Thyroid Function TestThyroid Function Test

Thyroid GlandThyroid GlandWeighs about 15-25 gramsComposed of 20-40 folliclesFollicles – site of thyroid hormone

synthesis and storage

THYROID HORMONE THYROID HORMONE SYNTHESIS AND SYNTHESIS AND METABOLISMMETABOLISM

Thyrotropin-Releasing Thyrotropin-Releasing Hormone (TRH)Hormone (TRH)Acts on the production of other

pituitary hormones especially prolactin

Not useful for thyroid disorders

Thyroid Stimulating Hormone Thyroid Stimulating Hormone (TSH)(TSH)Most important test of thyroid

functionConsists of two mono-covalently

linked alpha and beta subunitsAlpha subunits – has the same

amino acid sequences as LH, FSH and HCG

Beta subunits – carries specific information to the binding receptors for expression of hormonal activities

This test alone can identify virtually all instances of hyperthyroidism and hypothyroidism, except:◦damage to the hypothalamus or

pituitary◦thyroid hormone resistance◦interference with normal functioning

of the HPT axis due to medication. Hypothyroidism -TSH results are

clearly elevated

The radioimmunoassay for measuring TSH was first developed by Odell and colleagues in 1965

By the mid-1980s a ‘sensitive' immunometric TSH method using either monoclonal or polyclonal antibodies was developed which had an improved sensitivity to 0.1-0.2 mU/L

A third-generation nonisotopic immunometric TSH assay using a chemiluminescent label was developed in the 1990s; this is the assay method which is currently in common use

Non Thyroidal Illness (NTI)◦important cause for both increased

and decreased TSH results.◦tend to have low TSH results during

their acute illness◦then TSH rises to within or above the

reference range with resolution of the underlying illness

◦returns to the normal once the acute illness has resolved.

Limitations of TSH centered Limitations of TSH centered strategystrategyit assumes that hypothalamic–

pituitary function is intact and normal

it assumes that the patient is stable

ThyroxineThyroxinebind to various proteins in the

blood ◦ thyroid-binding globulin◦albumin◦Thyretin

measured by immunoassay after separating the hormone from its carrier protein

reference range is 5-12.5 μg/dL in adults

ThyroxineThyroxineoften used along with TSH primary hypothyroidism

◦low T4 and an increased TSH

primary hyperthyroidism◦elevated T4 and T3 along with a decreased

TSHT4 Thyrotoxicosis - serum T4, serum T3

levels within the reference range or low◦iodine-induced thyrotoxicosis, patients on

beta-blockers, amiodarone or large doses of steroids, and in thyrotoxic patients with NTI.

T3 thyrotoxicosis - suppressed TSH level associated with a normal to normal-low T4 and a high T3

T4 and T3 syndrome◦Severe nonthyroidal illness◦Poor prognosis◦Arise from a maladjusted central

inhibition of hypothalamic-releasing hormone (TRH)

Euthyroid hyperthyroxinemia◦ distinguished by the presence of an

increased serum T4 level in association with a normal TSH

◦seen in patients who are acutely hospitalized for psychiatric illness and in patients with familial dysalbuminemia

Free Thyroxine (FT4)Free Thyroxine (FT4)biologically active fraction of

thyroxine in circulating bloodmeasured by equilibrium dialysis,

a method that is not affected by changes in binding protein concentration or by nonthyroidal illness

Triiodothyronine Triiodothyronine measured by immunoassay, has a

reference interval typically in the range of 60-160 μg/dL (0.9-2.46 nmol/L)

helpful in confirming the diagnosis of hyperthyroidism, especially in patients with no or minimally elevated T4

90% of patients with hyperthyroidism, T4 and T3 values are increased, with the increase of T3 usually greater than that of T4

T3 thyrotoxicosis ◦occur in patients toxic nodular goiter or toxic adenoma

Reverse Triiodothyronine Reverse Triiodothyronine (rT(rT33) ) produced by 5-deiodination of T4

have little clinical usefulnesshigh in patients with NTI, whose

serum total T3 is decreasedincreased in:

◦healthy newborns◦patients with hyperthyroidism

(including factitious hyperthyroidism) ◦patients taking certain drugs,

including amiodarone and propranolol.

