Thyroid gland is one of the largest endocrine glands. The
thyroid gland is found in the neck, below the thyroid cartilage
The thyroid gland controls how quickly the body uses
energy, makes proteins, and controls how sensitive the body is
to other hormones.
It participates in these processes by producing thyroid
hormones, the principal ones being Tri-iodothyronine (T3)
and Thyroxine which can sometimes be referred to as
These hormones regulate the rate of metabolism and affect
the growth and rate of function of many other systems in the
T3 and T4 are synthesized from both Iodine and tyrosine. The
thyroid also produces calcitonin, which plays a role in calcium
Hormonal output from the thyroid is regulated by thyroid
stimulating Hormone (TSH) produced by the anterior pituitary,
which itself is regulated by thyrotropin-releasing
hormone (TRH) produced by the hypothalamus.
T4 has a longer plasma half- life than T3. However at
cellular level T3 is more active physiologically.
The thyroid gets its name from the Greek word for
"shield", due to the shape of the related thyroid
The most common problems of the thyroid gland
consist of an overactive thyroid gland, referred to
as hyperthyroidism, and an underactive thyroid
gland, referred to as hypothyroidism.
The thyroid gland is a butterfly-shaped organ and is
composed of two cone-like lobes.
The organ is situated on the anterior side of the neck, lying
against and around the larynx and trachea, reaching
posteriorly the oesophagus and carotid sheath.
Patients with a normally functioning thyroid gland are said to
be in a euthyroid state.
When this state is disrupted, thyroid disease may result. It
occurs four times more often in women than in men and may
occur at any age, but it peaks between the third and sixth
decades of life.
A family history of this disease often is present, especially for
the autoimmune thyroid diseases.
Diseases of the thyroid usually involve an alteration in the
quantity or quality of thyroid hormone secretion and may
manifest as hyperthyroidism or hypothyroidism.
Enlargement of Thyroid gland is called as Goiter.
Hypothyroidism results from a deficiency of thyroid hormone
secretion, causing a generalized slowing of the metabolism.
Sysmtoms include lethargy, constipation, dry coarse skin and
hair, paresthesias, cold intolerance, decreased sweating,
impaired memory, confusion and dementia, slow speech and
motor activity and anemia.
Hypothyroidism is usually caused by one of the three
1) Primary Hypothyroidism is failure of the thyroid to secrete
2) Secondary Hypothyroidism is failure of the anterior pituitary
to secrete TSH
3) Tertiary Hypothyroidism is failure of the Hypothalamus to
Thyrotoxicosis results when excessive amounts of thyroid
hormones are circulating and usually is due to hyperactivity of
the thyroid gland (Hyperthyroidism)
Its signs and symptoms include nervousness, fatigue, weight
loss, Heat intolerance , increased sweating, tachycardia, moist
skin and exophthalamos.
Thyroid Function tests:
Tests more specific for thyroid status or function can
be categorized as follow:
1. Measure the concentration of products secreted
by the thyroid gland.
2. Evaluate the integrity of the hypothalamic –
pituitary – thyroid axis.
3. Assess inherent thyroid gland function.
4. Detect antibodies to thyroid tissues.
Tests that directly or indirectly measure the
concentration of T4 and T3 includes –
• Free T4
• Total serum T4
• Serum T3 resin uptake
• Free T4 Index
• Total Serum T3
The integrity of hypothalamic pituitary thyroid axis
is assessed by measuring –
Normal Range: 0.8 – 2.7 ng/dl or 10 – 35 pmol/L
This test measure the unbound T4 in the serum and is the
most accurate reflection of thyroid metabolic status.
The low concentration of T4 in the serum ( Less than 1% of
total T4), makes accurate measurement difficult and is a
laborious process. Therefore, free T4 is assayed primarily
when T4 binding globulin alteration or Non-thyroidal illness
confirmed interpretation of Conventional tests.
Total Serum Thyroxine
Normal range: 4 – 12 µg/dL or 51 – 154 nmol/L
Although ultrasensitive TSH and free T4 assays
are gradually supplanting this RIA
(radioimmunoassay), total serum T4 still is the
standard initial screening test to assess thyroid
function because of its wide availability and quick
In most patients, the total serum T4 level is a
sensitive test for the functional status of the
thyroid gland. It is high in 90% of hyperthyroid
patients and low in 85% of hypothyroid
Conditions that increase or decrease thyroid-
binding protein result in an increased or
decreased total serum Thyroid
respectively, but do not affect the amount of
metabolically active free T4 in the circulation.
