EndocrinologyEndocrinology

Thyroid Function TestsThyroid Function TestsCase FCase F

Tu NguyenTu NguyenTuan TranTuan TranThi TrangThi Trang

Patient InformationPatient Information

Ms FF, aged in her late thirties, presSents Ms FF, aged in her late thirties, presSents withwith history of weight gain, tiredness, history of weight gain, tiredness, neck discomfort and goitre. Initial TFT neck discomfort and goitre. Initial TFT results were as follows:results were as follows:

TestsTests ResultsResults Recommended Recommended RangeRange

FT4FT4 10 pmol/L10 pmol/L 10 – 25 pmol/L10 – 25 pmol/L

FT3FT3 4.2 pmol/L4.2 pmol/L 3 – 8 pmol/L3 – 8 pmol/L

TSHTSH 45 mU/L45 mU/L 3 – 9 mU/L3 – 9 mU/L

QuestionsQuestions

Do these results reflect the diagnosis of Do these results reflect the diagnosis of Hashimoto’s thyroiditis. Is Ms FF Hashimoto’s thyroiditis. Is Ms FF hypothyroid?hypothyroid?

Explain whether measurements of all her Explain whether measurements of all her initial TFTs were warranted?initial TFTs were warranted?

Describe the approaches to measurement of Describe the approaches to measurement of autoantibodies in the evaluation of thyroid autoantibodies in the evaluation of thyroid function and the application of these results function and the application of these results in the diagnosis of thyroid dysfunction.in the diagnosis of thyroid dysfunction.

What is Hashimoto’s What is Hashimoto’s Thyroiditis?Thyroiditis?

Discovered by Dr Hakaru Hashimoto in Discovered by Dr Hakaru Hashimoto in 19121912Thyroiditis is inflammation of the thyroid Thyroiditis is inflammation of the thyroid glandglandHashimoto thyroiditis is the most common Hashimoto thyroiditis is the most common form of thyroiditisform of thyroiditisIt is an autoimmune disorder resulting in It is an autoimmune disorder resulting in gradual destruction of thyroid glandgradual destruction of thyroid gland

Common Symptoms of Common Symptoms of Hashimoto’s ThyroiditisHashimoto’s Thyroiditis

Patients may be asymptomatic but may Patients may be asymptomatic but may complain of:complain of:

fatiguefatigue

muscle weaknessmuscle weakness

weight gainweight gain

enlarged thyroid = goitreenlarged thyroid = goitre

Common Clinical FindingsCommon Clinical Findings

Definitive indicator of Hashimoto’s Definitive indicator of Hashimoto’s thyroiditis is the presence of thyroid – thyroiditis is the presence of thyroid – specific autoantibodies in the serumspecific autoantibodies in the serumTFTs can be normal but presence of high TFTs can be normal but presence of high antimicrosomal and less commonly antimicrosomal and less commonly antithyroglobulin in serumantithyroglobulin in serumTFTs abnormal (eg elevated TSH) with TFTs abnormal (eg elevated TSH) with presence of autoantibodiespresence of autoantibodies

Common Clinical FindingsCommon Clinical Findings

Do these results reflect the diagnosis of Do these results reflect the diagnosis of Hashimoto’s thyroiditis? Hashimoto’s thyroiditis?

YESYES

Is Ms FF hypothyroid? Is Ms FF hypothyroid? YESYES

Were the measurements of all Were the measurements of all the initial TFTs warranted?the initial TFTs warranted?

Thyroid Stimulating Hormone Thyroid Stimulating Hormone (TSH)(TSH)

TSH is the most valuable thyroid function TSH is the most valuable thyroid function test (according to the American test (according to the American Association of Clinical Endocrinologists)Association of Clinical Endocrinologists)

Detect primary and central Detect primary and central hypothyroidism and hyperthyroidism in hypothyroidism and hyperthyroidism in neonatal screeningneonatal screening

Free Thyroxine (FT4)Free Thyroxine (FT4)

Gives a more accurate measure of thyroid Gives a more accurate measure of thyroid function when the thyroid function status function when the thyroid function status is rapidly changingis rapidly changing

Hypothyroidism is detected by low to Hypothyroidism is detected by low to normal FT4 with elevated TSH levelsnormal FT4 with elevated TSH levels

