Production of Thyroid HormonesNIS (Na+/I- Sympoter)

TPO

Thyroid gland secretes tri and tetra –iodo thyronine also called as T3 and T4.

Derived from tyrosine on de-iodination.

Functions of thyroid hormones.

Necessary for proper functioning of almost all cells in our body and for biological processes.

Calorigenic effect or thermogenesis.

T4 stimulates RNA synthesis and thereby protein synthesis.

B. Functions of thyroid hormones

I. Increase BMR ( Basal Metabolic Rate )

↑cellular metabolic activity by :

• ↑ size, total membrane surface & number of mitochondria

• ↑ ATP formation

• ↑ active transport of ions ( Na+, K+ )

II. Promote growth & development of the brain during fetal life and for the first few years of postnatal life.

Transport of thyroid hormones

T4 and T3 are transported in blood by binding to plasma proteins called thyroxine binding globulin.

The bound form is biologically inactive.And FREE form is active. 

Thyroxine binding globulin carries 80% of T4 and 60% of T3.

Regulation of thyroid hormones.

TSH secretions are controlled by‐ Circulating levels of thyroid hormones.‐ Thyrotropinreleasing hormones.

Hypothalamic –pituitary –thyroid hormone axis is involved in feed back control.  

ASSESSMENT OF THYROID FUNCTION.

Measurement of T4 and T3  by ELISA.

Hyper thyroidism – both T4 and T3 are increased and TSH is decreased.

Hypothyroidism – bothT4 and T3 are decreased and TSH is increased due to feed back inhibition.

When hypothyroidism is due to hypothalamic or pitutary causes TSH,T4 and T3 are all decreased.

Normal T4 and T3 values.T4 = 5 to 12.5 μgm/dl.T3 =70 to200 η gm/dl.

Estimation of free serum T3 and T4 :

Free serum T3andT4 in blood not bound to proteins is independent of changes in(TBG ).

It provides more reliable diagnosis of thyroid dysfunction than measurement of total T4and T3.

Free T4 = 10 – 27 pmol/lFree T3=    3‐ 9   pmol/l

Clinical interpretation: 

↑ values are assosciated with hyper thyroidism andthyrotoxicosis.

↓ Hypothyroidism.

Thyroxin binding globulin: Almost all thyroid hormones are bound to protein, TBG.TBG conc affects total plasma conc of T4and T3.Normal values of TBG12‐ 28micro gm/dl. 

TBG level is increased in:- Hypothyroidism- Pregnancy- Oestrogen therapyTBG level is decresed in :- Hyperthyroidism-Nephrotic syndrome- Liver disease.

Resin  Uptake Test:

Labelled hormone 125I  T3 is used.T3 uptake is % of labelled hormone taken up by resin and is inversely related to unoccupied binding sites onTBG.Serum Thyroid stimulating hormone(TSH)Most sensitive ,specific and reliable test of thyroid status.Anterior pitutary TSH      release of stored thyroid hormones.

Normal values of serum TSH2 – 6 micro units/ml.Clinical interpretation:Increased levels are seen in primary hypothyroidism due to absence of negetaive feed back control on pitutary.Decreased levels are seen inPrimary(thyroid gland failure)Secondary (anterior pitutary failure)Tertiary (hypothalamic failure).

THYROID ANTIBODIES

Measuring thyroid antibodies helps to demonstrate presence of auto immune disorders.Thyroid peroxidase and thyroglobulins -

Hashimato’s thyroiditis and Grave’s disease.

Thyroid scanning :Ultra sound sonographyCT scanMRI scan

For the presence of thyroid mass ,cysts and solid tumours.

Hyperthyroidism(Toxic Goitor, Thyrotoxicosis, Graves’ disease )Causes : hyperplasia

long-acting thyroid stimulator (LATS)( globulin antibody )

Symptoms : intolerance to heat increase sweatingdiarrhea muscle weakness nervousness psychic disordersextreme fatigue tremor of the hand

“ Exophthalmos” ( protrusion of the eyeballs ) :edematous swelling of the retro-orbital tissues and

degeneration of the extraocular muscle

Diagnosis

(1) free thyroxine

(2) BMR

(3) rate of uptake of iodine

(4) PBI ( protein binding iodine )

(5) TPO Ab, Tg AB, TSH-R[stim] Ab, TSH-R[block] Ab

Treatment

(1) surgical removal of the thyroid gland

(2) antithyroid drug: propylthiouracil

HypothyroidismCauses : endemic goiters

idiopathic nontoxic colloid goiter

Symptoms : extreme somnolence ( 14-16 hrs/day )

cretinism ( infant or childhood )depressed growth of hair & scaliness of the skinmuscle sluggishness constipation

slow heart rate mental sluggishness↓cardiac output frog-like husky voice↓blood volume arterosclerosis↑ body weight myxedema

Diagnosis : same as hyperthyroidism

Treatment : thyroid extract

Goiter

Low T3 & T4

Excess TSH

Negative feedback

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