Thyroid function tests

SCHOOL OF PHARMACEUTICAL SCIENCES
DEPARTMENT OF PHARMACY PRACTICE
& PHARM D
ASSIGNMENT – 01
TOPIC: THYROID FUNCTION TEST
SUBJECT : CLINCAL PHARMACY (THEORY)
COURSE : PHARM D - IV YEAR
BATCH : 2010 - 2016
SUBMITTED ON : July’ 2013
SUBMITTED TO : Dr. Aswathy Rajan
SUBMITTED BY : Mohammed. Sulaiman Sait. J
HOD : Dr. J. ANBU

1
INDEX :-
S.NO TOPIC PAGE NUMBER
1. INTRODUCTION- THE THYROID GLAND,THYROID SYTEM, ITS
FUNCTIONS AND REGULATIONS
2
2. DISORDERS OF THE THYROID SYSTEM 4
3. DIAGNOSTIC TESTS AND THEIR SIGNIFICANCE 5
4. THYROID STIMULATING HORMONE (TSH) TEST 5
5. TOTAL THYROXINE 6
6. FREE THYROXINE 6
7. TOTAL TRIIODOTHYRONINE 7
8. FREE TRIIODOTHYRONINE 8
9. THYROID HORMONE UPTAKE 8
10. SECRETORY CAPACITY (GT) 9
11. REFERENCES 10

2
INTRODUCTION- THE THYROID GLAND, THYROID
SYSTEM, ITS FUNCTIONS AND REGULATIONS
The thyroid gland or simply, the thyroid Gland is one of the largest endocrine
glands. The thyroid gland is found in the neck, below the thyroid cartilage (which forms
the laryngeal prominence, or "Adam's apple"). 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 triiodothyronine (T3) and thyroxine which can sometimes be referred to as
tetraiodothyronine (T4). These hormones regulate the growth and rate of function of many
other systems in the body. T3 and T4 are synthesized from iodine and tyrosine. The thyroid also
produces calcitonin, which plays a role in calcium homeostasis.
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.
T3 and T4 production and action
Thyroxine (T4) is synthesised by the follicular cells from free tyrosine and on the tyrosine
residues of the protein called thyroglobulin (Tg).Iodine is captured with the "iodine trap" by
the hydrogen peroxide generated by the enzyme thyroid peroxidase (TPO) and linked to the 3'
and 5' sites of the benzene ring of the tyrosine residues on Tg, and on free tyrosine. Upon
stimulation by the thyroid-stimulating hormone (TSH), the follicular cells reabsorb Tg and cleave
the iodinated tyrosines from Tg in lysosomes, forming T4 and T3 (in T3, one iodine atom is

3
absent compared to T4), and releasing them into the blood. Deiodinase enzymes convert T4 to
T3. Thyroid hormone secreted from the gland is about 80-90% T4 and about 10-20% T3.
Cells of the developing brain are a major target for the thyroid hormones T3 and T4. Thyroid
hormones play a particularly crucial role in brain maturation during fetal development. A
transport protein that seems to be important for T4 transport across the blood–brain
barrier(OATP1C1) has been identified. A second transport protein (MCT8) is important for
T3 transport across brain cell membranes.
Non-genomic actions of T4 are those that are not initiated by liganding of the hormone to
intranuclear thyroid receptor. These may begin at the plasma membrane or within cytoplasm.
Plasma membrane-initiated actions begin at a receptor on the integrin alphaV beta3 that
activates ERK1/2. This binding culminates in local membrane actions on ion transport systems
such as the Na(+)/H(+) exchanger or complex cellular events including cell proliferation. These
integrins are concentrated on cells of the vasculature and on some types of tumor cells, which
in part explains the proangiogenic effects of iodothyronines and proliferative actions of thyroid
hormone on some cancers including gliomas. T4 also acts on the mitochondrial genome via
imported isoforms of nuclear thyroid receptors to affect several mitochondrial transcription
factors. Regulation of actin polymerization by T4 is critical to cell migration in neurons and glial
cells and is important to brain development.
T3 and T4 regulation
The production of thyroxine and triiodothyronine is regulated by thyroid-stimulating hormone
(TSH), released by theanterior pituitary. The thyroid and thyrotropes form a negative feedback
loop: TSH production is suppressed when the T4levels are high.[19] The TSH production itself is
modulated by thyrotropin-releasing hormone (TRH), which is produced by
the hypothalamus and secreted at an increased rate in situations such as cold exposure (to
stimulate thermogenesis). TSH production is blunted by somatostatin (SRIH), rising levels
of glucocorticoids and sex hormones (estrogen andtestosterone), and excessively high blood
iodide concentration.
An additional hormone produced by the thyroid contributes to the regulation of
blood calcium levels. Parafollicular cellsproduce calcitonin in response to hypercalcemia.
Calcitonin stimulates movement of calcium into bone, in opposition to the effects
of parathyroid hormone (PTH). However, calcitonin seems far less essential than PTH, as
calcium metabolism remains clinically normal after removal of the thyroid (thyroidectomy), but
not the parathyroids.

