Health

1. THYROID GLAND And
THYROID GLAND And
Diseases Of Thyroid Gland
Diseases Of Thyroid Gland
Thomas Leteipa
Thomas Leteipa
MCMFamily med,
MCMFamily med,
bsc clinmed,dip
bsc clinmed,dip
clinmed
clinmed

2. Thyroid gland
Thyroid gland
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The thyroid gland is one of the
The thyroid gland is one of the
largest endocrine glands.
largest endocrine glands.
The thyroid gland is located
The thyroid gland is located
immediately below the larynx
immediately below the larynx
and anterior to the upper part of
and anterior to the upper part of
the trachea. It weighs about 15-
the trachea. It weighs about 15-
20g.
20g.
It consists of 2 lateral lobes
It consists of 2 lateral lobes
connected by a narrow band of
connected by a narrow band of
thyroid tissue called the isthmus.
thyroid tissue called the isthmus.
The isthmus usually overlies the
The isthmus usually overlies the
region
region from the 2
from the 2nd
nd to 4
to 4th
th
tracheal cartilage.
tracheal cartilage.

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4 tiny parathyroid glands located
4 tiny parathyroid glands located
posteriorly at each pole of
posteriorly at each pole of
thyroid gland.
thyroid gland.
Hormone secreted-
Hormone secreted-
Thyroxine(T4)
Thyroxine(T4)
Tri iodothyronine (T3)
Tri iodothyronine (T3)
Reverse T3
Reverse T3
Calcitonin
Calcitonin

4. HISTOLOGY
HISTOLOGY
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The lobes of the thyroid
The lobes of the thyroid
contain many hollow,
contain many hollow,
spherical structure called
spherical structure called
follicles, which are the
follicles, which are the
functional units of the
functional units of the
thyroid gland.
thyroid gland.
Between the follicles there
Between the follicles there
are C cells, which secrete
are C cells, which secrete
calcitonin.
calcitonin.
Each follicle is filled with a
Each follicle is filled with a
thick sticky substance
thick sticky substance
called colloid.
called colloid.

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The major constituent of colloid is a
The major constituent of colloid is a
large glycoprotein called thyroglobulin.
large glycoprotein called thyroglobulin.
Unlike other endocrine glands, which
Unlike other endocrine glands, which
secretes their hormones once they
secretes their hormones once they
are produced, the thyroid gland stores
are produced, the thyroid gland stores
considerable amount of the thyroid
considerable amount of the thyroid
hormones in the colloid until they are
hormones in the colloid until they are
needed by the body.
needed by the body.

6. Iodine
Iodine
Metabolism
Metabolism
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Raw material, essential for thyroid
Raw material, essential for thyroid
synthesis
synthesis
Source-
Source-
Sea foods, milk, iodized salt.
Sea foods, milk, iodized salt.
Daily req- 100-200 microgram/day
Daily req- 100-200 microgram/day
From the total amount of Iodine
From the total amount of Iodine
entering the ECF,
entering the ECF, 20% enters the
20% enters the
thyroid gland and 80% excreted in urine.
thyroid gland and 80% excreted in urine.
Thyroid contain 95% of total iodine
Thyroid contain 95% of total iodine
content of body.
content of body.

7. 
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Thyroid gland stores enough
Thyroid gland stores enough
hormone to maintain euthyroid state
hormone to maintain euthyroid state
for 3 months.
for 3 months.
Daily secretion-
Daily secretion-
93%
93%Thyroxine (3-8 mgm/dl)
Thyroxine (3-8 mgm/dl)
7%
7% T3(0.15 mgm/dl)
T3(0.15 mgm/dl)
T3 is 4 times more potent than T4
T3 is 4 times more potent than T4

8. REGULATION OF THYROID
REGULATION OF THYROID
HORMONE SECRETION
HORMONE SECRETION
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Thyrotropin Releasing Hormone
Thyrotropin Releasing Hormone
(TRH)
(TRH)
A tripeptide: pyro-Glutamate-
A tripeptide: pyro-Glutamate-
histidine-proline-amide
histidine-proline-amide
Synthesized from a 29 kDa
Synthesized from a 29 kDa
precursor protein
precursor protein
Produced by hypothalamus
Produced by hypothalamus
Thyrotropin (TSH; Thyroid
Thyrotropin (TSH; Thyroid
Stimulating Hormone)
Stimulating Hormone)
28 kDa glycoprotein dimer
28 kDa glycoprotein dimer
composed of alpha and beta chains.
composed of alpha and beta chains.

9. Autoregulatio
Autoregulatio
n
n
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Depending upon the body Iodine
Depending upon the body Iodine
availability-
availability-
↑
↑ Iodine
Iodine ingestion- Thyroid gland
ingestion- Thyroid gland
depressed
depressed
↓
↓ Iodine
Iodine ingestion- Hyperactive
ingestion- Hyperactive
High dose of iodine
High dose of iodine ↓
↓ the formation
the formation
and release of thyroid hormone,
and release of thyroid hormone,
called
called Wolff Chaikoff effect.
Wolff Chaikoff effect.
Done by-
Done by-
↓
↓ iodine trapping
iodine trapping
Preventing oxidation of Iodide to
Preventing oxidation of Iodide to
iodine.
iodine.
Preventing incorporation of iodine to
Preventing incorporation of iodine to

10. SYNTHESIS, STORAGE &
SYNTHESIS, STORAGE &
SECRETION
SECRETION
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Iodine trapping
Iodine trapping
Synthesis and secretion of
Synthesis and secretion of
thyroglobulin
thyroglobulin
Oxidation of iodine
Oxidation of iodine
Organification of
Organification of
thyroglobulin
thyroglobulin
Coupling reaction
Coupling reaction
Storage
Storage
Secretion
Secretion

