THYROID FUNCTION TESTS
Dr Anu Mariam Varghese
2nd MD Scholar
Dept of Agadatantra
GAVC, TVM

CONTENTS
• Thyroid statistics
• Thyroid gland-Basics
• Hormones
• Synthesis of thyroid hormones
• How it functions
• Negative feedback system
• When to suspect thyroid disease
• Diseases affecting thyroid gland
• Thyroid function tests-Indications, TSH,TRH,T4,T3 etc.
• Thyroid examination
• Thyroid Scan-RAIU test
• CT Scan, PET Scan
• FNAC thyroid
• Biopsy

CONTENTS
• Management
• Diet in thyroid
• Thyroid and pregnancy
• Thyroid and peadiatrics
• DM and thyroid disorders
• Thyroid and HTN
• Thyroid and dermatology
• Thyroid and dyslipedemia
• Thyroid and infertility
• Thyroid –Comorbidities and complications
• Thyroid and Covid -19
• Cases
• References

THYROID STATISTICS
• 42 millions people in India have thyroid disorders.
• 2nd most common endocrine disorder in India
• Subclinical hypothyroidism is 11%.
• Hyperthyroidism present in <2%
• About 12% adults have a palpable goitre.
• 1/10 adults have hypothyroidism (only 2% in the UK and 4-6% in
USA)
• Among cancers, thyroid cancer 0.1-0.2 %
• Congenital hypothyroidism occurring in 1 out of 2640 neonates
(India ) and the worldwide average value of 1 in 3800 subjects.

THYOID GLAND
• Second largest endocrine gland.
• Small butterfly shaped gland located at the base of neck.
• Controlled by the hypothalamus and pituitary.

HORMONES
• Triodothyronine T3
• Tetraiodothyronine/Throxine T4
(produced by follicles)
• T4 kidney, liver, spleen T3
monodeiodinase
• T3 is 10x more active than T4

TSH
• Thyrothrophin (TSH) is a pituitary hormone.
• Controlled by TRH- thyrotrophin releasing hormone from
hypothalamus
CALCITONIN
Produced by thyroid (parafollicular cells) to regulate serum
calcium levels

SYNTHESIS OF THYROID HORMONES

Steps in thyroid synthesis
TRH release from hypothalamus Ant Pituitary
to release TSH TSH stimulates follicular cells to
synthesis TGB(Thyroglobulin) Iodine trapping
Oxidation of Iodide (TPO ) Iodination of
Tyrosine amminoacid Coupling of DIT’s and MIT’s
Endocytosis of TGB with T3 and T4
Lysosomal enzymes cleaves T3 &T4 out of Thyroglobulin
Exocytosis T4 &T3 blood plasma

FUNCTION
Mental growth & maturation
BMR Physical growth&
maturation
Sensitivity to adrenergic system

↓ Cellular ATP
↑ O2 usage
↑ Metabolic rate
↑ Heat production
↑ Number of Mitochondria
(Hypertrophy)
CELL
C6H12O6 +6 O2
6CO2+6H2O+HEAT

Glycogenolysis
↑ Glucose in blood
Gluconeogenesis
↑ LDL uptake

↑ Cardiac output/BP
↑Heart rate/BP

↑ Dendrites
↑ Myelination
↑ no of synapses

Balance b/w osteoblasts & osteoclasts
Interstitial growth
Regulating endochondral ossification
Bone remodelling

Lipolysis

Protein metabolism
balance

Sweat production
Regulates body temperature

↑ Secretions
↑ Motility

Development of RS
Synthesis of SHBG
Regulates level of sex hormones

NEGATIVE FEEDBACK SYSTEM
TRH TSH The disruption of any of
these mechanisms can
cause abnormal levels
of T3 and T4 leading
thyroid disease.
T3 & T4 Thyroid

WHENTO SUSPECTTHYROIDDISEASE?
• Fatigue and sleep disorders
• Weight changes
• Mood and mental changes
• Bowel problems
• Muscle or joint problems
• Irregular periods, fertility and libido problems
• Hair and skin changes
• Body temperature
• Cholesterol issues
• High BP
• Heart rate
• Neck enlargement (goitre)
• Risk factors: Family history, age , gender

Diseases affecting thyroid gland?
• Over functioning
• Underfunctioning
• Enlargement (Goitre) uniform, solitary nodule, multiple
nodules.
• Thyroiditis
• Pregnancy related problems

Thyroid Function Tests
• Blood tests
 Serum TSH (Ultrasensitive assay)
 Serum total T3
 Serum total T4
 Serum free T4 (or T3)
• Thyroid scanning – USG, Radioactive Iodine/Tc
• FNAC
• CT scanning
• PET scanning
• Biopsy.

