Thyroid Function

By: Kerfelcel B. Retoriano,RMT,MT(ASCPI),MPH

THE THYROID GLAND

butterfly shaped gland consist of two lobes (one on either side of the trachea) located in the lower part of the neck , just below the larynx lobes are connected by a narrow band called the isthmus By 11 weeks of gestation, the gland begins to produce measurable amounts of hormone

 Regulated by secretion of TSH (pituitary) and TRH(hypotahalamus) Iodide->reaches the thyroid->oxidized->combine w/tyrosine residues in the thyroglobulin molecule forming MIT and DIT w/c are coupled to from T3 and T4.

Follicle-

fundamental structural unit of the thyroid gland , tiny bags or sacs

2 types of cell : follicular cells are secrete T3 and T4 , some

inactive rT3 T3/T4 precursors (MIT-monoiodotyrosine; DIT-diodotyrosine)

Parafollicular or C cells produce calcitonin ,calcium regulation

 Functions of thyroid hormones:

for tissue growth/regulation of growth ,development and sexual maturation

for development of CNS

elevated heat production ; energy expenditure control of oxygen consumption it influence carbohydrate and protein metabolism; for energy conservation stimulation of heart rate and contraction synthesis and degradation of cholesterol and trigycerides enhance sensitivity of beta-adrenergic receptors to catecholamines.

Hypothalamic-PituitaryThyroid Axis

Thyroglobulin
acts as preformed matrix containing tyrosyl groups ; glycoprotein;stored in the follicular colloid of the thyroid g l a n d . Weighs about 15-25 g. It is divided into lobules each of which is composed of 2040 follicles separated by highly v a s c u l a r c o n n e c t i v e t i s s u e . follicles are ring-shaped structures, in which a single cell band of follicular cells surrounds a closed cavity containing colloid, thyroid hormone, thyroglobulin (Tg), and a variety of other gly-coproteins follicular cells rest on a basement membrane that is rich in glycoprotein that separates the cells from surrounding capillaries. The apex of the follicular cells has microvilli that extend into the colloid, where iodination, exocytosis, and the initial phase of hormone secretion occur.

Thyroglobulin
follicles are sites of thyroid hormone synthesis and storage. The thyroid gland also contains parafollicular cells, or C cells, which are responsible for the synthesis and secretion of calcitonin, a hormone important in calcium metabolism. Hypothalamus secretes TRH which also stimulates anterior pituitary to secrete TSH. TSH stimulates thyroid hormone synthesis and secretion by the thyroid gland.

Thyroglobulin
Negative feedback on hypothalamus and pituitary gland maintain TSH conc. In narrow limits 100 % of T4 and 20% of T3 is thyroid origin, the remaining 80% of T3 is produced enzymatically in non-thyroidal tissues by 5-monodeiodination of T4. 70% of T4 bound to TBG; 20% of T4 bound to transthyretin (formerly prealbumin) ; 10% of T4 bound to albumin.

Classification of Thyroid Disorders

1. Hyperthyroidism 2. Hypothyroidsim 3. Euthyroidism

Classification of Thyroid Disorders

1. Hyperthyroidism caused by heat intolerance, tachycardia, weight loss, weakness, emotional ability, and tremor , Graves disease ( antiboides to TSH receptor), toxic adenoma,toxic multinodular adenoma,exogenous iodine and iodine containing drugs. Excessive T3 and T4 production , ectopic thyroid tissue,pituitary tumor, TSHsecreting pituitary tumors and thyroid carcinoma. Symptoms: 1.1 thyrotoxicosis causes decreased weight and normal appetite, fatigue, heart palpitations, goiter, eyelid retraction, oligomenorrhea, diarrhea, angina, sweating, tremors, muscle weakness ,heat intolerance 1.2 thyroid storm is a rare medical crisis characterized by hyperexia , dehydration and cardiac failure.