Hyperthyroidism is detected by elevated Hyperthyroidism is detected by elevated FT4 with low TSH levelsFT4 with low TSH levels

Free Triiodothyronine (FT3)Free Triiodothyronine (FT3)

Gives a measure of thyroid functionGives a measure of thyroid function

Used in diagnosis of hyperthyroidismUsed in diagnosis of hyperthyroidism

Hyperthyroidism is detected by elevated Hyperthyroidism is detected by elevated FT3 with low TSH levelsFT3 with low TSH levels

Diagnosis of Thyroid FunctionDiagnosis of Thyroid Function

The first diagnostic The first diagnostic test is the measure of test is the measure of TSHTSH

If TSH is low, further If TSH is low, further tests of FT4 and FT3 tests of FT4 and FT3 are requiredare required

if FT4 or FT3 is if FT4 or FT3 is elevated then the elevated then the diagnosis is diagnosis is hyperthyroidism hyperthyroidism

HyperthyroidismHyperthyroidism

TSHTSH

FT4FT4

FT3FT3

Diagnosis of Thyroid FunctionDiagnosis of Thyroid Function

If TSH is elevated, If TSH is elevated, further test of FT4 is further test of FT4 is requiredrequired

if FT4 is low to normal if FT4 is low to normal then the diagnosis is then the diagnosis is primary primary hypothyroidism hypothyroidism (Hashimoto’s (Hashimoto’s Thyroiditis) Thyroiditis)

Primary Primary HypothyroidismHypothyroidism

TSHTSH

FT4FT4

Diagnosis of Thyroid FunctionDiagnosis of Thyroid Function

If TSH is normal or If TSH is normal or low and FT4 is low low and FT4 is low then diagnosis is then diagnosis is secondary secondary hypothyroidism (due hypothyroidism (due to pituitary or to pituitary or hypothalamic disease)hypothalamic disease)

Secondary Secondary HypothyroidismHypothyroidism

TSHTSH

FT4FT4

Diagnosis for Mrs FFDiagnosis for Mrs FF

Mrs FF has elevated TSHMrs FF has elevated TSH

Therefore need to test for FT4Therefore need to test for FT4

Mrs FF also has normal FT4Mrs FF also has normal FT4

Therefore Mrs FF was diagnosed with Hashimoto’s Therefore Mrs FF was diagnosed with Hashimoto’s thyroiditis (primary hypothyroidism)thyroiditis (primary hypothyroidism)

Therefore only TSH and FT4 tests would be needed to Therefore only TSH and FT4 tests would be needed to warrant Mrs FF’s diagnosis of Hashimoto’s Thyroiditiswarrant Mrs FF’s diagnosis of Hashimoto’s Thyroiditis

TestsTests ResultsResults Recommended Recommended RangeRange

FT4FT4 10 pmol/L10 pmol/L 10 – 25 pmol/L10 – 25 pmol/L

FT3FT3 4.2 pmol/L4.2 pmol/L 3 – 8 pmol/L3 – 8 pmol/L

TSHTSH 45 mU/L45 mU/L 3 – 9 mU/L3 – 9 mU/L

Describe approaches to the Describe approaches to the measurement of thyroid measurement of thyroid

autoantibodies in the autoantibodies in the evaluation of thyroid function evaluation of thyroid function and the application of these and the application of these results in diagnosis of the results in diagnosis of the

nature of the thyroid functionnature of the thyroid function

Screening for thyroid Screening for thyroid autoimmunityautoimmunity

Determination of thyroid peroxidase Determination of thyroid peroxidase antibodies (TPOAb)antibodies (TPOAb)

Determination of thyroglobulin antibodies Determination of thyroglobulin antibodies (TgAb)(TgAb)

Are measure to confirmAre measure to confirm or rule out or rule out autoimmune diseaseautoimmune disease

Screening for thyroid Screening for thyroid autoimmunityautoimmunity

TPOAb and TgAb determination helps to TPOAb and TgAb determination helps to distinguish individuals with thyroid distinguish individuals with thyroid autoimmunity from patients with non-autoimmunity from patients with non-thyroid autoimmune diseases such as:thyroid autoimmune diseases such as:

Addison’s disease Addison’s disease Grave’s diseaseGrave’s diseaseHashimoto’s thyroiditisHashimoto’s thyroiditisType 1 diabetesType 1 diabetes

