Jimma Oromia , Ethiopia By Tegene Alemu Gemechu

1. PHYSIOLOGY OF THYROID GLAND
Moderators –
 Dr ASHEBIR (Ass’t Professor AND CONSULTANT of
GENERAL Surgery )
Dr. GUTU (Ass’t Professor AND CONSULTANT of GENERAL
Surgery)
Dr. MIKIAS (Ass’t Professor AND CONSULTANT of GENERAL
Surgery)
Presenter –Dr Tegene (GSR1)

2. Outline
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 Objective
 Introduction
 Thyroid hormone synthesis and regulation
 Effect of the Thyroid hormone on the body
 Clinical correlation

3. Objective
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 To understand basic physiology of thyroid gland
 To understand Thyroid Hormone synthesis and
regulation
 To know the effect of thyroid hormone in specific Body
Organ

4. INTRODUCTION
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● Embryology
From median bud of pharynx
♦ thyroglossal duct
♦ follicular
From neural crest
♦ c-cells (parafollicular) ☞calcitonin
● Developmental abnormalities
Ectopic thyroid Thyroglossal duct anomalies
♦Lingual thyroid ●Thyroglossal cyst
♦ Thyroglossal (median) thyroid ● Thyroglossal fistula
♦ lateral aberrant thyroid

5. Introduction -Anatomy
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6. Introduction Anatomy
..
Blood supply
One of the richly supplied organ of the body-160
ml/min/100 g tissue
Thus Even when all major arteries are ligated, remnants of
thyroid often survive from other small branches derived
from laryngeal and tracheo -esophageal arteries
AA Sup. thyroid aa (bb.of ECA)
Inf. thyroid aa (thyrocervical trunk)
Ima aa in 3%
veins Sup. thyroid vv
Middle thyroid vv
Inf. thyroid vv
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7. Introduction Anatomy ..LN
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 Important when considering surgical treatment of thyroid Ca
 It has Rich lymphatics that drain it in almost every direction
present immediately beneath the true capsule
 Communicate between lobes through the isthmus
 The LNs of neck divided between the central and lateral neck
compartment by carotid sheath
 Central ( level VI & VII ) (Most thyroid Ca drain directly to
central nodal basins (level VI))
 Lateral( level II-V)

8. Introduction Anatomy
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SNS
Superior,middle, and
inferior
cervicalsympathetic
ganglia
Vasomotor -
>Vasoconstrictor, not
secretomotor.
 PSNS
Derived from the vagus
nerve and reach the gland
via branches of the

9. Introduction
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 Life time Risk to develop thyroid dysfunction is
common.
 Thyroid disease is more common in women
(Hormone)
 Variable clinical presentations depending on age of
patient , degree of dysfunction, comorbid and
duration of disease.
 Clinical Dx difficult and easily confirmed biochemically

10. Physiology of the Thyroid Gland
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Key Features
The functional unit of the thyroid
gland is the follicle
Thyroid follicles are composed of a
single layer of epithelial cells (thyroid
follicular cells) surrounding a central
space filled with colloid.
The follicular cells synthesize Tg, a
large tyrosine-rich glycoprotein, and
secrete it into the lumen of the follicle;
colloid is essentially a pool of Tg.

11. Cont…
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Key thyroid hormones include TRH, TSH, T4, and T3.
Only 1% of total thyroid hormone is in the unbound or
free state and available for metabolic purposes.
The rest is bound to globulin, prealbumin, and
albumin.
Calcitonin is a peptide produced by the parafollicular
cells of the thyroid gland.
 It reduces resorption of calcium in the bone and
lowers the serum calcium

12. Iodine Metabolism
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 The average daily iodine requirement is 0.1 mg in adult .
 Iodine riche foods -fish, sea food, milk,and eggs or as
additives in bread or salt.
 Converted to Iodide in stomach & jejunum and absorbed
into bloodstream
 Iodide is actively transported to thyroid follicular cell.

13. Thyroid Hormone Synthesis
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Iodide trapping
Critical first step in thyroid
hormone synthesis
It is active transport of
iodide across the basement
membrane via
sodium/iodine symporter
(NIS)
Selective gene expression of Na/I symporeter in
the thyroid allows
 Isotopic scanning,
 Treatment of hyperthyroidism,
 Ablation of thyroid cancer

14. CONT…
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Oxidation
Oxidation of I- to I2
Iodination (organification)
Iodination of tyrosine
residues on Tg, to form
(MIT) and (DIT)
Coupling
To form T4,T3,rT3 from DIT
and MIT molecules
All this 3 step is catalyzed by
enzyme TPO