Classification of Thyroid Disorders

Hypothyroidism caused by atrophic hypothyroidism(most common), Autoimmune hypothyroidism(Hashimotos), Post-surgery, radio active therapy or anti-thyroid drug therapy, congenital hypothyroidism and the ff: a. Primary Hypothyroidism failure of the thyroid itself to secrete adequate amount of thyroid hormone. b. Secondary hypothyroidism occurs when TSH secretion is decreased as a result of a pituitary disorder.. c. Tertiary Hypothyroidism- Result of hypothalamic dysfunction Symptoms: 1.1 hoarseness, cold sensitivity, dry skin, con-stipation, bradycardia, muscle weakness , myxedema coma ( advanced stage of thyroid deficiency progressive stupor, hypothermia and hypoventilation). Euthyroidism goiter, thyroid adenoma , thyroid carcinoma

Thyroid Hormone Synthesis and Metabolism

Major component of thyroid hormone is iodine; major source is dietary intake or deiodination of organic iodine-containing moiety within the gland serves as another source. Iodination of tyrosine residues in the thyroglobulin results in formation of monoiodotyrosine (MIT) and diiodotyrosine (DIT) TSH stimulates synthesis of thyroid hormones T4 is secreted 100% in the thyroid gland.-

Thyroid Hormone Synthesis and Metabolism

Conversion of T4 and T3 takes place in many tissues, particularly the liver and the kidney Protein-bound thyroid hormones do not enter cells, are considered to be biologically inert, and function as storage reservoirs for circulating thyroid hormones free hormones (FT3 and FT4) are the physiologically active portions of the thyroid hormones. The minute levels of free hormone fractions readily enters cells by specific membrane transport mechanism to exert their biological effects. The effects are mediated by T3 receptors located in the nucleus of the cell Reverse T3 is produced by removal of one iodine from the inner ring of T4 metabolically inactive; product of T4 metabolism. The hypothalamic-pituitary-thyroid axis(HPTA) is the neuroendocrine system that regulates the production and secretion of thyroid hormones Iodine intake below 50ug /day= deficiency of hormone secretion.

Hypothalamic-PituitaryThyroid Axis
Hypothalamic hormone = TRH Pituitary Hormone = TSH Serum free T4 and free T3 TRH enhances TSH synthesis , stimulates the secretion of preformed TSH from the thyrotrophs resulting in the secretion of bioactive TSH

Thyroxine (total T4)

it is the main thyroid hormone released from the thyroid gland. T4 measurements are often used along with TSH and can be important in interpreting TSH results

reference range is 512.5 ug/L in adults, with slightly lower results for certain pediatric age group
Distribution of total T4
70% is bound to TBG 20% bound to trnsthyretin (formerly called thyroxine-binding prealbumin)

Thyroxine (total T4)

thyroid disorders and their relation to Total T4:
Primary hypothyroidism decreased T4 level with an elevated TSH level . Symptomsinclude fatigue, weight gain, decreased mental and physical output , cold intolerance.

Hyperthyroidism elevated T4 and T3 levels and decreased TSH level. Symptoms include weight loss, heat intolerance, hair loss , nervousness, tachycardia and tremors.
T4 thyrotoxicosis-it is hyperthyroidism with an elevated serum T4 , but with serum T3 levels within the reference interval or low.

Low T3 and low T4 syndrome severe nonthyroidal illness, which is associated with decreased T3 and T4 levels; it is associated with poor prognosis.

Thyroxine (total T4)

analytical method: immunoassays Reference Interval: 5- 12.5 ug/dL (71-161 nmol/L) T3 uptake test - classical method of adjust- ing a total T4 measurement for alterations in binding protein. A T3-UP result is a relative measurement of the unoccupied binding sites of all circulating proteins. It was originally performed by saturating available binding sites with radiolabeled T3, then measuring the unbound T3 by adsorbing it onto a resin (hence the term T3 resin uptake)

FREE THYROXINE
biologically active fraction of T4 in circulating blood. Reference method of measurement is by equilibrium dialysis method not affected by changes in binding protein concentration.

