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Transcript
THYROID GLAND
Dr. Hany Ahmed
Assistant Professor
Al Maarefa College
Objectives
The student should be able to:
• Describe thyroid uptake of iodine.
• Know basic steps involved in biosynthesis of T3 & T4.
• Identify the bound forms of T3 and T4 in circulation.
• Know the biological effects of T3 and T4.
• Describe the regulation of thyroid hormones secretion.
• Know thyroid function tests.
• Identify thyroid hormone receptors.
• Describe thyroid hormone resistance.
• Thyrocalcitonin.
Physiologic Anatomy of Thyroid Gland
• Located immediately below
the larynx on each side and
anterior to the trachea.
• Secretes thyroxine and
triiodothyronine, commonly
called T4 and T3 , respectively.
THYROID GLAND
 Cells of Thyroid gland:
1- Follicular A Cells secrete Thyroxin (T4) & Tri
iodothyronine (T3).
2- Parafollicular C Cells secrete ThyroCalcitonin.
 Functions of Thyroid:
Required for
• 1- Normal metabolism.
• 2- Growth & maturation.
• 3- Ca+2 regulation.
Thyroid gland
 Thyroid gland maintains the level of metabolism in the tissues
that is optimal for their normal functioning.
 Thyroid hormones stimulate the O2 consumption of most of the
cells in the body.
 Help to regulate the lipid & carbohydrate metabolism & are
necessary for normal growth & maturation.
 Thyroid gland is not essential for life but its absence causes:
– Mental & Physical slowing.
– Poor resistance to cold.
– In children mental retardation & dwarfism.
Unique features of thyroid hormone
synthesis
• Thyroid hormones contain large amount of
iodine.
• Synthesis of thyroid hormones are partly
intracellular & partly extra cellular and are
stored in follicular lumen.
• T4 is a major secretary product of thyroid gland
but it is not the most active form.
Iodine requirement
• Iodine is essential for synthesis of thyroid
hormones.
• About 1 mg/week iodine is required to prevent
• iodine deficiency.
• Minimum daily iodine intake is 150 µg in adults
& average dietary intake is approximately
500 µg/day.
• Normal plasma iodine level is 0.3 µg/dl.
Formation & Secretion of thyroid hormones
1) Iodide Trap (iodide pump):
• It is an active transport mechanism in basal membrane.
• Intra-cellular thyroid iodide /plasma iodide ratio = 50: 1.
• Stimulated by TSH & Inhibited by Thiocyanate & Perchlorate ions.
2) Oxidation of Iodide to Iodine:
• Oxidation by peroxidase enzyme in apical membrane.
• Inhibited by Thiouracil & Carbimazol (by competitive inhibition).
3) Iodination of Tyrosine:
• Organification of iodine to form Monoiodotyrosine (MIT) &
Diiodotyrosine (DIT).
• Stimulated by TSH & Inhibited by Antithyroid drugs.
Formation & Secretion of thyroid hormones
4- Coupling Reaction:
• 2 molecules of DIT Thyroxin (T4) + Alanine.
• DIT + MIT Tri iodothyronine (T3).
• Stimulated by TSH & Inhibited by Antithyroid drugs.
5- Storage:
• MIT, DIT, T3 & T4 are stored in colloid bound to thyroglobulin.
6- Release:
• Thyroglobulin colloid is taken into the cells by endocytosis
then by a protease enzyme  release of T4, T3, MIT & DIT.
• Stimulated by TSH && Inhibited by Antithyroid drugs.
Formation & Secretion of thyroid hormones
7- Deiodination:
• Lysis of released MIT & DIT by deiodinase enzyme. So, iodine &
tyrosine used for new hormonal synthesis (intra thyroidal iodine
cycle).
8- Transport of T3 and T4: Bound to plasma proteins and ˂ 1% free.
• Thyroxin - binding globulin  binds T3 and T4.
• Albumin  binds T3 and T4.
• Thyroxin - binding prealbumin  binds only T4.
9- Peripheral Conversions:
• Peripheral conversions of T4 to either T3 (active) or rT3 (inactive).
N.B. T3 is 5 times more active than T4.
Thyroxine Binding Globulin (TBG)
• In circulation, most of T3 & T4 are bound
to thyroxine binding globulin (TBG).
• In hepatic failure, TBG level decreases →
decrease in total thyroid hormone level.
• In pregnancy, TBG level increases →
increase in total thyroid hormone level.
Synthesis, storage, and secretion of
thyroid hormone
ACTIONS OF THYROID HORMONES
Metabolic Actions of thyroid hormones
1) General metabolism (Calorigenesis):  O2 consumption, heat
production,  Na+ - K+ ATPase &  BMR.
2) ↑ Blood Glucose by  glycogenolysis & gluconeogenesis. They
increase glucose uptake by tissues.
3) ↓ Blood Cholesterol & phospholipids: By  cholesterol
excretion in bile.
4) ↑ Protein synthesis:
* In normal level of thyroid hormones  normal protein
synthesis.
*  Thyroid hormones (as in myxedema)   protein
anabolism.
*  Thyroid hormones (as in thyrotoxicosis)   catabolic
activity.
Growth & maturation
Thyroxin is necessary for growth and
maturation of most tissues through:
• Stimulation of protein synthesis.
• Acts synergistically with growth hormone &
somatomedins to promote bone formation
• Stimulate bone maturation.
