolerance to cold (lack of the calorigenic effect)
3. Gain excessive weight.
4. Easily fatigued (lower energy production)
5. Slow, weak pulse (caused by a reduction in the rate and strength of
cardiac contraction and lowered cardiac output)
6. Exhibits slow reflexes and slow mental responsiveness (because of the
effect on the nervous system; characterized by slow speech, and poor
memory).
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THYROID GLAND
ABNORMALITIES
Hypothyroidism
Cretinism (Children):
– Results from hypothyroidism from birth
– Characterized by dwarfism & mental retardation as well as other
general symptoms of thyroid deficiency.
– At birth, child appears normal because thyroxine is received from
mother through placenta
– Symptoms: stop growth, abnormal bone development, low body
temperature, lethargy, severly mentally retarded (short limbs, a large
protruding tongue, coars dry skin, poor abdominal muscle, tone and an
umbilical hernia).
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THYROID GLAND
ABNORMALITIES
Myxedema (Adult)
Puffy appearance, primarily of face, hands, and feet
–Term often used for myxedema in adults
Symptoms: The patient becomes sluggish both mentally and physically
and often feels cold. The hair becomes dry and the skin becomes
dry and waxy. The tissues of the face swell.
Treatment:
– If diagnosed early, can be treated by administrating of T4.
– Exception, if hypothyroidism caused by iodine deficiency; treated by
dietary iodine.
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MYXEDEMA
Copyright © 2007 Elsevier Inc
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THYROID GLAND
ABNORMALITIES
THYROTOXICOSIS:
• Excessive quantities of thyroid hormone.
• Causes: hyperthyroidism, thyroiditis, and excessive
exogenous thyroid hormone.
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THYROID GLAND
ABNORMALITIES
Hyperthyroidism
Causes:
Secondary:
1. Over secreation of hypothalamic or pituitary secretion
(↑T3 and T4; ↑TRH and/or ↑TSH) Goiter
2. Over activity of thyroid in absence of overstimulation, e.g thyroid
tumor, that not accompanied by a goiter. (though a goiter does not
develop, a tumor may cause enlargement of thyroid, depending on
nature or size of tumor)
•Secretion of excessive amounts of T3 and T4 inhibits TSH, so there is
no growth of the thyroid.
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THYROID GLAND
ABNORMALITIES
Symptoms of hyperthyroidism:
1. Increased BMR.
2. Poor tolerance to hot
3. Excessive weight loss.
4. Easily fatigued (lower energy production)
5. Palpitations.
6. Excessive mental alertness, irritable, tense, anxious and
excessively emotional.
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THYROID GLAND
ABNORMALITIES
Hyperthyroidism
– Graves’ disease
– Autoimmune disease
– Body mistakenly produces thyroid-stimulating immunoglobulins (TSI)
also known as long-acting thyroid stimulator (LATS),
– Antibodies act like TSH & stimulate thyroid gland to grow and over
secrete thyroid hormones.
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THYROID GLAND
ABNORMALITIES
Graves Disease
Risk factors include stress, increased iodine intake,
smoking and unidentified environmental factors
Exothalamus is associated in 50% of cases
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(↑T3 & T4; ↓ TSH)
Goiter
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(A) Characteristic signs of Graves' orbitopathy (A) subsequently corrected by orbital decompression surgery
(B). Note the thyroid stare, the asymmetry, the proptosis, and the periorbital edema before correction
Copyright © 2007 Elsevier Inc
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INDUCTION OF GOITER BY HYPOAND HYPERTHYROID STATES
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TREATMENT METHODOLOGIES
Treatment Goals for Hyperthyroidism:
• Inhibit or decrease synthesis and secretion of thyroid
hormone
• Limit symptoms of hyperthyroidism
• Surgical removal of a portion of the over-secreting thyroid
• Administration of radioactive iodine
• Use of antithyroid drugs
Treatment Goal for Hypothyroidism:
• Return of serum TSH levels to normal
• Synthetic thyroxine - levothyroxine
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REFERENCES
 Human physiology, Lauralee Sherwood, seventh
edition.
 Text book physiology by Guyton &Hall,11th
edition.
 Physiology by Berne and Levy, sixth edition.
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