It has been used alone or in conjunction with TSH to diagnose thyroid dysfunction because of its advantage in states of altered protein binding.
Thyroid disorders and their relation to FT4:
Hyperthyroidism elevated FT4 levels Hypothyroidism- decreased FT4 levels

FREE THYROXINE
Other methods.
Ultrafiltration using pressure to push the plasma sample through a dialysis membrane. Symmetrical dialysis plasma is dialyzed against itself, using a radioactive tracer added on one side to measure the rate of diffusion of FT4 which is proportional to its concentration. Mass spectrometry simultaneous measure of FT4 and FT3. Immunoassays FT4 index (from total T4 and unbound T4 sites serum proteins

MAJOR THYROID HORMONES

MAJOR THYROID HORMONES

TRIIODOTHYRONINE (T3) REVERSE TRIODOTHYRONINE (rT3) TETRAIODOTHYRONINE(T4)

TRIIODOTHYRONINE (T3)
also know as the 3,5,3 triidothyronine it is less tightly bound to serum proteins than T4 . Greater proportion of T3 exists in the free , diffusible state, non-protein bound. it has the most active thyroid hormonal activity almost 75-80% is produced from the tissue deiodination of T4. The principal application of this hormone is in diagnosing T3 thyrotoxicosis Better indicator of recovery form hyperthyroidism as well as the recognition of recurrence of hyperthyroidism. Helpful in confirming the diagnosis of hyperthyroidism.

TRIIODOTHYRONINE (T3)
An increase in the plasma level is the first abnormality seen in cases of hyperthyroidism. Thyroid disorders and their relation to T3:
T3 thyrotoxicosis- it is hyperthyroidism with elevated T3 levels in the presence of T4 and FT4 levels that are within the reference interval . Most of the patients have Graves disease and may occur in patients with toxic nodular goiter and toxic adenoma. Hyperthyroidism it may occur in patients with elevated serum T3 levels but the T4 levels are within the usual reference interval . It is seen during the early course of treatment and also during relapse after treatment. Hypothyroidism serum T3 levels are within the reference range.

TRIIODOTHYRONINE (T3)
Analytical Method : immunoassays Reference values: 80-200 ng/dL or 1.2 3.1 nmol/L(adult)
105 245 ng/dL or 1.8 3.8 nmol/L (children 1-14 yrs old) 60-160 ng/dL (0.92-2.46 nmol/L)

REVERSE TRIIODOTHYRONINE (rT3)

it is the major metabolite of thyronine and produced by 5-deiodination of T4.

TETRAIODOTHYRONINE(T4)
3,5,35 tetraiodothyronine principal secretory product the major function of organic iodine in the circulation a prohormone for T3 production all circulating T4 originates in the thyroid gland the amount of serum T4 is a good indicator of the thyroid secretory rate. Elevated thyroxine causes inhibition of TSH secretion, vice versa Reference values: 5.5 -12.5 ug/dL or 71-161 nmol/L (adult)
11.8 22.6 ug/dL orn 152-292 nmol/L (neonate)

OTHER HORMONES

OTHER HORMONES
THYROTROPIN RELEASING HORMONE THYROID STIMULATING HORMONE THYROGLOBULIN

THYROTROPIN RELEASING HORMONE

- a modified tripeptide( pyroglutamyl-histidyl proline amide) derived from a large prepro-TRH molecule. - regulate their own production by feedback inhibi- tion to synthesis of TRH and TSH in the hypothalamus and pituitary, - TRH acts also on the production of other pituitary hormones, especially prolactin. Leptin plays a significant role in the regulation of the TRH gene.

