Thyroid function tests

DrNeha Mahajan
MD Pathology
HPT axis
CLASSIFICATION OF TESTS BASED ON FUNCTIONS OF THYROID

Tests measuring blood levels of thyroid hormones:

•Sr PBI
•Circulating T3 and T4 level
•Circulating TSH level
•Plasma tyrosine level

Tests based on primary function if thyroid viz substrate input &

hormone synthesis:
• RIU(Radioiodine uptake studies)
•PBI131
•T3 suppression test
•TSH stimulation test
•TRH stimulation test

Tests based on metabolic effects of thyroid hormones

•BMR
•Sr cholestrol
•Sr creatine level
•Sr uric acid level
•Sr CK enzyme
Scanning of thyroid gland

Immunological tests to detect autoimmune diseases of thyroid gland:

•Agar gel diffusion test(PPT test)
•TRCH test: tanned red cell haemagglutination test
•Complement fixation test
 Indications of TFT

• 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
Abnormalities of thyroid
 Hypothyroidism
Causes:
PRIMARY: (high TSH)
•Autoimmune : Hashimoto`s, Atrophic
•Iatrogenic: I131 t/t, subtotal/total thyroidectomy, external irradiation of neck for Ca
•Drugs: I excess, lithium, antithyroid drugs, p- aminosalicylic acid,Interferon
•Congenital hypothyroidism: absent/ectopic thyroid gland, dyshormonogenesis, TSHR
mutation
•Iodine deficiency
•Infiltrative disorders

SECONDARY: (Low TSH)

•Hypopitutarism: tumors, surgery, irradiation ,infiltrative disorders, sheehan`s
syndrome,trauma
•Isolated TSH deficiency or inactivity

TERTIARY : (LOW TSH ,Low TRH)

Diseases of hypothalamus

TRANSIENT: silent / postpartum thyroiditis, subacute thyroiditis

 Clinical Features of Hypothyroidism

Tiredness Puffy Eyes

Forgetfulness/Slower Thinking Enlarged Thyroid (Goiter)

Moodiness/ Irritability Hoarseness/
Deepening of Voice
Depression
Persistent Dry or Sore Throat
Inability to Concentrate
Thinning Hair/Hair Loss Difficulty Swallowing
Loss of Body Hair Slower Heartbeat

Dry, Patchy Skin Menstrual Irregularities/

Heavy Period
Weight Gain Infertility
Cold Intolerance
Elevated Cholesterol Constipation
Muscle Weakness/
Family History of Thyroid Cramps
Disease or Diabetes
 TSH/FT4

TSH TSH TSH

T4 N FT4 FT4

Thyoid Subclinical Sec/tertiary

microsomal Ab Hypothyroidism Hypothyroidism

Increased normal Little or Delayed

TSH response TSH response

Hashimoto`s Cong T4
Thyroiditis synthesis
Secondary Tertiary
(pitutary)
 Hyperthyroidism
Causes:
PRIMARY HYPERTHYROIDISM
Grave`s disease
Toxic MNG
Toxic Adenoma
Functioning thyroid carcinoma mets
Activating mutation of TSH receptor
Struma ovarii
Drugs: iodine excess(Jod basedow phenomenon)
SECONDARY HYPERTHYROISM
TSH secreting pitutary adenoma
TRH syndrome
Chorionic gonadotropin secreting tumors
Gestational thyrotoxicosis

THYROTOXICOSIS WITHOUT HYPERTHYROIDISM

Subacute thyroiditis
Silent thyroiditis
Other causes of thyroid destruction: amiodarone,radiation,infarction of adenoma
Ingestion of excess thyroid hormone
Signs and Symptoms of Hyperthyroidism

Hoarseness/
Nervousness/Tremor Deepening of Voice

Mental Disturbances/ Persistent Dry or Sore Throat

Irritability
Difficulty Swallowing
Difficulty Sleeping
Bulging Eyes/Unblinking Stare/ Palpitations/
Vision Changes Tachycardia

