Download MBBS General Surgery PPT 16 Thyroid Physiology Function Test Lecture Notes

Physiology of Thyroid

Discussion points.......

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Thyroid hormone

Production of Thyroid Hormones.

Transport of T3 and T4.

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Regulation of Thyroid Hormones.

Actions of Thyroid Hormones.
Thyroid Hormone

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. There are two biological y active thyroid hormones:

Tetraiodothyronine (T4)- also k/a thyroxine.

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Triiodothyronine (T3)- Derived from modification of tyrosine.

. Thyroid secretes-

. 80mg of T4 per day

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. 5mg of T3 per day

. Additional 25mg/day of T3 is produced by peripheral conversion of T4.

. T3 has a much greater biological activity about 10 folds than T4.

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Production of Thyroid Hormones
IODINE Metabolism:

. Dietary iodine is absorbed in the GI tract.

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Taken up by the thyroid gland

Or removed from the body by the kidneys.

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. 80% of the iodine is lost in urine.

. 20 % is taken up by the Thyroid follicular cells.
Production of Thyroid Hormones.......
IODINE Metabolism:

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. Transport of iodide into follicular cel s is dependent

upon a Na+/I- co-transport system.

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. Iodide(I?) taken up by the thyroid gland is oxidized by

peroxide in the lumen of the follicle.

. Oxidized iodine(I) can then be used in production of

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thyroid hormones.

Production of Thyroid Hormones...........
Production Of Thyroglobulin:

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Pituitary produces TSH, which binds to follicle cell

receptors.

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Follicle cells produce thyroglobulin (glycoprotein).

Thyroglobulin is released into the colloid space.

It 's tyrosine residues are iodinated by I.

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This results in formation of monoiodotyrosine or

diiodotyrosine.
Production of Thyroid Hormones...........

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. Thyroid hormone production and

release:

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T4 is approximately 95%.

T3 is 5%.

Transport of Thyroid Hormones

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. Thyroid hormones are lipid-soluble.

. Found in the circulation associated with binding proteins:

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Thyroid Hormone-Binding Globulin(TBG) (~70% of hormone)

Pre-albumin(Transthyretin) (~15%)

Albumin (~15%)

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. Less than 1% of thyroid hormone is found free in the circulation.

. Only free and albumin-bound thyroid hormone is biologically available to tissues.
Conversion of T4 to T3

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. T4 is converted to T3 in peripheral tissues by the

enzyme 5'monodeiodinase.

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. Large amount of T4 (25%) is converted to T3 in

peripheral tissues.

. Conversion takes place mainly in the Liver and

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Kidneys.

T3 formed is then released to the blood stream.

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Equal amount of "Reverse T3" may also be formed

(no biological activity).

Regulation of Thyroid Hormones

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. Thyroid hormone synthesis and secretion is

regulated by two main mechanisms:

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Regulation by the Hypothalamus and Anterior

Pituitary.

"Auto Regulation" mechanism, which reflects

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the available levels of iodine.
Regulation of Thyroid Hormones........
Auto Regulation of Thyroid Hormone production.

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. Rate of iodine uptake and incorporation into thyroglobulin is influenced by the

amount of iodide available: -

Low iodide levels increase iodine transport into follicular cells

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High iodide levels decrease iodine transport into follicular cells

Thus, there is negative feedback regulation of iodide transport by iodide.

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Regulation of Thyroid Hormones.......

. Neuroendocrine Regulation of Thyroid

hormones:

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Hypothalamo-pituitary-thyroid axis.
Regulation of Thyroid Hormones.......

. Influence of TRH:

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TRH is a hypothalamic releasing factor.

Travels through the pituitary portal system

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Act on Anterior Pituitary Thyrotrophic cells.

TRH acts through G protein-coupled receptors

Activates the IP3 (Ca2+) and DAG (PKC) pathways

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Cause increased production and release of TSH.

Regulation of Thyroid Hormones.......

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. Role of TSH-

TSH (glycoprotein) composed of two subunits:

Alpha subunit (common to LH, FSH, TSH, hCG)

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Beta subunit- specific for receptor binding and biological activity.

Action of TSH on Thyroid:

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TSH acts on fol icular cel s of the thyroid.

Increases iodide transport into fol icular cel s

Increases production and iodination of thyroglobulin

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Increases endocytosis of col oid from lumen into fol icular cel s
Regulation of Thyroid Hormones.......

.Regulation of TSH release from the anterior

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pituitary:

TSH release is influenced by-

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Hypothalamic TRH.

Thyroid hormones themselves.

Thyroid hormones exert NEGATIVE FEEDBACK on TSH

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release:

Inhibition of TSH synthesis.

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Decrease in pituitary receptors for TRH.

Regulation of Thyroid Hormones.......

.Other Factors Regulating Thyroid Hormone levels:

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Diet:

High carbohydrate diet- increases T3 levels, resulting in increased metabolic rate (diet-induced thermogenesis).

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Low carbohydrate diet- decrease T3 levels, resulting in decreased metabolic rate.