THYROID-STIMULATING HORMONE
-glycoprotein with a and b subunits. , synthesized in the anterior pituitary gland that controls the biosynthesis and release of thyroid hormones from thyroglobulin. LH, FSH and hCG A subunit has the same amino acid sequences as

B subunit- carries the specific information to the binding receptors for expression of hormonal actitivies.

it is regulated by the hypothalamus through TRH as well as negative feedback from the thyroid hormones. Most important test in determining thyroid dysfunction measured commonly by 3rd generation assay that can measure down to 0.005 mU/L. decreased in hypothyroidism.

THYROID-STIMULATING HORMONE
-Thyroid Disorders and their relation to TSH:
Hypothyroidism

a.1 primary hypothyroidism TSH levels are markedly elevated a.2 secondary hypothyroidism TSH secretion is decreased as a result of pituitary disorder. a.3 subclinical hypothyroidism-elevated TSH levels but with T4 and FT4 levels are within the reference interval. b. Nonthyroidal Illness TSH levels may be increased or decreased.

c. Subclinical hyperthyroidism TSH levels are decreased with T4 and T3 levels within reference interval.

THYROID-STIMULATING HORMONE
Reference Interval: 0.5-5 uIU/mL
TSH and free T3 for hyperthyroidism. Over production of T3 with normal to low-normal T4 (T3 thyrotoxicosis). Overproduction of T4 with normal to low-normal T3 (T4 thyrotoxicosis).TRIIODOTHYRONINE (T3)
-Measured by immunoassay , reference interval typically in the range of 60160 ug/dl (0.92.46 nmol/L).

less bound to serum protein compared to T4. not useful in evaluating patients suspected of having hypothyroidism bec. T3 levels are within the reference interval.

THYROGLOBULIN
synthesized and secreted by the follicles . Present in serum in the range up to 30 ng/ml(45 pmol/L). - it reflects thyroid mass, thyroid injury, and TSH receptor stimulation. -useful in monitoring the course of thyroid disease or response to treatment but not recommended in pre-operative identification of thyroid malignancy.

Conditions: Graves disease Thyroiditis Nodular goiter Reference Interval: up t0 30 ng/ml (up to 45 pmol/L)

THYROID HORMONE BINDING PROTEINS

THYROID HORMONE BINDING PROTEINS

THYROXINE-BINDING GLOBULIN THYROXINE-BINDING PREALBUMIN (TRANSTHYRETIN) THYROXINE-BINDING ALBUMIN

THYROXINE-BINDING GLOBULIN
main serum carrier for T3 and T4. Measurement is helpful if serum T3 and T4 levels do not agree with other laboratory parameters of thyroid function or not compatible with clinical findings. Measured by immunoassay range : 13-39 ug/dl (150-360 nmol/L-Henrys) in healthy individuals. Transports 70-75% of total T4 Transports majority of T3 (affinity for T3 is lower than T4)

THYROXINE-BINDING GLOBULIN
Increased TBG are seen in the following: liver disease drugs genetic deficiency

pregnancy and in newborN

Decreased TBG are seen in the following: liver failure drug administration by androgen & glucocorticoids malnutrition genetic (complete and partial deficiency) nephrotic syndrome

THYROXINE-BINDING PREALBUMIN(TRANSTHYRETIN)
transports 15-20% of total T4 - T3 has no affinity for prealbumin

THYROXINE-BINDING ALBUMIN
transports T3 - transports 10% of T4

THYROID AUTOANTIBODIES

THYROID AUTOANTIBODIES
- autoimmune thyroid disease causes cellular damage and alters thyroid gland function. 3 thyroid autoantigens: TPO (thyroperoxidase) TPO Abs responsible in hypothyroidism in Hashimotos and atrophic thyroiditis Tg(thyroglobulin) TSH receptor (TR) also known as TRAbs or thyroid stimulating Ig or long acting thyroid stimulators (LATS). Ig induced goiter and hyperthyroidism in Graves Disease. It is the preferred term for autoantibodies to the TSH receptor.

