Thyroid

Hyperthyroidism & Hypothyroidism

Objectives:
❖ Describe the synthesis of thyroid ❖ Identify the terms goiter, hypo and
hormones. hyperthyroidism.
❖ Diagram the control over the ❖ List the causes and types of goiter,
thyroid gland. hypo and hyperthyroidism.
❖ Compare between the hormones ❖ Discusses the clinical picture of hypo
released by the thyroid gland. and hyperthyroidism.
❖ Discuss the actions of the thyroid ❖ Explain the laboratory tests to
hormones. diagnose hypo and hyperthyroidism.
❖ Outline management regimen for
hypo and hyperthyroidism.
Done by :

➔ Team leaders: Rahaf AlShammari, Abdulelah AlDossari

➔ Team members:
◆ Yazeed AlKhayyal, Abdulhakim bin Onayq
◆ Alanoud Alessa, Lujain AlZaid
◆ Khalid Almutairi, Abdulelah Alsaeed
◆ Noura Al hassan, Abduljabbar AlYamani
◆ Fahad AlNahabi, Hesham AlShaya
◆ Majd AlBarrak, Shahad AlZahrani Colour index:
◆ Abdullah AlZaid, Hesham AlMousa ● Important
◆ Dana AlKadi, Hadeel AlMakinzy ● Numbers
◆ Shahad AlTayyash, Norah AlKadi
● Extra

‫َوأَن ﻟﱠﯾْسَ ﻟ ِْﻺِﻧﺳَ ﺎ ِن إ ﱠِﻻ ﻣَﺎ ﺳَ ﻌَ ٰﻰ‬

 Thyroid Gland
● It is located below the larynx
on either sides and anterior to
the trachea.

● The first recognized

endocrine gland.

● 20g in adult.

Hormones

T4 T3
tetraiodothyronine (Triiodothyronine)
10%. Reverse T3 Calcitonin
(thyroxine) Inactive
“but it's more active than T4”
90%.

If we move iodine ion to the other side, we will get reverse T3

which is inactive.
Why don’t we have reverse T4?
Because the rings are fully occupied by iodine ions.

*Colloid stores the hormone.

Synthesis *Parafollicular cells secretes calcitonin.
Follicular cells synthesize T3 and T4.

T3 , T4
Calcitonin

2
 In = out
* Three unique features
No iodine,
1- Contains a large amount of iodine.* no thyroid
- supplied in diet, 1mg/week. hormones.

2- Synthesis is partially intracellular *inside the

follicular cells* and partially extracellular*inside the colloid*.

3- T4 is the major product.

Thyroid Hormones [T3 - T4]

Biosynthesis (by the follicular cells):
1. Iodide pump/ trap (NIS)
2. Thyroglobulin synthesis.
3. Oxidation of iodide to iodine.
4. Iodination of tyrosine, to form
○ Mono-iodotyrosine (MIT)
○ Di-iodotyrosine (DIT)
5. Coupling;
○ MIT + DIT = Tri-iodothyronine, ( T3).
○ DIT + DIT = Tetra-iodothyronine, (T4)/ Thyroxine.
6. Release.

Colloid

1
3

Interstitial
fluid
4,5

3
Steps in Biosynthesis:
1 Thyroglobulin formation and transport:
● Glycoprotein.
● Tyrosine.
● Rough endoplasmic reticulum and Golgi apparatus.
It is active transport because the concentration of
2 Iodide pump or iodide trap: iodine in the thyroid is greater than in blood vessels.
Wolff-chaikoff effect:
● Active transport.”Na/I cotransporter” Briefly, if iodine conc. in the blood is low, the body will
● It is stimulated by TSH. increase the uptake of iodine by increasing effect of
iodine pump and vice versa.
● Wolff-chaikoff effect
○ (A reduction in thyroid hormone levels caused by
administration of a large amount of iodine).
Ratio of concentration from 30-250 times.
¥ decrease
● Wolff-chaikoff effect
^ increase

^ iodine conc. > ¥ effect of iodine pump > ¥ iodine uptake

3 Oxidation of iodide to iodine: ¥ iodine conc. > ^ effect of iodine pump > ^ iodine uptake

● Thyroid peroxidase.
○ It is located in or attached to the apical membrane.