11. Iodide
Iodide
trapping
trapping
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Plasma iodide enters through the
Plasma iodide enters through the
sodium iodide symporter (NIS) at the
sodium iodide symporter (NIS) at the
baso lateral membrane of thyrocyte
baso lateral membrane of thyrocyte
facing the capillaries.
facing the capillaries.
It transport 2 Na+,
It transport 2 Na+,1
1 I- into cell, against
I- into cell, against
electrochemical gradient.
electrochemical gradient.
Energy given- Na+ K+ ATPase pump
Energy given- Na+ K+ ATPase pump
Process- secondary active transport
Process- secondary active transport
TSH promote this uptake.
TSH promote this uptake.
Anti thyroid drugs- Thiocynate,
Anti thyroid drugs- Thiocynate,
Perchlorate inhibit this
Perchlorate inhibit this

12. Synthesis and Secretion of
Synthesis and Secretion of
Thyroglobulins
Thyroglobulins
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•Thyroglobulin (Tg), a large glycoprotein,
•Thyroglobulin (Tg), a large glycoprotein,
is synthesized within the thyroid cell by
is synthesized within the thyroid cell by
RE Reticulum, then modified in Golgi
RE Reticulum, then modified in Golgi
Apparatus and packed into secretary
Apparatus and packed into secretary
vesicle.
vesicle.
Tg released in the lumen by exocytosis.
Tg released in the lumen by exocytosis.
Each molecule of Tg- 123 tyrosine
Each molecule of Tg- 123 tyrosine
residue, which serve as subtract for
residue, which serve as subtract for
iodine for synthesis of hormone.
iodine for synthesis of hormone.

13. Oxidation of
Oxidation of
iodine
iodine
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Once within the gland, iodide rapidly moves
Once within the gland, iodide rapidly moves
to apical surface of epithelial cell.
to apical surface of epithelial cell.
From there ,it is transported into the lumen
From there ,it is transported into the lumen
of follicle by Chloride Iodide ion counter
of follicle by Chloride Iodide ion counter
transporter Pendrin.
transporter Pendrin.
Thyroid peroxidase (TPO) sits on the luminal
Thyroid peroxidase (TPO) sits on the luminal
membrane. Iodide ion immediately oxidized
membrane. Iodide ion immediately oxidized
into iodine by TPO and its accompanying
into iodine by TPO and its accompanying
H2O2.
H2O2.
Anti thyroid drugs- Thiouracil,Methemazole
Anti thyroid drugs- Thiouracil,Methemazole
inhibit this conversion.
inhibit this conversion.

14. Organification of
Organification of
thyroglobulin
thyroglobulin
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Binding of iodine with Tg molecule
Binding of iodine with Tg molecule
Oxidized iodine bind directly with
Oxidized iodine bind directly with
tyrosine.
tyrosine.
After release Tg into lumen, Iodine
After release Tg into lumen, Iodine
binds about 1/6 th tyrosine residue
binds about 1/6 th tyrosine residue
in Tg.
in Tg.
Iodinates specific tyrosines in Tg,
Iodinates specific tyrosines in Tg,
creating mono-and di-iodotyrosines.
creating mono-and di-iodotyrosines.

15. Coupling reaction
Coupling reaction
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•The iodotyrosines combine to form
•The iodotyrosines combine to form
T3 and T4 within the Tg protein.
T3 and T4 within the Tg protein.
TPO(thyroid peroxidase) both involve
TPO(thyroid peroxidase) both involve
in iodination and coupling reaction.
in iodination and coupling reaction.
MIT+ DIT
MIT+ DIT T3
T3
DIT+ DIT
DIT+ DIT T4
T4
DIT+MIT
DIT+MIT reverse T3
reverse T3

16. Storage
Storage
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MIT, DIT, T3,T4 are all in peptide
MIT, DIT, T3,T4 are all in peptide
linkage with Tg which occurs as a
linkage with Tg which occurs as a
colloidal aggregate with in the
colloidal aggregate with in the
follicle.
follicle.
Store is sufficient to supply for 2-3
Store is sufficient to supply for 2-3
months.
months.

17. Secretion
Secretion
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Tg itself is not release into circulation.
Tg itself is not release into circulation.
T3,T4 must cleaved from Tg and release.
T3,T4 must cleaved from Tg and release.
The apical surface of thyroid cells send
The apical surface of thyroid cells send
pseudopodia which close around small
pseudopodia which close around small
portion of colloid to form pinocytic
portion of colloid to form pinocytic
vesicle that enter apex of thyroid cell by
vesicle that enter apex of thyroid cell by
endocytosis.
endocytosis.
Endocytosis facilitated by Tg receptor
Endocytosis facilitated by Tg receptor
Megalin on apical membrane.
Megalin on apical membrane.
Lysosome fuse with this vesicle to form
Lysosome fuse with this vesicle to form
digestive vesicle.
digestive vesicle.

18. 
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Protease digest the Tg molecule
Protease digest the Tg molecule
releasing MIT, DIT, T3,T4
releasing MIT, DIT, T3,T4
As T3, T4 lipid soluble,they diffuse
As T3, T4 lipid soluble,they diffuse
through plasma membrane into
through plasma membrane into
interstitial fluid then into blood.
interstitial fluid then into blood.
MIT, DIT rapidly deiodinated in
MIT, DIT rapidly deiodinated in
follicular cell by the enzyme
follicular cell by the enzyme
Iodotyrosine deiodinase.
Iodotyrosine deiodinase.
Iodine is reutilized to produce
Iodine is reutilized to produce
thyroid hormone.
thyroid hormone.

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In patient with congenital absence of
In patient with congenital absence of
deiodinase enzyme MIT, DIT appear in
deiodinase enzyme MIT, DIT appear in
urine and there are symptoms of iodine
urine and there are symptoms of iodine
deficiency.
deficiency.
Salivary gland, gastric mucosa,placenta,
Salivary gland, gastric mucosa,placenta,
cilliary body of eye,choroid plexus,
cilliary body of eye,choroid plexus,
mammary gland, post pitutary and
mammary gland, post pitutary and
adreanal cortex also transport iodide.
adreanal cortex also transport iodide.
There uptake are not dependent by TSH
There uptake are not dependent by TSH
and they can't form thyroid hormone.
and they can't form thyroid hormone.

