Thyroid Function
Tests
R. C. Gupta
M.D. (Biochemistry)
Jaipur (Rajasthan), India
Thyroid function tests are commonly done
to diagnose hyper- and hypo-thyroidism
Most patients with thyroid disorders have
only isolated signs and symptoms
A clinical diagnosis is usually difficult
Diagnosis often requires laboratory tests
Dietary iodide is absorbed by the alimentary
tract, and released into circulation
Some of it is excreted in urine
Some is taken up by the thyroid gland, and
is converted into iodine
Production of thyroid hormones
Iodine reacts with the tyrosine residues of
thyroglobulin
Tyrosine is converted into mono-iodo-
tyrosine (MIT) and di-iodo-tyrosine (DIT)
Two DIT residues react with each other to
form tetra-iodo-thyronine (thyroxine or T4)
One residue each of MIT and DIT react to
form tri-iodo-thyronine (T3)
T3 and T4 are stored in thyroid acini,
attached to thyroglobulin
The hormones are released into blood
as and when needed
They are transported in circulation by
thyroxine-binding globulin (TBG)
The TBG-bound hormones are inactive
Small amounts of T3 and T4 are released
from TBG
These exist as free T3 and T4 in circulation
Free T3 and T4 are the biologically active
forms of the hormones
T4 is more abundant than T3 but T3 is
more powerful
Synthesis and release of T3 and T4 are
increased by thyroid-stimulating hormone
(TSH) of anterior pituitary
TSH secretion is increased by thyrotropin-
releasing hormone (TRH) of hypothalamus
High blood levels of T3 and T4 cause feed-
back inhibition of TSH and TRH secretion
Before the advent of radio-immuno-
assay for hormones, tests for thyroid
function were indirect and non-specific
Some of the older tests are:
• Basal metabolic rate
• Serum cholesterol
• Serum protein-bound iodine
• Radioactive iodine uptake
Thyroid hormones stimulate all metabolic
activities
This increases the basal metabolic rate
(BMR)
Hence, BMR is raised in hyperthyroidism
and lowered in hypothyroidism
Basal metabolic rate
However, BMR is affected by a number of
physiological and pathological conditions
Therefore, this test lacks specificity
Serum cholesterol level is decreased in
hyperthyroidism and increased in hypo-
thyroidism
But this test is non-specific because serum
cholesterol can become abnormal in a
number of other diseases
Serum cholesterol
In this test, the iodine bound to serum
proteins is measured
Most of the protein-bound iodine (PBI) is
present in T3 and T4
Serum protein-bound iodine
Serum PBI is increased in hyperthyroidism
and decreased in hypothyroidism
However, accuracy of PBI measurement is
poor
This test measures the uptake of circulating
iodide by the thyroid gland
A small dose of a radioactive isotope of
iodine (5 µc of Na131I) is given to the
subject orally in a fasting condition
Radioactive iodine uptake
The radioactivity over the thyroid gland is
measured by a Geiger Muller counter after
2, 24 and 48 hours
This is a measure of the radioactive iodine
present in the thyroid gland
The normal uptake of the ingested dose is:
▪ 1.5-15% at two hours
▪ 25-50% at 24 hours
▪ 15-40 % at 48 hours
Radio-active iodine uptake is increased in
hyperthyroidism and is decreased in hypo-
thyroidism
Sensitive and specific methods of
hormone assays are available now
Hence, the older tests have now become
obsolete
Thyroid function tests commonly done
now are:
• Serum T3 and T4
• Serum Free T3 (FT3) and Free T4 (FT4)
• Serum TSH
• Thyroperoxidase antibodies (TPO Ab)
• TRH stimulation test
Normal range of total T4 in serum is 5-12
µg/dl
It is increased in hyperthyroidism and is
decreased in hypothyroidism
Serum T4
The normal range of total T3 in serum is
0.1-0.2 µg/dl
It is increased in hyperthyroidism and is
decreased in hypothyroidism
An increase in serum T3 with normal T4 is
seen in T3 toxicosis
Serum T3
Sometimes, serum total T4 may be normal
despite the presence of a thyroid disorder
In such cases, measurement of serum FT4
can clinch the diagnosis
Normal range of serum FT4 is 0.8-2 ng/dl
It is increased in hyperthyroidism and is
decreased in hypothyroidism
Serum Free T4 (FT4)
Like serum FT4, serum FT3 may be very