Enlarged Thyroid (Goiter) Impaired Fertility

Weight Loss or Gain
Menstrual Irregularities/
Light Period Heat Intolerance
Increased Sweating
Frequent Bowel Movements
Sudden Paralysis
Warm, Moist Palms

Family History of
First-Trimester Miscarriage/
Thyroid Disease
Excessive Vomiting in Pregnancy
or Diabetes
 Evaluation of hyperthyroidism
TSH, fT4

Low TSH,high fT4 Low TSH,normal fT4 High TSH,highfT4

Primary Measure FT3

hyperthyroidism Pitutary adenoma
(secondary hyperthyroidism
Thyroid hormone resistance
TRAb +ve TRAb –ve Normal High
Diffuse uptake Nodular uptake
TRH test

TRAb-ve
•Subclinical/mild T3
Irregular uptake response
•NTI thyrotoxicosis
•Drugs
No response
Grave`s
disease
Toxic MNG Toxic Resistance to Pitutary
adenoma thyroid hormone adenoma
 TSH
•First line test in Thyroid function tests
•Normal TSH level excludes thyroid dysfunction

Uses:
•Screening for euthyroidism
•Screening of hypothyroidism in newborns
•Diagnosis of 1 & 2 hypothyroidism
•Diagnosis of clinical & subclinical hyperthyroidism
•Follow up of T3 & T4 replacement therapy in hypothyroidism
 TSH
Increase Decrease
• Primary hypothyroidism • Primary hyperthyroidism
• Addison`s disease • Hashimoto`s thyroiditis
• Anti TSH antibodies • Hypothyroidism(2 or 3)
• PreEclampsia sometimes
• Hypothermia,fasting state • Organic brain syndrome
• Pitutary adenoma • Drugs:
• Postoperatively ASA,heparin,ketoconazole,T3,d
• Acute psychiatric illness opamine,
glucocorticoids,octreotide
• Thyroiditis
• Drugs:Amiodarone,bensarazide
,clomiphene, iopanoic acid,
lithium, methimazole,
metoclopramide,morphine,prop
ylthiouracil,radiographic dyes
 Methods of TSH estimation
•Radioimmunoassay
•Immunometric assay
•Chemiluminiscent & flourescent techniques(3rd gen)

•Normal values: TSH 0.4 to 4mU/L

 Total thyroxine

•Total thyroxine includes free as well as protein bound

thyroxine.

•Normal levels:5 to 12.5ug/dL, largely bound to transport

protein espTBG.

• T4 combined with TSH gives the best measurement of thyroid

function.
 Thyroxine

Increase Decrease
• Hyperthyroidism • Primary hypothyroidism
• Factitious • Secondary/pitutary
hyperthyroidism hypothyroidism
• Pitutary TSH secreting • Severe non thyroidal
pitutary tumor illness
• Raised TBG • Decrease TBG
 Free T4
•Small fraction of total T4 unbound to protein

•Metabolically active form

•0.05% of total T4

•Do not get affected by TBG levels or NTI

•Measurement useful in conditions where TBG levels

are affected

•Normal levels:0.89- 1.76ng/dL

 TBG(Thyroid binding globulin)
Main sr.carrier protein for both T4 & T3
(13-39ug/dL)
Increase Decrease
• Drugs:Clofibrate,estrogen,O.c • Drugs:Androgens
Pills,Heroin.methadone ,glucocorticoids,phenytoin,larg
• Genetic e doses of salicylates
• Acute & chronic hepatitis • Malnutrition
• Pregnancy • Hypoproteinemia,nephrotic
• Acute intermittent porphyria syndrome
• Angioneurotic edema • Acromegaly,cushing`s
syndrome
• Hyperproteinemia
• Liver failure
• Sepsis
 Free and Total T3

•T3 levels not routinely done

•Normal plasma level T3 are very low
•Metabolically more active, shorter half life,faster turn over
•Free T3 0.5% of total
•Free T3 measurement useful with altered protein level
•T3 level:80 to 180ng/dl
•fT3 level:1.5 – 4.1pg/mL
•Measured by immunoassays

Uses:
•Diagnosis of T3 thyrotoxicosis
•Early diagnosis of hyperthyroidism
 Thyroglobulin

