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THYROID FUNCTION TESTS
Numan Sikandar
THYROIDFUNCTIONTESTS
 Biochemical tests for diagnosis of a thyroid disorder are called as thyroid function
tests. The first-line tests are serum TSH, total T4 or free T4, and total T3 and free
T3
 Assessment of thyroid hormone secretion can be made by measuring plasma TSH
as well as either fT4 or total T4 [sometimes also free T3 (fT3 ) or total T3 ]. Each
test has its advantages and disadvantages, although probably most laboratories
now offer fT4 and fT3 assays rather than total hormone concentrations.
 A variety of non-thyroidal diseases can alter the results of thyroid function tests in
patients with normal thyroid status. These disorders include infections, liver
disease, malignancy, trauma, surgery, renal failure, and cardiac failure. To avoid
misinterpretation, thyroid function tests should not be performed during an acute
non-thyroidal illness
Plasma thyroid-stimulatinghormone
 The measurement of plasma TSH provides the single most sensitive, specific and reliable test of
thyroid status.
 Concentrations of TSH are high in primary hypothyroidism and low in secondary or pituitary
hypothyroidism.
 In hyperthyroidism, high plasma T4 and T3 concentrations suppress TSH release from the
pituitary, resulting in very low or undetectable plasma TSH concentrations.
 Plasma TSH assays are used as first-line assays for thyroid function assessment.
NORMALRANGES OF TSH:
0.3 – 5.0 mIU/L
 When T4 and T3 are too high TSH secretion Decreases.
 When T4 and T3 are too low TSH secretion Increases.
 In primary hypothyroidism TSH level is elevated.(bcz of lack of feedback effect)
 In primary hyperthyroidism TSH level is decreased.(due to negative feedback by T3 and T4)
 In secondary hypothyroidism TSH level is decreased
 In secondary hyperthyroidism TSH level is increased
CLINICAL INTERPRETATION OF TSH
 CAUSES OF INCREASED TSH IN BLOOD:
❖ Hypothyroidism
❖ Hashimotothyroiditis
❖ Pituitary gland tumor
❖ Insufficient dose of thyroid hormone
 CAUSES OF DECREASED TSH IN BLOOD:
❖ Excess dose of thyroid hormone
❖ Goiter
❖ Pituitary gland disorder
❖ Grave’s disease
Plasmatotalthyroxineorfree thyroxineassays
 Plasma T4 is more than 99 per cent protein bound; therefore, plasma total T4 assays
reflect the protein bound rather than the free hormone fraction.
 Total T4 reflects fT4 concentrations, unless there are abnormalities of binding proteins.
 In the euthyroid state, about a third of the binding sites on TBG are occupied by T4
and the remainder are unoccupied, irrespective of the concentration of the binding
protein.
 In hyperthyroidism, both plasma total and fT4 concentrations are increased and the
number of unoccupied binding sites on TBG is decreased.
 In hypothyroidism, the opposite of the above occurs.
 Free thyroid hormone concentrations provide more reliable means of diagnosing
thyroid dysfunction than measurement of total serum T3 and T4.
Free thyroxine TSH levels High TSH levels Low
High Secondary hyperthyroidism primary hyperthyroidism
low primary hypothyroidism secondary hypothyroidism
NORMAL RANGE FOR T4:
Total T4: 5.0-12.0 ug/dl
free T4: 9-16 pmol/L
CONDITION NORMAL HYPERTHYROIDISM HYPOTHYROIDISM
PRIMARY
HYPOTHYROIDISM
SECONDARY
TSH normal low high low
T4 normal high low low
Plasma totalorfreetri-iodothyronine
 Total T3 or fT3 concentrations may help in the diagnosis of hyperthyroidism but are
not usually used routinely to diagnose hypothyroidism because normal plasma
concentrations are very low. In hyperthyroidism, the increase in plasma T3 or fT3
concentrations is greater, and usually occurs earlier than that of T4 or fT4 .
 Occasionally in hyperthyroidism the plasma T3 or fT3 concentrations are elevated
but not those of T4 or fT4 (T3 toxicosis). Like T4 , T3 is bound to protein. It is usually
preferable to measure the plasma concentration of fT3 rather than total T3 , as the
latter may be altered by changes in the plasma concentrations of TBG
 NORMAL RANGE FOR T3:
Total T3 : 70 -200 ng/dL
free T3 : 3.7-6.5 pmol/L
SERUM TOTAL T4AND T3
 Changes in total thyroid hormone concentration are far less sensitive indices
of thyroid function than is TSH; for this reason they shouldnot be measured
alone.
 The concentration of total serum thyroxine can be affected by changes in
the concentration of thyroid binding globulin TBG, in the absence of thyoid
disease.
 Because more than 99.9 % of thyroid hormone is protein bound.
 Serum total T4 and T3 are clinically meaningful only if the functional levels of
thyroid –binding proteins in blood are known.
 This test is a good index of thyroid function whenTBG is normal.
