Brent Thyroid Function Testing

1. Auflage 2010
ISBN: 978-1-4419-1485-9
Verlag: Springer
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, Band 28, 293 Seiten

Reihe: Endocrine Updates

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.

Autoren/Hrsg.

Brent, Gregory A.

Inhaltsverzeichnis

1;Preface;6
2;Contents;9
3;Contributors;16
4;Thyroid Hormone Metabolism;19
4.1;1.1 Introduction;19
4.2;1.2 Thyroid Hormone Synthesis and Plasma Transport;20
4.3;1.3 Thyroid Hormone Action;23
4.4;1.4 Thyroid Hormone Metabolism;23
4.5;1.5 Alternative Pathways of Thyroid Hormone Metabolism;23
4.5.1;1.5.1 Conjugation;23
4.5.2;1.5.2 Alanine Side-Chain Modification;24
4.6;1.6 Thyroid Hormone Deiodination;25
4.7;1.7 The Iodothyronine Deiodinase Enzyme Family;26
4.7.1;1.7.1 Type 1 Deiodinase (D1);27
4.7.2;1.7.2 Type 2 Deiodinase (D2);27
4.7.3;1.7.3 Type 3 Deiodinase (D3);28
4.8;1.8 Thyroid Hormone Metabolism and T3 Homeostasis;28
4.8.1;1.8.1 Iodine Deficiency;28
4.8.2;1.8.2 Hypothyroidism;29
4.8.3;1.8.3 Hyperthyroidism;30
4.9;1.9 Altered Thyroid Hormone Metabolism as a Cause of Abnormal Thyroid Function Testing;30
4.9.1;1.9.1 Low-T3 Syndrome;31
4.9.2;1.9.2 Medications that Alter Thyroid Hormone Metabolism;32
4.9.3;1.9.3 Tumoral D3 and Consumptive Hypothyroidism;33
4.9.4;1.9.4 Tumoral D2 in Metastatic Follicular Thyroid Carcinoma;33
4.9.5;1.9.5 Selenium Deficiency and Inborn Errors in Selenoprotein Synthesis;34
4.10;References;34
5;Genetic Influences on Thyroid Function Tests;39
5.1;2.1 The Hypothalamus-Pituitary-Thyroid Axis;39
5.2;2.2 Influence of Genetic Variation on Thyroid Function Tests;41
5.3;2.3 Genetic Variation in Thyroid-Regulating Genes: TRH, TRHR, TSH, TSHR;43
5.4;2.4 Genetic Variation in Thyroid Transcription Factors: PAX8, TTF1, TTF2;44
5.5;2.5 Genetic Variation in Thyroid Hormone Synthesis Genes: NIS, Pendrin, Tg, TPO, DUOX2, DEHAL;45
5.6;2.6 Genetic Variation in Thyroid Hormone Receptor Genes: TR;47
5.7;, TR;47
5.8;2.7 Genetic Variation in Serum TH Transport Proteins: TBG, TTR, and Albumin;48
5.9;2.8 Genetic Variation in TH Transporters: MCT8, MCT10, OATPs;49
5.9.1;2.8.1 MCT8 and MCT10;49
5.9.2;2.8.2 OATP1A2, 1B1, 1B3, and 1C1;50
5.10;2.9 Genetic Variation in Deiodinases: D1, D2, D3;53
5.11;2.10 Genome-Wide Association (GWA) Studies;54
5.12;2.11 Concluding Remarks;54
5.13;References;55
6;Influence of Iodine Deficiency and Excess on Thyroid Function Tests;62
6.1;3.1 Introduction;62
6.2;3.2 Iodine Metabolism and Thyroid Function;64
6.3;3.3 Thyroid Adaptation to Iodine Deficiency;64
6.4;3.4 Epidemiology of Thyroid Function in Areas of Low Iodine Intake;66
6.4.1;3.4.1 Adults;66
6.4.2;3.4.2 Pregnancy;67
6.4.3;3.4.3 Newborns;69
6.4.4;3.4.4 Children;71
6.5;3.5 Introducing/Increasing Iodine Intakes and/or Iodine Excess: Effects on Thyroid Function in Populations;73