useful in the diagnosis of subtle disorders
of thyroid gland
Normal range of serum FT3 is 0.3-0.6
ng/dl
Serum Free T3 (FT3)
Serum TSH can differentiate between
primary thyroid disorders and those
secondary to pituitary/hypothalamic disease
In primary hyperthyroidism, serum TSH is
decreased due to feedback inhibition
In hyperthyroidism secondary to pituitary or
hypothalamic disease, serum TSH is raised
Serum TSH
In primary hypothyroidism, serum TSH is
high due to lack of feedback inhibition
In hypothyroidism secondary to pituitary
or hypothalamic disease, it is decreased
The normal range of serum TSH is 0.5-5
µU/ml
Hypothyroidism can sometimes occur due
to Hashimoto’s thyroiditis or post-partum
thyroiditis
In such cases, the disease results from
an autoimmune response against thyro-
peroxidase
Thyroperoxidase antibodies
(TPO Ab)
The autoimmune disorder can be
diagnosed by detection of thyro-
peroxidase antibodies in serum
Thyroperoxidase antibodies are present
in serum in Hashimoto’s thyroiditis and
post-partum thyroiditis
Anterior pituitary is stimulated by TRH
administration
Serum T3, T4 and TSH are measured
after stimulation
This can distinguish between thyroid
disorders of hypothalamic origin and
pituitary origin
TRH stimulation test
TRH stimulation test is rarely required in
hyperthyroidism
It is useful in hypothyroidism with low T3,
low T4 and low TSH
In such cases, a response to TRH
stimulation points to hypothalamic origin
of hypothyroidism
Subclinical hypothyroidism usually results
from autoimmune thyroiditis
The patients have vague symptoms,
normal serum T4 and high serum TSH
These patients can progress to frank
hypothyroidism later on
Subclinical hypothyroidism
It is recommended that these patients
should be screened for TPO antibodies
If TPO antibodies are present, treatment
is indicated
If TPO antibodies are absent, annual
follow up is recommended
Thyroid function tests

Thyroid function tests

  • 1.
    Thyroid Function Tests R. C.Gupta M.D. (Biochemistry) Jaipur (Rajasthan), India
  • 2.
    Thyroid function testsare commonly done to diagnose hyper- and hypo-thyroidism Most patients with thyroid disorders have only isolated signs and symptoms A clinical diagnosis is usually difficult Diagnosis often requires laboratory tests
  • 3.
    Dietary iodide isabsorbed by the alimentary tract, and released into circulation Some of it is excreted in urine Some is taken up by the thyroid gland, and is converted into iodine Production of thyroid hormones
  • 4.
    Iodine reacts withthe tyrosine residues of thyroglobulin Tyrosine is converted into mono-iodo- tyrosine (MIT) and di-iodo-tyrosine (DIT) Two DIT residues react with each other to form tetra-iodo-thyronine (thyroxine or T4) One residue each of MIT and DIT react to form tri-iodo-thyronine (T3)
  • 5.
    T3 and T4are stored in thyroid acini, attached to thyroglobulin The hormones are released into blood as and when needed They are transported in circulation by thyroxine-binding globulin (TBG)
  • 6.
    The TBG-bound hormonesare inactive Small amounts of T3 and T4 are released from TBG These exist as free T3 and T4 in circulation
  • 7.
    Free T3 andT4 are the biologically active forms of the hormones T4 is more abundant than T3 but T3 is more powerful
  • 8.
    Synthesis and releaseof T3 and T4 are increased by thyroid-stimulating hormone (TSH) of anterior pituitary TSH secretion is increased by thyrotropin- releasing hormone (TRH) of hypothalamus High blood levels of T3 and T4 cause feed- back inhibition of TSH and TRH secretion
  • 10.
    Before the adventof radio-immuno- assay for hormones, tests for thyroid function were indirect and non-specific Some of the older tests are: • Basal metabolic rate • Serum cholesterol • Serum protein-bound iodine • Radioactive iodine uptake
  • 11.
    Thyroid hormones stimulateall metabolic activities This increases the basal metabolic rate (BMR) Hence, BMR is raised in hyperthyroidism and lowered in hypothyroidism Basal metabolic rate
  • 12.
    However, BMR isaffected by a number of physiological and pathological conditions Therefore, this test lacks specificity
  • 13.