CLINICAL INTERPRETATION OF T3 ANDT4
 CAUSES OF INCREASED T4 AND T3 IN BLOOD:
❖ Hyperthyroidism
❖ Grave’s disease
❖ Goiter
❖ Thyroiditis
❖ Overdose of thyroxine replacement therapy
❖ Increased concentration of TBG (as in pregnancy and with estrogen therapy).
 CAUSES OF DECREASED T4 AND T3 IN BLOOD:
❖ Hypothyroidism
❖ Thyroiditis
❖ Pituitary gland disorder
❖ Thyroid surgery
❖ Thyroid radiation treatment
❖ Decreased concentration of TBG (as in nephrosis due to loss of TBG in urine and in liver disease in
which there is a decreased synthesis of TBG)
Thyrotrophin-releasinghormonetest
 The TRH test is used to confirm the diagnosis of secondary hypothyroidism, or
occasionally to diagnose early primary hypothyroidism. Since the development of
sensitive TSH assays, it is rarely used to diagnose hyperthyroidism, although it may
have a place in the differential diagnosis of thyroid resistance syndrome or TSH-
secreting pituitary tumours (TSHomas).
 In hypothyroidism TRH stimulation causes release of high levels of TSH
 In hyperthyroidism feedback inhibition by high levels of thyroid hormones
surpasses the stimulating effect of TRH on TSH, resulting in blunted TSH response.
 BMR is increased in hyperthyroidism and decreased in hypothyroidism.
 Serum cholesterol levels are decreased in hyperthyroidism and are increased in
hypothyroidism.
Total T4 Total T3 ft4 ft4 TBG TSH
Euthyroid normal normal normal normal normal normal
Hyper thyroid inc inc inc inc normal Dec if pri
inc if sec
T3toxicosis normal inc normal inc normal dec
Hypo thyroid dec dec dec dec normal Inc if pri
dec if sec
TBG Excess inc inc normal normal inc normal
TBG Defici dec dec normal normal dec normal
T4 displacement
by drug
dec normal Nor/dec normal normal normal
STRATEGY FOR THYROID FUNCTION TESTING AND
INTERPRETATION
Test results Interpretations
TSH Normal, FT4 Normal Euthyroid
Low TSH, Low FT4 Secondary hypothyroidism
High TSH, Normal FT4 Subclinical hypothyroidism
High TSH, Low FT4 Primary hypothyroidism
Low TSH, Normal FT4, Normal FT3 Subclinical
Low TSH, Normal FT4, High FT3 T3 toxicosis
Low TSH, High FT4 Primary hyperthyroidism
Thyroid Function Tests and clinical interpretation

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Thyroid Function Tests and clinical interpretation

  • 2. THYROIDFUNCTIONTESTS  Biochemical tests for diagnosis of a thyroid disorder are called as thyroid function tests. The first-line tests are serum TSH, total T4 or free T4, and total T3 and free T3  Assessment of thyroid hormone secretion can be made by measuring plasma TSH as well as either fT4 or total T4 [sometimes also free T3 (fT3 ) or total T3 ]. Each test has its advantages and disadvantages, although probably most laboratories now offer fT4 and fT3 assays rather than total hormone concentrations.  A variety of non-thyroidal diseases can alter the results of thyroid function tests in patients with normal thyroid status. These disorders include infections, liver disease, malignancy, trauma, surgery, renal failure, and cardiac failure. To avoid misinterpretation, thyroid function tests should not be performed during an acute non-thyroidal illness
  • 3. Plasma thyroid-stimulatinghormone  The measurement of plasma TSH provides the single most sensitive, specific and reliable test of thyroid status.  Concentrations of TSH are high in primary hypothyroidism and low in secondary or pituitary hypothyroidism.  In hyperthyroidism, high plasma T4 and T3 concentrations suppress TSH release from the pituitary, resulting in very low or undetectable plasma TSH concentrations.  Plasma TSH assays are used as first-line assays for thyroid function assessment. NORMALRANGES OF TSH: 0.3 – 5.0 mIU/L  When T4 and T3 are too high TSH secretion Decreases.  When T4 and T3 are too low TSH secretion Increases.  In primary hypothyroidism TSH level is elevated.(bcz of lack of feedback effect)  In primary hyperthyroidism TSH level is decreased.(due to negative feedback by T3 and T4)  In secondary hypothyroidism TSH level is decreased  In secondary hyperthyroidism TSH level is increased
  • 4. CLINICAL INTERPRETATION OF TSH  CAUSES OF INCREASED TSH IN BLOOD: ❖ Hypothyroidism ❖ Hashimotothyroiditis ❖ Pituitary gland tumor ❖ Insufficient dose of thyroid hormone  CAUSES OF DECREASED TSH IN BLOOD: ❖ Excess dose of thyroid hormone ❖ Goiter ❖ Pituitary gland disorder ❖ Grave’s disease
  • 5. Plasmatotalthyroxineorfree thyroxineassays  Plasma T4 is more than 99 per cent protein bound; therefore, plasma total T4 assays reflect the protein bound rather than the free hormone fraction.  Total T4 reflects fT4 concentrations, unless there are abnormalities of binding proteins.  In the euthyroid state, about a third of the binding sites on TBG are occupied by T4 and the remainder are unoccupied, irrespective of the concentration of the binding protein.  In hyperthyroidism, both plasma total and fT4 concentrations are increased and the number of unoccupied binding sites on TBG is decreased.  In hypothyroidism, the opposite of the above occurs.  Free thyroid hormone concentrations provide more reliable means of diagnosing thyroid dysfunction than measurement of total serum T3 and T4.