Cold Stress: increases T3 levels in other animals, but not in humans.

Any condition that increases body energy requirements (e.g., pregnancy, prolonged cold) stimulates

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hypothalamus.
Actions of Thyroid Hormones

1. Essential for normal growth of tissues, including the nervous system.

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Lack of TH during development results in short stature and mental deficits (cretinism).

2. Thyroid hormone stimulates or increase Basal Metabolic Rate(BMR).

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3. Required for GH and prolactin production and secretion

4. Required for GH action

5. Increases intestinal glucose reabsorption (glucose transporter)

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6. Increases mitochondrial oxidative phosphorylation (ATP production)

7. Increases activity of adrenal medulla (sympathetic; glucose production)

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8. Induces enzyme synthesis

Result: stimulation of growth of tissues/increased metabolic rate/Increased heat production (calorigenic effect)

Actions of Thyroid Hormones.....

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.Effects of Thyroid Hormone On Nutrient sources:

Effects on PROTEIN synthesis and degradation:

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Low level of TH- increased protein synthesis (low metabolic rate; growth)

High level- increased protein degradation (high metabolic rate; energy)

Effects on CARBOHYDRATES:

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low doses of TH- increase glycogen synthesis (low metabolic rate; storage of energy)

high doses- increase glycogen breakdown (high metabolic rate; glucose production
Actions of Thyroid Hormones.....

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.One Major Target Gene Of T3:

Na+/K+ ATPase Pump:

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o Pumps sodium and potassium across cel membranes to maintain resting membrane potential
o Activity of the Na+/K+ pump uses up energy, in the form of ATP
o About 1/3rd of al ATP in the body is used by the Na+/K+ ATPase

T3 increases the synthesis of Na+/K+ pumps, markedly increasing ATP consumption (BMR increases).

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T3 also acts on mitochondria to increase AT P synthesis (size and number of mitochondria wil increase).

The resulting increased metabolic rate increases thermogenesis (heat production).

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Actions of Thyroid Hormones.....

.Thyroid hormone actions which increase oxygen consumption

Increase mitochondrial size, number and key enzymes.

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Increase plasma membrane Na-K ATPase activity.

Increase futile(ineffective) thermogenic energy cycles.

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Decrease superoxide dismutase activity.

.Effects of thyroid hormones on the cardiovascular system

Increase heart rate

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Increase force of cardiac contractions

Increase stroke volume

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Increase Cardiac output

Up-regulate catecholamine receptors
Actions of Thyroid Hormones.....

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.Effects of thyroid hormones on the Respiratory System:

Increase resting respiratory rate

Increase minute ventilation

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Increase ventilatory response to hypercapnia and hypoxia

.Effects of thyroid hormones on the Renal System:

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Increase blood flow

Increase glomerular filtration rate(GFR)

.Effects of thyroid hormones on Oxygen-carrying Capacity:

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Increase RBC mass

Increase oxygen dissociation from hemoglobin

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Actions of Thyroid Hormones.....

. Effects of thyroid hormones on intermediary metabolism

Increase glucose absorption from the GI tract

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Increase carbohydrate, lipid and protein turnover

Down-regulate insulin receptors

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Increase substrate availability

. Effects thyroid hormones in growth and tissue development:

Increase growth and maturation of bone.

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Increase tooth development and eruption.

Increase growth and maturation of epidermis, hair fol icles and nails.

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Increase rate and force of skeletal muscle contraction.

Inhibits synthesis and increases degradation of mucopolysaccharides in subcutaneous tissue.
Thyroid function test

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Thyroid function tests

.Biochemical tests used to investigate thyroid function:

Tests that establish whether there is thyroid dysfunction-

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TSH

T4

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T3

Tests to know the cause of thyroid dysfunction-

Thyroid auto-antibody

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Serum thyroglobulin measurements

Thyroid enzyme activities
Thyroid function tests......

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. TSH:

The single most sensitive, specific and reliable test of thyroid status.

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. Total T4 and Total T3:

More than 99% of T4 and T3 circulate in plasma bound to protein.

Both change if [TBG] alters (e.g. in pregnancy).

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. Free T4 and Free T3:

Free thyroid hormone concentrations are independent of changes in TBGs.

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More reliable for diagnosis of thyroid dysfunction.

Thyroid function tests......

.Indications of TFT:

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Diagnosing thyroid disorder in symptomatic person

Screening new-born for hypothyroidism

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Monitoring thyroid replacement therapy in hypothyroidism patients

Diagnosis & monitoring female infertility patients

Screening adults for thyroid disorders

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Thyroid function tests......

. TSH:

First line test in Thyroid function tests

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Normal TSH level excludes thyroid dysfunction

Uses:

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Screening for euthyroidism

Screening of hypothyroidism in newborns

Diagnosis of 1 & 2 hypothyroidism

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Diagnosis of clinical & subclinical hyperthyroidism

Follow up of T3 & T4 replacement therapy in hypothyroidism

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Methods of TSH estimation

Radioimmunoassay/ Immunometric assay/ Chemiluminiscent & flourescent techniques.

