THYROID HORMONE

BY Dr.Sadia Moazzam

PHYSIOLOGICAL ANATOMY OF THYROID HORMONE two lobes lying across the trachea four parathyroid glands lie behind it large gland;15-20 grams; 4X3X2 cm gland;15 derived from pharyngeal endoderm  high blood supply via thyroid artery Composed of two distinct cell types: types: 1. C (clear) cells or parafollicular cells secrete calcitonin, a calcium regulating hormone 2. Follicular cells secrete thyroid hormone T3& T4
  

Formation and secretion of thyroglobulin by the thyroid cells  Golgi apparatus and endoplasmic reticulum of thyroid cells secrete thyroglobulin in the follicles  Each thyroglobulin contain 70 tyrosine amino acids  Thyroid hormone is formed by binding of tyrosine with iodine

Comparison between ThyroxineT4 and Triiodothyronine T3 T3 more Rapid and intense as compare to T4 4 times more potent than T4 Present in blood in small quantity

NORMAL VALUES plasma T4 level in adults =8 ug/D (103 nmol/L), plasma T3 level is approximately 0.15 ug/dL (2.3 nmol/L).

Iodine Requirement for The Formation Of Thyroid Hormone 50 milligrams/ each year (1mg/week) Deficiency Simple Goitre Prevention Iodized table salt Composition 1 part sodium iodide. 100,000 parts sodium chloride

SYNTHESIS OF THYROID HORMONE

1. Iodide trapping ( Na+/I- symporter Na+/INormal gland can store 30 times of iodides in thyroid gland In hyperactivity it can store upto 250 times of iodide FACTOR AFFECTING TSH stimulates the activity of iodide pump Hypophysectomy diminishes the activity of iodide pump

Oxidation of the Iodide (hydrogen peroxide) Conversion of iodides into oxidized form of iodine Io or I3 Capable of binding directly with tyrosine amino acid Promoted by the enzyme Hydrogen peroxidase Located at the apical border of the cells Heriditary absence of enzyme leads to HYPOTHYROID GOITRE
2.

Organification of Thyroglobulin (iodinase enzyme) Binding of iodine with tyrosine is called Organification of Thyroglobulin a. 1 iodine binds with tyrosine to form monoiodotyrosine b. iodine binds with tyrosine to form diiodotyrosine c. Monoiodotyrosine + diiodotyrosine= triiodotyrosine T3 d. 2 diiodotyrosine binds to form thyroxine T4
3.

Follicular Cells Secrete Two Iodine Containing Hormones Derived From the Amino Acid TYROSINE

STORAGE OF THYROID HORMONE  Usually stored in thyroid gland  30 times thyroxine T4 molecule and few triiodotyrosineT3  Stored hormone can be used for 2-3 months 2-

RELEASE OF THROID HORMONE

 Thyroid

cells send pseudopodial extensions around colloid to form pinocytic vesicles  Vesicles binds with lysosomes  Digest the vesicles by the proteases present in the lysosomes  Release of T3 & T4 into blood  93% T4  7% T3

RELEASE OF THROID HORMONE--contd HORMONE T4

is converted to T3 before binding to its receptors inside the cell  T3 biologically more potent of two hormones  Three quarters of the iodinated tyrosine in the thyroglobulin never becomes thyroid hormones and Iodine is cleaved by deiodinase enzyme is used later for synthesis of thyroid hormone  Congenital absence of this deiodinase enzyme leads to iodine-deficiency iodine-

TRANSPORT OF THYROID HORMONE FROM BLOOD TO TISSUES  99% bound to thyroid binding globulins (TBG)and albumins  1% Free hormone (active form)  Thyroxine and Triiodothyronine Are Released Slowly to Tissue Cells  half life of T4 is 6 days half life of T3 is 1 day

Thyroid Hormones Have Slow Onset and Long Duration of Action.  Latent period of T4 6-12 day 6 Latent period of T3 6-12 hours 6-

PHYSIOLOGIC FUNCTIONS OF THE THYROID HORMONES

1)

THYROID HORMONES INCREASE THE TRANSCRIPTION OF LARGE NUMBER OF GENES Most of the Thyroxine T4 secreted by the Thyroid Is Converted toTriiodothyronine T3. T3. Thyroid Hormones Activate Nuclear Receptors. Receptors. DNA transcription RNA translation Large number of protein enzymes, structural proteins, transport proteins and other substances are synthesized Net result is generalized increase in functional activity throughout the body.