  • 6. Free thyroxine TSH levels High TSH levels Low High Secondary hyperthyroidism primary hyperthyroidism low primary hypothyroidism secondary hypothyroidism NORMAL RANGE FOR T4: Total T4: 5.0-12.0 ug/dl free T4: 9-16 pmol/L CONDITION NORMAL HYPERTHYROIDISM HYPOTHYROIDISM PRIMARY HYPOTHYROIDISM SECONDARY TSH normal low high low T4 normal high low low
  • 7. Plasma totalorfreetri-iodothyronine  Total T3 or fT3 concentrations may help in the diagnosis of hyperthyroidism but are not usually used routinely to diagnose hypothyroidism because normal plasma concentrations are very low. In hyperthyroidism, the increase in plasma T3 or fT3 concentrations is greater, and usually occurs earlier than that of T4 or fT4 .  Occasionally in hyperthyroidism the plasma T3 or fT3 concentrations are elevated but not those of T4 or fT4 (T3 toxicosis). Like T4 , T3 is bound to protein. It is usually preferable to measure the plasma concentration of fT3 rather than total T3 , as the latter may be altered by changes in the plasma concentrations of TBG  NORMAL RANGE FOR T3: Total T3 : 70 -200 ng/dL free T3 : 3.7-6.5 pmol/L
  • 8. SERUM TOTAL T4AND T3  Changes in total thyroid hormone concentration are far less sensitive indices of thyroid function than is TSH; for this reason they shouldnot be measured alone.  The concentration of total serum thyroxine can be affected by changes in the concentration of thyroid binding globulin TBG, in the absence of thyoid disease.  Because more than 99.9 % of thyroid hormone is protein bound.  Serum total T4 and T3 are clinically meaningful only if the functional levels of thyroid –binding proteins in blood are known.  This test is a good index of thyroid function whenTBG is normal.
  • 9. CLINICAL INTERPRETATION OF T3 ANDT4  CAUSES OF INCREASED T4 AND T3 IN BLOOD: ❖ Hyperthyroidism ❖ Grave’s disease ❖ Goiter ❖ Thyroiditis ❖ Overdose of thyroxine replacement therapy ❖ Increased concentration of TBG (as in pregnancy and with estrogen therapy).  CAUSES OF DECREASED T4 AND T3 IN BLOOD: ❖ Hypothyroidism ❖ Thyroiditis ❖ Pituitary gland disorder ❖ Thyroid surgery ❖ Thyroid radiation treatment ❖ Decreased concentration of TBG (as in nephrosis due to loss of TBG in urine and in liver disease in which there is a decreased synthesis of TBG)
  • 10. Thyrotrophin-releasinghormonetest  The TRH test is used to confirm the diagnosis of secondary hypothyroidism, or occasionally to diagnose early primary hypothyroidism. Since the development of sensitive TSH assays, it is rarely used to diagnose hyperthyroidism, although it may have a place in the differential diagnosis of thyroid resistance syndrome or TSH- secreting pituitary tumours (TSHomas).  In hypothyroidism TRH stimulation causes release of high levels of TSH  In hyperthyroidism feedback inhibition by high levels of thyroid hormones surpasses the stimulating effect of TRH on TSH, resulting in blunted TSH response.  BMR is increased in hyperthyroidism and decreased in hypothyroidism.  Serum cholesterol levels are decreased in hyperthyroidism and are increased in hypothyroidism.
  • 11. Total T4 Total T3 ft4 ft4 TBG TSH Euthyroid normal normal normal normal normal normal Hyper thyroid inc inc inc inc normal Dec if pri inc if sec T3toxicosis normal inc normal inc normal dec Hypo thyroid dec dec dec dec normal Inc if pri dec if sec TBG Excess inc inc normal normal inc normal TBG Defici dec dec normal normal dec normal T4 displacement by drug dec normal Nor/dec normal normal normal STRATEGY FOR THYROID FUNCTION TESTING AND INTERPRETATION
  • 12. Test results Interpretations TSH Normal, FT4 Normal Euthyroid Low TSH, Low FT4 Secondary hypothyroidism High TSH, Normal FT4 Subclinical hypothyroidism High TSH, Low FT4 Primary hypothyroidism Low TSH, Normal FT4, Normal FT3 Subclinical Low TSH, Normal FT4, High FT3 T3 toxicosis Low TSH, High FT4 Primary hyperthyroidism