INDICATIONS OF TFT
• To evaluate integrity of hypothalamic-pituitary-thyroid
axis.
• Diagnosing thyroid disorder in symptomatic person.
• Screening newborns for hypothyroidism.
• Monitoring thyroid replacement therapy in
hypothyroidism patients.
• Diagnosis & monitoring female infertility patients.
• Screening adults for thyroid disorders

NORMAL VALUE
THYROID FUNCTION
TEST
MEASUREMENT NORMAL RANGE
Total T4 (TT4) Bound & Free T4 5.0-11.0 ug/dL
Free T4 (FT4) Free T4 0.9-1.7 ng/dL
Total T3 (TT3) Bound & Free T3 100-200 ng/dL
T3 Resin Uptake Binding capacity of TBG 22-34%
TSH Thyroid stimulating
hormone
0.4-4.5 mIU/mL

TSH
• First line test in Thyroid function tests
USES
• Screening in euthyroidism.
• Screening of hypothyroidism in newborns.
• Diagnosis of 1 & 2 hypothyroidism.
• Diagnosis of clinical and subclinical hypothyroidism.
• Follow up of T3 & T4 replacement therapy in
hypothyroidism.

METHODS OF TSH ESTIMATION
• Radioimmunoassay
• Immunometric assay
• Chemiluminiscent & flourescent technique (3rd gen)

TSH
INCREASE DECREASE
* Primary hypothyrodism * 1⁰ Hyperthyroidsm
* Addison’s disease * Hashimotto’s
*Anti TSH antibodies thyroiditis
* PreEclampsia * Hypothyroidism ( 2or3)
* Hypothermia, fasting rate sometimes
*Pituitary adenoma * Organic brain syndrome
*Postoperatively * Drugs- ASA, heparin
*Acute psychiatric disease
*Thyroiditis
* Drugs-Amiodarone, radiographic dyes

TSH
• Best way to initially test thyroid function.
• Changes in TSH – “early warning system”
• Symptomatic 1⁰ hypothyroidism- >20mu/L
• Mild symptomatic 1⁰ hypothyroidism : 10-20 mu/L
• 1⁰ hyperthyroidism :<0.05 mu/L
• In 2⁰hypothyroidism low TSH levels, prevent making enough TSH to
stimulate thyroid.

TRH
• Regulates TSH secretion from pituitary.
• TSH rise of 5microunits/ml over baseline- euthyroid state
• Significant increase rule out hyperthyroidism.

Difference between T3 and T4
T3 T4
Secretion 30 microgram/day 80 microgram /day
Source 20-25% by gland
75-80% by conversion
Solely by gland
Half life 1 day 7 days
Potency 10 times more potent
than T4
Potent
Binding 0.2% in unbound 0.02% in unbound
Binds to
Thyroxine binding globulin
Thyroxine binding free albumin
Albumin
Apolipoproteins

T4 TESTS
• Total T4 measure bound and free hormones-change when binding proteins
differ.
• Free T4(FT4) or free T4index (FT4I) –more accurately reflect hypothyroidism
• Elevated TSH and low FT4 or FTI → 1⁰ hypothyroidism
• Low TSH and low FT4 or FTI → 2 ⁰ hypothyroidism
• Low TSH with an elevated FT4 or FTI is found in individuals who
have hyperthyroidism.
• Increased total serum T4 →hyperthyroidism or increased con of thyroid
binding proteins
• Decreased total serum T4 →hypothyroidism or decreased con of thyroid
binding proteins/ non thyroid diseases.

Free T4 index
• Total Serum T4(mg/dl) x T3 resin uptake(%)
• High in hyperthyroidism
• Low in hypothyroidism.

