Thyroid function tests are utilized by essentially all medical
practitioners, across every clinical setting, in patients from
newborns to the elderly. They are the most frequently measured
endocrine tests. The sensitive thyrotropin (TSH) assay reflects
thyroid hormone feedback to the pituitary, and is diagnostic of
both thyroid h- mone excess as well as deficiency. The log-linear
relationship between serum TSH and thyroxine concentrations means
that small changes in serum thyroxine are amplified by changes in
serum TSH. The availability of the sensitive TSH assay in
essentially all clinical laboratories has improved and simplified
the assessment of thyroid function for the diagnosis of thyroid
disease and to monitor treatment. Serum free thyroxine and
thyrotropin concentrations, as well as other thyroid tests, can be
measured utilizing an automated immunoassay platform that provides
rapid and accurate results. This simplified approach to thyroid
assessment, often requ- ing only a serum TSH measurement, and rapid
availability of the thyroid function tests results, has expanded
the scope of thyroid testing and clinicians ordering and
interpretingth yroid tests. There remain, however, many challenges
in selecting the appropriate thyroid function test to order, the
correct interpretation of results, and applying these results to
the diagnosis and management of thyroid diseases. It is especially
important to be aware of limitations of thyroid function tests, as
well as special clinical c- cumstances that can influence thyroid
function measurements. The serum TSH concentration, for example,
may not accurately reflect thyroid status in many si- ations
including after prolonged hyperthyroidism when serum TSH remains s-
pressed for months, in the presence of hypothalamic or pituitary
disease, or due to a number of interfering medications. The serum
free thyroxine, measured by the analog method, is not accurate with
high or low serum binding proteins and d- ing pregnancy.
Hospitalized patients often have thyroid function test
abnormalities that are transient and return to normal after
recovery from the acute illness. Iodine excessand deficiency
candramatically influence thyroid function tests. Significant
insights have been gained into the regulation of thyroid hormone
synthesis and especially the role of thyroid hormone metabolism in
supplying t- sues locally with an adequate supply of thyroid
hormone. In a number of instances, these factors influence the
selection and interpretation of thyroid function tests.
Polymorphisms, common sequence variations, in genes of components
that regulate thyroid function and thyroid hormone action may also
contribute to variability in thyroid function tests in a
population. v vi Preface This volume draws on an outstanding
international panel of experts in thyroid function tests and
thyroid function assessment. They represent clinicians, clinical
researchers, and basic science researchers, all with a focus on
some aspect of the assessment of thyroid function. The chapters all
provide a clinical perspective, but are informed by themost recent
scientific advancements. The first section of the book (Chaps. 1-3)
presents the most recent advances in thyroid physiology, a review
of genetic influences on thyroid function tests, and a discussion
on the influence of iodine on thyroid function. In Chap. 1, Drs.
Huang and de Castro Neves describe thyroid hormone metabolism,
emphasizing the key role of thyroid hormone activation and
inactivation in thyroid hormone action. Dr. Visser is a world
leader in studies of thyroid metabolism and genetic influences on
thyroid function. In Chap. 2, Dr. Visser and his colleagues, Drs.
van der Deure, Medici, and Peeters, provide a clear view of this
important and r- idly expanding field. The population variation in
the TSH "set point" (relationship between serum TSH and thyroxine
in an individual), for example, is thought to be genetically
determined, and influences the evaluation of thyroid function and
thyroid function targets for treatment of thyroid disease. Dr.
Zimmerman, an int- nationally recognized expert in iodine, and his
colleague, Dr. Andersson, provide in Chap. 3 an in-depth treatment
of the most significant influence on thyroid function throughout
the world-iodine intake. The influence of iodine deficiency and
excess on individual thyroid function is discussed, as well as the
population effects on t- roid diseases and especially fetal and
neonatalde velopment. The basics of thyroid function measurements,
approaches, limitations, and cl- ical applications are described
for the major categories of thyroid function tests (Chaps. 4-7).
The authors of these chapters are innovators in the field, strongly
id- tified with the origination or significant refinement of the
core tests utilized in t- roid assessment. In Chap. 4, Dr. Hershman
describes the measurement of TSH, the clinical application and
utilization. This remains the cornerstone of thyroid testing, but
must be interpreted with an understanding of the dynamics of
thyroid regulation. An active controversy in thyroid measurement
involves the appropriate use of serum thyroxine measurements and
especially the value of the analog free thyroxine me- urement, the
most commonly used thyroxine assay. In Chap. 5, Dr. Stockigt p-
vides a detailed assessment of thyroxine and triiodothyronine
measurements and a clear message for their use and limitations. The
most common etiology of thyroid disease is autoimmune, and the
appropriate use of thyroid autoantibody measu- ments remains
confusing to many clinicians. In Chap. 6, Dr. Weetman and his c-
league, Dr. Ajjan, clearly describe the range of thyroid
autoantibody tests and how they should be utilized clinically.
Thyroglobulin measurement is the key tumor marker to follow thyroid
cancer patients and Dr. Spencer and her colleague, Ivana Petrovic,
describe the essential features of this measurement in Chap. 7. It
is ess- tial that clinicians using thyroglobulin measurements to
monitor thyroid cancer are aware of the performance of the assay
being used and the factors that can interfere with the measurement.
Application of thyroid function testing to the key clinical
settings is discussed by expert clinicians and clinical researchers
in Chaps.8-13. The appropriate selec- Preface vii tion of thyroid
function tests in the diagnosis and monitoring of thyroid disease
in the ambulatory setting is discussed by Drs. Farwell and Leung in
Chap. 8. This is the most common setting for thyroid function test
measurement and a rational approach is described. Specific issues
of thyroid function in infants and children are discussed in Chap.
9 by Drs. LaFranchi and Balogh. Screening for thyroid disease among
newborns has been a highly effective approach to prevent mental
retar- tion. The assessment of thyroid function in newborns,
especially premature infants, is challenging as are the
interpretation of thyroid function tests in infancy through
childhood. Illness has a significant impact on thyroid function
tests and assessment in this group is described by Drs. LoPresti
and Patil in Chap. 10. A logical approach to these patients is
provided as are ways to identify those patients with thyroid
disease that need to be treated. Assessment of thyroid function in
pregnancy is ch- lenging and is being increasing recognized as a
crucial time to normalize maternal thyroid status. Adverse outcome
for mother and her child can result from thyroid hormone deficiency
or excess. In Chap.11, Drs. Lazarus, Soldin, and Evans ca- fully
describe the use and limitations of thyroid tests in pregnancy and
provide an approach to testing and monitoring thyroid function. The
incidence of autoimmune thyroid disease increases significantly
with age and in Chap. 12 Dr. Samuels p- vides a clear approach to
the assessment of thyroid status in the elderly and interp- tation
of thyroid studies. The influence of drugs on thyroid function
testing remains a major clinical issue with recognition of an ever
increasing list of medications that influence thyroid function and
thyroid testing. In Chap. 13, Drs. Pearce and An- thakrishnan
comprehensively describe these medications with a special emphasis
on their mechanism of action and on iodine-containing medications.
I am most grateful to my colleagues for their enthusiasm and
willingness to p- vide such outstanding contributions to this book.
The editorial team at Springer is excellent and has been highly
supportive and effective. My special thanks to E- tor Laura Walsh,
Associate Editor Dianne Wuori, Editorial Assistant Stacy Lazar,
Senior Production Editor Jenny Wolkowicki and Crest Premedia
Solutions for final production.
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