20. Plasma thyroid hormone binding
Plasma thyroid hormone binding
proteins
proteins
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~99.97% of plasma T4 and 99.7% of T3
~99.97% of plasma T4 and 99.7% of T3
are non-covalently bound to proteins.
are non-covalently bound to proteins.
Thyroxine Binding Globulin(TBG) is the
Thyroxine Binding Globulin(TBG) is the
major binding protein for T4 and T3. TBG’s
major binding protein for T4 and T3. TBG’s
affinity for T4 is ~10-fold greater than for
affinity for T4 is ~10-fold greater than for
T3.
T3.
Transthyretin also carries some T4.
Transthyretin also carries some T4.
Albumin carries small amounts of T4 and
Albumin carries small amounts of T4 and
T3.
T3.
TBG, transthyretin and albumin are made
TBG, transthyretin and albumin are made

21. Importance of free
Importance of free
versus protein-bound
versus protein-bound
hormone
hormone
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Only free T4 and free T3 are
Only free T4 and free T3 are
biologically active and regulated by
biologically active and regulated by
feedback loops.
feedback loops.
Therefore conditions that alter TBG
Therefore conditions that alter TBG
levels alter total T4 and T3, but do not
levels alter total T4 and T3, but do not
alter free T4 and free T3.
alter free T4 and free T3.
Pregnancy
Pregnancy
Acute hepatitis
Acute hepatitis
Chronic liver failure
Chronic liver failure

22. PHYSIOLOGICAL EFFECTS OF
PHYSIOLOGICAL EFFECTS OF
THYROID HORMONES
THYROID HORMONES
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Metabolic rate and heat production:
Metabolic rate and heat production:
↑
↑ metabolic activities
metabolic activities
↑
↑ O
O₂
₂ consumption to most metabolically
consumption to most metabolically
active tissues
active tissues
BMR can
BMR can ↑
↑ by 60 – 100%
by 60 – 100%
Since
Since ↑
↑ metabolism results in
metabolism results in ↑
↑ heat
heat
production
production →
→ thyroid hormone effects is
thyroid hormone effects is
calorigenic
calorigenic
Intermediary metabolism:
Intermediary metabolism:
Modulates rates of many specific
Modulates rates of many specific
reactions involved in metabolism
reactions involved in metabolism

23. 
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Sympathomimetic effect-
Sympathomimetic effect-
Sympathomimetic: any action similar to one
Sympathomimetic: any action similar to one
produced by the sympathetic nervous
produced by the sympathetic nervous
system
system
Thyroid hormone
Thyroid hormone ↑
↑ target cell
target cell
responsiveness to catecholamines
responsiveness to catecholamines
The cardiovascular system:
The cardiovascular system:
↑
↑ the heart’s responsiveness to circulating
the heart’s responsiveness to circulating
catecholamines.
catecholamines.
↑
↑ heart rate and force of contraction
heart rate and force of contraction →
→ ↑
↑
CO
CO
In response to the heat load
In response to the heat load →
→ peripheral
peripheral

25. Laboratory Evaluation and
Laboratory Evaluation and
Imaging Studies of
Imaging Studies of
Thyroid
Thyroid
Functio
Functio
n
n
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Serum T4
Serum T4
Serum T3
Serum T3
TSH
TSH
Anti-thyroid antibodies
Anti-thyroid antibodies
Thyroid stimulating
Thyroid stimulating
Immunoglobulins
Immunoglobulins
Thyroid uptake and scan
Thyroid uptake and scan
Thyroid Ultra sound
Thyroid Ultra sound

26. Serum Thyroxine (T4)
Serum Thyroxine (T4)
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Measure free T4, not total T4
Measure free T4, not total T4
Only free T4 is biologically active
Only free T4 is biologically active
Conditions that alter TBG alter total T4 but
Conditions that alter TBG alter total T4 but
not free T4
not free T4
Pregnancy raises total T4
Pregnancy raises total T4
Chronic liver failure lowers total T4
Chronic liver failure lowers total T4
•High in hyperthyroidism
•High in hyperthyroidism
Low in hypothyroidism
Low in hypothyroidism

27. Serum Triiodothyronine (T3)
Serum Triiodothyronine (T3)
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High in hyperthyroidism
High in hyperthyroidism
•Low in hypothyroidism
•Low in hypothyroidism
But generally not worth measuring in
But generally not worth measuring in
hypothyroidism because T3 is less
hypothyroidism because T3 is less
sensitive and less specific than the
sensitive and less specific than the
decrease in free T4
decrease in free T4
•Measurement of free T3 is preferable to
•Measurement of free T3 is preferable to
total T3.
total T3.

28. Serum Thyrotropin (Thyroid
Serum Thyrotropin (Thyroid
Stimulating Hormone; TSH)
Stimulating Hormone; TSH)
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TSH is LOW in hyperthyroidism
TSH is LOW in hyperthyroidism
TSH is HIGH in hypothyroidism
TSH is HIGH in hypothyroidism
TSH is the most sensitive screening
TSH is the most sensitive screening
test for hyperthyroidism and primary
test for hyperthyroidism and primary
hypothyroidism
hypothyroidism
TSH within the normal range excludes
TSH within the normal range excludes
these diagnoses
these diagnoses

29. Antithyroid
Antithyroid
Antibodies
Antibodies
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Antimicrosomal antibodies (
Antimicrosomal antibodies (thyroid
thyroid
peroxidase antibodies)
peroxidase antibodies)
•Anti-thyroglobulin antibodies
•Anti-thyroglobulin antibodies
•Present in ~95% of Hashimoto’s and
•Present in ~95% of Hashimoto’s and
~60% of Graves’ patients at the time
~60% of Graves’ patients at the time
of diagnosis
of diagnosis
•Usually not very helpful in making a
•Usually not very helpful in making a
diagnosis or guiding therapy
diagnosis or guiding therapy