T3 TESTS
• T3 tests –diagnosis/ determine the severity of hyperthyroidism.
• In some individuals -low TSH, only T3 is elevated and FT4 or FTI
is normal.
• T3 testing-rarely helpful in hypothyroidism, since it is last test
to become abnormal.
• Measurement of free T3 is possible, but is often not reliable - not
typically helpful.
• Reverse T3 -biologically inactive- not clinically useful
• Total T3 –used to detect T3 toxicosis (increase T3 &normal T4)

Serum T3 resin uptake
• Thyroid hormone binding ratio
• The T3 resin uptake is high when thyroid binding protein is low
and viceversa.
• Increase in T3 resin uptake – consistent with hyperthyroidism
• Decrease in T3 resin uptake – consistent with hypothyroidism

THYROID ANTIBODY TESTS
• A thyroid antibodies test is used to help diagnose autoimmune
disorders of the thyroid.
• + ve Anti-thyroid peroxidase (TPO) and / or Anti-thyroglobulin
antibodies(Tg) - Hypothyroidism - Hashimoto’s thyroiditis.
• Stimulatory TSH receptor antibody (TSI).
• Thyrotropin receptor antibody test (TSHR or TRAb), which detects
both stimulating and blocking antibodies
Hyperthyroidism-Grave’s disease.

NORMAL VALUES
• TPO antibody: Serum level should be less than 9 IU/mL.
• Anti-Tg antibody: Serum level should be less than 4 IU/mL.
• Thyroid-stimulating immunoglobulin antibody (TSI):
This value should be less than 1.75 IU/L.

DISEASES
• Hypothyrodism – Under activity
• Prevalence
Affect 5-17 % of population
Females > Males
Higher in >60 years old
• Types –Primary, Secondary,Teritary
Hashimoto’s thyoditis
Postoperative hyporthyrodism
Postpartum hyporthyrodism
Iatrogenic hyporthyrodism

CAUSES OF HYPOTHYROIDISM
PRIMARY (95%) SECONDARY (5%) TERTIARY (RARE)
• Iodine deficiency
• Excess iodide intake
• Thyroid ablation
• Hashimoto’s
thyroiditis
• Sub acute thyroiditis
• Genetic abnormalities
• Goiterogenic food
• Drugs
-Lithium
-Amiodarone
• Idiopathic
• Hypopituitarism
- Adenoma
- congenital
- neoplasms
- Ablative therapy
- Pituitary destruction
• Pituitary necrosis
(Sheehan’s syndrome)
• Hypothalamic
dysfunction

Hyperthyroidism [Thyrotoxicosis]–Overactivity
• Prevalence
Affect 5-17 % of population
Females > Males
More common in younger persons
• Types -Primary ,Secondary
Graves disease
Thyroid storm
Toxic thyroid nodule
Thyroiditis
Iatrogenic hyperthyroidism

CAUSES OF HYPERTHYROIDISM
PRIMARY SECONDARY
• Graves’s disease
• Toxic multinodular goitre
• Solitary toxic adenoma
• Thyroiditis
-Subacute
-Postpartum
• Iodide-induced
• Follicular carcinoma
• TSH induced
• TSH secreting pituitary
adenoma
-Choriocarcinoma
-Hydatidiform mole
• Iatrogenic hyperthyroidism
• Ectopic thyroid issue

THYROID EXAMINATION
WHAT ALL THINGS TO LOOK FOR IN A PATIENT WITH SUSPECTED
THYROID DISEASES ?
1. Proper history from the patient
2. General examination
3. Thyroid examination
4. System examination

INSPECTION
Anterior Approach and Lateral Approach
• Behaviour
• Hands
• Pulse
• Face
• Eyes
• Thyroid

PALPATION
Normally thyroid gland is not palpable .
• Examination is best carried out from behind, with neck
slightly extended
• Ask pt to slightly flex their neck.
• Assess * size
*Symmetry
*Consistency
*Masses
*Palpable thrill

PROCEDURE
1.Place the 3 middle fingers of each hand along the midline of the neck below the chin
2.Locate the upper edge of the thyroid cartilage(Adam’s apple).
3.Move inferiorly until you reach the cricoid cartilage/ring
4.The first two rings of the trachea are located below the cricoid cartilage and the thyroid
isthmus overlies this area.
5.Palpate the thyroid isthmus using the pads of your fingers(index fingers)
6.Palpate each lateral lobe of the thyroid including inferior border in turn by moving your
fingers down and slightly laterally from the isthmus.
7.Ask the patient to swallow some water , whilst you feel for symmetrical elevation
/superior movement of the thyroid lobes.
8.Ask the patient to protrude their tongue once more.
If mass note- Assess –position,shape,tenderness,consisteny,mobility

PERCUSSION
• Percuss downwards from the sternal notch.
AUSCULTATION
Auscultate each lobe of the thyroid for a bruit.

