Thyroid function test , made by dr.boskey,surat

Dr. Boskey . P . GandhiConsultant pathologist at

Jaymala path lab,chhayado trust,

surat

SPECTRUM OF THYROID DISEASE

Severe

mild

Subclinical

EpidemiologyAccording to the Indian Thyroid Society, it is estimated

that 4.2 crore people in the country are suffering from

thyroid disorders with almost 90 per cent undiagnosed.

As brand ambassador for the Abbott India Ltd healthcare

company, kajol is urging women to take thyroid tests so

that they can take timely medical advice and avoid

complications. –

See more at: http://www.bollywood.com/kajol-urges-women-take-

thyroid-test#sthash.ewxasQAt.dpuf

Even with the efforts in the past decade, we still

have a long way to go in terms of thyroid awareness.

As part of a pre cautionary measure, women should

check their TSH level as soon as pregnancy has

confirmed," said R V Jayakumar, President of The

Indian Thyroid Society.

Read more

at: http://indiatoday.intoday.in/story/Kajol+to+create+awareness+about

+Thyroid+/1/97851.html

Oprah win Frey

Owner of most famous oprah win Frey talk show in America.

Having hashimoto’s thyroiditis.

Anatomy of Thyroid gland

The thyroid gland

is a butterfly-shaped endocrine gland that is normally located anterior side of the neck lying in front & around the larynx & trachea just below the laryngeal prominence.(Adam’s apple)

*Biosynthesis of thyroid hormones:-

Steps:1. Iodide (I-) enters the thryroid cell via sodium iodide symporter2. It enters the colloid through pendrin receptor3. It is oxidized into Iodine (I0) by peroxidase enzyme4. Then it is organified into MIT and DIT (mono and di iodo thyronine)5. Then after coupling it forms T3 (Tri iodo thyronine) and T4 (Thyroxine)6. T3 and T4 conjugate with TBG (thyroid binding globulin)7. conjugated TBG is stored in colloid till required8. While releasing into blood stream, it is first endocytosed into thyroid cell and then de -coupled to form, T3 and T4 with MIT and DIT9. MIT and DIT can be reutilized for coupling10. T3 and T4 are released into the blood stream

*What happens to thyroid hormones after

release

*Concept of FT3 and FT4

1. Out of the total T3 and T4 in circulation, most of it remains bound to thyroid bindingglobulin *, prealbumin and albumin. (*note :this is not thyroglobulin)2. Only about 0.05% of each T3 and T4 remains free in circulation. This is FT3 and FT4.3. These are better indicators for thyroid function than total T3 and Total T4.(total=bound+free)4. For example in pregnancy, level of thyroid binding globulin rises; hence though total T3and total T4 remains same, level of FT3 and FT4 decreases.

CLASSIFICATION OF THYROID DISEASE

HYPO THYROIDISM-

MOST COMMON

HYPER THYROIDISM

SUB CLINICAL CASES-1.HYPO

2.HYPER (ASYMPTO-

MATIC CASES)

Hypothyroidism*Causes:

Primary Hypothyroidism ( High TSH, low T3 and T4)

1. Iodine deficiency

2. Goitrogens (excess amount interfere in iodine uptake)

SOY products

strawberry,

Sweet potatoes

cabbage, cauliflower, spinach

Broccoli

Millet e. t .c

3. Hashimoto’s

(anti microsomal antibodies)

4. Iatrogenic – surgery

Anti thyroid drugs,

Radiation

Continue……..Secondary hypothyroidism (Low TSH with normal TRH

i.e. pituitary problem

diseases of pituitary

Tertiary hypothyroidism (LOW TSH, Low TRH)

i.e. hypothalamic problem1. diseases of the hypothalamus

Exaggerated response to TSH RH stimulation

Rise and Delayed response to TSH-RH stimulation

Common Signs and Symptomsof Hypothyroidism

Dry skin

Brittle and lustreless hair

Weight gain

Tiredness

Constipation

Muscle aches

Bradycardia

Cold intolerance

Depression

Memory Loss

Mentrualabnormality

Lab abnormalities in hypothyroidism

Hyper lipidemia

Anemia(mac rocytic-due to vit B12 def)

High LDH

High CPK

Hyper prolactemia

Hypo natremia

*HyperthyroidismCauses:Primary hyperthyroidismLow TSH, High T4

Secondary HyperthyroidismHigh TSH, High T4Pituitary/Para neo plasticsyndrome

Factitious Hyperthyroidism

1. Grave’s disease

2. Toxicity in

Multi nodular goitre

3. toxicity in adenoma

4. Sub acute thyroiditis

1. TSH secretingpituitary adenoma2. Tropho blastic tumoursthat secrete TSH(chorio carcinoma, H. mole)

Exogenous ingestion of large dose of thyroid hormone.

