‫‪SAWA UNIVERSITY‬‬

‫ﻋﻨﻮان اﻟﻤﺤﺎﺿﺮة‬
‫‪Lecture No. 25-26‬‬
‫‪Thyroid gland‬‬
‫ﺟﺎﻣﻌﺔ ﺳﺎوة‬
‫*ﻠ‪,‬ﺔ اﻟﺘﻘﻨ‪,‬ﺎت اﻟﺼﺤ‪,‬ﺔ واﻟﻄﺒ‪,‬ﺔ‬
‫ﻗﺴﻢ ﺗﻘﻨ‪,‬ﺎت اﻟﻤﺨﺘ>=ات اﻟﻄﺒ‪,‬ﺔ‬
‫اﻟﻤﺮﺣﻠﺔ‪ :‬اﻟﺮا‪B‬ﻌﺔ‬
‫‪2026-2025‬‬
‫اﺳﻢ اﻟﻤﺤﺎ‪ HI‬أ‪.‬د‪ .‬ﻛرﯾﻣﺔ ﻋﺎﻛول اﻟﺻﺎﻟﺣﻲ‬
‫اﻟ‪K‬ﻮرس ‪ :2‬رﻗﻢ اﻟﻤﺤﺎ‪HI‬ة‪1 :‬‬
• The human thyroid gland is a major
component of the endocrine
system.
• Thyroid hormones perform many
important functions.
• They exert powerful and essential
regulatory influences on growth,
differentiation, cellular
metabolism, and general hormonal
balance of the body, as well as on
the maintenance of metabolic
activity and the development of
the skeletal and organ system.
• The hormones Thyroxine (T4) and
Triiodothyronine (T3) are secreted
from the thyroid gland and regulated
by a sensitive feedback system
involving the hypothalamus and
pituitary gland.
• Thehypothalamus is an
endocrine gland in the brain releases
the thyrotropin releasing hormone
(TRH), which stimulates the pituitary
to release the thyroid stimulating
hormone (TSH).
• This causes the thyroid to release T3
and T4 and these in turn regulate
the release of TRH and TSH via a
feedback control mechanism.
Synthesis of T3 and T4
Thyroglobulin (Tg) is a large tyrosine-rich protein
bind to iodine after oxidation of iodide, a reaction
catalysed by thyroid peroxidase (TPO) and release
monoiodotyrosin (MIT) and di-iodotyrosine (DIT).
Then peroxidase links 2 DIT to form T4 or one DIT
and one MIT to form T3 released by thyroid gland
cells in the circulation.
In liver deiodinases enzymes covert about 1/3 of the T4
into T3.
 Oxidation

Iodide Iodine + Thyroglobulin (Tg) Monoiodotyrosin +

. TPO Di-iodotyrosine

Monoiodotyrosine + Diiodotyrosine Triiodothyronine (T3)

71

Diiodotyrosine + Diiodotyrosine Thyroxine (T4)