INCREASE drug

DECREASE drugs

Clofibrate estrogens,oral Androgens glucocorticoids contraceptives,5-fluororacil Heroin Methadone

Genetic Acute or Chronic active hepatitis genetic Complete deficiency partal liver failure

Pregnancy
idiopathic

malnutrition
Nephrotic syndrome ,idiopathic

Screening Program for Detection of Neonatal Hypothyroidism

The significance of early detection and treatment in neonates is to eliminate severe mental retardation associated with thyroid hormone deficiency. Screening test include: -T4, TSH, Combination Test (T4 & TSH)

Specimens: dry blood spots , cord serum Consideration: Elevated TSH is the most sensitive test for neonatal screening Recommendation: It is recommended that very low-birthweight infants should have
additional screening at 2 & 4-6 weeks to detect late onset , transient hypothyroidism.

Thyroid Disorders

Clinical Disorders
1. HYPERTHYROIDISM 2. HYPOTHYROIDISM

1. HYPERTHYROIDISM
-refers to excess of circulating thyroid hormone -Primary hyperthyroidism elevated T3 and T4 ,decreased TSH -Secondary Hyperthyroidism increased TSH and T4 (due to primary lesion in the pituitary gland)

Thyrotoxicosis is applied to a group of syndrome caused by high levels of free thyroid hormones in the circulation.
TSH is low , FT4 is normal but increased FT3-T3 thyrotoxicosis or Plummers Disease.

Graves Disease (diffuse toxic goiter) -the most common cause of thyrotoxicosis , auto immune disease

1. HYPERTHYROIDISM
most common cause of increased T3 and T4 , decreased TSH.
it occurs 6x more commonly in women than in men caused by circulating autoantibodies to the TSH receptor stimulating and blocking antibodies features: exophthalmos (bulging eyes), pretibial myxedema Diagnostic Test : TSH receptor antibody test

Riedels thyroiditis the thyroid turns into a woody or stony-hard masses

Subclinical hyperthyroidism shows no clinical symptoms but TSH level is low , and FT4 and FT4 normal Subacute granulomatous,Subacute nonsuppurative thyroiditis/ De Quervains thyroiditis (painful thyroiditis) associated with neck pain , low-grade fever and swings in thyroid function tests. thyroidal peroxidase (TPO) antibodies are absent , ESR and thyroglobulin levels are
elevated.

1. HYPERTHYROIDISM
TREATMENT: antithyroid drugs may lead to remission but relapse can occur as much as many years later Radioactive iodine and surgerymay lead to hypothyroidism in 35% of cases Beta-adrenergic blocking drugs relieve the symptoms but do not cure

DIAGNOSIS OF HYPERTHYROIDISM
TSH and FT4
High TSH,High FT4
TRH Stimulation Test

No TSH, High FT4

Thyroid antibody measuremennt

Low TSH, Normal FT4

FT3
normal high

No response Secondary hyperthyroidis m(pituitary tumor)

Normal respons e Ecto pic thyro id tissu e

positive

negative

Autoimmune hyperthyroidis m(graves disease

Toxic mutinodular adenoma

Subclini cal hypothy roidism

thyrotoxicosis

2.HYPOTHYROIDISM
develops whenever insufficient amounts of thyroid hormone are available to tissue treated with thyroid hormone replacement therapy (levothyroxine)

Hypothyroidism
A. Primary Hypothyroidism B. Secondary Hypothyroidism C. Tertiary Hypothyroidism D. Congenital Hypothyroidism /Cretinism E. Subclinical Hypothyroidism

Primary Hypothyroidism
primarily due to deficiency of elemental iodine (dec. T3 and T4, inc. TSH)
it is also caused by destruction or ablation of the thyroid gland

Other causes: surgical removal of the gland ; used of radioactive iodine for hyperthyroidism treatment ; radiation exposure, drugs such as lithium.