Common Signs and Symptomsof Hyper thyroidism

Worm moist skin

Hair loss

Weight loss

Nervousness

Increased bowel movements

Muscle weakness

Tachycardia

Heatintolerance

insomnia

Difficulty in concentrating

Light or Absent periods

Laboratory findings in Hyperthyroidism

• TSH nearly undetectable

• Elevated FT4 or FT3

• Mild leuko penia

• N/N anemia

• ESR elevated

• ↑ed hepato cellular enzymes

• Mild ↑ Ca++

• ↓ Albumin

• ↓ Cholesterol

TRH Stimulation testIndication:

To rule out secondary or tertiary hypo/hyper thyroidism

Baseline sample collected for estimation of basal serum TSH levels

↓

Inject TRH (200 to 500 ug i.v)

↓

Measure TSH at 20 & 60 mins

Baseline TSH

20 min TSH

60 min TSH

interpretation

Normal Rise of>2mU/L

Small decline

normal

Hypothyroidism

Elevated Further rise Small decline

Primary hypothyroidism

Low No rise Secondaryhypothyroidism(pituitary)

Low rise Further rise(delayed)

Hypothalamichypothyroidism

Hyperthyroidism

elevated rise Thyroid hormoneresistance

elevated No rise Pituitaryadenoma/ paraneoplastic

Subclinical Thyroid Disease

Asymptomatic

Among the group with sub clinical thyroid disease, 73.8% are hypothyroid and 26.2% are hyperthyroid.

TSH outside the reference interval but normal serum levels of T3 and T4

The prevalence of SCH is about 4% to 10% in the general population and may be as high as 20 percent in women older than 60 yearsAnti thyroid antibodies can be detected in 80% of patients with SCH.80% of patients with SCH have a serum TSH of less than 10 mIU/L.

To treat or not to treat –Strict follow up

Suspicion of thyroid disease based on clinical signs and symptoms

Screening for thyroid disease

Evaluation of treatment for thyroid disease.

Thyroid Disease – Who Is At Risk ?

All newborns (neonatal screening)

personal history of thyroid disease

strong family history of thyroid disease

Have an autoimmune disease, such as Type 1 Diabetes Some genetic conditions (e.g. Down, Turnersyndromes)

past history of neck irradiation

drug therapies such as lithium and amio darone

Investigation and Management of Primary Thyroid Dysfunction. Toward Optimized Practice Program, Edmonton: AB, 2008 Update.

Contd…women over age 35

elderly patients

Pregnant women during the first trimester

women 6 weeks to 6 months post-partum

Have elevated lipid levels

THYROID FUNCTION TESTING IN AMBULATORY PRACTICE

Suspected case↓

normal ← S.TSH →high

↓ ↓

euthyroid low

↓

Sub clinical hyper← low/normal ← Order FT4→high→Overt hyper

↓ ↓

Order TT3 Confirm with TT3

↓ ↓ ↓

High low normal

↓ ↓ ↓

T3 central follow up

Thyro hypo

toxicosis

Continue…….S.TSH

↓

high

↓Overt hypo← Low← Order FT4→normal→Subclinical hypo

↓

high

↓

normal/low ← Order TT3→high→Secondary hyper

↓

T4 Assay interference

↓

Repeat with diff method

To screen or not to screen for thyroid dysfunction

American Association of Clinical Endocrinologist (AACE), American Academy of Family Physicians (AAFP), The American College of Physician (ACP) and the American Thyroid Association (ATA) vary greatly in their recommendations.

ATA recommending routine screening at age 35 then every five years.

BLOOD test to evaluate thyroid disease:TSH ,T4 ,T3

FT4 , FT3: Free hormone(Active metabolite)

rT3 :(inactive metabolite)high in NTI , newborn, hyperthyroidism

Thyro globulin mesurement

Thyroid antibodies: AntiTPO antibodies, (microsomal) TSH receptor AbsAnti TG antibodies

Urinary iodine mesurement

Thyroxine binding globulin:

• RadioimmunoassayRIA

• Enzyme-linked immunosorbant assayELISA

• Chemiluminescent immunoassayCLIA

• Fluorescent immunoassayFIA

Principle of FT4 measurement by immunoassay method.

High affinity hormone Abs measure free hormone as a fraction of binding site occupancy. Means ( unoccupied Abs sites are inversely proportional to free hormone.)

Hormone labeled tracer quantified free hormone level & passing signals which are converted to concentration using calibrators.