4
DISORDERS OF THE THYROID SYSTEM
Thyroid disorders include
HYPERTHYROIDISM (abnormally increased activity of the thyroid gland),
HYPOTHYROIDISM (abnormally decreased activity of the thyroid gland) and
THYROID NODULES, which are generally benign THYROID NEOPLASMS, but may be thyroid
cancers
(i) HYPERTHYROIDISM Hyperthyroidism, or overactive thyroid, is the
overproduction of the thyroid hormones T3 and T4, and is most commonly
caused by the development of Graves' disease,[citation needed] an autoimmune
disease in which antibodies are produced which stimulate the thyroid to secrete
excessive quantities of thyroid hormones. The disease can result in the
formation of a toxic goiter as a result of thyroid growth in response to a lack
ofnegative feedback mechanisms. It presents with symptoms such as a thyroid
goiter, protruding eyes (exopthalmos), palpitations,
excess sweating, diarrhea, weight loss, muscle weakness and unusual sensitivity
to heat. The appetite is often increased.
(ii) HYPOTHYROIDISM Hypothyroidism is the underproduction of the thyroid
hormones T3 and T4. Hypothyroid disorders may occur as a result of :
- Congenital thyroid abnormalities (Thyroid deficiency at birth. See congenital
hypothyroidism),
- Autoimmune disorders such as Hashimoto's thyroiditis,
- Iodine deficiency (more likely in poorer countries) or
- The removal of the thyroid following surgery to treat severe hyperthyroidism
and/or thyroid cancer.
Typical symptoms are abnormal weight gain, tiredness, baldness, cold
intolerance, and bradycardia. Hypothyroidism is treated with hormone
replacement therapy, such as levothyroxine, which is typically required for the
rest of the patient's life. Thyroid hormone treatment is given under the care of
a physician and may take a few weeks to become effective
(iii) THYROID NODULES In most cases, thyroid cancer presents as a painless mass in
the neck. It is very unusual for thyroid cancers to present with symptoms, unless
they have been neglected. One may be able to feel a hard nodule in the neck.
Diagnosis is made using a needle biopsy and various radiological studies