THYROID SCAN

ADVANTAGES
• Information regarding size, shape, position of gland
• Functional classification of nodules
• To differentiate various causes of thyrotoxicosis.
• In ectopic or metastatic sites.
• Distinguishes diffuse glandular activity from patchy pattern
seen in goitre.
• In association with thyroid suppression regimes, TSH
dependent or autonomous nature of hot nodules.

CONTRAIND
INDICATIONS
• Thyroid nodules
• Diffuse or multinodular goitre
• Clinical hypo-or hyperthyroidism
• Evaluation of substernal mass
• R/O Ectopic thyroid issue
• Subacute thyroiditis, early phase
• Patient with previous h/o of H&N
radiation
CONTRAINDICATIONS
• Pregnancy
• Lactation

Radioactive iodine uptake (RAIU) test
• RAIU test with thyroid scan.
• A radioactive material called a radioisotope, or radionuclide
“tracer,” is given before the test through an injection, a
liquid, or a tablet tracer releases gamma rays
when it’s in your body A gamma camera or
scanner can detect this type of energy from outside your body
The camera scans your thyroid area
Process images and interpet

Normal scan

CT SCAN
• The CT scan is an x-ray test that makes detailed cross-sectional
images .
• It can help determine the location and size of thyroid cancers
and whether they have spread to nearby areas
• Preoperative planning in patients with symptomatic goitre.

PET SCAN
• Fluorine-18-fluorodeoxyglucose (FDG) Positron Emission
Tomography (PET)
• Used to detect local recurrence and distant metastases
of thyroid carcinoma, especially in those patients who present
with high serum Tg, but negative I-131.

FNAC THYROID
INDICATIONS
• Diagnosis of diffuse non toxic goitre, solitary or dominant thyroid
nodule.
• Thyroid nodule over 1 cm in diameter.
• Confirmation of clinically obvious malignancy.
• For defining prognostic parameters.
LIMITATIONS
• Inability to distinguish between follicular adenoma and carcinoma
CONTRAINDICATIONS
Nil.

COMPLICATIONS
• Local hemorrhage and hematoma.
• Transient laryngeal nerve paresis.
• Tracheal puncture.
• Rarely, needling causes formation of a hot nodule.
MATERIALS
• Syringes and syringe holder
• 22-25 gauge needle
• Cotton swabs
• Alcohol bottles for wet fixation.

Rapid smearing Air dried stained with giemsa Alcohol fixed
smears stained with Pap Analysis

BIOPSY
INDICATIONS
• Nodule size > 2cm diameter.
• Regional adenopathy.
• To find cause of nodule/goitre.
• Presence of distant metastases.
• Prior head or neck irradiation.
• Rapidly growing lesion.
• Development of hoarseness, progressive dysphagia, or
shortness of breath.
• Family history of papillary thyroid cancer.

TYPES
• Fine needle aspiration (FNA) biopsy.
• Core needle biopsy.
• Surgical biopsy.

Management
• Symptomatic management
• Drug therapy –Anti thyroid / Synthetic TH supplements
• Surgery

DIET IN THYROID
WHAT WE HAVE TO GET * Iodine
* Tyrosine
* Selenium
OTHERS INTERFERE * Vit D
* Calcium

Iodine Tyrosine Selenium
Cheese
Cows milk
Eggs
Frozen Yogurt
Ice Cream
Iodine-containing
multivitamins
Iodized table salt
Saltwater fish
Seaweed (including
kelp, dulce, nori)
Shellfish
Yogurt
Poultry
Seaweed
Peanuts
Pumpkin seeds
Avacados
Bananas
Chicken
Turkey
Almonds
Sesame seeds
Brown rice
Mustard seeds
Oats
Brazil nuts
Crimini mushrooms
Sunflower seeds
Whole wheat bread
Pinto beans
Shitake mushrooms
Tuna
Beef, Pork
Eggs
Chicken
Fish, shelfish
lentils
Cottage cheese