Normal values: TSH 0.4 to 4mU/L

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Thyroid function tests......

. Total thyroxine:

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Total thyroxine includes free as well as protein bound thyroxine.

Normal levels: 5 to 12.5ug/dL, largely bound to transport protein espTBG.

. Free T4:

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Small fraction of total T4 unbound to protein

Metabolically active form and (0.05%) of total T4

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Do not get affected by TBG levels.

Measurement useful in conditions where TBG levels are affected

Normal levels: 0.89- 1.76ng/dL

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Thyroid function tests......

. Free and Total T3

Normal plasma level T3 are very low.

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Metabolical y more active, shorter half life, faster turn over.

Free T3 ? (0.5%) of total and useful with altered protein level.

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T3 level: 80 to 180ng/dl and fT3 level: 1.5 ? 4.1pg/mL.

Measured by immunoassays.

Uses:

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Diagnosis of T3 thyrotoxicosis

Early diagnosis of hyperthyroidism

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Thyroid function tests......

. Thyroglobulin:

Synthesised & secreted by thyroid follicles(30ng/ml)

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Reflects thyroid mass, thyroid injury & TSH receptor stimulation

Raised level- Grave`s disease/ Thyroiditis/ Nodular goitre

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Indications:

Monitoring recurrence of certain variants of thyroid Ca

Thyroid dysgenesis in Congenital hypothyroidism

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Follow up of patients with thyroid malignancy
Thyroid function tests......

. Thyroid Autoantibodies:

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Diagnosing autoimmune diseases

Autoantibodies-

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Anti-Tg antibody

Anti-microsomal antibody

TSH-Receptor antibody (inhibitory or stimulatory)

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non Tg colloid antigen

Thyroid function tests......

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. Anti-Tg antibodies:

Methods:

Agar gel diffusion precipitation test

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Tanned red cell haem agglutination tests(TRCH test)

ELISA/ Immunofluorescence of tissue section/ RIA

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Positive:

Hashimoto`s thyroiditis

Grave`s disease

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Myxoedema

Nontoxic goitre

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Thyroid ca

Pernicious anaemia
Thyroid function tests......

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. Anti-microsomal Abs (also k/a Anti-TPO Abs):

Methods:

CFT

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Immunofluorescence tests

TRCH assay/ ELISA/ RIA

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Positive:

Grave`s disease

Hashimoto`s thyroiditis

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More frequently positive for autoimmune diseases than Tg Ab.

Thyroid function tests......

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. Thyroid receptor antibody:

2-Types:

TBI- Grave`s disease.

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TSIgs- Grave`s disease/ Predicting relapse or remission in hyperthyroidism/ development of neonatal

hyperthyroidism.
Thyroid function tests......

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. Thyroid scan

Advantages:

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Distinguishes diffuse glandular activity from patchy pattern seen in goitre

Functional classification of nodules: Warm, Hot, Cold

In association with thyroid suppression regimes, TSH dependent or autonomous nature of hot nodules

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Information regarding size, shape, position of gland

Identification & localisation of functioning thyroid tissue in ectopic or metastatic sites

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Helps on differentiating various causes of thyrotoxicosis

Thyroid function tests......

. Thyroid scan

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Indications:

Thyroid nodule

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Diffuse or multinodular goitre

Clinical hyper- or hypothyroidism

Evaluation of substernal mass

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R/O Ectopic thyroid tissue

Subacute thyroiditis, early phase

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Contraindications:

Pregnancy

Lactation

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Thyroid function tests......

. Whole body scan I-131:

Post-operative evaluation for thyroid remnant or functioning metastasis

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Follow up patients after I-131 ablation or I-131 treatment

Serum Tg rising

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Suspected tumour recurrence

Suspected functioning metastases (either local or distant metastases)

Radiological imaging

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. Ultrasound

Scoring-

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five categories of ultrasound findings.

Higher the score

Higher the TR (TI-RADS) level

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and likelihood of malignancy.
Cytology of thyroid

. FNAC thyroid:

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Indications:

Diagnosis of diffuse non toxic goitre

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Diagnosis of solitary or dominant thyroid nodule

Confirmation of clinically obvious malignancy

Complications:

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Local haemorrhage & haematoma.

Transient laryngeal nerve paresis.

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Tracheal puncture

Rarely, needling causes formation of a hot nodule

Main limitation: Inability to distinguish between follicular adenoma & carcinoma.

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Cytology of thyroid....

.FNAC thyroid

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Procedure:

Materials-

? Syringes & syringe holder(pistol)

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? 22-25 gauge needle

? Cotton Swabs

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? Alcohol bottles for wet fixation
Cytology of thyroid....

. FNAC thyroid:

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Smearing, fixation & staining

Rapid smearing

Air dried stained with giemsa

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Alcohol fixed smears stained with Pap

Sample adequacy

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Six groups of fol icular cel s

Each containing 10 to 20 cel s on two separate slides