15. CONT…
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Hydrolysis
Tg is endocytosed, fused
with a lysosome, and
hydrolyzed to release free T3
and T4 MIT, and DIT
MIT and DIT are deiodinated
(by dehalogenase
/deiodinase) to yield iodide,
which is reused in the
thyrocyte.
Homozygous mutations in DEHAL1, the gene that encodes
iodotyrosine deiodinase results in iodotyrosine deiodinase
deficiency (ITDD) with hereditary and sometimes severe
hypothyroidism and goiter

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19. CONT…
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In the euthyroid state, All T4 is produced
and released by the thyroid gland, only
20% of the total T3 is produced by the
thyroid gland
80 % of T3 is produced by peripheral
deiodination of T4 in the
Liver
Muscles
Kidney, and anterior pituitary,
a reaction that is catalyzed by 5′-
mono-deiodinase
RT3 –inactive T3

20. Thyroid Hormone Functions
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 Affect almost every system in the body
 General effect is to activate nuclear transcription of large
numbers of genes
 Help in brain and somatic development of infants
 Responsible for maintaining respiratory center of the brain.
 Have positive inotropic and chronotropic effects on the
heart
 Increase GI motility, leading to diarrhea in hyperthyroidism
and constipation in hypothyroidism

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 Increase libido
 Increase bone and protein turnover and the speed of
muscle contraction and relaxation
 Increase wakefulness but patient will still be tired
 Increase oxygen consumption, BMR, and heat
production

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TH Functions

23. Thyroid physiology and
pregnancy
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 TBG Increase by 50% by the end of the 1st trimester.
 Elevate T3 & T4
 Estrogen and hCG effect (Weak TSH like activity , Small
Increase FT4)
 Increase in thyroid binding globulin (estrogen)
 As a result of decreased globulin clearance
 Decrease in TSH (HcG) – thyrotropic activity increase
TH, Suppression TSH

24. Thyroid Hormone Control
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 TSH regulators
Stimulators
TRH
Low thyroid
hormones
Suppressors
High thyroid
hormones
Glucocorticoids
Dopamine
Somatostatin
Their overall effect on
TSH is small

25. CONT…
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 The thyroid gland also is capable of autoregulation,
which allows it to modify its function independent of
TSH.
 As an adaptation to low iodide intake, the gland
preferentially synthesizes T3 rather than T4, thereby
increasing the efficiency of secreted hormone
 In situations of iodine excess, iodide transport,
peroxide generation, and synthesis and secretion of
thyroid hormones are inhibited

26. CONT …
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Other regulators
 Epinephrine and HcG hormones directly stimulate thyroid
hormone production
 Glucocorticoids inhibit thyroid hormone production
Euthyroid sick syndrome (non-thyroidal illness
syndrome)
In severely ill patients, chronic hyperthermia and chronic
starvation- peripheral thyroid hormones may be reduced,
without a compensatory increase in TSH levels.

27. Inhibition of Thyroid Synthesis
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 Drugs
 The thionamide (PTU)and methimazole – X -TPO
=>They act by inhibiting oxidation, organification, and coupling .
Methimazole -has longer activity and requires a single daily
dose
 However, it has the capability of crossing the placenta and can
affect fetal development in pregnant patients
 Side effects: Agranulocytosis (<1% of cases), rash,
arthralgias, neuritis, and liver damage.
PTU also inhibits the peripheral conversion of T4 to T3

28. TH Inhibitors …
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 β-Blockers
 Although β-blockers do not directly inhibit thyroid
hormone synthesis.
 valuable in controlling peripheral sensitivity to
catecholamines by blocking their effects
 Cardiovascular symptoms such as an increased pulse rate,
tremor, and anxiousness can be improved, but the
hypermetabolic state can remain or progress with this
treatment alone

29. TH Inhibitors …
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 Corticosteroids
 Exogenous glucocorticoids can effectively suppress
the pituitary-thyroid axis
 they periphery to inhibit peripheral conversion of T4 to
T3
 This effectively lowers serum T3 levels, thus allowing
steroids to be used as a rapid inhibitory agent in
hyperthyroid conditions

30. TH Inhibitors …
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 Iodine
 Given in large doses after the administration of an
antithyroid medication, iodine can inhibit thyroid
hormone release by altering the organic binding process
Wolff-Chaikoff effect: excessively large doses of
iodide cause an initial increase in organification
followed by suppressive effects

31. Cont …
 ↑ing doses of I- ⇨↑ hormone
synthesis initially
 Higher doses cause cessation
of hormone formation.
 This effect is countered by the
I- leak from normal thyroid
tissue
 Patients with autoimmune
thyroiditis may fail to adapt
and become hypothyroid.
 Opposite of the Wolff-Chaikoff effect
 Excessive iodine loads induce
hyperthyroidism
 Observed in hyperthyroid disease processes
 Graves’ disease
 Toxic multinodular goiter
 Toxic adenoma
 This effect may lead to symptomatic
thyrotoxicosis in pts who receive large I-doses
☞Dietary changes
☞Contrast administration
☞Iodine containing medication
(Amiodarone)
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Physiology of Thyroid Gland
Wolff-Chaikoff Effect Jod-Basedow Effect

