Thyroid Function Tests

Dr. Abhinav Manish

MBBS. MD.
Set of Biochemical Test’s carried out in
clinical laboratory for assessing the
functional status of Thyroid Gland.
Thyroid hormones:-
Tetra Iodothyronine / Thyroxine (T4)
Tri Iodothyronine (T3)
Binds to:(For Transportation)
 Thyroxine binding globulin (TBG)
 Thyroxine binding pre albumin (TBPA)
 Albumin
 Free fractions are metabolically active
and T3 is More
Potential and Biologically Very active
Thyroid hormone thanT4
 Differences between T3 and T4
Biochemical Tri Iodothyronine Thyroxine (T4)
Feature (T3)
Secretion 30 microgram /day 80 microgram
/day
Source 20 – 25% by gland Thyroid gland
75 - 80% by
conversion

Half-life 1 day 7 days

Potency 3-4 times more potent Potent

than T4
Binding 0.2% in unbound 0.02% in unbound
 Function of Thyroid Hormones
 Thyroid hormones play important role in basal metabolism
(BMR)
 Increases cellular metabolism
 Increased oxidation of carbohydrate
 Increased cholesterol degradation
 Stimulate RNA & protein synthesis.
 Increases blood glucose level.
 Responsible for maturation of brain.
 High conc. Of T3 causes protein catabolism.
 Significance of TFT
 The test reports of TFT assess the functional status of the
thyroid gland as
 Euthyroid (Normal functioning)
 Hyperthyroid (Hyper functioning)
 Hypothyroid (Hypo functioning)
 Assess the degree of thyroid dysfunction.
 Help to evaluate the cause for the thyroid dysfunction i.e.,

find out pituitary defect or thyroid gland defect

(differentiate b/w primary & secondary hypothyroidism)
 TFT also has prognostic significance after drug
therapy.
 TFT based on immunological test are helpful in

detecting & diagnosing autoimmune disorders of

thyroid gland
 Graves disease (leads to hyperthyroidism)
 Hashimotos thyroiditis (leads to
hypothyroidism)
 Classification of Thyroid Function Test
1. Test to check the primary function of the thyroid gland –
a) Radio iodine uptake studies (RIU)/Replaced with Tm-
99
b) T3 suppression test
c) TSH stimulation test
d) TRH stimulation test
2. Test measuring blood levels of thyroid hormones
e) Estimation of blood T3 & T4 levels
f) Estimation of blood TSH level
g) Estimation of blood FT3 & FT4 levels(Immunological
active)
 3. Test based on metabolic effect of thyroid hormones
a) Determination of BMR
b) Estimation of serum cholesterol
c) Estimation of serum uric acid
d) Estimation of Creatine Kinase (CK) activity
4. Scanning of thyroid gland
5. Immunological test to detect autoimmune disease of
thyroid gland. (Auto-antibodies)
e) Elisa techniques
f) Radio immunoassay (RIA)
 Normal Ranges

1. TSH 0.35-5.50 µU/ml

2. T3 0.60-1.81 ng/ml
3. T4 4.5-10.9 µg/dl.
4. FT3 2.2-4.3 pg/ ml
5. FT4 0.8-2.8ng/dl
Laboratory Evaluation of Thyroid Hormones

 Thyroid Stimulating Hormone / TSH

(First thing you assess)
 Normal range 0.35-5.50 µU/ml
 Normal result excludes a primary

abnormality of function.
 Free Thyroxin /FT4 (if abnormal TSH is present)
 Normal range 0.8 – 2.8 ng/dl
 Elevated – Hyperthyroidism
 Suppression – Hypothyroidism
 Hypothyroidism- decrease blood level of T3 & T4

while increase blood level of TSH

 Hyperthyroidism - increase blood level of T3, T4

while TSH is decreased.

 Subclinical Hypothyroidism- Normal blood level of

T3, T4 while TSH is increased.