    

NORMAL Thyroid Hormones Activate Nuclear Receptors and cause synthesis of proteins

HYPOTHYROID Decrease secretion cause decreased activation of nuclear receptors and decreased synthesis of proteins

HYPERTHYROID Increase secretion cause increased activation of nuclear receptors and increased synthesis of proteins

2. CALOROGENIC EFFECT
   

Increases BMR by increasing the number and activity of Mitochondria. Increase Active Transport of Ions Through Cell Membranes Increased activity of the enzyme Na+-K+ Na+ATPase. Increase O2 consumption of all metabolically active tissues ( exceptions are adult brain, testes, uterus, lymph nodes, spleen, and anterior pituitary

NORMAL
Maintains

BMR

HYPOTHYROI D Decreased activity increase the BMR by 404050% Gains body weight


HYPERTHYROI D Increased activity increase the BMR by 60 -100%

Maintains

Lean

body weight

3) EFFECT OF THYROID HORMONE ON GROWTH

NORMAL HYPOTHYROID HYPERTHYROID Promote Growth is Excessive skeletal growth and greatly retarded. growth development  Mental (epiphyses close early so eventually short) of skeletal retardation bones and brain during fetal, 1-2 1year of postnatal life

4) METABOLIC EFFECTS OF THROID HORMONE a) Stimulation of Carbohydrate Metabolism.  rapid uptake of glucose by the cells  enhanced glycolysis  enhanced gluconeogenesis,  increased rate of absorption from the gastrointestinal tract  increased insulin secretion

b) Stimulation of Fat Metabolism. Metabolism.

   

Increased lipolysis Increased fatty acid conc. in blood Increased oxidation of fatty acids In hyperthroidism, decreased cholesterol,phospholipids and triglycerides . Increased cholesterol secretion in lipids bile and feces. Increased numbers of low-density lowlipoprotein receptors on the liver cells. In hypothroidism, decreased cholesterol, phospholipids and triglycerides.

c) Increased Requirement for Vitamins. vitamins are essential parts of some of the enzymes or coenzymes vitamin deficiency can occur when excess thyroid hormone is secreted,

NORMAL Promote glucose utilization

HYPOTHYROID HYPERTHYROID Decrease glucose Increased glucose utilization by cells utilization by cells Increased oxidation of fatty acid and decreased cholesterol in plasma Increased demand of vitamins

Mobilize fat Decreased oxidation of fatty and cause acid and lipolysis increased cholesterol and atherosclerosis Utilization of Decrease demand vitamins as of vitamins enzymes

NORMAL
CVS Maintains heart rate at 72/min Maintains strength RESPIRATIO NUtilization of O2 GIT Increase food intake

HYPOTHYROID HYPERTHYROID
Bradycardia Decrease chronotropic effect Decrease rate and depth Decrease GIT motility (constipation) Tacycardia Decrease chronotropic effect Increase rate and depth Increase GIT motility (Diarrhoe)

NORMAL
CNS Promote cerebration MUSCLE Promote vigor

HYPOTHYROID
Decrease cerebration

HYPERTHYROID
Increase cerebration Tremors, nervousness Hyperactive muscle weakness due to protein catabolism Sleep 12-14 hours 12-

sluggish

SLEEP

Hyperactivity of brain Exitable synapses

11.Effect on Other Endocrine Glands

1. 2.

 

Potentiate the effect of growth hormone Increases the rate of glucose metabolism increases the need for parathyroid hormone. increased rate of glucocorticoid secretion by the adrenal glands.

12.Effect of Thyroid Hormone on Sexual Function.

Hypothyroidism leads to infertility in men and in women can cause menorrhagia or polymenorrhea

REGULATION OF THYROID HORMONE SECRETION 1. TRH 2. TSH 3. Cold 4. Emotional reactions 5. Feedback effect of Thyroid Hormone to decrease Anterior Pituitary secretion of TSH

TRH

TSH

TSH  Increased proteolysis of the thyroglobulin  Increased activity of the iodide pump, pump,  Increased iodination of tyrosine  Increased size and increased secretory activity of the thyroid cells  Increased number of thyroid cells

ANTITHYROID DRUGS

1. Thiocyanate Ions Decrease Iodide Trapping.  Competitive inhibition of iodide transport into the cell  Inhibition of the iodide-trapping mechanism iodide Prevents the thyroglobulin from being iodinated  Deficiency of thyroid hormone  Leads to increased secretion of TSH by the anterior pituitary gland  Overgrowth of the thyroid gland i.e. goitre

PROPYLTHIOURACIL (methimazole and carbimazole)

   

Block the peroxidase enzyme that is required for iodination of tyrosine Prevents formation of thyroid hormone Absence of thyroxine and triiodothyronine in the thyroglobulin Feedback enhancement of TSH secretion by the anterior pituitary gland Formation of goiter.