Primary Hypothyroidism
a.1 Hashimotos disease ( chronic autoimmune thyroiditis) decreased T3 and T4, inc. TSH most common cause of primary hypothyroidism

Primary Hypothyroidism
the thyroid is replaced by a nest of lymphoid tissue sensitized T
lymphocytes/autoantibodies bind to cell membrane causing cell lysis and inflammatory reaction. -autoantibodies present antithyroglobulin & antimicrosomal abs. -associated with enlargement of the thyroid (goiter)

methods for testing: TPO antibody = (+) result , TSH = increased

Primary Hypothyroidism
a.2 Myxedema -decreased T3 and T4,inc. TSH describes the peculiar nonpitting swelling of the skin

the skin becomes infiltrated by mucopolysaccharides

- clinical features: puffy face , weight gain, slow speech, eyebrows thinned, dry and yellow skin. myxedema coma severe form of primary hypothyroidism

Secondary Hypothyroidism
due to pituitary destruction or pituitary adenoma T3 and T4 low levels, TSH is also decreased

Tertiary Hypothyroidism
due to hypothalamic disease T3 and T4 low levels , TSH is also decreased.

Cogenital Hypothyroidism/Cretinism
defects in the development or function of the gland physical and mental development of the child are retarded screening test : T4 (decreased) confirmatory test : TSH (increased)

Subclinical Hypothyroidism
T3 and T4 normal, TSH is slightly increased.

Treatment for Hypothyroidism

replacement therapy T3 is preferred for treatment owing to short halflife , w/c allows for quicker adjustment of therapeutic levels.

Patient Preparation, Specimen Collection and Storage ,reference range

Test

Patient Preparation

Specimen Collection

Specimen Storage

Reference Range

TSH

Exhibits diurnal variation 2-4am = highest levels

5-6 pm= lowest levels

serum preferable
plasma acceptable depending on the method used no hemolysis or lipemia Serum, Plasma (heparin or EDTA) No hemolysis or lipemia Centrifuged turbid samples before tetsing

Stable 5-7 days at 2-8C, 1 month if frozen

0.5-5.75 MIU/L
NOTE: varies with method and reference population , increases after age 55
4.6-11 ug/dl(higher in premenopausal women owing to estrogen NOTE: varies consideration owing to fluctuation in TBG levels higher during pregnancy

T4

Nonfasting specimen is acceptable

Stable 7-14 days at room temp or 2-8 C, 1 month if frozen Cannot be repeatedly frozen and thawed

T3

Same as T4

70-204 ng/dl Note: decreases after age 50

Test for Thyroid Function

1. 2. TRH stimulation test (Thyrotropin Releasing Hormone) TST Test

3.
4. 5. 6. 7. 8. 9.

Radioactive Iodine Uptake (RAIU)

Thyroglubulin Assay Reverse T3 (rT3) Free Thyroxine Index (FT4 or T7) Total T3 (TT3) , Free T3(FT3) and Free T4 (FT4) T3 Uptake test Thyroxine binding globulin (TBG)test

10. Fine Needle aspiration 11. Recombianat Human TSH 12. Tanned Erythrocyte Hemagglutination method

13. Serum calcitonin test

Test for Thyroid Function

1.TRH stimulation test (Thyrotropin Releasing Hormone ) the most specific and sensitive test for diagnosing thyroid disease.

it measures the relationship between TSH and TRH.

it is used to differentiate euthyroid and hyperthyroid patients who both had undetectable TSH levels. it may also be helpful in the detection of thyroid hormone resistance syndromes. it is used to confirm borderline causes and euthyroid Graves disease. dose levels: 500 ug TRH by IV

increased levels : primary hypothyroidism

decreased levels: hyperthyroidism

Test for Thyroid Function

2. 2. TST test most common important thyroid function test; best screening test. the most clinically sensitive assay for the detection of primary thyroid disorders

it helps in the early detection of hypothyroidism

it is used to differentiate primary hypothyroidism from secondary hypothyroidism. it is used to monitor and adjust thyroid hormone replacement therapy reference values: 0.5 5 uU/ml