AVOID….
• Cabbage
• Cauliflower
• Broccoli
• Coffee
• Alcohol even red wine
• Soy foods
• Carbonated drinks
• Fast foods
• Raddish
• Horse raddish
• chocolates
• Millet
• Sweet potatoes
• Potatoes
• Maple syrup
• Dried fruits
• White bread
• White rice
• White pasta
• Sweets
• Cafffeinated energy
drinks

Thyroid and pregnanacy
INCIDENCE
Hyperthyroidism- 2 per 1000 pregnancies
Hypothyroidism
• first time Dx in pregnancy
• Hypothyroid women either discontinue thyroid therapy or
who need larger doses.
• Hyperthyroid women on excessive amount of antithyroid
drugs.
• T3 &T4 can cross placenta, TSH not

• Thyroid stimulating antibodies in maternal
Cross placenta Produce neonatal thyrotoxicosis with
increased neonatal death.
• Gestational transient thyrotoxicosis (1st trimester)
High hCG levels TSH receptor stimulation and
temporary hyperthyroidism
• 20 week gestation
-Reduced hepatic clearance
- Estrogen –induced change in the structure of TBG that prolongs
serum half-life Plasma TBG increases 2.5 fold
25-45% increase in serum total T4
- Total T3 icreases by about 30% in 1st trimester and by 50% to 65
% later

Complications
MATERNAL
• Anemia
• Miscarriage
• Preterm labour
• Preeclampsia
• Congestive cardiac
failure.
• Placenta abruptio
• Thyroid storm
• Infection
• Postpartum hemorrhage
FOETAL
• Mental retardation
• Still birth
• IUGR
• Prematurity
• Hyper/Hypothyroidism
• Increased morbidity and
mortality

PEADIATRICS AND THYROID
Thyroid hormones growth, development, maturation
and brain functions are unique to pediatric age group.
Congenital and acquired disorders of thyroid gland -
constituting nearly 25-30% of all endocrinopathies.
The three major clinical forms of thyroid disorders are
1.Primary hypothyroidism (75%)
2.Goiters ( thyromegaly)- of which nearly 20%, no
alterations in thyroid function.
3.Hyperthyroidism or thyrotoxicosis in 5%

CONGENITALHYPOTHYDOISM-CRETINISM
Thyroid dysgenesis
- Aplasia, hypoplasia
- Ectopic or lingual thyroid gland.
 Iodine deficiency.
Autoimmune thyroiditis- antibody mediated
destruction
Iatrogenic
-Antithyroid drugs and goitrogens
-Irradiation
-Post thyroidectomy

CONGENITAL
HYPERTHYRODISM
• Rare compared to hypo
CAUSES – Antibody mediated –maternal graves
disease
- Pendred syndrome
- Bamfroth Lazarus syndrome
- Brain lung thyroid syndrome.

DM and Thyroid disorders
• Both are disorders of endocrine system.
• Thyroid plays imp role glucose metabolism –Glycogenolysis
and gluconeogeneis, insulin secretion
• Hyperthyroidism Hyperglycemia
• Hypothyroidism Hypoglycemia ,
also increase susceptibility to hypoglycemia thus complicating
diabetes management.
• Hypothyroidism cause insulin resistance further can also leads
to hypergycemia ie Type II Diabetes mellitus

• Hyperthyroidism due to autoimmune causes leads to Type 1
Diabetes mellitus

Thyroid and HTN
HYPERTHYROIDIM
elevated T3 & T4 can cause 1. ↑ HR
2.↑ NE, E receptor sensitivity
Increase contractibility, vasoconstriction
Increase BP
HYPOTHYROIDISM
Low T3 & T4 Acts on kidney causes Sodium retention
Na retention ↑ses Blood volume ↑ses
Increased BP ,T3 &T4 also increases diastolic BP.