IODIDES IN HIGH CONCENTRATIONS

       

100 times the normal plasma level Reduced iodide trapping Iodination of tyrosine to form thyroid hormones is also decreased. Normal endocytosis of colloid from the follicles by the thyroid glandular cells Immediate shutdown of thyroid hormone secretion Decrease all phases of thyroid activity Decrease size of thyroid gland Use before surgical removal

DISEASES OF THE THYROID

HYPERTHYROIDISM Toxic Goiter Thyrotoxicosis Graves Disease

GRAVES S DISEASE 6060-80% cases More commen in women Autoimmune disease Antibodies to the TSH recepter stimulate the recepters (TSI) Marked increase in T3 and T4 secretion Enlargement of thyroid gland

THYROID ADENOMA
 Localized

adenoma (a tumor)  Secretes large quantities of thyroid hormone  Secretory function in the remainder of the thyroid gland is almost totally inhibited by the negative inhibition of the production of TSH by the pituitary gland

OTHER CAUSES OF HYPERTHYROIDISM 1. Toxic multinodular goitre 2. TSH secreting pituitary tumor 3. Exogenous administration of T3 and T4

Type
Hyperthyroidism Tumor of pituitary gland Exogenous T3&T4

TRH

TSH

T3&T4

Symptoms of Hyperthyroidism 1. High state of excitability 2 Intolerance to heat 3 Palpitation 4 Increased sweating, 5 Weight loss 6 Muscle weakness, 7 Nervousness 8 Extreme fatigue

Signs of Hyperthyroidism 1. Tachycardia 2. Resting tremors 3. Exolphthalmos Exolphthalmos (antibodies that react against
retroorbital tissues)

protrusion of the eyeballs  Optic nerve damage  epithelial surfaces of the eyes become dry and irritated


Treatment in Hyperthyroidism 1. Surgical removal of most of the thyroid gland.  Administeration of propylthiouracil for several weeks to reduce BMR  Iodides for 1 to 2 weeks immediately before operation to reduce the size 2 Radioactive Iodine  Destroy most of the secretory cells of the thyroid gland.

HYPOTHYROIDISM

CAUSES OF HYPOTHYROIDISM 1 Endemic Colloid Goiter Caused by Dietary Iodide Deficiency. Deficiency.
    

Lack of iodine prevents production of both thyroxine and triiodothyronine. No hormone is available to inhibit production of TSH by the anterior pituitary To secrete excessively large quantities of TSH. Secrete tremendous amounts of thyroglobulin colloid into the follicles Thyroid gland may increase to 10 to 20 times normal size.

2.Idiopathic nontoxic colloid goiter.

    

Enlarged thyroid glands in people who do not have iodine deficiency The secretion of hormone is depressed Patients show signs of mild thyroiditis; Increased TSH secretion and progressive growth of the noninflamed portions of the gland. these glands usually are nodular, with some portions of the gland growing while other portions are being destroyed by thyroiditis.

 

The thyroid glands of most of these patients first have autoimmune thyroiditis, (HASHIMOTO THYROIDITIS) THYROIDITIS) progressive deterioration and finally fibrosis of the gland diminished or absent secretion of thyroid hormone.

CHARACTERISTICS OF HYPOTHYROIDISM
1 2 3 4 5 6

Fatigue and extreme somnolence slowed heart rate decreased cardiac output increased bodyweight mental sluggishness, froglike husky voice,

Hypothyroidism in adults Myxedema.

1 2 3

Bagginess under the eyes swelling of the face. Increased quantities of hyaluronic acid and chondroitin sulfate bound with protein form excessive tissue gel Increased cholesterol leads to atherosclerosis

Hypothyroidism during fetal life, infancy, or childhood. CRETINISM 1 Congenital cretinism 2 Endemic cretinism

Congenital cretinism Congenital lack of a thyroid gland Endemic cretinism Genetic defect of the gland, or from iodine lack in the diet

Characteristics of cretinism
      

Neonate s movements are sluggish Both physical and mental growth greatly retarded. disproportionate rate of growth, Skeletal growth is stopped earlier as compared to soft tissue growth Child is obese, stocky Tongue is enlarged and it obstructs swallowing and breathing

TREATMENT
Mental retardation is partially reversible with immediate post partum thyroid therapy (2-3 (2months)

PUBERTY GOITRE
Cause  Increased production of Thyroid binding globulin  Decreased level of free thyroid hormone  Increased production of TSH by the negative feed back mechanism  Increased production of thyroglobulin  Enlarged thyroid gland----goitre gland----goitre