    Serum cholesterol levelis decreased in hyperthyroidism and increased in hypo- thyroidism But this test is non-specific because serum cholesterol can become abnormal in a number of other diseases Serum cholesterol
  • 14.
    In this test,the iodine bound to serum proteins is measured Most of the protein-bound iodine (PBI) is present in T3 and T4 Serum protein-bound iodine
  • 15.
    Serum PBI isincreased in hyperthyroidism and decreased in hypothyroidism However, accuracy of PBI measurement is poor
  • 16.
    This test measuresthe uptake of circulating iodide by the thyroid gland A small dose of a radioactive isotope of iodine (5 µc of Na131I) is given to the subject orally in a fasting condition Radioactive iodine uptake
  • 17.
    The radioactivity overthe thyroid gland is measured by a Geiger Muller counter after 2, 24 and 48 hours This is a measure of the radioactive iodine present in the thyroid gland
  • 18.
    The normal uptakeof the ingested dose is: ▪ 1.5-15% at two hours ▪ 25-50% at 24 hours ▪ 15-40 % at 48 hours Radio-active iodine uptake is increased in hyperthyroidism and is decreased in hypo- thyroidism
  • 19.
    Sensitive and specificmethods of hormone assays are available now Hence, the older tests have now become obsolete
  • 20.
    Thyroid function testscommonly done now are: • Serum T3 and T4 • Serum Free T3 (FT3) and Free T4 (FT4) • Serum TSH • Thyroperoxidase antibodies (TPO Ab) • TRH stimulation test
  • 21.
    Normal range oftotal T4 in serum is 5-12 µg/dl It is increased in hyperthyroidism and is decreased in hypothyroidism Serum T4
  • 22.
    The normal rangeof total T3 in serum is 0.1-0.2 µg/dl It is increased in hyperthyroidism and is decreased in hypothyroidism An increase in serum T3 with normal T4 is seen in T3 toxicosis Serum T3
  • 23.
    Sometimes, serum totalT4 may be normal despite the presence of a thyroid disorder In such cases, measurement of serum FT4 can clinch the diagnosis Normal range of serum FT4 is 0.8-2 ng/dl It is increased in hyperthyroidism and is decreased in hypothyroidism Serum Free T4 (FT4)
  • 24.
    Like serum FT4,serum FT3 may be very useful in the diagnosis of subtle disorders of thyroid gland Normal range of serum FT3 is 0.3-0.6 ng/dl Serum Free T3 (FT3)
  • 25.
    Serum TSH candifferentiate between primary thyroid disorders and those secondary to pituitary/hypothalamic disease In primary hyperthyroidism, serum TSH is decreased due to feedback inhibition In hyperthyroidism secondary to pituitary or hypothalamic disease, serum TSH is raised Serum TSH
  • 26.
    In primary hypothyroidism,serum TSH is high due to lack of feedback inhibition In hypothyroidism secondary to pituitary or hypothalamic disease, it is decreased The normal range of serum TSH is 0.5-5 µU/ml
  • 27.
    Hypothyroidism can sometimesoccur due to Hashimoto’s thyroiditis or post-partum thyroiditis In such cases, the disease results from an autoimmune response against thyro- peroxidase Thyroperoxidase antibodies (TPO Ab)
  • 28.
    The autoimmune disordercan be diagnosed by detection of thyro- peroxidase antibodies in serum Thyroperoxidase antibodies are present in serum in Hashimoto’s thyroiditis and post-partum thyroiditis
  • 29.
    Anterior pituitary isstimulated by TRH administration Serum T3, T4 and TSH are measured after stimulation This can distinguish between thyroid disorders of hypothalamic origin and pituitary origin TRH stimulation test
  • 30.
    TRH stimulation testis rarely required in hyperthyroidism It is useful in hypothyroidism with low T3, low T4 and low TSH In such cases, a response to TRH stimulation points to hypothalamic origin of hypothyroidism
  • 31.
    Subclinical hypothyroidism usuallyresults from autoimmune thyroiditis The patients have vague symptoms, normal serum T4 and high serum TSH These patients can progress to frank hypothyroidism later on Subclinical hypothyroidism
  • 32.
    It is recommendedthat these patients should be screened for TPO antibodies If TPO antibodies are present, treatment is indicated If TPO antibodies are absent, annual follow up is recommended