Synthesised & secreted by thyroid follicles(30ng/ml)

Reflects throid mass,thyroid injury & TSH receptor stimulation
Tg Grave`s disease
Thyroiditis
Nodular goitre

Indications :Monitoring recurrence of certain variants of thyroid Ca

Thyroid dysgenesis in Congenital hypothyroidism
Follow up of patients with thyroid malignancy
 Thyroid Autoantibodies

•Diagnosing autoimmune diseases

•Autoantibodies :Tg,Thyroid microsomal Ag, TSH receptor, non
Tg colloid antigen,TSH,T4

Anti Tg antibodies

Methods: Agar gel diffusion precipitation test

Tanned red cell haemagglutination tests(TRCH test)
ELISA
Immunoflourescence of tissue section
RIA
Positive: Hashimoto`s thyroiditis,Grave`s
disease,myxedema,nontoxic goitre,thyroid ca,pernicious anaemia
 Antimicrosomal Abs

•Methods: CFT,Immunoflourescence tests,TRCH

assay,ELISA,RIA
•Positive in grave`s disease & Hashimoto`s thyroiditis
•More frequently positive for autoimmune diseases than
Tg Ab

Thyroid receptor antibody

Types:
•TBI (Grave`s disease)
•TSIgs ( Grave`s disease,predicting relapse or remission
in hyperthyoid, development of neonatal
hyperthyroidism)
 Radioiodine uptake studies
Correlates with functional activity of thyroid gland
•Tracer dose of I131 orally followed by measurement of amount
of radioactivity over thyroid gland at 2 hrs and again at 24hrs
•Normal radioactive uptake 20 to 40 % of administered dose
at 24 hr

•Increased Uptake : Decreased uptake:

•hyperthyroidism due to •hypothyroidism

grave`s disease, •subacute thyroiditis,
•toxic MNG, •large I 2 doses, thyroid
•toxic adenoma, hormone
•TSH secreting tumor •factitious hyperthyroidism
 TRH stimulation tests
Uses: Confirms diagnosis of secondary hypothyroidism
Evaluation of suspected hypothalamic disease
Procedure:
TRH injected iv(200 0r 500ug) followed by measurement of
serum TSH at 20 & 60 min

Interpretation:
Peak response in normal 4 times elevation of TSH
Primary hypothyroidism: exaggerated & prolonged
response
Secondary hypothyroidism: blunted response
Tertiary hypothyroidism: response is delayed
 T3suppression test

Use: differentiates boderline high normal from primary

hyperthyroidism(grave`s disease)

Procedure: After 24 hr RIU studies & obtaining basal value

and serum T4 values,20 ug of T3 four times a day is
given for 7 to 10 days
RIU is repeated after administration & serum T4 values are
also determined
Interpretation:
A suppression is indicated by the 24 hrs RIU falling to <
50% of initial uptake & totalT4 to approx 2ug/ml or less

Non suppression indicates autonomous thyroid

function.(Grave`s disease)
 TSH stimulation test

Use:Differentiates primary from secondary hypothyroidism

Procedure: After 24hr RIU studies,3 injections of TSH, each 5

USP units are given at 24 hrs interval
24hr RIU is measured after 42 hrs after final TSH dose.

Interpretation:
In primary hypothyroidism, failure of stimulation of gland
In secondary hypothyroidism, stimulation of gland showing
increased RIU.
Tests based on metabolic effects of
thyroid hormones
BMR:
Between 5% & 20% normal
Euthyroid state : -10% to 10% of normal
Hyperthyroidism:50% to 75%
Hypothyroidism: < -20%
Sr. CHOLESTROL LEVEL:
260mg% hypothyroidism
Sr. CREATINE LEVEL
0.6mg% hyperthyroidism
Sr. URIC ACID LEVEL:
Myxedema 6.5 to 11mg%
Sr. CK LEVELS & HYPERCALCEMIA
Thyroid scan
 Advantages /Uses of scintiscan