 Subclinical Hyperthyroidism- Normal blood level of

T3, T4 while TSH is decreased.

Test to determine the etiology of thyroid dysfunction.
 Anti – TPO. Antithyroid Peroxidase antibody.
 Used to detect autoimmune thyroid disease
 Up to 80% of those with graves disease have TPO

antibodies.
 90% of those with Hashimoto’s Thyroiditis have

TPO antibody.
Thyroid scanning & ultrasound
 Nuclear imaging
 Ultrasound
 Thyroid disorders

Hypothyroidism
 Primary
 Secondary
 Tertiary

Hyperthyroidism
 Hypothyroidism
Insufficiency in the amount of thyroid hormone in the body.
1) Primary Hypothyroidism:-
 Thyroid gland failure despite proper stimulation from the

pituitary.
2) Secondary Hypothyroidism:-
 Failure of the pituitary to produce TSH to stimulate the

thyroid gland.
3) Tertiary Hypothyroidism:-
 Failure of the hypothalamus.
 Symptoms of hypothyroidism
 Enlargement of gland
 Constipation
 Dry and coarse skin and hair
 Facial puffiness
 Cold intolerance
 Decreased sweating
 Impaired memory
 Confusion
 Dementia
 Low speech and motor activity
 Anemia
 Causes of hypothyroidism
Primary Secondary Tertiary
Iodine deficiency Hypopituitarism Hypothalamic
dysfunction
Excess iodide intake - Adenoma
Thyroid Surgery - therapy
Hashimoto’s thyroiditis - Pituitary
destruction
Sub acute thyroiditis
Genetic abnormalities
Goiterogenic food (cabbage)

Drugs
– Lithium, Amiodarone,
Anti thyroid agents
 Symptoms of hyperthyroidism
 Nervousness
 Fatigue
 Weight loss
 Heat intolerance
 Increased sweating
 Tachycardia
 Warm and moist skin
 Tremors
 Thyroid disorders - Causes of Hyperthyroidism

a) Overproduction of thyroid hormones

a) Grave’s disease
b) TSH secreting pituitary adenomas
c) Multi nodular goiter
b) Leaking thyroid hormone due to thyroid destruction
a) Lymphocytic thyroiditis
b) Sub acute thyroiditis
c) Radiation
c) Drugs
a) Thyroid replacement drugs
b) Amiodarone
Metastatic thyroid carcinoma
 Order Of Testing
Perform TSH