30. Thyroid Stimulating
Thyroid Stimulating
Immunoglobulins
Immunoglobulins
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Is present in Graves’ disease
Is present in Graves’ disease

31. Imaging
Imaging
studies
studies
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Thyroid uptake and scan
Thyroid uptake and scan
•Thyroid US
•Thyroid US
•Neck CT
•Neck CT

32. Thyroid uptake and scan
Thyroid uptake and scan
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I-123
I-123
I-131
I-131
Technetium 99
Technetium 99
*Radiotracer:
*Radiotracer:
Injectable IV: Technetium (15
Injectable IV: Technetium (15
min later: scan)
min later: scan)
Oral: 131 I and 123 I;(24 h
Oral: 131 I and 123 I;(24 h
later: scan/uptake)
later: scan/uptake)
Scan: structure
Scan: structure
Uptake: function
Uptake: function
Obtain pregnancy test before
Obtain pregnancy test before
the test
the test

33. Radioiodine Uptake
Radioiodine Uptake
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Used to evaluate the cause of
Used to evaluate the cause of
hyperthyroidism
hyperthyroidism
High if the thyroid is hyper-functioning,
High if the thyroid is hyper-functioning, e.g.
e.g.
Graves’ disease
Graves’ disease
Low if thyroid hormone is leaking out of
Low if thyroid hormone is leaking out of
damaged thyroid cells (subacute thyroiditis)
damaged thyroid cells (subacute thyroiditis)
or the patient is taking excess exogenous
or the patient is taking excess exogenous
thyroid hormone
thyroid hormone
Expressed as a
Expressed as a NUMBER(e.g., 35%)
NUMBER(e.g., 35%)
Used to calculate the dose of I-131 to treat
Used to calculate the dose of I-131 to treat
hyper-functioning thyroid tissue or cancer.
hyper-functioning thyroid tissue or cancer.

34. Thyroid Scan (nuclear
Thyroid Scan (nuclear
medicine)
medicine)
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Primary use is to
Primary use is to
determine whether
determine whether
palpated nodules are
palpated nodules are
functional or non-
functional or non-
functional.
functional.
“Hot” nodules concentrate
“Hot” nodules concentrate
the radionuclide and are
the radionuclide and are
essentially always benign.
essentially always benign.
“Cold” nodules are usually
“Cold” nodules are usually
benign but are sometimes
benign but are sometimes
malignant.
malignant.
The majority, perhaps
The majority, perhaps
90%, of palpable nodules
90%, of palpable nodules
are cold.
are cold.

35. Thyroid Ultra
Thyroid Ultra
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Sonography
Sonography
Painless, quick, no
Painless, quick, no
contrast material, no
contrast material, no
radiation
radiation
Can be used in
Can be used in
pregnancy, while on L-
pregnancy, while on L-
thyroxine therapy, after
thyroxine therapy, after
exogenous iodine
exogenous iodine
exposure
exposure
Can detect thyroid
Can detect thyroid
nodules as small as 2-3
nodules as small as 2-3
mm and provide
mm and provide
guidance for FNA biops
guidance for FNA biopsy
y

36. Indications for thyroid
Indications for thyroid
US
US
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Goiter
Goiter
If thyroid gland is normal on
If thyroid gland is normal on
physical exam:
physical exam:
External radiation during childhood
External radiation during childhood
History of familial thyroid cancer
History of familial thyroid cancer
Lymph node metastases
Lymph node metastases
Prior to parathyroid surgery
Prior to parathyroid surgery

37. Diseases Of Thyroid
Diseases Of Thyroid
Gland
Gland
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DIVIDED INTO:
DIVIDED INTO:
HYPOTHYROIDISM
HYPOTHYROIDISM (Gland destruction)
(Gland destruction)
Under-production of thyroid
Under-production of thyroid
hormones
hormones
Myxoedema (Gull Disease)
Myxoedema (Gull Disease)
Cretinism
Cretinism
Thyroiditis
Thyroiditis
HYPERTHYROIDISM
HYPERTHYROIDISM (thyrotoxicosis)
(thyrotoxicosis)
Over-production of thyroid hormone
Over-production of thyroid hormone
Grave’s Disease
Grave’s Disease
Thyrotoxicosis
Thyrotoxicosis
GOITER-
GOITER- Diffuse and multi-nodular
Diffuse and multi-nodular
NEOPLASTIC PROCESSES
NEOPLASTIC PROCESSES
Beningn
Beningn
Malignant
Malignant

38. Hypothyroidism
Hypothyroidism
Resulting from reduced circulating level of T3
Resulting from reduced circulating level of T3
and T4
and T4

39. Causes of
Causes of
Hypothyroidism
Hypothyroidism
◦
◦
1.
1.
2.
2.
3.
3.
4.
4.
5.
5.
6.
6.
7.
7.
◦
◦
Primary
Primary
Dietary Iodide deficiency
Dietary Iodide deficiency
Iodine defficiency
Iodine defficiency
Autoimmune (Hashimoto´s Thyroiditis)
Autoimmune (Hashimoto´s Thyroiditis)
Drugs: amiodarone, lithium, thiocyanates, phenylbutazone,
Drugs: amiodarone, lithium, thiocyanates, phenylbutazone,
sulfonylureas
sulfonylureas
Iatrogenic- Surgical removal of the thyroid gland and radiation
Iatrogenic- Surgical removal of the thyroid gland and radiation
treatment
treatment
Congenital (1 in 3000 to 4000)
Congenital (1 in 3000 to 4000)
Infiltrative disorders
Infiltrative disorders
Secondary
Secondary
Pituitary gland destruction
Pituitary gland destruction
Isolated TSH deficiency
Isolated TSH deficiency
Bexarotene(anti cancer drug) treatment
Bexarotene(anti cancer drug) treatment
Hypothalamic disorders
Hypothalamic disorders

40. 