T4 and T3 may stay free in plasma or bind to several serum proteins main
•T4 and T3 may or bind to
several serum proteins mainly; thyroid binding
globulin (TBG), transthyretin and albumin. Only about
0.02% of T4 and 0.3% of T3 is free in plasma.
•Thyrotoxicosis is a characteristic feature of
overproduction of the thyroid hormone; Thyroxine
(T4) and Triiodothyronine (T3).
• This is known as hyperthyroidism in which the level
of these hormones increased above normal level of
blood.
•Thyrotoxicosis can occur
for other reasons as:
• ingestion of exogenous
thyroid hormone as
tablets,
•toxic thyroid
•adenoma,
•thyroiditis
•and anti-arrhythmic
drug.
•Autoimmune thyroid disease is broadly classified into
categories on the basis of the effect on gland function:
Ø autoimmune hyperthyroidism is seen in Graves’s disease
Øand hypothyroidism is seen in Hashimotos thyroiditis.
• Patient’s serum also containing different types of auto-antibody that
directed against different thyroid self antigens
mainly Tg, Tpo, thyroid growth stimulating Ig (TGI) and thyroid stimulating
hormone receptor (TSH-R).
• Two types of anti-TSH-R antibodies may exist in the patient serum:
1. Stimulatory (Thyroid Stimulating Ig or TSI).
2. Blocking or inhibitory (Thyroid Binding Inhibitory Ig or TBII).
Graves’s disease
• It is the most common cause of hyperthyroidism which
driven by an autoimmune mechanism.
• Graves’s disease has a peak incidence in the 3rd and 4th decades and is
found in approximately 0.1-0.5 % of the general population.
• It is more common in women than man (7:1).
Predispositions to Graves’s disease include living in an area of high iodine
intake, female sex, stress and possession of HLA-DR3, which confer a
relative risk of disease.
• In Graves’s disease the
dominant type of anti-TSH-
R Abs is the TSI, however,
the presence of both types
of Ab (TSI &TBII) in some
patients may explain the
fluctuation from over
activity to under activity of
the gland.
• The TSI mimic the TSH in its
action, even more, it has a
more prolonged action on
the activation of thyroid
gland cells than TSH do.
•Pathogenesis of Graves’s
disease depends on the
humoral and cell-mediated
immunity participation.
•However, T cells (TH2,
CD8+) are responsible for
the glandular thyroid T
cells infiltration, whereas
the antibodies are acting
as a disturbing factor for
the normal
•physiological function of the gland.
•A clear application for that is the autoimmune
syndrome in neonates which is caused by the
transplacental transfer of IgG which cause a
transient disturbance in the endocrine physiology
that disappears with time after birth in
proportion with the half-life time of IgG without any
significant damage of the target organs.
•The level of thyroid Abs in pregnant women with
Graves’s disease and Hashimotos thyroiditis
decreased during pregnancy, but increased again
after word.
Symptoms
Patients typically present with the symptoms or signs of :
Øhyperthyroidism (palpitations, tachycardia,
arrhythmias, heat intolerance, increased appetite with
weight loss, diarrhea, weakness and proximal myopathy,
nervousness and tremor).
ØOne characteristic feature of Graves’s disease is eye
disease characterized by protrusion of the eyeball and
lid retraction resulting from tissue inflammation in the
retro-orbital space.
ØGoiter which is an enlargement or hypertrophy of the
thyroid tissue is of diffuse pattern in Graves’s disease.
Diagnosis
Laboratory findings are of
1. Elevated thyroid hormones- thyroxine (T4) and triiodothyronine
(T3)- with suppressed levels of thyroid stimulating hormone(TSH).
2. Measuring of auto-Abs
q Anti-TSH-R in most case (TSI, TGI).
qAnti-TPO in 50% of cases (more common in Hashimotos thyroiditis) and
anti-Tg in less cases.
qThyroid growth stimulating Ig (TGI) is seen in the serum of Graves’s disease
patient with goiter and in some patients with toxic multinodula and non-toxic
goiter.
The titer of these Ab is correlated with the size of goiter,
but not associated with the level of T4 and T3 as the
case with TSI in which there is strong association
between the high level of T4 and T3 and the level of TSI.
3. The radioactive iodine uptake test and thyroid scan
test. The uptake test uses radioactive iodine (I-123)
injected or taken orally on an empty stomach to measure
the amount of iodine absorbed by the thyroid gland.
Person with hyperthyroidism absorb too much iodine.
ØThe thyroid scan producing images is typically
conducted in connection with the uptake test to allow
visual examination of the over- functioning gland.
Hashimotos thyroiditis
•Hashimotos thyroiditis (autoimmune
thyroiditis) is a chronic disease typically
characterized by enlargement (goiter) and
dense lymphatic infiltration of the thyroid
gland.
•It is four times more common in women
and has incidence of approximately 0.5% in
the general population; the incidence peaks
in middle age.
Causes
•HLA-DR5 gene most strongly implicated
conferring a relative risk. In addition, HT may be
associated with polymorphism of CTLA-4 gene.
•Environmental factors (high iodine intake,
infection as chronic HCV, certain drugs, exposure
to radioactive isotypes, presence of other
autoimmune diseases as celiac disease and type 1
diabetes.
• Pathogenesis of
Hashimotos thyroiditis
depends on the humoral
and cell-mediated
immunity participation.
However, T cells (CD4+
(TH1), CD8+) are
responsible for the
destruction of thyroid
tissue that targeting the
auto antigens Tg and Tpo.
Microbial mimicry by viral
or bacterial antigens may
drive this destructive
mechanism.
Symptoms
• Patients usually complain of goiter as the main
symptom, with an enlarged, firm, sometimes nodular
thyroid gland on examination.
• At presentation, patients may still be euthyroid, but
with time the pathological processes result in loss of
thyroid tissue and hypothyroidism. Symptoms and signs
of hypothyroidism may be seen at the first consultation
(fatigue, cold intolerance, dryness of skin, anorexia,
weight gain, menstrual disturbance, huskiness of voice,
mental slowing, abnormal reflexes).
• Diagnosis
1. Low level of free T3 and free T4.
2. Low level of total T3 and free T4.
3. High level of TSH.
4. Measuring of auto-Abs Anti-Tg Ab is found in 90% of cases.

