5.2.
Thyroid Function
Anatomy, Physiology &
Disorders
Learning Objectives
Upon completion of this lecture the student will be able
to:
1. Define terms related to thyroid function
2. Discuss the source and metabolism of thyroid
hormones
3. Explain the clinical significance of thyroid hormone
results
4. Describe methods of analysis of thyroid hormones
Learning Objectives
Upon completion of this lecture the student will
be able to:
5. Interpret thyroid hormone results compared to
the reference ranges.
6. Discuss sources of error in thyroid hormone
analysis.
Outline of Instruction
Introduction
Source
Clinical Significance
Methods of Analysis
Specimens
Quality Control
Interpretation of Results
Sources of Error
Documentation and Reporting
Summary
Introduction to Thyroid
Function
Definition to terms:
Thyroid gland: small tissue situated in the neck just below
the larynx producing hormones that affect metabolism and
growth.
Thyroxine: 3, 5, 3’, 5’ –tetraiodothyronine or T4; produced by
the thyroid gland
Triiodotyrosine: 3, 5, 3’- triiodotyrosine, T 3; produced from the
thyroid gland and peripheral tissues
Reverse T3: 3, 3’, 5’ triiodotyrosine; inactive T3
Deiodinazation: biochemical process of removing iodine
Location of Thyroid Gland
Thyroid Anatomy
Thyroid Biochemistry and Metabolic
Pathways
Precursor hormones are:
Monoiodotyrosine (MIT)
Diiodotyrosine (DIT)
Iodine and tyrosine
derived
Circulating thyroid
hormones are
Thyroxine (T4)
Triiodotyrosine (T3)
Thyroid Biochemistry and
Metabolic Pathways
Step 1: I- trapped in thyroid gland
Step 2: I- oxidized to I2
Step 3: I2 reacts with tyrosine in thyroid cells
MIT and DIT
Step 4: 2 DIT T4; MIT+ DIT T3
Thyroid Anatomy: Cells
Follicular cells
synthesize
thyroglobulin and
thyroxine and T3
Colloid cells provide
Iodine
Capillaries transfer
hormones to
circulation
Thyroid Biochemistry and
Metabolic Pathways
Thyroid gland makes T4
Peripheral tissues make T3 from T4
Deiodination
Thyroid makes some reverse T3
Inactive form
Thyroid binding globulin
Binds to majority of T4 and T3
Only free T4 and T3 is active
Function of Thyroid Hormones
Releasing Ant. Pit. Thyroid Action
Hormone Hormone Hormone
TRH TSH T3 and T4 Increases
metabolic
rate of
cells, ATP
and heat
production,
breakdown
of liver
glycogen,
calorigenic
.
Endocrine Control: Thyroid
Function
Clinical Significance: Primary
Hyperthyroidism
Disease of the primary organ (thyroid)
Increased Free T4 and total T4 and T3
Decreased TSH
Symptoms:
Increasedheart rate and metabolism
Problems with eyes
Many other symptoms
Secondary Hyperthyroidism
Disease of the secondary organ (pituitary)
Increased Free T4 and total T4 and T3
Increased TSH
Symptoms:
Increasedheart rate and metabolism
Problems with eyes
Many other symptoms
Clinical Significance: Primary
Hypothyroidism
Disease of the primary organ (thyroid)
Decreased Free T4 and total T4 and T3
Increased TSH
Symptoms:
Decreased heart rate and metabolism
Failure to thrive and retardation in children
Many other symptoms
Clinical Significance:
Secondary Hypothyroidism
Disease of the secondary organ (pituitary)
Decreased Free T4 and total T4 and T3
Decreased TSH (and other pituitary hormones)
Symptoms:
Decreased heart rate and metabolism
Many other symptoms
Principles of Methods:
Thyroid Hormone Analysis
Immunoassay Procedures:
Competitive RIA for Total T4 or T3
Method
Determine amount of Ab needed to bind to a
known amount of labeled Ag
Prior to Test
+ ↔
– Use predetermined
amounts of labeled Labeled
Ag
Ag and Ab and add a
sample containing Test
unlabeled Ag as a
competitor + + ↔ +
Labeled Patient’s
Ag sample
Principles of Methods:
Thyroid Analysis
Chemilumiscent Immunoassay
Patient T4 + peroxidase labeled-anti-T4 Ag-Ab-label
complex
Ag-Ab-label complex + luminol –(peroxidase) oxidized
product emitting light
Measured in luminometer
Note: this same procedue may be used for T3
but antibody specifity is to T3.
Specimens for Thyroid
Analysis
Serum
Heparinized or EDTA plasma
Whole blood from Capillary
Quality Control
A normal & abnormal quality control sample
should be analyzed along with patient samples,
using Westgard or other quality control rules for
acceptance or rejection of the analytical run.
Assayedknown samples
Commercially manufactured (Humastar)
Validate patient results
Detects analytical errors.
Interpretation of Results
Thyroid Hormone Reference Ranges
T adult 5.1 to 11.0 µg/dL(66 -142 nmol/L)
4:
T3 adult 70 to 200 ng/dL (1.08 to 3.08 nmol/L)
%T3U: 25 to 35%.
Free T4: adult 5.6-11.7 g/dL
Free T3: adult 80-210 ng/dL
Ranges are method dependent and age adjusted.
Patient results should be compared with the appropriate reference ranges
Sources of Error in Thyroid
Analysis
Hemolyzed specimens
Wrong anticoagulant
Lipemic
Turbidity from lipids
Specimen exposed to heat or sunlight
Poorly maintained or poorly calibrated
instrument.
Reporting and Documentation
To avoid post-analytic errors,
Report the patient result with :
right name and result
Include reference ranges
Timely manner
QC and patient results should be documented in
logbook and retained in lab
Summary
Thyroid hormone metabolism, regulation,
mechanism of action were discussed.
Determination of thyroid hormones (T3, T4, FT4,
FT3, FT4I, TBG and RT3U) including principle of
methods, calculations, specimens, interpretation
of results, sources of error, quality control and
documentation and reporting of results were
discussed.
References
Burtis, Carl A., and Ashwood, Edward R.. Tietz:
Fundamentals of Clinical Chemistry. Philadelphia, 2001
Arneson, W and J Brickell: Clinical Chemistry: A
Laboratory Perspective 1st ed. 2007 FA Davis