Hypothyroidism appears in 3
Hypothyroidism appears in 3
forms-
forms-
1. Myxoedema (Gull Disease)
1. Myxoedema (Gull Disease)
2. Cretinism
2. Cretinism
3. Thyroiditis
3. Thyroiditis

41. Myxoedema (Gull
Myxoedema (Gull
Disease)
Disease)




























hypothyroidism developing in adults,
hypothyroidism developing in adults,
deposition of excess mucoprotein in skin of
deposition of excess mucoprotein in skin of
forearm,
forearm,
Leg, feet
Leg, feet
Features-
Features-
Enlargement of thyroid gland (Goiter)
Enlargement of thyroid gland (Goiter)
Lack of interest in daily household chores.
Lack of interest in daily household chores.
slowing of physical and mental activity
slowing of physical and mental activity
generalized fatigue, dull look
generalized fatigue, dull look
apathy
apathy
overweight
overweight
CO
CO
-
- shortness of breath
shortness of breath
-
- exercise capacity
exercise capacity
Sympathetic activity
Sympathetic activity
-
- constipation
constipation
- sweating
- sweating

42. 































Skin
Skin-dry, thicken, yellow(carotinemia), cool ( blood flow)
-dry, thicken, yellow(carotinemia), cool ( blood flow)
edema, puffy face, periorbital swelling.
edema, puffy face, periorbital swelling.
Ptosis ( drooping of upper eyelid)
Ptosis ( drooping of upper eyelid)
coarse hair
coarse hair
broadening of facial features
broadening of facial features
enlarged tongue
enlarged tongue
deepening of voice (telephonic voice)
deepening of voice (telephonic voice)
Calorigenic action-
Calorigenic action- BMR decreases to 30-40%
BMR decreases to 30-40%
cold-intolerant
cold-intolerant
Bone marrow-
Bone marrow- anemia ( normocytic, normochromic)
anemia ( normocytic, normochromic)
Menstrual irregularities
Menstrual irregularities
Carbohydrate metabolism-
Carbohydrate metabolism- Low blood sugar
Low blood sugar
Lipid metabolism-
Lipid metabolism- Increased serum Cholesterols, TGs,
Increased serum Cholesterols, TGs,
phospholipids
phospholipids
CNS
CNS- Myxedematous madness (psychosis)
- Myxedematous madness (psychosis)
Knee jerk reaction time increased
Knee jerk reaction time increased
Memory loss
Memory loss

43. Cretinis
Cretinis
m
m










hypothyroidism developing
hypothyroidism developing
in infancy/early childhood, due to
in infancy/early childhood, due to
maternal iodine deficiency.
maternal iodine deficiency.
Listless, somnolent, apathetic to play,
Listless, somnolent, apathetic to play,
devoid of initiatives.
devoid of initiatives.
Features-
Features-
Severe mental retardation (imbeciles-
Severe mental retardation (imbeciles-
IQ-25- 49)
IQ-25- 49)
Occurs in iodine deficient areas of world
Occurs in iodine deficient areas of world
(i.e. Himalayas, China, Africa)
(i.e. Himalayas, China, Africa)

44. 



















Clinical-
Clinical-
Impaired skeletal development
Impaired skeletal development
Impaired CNS development
Impaired CNS development
Inadequate maternal thyroid hormone prior to fetal thyroid
Inadequate maternal thyroid hormone prior to fetal thyroid
gland
gland
formation severe mental retardation
formation severe mental retardation
Often deaf and mute
Often deaf and mute
Dwarfism and stunted growth
Dwarfism and stunted growth
Thick, coars, dry skin
Thick, coars, dry skin
Protruded abdomen (pot belly-Splanchnomegaly) and
Protruded abdomen (pot belly-Splanchnomegaly) and
enlarged
enlarged
tongue
tongue
Failure of sexual developments
Failure of sexual developments
Delayed milestones-
Delayed milestones-
Length of the child fails to increase
Length of the child fails to increase
Dentition is delayed
Dentition is delayed
Delayed sitting up and head holding
Delayed sitting up and head holding
Delayed walking
Delayed walking
Delayed closure of ant fontanels
Delayed closure of ant fontanels
Delayed standing up and speech
Delayed standing up and speech

45. 





On the left, a euthyroid
On the left, a euthyroid
6 year old girl at the
6 year old girl at the
50th height percentile
50th height percentile
(105 cm).
(105 cm).
On the right, a 17 year
On the right, a 17 year
old girl with a height of
old girl with a height of
100 cm, mental
100 cm, mental
retardation, myxedema
retardation, myxedema
and a TSH of 288
and a TSH of 288
(normal 0.3-5.5).
(normal 0.3-5.5).
(Werner & Ingbar’s The Thyroid, 8th Edition,
(Werner & Ingbar’s The Thyroid, 8th Edition,
page 744.)
page 744.)

46. Lab Findings-
Lab Findings-








Increased TSH
Increased TSH
Decreased free T4
Decreased free T4
Decreased FT3
Decreased FT3
Anti-TPO(ant thyroid peroxidase) and
Anti-TPO(ant thyroid peroxidase) and
anti-Tg Abs (Hashimoto’s)
anti-Tg Abs (Hashimoto’s)

47. Hypothyroidism: Therapy
Hypothyroidism: Therapy








L-Thyroxine
L-Thyroxine
(levothyroxine; T4)
(levothyroxine; T4)
Goals-
Goals-
Alleviate
Alleviate
symptoms
symptoms
Normalize TSH
Normalize TSH

48. Thyroiditis
Thyroiditis
Inflammation of
Inflammation of
thyroid
thyroid
Types:
Types:

 a) Hashimoto
a) Hashimoto
thyroiditis
thyroiditis
1) gradual thyroid failure due
1) gradual thyroid failure due
to autoimmune destruction of thyroid
to autoimmune destruction of thyroid
2) 45-65 yrs
2) 45-65 yrs
3) 10:1 female predominance
3) 10:1 female predominance
4) major cause of non endemic
4) major cause of non endemic
goiter in
goiter in
childre
childre
n
n 5) genetic component- patients
5) genetic component- patients
with Turner syndrome have circulating
with Turner syndrome have circulating
anti-thyroid Ab
anti-thyroid Ab

49. 