vAnti-TPO Ab correlate with the severity of the disease.

vBoth Abs contribute in decreasing the uptake of iodine
leading to hypothyroidism.
vOther auto-Ab are detected (anti- TSH-R blocking Abs(low),
anti-thyrotropin-R Ab, anti-second colloid Ag) these antibodies
have an inhibitory effect on the production of the thyroid
hormones.
 Graves’s disease Hashimotos thyroiditis
1. Hyperactivity 1. Fatigue, lethergy
2. Weight loss with increase of 2. Weight again
Appetite
3. Heat intolerance 3. Cold intolerance
4. Thirst/polyuria 4. Dry coarse skin
5. Diffuse goiter 5. Rubbery, nodular goiter
6. Ophthalamopathy, eyelid 6. Facial edema (myxodema)
Retraction, exophthalmous,
peri-orbital odema
7. Tachycardia 7. Mostly bradycardia
8. Free T3 8. Free T3 N-
Free T4 Free T4
Total T3 Total T3 N-
Total T4 Total T4
Anti-Tg N(rarely in few cases) Anti-Tg
Anti-TPO N (slightly in 50% Anti-TPO
of cases)
Anti-TSH-R Anti-TSH-R N
TSH TSH
9. Treatment 9. thyroxine
Anti-thyroid drugs
Radioactive iodine
Thyroidectomy
10. TH2 10. TH1
1. The primary physiological role of 4. Monoiodotyrosine (MIT) and
thyroid hormones is regulation of: diiodotyrosine (DIT) are formed by:
A. Electrolyte balance only A. Coupling reaction
B. Calcium metabolism B. Deiodination
C. Cellular metabolism and growth C. Iodination of thyroglobulin
D. Immune tolerance D. Peripheral conversion
E. Blood pressure E. Proteolysis
2. Thyroid hormone secretion is directly 5. Thyroxine (T4) is synthesized by coupling
stimulated by: of:
A. TRH from hypothalamus A. MIT + MIT
B. TSH from pituitary B. MIT + DIT
C. T3 from thyroid C. DIT + DIT
D. T4 from thyroid D. T3 + iodine
E. Somatostatin E. T3 + DIT
6. Approximately one-third of circulating T4 is
3. Which enzyme catalyzes oxidation of converted to T3 in the:
iodide during thyroid hormone synthesis?
A. Kidney
A. Deiodinase B. Thyroid gland
B. Thyroid peroxidase C. Spleen
C. Iodotyrosine dehalogenase D. Liver
D. Aromatase E. Pituitary
E. Transaminase
7. The major thyroid hormone-binding protein in plasma is: 10. Which of the following is NOT a cause
A. Albumin of thyrotoxicosis?
B. Transthyretin A. Exogenous thyroid hormone ingestion
C. Thyroid binding globulin B. Toxic thyroid adenoma
D. Prealbumin
C. Thyroiditis
E. Globulin-α2
8. The biologically active fraction of thyroid hormones in plasma D. Anti-arrhythmic drugs
is: E. Hashimoto’s thyroiditis (late stage)
A. Protein-bound T3 and T4 11. Autoimmune hyperthyroidism is
B. Free T3 and free T4 classically associated with:
C. Albumin-bound hormones A. Hashimoto’s thyroiditis
D. TSH-bound T4 B. Subacute thyroiditis
E. Thyroglobulin-bound hormones C. Graves’ disease
D. Iodine deficiency
9. Thyrotoxicosis differs from hyperthyroidism because it:
E. Thyroid carcinoma
A. Always involves autoimmune disease
B. Can occur without increased hormone synthesis 12. The most important autoantibody
C. Occurs only in Graves’ disease responsible for Graves’ disease is:
D. Is limited to iodine deficiency A. Anti-TPO
E. Causes hypothyroidism B. Anti-Tg
C. Anti-TSH receptor (stimulatory)
D. Anti-iodide transporter
E. Anti-deiodinase
13. Thyroid-stimulating immunoglobulin (TSI)