THYROID AND DERMATOLOGY
HYPOTHYROIDISM
1.Ichthyotic skin
• Resembles ichthyosis vulgaris
• skin cold and pale
• first clinical manifestation
2.Facies
• Broad nose, thick lips, upper lid droop, face expressionless.
• May have melasma like pigmentation.
3.Hair
• Dry,coarse, brittle hair
• Alopecia –patchy or diffuse ( first symptom of hypothyroidsm)
• Supraciliary madarosis typical

HYPERTHYROIDISM
1.Skin
• Cold, moist, smooth
• Palmoplantar hyperhidrosis
2.Flush
• Persistant flush
• Palmar erythema
3.Pigmentary changes
• Hyperpigmentaion of face , vitiligo – occassional
• Pretibial myxedema

THYROID AND DYSLIPIDEMIA
• Thyroid hormones regulates Lipolysis, LDL uptake
• Hyperthyroidism Hypolipidemia
• Hypothyroidism Hyperlipidemia

THYROID AND INFERTILITY
• Prevalence of hypothyroidism in women in reproductive age is 2%
and 4%.
• Males –rare -0.1%
• Increased TSH ↑ses prolactin
↑ses FSH ,LH ↓ses estrogen, Testosterone
Males - ↓ ses sperm production, Sexual drive ↓ ses , Libido
Females- Decreased ovulation, anovulation, menstrual abnormalities
(amenorrhea, oligomenorrhea)
INFERTILITY

Hyperthyroidism
High T3 & T4 act on liver produce TBG
Binds with T4 produce other globulin SHBG
Binds estrogen & Testosterone ↓es circulating estrogen and
testosterone in blood
Males - ↓ses sperm production, low libido, ↓ ses masculinisation
Females-Anovulation, Amenorrhea, Oligmenrhea
INFERTILITY

THYROID-COMORBIDITIES&COMPLICATION
• Myxedema Coma
• Thyroid storm
• Heart problems
• Mental health issues
• Peripheral neuropathy
• Infertility
• Metabolic syndromes
• HTN, DM, Dyslipidemia

THYROID AND COVID -19
• There is no association b/w novel corona virus and
thyroid abnormalities so far.
• Vaccination do not interfere with thyroid medications.

CASE 1
A 50 year old housewife complains of progressive weight gain of 20
pounds ( 9 kg) in 1 year, fatigue, slight memory loss, slow speech, dry
skin, constipation, and cold intolerance
.
Physical examination : moderately obese, speaks slowly, puffy face,
with pale, cool, dry, and thick skin. The thyroid gland is slightly
enlarged, firm, not nodular, mobile, and not tender. The deep tendon
reflex time is delayed.
Laboratory studies: CBC and differential WBC are normal.
Serum T4 - 3.8 ug/dl, serum TSH is 23.0 uU/ml
Diagnosis : Primary hypothyroidism

CASE 2
:A 35 year old nurse complained of nervousness, mood swings,
weakness, and palpitations with exertion for the past 6 months.
Recently, she noticed excessive sweating and wanted to sleep with
fewer blankets than her husband. Menstrual periods had been regular
but there was less bleeding.
• Physical examination: Pulse -92/minute and BP -130/60. She
appeared anxious, with a smooth, warm, and moist skin, a fine
tremor, she couldn't rise from a deep knee bend without aid
• Laboratory studies: Serum T4=15.6 ug/dl and serum T3=185 ng/dl.
• Diagnosis : Primary Hyperthyroidism

REFERENCES
• American thyroid association guidelines
• European thyroid association guidelines
• Thyroid disorders, Kottakkal Ayurveda Series 167.
• Wikipedia
• Davidson’s principles &practice of medicine-22nd edition
• Illustrated synopsis of Dermatology and sexually transmitted
diseases,Neena Khanna-6th Edition; page no 399
• Desai PM. Disorders of the Thyroid Gland in India. Indian J Pediatr
1997;64:11-20
• Principles of Anatomy and Physiology –Gerald J Tortora-12th edition
• IAP Textbook of peadiatrics-7th edition
• Usha Menon V, Sundaram KR, Unnikrishnan AG, Jayakumar RV, Nair
V, Kumar H. High prevalence of undetected thyroid disorders in an
iodine sufficient adult south Indian population. J Indian Med Assoc
2009;107:72-7

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