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THYROID FUNCTION TESTS. CASE D. Alison Wong Meme Phung Zhi Yuan Quek. CASE. Mr. AR, aged 55 years Recently been prescribed amiodarone as treatment for atrial tachyarrhythmia Medications on a regular basis: - Digoxin 62.5 mcg 3 mane - Warfarin 4 mg d as directed. AMIODARONE.
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THYROID FUNCTION TESTS CASE D Alison Wong Meme Phung Zhi Yuan Quek
CASE • Mr. AR, aged 55 years • Recently been prescribed amiodarone as treatment for atrial tachyarrhythmia • Medications on a regular basis: - Digoxin 62.5 mcg 3 mane - Warfarin 4 mg d as directed
AMIODARONE • Remarkable structural resemblance to thyroid hormones • Iodine-rich benzofuran derivative • 37% by weight is organic iodine
EFFECTS OF AMIODARONE ON THYROID FUNCTION • Effects on thyroid physiology • peripheral 5’-deiodination of thyroxine (T4)to triiodothyronine (T3) • in the serum levels of T4 and rT3 and a in the serum levels of T3 • entry of T4 and T3 into peripheral tissue inhibited
early phase of treatment, thyroid-stimulating hormone (TSH) levels also in response to the T3 levels • as treatment continues, the serum TSH levels often fall back to normal as the total T4 concentration rises
Changes in thyroid function test results with development of hyperthyroidism and hypothyroidism
Amiodarone-induced thyrotoxicosis • excessive synthesis of thyroid hormone induced by iodine • excessive in T4 level alone may not be diagnostic • diagnosis straightforward if T3 or FT3 and TSH suppressed • onset of thyrotoxicosis in T4 levels, in T3 levels and a dramatic in TSH levels
suppression of TSH levels possible in subclinical episodes • single abnormal TSH insufficient • subclinical episodes represented by suppressed TSH, T3 & FT3 at lower end of reference range, T4 or FT4
Amiodarone-induced hypothyroidism • iodide released by amiodarone metabolism inhibits thyroid hormone biosynthesis and release • subclinical hypothyroidism moderately TSH levels • additional tests needed • diagnosis confirmed by TSH with low T4 or FT4 • low T3 or FT3 unreliable indicator
CONCERNS • Digoxin and Amiodarone - digoxin toxicity • Warfarin and Amiodarone - increased risk of bleeding
THYROID BINDING GLOBULIN (TBG) • Analytical protocols for measurement of TBG • Clinical applications of measuring TBG in evaluating thyroid function.
T3 and T4 • Poorly soluble in plasma • Transported primarily by TBG • TBG = a plasma protein that carries 70-75% of circulating T4 and T3. • Remaining 25-30% of T4 transported by albumin and prealbumin. • T3 no affinity for prealbumin and circulates only with TBG and albumin.
Thyroid Hormone Transport Thyroid binding Globulin Bound T3 and T4 Serum Less than 1% Cell Equilibrium between bound and free hormone exists
Bound T3 inactive • Free T3 active • Bound and free hormone exist in equilibrium
T4 higher affinity for TBG in plasma than T3. 99.95% bound, ~0.05% free • Total T4 is a direct measure of T4 • Estimate of total T4 • approximated by amount of bound thyroxine Under conditions with normal TBG concentrations, the total T4 level reflects the functional state of the thyroid.
PROBLEMS WITH TBG MEASUREMENTS • Changes in TBG levels : will dramatically alter the total T4 concentration, without affecting the unbound freeT4 level. do not reflect a change in thyroid status equilibrium between the free and bound hormones is maintained • remain euthyroid by the normal free thyroid hormone and TSH concentrations • patient may be physiologically normal but have an abnormal total serum T4 level
There are several conditions that can affect ( or ) TBG levels.
CONDITIONS ASSOCIATED WITH INCREASED TBG SYNTHESIS AND PLASMA LEVELS • Oestrogen effects – pregnancy, oral contraceptives • Infectious Hepatitis • Biliary cirrhosis • Genetic determination - increased genetically by an X-linked abnormality
CONDITIONS ASSOCIATED WITH DECREASED TBG SYNTHESIS AND PLASMA LEVELS • Severe liver disease • Androgens and anabolic steroids • High doses of glucocorticoids • Large doses of phenytoin, aspirin and their derivatives • Nephrotic syndrome • Genetic determination
T3 RESIN UPTAKE (T3RU) • Measures the amount of unsaturated binding sites on the thyroid hormone transport proteins • Provides an indirect estimate of the binding capacity of the plasma thyroid-binding proteins
Proportion of labelled T3 will bind to available sites on the serum TBG; excess will bind to the resin • resin uptake is inversely proportional to the total TBG • 80% sensitivity for hyperthyroidism • 50-60% sensitivity for hypothyroidism
T3U VALUES • %T3U = camp/cpmR X %T3UR • Typical values for %T3U are 25-30% • Increased Values = Hyperthyroidism • Decreased Values = Hypothyroidism
FREE THYROXINE INDEX (FTI) • Is a reflection of the amount of free T4 • A calculated value correct for changes in TBG concentrations • FTI = (Total T4) X (T3 Resin Uptake) (T4 RU Control)
FTI • Normal FTI: euthyroid subjects, pregnancy, women taking estrogens, patient with nephrosis or hepatitis and persons taking drugs that elevate T3U • Increased FTI: hyperthyroidism • Decreased FTI: hypothyroidism