Central nervous system
• Perinatal period:
– Maturation of the CNS is absolutely dependent on
thyroid hormone.
– Thyroid hormones deficiency causes irreversible
mental retardation.
• Adulthood:
– Hperthyroidism causes hyperexcitability and
irritability.
– Hypothyroidism causes decrease mental capacity
& impaired memory.
Autonomic nervous system
• Has same actions as sympathetic stimulation.
• Up-regulate β1 adrenergic receptors in the
heart (permissive action).
Cardiovascular system
•  Heart rate ( Rhythmicity) due to: O2
consumption &  Sensitivity of SAN to
adrenaline ( number of β receptors).
•  COP by: Direct action on heart & Potentiating
chronotropic & inotropic effects of circulating
catecholamine ( number & affinity of β
receptors to catecholamine).
•  Systolic &  diastolic ABP   pulse
pressure.
•  Peripheral resistance by VD (due to 
metabolites).
Other actions
•  Conversion of B-Carotenes to vitamin A.
• Erythropoiesis.
• Galactopoiesis
• GIT:  Motility, absorption and appetite.
• Respiratory system:  Pulmonary ventilation.
• Renal effect: Diuresis &  excretion of K+, Ca++ & Po4 in
urine.
•
Muscles:  Or  thyroid hormones  muscular weakness.
Thyrotoxic myopathy occurs with thyrotoxicosis.
Regulation of thyroid hormone secretion
REGULATION OF THYROID SECRETION
1- Hypothalamic TRF: TRF   TSH   Thyroxin.
↓ Thyroxin  ↑ TRF.
↑ Thyroxin  ↓ TRF.
2- Thyrotropin (=TSH):
• Secreted from anterior pituitary gland under effect of hypothalamic TRF.
3- Long Acting Thyroid Stimulator (LATS):
• Auto-antibodies formed by lymphocytes & have similar function as TSH
• Stimulating thyroid gland but with long acting effect  thyrotoxicosis.
4- Iodine Supply:
• Excess iodine depends on state of person:
• Normal person: Excess iodine  stored in gland without any  in
thyroxin.
• Hypothyroidism (with  I2 content,  T4 & enlargement of gland due to –
ve feed back  in TSH): Excess iodine inactivates TSH  the gland returns
to normal condition and  hyperplasia.
• Hyperthyroidism Excess iodine inactivates TSH   T4 formation &
vascularity of gland (Wolff-Chaikoff effect).
5- Autonomic nervous system:
• Sympathetic  stimulate thyroid secretion and effects.
THYROID FUNCTION TESTS
1- Serum T3 , T4 and TSH.
2- Protein-Bound Iodine (PBI):
• Normal range from 3.5-8 micrograms/100 ml.
• It decreases in hypothyroidism & increases in hyperthyroidism.
3- Uptake of Radioactive iodine (I131):
• Oral radioactive iodine is given & Determine thyroid uptake of
iodine.
• Normal gland take = 4% in one hour.
• May be 25% in hyperthyroidism & 1% in hypothyroidism.
4- Basal Metabolic Rate (BMR): (non specific test)
• Normally BMR = 40 C/m2 /hour ±15% around standard.
• In hyperthyroidism + 50%
in hypothyroidism  - 40%.
5- Serum Cholesterol: (non specific test)
• Normal = 150 to 250 mg/100 ml.
• It decreases in hyperthyroidism & increases in hypothyroidism.
THYROID HORMONE RECEPTORS
• The receptors of thyroid hormones present in
nuclei.
• Thyroid hormone-receptor complex binds to DNA
 expression of specific genes  formation of
mRNA  production of enzymes.
• Types of thyroid hormone receptors:
1- hTRα receptors: (for general metabolic function
all over the body).
2- hTRβ receptors: In brain (for development & TSH
secretion).
Types of thyroid hormone receptors
THYROID HORMONE RESISTANCE
• Pituitary resistance: a resistance to effect of T3
and T4 in Brain & Pituitary due to defect in hTRβ
receptors. Patients are not clinically hypothyroid
(high plasma levels of T3 and T4 and hTRα
receptors are unaffected). High non-suppressible
TSH.
• Attention Deficit - Hyperactivity Disorder:
Children who are overactive
• And impulsive with thyroid hormone resistance
(resistance in hTRβ receptors).
THYROCALCITONIN
• Ca++ lowering hormone, secreted by parafollicular
C cells. Polypeptide hormone with MW 3600. It is
secreted due to Ca++ level in plasma.
• Action:
• If injected   plasma Ca++ level by 
mobilization of Ca++ from bone & block action of
PTH.
•  Osteoclast activity and number.
•  Ca++, P04 & Na+ excretion in urine.
• N.B.: The hormone is relatively inactive in adult
humans.
References
 Human physiology, Lauralee Sherwood, seventh
edition.
 Text book physiology by Guyton &Hall,11th
edition.
 Text book of physiology by Linda .S .Costanzo third
edition
29
‫يا خير من دفنت فى القاع أعظمه *** فطاب من طيبهن القاع واألكم‬
‫نفسي الفدا لقبر انت ساكنه **** فيه العفاف وفيه الجود والكرم‬
‫األبيات الرائعه مكتوبه على األعمده التى تلتصق بقبر رسول هللا‬
‫صلي هللا على محمد صلى هللا عليه وسلم‬
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