Thyroglobulin (Tg) Thyroglobulin (Tg)

synthesized and secreted by the follicles

present in the serum of normal individuals in the range of up to about 30 ng/mL (45 pmol/L)

Increases in: ◦Graves' disease◦Thyroiditis◦nodular goiter

Thyroglobulin (Tg) Thyroglobulin (Tg)

routine measurement is never indicated

use in monitoring recurrence of certain variants of thyroid cancer◦helpful in patients with well-

differentiated thyroid carcinoma but not in those who have undifferentiated tumors or medullary thyroid cancer

distinguish subacute thyroiditis from thyrotoxicosis factitia

Thyroxine-Binding Globulin Thyroxine-Binding Globulin (TBG) (TBG) the main serum carrier protein

for both T4 and T3

measured by immunoassayRanging from 13-39 μg/dL (150-

360 nmol/L) in healthy individuals

Thyroid Autoantibodies Thyroid Autoantibodies Autoimmune thyroid disease

causes cellular damage and alters thyroid gland function

Cellular damage occurs when the autoantibodies or the sensitized T lymphocytes bind to thyroid cell membranes causing cell lysis and inflammatory reactions

Thyroid Autoantibodies Thyroid Autoantibodies There are three thyroid

autoantigens responsible for the autoimmune thyroid disorders: ◦thyroperoxidase (TPO)◦thyroglobulin (Tg) ◦ TSH receptor (TR)

Thyroid Autoantibodies Thyroid Autoantibodies TPO antibodies (TPOAb)

◦involved in the tissue destructive process associated with hypothyroidism in Hashimoto's and atrophic thyroiditis

TgAb◦even in low concentrations can interfere

with the anti-Tg antibody used in the immunoassay for Tg measurement.

◦Thus, the TgAb concentration should be measured in all patients prior to Tg analysis.

◦In iodide-deficient areas, serum TgAb measurement can be used to detect autoimmune thyroid disease in patients with a goiter and for monitoring iodide therapy in endemic areas

TSH receptor antibodies (TRAb) ◦previously known as thyroid-

stimulating immunoglobulin (TSI) or long-acting thyroid stimulators (LATS).

◦classified as stimulating or blocking antibodies

◦measurement is used to predict the risk of thyroid dysfunction in newborns of mothers with Graves' disease as a result of transplacental passage of maternal TRAb

The effects of drugs on The effects of drugs on thyroid functionthyroid function

Amiodarone

Thyroid function should be checked prior to commencing amiodarone.

Mildly abnormal thyroid function tests often occur in the first six months of treatment (mild TSH and FT4 elevation).

Patients on long term therapy should be monitored with 6 monthly TSH and FT4 tests. An early repeat should be arranged if there are abnormalities of concern (such as falling TSH) or the patient develops symptoms of thyroid dysfunction.

Lithium

Can lead to hypothyroidism, especially in patients with underlying autoimmune thyroid disease. An annual check of thyroid function is recommended.

Thyroid Illness Thyroid Illness Hyperthyroidism

◦ may present with one or all of the following signs and symptoms: weight loss sweating heat intolerance palpitations insomnia increased bowel movement tremors infertility or amenorrhea

Hyperthyroidism◦have suppressed TSH values with the

exception of those few individuals who have secondary hyperthyroidism caused by TSH-producing pituitary tumors

Subclinical hyperthyroidism ◦ defined as low TSH (< 0.1 μIU/mL) with levels of

T4 and T3 within the reference values without any signs or symptoms of hyperthyroidism

◦ particularly important in patients who are over 60 as they have increased risk of atrial fibrillation, increased cardiovascular mortality and osteoporosis.

Primary hypothyroidism ◦present with one or all of the

following signs and symptoms: cold intolerance constipation water retention hypercholesterolemia depression pretibial myxedema periorbital edema elevated TSH with low T4 and T3

Secondary hypothyroidism◦TSH is low in patients

Subclinical hypothyroidism ◦have elevated TSH levels (> 4.5 μU/mL)

but both T4 and T3 are within the reference range

In 2004, the 13-member expert panel led by Surks published their findings in the January issue of JAMA and recommended TSH reference limits of 0.4-4.5 μU/mL and that patients with TSH ranges from 4.5-10 mU/L not be routinely treated

The 2002 AACE guidelines ( American Association of Clinical Endocrinologists, 2002 ) recommend treatment of those with TSH > 10 μU/mL or those with goiter and positive TPOAb whose TSH is between 4.5-10 μU/mL

Screening for thyroid disease Screening for thyroid disease

The American Thyroid Association guidelines recommend screening at age 35 and every 5 years thereafter

There is mounting evidence to indicate that a persistent TSH abnormality may lead to major risks if left untreated.

One study reported a higher cardiovascular mortality rate in patients with chronically low TSH

Numerous reports indicate that mild hypothyroidism in early pregnancy increases fetal loss and impairs the IQ of the offspring

It is important to always confirm any TSH abnormality in a fresh specimen drawn 3 weeks later before making the diagnosis of mild abnormalities.

Thyroid tests in the Thyroid tests in the pregnant patientpregnant patient

Thyroid screening in women planning pregnancy, and those who are pregnant, has been advocated by some groups. At this stage screening these groups remains controversial and is not recommended, unless there are symptoms of thyroid disease.

TSH may be temporarily suppressed during the first trimester of pregnancy, due to the thyroid stimulating effect of hCG. FT4 levels tend to fall slowly in the second half of pregnancy.