4 Organification of thyroglobulin:
● Binding of iodine with thyroglobulin.
● Catalyzed by thyroid peroxidase, to form MIT/DIT
● Remain attached to thyroglobulin until the gland stimulated to
secrete.

5 Coupling reaction:

DIT + DIT → T4 (faster)

DIT + MIT → T3
● Catalyzed by thyroid peroxidase.
● It is stored as colloid.
● Is sufficient for 2-3 months. So, if the patient has any problem the
symptoms won’t appears immediately, it takes time.

6 Endocytosis of thyroglobulin. By taking them from colloid to inside the follicular cells.

7 Fusion of lysosomes immediately with the vesicles.

Hydrolysis of the peptide bond to release

8 DIT+MIT+T4+T3 from the thyroglobulin.

9 Delivery of T4 and T3 to the systemic circulation.

10 Deiodination of DIT and MIT by thyroid deiodinase (recycling). 4

 Intracellular Extracellular: colloid

Thyroid Hormones in The Circulation:

Bound Unbound
“Free” “active form”
● 70- 80% bound to
thyroxine-binding globulin ● 0.03% of T4
(TBG) synthesized in the liver. ● 0.3% of T3
● The reminder is bound to
albumin.

In hepatic failure:
↓TBG → ↑free T3/T4 → inhibition of thyroid secretion.
Feedback mechanism
In pregnancy:
↑Estrogen → ↑TBG → ↓free T3/T4 → stimulation of thyroid secretion.
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 Release of T4 and T3 to The Tissue

1. The release is slow because of the high affinity of the plasma

binding proteins.
● ½ of T4 in the blood is released every 6 days.
● ½ of T3 in the blood is released every one day.

2. T4 & T3 readily diffuse through the cell membrane.

3. Stored in the targeted tissues (days to weeks).

4. Most of T4 is deionized to T3 by iodinase enzyme. At tissue level

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5. In the nucleus, T3 mainly binds to “thyroid hormone receptor” and
influence transcription of genes.
 Action of Thyroid Hormones
● Before binding to the nuclear receptors 90% of T4 is converted to T3.
How ? Doctor nervana said read it

Activation of thyroid
T3 + Nuclear receptor
regulating element on DNA
Mimic steroid hormones as their target
either on cytoplasm or in the nucleus.

DNA transcription
translation of mRNA formation of mRNA
specific protein
synthesis
(target tissue specific)

Action of Thyroid Hormones

● Is the energy requirement under basal condition.
(mental and physical rest 12-18 hours after a meal).
Basal Metabolic ● Complete lack of thyroid hormones.
Rate (BMR): (40-50% decrease in BMR).
● Extreme increase of thyroid hormones.
(60-100% increase in BMR).

The aim is to increase

expression of glucose Effects on 1- increase glucose uptake by the cells.
to the cells, so that it 2- increase glycogenolysis.
can be utilized and carbohydrate
3- increase gluconeogenesis.
used in energy metabolism 4- increase absorption from the GIT.
production

1- Increase lipolysis.
Effects on fat 2- decrease plasma cholesterol by increase
loss in feces. Because GI motility increases. Lead to
metabolism diarrhea and steatorrhea.
3- Increase oxidation of free fatty acids.
Metabolism
Effect on protein overall effect is catabolic leading to decrease
metabolism in muscle mass. Thin patients.

The metabolic
effects are due to 1- Cytochrome oxidase.
induction of 2- NADPH cytochrome C reductase.
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metabolic 3- Alpha- glycerophosphate dehydrogenase.
enzymes: 4- Malic enzymes.
Dr nervana said read it 5- Several proteolytic enzymes
 Action of Thyroid Hormones

● Thyroid hormones are essential for

maturation of the CNS.
● decrease of hormones secretion
Perinatal
period ● Irreversible mental retardation
● Screening is necessary to introduce
hormone replacement.

CNS ● Increase in thyroid hormone

secretion:
1-hyperexcitability.
2- irritability.
● Decrease in thyroid hormones
In adult
secretion:
1- slow movement.
2- impaired memory.
3- decrease mental capacity.