32. Thyroid Hormone Metabolism
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 Thyroid hormones are metabolized by
deiodination & by conjugating with glucuronide
and sulfate
 3 types of deiodinase
The deiodinases are selenoproteins, and the thyroid has more selenium
per gram of tissue than any other organ.
Selenium deficiency exacerbate both autoimmune and endemic
cretinism

33. Congenital /Endemic
Hypothyroidism
 Most newborn babies with congenital hypothyroidism
have few or no clinical manifestations of thyroid
hormone deficiency, and the majority of cases are
sporadic
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34. CONT …
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 Peripheral conversion of T4 to T3 is inhibited by:
 Drugs
PTU
Glucocorticoids
Propranolol
 Conditions
Acute illness
Starvation
Massive hemangioma

35. Thyroid Hormone
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 Majority of circulating hormone is T4
98.5% T4 1.5% T3
T3 is 3-4x more active than T4.
 In peripheral tissues,
T4 converted to T3 or reverse T3 (rT3), which is
inactive.
 Total Hormone load is influenced by serum binding
proteins
Albumin 15%
Thyroid Binding Globulin 70%
Transthyretin 10%
● 99% of T4 and 98% of T3 is bound to protein
● only the free forms (unbound) are active
.

36. Hormone Binding Factors
 ↑ed TBG ☞ ↑ed total T3, T4
 High estrogen states (pregnancy, OCP, Tamoxifen)
 Liver disease (early)
 ↓ed TBG ☞ ↓ed total T3, T4
 Androgens or anabolic steroids
 Liver disease (late)
 Binding Site Competition
 NSAID’s
 Furosemide IV
 Anticonvulsants (Phenytoin, Carbamazepine)
 T4 has a half life of approximately 7 -10 days
 T3 has a half-life of about 1 day
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37. Measurement of TH levels
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38. CONT …
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Physiology of Thyroid Gland
Hypothyroidism Hyperthyroidism

39. Thyroid Evaluation
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 TRH
 TSH
 Total T3, T4
 Free T3, T4
 RAIU (isotope scanning)
 Thyroglobulin
 Antibodies: Anti-TPO, Anti-TSHr

40. CONT…
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 Serum TSH
 Serum TSH levels reflect the ability of the anterior
pituitary to detect free T4 levels
 Small changes in free T4 lead to a large shift in TSH
levels
The ultrasensitive TSH assay -
Most sensitive and specific test for the diagnosis of
hyper- and hypothyroidism
 For optimizing T4 therapy
Less affected by non-thyroidal disease processes and
thyroid hormone-binding proteins

41. CONT..
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 Total T4 and T3
 Total T4 levels reflect the output from the thyroid gland.
 T3 levels are more indicative of peripheral thyroid
hormone metabolism.
Total T3
 Measurement of total T3 levels is important in clinically
hyperthyroid patients with normal T4 levels, who may have
T3 thyrotoxicosis

42. Thyroglobulin (Tg)
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 Tg is a protein precursor & Storage form of TH.
 Large glycoprotein is stored as colloid
 Serum Tg reflect the mass of normal and malignant
thyroid.
 It Is a tumor marker In patient with differentiated
recurrent thyroid cancer and evaluate efficacy of Rx
after thyroidectomy and Radioactive iodine.

43. Thyroid antibody
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 Autoimmune disease, where IgG Ab formed against thyroid
protein
 More than 90% of autoimmune disease are GD (Hyperthyrodism)
& Hashimoto's thyroditis (Hypothyroidism)
 These include anti-Tg, anti-TPO, thyroid-stimulating
immunoglobulin (TSI), and anti-microsomal antibodies
 Antibody levels do not determine thyroid function, but rather
indicate the underlying disorder, usually an autoimmune
thyroiditis.

44. IMAGING -
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 Radioactive Iodine Uptake Test -(RAIU)
measures radioactivity after I123 administration.
 Elevated RAIU with hyperthyroid symptoms
 Graves’ dd.
 Toxic goiter
 Low RAIU with hyperthyroid symptoms
 Thyroiditis (Subacute, Active Hashimoto’s)
 Hormone ingestion (Thyrotoxicosis factitia)
 Excess I- intake in Graves’ (Jod-Basedow effect)
 Ectopic thyroid carcinoma (Struma ovarii)
*Note - This Is A Function Test, Not An Imaging Test.

45. RAI Scanning
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RAIU => Decreased in thyroiditis

46. Cont ..
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Other options
Technetium Tc 99m pertechnetate scan
It also has the advantage of having a shorter
half-life and minimizes radiation exposure

47. REFERENCE
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