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DOCUMENT INFORMATION
Std. Num.: 03000664 Type: Doc Del (Journal Article)
Publication: Clinical Endocrinology Copies: 1
Publisher: Urgency: Normal
Vol(Iss) Pg: 58 (2) p.138-40 Genre: Journal Article
Date 2/2003 Total Fee: $59.00

Title: Laboratory medicine practice guidelines: laboratory support for the diagnosis and monitoring of thyroid disease

Author(s): Demers, L M; Spencer, C A

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Clinical Endocrinology (2003) 58, 138–140

Commentary
Blackwell Science, Ltd

Laboratory medicine practice guidelines: laboratory

support for the diagnosis and monitoring of
thyroid disease

L. M. Demers and C. A. Spencer* The review process was initiated at the International Thyroid
Department of Pathology and Medicine, The Pennsylvania Congress in Kyoto in October 2000, after which the guidelines
State University College of Medicine, Hershey, USA and were displayed electronically in addition to being distributed
*University of Southern California, Edmondson Building, to more than 100 thyroid specialists, representing diverse
Los Angeles, USA. professional associations worldwide, for consensus-building.
The information contained in the monograph is presented
(Received 31 May 2002; returned for revision 13 June 2002; finally in discrete chapters. Each chapter covers the clinical utility of a
revised 3 July 2002; accepted 21 August 2002) specific test, and contains focused guidelines that describe
the physiological strengths and limitations of the test together
with its optimal technical performance parameters. Most of the
guidelines appeared to have greater than 95% consensus;
Quality thyroid tests are essential for diagnosing and managing
however, there were some geographically sensitive differences in
thyroid conditions. Indeed, mild (subclinical) hypo- and hyper-
practice patterns.
thyroidism are by definition conditions that are recognized by
their biochemical profile, typified by an abnormal serum TSH
concentration associated with normal range free thyroid hormone Pre-analytical factors
(FT4 and FT3) levels. The National Academy of Clinical
The chapter on pre-analytical factors presents background infor-
Biochemistry (NACB) has recently published a consensus
mation on the physiological variables that can influence both the
monograph entitled Laboratory Medicine Practice Guidelines:
level of circulating thyroid hormone concentrations and the inter-
Laboratory Support for the Diagnosis and Monitoring of Thyroid
pretation of thyroid test results. The biological variability of total
Disease that reviews the clinical utility and technical perform-
and free thyroid hormones, TSH and thyroglobulin is tabulated,
ance of current thyroid tests (Demers & Spencer, 2002). The
and the differences in absolute thyroid test values that are
current scientific literature abounds with articles relating to thyroid
considered clinically significant are given as a guideline. This
conditions, strategies for thyroid testing and the technical
section also addresses interferences, and includes a table 1isting
performance of different thyroid methodologies. This monograph
the reasons for FT4/TSH discordances that can cause a mis-
was prompted by the need to develop a consensus concerning
interpretation of results. The influence of physiological factors
these issues as well as to address the unusual thyroid problems
such as age and pregnancy, as well as pathological factors such
that challenge the diagnostic accuracy of the thyroid tests
as hospitalization, medications and severe NTI, are discussed
currently available. These atypical presentations account for a
in light of their influence on thyroid test values.
disproportionately large expenditure of laboratory resources to
determine the correct diagnosis (Kricka, 2000). In ambulatory
patients these unusual presentations include: binding protein Total thyroxine (TT4) and triiodothyronine (T T3)
abnormalities that affect the diagnostic accuracy of FT4 tests; the measurements
presence of thyroglobulin (Tg) autoantibodies that interfere with
This section describes the different assays available, the influence
serum Tg measurements; and medications that compromise the
of binding protein abnormalities on total thyroid hormone meas-
in vivo and in vitro metabolism of thyroid hormones and influ-
urements and their interpretation. The section also discusses the
ence the diagnostic accuracy of TSH measurements. In addition,
appropriate clinical use of total thyroid hormone measurements
severe forms of non-thyroidal illnesses (NTI) have a myriad of
and recommends the use of free thyroid hormone testing over
effects on thyroid test results.
total hormone measurement in the majority of clinical situations.
This monograph is unique because it contains consensus
guidelines that were developed by a process of global review.
Free thyroxine (FT4) and free triiodothyronine (F T3)
Correspondence: Carole Spencer, University of Southern California, estimate measurements
Edmondson Building, 1840 North Soto Street, Los Angeles, CA 90032.
E-mail: cspencer@usc.edu This section describes the methodological basis for direct