Because of increasing Cardiac output

demand by the cells,
● Increase heart rate & stroke volume. up to 60%
the body compensate ● Decrease peripheral resistance.*peripheral vasodilation*
by increasing cardiac ● End result is increase delivery of oxygenated blood
output to deliver more
oxygenated blood. to the tissues.

The cardiovascular effects are due to:

Cardiovascular 1- Thyroid hormones potentiate the effect of
system catecholamine in the circulation leads to activation of
β-adrenergic receptors.
2- Direct induction of:
a) myocardial β-adrenergic receptors.
b) sarcoplasmic reticulum. To increase calcium source.
c) Ca+2 ATPase. That return Calcium to sarcoplasmic reticulum.
d) myosine.

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 Action of Thyroid Hormones
Effects on bone: Potentiate effect of growth
hormone.”Permissiveness”
Effects on Respiration:
a) promote bone formation. 1- increase ventilation rate.
b) promote ossification. 2- increase dissociation of oxygen from Hb
by increasing RBC 2,3-DPG (2,3
c) promote fusion of boneplate.
diphosphoglycerate).”Increasing unloading of
d) promote bone maturation. oxygen by shifting the curve to the right”

Effects on the GIT: Effects on Autonomic nervous

1- increase appetite and food intake.
system:
Produced the same action as catecholamines
2- increase of digestive juices secretion. via
3- increase of G.I tract motility. β-adrenergic receptors including:
excess secretion diarrhea. a) increase BMR.

Lack of secretion constipation. b) increase heat production.

c) increase heart rate.
d) increase stroke volume.
i.e. β-blocker (propranolol) is used in
treatment of hyperthyroidism.

Summary

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REGULATION OF HORMONES SECRETION
It is regulated by the hypothalamic-pituitary axis.

Heat center
Normally we have low
Thyroid hormone bc. of
our hot environment

1- Thyrotropin-releasing hormone (TRH):

● Tripeptide.
● Paraventricular nuclei of the hypothalamus.
● Act on the thyrotrophs of the anterior pituitary.
● Transcription and secretion of TSH.
● Phospholipid second messenger system.

2- Thyroid-stimulating hormone (TSH):

● Glycoprotein.
● Anterior pituitary.
● Regulate metabolism , secretion and growth of thyroid gland (trophic effect)
● TSH secretion started at 11-12 of gestational weeks.
● TSH + receptor activation of adenylyl cyclase via Gs protein
cAMP activation of protein kinase multiple phosphorylation secretion
and thyroid growth. Dr nervana said just read its involved in biochem

Action of TSH:
1. Increase proteolysis of the thyroglobulin.
2. Increase pump activity.
3. Increase iodination of tyrosine.
4. Increase coupling reaction.
5. Trophic effect.

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 Increase apetite
Thyroid Diseases can be described in terms of function
‫ ﺗﺟﯾك وﺣدة ﻣﺧﻔﻔﮫ ﻣﻼﺑﺳﮭﺎ ﺟﺎﻟﺳﮫ ﻋﻠﻰ طﺎوﻟﺔ اﻷﻛل وراﯾﺣﺔ وﺟﺎﯾﮫ ﻋﻠﻰ‬:‫ﻧﯾﻣوﻧك اﻟدﻛﺗور‬
‫دورة اﻟﻣﯾﺎة‬
diarrhea
Heat intolerance + Common in
weight loss female
Hyperthyroidism (Euthyroid, hypothyroid & hyperthyroid), size (enlarged =
goiter). Goiter can be Eu,hypo or hyper.

Overactivity of the thyroid gland. Activity of the gland:

Female : Male ratio 8 : 1. ● 5-10 times increase in secretion.
● 2-3 times increase in size.

Causes Diagnosis
Graves’ Disease: Goiter in 95%

- Autoimmune disorder Skin:

- Increased circulating level of Thyroid - Smooth, warm and moist.
Stimulating Immunoglobulins (TSI) - Heat intolerance, night sweating
- 95%
- 4-8 times more common in female than Musculoskeletal:
male - Muscle atrophy.

Neurological:
Thyroid gland tumor: - Tremors.
- Enhanced reflexes.
- 95% is benign - Irritability.
- History of head and neck irradiation.
- Family history Cardiovascular:
- Common in breast cancer patients who - Increase heart rate.
had radiation therapy - Increase stroke volume.
- Arrhythmias.
Exogenous T3 & T4: - Hypertension.

