Clinical Chemistry 42:1 125-134 (1996)

Remarkable technical advances have permitted analytical measurement of thyrotropin (TSH) and estimates of free thyroxine (FT4) with precision, accuracy, and favorable economics. Combined with an increased appreciation of the key insights into the pituitary-thyroid relation, preanalytical considerations infrequently introduce confounding variables. In reviewing thyroid data, preanalytical considerations include physiological and specimen-based issues. Central to the improvement in thyroid assessment is the recognition that physiological individuals maintain their FT4 within narrow limits. When this deviates, there is a logarithmic response of the TSH concentration to the arithmetic shift in FT4. In effect, the TSH deviation magnifies the subtle shift in FT4. Artifact and other nonthyroid-related preanalytical considerations are infrequently the cause of nonconcordance when discrepancy occurs between the reported values for FT4 and TSH. When abnormalities of TSH and FT4 are encountered, the probability strongly favors a disease state rather than a preanalytical variable. Infrequent but real extrathyroidal pathophysiological states are increasingly recognized as a result of the reliable assessment of the pituitary-thyroid relation.

CME July 2006 Vol.24 No.7 Tam metin için tıklayınız

Clinicians rely on the laboratory for quality testing in order to make decisions concerning diagnoses and cost-effective management of thyroid disorders. Because of the diverse clinical presentations of thyroid dysfunction (the majority of thyroid disease symptoms are often subtle and nonspecific in presentation), initial requests for assessing thyroid function are often made.
When the clinical suspicion is strong (e.g. in a patient who exhibits overt symptoms and signs of hyperthyroidism), thyroid function tests are helpful in confirming the diagnosis.
However, situations may occur where clinicians receive ‘abnormal’ test results that appear to be discordant with the clinical findings, and which also occur in the absence of a clearly definable thyroid disease. Such test results may be misinterpreted, the unfortunate outcome being that inappropriate management may be instituted.
Thus, while clinicians may be alert to the possibility of thyroid dysfunction, they may not be familiar with the interpretation of laboratory tests, or with the various factors that can compromise the laboratory tests. Good communication between the requesting clinician and the laboratory is therefore essential for correct interpretation.
Much of the difficulty in diagnosing thyroid dysfunction arises from a lack of awareness regarding the complexities in the biology of thyroid physiology and pathophysiology, limitations of the test methods in terms of diagnostic accuracy, and misunderstanding the meaning of thyroid function results in the clinical context.
This article aims to address these issues by discussing the variables (pre-analytical and analytical – see Table I) that affect the interpretation of test results, in the hope that clinicians will have a better understanding of how to interpret discrepant test results in the clinical context.

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Contents
Guidelines development group 4
Notes on the development and use of the guidelines 5
Types of evidence and the grading of recommendations 7
Abbreviations 8
Presentation conventions 9
Acknowledgements 10

1. Introduction
1.1 Thyroid disease 11
1.2 Thyroid function tests 11
1.3 The patient perspective 11
1.4 The physician perspective 12
1.5 The laboratory perspective 12
1.6 The need for national guidelines 12
2. Indications for thyroid function testing
2.1 Introduction 15
2.2 Screening for thyroid dysfunction 15
2.2 Surveillance of thyroid function 20
2.3 Monitoring of thyroid function 22
3. Hypothyroidism
3.1 Primary hypothyroidism 24
3.2 Subclinical (mild) hypothyroidism 27
3.3 Secondary hypothyroidism 28
3.4 Congenital hypothyroidism 30
4. Hyperthyroidism
4.1 Primary hyperthyroidism 32
4.2 Subclinical (mild) hyperthyroidism 36
4.3 Inappropriate TSH 37
5. Thyroid function in pregnancy
5.1 Introduction 39
5.2 Hypothyroidism 39
5.3 Hyperthyroidism 40
5.4 Post-partum thyroiditis 42
5.5 Screening for thyroid disease during pregnancy 42
5.6 Neonatal thyroid assessment 43
6. Thyroid function testing in thyroid cancer
6.1 Introduction 46
6.2 Differentiated thyroid cancer 46
6.3 Medullary thyroid cancer 49
6.4 Anaplastic thyroid cancer 51 3
Contents (continued)
7. Laboratory aspects of thyroid function testing
7.1 Introduction 52
7.2 Biochemical investigations for thyroid function 52
7.3 Tests to establish if there is thyroid dysfunction 52
7.4 Selective use of thyroid function tests 54
7.5 Reference ranges 55
7.6 Quality control and quality assurance 56
7.7 Interpreting results of thyroid function tests 57
7.8 Follow-up of unusual test results 61
7.9 Laboratory tests used to determine the cause of thyroid dysfunction 61
7.10 Recommended protocol for determining functional sensitivity 66
7.11 Drugs that alter thyroid hormone synthesis, secretion & metabolism 66
8. Areas for further studies 68
Appendix 1 References 69