138 © 2003 Blackwell Publishing Ltd


equilibrium dialysis as well as the two-test index and single
test immunoassay approaches for estimating free hormone
concentrations. The clinical utility of free hormone measurements
is described for a variety of clinical situations that include:
infancy, pregnancy, genetic abnormalities in binding proteins,
thyroid hormone auto-antibodies, hypo- and hyperthyroidism
and medications that can inhibit hormone synthesis and
bioavailability.
Thyrotrophin, thyroid stimulating hormone (TSH)
measurements
Improvements in the sensitivity of current methods used for
measuring serum TSH have propelled TSH testing into the fore-
front of diagnosing both mild (subclinical) and overt hypo-
thyroidism and hyperthyroidism. Current TSH IMA methods
generally have a functional sensitivity below 0·02 mIU/ l. How-
ever, external quality control data shows that some TSH methods
have not yet achieved optimal sensitivity. Guidelines are provided
for assessing TSH assay performance, for establishing appropri-
ate TSH reference intervals for different populations (newborn,
pregnancy and the elderly) and for investigating TSH values that
are discordant with the thyroid hormone status or clinical features
of the patient. The clinical use of TSH measurements for case-
finding, thyroid screening of at-risk patients and for optimizing
the L-T4 treatment dose is also discussed. The best approaches
for investigating misleading serum TSH values typical of pitu-
itary dysfunction, NTI and thyroid hormone resistance are
summarized in this section.
Thyroid autoantibody tests (TPOAb, TgAb and TRAb)
This section reviews recent methodological advances in thyroid
autoantibody testing including current quantitative immunoassay
methods for thyroid peroxidase antibodies (TPOAb) and thyro-
globulin antibodies (TgAb). Reasons for the widely disparate
values reported by different manufacturers’ tests are also discussed.
Data showing that TPOAb is a more diagnostically sensitive marker
for autoimmune thyroid dysfunction than TgAb is presented.
Current bioassays and receptor methods for detecting both block-
ing and stimulating TSH-receptor antibodies (TRAb) are dis-
cussed, together with the clinical use of TRAb measurements.
Serum thyroglobulin (Tg) testing
The current status of serum Tg methods is reviewed together
with the technical limitations of this test. Protocols are provided
for determining functional sensitivity, assessing within-run pre-
cision, detecting ‘hook’ effects and establishing the reference range.
Recommendations are made concerning TgAb-interference
problems that include the elimination of recovery studies. The
© 2003 Blackwell Publishing Ltd, Clinical Endocrinology, 58, 138–140
Laboratory medicine practice guidelines 139
1
clinical utility of serum Tg measurements in the preoperative, early
and long-term postoperative phases of managing patients with differ-
entiated thyroid carcinomas is discussed, together with the use of
recombinant human TSH (rhTSH)-stimulated serum Tg testing.
Calcitonin (CT) and ret proto-oncogene measurements
Post-transcriptional CT maturation is reviewed and the sensitivity
and specificity of current CT methods is discussed relative to
basal and provocative CT testing for medullary thyroid carci-
noma. In the section on ret proto-oncogene testing for multiple
endocrine neoplasia (MEN) mutations, an algorithm for the
genetic screening of at-risk relatives is presented.
Urinary iodine measurement
This section contains the most comprehensive technical aspects of
iodine measurement techniques available anywhere. The impor-
tance of urinary iodine measurements as an epidemiological test
for assessing the iodine status of populations is reviewed, with
a focus on iodine status during pregnancy and the neonatal period.
Thyroid fine needle aspiration (FNA) and cytology
This section summarizes the risk factors for the various types of
thyroid carcinomas. The indications for FNA and some condi-
tions under which ultrasound-guided FNA may be diagnostically
helpful are presented. The cytological features of benign and
malignant lesions are summarized, together with guidelines for
the follow-up of patients with benign diagnoses or inadequate/
non-diagnostic FNA. These guidelines are geographically sens-
itive to some degree, specifically with respect to who should
perform FNA, how to select the cytologist and the approach for
follow-up of patients with benign cytology. The recommenda-
tions should be modified according to local conditions or national
guidelines where appropriate.
Screening for congenital hypothyroidism (CH)
Screening for CH is usually carried out with TT4 or TSH meas-
urements from blood spots by special contract laboratories that
operate under the control of a national quality assurance program.
The relative advantages and disadvantages of TT4 vs. TSH testing
are discussed. In addition, practical details concerning specimen
acquisition, confirmation testing, treatment and follow-up of
affected individuals are provided as guidelines.
The laboratory–physician interface
The final section describes the importance of the laboratory–
physician interface to facilitate the proper interpretation and use
140 L. M. Demers et al.
of thyroid tests. Specifically, physicians should expect their labor-
atory to provide accurate and precise test results and, where
possible, help investigate discordant results, whether the tests
are performed locally or by a reference laboratory. Laboratories
should also provide data to the physicians regarding potential
drug interactions, reference intervals, functional sensitivities
of the thyroid assays as well as method interferences. Similarly,
clinical laboratories should expect their physician-users to have a
realistic understanding of the test limitations and provide relevant
clinical information with the submission of the test specimen.
Without a strong, collegial laboratory–physician interface, the
quality of laboratory support for diagnosis and monitoring treat-
ment of thyroid disorders will undoubtedly be compromised.
Conclusions
Considering the wide diversity in health-care practices world-
wide, there was surprisingly uniform consensus for most of the
© 2003 Blackwell Publishing Ltd, Clinical Endocrinology, 58, 138– 140
guidelines contained in this monograph. However, national and
local issues will need to be taken into account when using
these guidelines in clinical practice. Specifically, the guidelines
will need to be applied in accord with local access to quality
biochemical and genetic testing, as well as support services
such as ultrasonography. Further, reimbursement issues un-
doubtedly influence the strategy for thyroid testing in some
countries. Hopefully, this monograph will provide a forum for
discussion and the basis for developing new national guidelines
where needed.
References
Demers, L.M. & Spencer, C.A., eds (2002) Laboratory Medicine Prac-
tice Guidelines: Laboratory Support for the Diagnosis and Monitoring
of Thyroid Disease. Washington, DC: National Academy of Clinical
Biochemistry (www.nacb.org).
Kricka, L.J. (2000) Interferences in immunoassay − still a threat. Clinical
Chemistry, 46, 1037–1038.