Increased TSH a. Primary hypothyroidism b. Hashimotos thyroiditis c. Thyrotoxicosis due to pituitary tumor d. TSH antibodies e. Thyroid hormone resistance hormone in hypothyroidism

Decreased TSH a. Primary hyperthyroidism b. Secondary and tertiary hypothyroidism c. Treated Graves disease d.Euthyroid sick disease e. Over replacement of thyroid

Test for Thyroid Function

3. 3.Radioactive Iodine Uptake (RAIU) it used to measure the ability of the thyroid gland to trap iodine it is helpful in establishing the cause of hyperthyroidism
-high uptake indicates metabolically active gland (active hormone production)

high uptake + TSH deficiency = autonomous thyroid activity.

Test for Thyroid Function

4. .Thyroglobulin (Tg) assay it is normally used as a post operative marker of thyroid cancer
-it is used in monitoring the course of metastatic or recurrence of thyroid cancer.
-increased levels: untreated and metastatic differentiated thyroid cancer, hyperthyroidism

decreased levels: infants with goitorous hypothyroidism, thyrotoxicosis factitia

-reference values: 3-42 ng/ml or ug/ml (adult) 38-48 ng/ml or ug/ml (infant)

methods for testing : double antibody RIA, ELISA, IRMA and immnochemiluminescent assay (ICMA) methods for testing.

Test for Thyroid Function

5. 5.Reverse T3 (rT3) used to assessed borderline or conflicting laboratory results.

it identifies patients with euthyroid sick syndrome (elevated r T3)

r T3 is formed by removal of one iodine from the inner ring of T4 and endproduct of T4 metabolism.
-reference values : 38-44 ng/dL

Test for Thyroid Function

6. 6.Free Thyroxine Index (FT4I or T7) it indirectly assesses the level of free T4 in blood

it is based on the equilibrium relationship of bound T4 and FT4

-it is important in correcting euthyroid individuals -it is elevated in hyperthyroidism and decreased in hypothyroidism -reference method: equilibrium dialysis -reference values: 4-12%

FT4I = TT4 x T3U (%) or TT4 x THBR 100

Test for Thyroid Function

7. 7.Total T3 (TT3) , Free T3(FT3) and Free T4(FT4) FT4 test is used to differentiate drug induced TSH elevation and hypothyroidism
-the value of TT3 or FT3 is in confirming hyperthyroidism -direct/reference method: Equilibrium dialysis (FT4)

8.T3 Uptake test measures the number of available binding sites of the thyroxine-binding proteins, most notably TBG.
-elevated TBG results to decreased T3 uptake and vice versa.

it does not measure the level of thyroid hormones in serum a known amount of radiolabeled T3 is added to the test serum. estrogen increases TBG while androgens depresses TBG. increased levels: hyperthyroidism, euthyroid patients , chronic liver disease. decreased levels : hypothyroidism , oral contraceptives , pregnancy , acute hepatitis
reference values: 25-35%

Test for Thyroid Function

9.Thyroxine binding globulin (TBG) test
-it is used to confirm results of FT3 or FT4 or abnormalities in the relationship of the total thyroxine (TT4) and THBR test. -it is useful to distinguish between hyperthyroidism causing high thyroxine levels and euthyroidism with increased binding by TBG and increased thyroxine.

-total serum T3 and T4 are dependent on the amount of TBG.

-Increased levels: hypothyroidism , pregnancy , estrogen -decreased levels: anabolic steroids, nephrosis measurement: % T4 uptake(patient)

% T4 uptake(reference)

Test for Thyroid Function

10.Fine needle aspiration most accurate tool ion the evaluation of thyroid nodules 11. Recombinant Human TSH - used to test patients with thyroid cancers for the presence of residual or recurrent disease.