Factors limit the validity of free T4 IMMUNO ASSAY method

1.Dilution effects & protein dependence: dissociation of bound ligand occurs with sample dilution

2.Anomalous protein binding of tracer: Certain tracer used in FT4 assay have high binding capacity to protein(albumin)→ so in serum less tracer available for free Abs binding site→ false high FT4;while (in dialysis pts ,low protein →more tracer bind to Abs→ False Low FT4.)

3.Heparin effect: Heparin induce sample→↑ed lipase activity(if TG is high, Albumin is low, temp is prolong at 37C→high non esterified fatty acid →inhibit binding of T4 to serum protein in vitro only→ false high FT4.

4.Dysalbuminemic hyper thyroxinemia pts have abnormal proteins which bind T4 ,so spurious result of FT4 varies depending on labs.

Most accurate methods are: Equilibrium dialysis(time consumable), Ultra filtration(avoid dilution effect) , mass spectroscopy.

When FT4 is not correlate persistently with other parameter, method should be change.

Thyro globulin measurement

Thyroglobulin: One kind of organ specific protein.

Increased in Thyroid mass , injury , inflammation , TSH stimulation.

Indication in practice:

1.congenital hypothyroidism(thyroid dysgenesis(low)/dyshormonogenesis(high))

2.endemic goiter area, to monitor iodine supplementation.

3.Differentiated thyroid cancer cases ,after Sx to monitor recurrence

4.Thyrotoxicosis factitia: endogenous thyrotoxicosis(↑TG),exogenous ingestion of thyroid hormone(↓TG)

Normal range of TG :10-13ug/L in euthyroid subject.

Method: immunoassay , RIA

By immunoassay : minimal Tg abs in sample interfere with TG(low) measurement. So TGAb should be measure in all sample priror to TG analysis.If Abs present, RIA method S/b used.(low interference)

Thyroxin binding globulinMain carrier protein of T3 &T4

Measure by immunoassay

Normal Range:12 to 28 gm/dl.

Indicated ,when T3,T4 level do not agree with other parameter.

Increase TBG Decrease TBG

Liver disease Liver failure

Pregnancy, new born Malnutrition, nephrotic SX

Genetic disease Genetic disease

Drugs: Estrogen, 5-florouracil,clofibrate ,methadone

Drugs: Androgens, gluco corticoids

Drugs alter thyroid function testAlter secretion of T3,T4

↑ TBG ↓ TBG Competition with binding protein

Induction of metabolism

Activation from T4 to T3

CentrlTSH suppresion

Thionamide

Estrogen Androgen

Aspirin Phenytoin Amiodarone

Dopamine

Ethionamide

Narcotics Danazol Heparin Carbemazepine

Propylthiourecil

Dobutamine

Lithium 5-FU Nicotinic acid

Furosemide(high dose)

Phenobarbitone

Dexamethasone

Octreotide

Clofibrate

L-asparaginase

Rifampicin Radiographic agent

Oxcarbemazepine

Sick Euthyroid SyndromeThyroid related changes that occur during systemic illness in the absence of intrinsic thyroid disease

The syndrome is acute, reversible, and occurs commonly after surgery, starvation and in many acute febrile illnesses, These changes may be observed in up to 75% of hospitalized patients

Any abnormality in hormone level is possible, usually low fT3 and tT3

Thyroid Disorders in Elderly Patients, S Med J 2005;98(5):543-549

Critically ill pt (hospitalization) stage i.e1. infections2. liver diseases3. malignancies4. trauma5. surgery6. renal failure7. cardiac failureDecresed D1→T4 to T3 conversion inhibited. →high T4,low T3Incrased D3→inactivation of t4 to rt3→high rT3

TSH will remain normal. All parameters are normal on recovery.

THYROID FUCTION TEST DURING PREGNANCY

Physiologial changes during pregnancy:

(TSH ↓, T3,T4↑) Because:

hepatic & estrogen induce TBG ↑ ed

B- hcg mimicking TSH, Stimulate Thyroid gland

↑ plasma volume→↑ T4 & T3 pool size.

High iodine clearance →more demand

↑D3 from placental mass → more degradation of T3,T4

Gestational variation of TFT

0

1

2

3

4

5

6

10weeks 20weeks 30weeks 40weeks

TSH

FT3

FT4

Trimester specific referance range of TFT

TSH(mIu/L) FT3(pmol/L) FT4(pmol/L)

Trimester-1 2.1(0.6-5) 4.4(1.9-5.8) 14.4(12-19.4)

Trimester-2 2.4(0.4-5.7) 4.3(3.2-5.7) 13.4(9.4-19.4)

Trimester-3

(Roche-cobas-e411/Elecsys) instrument specific

2.1(0.7-5.7) 4.1(3.3-5.1) 13.2(11.3-17.7)

According to endocrine society of india

In lab report ,ref range s/b trimester specific & depands upon instrument

Method use by lab

Ethicity

Iodine status of population

Age

Subclinical hypothyroidism with pregnancy

Associated with hypertension and toxaemia

Subclinical hypothyroidism is associated with ovulatory dysfunction and infertility..