Clinical:
Clinical:
1)
1) progressive depletion of thyroid epithelial
progressive depletion of thyroid epithelial
cells
cells
2)
2) replaced with mononuclear cells and
replaced with mononuclear cells and
fibrosis
fibrosis
3)
3) comes to clinical attention as painless
comes to clinical attention as painless
enlargement of thyroid with some degree of
enlargement of thyroid with some degree of
hypothyroidism
hypothyroidism
4)
4) hypothyroidism progresses slowly
hypothyroidism progresses slowly
5)
5) can be preceded by “hashitoxicosis”
can be preceded by “hashitoxicosis”
(transient hyperthyroidism caused by
(transient hyperthyroidism caused by
inflammation associated with Hashimoto's
inflammation associated with Hashimoto's
thyroiditis
thyroiditis)
)
6)
6) patients at risk in developing other
patients at risk in developing other

50. 
 b) Subacute (granulomatous)
b) Subacute (granulomatous)
thyroiditis
thyroiditis
[“ De Quervain thyroiditis”]
[“ De Quervain thyroiditis”]
















i)
i) occurs less often than Hashimoto
occurs less often than Hashimoto
ii)
ii) 30-50 yrs
30-50 yrs
iii)
iii) female preponderance 5:1
female preponderance 5:1
iv)
iv) caused by viral infection (Coxsackie virus,
caused by viral infection (Coxsackie virus,
mumps and adenoviruses)
mumps and adenoviruses)
v)
v) history of upper respiratory infection just
history of upper respiratory infection just
prior to onset of thyroiditis
prior to onset of thyroiditis
vi)
vi) seasonal incidence (summer peak)
seasonal incidence (summer peak)
vii)
vii) acute or gradual
acute or gradual
viii)
viii) painful presentation, radiating to jaw,
painful presentation, radiating to jaw,
throat, ears: especially when swallowing
throat, ears: especially when swallowing

51. 





ix)
ix) inflammation and hyperthyroidism
inflammation and hyperthyroidism
are transient
are transient
x)
x) self limited disease
self limited disease
c) Subacute lymphocytic (painless)
c) Subacute lymphocytic (painless)
thyroiditis
thyroiditis
i)
i)
ii)
ii)
uncommon
uncommon
hyperthyroid presentation
hyperthyroid presentation
-
- may present with any
may present with any
of signs of hyperthyroidism (no
of signs of hyperthyroidism (no
opthalmopathy,
opthalmopathy,as in Graves disease)
as in Graves disease)

52. 





d) Riedel thyroiditis
d) Riedel thyroiditis
i)
i) fibrosis of thyroid and
fibrosis of thyroid and
neighboring structures
neighboring structures
ii)
ii) presents as hard and fixed
presents as hard and fixed
thyroid which clinically is similar to
thyroid which clinically is similar to
CA
CA

53. Congenital
Congenital
Hypothyroidism
Hypothyroidism






◦
◦
Prevalence:
Prevalence: 1 in 3000 to 4000 newborns
1 in 3000 to 4000 newborns
Cause:
Cause: Dysgenesis
Dysgenesis 85%
85%
Treatment:
Treatment:
Supplemental treatment With Levothyroxine
Supplemental treatment With Levothyroxine
is “essential” for a normal C.N.S.
is “essential” for a normal C.N.S.
Development and prevention of mental
Development and prevention of mental
retardation
retardation

54. Hyperthyroidism
Hyperthyroidism








◦
◦
1)
1)
2)
2)
3)
3)
4)
4)
5)
5)
6)
6)
It is a condition resulting from increased
It is a condition resulting from increased
level of circulating FT4 and FT3
level of circulating FT4 and FT3
Cause-
Cause-
Thyrotoxicosis
Thyrotoxicosis
Causes of Thyrotoxicosis:
Causes of Thyrotoxicosis:
Primary Hyperthyroidism
Primary Hyperthyroidism
Grave´s disease( Exopthalmic Goiter)
Grave´s disease( Exopthalmic Goiter)
Toxic Multinodular Goiter
Toxic Multinodular Goiter
Toxic adenoma
Toxic adenoma
Functioning thyroid carcinoma metastases
Functioning thyroid carcinoma metastases
Activating mutation of TSH receptor
Activating mutation of TSH receptor
Drugs: Iodine excess
Drugs: Iodine excess

55. Graves
Graves
disease
disease


















Most common cause of endogenous
Most common cause of endogenous
hyperthyroidism
hyperthyroidism
Characteristics:
Characteristics:
a) hyperthyroidism
a) hyperthyroidism
i) diffuse enlargement of
i) diffuse enlargement of
thyroid
thyroid
ii) lymphocytic infiltration
ii) lymphocytic infiltration
b) infiltrative ophthalmopathy
b) infiltrative ophthalmopathy
i) with resultant
i) with resultant
exophthalmos
exophthalmos
c) localized infiltrative dermopathy
c) localized infiltrative dermopathy
i) “pretibial myxedema”
i) “pretibial myxedema”

56. 











peak incidence 20-40
peak incidence 20-40
female preponderance (7:1)
female preponderance (7:1)
familial link
familial link
Pathogenesis:
Pathogenesis:
a) autoimmune disorder
a) autoimmune disorder
b)Thyroid stimulating
b)Thyroid stimulating Ab (Long acting
Ab (Long acting
thyroid stimulator) action like TSH
thyroid stimulator) action like TSH
c)LATS (long acting thyroid
c)LATS (long acting thyroid
stimulator)protectors- prevent inactivation
stimulator)protectors- prevent inactivation
of LATS
of LATS










