Thyroid Function Tests TUTORIAL

Thyroid Function Tests
LEARNING OBJECTIVES
At the end of the lecture the student should be able to
• Explain Major thyroid disorders
• Name thyroid function tests.
• Describe the interpretation of thyroid function test in various thyroid diseases.
• Role of Long acting thyroid stimulator in grave disease.
Biosynthesis, Secretion, And Transport of Thyroid hormones
• Iodine is the most important element in the biosynthesis of thyroid hormones.
• Thyroglobulin acts as a performed matrix containing tyrosyl groups to which the reactive
iodine attaches to form the hydroxyl residues of monoiodotyrosine (MIT) and
diiodotyrosine (DIT).
• The coupling of two DIT molecules forms T4 .
• The coupling of one DIT molecules and one MIT molecule results in the formation of T3 or
reverse T3 (rT3)
• Almost all circulating T4 and T3 hormones are bound to serum proteins ( thyroid
hormone-binding proteins )
• Only 0.03 % of T4 and 0.3 % of T3 are not bound to proteins . These fractions, called free
T4 (FT4) and free T3 (FT3), are the physiologically active portions of the thyroid
hormones .

• T3 is the most biologically active thyroid hormone and is three to four times more potent
than T4. T3 is more active because it is not as tightly bound to the serum proteins as is T4,
and has a greater affinity to target tissue receptors
Actions of thyroid hormone
• Regulation of carbohydrate, lipid, and protein metabolism .
• Central nervous system activity and brain development
• Cardiovascular stimulation
• Bone and tissue growth and development
• Gastrointestinal regulation
• Sexual maturation
Thyroid function tests
Specimen collection :
• Specimens are routinely collected in a clot tube, although anticoagulants can be used .
• Specimens free of lipemia or hemolysis are preferred .
The tests used to investigate thyroid function can be grouped into:
• Tests that establish whether there is thyroid dysfunction ( TSH,T4 and T3 measurements)
• Tests to know the cause of thyroid dysfunction
(thyroid auto-antibody and serum thyroglobulin measurements, thyroid enzyme activities,
biopsy of the thyroid, ultrasound and isotopic thyroid scanning )
TSH :
- The single most sensitive, specific and reliable test of thyroid status .

- In primary hypothyroidism, [TSH] is increased.
- In primary hyperthyroidism, [TSH] is decrease or undetectable
Total T4 and Total T3 :
- More than 99% of T4 and T3 circulate in plasma bound to protein
- Both [total T4] and [total T3] change if [TBG] alters, e.g. in pregnancy
Free T4 and Free T3
Free thyroid hormone concentrations are independent of changes in
the concentration of thyroid-hormone binding proteins → more
reliable for diagnosis of
thyroid dysfunction
Signs and symptoms provide the best indication to request thyroid tests
Interpreting results of thyroid function tests
Primary hyperthyroidism
- Plasma [TSH] : ↓ due to feedback inhibition on the pituitary
- Plasma free and total T4 and T3 concentrations : ↑
In a very small percentage of hyperthyroid patients, plasma [total T4] and [freeT4]
are both normal, whereas both plasma [total T3] and [freeT3] are
increased ; this condition is known as
T3 hyperthyroidism or T3 thyrotoxicosis .
Primary hypothyroidism :
Plasma [TSH] : ↑
Plasma [free T4] and [total T4] : ↓
Plasma free T3 and total T3 measurements are of no value here, since normal concentrations
are often observed .
Sub clinical primary thyroid disease
Plasma [TSH] : abnormal
Thyroid hormone levels : normal
[TSH] : low → sub clinical hyperthyroidism
[TSH] : elevated → sub clinical hypothyroidism
Before the diagnosis of sub clinical thyroid disease can be made, causes of an abnormal plasma

[TSH] other than thyroid disease must be excluded
eg : - pregnancy
- drug treatment
Secondary thyroid disorders
• Central (pituitary) hypothyroidism :
[TSH] & thyroid hormone levels → low
• Hyperthyroidism due to a TSH-secreting tumor
very rarely
Plasma TSH is widely used to screen for congenital hypothyroidism in the neonate
( the incidence about one in 4000 live births)
Thyroglobulin
Levels are increased in all types of thyrotoxicosis, except thyrotoxicosis factita caused
by self-administration of thyroid hormone.
The main role for thyroglobulin is in the follow-up of thyroid cancer patients. After
total thyroidectomy and radioablation, thyroglobulin levels should be undetectable;
measurable levels (>1 to 2ng/mL) suggest incomplete ablation or recurrent cancer.
Thyroid autoantibodies
The key reason for the measurement of these antibodies is almost entirely for the
management of those with abnormal thyroid function.
Autoimmune thyroid disease is detected most easily by measuring circulating antibodies
against thyroid peroxidase and thyroglobulin (Thyroid peroxidase antibodies are also
known as anti-TPO or antimicrosomal antibodies).
In subclinical disease, the presence of thyroid antibodies increases the long-term risk of
progression to clinically significant thyroid disease about two-fold. Almost all patients
with autoimmune hypothyroidism and up to 80% of those with Graves’ disease have TPO
antibodies, usually at high levels, although about 5 to 15% of euthyroid women and up to
2% of euthyroid men will also have thyroid antibodies.
Thyroid stimulating antibody –
• (Previously called long-acting thyroid stimulating antibodies or LATS) has a role in
the diagnosis of Graves disease where other test results are ambiguous.

• It may also be useful in pregnant women with Graves disease, to determine the
likelihood of fetal thyrotoxicosis.
References
• Topliss DJ, Eastman CJ. Diagnosis and management of hyperthyroidism and
hypothyroidism. MJA 2004;180:186-93.
• White GH, Walmsley RN. Can the initial clinical assessment of thyroid function
be improved? Lancet 1978;2:933-5.
• Weetman AP. Hypothyroidism: screening and subclinical disease. BMJ
1997;314:1175.
• Helfand M, Redfern C. Screening for Thyroid Disease. Ann Intern Med
1998;129:144-58
• Stockigt JR. Case finding and screening strategies for thyroid dysfunction.
Clin Chim Acta 2002; 315: 111-124.
• Helfland M, Crapo LM. Screening for thyroid disease. Ann Int Med 1990;
112:840-9.
• Viera, Anthony J. Thyroid Function Testing in Outpatients: Are Both Sensitive
Thyrotropin (sTSH) and Free Thyroxine (FT4) Necessary? Fam Med
2003;35:408-10
• Waise A, Belchetz PE. Unsuspected central hypothyroidism. BMJ
2000;321:1275-7.
• Cooper DS. Subclinical Hypothyroidism. N Engl J Med 2001;345:260-5.
• Alexander EK et al. Timing and Magnitude of Increases in Levothyroxine
Requirements during Pregnancy in Women with Hypothyroidism. N Eng J Med
2004;351:241-9.
• Demers LM, Spencer CA. The National Academy of Clinical Biochemistry
Laboratory Medicine Practice Guidelines. Laboratory support for the
diagnosis and monitoring of thyroid disease. Washington (DC): National
Academy of Clinical Biochemistry (NACB); 2002.
(http://www.nacb.org/lmpg/thyroid_lmpg_pub.stm) accessed 24 September
2005.
• Gill M. A handbook for the Interpretation of Laboratory Tests. Diagnostic
Medlab, Auckland, August 2000.
THANKS