Undetected SCH during pregnancy may adversely affect the neuropsychological development ,survival of the fetus

Screening of TFT during pregnancyAccording to endocrine society of india:

S/S of thyroid disease

previous H/O of thyroid disease

Family history of thyroid disease.

Autoimmune dis: i.e Hashimoto,type-1 diabetes,

H/O irradiation

Previous H/O miscarriage, infertility, preterm delivery.

Although

Studies suggest that All pregnant women s/b screen for TSH & AntiTPO(more responsible for post partum thyroiditis) in 1st trimester.

THYROID FUNCTION IN INFANTSchanges of thyroid hormone in first 120 hrs of life

0

1

2

3

4

5

6

Born 24hrs 48hrs 72hrs 96hrs 120hrs

TSH

RT3

T3

T4

Normal range of TFT in infant & childrenAge FT4(n

g/dl)T4(ug/dl

FT3(pg/dl)

T3(ng/ml

TSH(mu/L)

TBG(mg/dl)

Cord blood 0.9-2.2 7.4-13.0 15-75 1.0-17.4 2.5-5.1

1-4 days 2.2-5.3↑

14.0-28.4↑

180-760 100-740↑ 1.0-39.0↑

2-20weeks 0.9-2.3↓

7.2-15.7↓

185-770 105-245↓ 1.7-9.1↓ 2.1-6.0

5-24 months

0.8-1.8↓

7.2-15.7 215-770 105-269 0.8-8.2

2-7 years 1.0-2.1↑

6.0-14.2 215-700 94-241 0.7-5.7↓ 2.0-5.3

8-20 yrs o.8-1.9 4.7-12.4↓

230-650 80-210 0.7-5.7 1.8-4.2

21-45 years 0.9-2.5 5.3-10.5↓

210-440 70-204 0.4-4.2 1.8-4.2

SCREENING OF INFANTS-WHY?S/S not develop up to 3-6 months

Most common cause congenital hypothyroidism is thyroid dysgenesis / dys hormono genesis.

It affects neuro psychological status & growth of body.

In united states ,its routine screening

World wide 25% newborn babies undergo screening tests.

Some program screen at 2-5 days, while others screen at 2-6 weeks of life.

SCREENING OF INFANTS2 APPROCHES:

1. Initial T4 measuring followed by TSH , if T4 is low

2. Primary TSH determination.

Pre term babies

Preterm term baby has their own unique set of thyroid function tests & its directly co relate with gestation age & birth wts.

Usually preterm babies have” low T4-non elevated TSH “ result in screening programe.

Because1.discontinuation of maternal T4.

2.immaturity of hypothalamic-pitutary stimulation(low TSH surge).

3.immaturity in thyroid hormone production.

. 4.low iodine intake( due to i.v fluids).

repeat test is indicated in most cases.

Cancer thyroidThyroid carcinoma occurs relatively infrequently compared to the common occurrence of benign thyroid disease

Thyroglobulin Assays:

Determines the amount of thyroid tissue after a thyroidectomy iethere should be no thyroglobulin after complete thyroid gland removal.

Used to monitor the recurrence of the common thyroid cancers (follicular cell–derived tumors)

Tg measurements should always be interpreted in the context of simultaneous measurement of Tg autoantibodies (TgAB). TgABoccur in about 20% of thyroid cancer patients and can lead to falsely low Tg measurements

Calcitonin Assay:

Used to detect and monitor the recurrence of medullary thyroid cancer

NEW UPDATES1.NAFLD,Female,obesity----Hypo thyrodism S/b rule out.(metabolic syndrome)

2.Chronic HCV infection in children →mimic structure thyroid cells → Anti TPO, Anti TG antibodies produce→Sub clinical hypothyroidism →Overt hypothyroidism →So screening is mandatory before starting treatment

3.Steroid responsive nephrotic syndrome relaps pts may have hypothyroidism(temporary) because (they have oxidative stress in body ↘ affect kidney↘↑ed permeability of GBM↘ loss of TG↘low T3,T4 ↘high TSH)

Improve with remission

No need for thyroid treatment.

Take home messageWhen FT4 level dose not match with other parameter ,it should be repeated by more accurate method.

Trimester specific reference range should be included in report.

In case of thyrotoxicosis factatia ,TG is more useful parameter.

AntiTgAb S/b screen in all samples demand for TG measurement by immunoassay method.

Sick euthyroid Sx is identified by high rT3 level.

ReferancesTodd & Henry

Springer

Indian thyroid society manual

Internet

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