5
DIAGNOSTIC TESTS AND THEIR SIGNIFICANCE
Thyroid function tests (TFTs) is a collective term for blood tests used to check the function of
the thyroid.
TFTs may be requested if a patient is thought to suffer from hyperthyroidism (overactive
thyroid) or hypothyroidism (underactive thyroid), or to monitor the effectiveness of either
thyroid-suppression or hormone replacement therapy.
(i) THYROID STIMULATING HORMONE
Thyroid-stimulating hormone (also known as TSH or thyrotropin) is a hormone that
stimulates the thyroid gland to produce thyroxine (T4), and then triiodothyronine (T3) which
stimulates the metabolism of almost every tissue in the body. It is a glycoprotein hormone
synthesized and secreted by thyrotrope cells in the anterior pituitary gland, which regulates the
endocrine function of the thyroid gland.
 Diagnosis
TSH concentrations are measured as part of a thyroid function test in patients suspected of
having an excess (hyperthyroidism) or deficiency (hypothyroidism) of thyroid hormones.
Interpretation of the results depends on both the TSH and T4 concentrations. In some
situations measurement of T3 may also be useful.
TSH test is based on the way TSH and thyroid hormones work together. Normally, the
pituitary boosts TSH production when thyroid hormone levels in the blood are low. The
thyroid responds by making more hormone. Then, when the body has enough thyroid
hormone circulating in the blood, TSH output drops. The cycle repeats con- tinuously to
maintain a healthy level of thyroid hormone in the body. The TSH test measures the amount
of TSH being secreted by the pituitary.
In adults, a standard reference range is between 0.4 and 3.0 µIU/mL (equivalent to mIU/L),
but values vary slightly among labs. In the UK, guidelines issued by the Association for
Clinical Biochemistry suggest a reference range of 0.4-4.5 mIU/L. It expected the normal
range for adults to be reduced to 0.4–2.5 µIU/mL, because research had shown that adults
with an initially measured TSH level of over 2.0 µIU/mL had "an increased odds ratio of
developing hypothyroidism over the [following] 20 years, especially if thyroid antibodies
were elevated".
TSH concentrations in children are normally higher than in adults.

6
(II) TOTAL THYROXINE
Total thyroxine (Total T4) is generally elevated in hyperthyroidism and decreased
in hypothyroidism. It is usually slightly elevated in pregnancy secondary to increased levels
of thyroid binding globulin (TBG).
Reference ranges:
Lower limit Upper limit Unit
4 (M) , 5.5(FM) 11(M) , 12.3(FM) μg/dL
60 140(M) , 160 (FM) nmol/L
(III)FREE THYROXINE
Free thyroxine (Free T4) is generally elevated in hyperthyroidism and decreased
in hypothyroidism.[2]
Patient type Lower limit Upper limit Unit
Normal adult
0.7, 0.8 1.4, 1.5 ng/dL
9, 10, 18, 23 pmol/L
Infant 0–3 d
2.0 5.0 ng/dL
26 65 pmol/L
Infant 3–30 d
0.9 2.2 ng/dL
12 30 pmol/L
Child/Adolescent
31 d – 18 y
0.8 2.0 ng/dL
10 26 pmol/L

7
Pregnant
0.5 1.0 ng/dL
6.5 13 pmol/L
(IV) TOTAL TRIIODOTHYROXINE
Total triiodothyronine (Total T3) also known as T3, is a thyroid hormone. It affects almost
every physiological process in the body, including growth and development, metabolism, body
temperature, and heart rate.
Production of T3 and its prohormone thyroxine (T4) is activated by thyroid-stimulating
hormone (TSH), which is released from the pituitary gland. This pathway is regulated via a
closed-loop feedback process: Elevated concentrations of T3, and T4 in the blood plasma inhibit
the production of TSH in the pituitary gland. As concentrations of these hormones decrease,
the pituitary gland increases production of TSH, and by these processes, afeedback control
system is set up to regulate the amount of thyroid hormones that are in the bloodstream
 DIAGNOSIS AND MEASUREMENT
Triiodothyronine can be measured as free triiodothyronine, which is an indicator of
triiodothyronine activity in the body. It can also be measured as total triiodothyronine,
which also depends on the triiodothyronine that is bound to thyroxine-binding globulin.
Only about 20 percent of the T3 circulating in the blood comes from the thyroid gland,
while all of the circulating T4 comes from the thyroid. The remaining 80 percent of circu-
lating T3 comes from various cells all over the body where T4 is converted to T3. T3 is
far more active than T4 and, like T4, exists in both bound and free states. In some cases
of hyperthyroidism, FT4 is normal but free T3 (FT3) is elevated, so measuring both forms
is useful if hyperthyroidism is suspected. The normal FT3 range is about 0.2 to 0.5 ng/dL.
The T3 test is not useful in diagnosing hypothyroidism because levels are not reduced
until the hypothyroidism is severe
Total triiodothyronine (Total T3) is generally elevated in hyperthyroidism and decreased
in hypothyroidism.[2]
Reference ranges:

8
Test Lower limit Upper limit Unit
Total triiodothyronine
60(M) , 75(FM) 175(M), 181(FM) ng/dL
0.9(M), 1.1(FM) 2.5(M) , 2.7(FM) nmol/L
(V) FREE TRIIODOTHYROXINE
Free triiodothyronine (Free T3) is generally elevated in hyperthyroidism and decreased in
hypothyroidism.
Reference ranges:
Normal adult
3.0 7.0 pg/mL
3.1 7.7 pmol/L
Children 2–16 y
3.0 7.0 pg/mL
1.5 9.2 pmol/L
(VI) Thyroid hormone uptake
Thyroid hormone uptake (Tuptake or T3 uptake) is a measure of the unbound thyroxine binding
globulins in the blood, that is, the TBG that is unsaturated with thyroid hormone. Unsaturated
TBG increases with decreased levels of thyroid hormones. It is not directly related to
triiodothyronine, despite the name T3 uptake.

9
Reference ranges:
Females 25 35 %
In pregnancy 15 25 %
Males 25 35 %
(VII) SECRETORY CAPACITY (GT)
Thyroid's secretory capacity (GT, also referred to as SPINA-GT) is the maximum stimulated
amount of thyroxine the thyroid can produce in one second. GT is elevated in hyperthyroidism
and reduced in hypothyroidism.
GT is calculated with
or
: Dilution factor for T4 (reciprocal of apparent volume of distribution, 0.1 l−1)
: Clearance exponent for T4 (1.1e-6 sec−1)
K41: Dissociation constant T4-TBG (2e10 l/mol)
K42: Dissociation constant T4-TBPA (2e8 l/mol)
DT: EC50 for TSH (2.75 mU/l)[20]
Lower limit Upper limit Unit
1.41 8.67 pmol/s

10
REFERENCES
1. The thyroid gland in Endocrinology: An Integrated Approach by Stephen Nussey and Saffron
Whitehead (2001)
2. Boron WF, Boulpaep E (2003). "Chapter 48: "synthesis of thyroid hormones"". Medical
Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders
3. Bianco AC, Salvatore D, Gereben B, Berry MJ, Larsen PR (2002). "Biochemistry, cellular and
molecular biology, and physiological roles of the iodothyronine
4. Johannes W. Dietrich (2002). Der Hypophysen-Schilddrüsen-Regelkreis. Berlin, Germany: Logos-
Verlag Berlin.
5. Thyroid Problems eMedicine Health. Retrieved on 2010-02-07
6. ^ Thyroid Disorders Information MedicineNet. Retrieved on 2010-02-07
7. Thyroid Function Tests In turn citing: Operational Medicine 2001, Health Care in Military
Settings, NAVMED P-5139, May 1, 2001, Bureau of Medicine and Surgery, Department of the
Navy, 2300 E Street NW, Washington, D.C., 20372-5300
8. Blood Test Results - Normal Ranges Bloodbook.Com
9. Demers, Laurence M.; Carole A. Spencer (2002). "LMPG: Laboratory Support for the Diagnosis
and Monitoring of Thyroid Disease". National Academy of Clinical Biochemistry(USA). Retrieved
2007-04-13
10. ^ Dietrich, J. W., K. Brisseau und B. O. Boehm (2008). "Resorption, Transport und
Bioverfügbarkeit von Schilddrüsenhormonen" [Absorption, transport and bio-availability of
iodothyronines]. Deutsche Medizinische Wochenschrift 133 (31/21):
11. "Hypothyroidism Causes, Symptoms, Diagnosis, Treatment Information Produced by Medical
Doctors", Retrieved on 2009-3-27
12. Dietrich, J. W., K. Brisseau und B. O. Boehm (2008). "Resorption, Transport und Bioverfügbarkeit
von Schilddrüsenhormonen" [Absorption, transport and bio-availability of iodothyronines].
Deutsche Medizinische Wochenschrift 133 (31/21): 1644-8. DOI 10.1055/s-0028-1082780

Thyroid function tests

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