LATS combine with receptors on thyroid cells
LATS combine with receptors on thyroid cells
plasma membrane and displace TSH from its
plasma membrane and displace TSH from its
binding sites.
binding sites.
Act via cAMP to cause prolonged action.
Act via cAMP to cause prolonged action.
Leads to-
Leads to-
Increased formation and release of T3,T4
Increased formation and release of T3,T4
Increased growth of thyroid gland
Increased growth of thyroid gland

57. Feature
Feature
s
s








Exopthalmos-
Exopthalmos-
Protrusion of the eye ball with visibility of sclera
Protrusion of the eye ball with visibility of sclera
between lower lid and cornea.
between lower lid and cornea.
Due to-
Due to-
retro-orbital connective tissue and ocular
retro-orbital connective tissue and ocular
muscles are increased
muscles are increased


ii)
ii)
iii)
iii)
iv)
iv)
v)
v)
i) inflammatory edema (cytokines
i) inflammatory edema (cytokines
induced)
induced)
T-cell infiltration
T-cell infiltration
fatty infiltration
fatty infiltration
mucopolysaccharide and water
mucopolysaccharide and water
accumulation
accumulation
these cause eye to bulge outward
these cause eye to bulge outward

58. 

























Lid retraction-
Lid retraction-
Visibility of sclera between upper lid and cornea
Visibility of sclera between upper lid and cornea
Due to overstimulation of levator palpebrae
Due to overstimulation of levator palpebrae
superiosis
superiosis
Calorigenic action-
Calorigenic action-
BMR
BMR ↑
↑ 30%-100%
30%-100%
Heat intolerance
Heat intolerance
Weight loss (thyrotoxic myopathy)
Weight loss (thyrotoxic myopathy)
Lactation
Lactation ↑
↑
Scanty periods
Scanty periods
Vitamine B & C deficiency
Vitamine B & C deficiency
CVS
CVS- tachycardia, high output cardiac failure
- tachycardia, high output cardiac failure
Thyroid diabetes
Thyroid diabetes
Decreased serum lipid levels
Decreased serum lipid levels

59. 















CNS
CNS- overexcitibility, tremors,irritability,
- overexcitibility, tremors,irritability,
nervousness
nervousness
Smooth, moist, warm skin
Smooth, moist, warm skin
Flushing of face and hands
Flushing of face and hands
Overgrown nails (
Overgrown nails (acropachy
acropachy), which may lift
), which may lift
off the nail bed (
off the nail bed (onycholysis
onycholysis)
)
Fine soft thinned scalp hair
Fine soft thinned scalp hair
Generalized itching (
Generalized itching (pruritus
pruritus)
)
Increased skin pigmentation
Increased skin pigmentation
“
“Pretibial myxedema
Pretibial myxedema”
”

60. Thyrotoxicosi
Thyrotoxicosi
s
s


◦
◦
◦
◦
◦
◦
◦
◦
◦
◦
◦
◦
◦
◦
◦
◦
◦
◦
◦
◦
Symptoms:
Symptoms:
Hyperactivity
Hyperactivity
Irritability
Irritability
Dysphoria
Dysphoria
Heat intolerance & sweating
Heat intolerance & sweating
Palpitations
Palpitations
Fatigue & weakness
Fatigue & weakness
Weight loss with increased
Weight loss with increased
appetite
appetite
Diarrhea
Diarrhea
Polyuria
Polyuria
Sexual dysfunction
Sexual dysfunction

61. 

◦
◦
◦
◦
◦
◦
◦
◦
◦
◦
◦
◦
◦
◦
◦
◦
◦
◦
◦
◦
Signs:
Signs:
Tachycardia
Tachycardia
Atrial fibrillation
Atrial fibrillation
Tremor
Tremor
Goiter
Goiter
Warm, moist skin
Warm, moist skin
Muscle weakness,
Muscle weakness,
myopathy
myopathy
Lid retraction or lag
Lid retraction or lag
Gynecomastia
Gynecomastia
* Exophtalmus
* Exophtalmus
* Pretibial myxedema
* Pretibial myxedema

62. Lab findings-
Lab findings-






Suppressed
Suppressed
TSH
TSH
Elevated Free
Elevated Free
T4
T4
Elevated Free
Elevated Free
T3
T3

63. Treatment:
Treatment:
◦
◦
◦
◦
◦
◦
Reducing thyroid hormone synthesis:
Reducing thyroid hormone synthesis:
Antithyroid drugs (Methimazole,
Antithyroid drugs (Methimazole,
Propylthyouracil)
Propylthyouracil)
Radioiodine (
Radioiodine (131
131I)
I)
Subtotal thyroidectomy
Subtotal thyroidectomy
Reducing Thyroid hormone effects:
Reducing Thyroid hormone effects:
Propranolol
Propranolol
Glucocorticoids
Glucocorticoids
Benzodiazepines
Benzodiazepines
Reducing peripheral conversion of T4 to T3
Reducing peripheral conversion of T4 to T3
Propylthyouracil
Propylthyouracil
Glucocorticoids
Glucocorticoids
Iodide
Iodide

64. Thyrotoxic crisis or Thyroid storm:
Thyrotoxic crisis or Thyroid storm:
It´s a life-threatening exacerbation of
It´s a life-threatening exacerbation of
thyrotoxicosis, acompanied by fever, delirium,
thyrotoxicosis, acompanied by fever, delirium,
seizures, coma, vomiting, diarrhea, jaundice.
seizures, coma, vomiting, diarrhea, jaundice.
Mortality rate reachs 30% even with treatment
Mortality rate reachs 30% even with treatment
It´s usually precipitated by acute illness, such as:
It´s usually precipitated by acute illness, such as:
Stroke, infection,trauma, diabeic ketoacidosis,
Stroke, infection,trauma, diabeic ketoacidosis,
surgery, radioiodine treatment
surgery, radioiodine treatment

65. 