G.I tract:
- Rare cause
- Weight loss.
- Ingestion of excessive amount of
- Diarrhea. -Increased appetite
thyroid hormone
Exophthalmos:
Excess TSH secretion: - Anxious staring expression.
- Protrusion of eyeballs.
- Disease of the Hypothalamus (TRH)
- Disease of the Pituitary (TSH) Others: Exophthalmos
- Menstrual cycle disturbance.
- Increased glomerular filtration rate.

Investigations Treatment
Serum T3, T4 ,TSH measurement. Medical therapy:
- With 3-4 monthly monitoring

Serum T3, T4 are High Surgery:

- TSH is Low in primary - Subtotal thyroidectomy
hyperthyroidism Indication for surgery:
- TSH is Elevated in secondary A) Relapse after medical treatment.
hyperthyroidism B) Drug intolerance.
C) Cosmetic.
D) Suspected malignancy.
 Mimic
Loss of apetite depression
Hypothyroidism
‫ ﺗﺟﯾك وﺣدة ﺳﻣﯾﻧﺔ ﻻﺑﺳﮫ ﻛل ﻣﻼﺑس اﻟدوﻻب ﻣﻧﺳدﺣﮫ ﻋﻠﻰ اﻟﻛﻧب واﻻﻛل ﻗداﻣﮭﺎ ﻣﺎ اﻧوﻛل‬:‫ﻧﯾﻣوﻧك اﻟدﻛﺗور‬
● Under activity of the thyroid gland. Cold intolerance Weight
Common
in female
● More common in females (30-60 years old) gain

Causes Diagnosis
Inherited abnormalities of thyroid Skin:
hormone synthesis: - Dry skin.
- Cold intolerance.
- Peroxidase defect.
- Iodide trapping defect. Musculoskeletal:
- Thyroglobulin defect. - ↑Muscle bulk.
- ↓Skeletal growth.
- hyporeflexia
- Muscle sluggishness. - stiffness All over
Endemic Colloid Goiter:
(Before table salt) Neurological:
- Slow movement.
↓Iodide →↓Hormone formation→ - Impaired memory.
↑TSH→↑Thyroglobulin→↑Size (>10 times)
- Decrease mental capacity. - dull

Cardiovascular:
Idiopathic Nontoxic Colloid Goiter: - ↓Heart rate. - Miniature ECG
- Iodine intake is normal - ↓Stroke volume. (small amputated)

Inflammation →↑Cell damage →↓Hormone G.I Tract:

secretion→↑TSH→↑Activity of normal
- Constipation
cells→↑Size - Decreased appetite
- Increased weight

Myxoedema:
An edematous appearance
Gland Destruction (Surgery).
throughout the body

Pituitary diseases or tumors. Others:

- Loss of libido
Hypothalamus diseases or tumors. - Menstrual cycle disturbance
- Decrease glomerular filtration rate.

Investigations Treatment
Serum T3, T4 are low L-Thyroxine
- TSH is elevated in primary - Starting dose is 25-50µg
hypothyroidism - 2-4 weeks period.
- TSH is low in secondary First response seen is weight loss.
hypothyroidism - gradual increase in dose is important
 Cretinism
● Extreme hypothyroidism during infancy and childhood (failure of growth).

1) Congenital lack of thyroid gland (Congenital Cretinism).

2) Genetic deficiency leading to failure to produce hormone.
Causes 3) Lack of Iodine in the diet (Endemic Cretinism)

1. Infant is normal at birth but abnormality appears within

weeks.
2. Protruding tongue.
Symptoms 3. Dwarf with short limbs.
4. Mental retardation.
5. Often presents with umbilical hernia.
6. Delayed eruption of teeth.

● Changes are irreversible unless treatment is given early.