TSH elevated TSH Decreased

Add FT4 Add FT4 + FT3

Normal FT4 Low FT4 Elevated FT4/ Normal

Consider Hypothyroidism, FT3 FT4/FT3
auto antibodies Consider Hyperthyroidism, Clinical
to assess Thyroxine Consider review
further risk therapy Antithyroid & consider
therapy repeat
in
6 months
 High T4 Normal T4 Low T4
High Irregular use of Subclinical Primary
TSH Thyroxine Amiodarone hypothyroidism hypothyroidism
Pituitary
hyperthyroidism
(TSH-producing
pituitary tumour-rare)
Thyroid hormones
resistance (very rare)
Normal As above Normal Some drugs
TSH Some drugs (steroids, (anticonvulsants,
beta-blockers, anti-T3, Anti-T4
NSAIDS) Pituitary or
Non-thyroidal illness hypothalamic
T4 replacement hypothyroidism,
(sometimes stablises Severe non-
with normal TSH & thyroidal illness
FT4)
 High T4 Normal T4 Low T4
Low Primary hyperthyroidism Subclinical Pituitary or
TSH hyperthyroidism hypothalamic
Subtle T4 over hypothyroidism,
replacement Severe non-
Non-thyroidal thyroidal illness
illness
Facial Appearance In Graves
Disease
 Case 1
 A 35 year old woman reported at Dr. K.K.B.M Subharti
hospital with a complaint of sleepiness, constipation and
sensitivity to cold. The doctor noticed a low heart rate
(BP-110/70 mmHg) and advised her to have a blood test.
Following are the biochemical findings. What is your
probable diagnosis?
TSH 10 µU/mL
T3 0.29 ng/ml
T4 3.0 µg/dl.
 Case 2
 A 36 year old young male reported at Dr. K.K.B.M
Subharti hospital visits the doctor with a complaint
sleeplessness, weight loss, weakness and excessive
sweating. The doctor noticed a rapid heart rate (BP-
150/90 mmHg) and nervousness and advised her to
have a blood test .Following are the biochemical
findings. What is your probable interoperation?
TSH 0.25 µU/mL
T3 3.0 ng/mL
T4 13 ng/ml.
 Case 3
 A 50 year old women were admitted to the hospital
due to increased heart rate, severe weakness, weight
loss and exophthalmoses (abnormal protrusion of
the eye). She was extremely irritable, could not
tolerate heat and was short of breath. Physical
examination revealed bilateral eyelid lag. The
plasma level of T3 and T4 showed high value.
 What is your probable diagnosis ?
 .
THANK YOU
Adrenal Function tests
1. Paired organ
2. Weight about 4 gms
3. Pyramidal in shape
4. Supra renal location (on the top of kidneys)
5. At the T12 level
6. Each divided in to:
◦ Cortex- outer part of the gland
◦ Medulla- inner part of gland
 Adrenal

Cortex Medulla

Zona Zona Zona Chromaffin

glomerulosa Fasiculata Reticularis cells
 Mineralocorticoid

 Regulates concentration of Na+ and K+.

◦ Kidney conserves Na+.
◦ Kidney excretes K+.
◦ Therefore, decreased aldosterone will lead to
hyperkalemia and hypornatremia.
 Responds to changes in composition of
plasma.

 Regulated by renin-angiotensin system of

kidney
 ACTH

Regulation of
adrenal gland
secretion

Cortisol
Cortisol
Pattern of cortisole level during the day
Adrenal Dysfunction

 Adrenal insufficiency  Cushing syndrome

 Low cortisol, High Cortisol
aldestrone Eg Addison  Hyperaldosteronism
disease High aldestrone
 Pheochromocytoma
High
catecholamine

Decrease function Increase function

.
Causes of Adrenal insufficiency

1. Congenital adrenal hyperplasia

2. Addison disease most common cause and it’s
acquired.
3. Infection (TB, sepsis)
4. Adrenoleukodystrophy very rare.

.
Test for Adrenal-ACTH axis.
 1. Insulin Stress test
 Gold Standard test
 After adequate hypoglycemia of <2.2 mmol/L

a normal rise of plasma cortisol up to

550nmol/L is observed.
Addison disease
1. Autoimmune
2. Isolated or associated with other
autoimmune disease
3. Presents with tiredness, weight loss, skin
pigmentation
4. Hypotension, hyponatremia, hyperkalemia
5. Aldestrone & cortisol low, high ACTH, high
renin
6. Low sodium , high potasium

.
1. ACTH stimulation test: diagnostic test by
giving synthetic ACTH (IV or IM) and
measuring the serum cortisol at 30 and 60
minutes. In normal individuals the baseline
cortisol should be doubled after the test
whereas in adrenal insufficiency, the baseline
(which is low) is only increased to 25% after
the test.
2. Adrenal antibodies
3. Treatment : cortisol + aldosterone
Hyperpigmentation

A Color Atlas of Endocrinology p97

Addisonian crisis

 Life threatening complication

 Severe vomiting and diarrhoea followed by
dehydration
 Low blood pressure and shock
 Hypoglycemia
 Loss of consciousness
 Treatment: IV fluids + IV hydrocortisone
Adrenal
insufficiency
with echomosis
is suggestive of
meningeococcal
septicemia.
Congenital Adrenal Hyperplasia
 Family of inherited disorders of adrenal
synthesis

