THYROID GLAND

Dr. Hany AhmedAssistant Professor of Physiology (MD, PhD).

Al Maarefa Colleges (KSA) & Zagazig University (ARE)

Specialist of Diabetes, Metabolism and Obesity Zagazig Obesity Management & Research Unit

ObjectivesThe 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:1) Thyroxine (T4)

2) Triiodothyronine (T3)

3) Calcitonin.

THYROID GLAND Cells of Thyroid gland:1- Follicular A Cells secrete Thyroxine (T4) & Tri

iodothyronine (T3).

2- Parafollicular C Cells secrete ThyroCalcitonin.

Functions of Thyroid gland: Required for• 1- Normal metabolism. • 2- Growth & maturation. • 3- Ca+2 regulation.

Formation & Secretion of thyroid hormones1) 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 Anti-thyroid drugs.

4- Coupling Reaction:• 2 molecules of DIT Thyroxine (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 protease enzyme release of T4, T3, MIT & DIT.• Stimulated by TSH && Inhibited by Anti-thyroid 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.

• Thyroxine - binding globulin (TBG) binds T3 and T4

• Albumin binds T3 and T4.

• Thyroxine- binding prealbumin (=transthyretin) binds only T4

Formation & Secretion of thyroid hormones

Thyroxine Binding Globulin (TBG)In circulation, > 99 % of T3 & T4 are bound to TBG.In hepatic failure, TBG level decreases → total thyroid hormones level.In pregnancy, TBG level increases → total thyroid hormones level.

9- Peripheral Conversions:• Peripheral conversions of T4 to either T3 (active) or rT3 (inactive).

N.B. T3 is 4 to 5 times more active than T4

Biosynthesis & secretion of thyroid hormones

ACTIONS OF THYROID HORMONES

1- Metabolic Actions of thyroid hormones 1) General metabolism (Calorigenesis): O2 consumption, heat

production, Na+ - K+ ATPase activity & BMR.2) ↑ Blood Glucose: by glucose GIT absorption. They increase

glucose uptake by tissues.3) ↓ Blood Cholesterol & phospholipids: By cholesterol

excretion in bile.4) ↑ Protein synthesis: * Normal level of thyroid hormones normal protein synthesis. * Thyroid hormones (in myxedema) protein anabolism. * Thyroid hormones (in thyrotoxicosis) catabolic activity.

2- 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 and maturation.

3- 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 decreased mental capacity & impaired memory.

4- Autonomic nervous system

• Has same actions as sympathetic stimulation.• Up-regulate β1 adrenergic receptors in the heart

(permissive action).

5- 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).

6- 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 SECRETION1- Hypothalamic TRF: TRFTSHThyroxin. ↓ 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.

IMPORTANT THYROID FUNCTION TESTS

1- Serum total and free T3 and T4

2- Serum TSH.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.

THYROID HORMONE RECEPTORSAND MECHANISM OF ACTION

• 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).

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 (Clear) cells. Polypeptide hormone with MW 3600. It is secreted due to Ca++ level in plasma.

• Action of calcitonin: 1) plasma Ca++ level by mobilization of Ca++

from bone & block action of PTH.2) Osteoclast activity and number (target cells).3) Ca++ & P04 excretion in urine.

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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

فى *** واألكم دفنت من خير يا القاع طيبهن من فطابأعظمه القاع

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