Treatment
 Summary
Hormones TH in circulation TH Actions

★ T4 + T3 (by ● Unbound ★ Increase in:

follicular cells) (small ANS , Respiration , carbohydrate anabolism ,
★ rT3 amount, lipid and protein catabolism , cardiac output ,
★ Calcitonin (by activated) GIT appetite and digestion , bone growth
parafollicular ● Bound(high ★ CNS:
cells) amount, Decrease in fetal life cause mental retardation,
bound to in adults it causes slow movement and memory
TGB) ★ BMR:
Loss of TH-> low BMR
High TH -> high BMR

Enzymes and stimulation Liver and pregnancy

● TSH - active transport of iodide ● Decrease TBG-> increase of free T3 and

● Thyroid peroxidase - oxidation of T4 -> Inhibition of thyroid secretion.
iodide to iodine, iodination
thyroglobulin and coupling of DIT ● Increase in estrogen levels-> Increase in
and MIT TGB ->Decrease in free levels of T3 & T4
● Thyroid deiodinase- deiodination of -> stimulation of thyroid secretions
DIT and MIT
● 5-Iodinase enzyme- deionization of
T4 to T3

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Questions

MCQs
Q1: Which of the following
physiological responses is greater for
triiodothyronine (T3) than for
thyroxine (T4)?
A) Secretion rate from the thyroid Q3: the effect of liver disease on
B) Plasma concentration thyroid hormones is:
C) Plasma half-life A) Decreased free hormones,
D) Affinity for nuclear receptors in stimulated thyroid secretion.
target tissues B) Increased free hormones,
stimulated thyroid secretion
Q2: A patient is administered C) Increased free hormones,
sufficient thyroxine (T4) to increase inhibited thyroid secretion.
plasma levels of the hormone D) Increased bound hormones,
several-fold. Which of the following inhibited thyroid secretion.
sets of changes is most likely in this
patient after several weeks of T4 Q4: The enzyme Thyroid Peroxidase
administration? contributes in which step in thyroid
A) Increased respiratory rate, hormones synthesis:
heart rate and plasma A) Deiodination of DIT and MIT
cholesterol conc. B) Coupling reaction
B) Increased respiratory rate, C) Iodide pump
heart rate and decreased D) Thyroglobulin formation
plasma cholesterol conc.
C) Increased respiratory rate, Q5) Perchlorate mechanism is:
plasma cholesterol conc and A) Inhibition of Na/I cotransport
decreased heart rate. B) Inhibition of peroxidase
D) Decreased respiratory rate, enzyme
heart rate and increased C) Stimulates thyroid secretion
plasma cholesterol conc. D) Decrease TBG levels
Answers

Q5: A
Q3: C
Q2: B

Q4: B
Q1: D

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Questions

MCQs

1/ Inhibition of the iodide pump would be

expected to cause which change?
A) Increased synthesis of T4
B) Increased synthesis of thyroglobulin
C) Increased metabolic rate
D) Decreased TSH secretion 4/ Which symptom would least likely be
associated with thyrotoxicosis?
2/ A patient has a goiter associated with A) Tachycardia
high plasma levels of both TRH and TSH. B) Increased appetite
Her heart rate is elevated. this patient most
C) Somnolence
likely has which condition?
A) An endemic goiter D) Increased sweating
B) A hypothalamic tumor secreting large
amounts of TRH 5/ A patient presents with tachycardia and
C) A pituitary tumor secreting large heat intolerance. You suspect Graves’
amounts of TSH disease. Which of the following is not
D) Graves’ disease consistent with your diagnosis?
A) Increased total and free T4
3/ A 46-year-old man has “puffy” skin and is B) Suppressed plasma [TSH]
lethargic. His plasma TSH concentration is C) Exophthalmos
low and increases markedly when he is given D) Decreased thyroid radioactive iodine
TRH. What is the most likely diagnosis? uptake
A) Hypothyroidism due to an abnormality
in the hypothalamus
6/ A 37-year-old woman presents to her
B) Hyperthyroidism due to an abnormality
physician with an enlarged thyroid gland
in the hypothalamus
and high plasma levels of T4 and T3.
C) Hyperthyroidism due to a thyroid tumor
Which of the following is likely to be
D) Hypothyroidism due to an abnormality
decreased?
in the pituitary
A) Heart rate
B) Cardiac output
C) Peripheral vascular resistance
D) Metabolic rate
Answers

5- D.
6- C.
4- C.
3- A.
2- B.
1- B.

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