 Autosomal Recessive

 Each disorder results from a deficiency of

one of the five enzymes necessary for
steroid synthesis

 21-hydroxylase  is the commonest

form
(90–95% of CAH cases)
Steroid biosynthetic enzymes
1) Cholesterol side chain cleavage=
desmolase)

2) 3-Hydoxysteroid dehydrogenase

3) 17 -Hydroxylase

4) 21-Hydroxylase

5) 11-Hydroxylase
Minerlocorticoid Glucocoticiod Sex Steroid
Desmolase

Cholesterol 17,20 lyase

Pregnenlolone 17 a
OH
17 OH Pregnenlolone DeHydroEpiAndrosterone
3 B HSD
3 B HSD 3 B HSD

Progesterone 17 a
OH
17 OH Progesterone Androstendione
21 OH
21 OH

Desoxycorticosterone 11 Desoxycortisol
11 OH
11 OH
Testosterone Estradiol
Corticosterone
18 OH Cortisol
18 OH Corticosterone
Aldosterone
• Desmolase is the first step in the pathway and if deficient all
three pathways will be stopped. Only female genitalia
because no androgens at all.

• 3BHSD deficiency: all 3 enzymes will be absent but will also

present with ambiguous genitalia because of high levels of
DHEA

• 17aOH: cortisol and androgens are deficient and males will

present with ambiguous genitalia. Aldosterone is present;
therefore, they will not develop adrenal crisis and will have
hypertension due to the excess aldosterone levels.
 Definitions

 Cushing’s Syndrome
◦ Excess cortisol in the blood

 Cushing’s Disease most common

◦ Excess cortisol in the blood due to an ACTH secreting pituitary
tumour, due to pituitary adenoma.
 Cushing’s syndrome
 Cushing’s Syndrome
◦ Results from increased adrenocortical
secretion of cortisol
◦ Causes include:
 ACTH-secreting tumor of the pituitary
(Cushing’s disease)
 excess secretion of cortisol by a neoplasm
within the adrenal cortex
 ectopic secretion of ACTH by a malignant
growth outside the adrenal gland
 excessive or prolonged administration of
steroids
Cushing’s syndrome
 Cushing’s Syndrome
◦ Characterized by:
 truncal obesity
 moon face
 buffalo hump
 acne, hirsutism
 abdominal striae
 hypertension
 psychiatric disturbances
 osteoporosis
 Amenorrhea
 Diabetes
 Establishing the Cause

 Serum ACTH, cortisol and urine free

cortisol (urine free cortisol is so sensitive, if
high you do the suppression test)
 Dexamethasone Suppression testing
 Localisation of the ACTH source
◦ Imaging (MRI) for pit pathologies
◦ CT scan for adrenal pathologies.
Treatment of Cushing’s syndrome
 Treatment of underline cause
 Surgery for neoplasia

.
Data interpretation
A 2 week old infant presents to hospital with 1 week
history of persistent vomiting and lethargy. On
examination the infant is 10% dehydrated and
unwell. He has normal male genitalia and both
gonads are palpable blood results are:

Sodium 115 mmol/L

Glucose 3.8 mmol/L; hypoglycemic <2.7mmol/L
Potassium 7.2 mmol/L

What two investigations would be most likely to

confirm the diagnosis?
How do you treat?
 This case could be CAH or hyponatremic dehydration,
so now we added the presence of hyperpigmentation
to the scenario to confirm CAH.
 The most important 2 investigations are: A. 17

hydroxyprogesterone as a screening test, it will be

high (blockage of 21OH will lead to its accumulation
of substrate before. B. ACTH stimulation test to
confirm the diagnosis.
 DNA study (CYP21) for 21 OH deficiency is done at

the end.
 Treatment: I.V fluid and I.V hydrocortisone for the

treatment of the crisis, and replacement of cortisol

and aldosterone for life.
 Not addisons because it doesn’t present in the first

few months of life.

Newborn Screening