Increased Total serum Thyroxine
An increased total serum T4 may indicate
Hyperthyroidism, elevated concentrations of thyroid-
binding proteins or non-thyroid illness.
The transient elevations might be due to TSH
secretion stimulated by a low T3 concentration.
Similarly, up to 20% of all patients admitted to
psychiatric hospitals have had transient total serum
T4 elevation on admission.
Decreased Total serum Thyroxine
A decreased total serum T4 may indicate hypothyroidism,
decreased concentrations of thyroid – binding proteins or non-
thyroid illness (also called “euthyroid sick syndrome”).
Non-thyroid illness may lower the total serum T4 concentration
with change in thyrometabolic status.
Typically in this syndrome, total serum T4 is decreased, total
serum T3 is decreased and TSH is Normal.
Neoplastic disease, DM, Burns, Trauma, liver disease, renal
failure, prolonged infections and cardiovascular disease are
non-thyroid illness that can lower Total serum T4
Mechanism Increase Total Serum T3
and Free T4
Decrease Total Serum T4
and Free T4
Interference in central
regulation of TSH
hypothalamic – Pituitary
Interference with thyroid
and/or release from
Altered thyroid hormone
Propranolol (High Dose)
absorption of exogenous
Soya bean flour
Drugs causing true alterations in total serum thyroxine
Serum Tri-iodothyroxine Resin Uptake
Normal range: 25-35 %
The T3 resin uptake test indirectly estimates the number of
binding sites on thyroid – binding protein occupied by T3.
This result is also referred to as thyroid hormone binding
The T3 resin uptake usually is high when the thyroid –
binding protein is low and vice versa.
Elevated T3 resin uptake concentrations are consistent with
hyperthyroidism, while decreased concentrations are
consistent with hypothyroidism.
The T3 resin uptake is low in hypothyroidism
because of the increased availability of
binding sites on the thyroid-binding globulin.
However, in non-thyroidal illness with a low
T4, the T3 resin uptake is elevated.
Therefore, the test may be used to
differentiate between true hypothyroidism and
a low T4 state caused by non-thyroid illness.
Free thyroxine Index
Normal range: 1.2 – 4.2
The free T4 index is the product of total serum T4 multiplied
by the percentage of T3 resin uptake :
Free T4 index = total serum T4 (mg/dl) T3 resin uptake (%)
The free T4 index adjusts for the effects of alterations in
thyroid – binding protein on the total serum T4 assay.
The index is high in hyperthyroidism and low in
Patients taking phenytoin or salicylates have
low total serum T4 and high T3 resin uptake
with a normal free T4 index.
Pregnant patients have high total serum T4
and low T3 resin uptake with a normal free T4
Total serum Tri-iodothyronine
Normal range : 78 – 195 ng/dL
As with the total serum T4 test, changes in thyroid –
bindings protein increase or decrease total serum T3 but do
not affect the metabolically active free T3 in the circulation.
Therefore, the patients thyro-metabolic status remains
The total serum T3 primarily is used as an
indicator of hyperthyroidism. This
Measurement usually is made to detect T3
toxicosis when T3 but not T4 is elevated.
Generally, the serum T3 assay is not a reliable
indicator of hypothyroidism because of the
lack of reliability in the low to normal range.
Thyroid Stimulating Hormone
Normal Range: 0.3 – 5 µU/mL
TSH assays have been useful in diagnosing primary
hypothyroidism, they have not been useful in
Almost all patients with symptomatic primary
hypothyroidism have TSH concentrations greater
than 20 mU/L
Those with mild signs or symptoms have TSH
values of 10 – 20 mU/L TSH concentrations often
become elevated before T4 Concentarations
The first generation TSH assay however can not
distinguish low normal from abnormaly Low
Values because their lower value of detection is
0.5 mU/L while the lower limit of basal TSH is 0.2
– 0.3 mU/L in most euthyroid persons.
Thyrotropin Releasing Hormone (TRH)
TRH is a hormone secreted by
Hypothalamus, regulates TSH secretion from the
The TRH test measures the ability of injected TRH
to stimulate the Pituitary to release TSH.
This test is the most indicator of Hyperthyroidism in
patients whose other thyroid function are equivocal
primarily with the older.