Dr. Boskey . P . Gandhi
Consultant pathologist at
Jaymala path lab,
SPECTRUM OF THYROID DISEASE
According 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
See more at: http://www.bollywood.com/kajol-urges-women-take-
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.
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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
1. Iodide (I-) enters the thryroid cell via sodium iodide symporter
2. It enters the colloid through pendrin receptor
3. It is oxidized into Iodine (I0) by peroxidase enzyme
4. 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 required
8. While releasing into blood stream, it is first endocytosed into thyroid cell and then
coupled to form, T3 and T4 with MIT and DIT
9. MIT and DIT can be reutilized for coupling
10. T3 and T4 are released into the blood stream
*What happens to thyroid hormones after
*Concept of FT3 and FT4
1. Out of the total T3 and T4 in circulation, most of it
remains bound to thyroid binding
globulin *, 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.
4. For example in pregnancy, level of thyroid binding
globulin rises; hence though total T3
and total T4 remains same, level of FT3 and FT4
Primary Hypothyroidism ( High TSH, low T3 and T4)
1. Iodine deficiency
2. Goitrogens (excess amount interfere in iodine uptake)
cabbage, cauliflower, spinach
Millet e. t .c
(anti microsomal antibodies)
4. Iatrogenic – surgery
Anti thyroid drugs,
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 Symptoms
Brittle and lustreless hair
Lab abnormalities in
Anemia(mac rocytic-due to vit B12 def)
Low TSH, High T4
High TSH, High T4
1. Grave’s disease
2. Toxicity in
Multi nodular goitre
3. toxicity in adenoma
4. Sub acute thyroiditis
1. TSH secreting
2. Tropho blastic tumours
that secrete TSH
Exogenous ingestion of
large dose of thyroid
Common Signs and Symptoms
of Hyper thyroidism
Worm moist skin
Increased bowel movements
Difficulty in concentrating
Light or Absent periods
TRH Stimulation test
To rule out secondary or tertiary hypo/hyper thyroidism
Baseline sample collected for estimation of basal serum
Inject TRH (200 to 500 ug i.v)
Measure TSH at 20 & 60 mins
Normal Rise of
Elevated Further rise Small
Low No rise Secondary
Low rise Further rise
elevated rise Thyroid hormone
elevated No rise Pituitary
Subclinical Thyroid Disease
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 years
Anti 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
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, Turner
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.
women over age 35
Pregnant women during the first trimester
women 6 weeks to 6 months post-partum
Have elevated lipid levels
THYROID FUNCTION TESTING IN AMBULATORY PRACTICE
normal ← S.TSH →high
Sub clinical hyper← low/normal ← Order FT4→high→Overt hyper
Order TT3 Confirm with TT3
↓ ↓ ↓
High low normal
↓ ↓ ↓
T3 central follow up
Overt hypo← Low← Order FT4→normal→Subclinical hypo
normal/low ← Order TT3→high→Secondary hyper
T4 Assay interference
Repeat with diff method
To screen or not to screen for
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 Abs
Anti TG antibodies
Urinary iodine mesurement
Thyroxine binding globulin:
Principle of FT4 measurement by
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
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
Indication in practice:
2.endemic goiter area, to monitor iodine supplementation.
3.Differentiated thyroid cancer cases ,after Sx to monitor
4.Thyrotoxicosis factitia: endogenous
thyrotoxicosis(↑TG),exogenous ingestion of thyroid
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
If Abs present, RIA method S/b
Thyroxin binding globulin
Main 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 alter thyroid function test
↑ TBG ↓ TBG Competitio
from T4 to
Aspirin Phenytoin Amio
Narcotics Danazol Heparin Carbema
Lithium 5-FU Nicotini
Sick Euthyroid Syndrome
Thyroid related changes that occur during
systemic illness in the absence of intrinsic
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.e
2. liver diseases
6. renal failure
7. cardiac failure
Decresed D1→T4 to T3 conversion inhibited.
→high T4,low T3
Incrased D3→inactivation of t4 to rt3
TSH will remain normal.
All parameters are normal on recovery.
THYROID FUCTION TEST DURING
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
Trimester specific referance range
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)
2.1(0.7-5.7) 4.1(3.3-5.1) 13.2(11.3-17.7)
According to endocrine society of
In lab report ,ref range s/b trimester specific &
depands upon instrument
Method use by lab
Iodine status of population
Subclinical hypothyroidism with
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 pregnancy
According 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,
Previous H/O miscarriage, infertility, preterm delivery.
Studies suggest that All pregnant women s/b screen for
TSH & AntiTPO(more responsible for post partum
thyroiditis) in 1st trimester.
THYROID FUNCTION IN INFANTS
changes of thyroid hormone in first 120 hrs of life
Born 24hrs 48hrs 72hrs 96hrs 120hrs
Normal range of TFT in infant &
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-
180-760 100-740↑ 1.0-39.0↑
185-770 105-245↓ 1.7-9.1↓ 2.1-6.0
7.2-15.7 215-770 105-269 0.8-8.2
2-7 years 1.0-
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-
230-650 80-210 0.7-5.7 1.8-4.2
21-45 years 0.9-2.5 5.3-
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
Some program screen at 2-5 days, while others screen
at 2-6 weeks of life.
SCREENING OF INFANTS
1. Initial T4 measuring followed by TSH , if T4 is
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 &
Usually preterm babies have” low T4-non elevated TSH “
result in screening programe.
1.discontinuation of maternal T4.
2.immaturity of hypothalamic-pitutary stimulation(low
3.immaturity in thyroid hormone production.
. 4.low iodine intake( due to i.v fluids).
repeat test is indicated in most
Thyroid carcinoma occurs relatively infrequently compared
to the common occurrence of benign thyroid disease
Determines the amount of thyroid tissue after a thyroidectomy ie
there should be no thyroglobulin after complete thyroid gland
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). TgAB
occur in about 20% of thyroid cancer patients and can lead to falsely
low Tg measurements
Used to detect and monitor the recurrence of medullary thyroid
1.NAFLD,Female,obesity----Hypo thyrodism S/b rule
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 message
When FT4 level dose not match with other parameter
,it should be repeated by more accurate method.
Trimester specific reference range should be included
In case of thyrotoxicosis factatia ,TG is more useful
AntiTgAb S/b screen in all samples demand for TG
measurement by immunoassay method.
Sick euthyroid Sx is identified by high rT3 level.
Todd & Henry
Indian thyroid society manual