 Distinguishes diffuse glandular activity from patchy

pattern seen in goitre
 Functional classification of nodules: warm,hot,cold
 In association with thyroid suppression regimes, TSH
dependent or autonomous nature of hot nodules
 Information regarding size, shape, position of gland
 Identification & localisation of functioning thyroid tissue in
ectopic or metastatic sites
 Helps on differentiating various causes of thyrotoxicosis
 Indications:
1.Thyroid nodule(s)
2. Diffuse or multinodular goiter
3. Clinical hyper- or hypothyroidism
4. Evaluation of substernal mass
5. R/O Ectopic thyroid tissue
6. Subacute thyroiditis, early phase
7. Patient with previous Hx of H & N radiation

Contraindications:
1.Pregnancy
2.Lactation
Normal thyroid scan
Cold nodule Hot nodule
 Hot nodule/Functioning

Hyperfunctioning adenoma(s)
 Anatomical variant
 Thyroid carcinoma 2%
 Compensatory hypertrophy
 Warm nodule/Isofunctioning

 Functioningadenoma
 Anatomical variant
 Thyroid carcinoma 4%
 Deep seated cold nodule
 Cold nodule/non functioning nodules

Colloidal cyst
 Hypofunctioning adenoma
 Thyroid carcinoma
15-25 %
 Others : focal thyroiditis,
abscess, hematoma,
lymphoma, metastasis,
parathyroid adenoma, lymph
node enlargement
(rare)
Grave`s disease

Diffuse enlargement
Homogenous uptake
Toxic MNG

Inhomogenous uptake
 Whole body scan I131
1.Post-operative evaluation for thyroid remnant or
functioning metastasis
2. Follow up patients after I-131 ablation or I-131 treatment
3. Serum Tg rising
4. Suspected tumor recurrence
5. Suspected functioning metastases, either local or distant
metastases
 FNAC thyroid

Indications:
Diagnosis of diffuse non toxic goitre
Diagnosis of solitary or dominant thyroid nodule
Confirmation of clinically obvious malignancy
To obtain material for special laboratory investigations aimed at
defining prognostic parameters.

Main limitation: Inability to distinguish between between follicular

adenoma & carcinoma.
Contraindications: No

Complications:
Local h`age & haematoma.
Transient laryngeal nerve paresis.
Tracheal puncture
Rarely,needling causes formation of a hot nodule
Materials

Syringes & syringe

holder(pistol)
22-25 guage needle
Cotton Swabs
Alcohol bottles for
wet fixation
FNAC aspiration technique
FNAC non aspiration technique
Smearing, fixation & staining

Rapid smearing
Air dried stained with
giemsa
Alcohol fixed smears
stained with Pap
 Sample adequacy

 Six groups of follicular cells, each containing 10 to 20

cells on two separate slides
 Presence of colloid indicates benign nature
 Bethesda system of reporting FNAC thyroid
1.Non diagnostic/Unsatisfactory
Cyst fluid only
Virtually acellular specimen
Other(obscuring blood,clotting artifacts)
2.Benign
Consistent with Benign follicular nodule(adenomatous,collloid nodule)
Consistent with lymphocytic(hashimoto`s thyroiditis) with proper clinical context
Consistent with granulomatous (subacute thyroiditis)
Other
3.Atypia of undetermined significance/Follicular lesion of undetermined
significance
4.Follicular neoplasm or suspicious for follicular neoplasm
Specify if hurthe(oncocytic type)
5.Suspicious for malignancy
Suspicious for papillary,medullary,metastatic,lymphoma,other
6.Malignant
Papillary thyroid Ca,poorly differentiated ca,medullary thyroid ca,undifferentiated
ca,Squamous cell ca,Ca with mixed features,metastatic carcinoma,NHL,other
 Approach to a case of thyroid enlargement

DIFFUSE
NODULAR CYSTIC
•Acute suppurative
•Follicular •Colloid cyst
thyroiditis
•Medullary •Cystic malignancy
•Subacute thyroiditis
•Papillary •Thyroglossal cyst
•Hashimoto`s thyroiditis
•Toxic nodule •Parathyroid cyst
•Adenomatous /colloid
goitre
•Painless /silent
thyroiditis
•Grave`s disease
•Invasive fibrosis
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Thank you 