Thyroid storm
Thyroid storm
i) abrupt onset of severe
i) abrupt onset of severe
hyperthyroidism
hyperthyroidism
ii) febrile, tachycardia
ii) febrile, tachycardia
iii) is a medical emergency
iii) is a medical emergency
- death from cardiac arrhythmias
- death from cardiac arrhythmias

66. Goiter
Goiter








Diffuse and multinodular
Diffuse and multinodular
enlargement of the thyroid
enlargement of the thyroid
most common manifestation of
most common manifestation of
thyroid disease
thyroid disease
most often caused by dietary
most often caused by dietary
iodine deficiency (i.e., impaired
iodine deficiency (i.e., impaired
synthesis of thyroid hormone)
synthesis of thyroid hormone)

67. 
 Two types:
Two types:
i)
i)
ii)
ii)
endemi
endemi
c
c
sporadi
sporadi
c
c
i)
i)
ii)
ii)
iii)
iii)
geographic area deficient in
geographic area deficient in
iodine
iodine
mountainous areas of world
mountainous areas of world
- Himalayas, Andes,Alps
- Himalayas, Andes,Alps
TSH
TSH

 Endemic goiter
Endemic goiter (<10%
(<10%
population)
population)
iv) can result from ingestion of
iv) can result from ingestion of
certain
certain




“
“goitrogens
goitrogens”- cabbage, cauliflower, Brussels,sprouts, turnips,
”- cabbage, cauliflower, Brussels,sprouts, turnips,
cassava
cassava
Contain Progoitrin/ Progoitrin activator( anti thyroid agent)
Contain Progoitrin/ Progoitrin activator( anti thyroid agent)
Prevent incorporation of iodine with
Prevent incorporation of iodine with
tyrosine.
tyrosine.

68. 
 Sporadic
Sporadic
goiter
goiter i)
i)
ii)
ii)
iii)
iii)
less frequent than
less frequent than
endemic
endemic
female preponderance
female preponderance
peak incidence near
peak incidence near
puberty
puberty
•
•








Multinodular goiter
Multinodular goiter
a) recurrent hyperplasia/
a) recurrent hyperplasia/
hypertrophy
hypertrophy
b) all simple nontoxic goiters evolve
b) all simple nontoxic goiters evolve
into multinodular goiters
into multinodular goiters
c) produce the most extreme
c) produce the most extreme
thyroid enlargements, often
thyroid enlargements, often
mistaken for
mistaken for
neoplasm
neoplasm
d) asymmetrically enlarged
d) asymmetrically enlarged
thyroid
thyroid

69. 



•
•
◦
◦
◦
◦
◦
◦
small % of patients may develop a
small % of patients may develop a
hyperfunctioning thyroid (nodule)
hyperfunctioning thyroid (nodule)
resulting in a “toxic multinodular
resulting in a “toxic multinodular
goiter”
goiter”
Plummer syndrome is example
Plummer syndrome is example
without dermopathy, nor-
without dermopathy, nor-
ophthalmopathy (as in Graves)
ophthalmopathy (as in Graves)
All goiters may cause “Mass Effects”
All goiters may cause “Mass Effects”
a) dysphagia
a) dysphagia
b) compression of large vessels
b) compression of large vessels
c) airway obstruction
c) airway obstruction

70. Thyroid
Thyroid
Neoplasms
Neoplasms






Adenomas
Adenomas
discrete solitary masses
discrete solitary masses
derived from follicular epithelium (i.
derived from follicular epithelium (i.
e., “follicular adenomas”)
e., “follicular adenomas”)
NOT transform into malignancy
NOT transform into malignancy

71. 



Usually present as unilateral painless
Usually present as unilateral painless
mass
mass
Take up less radioactive iodine
Take up less radioactive iodine
compared to normal thyroid
compared to normal thyroid
parenchymal cells
parenchymal cells
i)
i)
ii)
ii)


“cold” nodules
“cold” nodules
~10% of cold nodules
~10% of cold nodules
malignant
malignant
iii) “hot” nodules rarely
iii) “hot” nodules rarely
malignant
malignant

 Biopsy is “gold” standard for
Biopsy is “gold” standard for
diagnosis
diagnosis

72. 











Other benign tumors
Other benign tumors
a) cysts
a) cysts
b) lipomas
b) lipomas
c) hemangiomas
c) hemangiomas
d) dermoid cysts
d) dermoid cysts
e) teratomas (mainly in
e) teratomas (mainly in
infants)
infants)

73. •
•Thyroid Cancer typically appears as a "cold nodule". That is to say, it
Thyroid Cancer typically appears as a "cold nodule". That is to say, it
appears as a white area or defect in an otherwise black thyroid. A "
appears as a white area or defect in an otherwise black thyroid. A "
cold" area is NOT necessarily cancer. Indeed, most "cold nodules" are
cold" area is NOT necessarily cancer. Indeed, most "cold nodules" are
benign! Ultrasound, perhaps followed by biopsy, often plays an
benign! Ultrasound, perhaps followed by biopsy, often plays an
important role in differentiation
important role in differentiation
www.freelivedoctor.
www.freelivedoctor.

74. Thyroid Carcinomas
Thyroid Carcinomas


















most appear in adults
most appear in adults
papillary CA may present in childhood
papillary CA may present in childhood
female predominance (early and middle
female predominance (early and middle
adult)
adult)
childhood and late adulthood have equal
childhood and late adulthood have equal
gender distribution
gender distribution
Most CA are well differentiated:
Most CA are well differentiated:
a) papillary CA (~80% of cases)
a) papillary CA (~80% of cases)
b) follicular CA ( ~15% of cases)
b) follicular CA ( ~15% of cases)
c) medullary CA (~5% of cases)
c) medullary CA (~5% of cases)
d) anaplastic CA (< 5% of cases)
d) anaplastic CA (< 5% of cases)