12. Tanned erythrocyte Hemagglutination method a test for antithyroglobulin antibodies 13. Serum calcitonin test tumor marker for detecting residual thyroid metastasis in medullary thyroid carcinoma (MTC)

Notes to remember:
Free T4 and TSH are the best indicator of thyroid status Free T3 and T4 are more specific indicators of thyroid function than the measurements of total hormone because the values are not affected by the TBG amount. Patients with increased T4-binding protein have an elevated T3 or T4 but not free T4 or TSH.

Abnormal values of total T3 or T4 must be evaluated with TBG measurement.

Euthyroid sick syndrome is acutely ill but without thyroid disease low T3 and T4 , and normal or increased TSH but elevated T3

Notes to remember:
In severe hypothyroidism , total CK and LDH values rise moderately. Thyroid hormones affect synthesis , degradation and intermediate metabolism of adipose tissue and circulating lipids. Calcitonin is measured by two-site immunometric assays using monoclonal antibodies and it is also elevated in autoimmune thyroid disorder, hypercalcemia and all neuroendocrine tumors. Cutoff value for calcitonin is 10 ng/L (adults)

Disorders
1. Graves Disease 2.Primary Hypothyroidism 3. Hashimotos thyroiditis 4. Nonthyroidal Illness 5. Thyroid hormone resistance

T3
Inc, N/de c. N/de c. Dec. Inc.

T4
Inc.

TSH
Dec

FT4
Inc. Dec.

rT3
Inc.

Tg
Inc.

TBG
N N N N N

Dec. Inc. N/D ec N/D ec Inc. Inc. V N/Inc.

Dec, N/d ec.

N/dec Dec. N/d . ec. V Inc. N/In c Inc N. Inc.

Urinary Iodine Measurement

Dietary measurement for large populations

Screening Programs For Detection of Neonatal Hypothyroidism

Early detection of hypothyroidism in the neonatal period is critical to eliminate the severe mental retardation associated with thyroid hormone deficiency

Measure T4 and TSH for screening

Physiologic Variables
- Variables that can affect the tests: age, gender, race, season, phase of menstrual cycle, cigarette smoking, exercise, fasting, and phlebotomy- induced stasis have minor effects on thyroid function tests in ambulatory adults

Medications and Thyroid function Tests

Glucocorticoids in large doses suppress TSH and dec. the conversion of T4 to T3 Dopamine suppresses TSH Propanolol suppresses the conversion of T4 to T3 ( one of the reasons why it is used for the treatment of thyrotoxicosis Iodide, found in iodide-containing contrast media used in CT scans and coronary angiography or in solution to sterilize skin, and radiopaque dyes can cause both hyperthyroidism and hypothyroidism in susceptible patients Iodine containing drugs such as (amiodaron-antiarrhytmic agent) have complex effects on thyroid function. Can cause hypothyroidism or hyperthyroidism.

Medications and Thyroid function Tests

Lithium inhibits thyroid hormone synthesis and release. Drugs such as phenytoin , carbamazepine, salicylate, salsalate and furosemide inhibit thyroid binding to serum proteins causing dec levels of T4 , falsely low results of FT4.

Phenytoin can induce acceleration of T4 disposal and suppress TSH centrally.

Heparin stimulate in vitro Lipoprotein lipase and liberate free fatty acids which inhibits T4 binding to serum proteins and falsely elevate FT4. Medications such as phenobarbital, phenytoin, rifampin, and carbam- azepine increase the rate of thyroid hormone clearance by increasing the deiodination of T4 and T3.

Screening For Thyroid Disease

screening at age 35 for every 5 years.

Use of L-thyroxine
used to suppress TSH in patients with welldifferentiated thyroid carcinoma for w/c thyrotropin is considered a trophic factor

Calcitonin
secreted by the C-cells of the thyroid. Medullary thyroid carcinoma originates from the C cells. Use as a tumor marker For diagnosis of MTC, Pentagastrin(Pg) Test is performed