THE LANCET • Vol 357 • February 24, 2001

The introduction of sensitive thyrotropin assays and free thyroid hormone measurements has simplified the interpretation of thyroid function tests. However, important pitfalls and difficult cases still exist. In this review, thyroid function test results are grouped into six different patterns. We propose that if assays for thyrotropin, free T3, and free T4 are all done, knowledge of these patterns coupled with clinical details and simple additional tests allow a diagnosis to be made in almost all cases.

Endocrine Reviews 1997 Vol. 18, No. 3 404-432

I. Introduction
II. The Regulation of Thyroid Function in Normal Pregnancy
A. The thyroid hormone transport proteins
B. The thyroid hormones
1. Total thyroid hormones
2. Free thyroid hormones
3. Peripheral metabolism of thyroid hormones
C. The serum levels of thyroglobulin (TG)
D. The metabolism of iodine
E. The hypothalamic-pituitary control of thyroid function
and the role of hCG
1. Hypothalamic-pituitary-thyroid axis (HPTA)
2. Regulation of serum TSH
3. Thyrotropic action of hCG
F. A global view of thyroidal economy in pregnancy
III. Pathological Alterations of Thyroidal Regulation Associated
with Pregnancy
A. IDD
1. Consequences of iodine deficiency during pregnancy
2. Assessment of increased thyroidal stimulation
3. Gestational goitrogenesis and its prevention by
iodine supplementation
4. Consequences of iodine deficiency for the offspring
B. Hypothyroidism and pregnancy
1. Fertility and pregnancy outcome in hypothyroid
women
2. Thyroid hormone replacement in the hypothyroid
pregnant woman
3. Subclinical hypothyroidism in pregnancy
4. Euthyroid autoimmune thyroid disorders
(AITD) and pregnancy
5. AITD and the risk of miscarriage
C. Hyperthyroidism and pregnancy
1. GD in the pregnant woman
2. GTT
3. Hyperemesis gravidarum and hyperthyroidism
IV. Conclusions and Perspectives

LABORATORY SUPPORT FOR THE DIAGNOSIS AND MONITORING OF THYROID DISEASE
Laurence M. Demers, Ph.D., F.A.C.B. and Carole A. Spencer, Ph.D., F.A.C.B.

The National Academy of Clinical Biochemistry is the Academy of the American Association for Clinical Chemistry (AACE) and is dedicated to advancing the science and practice of clinical laboratory medicine through research, education, and professional development. The Academy publishes Laboratory Medicine Practice Guidelines (LMPG) for the application of clinical biochemistry to medical diagnosis and therapy.

Fulltext

Thyroid stimulating hormone (TSH) is the initial test for the diagnosis of primary hyperthyroidism and hypothyroidism. The measurement of TSH levels is the most sensitive and specific test for thyroid dysfunction. The new generation of sensitive immunoradiometric TSH assays can reliably detect a concentration as low as 0.01 mU/L. Reference values range between 0.15 mU/L and 6 mU/L, but some variations are possible in different laboratories. Sensitivity and specificity of TSH is in excess of 90 percent in detecting thyroid disease (Caldwell, 1985).