Thyroid Function

Biosynthesis, Secretion, And Transport of Thyroid hormones Iodine is the most important element in the biosynthesis of thyroid hormones. Thyroglobulin acts as a performed matrix containing tyrosyl groups to which the reactive iodine attaches to form the hydroxyl residues of monoiodotyrosine (MIT) and diiodotyrosine (DIT). The coupling of two DIT molecules forms T 4. The coupling of one DIT molecules and one MIT molecule results in the formation of T 3 or reverse T 3 (rT 3 ) Almost all circulating T 4 and T 3 hormones are bound to serum proteins ( thyroid hormone-binding proteins )

Only 0.03 % of T4 and 0.3 % of T3 are not bound to proteins. These fractions, called free T4 (FT4) and free T3 (FT3), are the physiologically active portions of the thyroid hormones. T3 is the most biologically active thyroid hormone and is three to four times more potent than T4. T3 is more active because it is not as tightly bound to the serum proteins as is T4, and has a greater affinity to target tissue receptors

Actions of thyroid hormone Regulation of carbohydrate, lipid, and protein metabolism. Central nervous system activity and brain development Cardiovascular stimulation Bone and tissue growth and development Gastrointestinal regulation Sexual maturation

Thyroid function tests Specimen collection : Specimens are routinely collected in a clot tube, although anticoagulants can be used. Specimens free of lipemia or hemolysis are preferred. The tests used to investigate thyroid function can be grouped into: Tests that establish whether there is thyroid dysfunction ( TSH,T4 and T3 measurements) Tests to know the cause of thyroid dysfunction (thyroid auto-antibody and serum thyroglobulin measurements, thyroid enzyme activities, biopsy of the thyroid, ultrasound and isotopic thyroid scanning ) (thyroid auto-antibody and serum thyroglobulin measurements, thyroid enzyme activities, biopsy of the thyroid, ultrasound and isotopic thyroid scanning )

TSH : TSH : - The single most sensitive, specific and reliable test of thyroid status. - The single most sensitive, specific and reliable test of thyroid status. - In primary hypothyroidism, [TSH] is increased. - In primary hypothyroidism, [TSH] is increased. - In primary hyperthyroidism, [TSH] is decrease or undetectable - In primary hyperthyroidism, [TSH] is decrease or undetectable Total T4 and Total T3 : Total T4 and Total T3 : - More than 99% of T4 and T3 circulate in plasma bound to protein - More than 99% of T4 and T3 circulate in plasma bound to protein - Both [total T4] and [total T3] change if [TBG] alters, e.g. in pregnancy - Both [total T4] and [total T3] change if [TBG] alters, e.g. in pregnancy Free T4 and Free T3 Free T4 and Free T3 Free thyroid hormone concentrations are independent of changes in the concentration of thyroid-hormone binding proteins → more reliable for diagnosis of thyroid dysfunction Free thyroid hormone concentrations are independent of changes in the concentration of thyroid-hormone binding proteins → more reliable for diagnosis of thyroid dysfunction

Interpreting results of thyroid function tests Primary hyperthyroidism - Plasma [TSH] : ↓ due to feedback inhibition on the pituitary - Plasma [TSH] : ↓ due to feedback inhibition on the pituitary - Plasma free and total T4 and T3 concentrations : ↑ - Plasma free and total T4 and T3 concentrations : ↑ In a very small percentage of hyperthyroid patients, plasma [total T4] and [freeT4] are both normal, whereas both plasma [total T3] and [freeT3] are increased ; this condition is known as In a very small percentage of hyperthyroid patients, plasma [total T4] and [freeT4] are both normal, whereas both plasma [total T3] and [freeT3] are increased ; this condition is known as T3 hyperthyroidism or T3 thyrotoxicosis. T3 hyperthyroidism or T3 thyrotoxicosis.

Primary hypothyroidism : Plasma [TSH] : ↑ Plasma [free T4] and [total T4] : ↓ Plasma free T3 and total T3 measurements are of no value here, since normal concentrations are often observed.

Sub clinical primary thyroid disease Plasma [TSH] : abnormal Thyroid hormone levels : normal [TSH] : low → sub clinical hyperthyroidism [TSH] : elevated → sub clinical hypothyroidism Before the diagnosis of sub clinical thyroid disease can be made, causes of an abnormal plasma [TSH] other than thyroid disease must be excluded eg : - pregnancy eg : - pregnancy - drug treatment - drug treatment

Secondary thyroid disorders Central (pituitary) hypothyroidism : [TSH] & thyroid hormone levels → low [TSH] & thyroid hormone levels → low Hyperthyroidism due to a TSH-secreting tumor very rarely very rarely Plasma TSH is widely used to screen for congenital hypothyroidism in the neonate Plasma TSH is widely used to screen for congenital hypothyroidism in the neonate ( the incidence about one in 4000 live births) ( the incidence about one in 4000 live births)