Differential diagnosisDifferential diagnosis

Presence of thyroid peroxidase Ab Presence of thyroid peroxidase Ab associate with: associate with:

Thyroid autoimmune disease Thyroid autoimmune disease

Focal thyroiditisFocal thyroiditis

Presence of thyroid peroxide Ab + Presence of thyroid peroxide Ab + elevated TSH in autoimmune thyroiditis elevated TSH in autoimmune thyroiditis suggest:suggest:

Progression of overt hypothyroidismProgression of overt hypothyroidism

Differential diagnosisDifferential diagnosis

Autoantibodies to thyroid peroxidase and, Autoantibodies to thyroid peroxidase and, less commonly, to thyroglobulin are less commonly, to thyroglobulin are present in almost all patients with present in almost all patients with Hashimoto’s thydoiditis Hashimoto’s thydoiditis

Thyroid peroxidase autoantibodies are Thyroid peroxidase autoantibodies are usually detected in patients with Grave’s usually detected in patients with Grave’s diseasedisease

Hashimoto’s thyroiditis: Hashimoto’s thyroiditis: an examplean example

In Hashimoto’s thyroiditis (i.e. chronic In Hashimoto’s thyroiditis (i.e. chronic inflammation of thyroid caused by inflammation of thyroid caused by autoimmune factors)autoimmune factors)

Lab findings early in the disease consists Lab findings early in the disease consists of normal T4 & TSH levels and high titers of of normal T4 & TSH levels and high titers of thyroid peroxidase antibodies and less thyroid peroxidase antibodies and less commonly anti-thyroglobulin antibodiescommonly anti-thyroglobulin antibodies

Screening for thyroid Screening for thyroid autoimmunityautoimmunity

Thyroid Ab measurement is not useful in Thyroid Ab measurement is not useful in differentiating between autoimmune differentiating between autoimmune thyroiditis and thyroid malignanciesthyroiditis and thyroid malignancies

Both these Ab are commonly measured by Both these Ab are commonly measured by RIA, ELISA or IRMA techniquesRIA, ELISA or IRMA techniques

Measurement of thyroid Measurement of thyroid autoantibodiesautoantibodies

Thyroid peroxidase autoantibody test has Thyroid peroxidase autoantibody test has replaced the older tanned red cell replaced the older tanned red cell agglutination test for thyroid anti-microsomal agglutination test for thyroid anti-microsomal autoantibodiesautoantibodiesReasons for replacement of new Reasons for replacement of new immunoassay methods because they are immunoassay methods because they are more sensitive, can be easily automated and more sensitive, can be easily automated and quantitativequantitativeDisadvantages: wide variability in sensitivity Disadvantages: wide variability in sensitivity and specificityand specificity

Clinical SignificanceClinical Significance

Thyroid autoantibodies are usually Thyroid autoantibodies are usually present in the serum of patient with present in the serum of patient with autoimmune thyroid diseaseautoimmune thyroid diseaseE.g. TSH receptor autoantibody are E.g. TSH receptor autoantibody are present in most patients with Grave’s present in most patients with Grave’s diseasediseaseAging is also associated with the Aging is also associated with the presence of thyroid autoantibodiespresence of thyroid autoantibodies

Clinical SignificanceClinical SignificanceBecause TSH receptor autoantibody has the Because TSH receptor autoantibody has the ability to pass through the placenta, its ability to pass through the placenta, its presence during pregnancy can complicate presence during pregnancy can complicate fetal functions fetal functions

Studies suggest that thyroid peroxidase Ab Studies suggest that thyroid peroxidase Ab may contribute to future thyroid may contribute to future thyroid dysfunction dysfunction

Thyroid peroxidase Ab is also involved in Thyroid peroxidase Ab is also involved in the development of autoimmune the development of autoimmune complications from treatment of other complications from treatment of other drugs drugs

Clinical SignificanceClinical Significance

Changes in autoantibody conc. will result in Changes in autoantibody conc. will result in changes in thyroid autoimmune disease changes in thyroid autoimmune disease activities activities However, thyroid autoantibody However, thyroid autoantibody measurements are not used for the measurements are not used for the treatment of autoimmune thyroid diseasetreatment of autoimmune thyroid disease

Because treatment is intended to correct Because treatment is intended to correct the thyroid dysfunction & not the the thyroid dysfunction & not the autoimmunity part of the diseaseautoimmunity part of the disease