causes hyperthyroidism by: 16. The eye manifestations of Graves’ disease
are caused by:
A. Blocking iodine uptake A. Excess T3 action on retina
B. Destroying thyroid follicles B. Increased intraocular pressure
C. Mimicking TSH action C. Retro-orbital inflammation
D. Inhibiting TSH secretion D. Direct antibody binding to cornea
E. Blocking thyroglobulin synthesis E. Sympathetic overstimulation only
14. Graves’ disease is most strongly associated 17. Which immune cells are mainly
with which HLA type? responsible for thyroid infiltration in Graves’
A. HLA-DR5 disease?
B. HLA-DR4 A. TH1 cells
C. HLA-DR3 B. TH2 and CD8⁺ T cells
D. HLA-B27 C. B cells only
E. HLA-DQ8 D. Neutrophils
15. The female-to-male ratio in Graves’
E. NK cells
disease is approximately: 18. Neonatal autoimmune thyroid dysfunction
occurs due to:
A. 2:1
B. 3:1 A. Fetal thyroid mutation
C. 5:1 B. Placental iodine excess
D. 7:1 C. Transplacental IgG transfer
E. 10:1 D. Maternal TSH deficiency
E. Congenital enzyme defect
19. In Graves’ disease, radioactive iodine 22. The HLA allele most strongly associated
uptake test typically shows: with Hashimoto’s thyroiditis is:
A. Low uptake A. HLA-DR3
B. Normal uptake B. HLA-DR4
C. Patchy uptake C. HLA-DR5
D. Diffusely increased uptake D. HLA-B27
E. No uptake E. HLA-DQ2
20. Anti-TPO antibodies in Graves’ disease are: 23. The dominant T-helper response in
A. Always present Hashimoto’s thyroiditis is:
B. Present in about 50% of cases A. TH2
C. Diagnostic of Graves’ disease B. TH17
D. More common than anti-TSH-R C. TH1
E. Absent in autoimmune thyroid disease D. Regulatory T cells
21. Hashimoto’s thyroiditis is primarily E. NK cell mediated
characterized by: 24. The principal mechanism of thyroid
A. Hyperthyroidism damage in Hashimoto’s thyroiditis is:
B. Thyroid atrophy without inflammation A. Excess TSH stimulation
C. Chronic lymphocytic infiltration B. Antibody-mediated hyperfunction
D. Nodular toxic goiter C. T-cell mediated destruction
E. Thyroid malignancy D. Iodine toxicity
E. Viral cytolysis
25. The most sensitive antibody marker for 28. The goiter in Hashimoto’s thyroiditis is
Hashimoto’s thyroiditis is: typically:
A. Anti-TSH-R A. Diffuse and soft
B. Anti-Tg B. Painful and tender
C. Anti-TPO C. Rubbery and nodular
D. Anti-MIT D. Absent
E. Anti-T3 E. Pulsatile
26. In established Hashimoto’s thyroiditis, 29. A major clinical difference between
laboratory findings typically show: Graves’ disease and Hashimoto’s thyroiditis
is:
A. High T3 and T4 with low TSH A. Presence of goiter
B. Normal TSH with high T4 B. Autoimmune etiology
C. Low T3 and T4 with high TSH C. Type of T-helper response
D. High TSH with normal T4 only D. Female predominance
E. Low TSH and normal T3 E. Association with iodine
27. Anti-thyroid antibodies in Hashimoto’s 30. Definitive treatment for Hashimoto’s
thyroiditis cause hypothyroidism mainly by: thyroiditis is:
A. Increasing hormone release A. Anti-thyroid drugs
B. Blocking iodine uptake B. Radioactive iodine
C. Destroying thyroid tissue C. Thyroidectomy
D. Stimulating TSH receptors D. Thyroxine replacement
E. Enhancing T4 conversion E. Immunosuppressive therapy