6.5.1;3.5.1 Cross-Sectional Studies: The Epidemiology of Thyroid Function in Areas of Low and High Iodine Intakes;74
6.5.2;3.5.2 High Iodine Intake Produces Thyroid Dysfunction in Children;75
6.5.3;3.5.3 Longitudinal Studies: The Effects of Increasing Iodine Intakes in Populations on Thyroid Function;76
6.6;3.6 Conclusions;78
6.7;References;78
7;Regulation of Thyroid Hormone Production and Measurement of Thyrotropin;87
7.1;4.1 Introduction;87
7.2;4.2 Production of Thyroid Hormone;87
7.2.1;4.2.1 Sodium/Iodide Symporter;87
7.2.2;4.2.2 Dietary Iodine Requirements;88
7.2.3;4.2.3 Thyroid Peroxidase;89
7.2.4;4.2.4 Hydrogen Peroxide Generation;89
7.2.5;4.2.5 Apical Iodide Transport;89
7.2.6;4.2.6 Thyroglobulin;90
7.3;4.3 TSH Biochemistry and Physiology;90
7.3.1;4.3.1 T3 Negative Regulation of TSH;91
7.4;4.4 Thyrotropin-Releasing Hormone;91
7.5;4.5 Diurnal Rhythmicity of TSH;92
7.6;4.6 Other Factors that Regulate TSH Secretion;93
7.7;4.7 Clinical Effects of TRH;94
7.8;4.8 Measurement of TSH;95
7.9;4.9 Normal Serum TSH Levels;96
7.10;4.10 Factors Affecting TSH Clinically;97
7.11;References;98
8;Measurements of Thyroxine and Triiodothyronine;101
8.1;5.1 Introduction;101
8.2;5.2 The Trophic–Target Gland Relationship;101
8.3;5.3 The Basis of Total and Free Thyroid Hormone Methodology;102
8.4;5.4 Total T4 and T3 Methods;104
8.5;5.5 Principles of Free T4 Methods;104
8.6;5.6 Factors that Limit the Validity of Free T4 Methods;106
8.7;5.7 Evaluation of Serum Free T4 Methods;111
8.8;5.8 Free T4 in Special Situations;112
8.8.1;5.8.1 Pregnancy;112
8.8.2;5.8.2 Thyrotoxicosis and Hypothyroidism;113
8.8.3;5.8.3 Thyroxine Replacement;114
8.8.4;5.8.4 Critical Illness;114
8.8.5;5.8.5 Premature Infants;116
8.9;5.9 Total T4 Measurement;117
8.10;5.10 Indications for Measurement of Serum T3;117
8.11;5.11 Approach to Anomalous Results;118
8.12;5.12 Conclusion;119
8.13;References;120
9;Thyroid Autoantibody Measurement;124
9.1;6.1 Introduction;124
9.2;6.2 Humoral Immunity in Autoimmune Thyroid Disease;125
9.2.1;6.2.1 Thyroid Autoantigens;125
9.2.2;6.2.2 The Role of Thyroid Autoantibodies in Disease Pathogenesis;126
9.3;6.3 Assays for Thyroid Antibodies;128
9.3.1;6.3.1 Thyroid Stimulating Hormone Receptor;128
9.3.2;6.3.2 Thyroid Peroxidase;129
9.3.3;6.3.3 Thyroglobulin;129
9.3.4;6.3.4 Sodium/Iodide Symporter;130
9.4;6.4 Clinical Applications of Antibody Measurement;130
9.4.1;6.4.1 Graves’ Disease;130
9.4.2;6.4.2 Graves’ Ophthalmopathy;131
9.4.3;6.4.3 Autoimmune Hypothyroidism;131
9.4.4;6.4.4 Pregnancy and Postpartum Thyroiditis;132
9.4.5;6.4.5 Differentiated Thyroid Cancer;133
9.5;6.5 Recommendation for the Use of Thyroid Autoantibodies in Clinical Practice;133
9.6;6.6 Conclusion;134
9.7;References;135
10;Thyroglobulin Measurement;140
10.1;7.1 Tg Biosynthesis and Metabolic Clearance;140
10.2;7.2 Tg Assay Methodology: Technical Issues;141
10.2.1;7.2.1 Standardization/Specificity;142
10.2.2;7.2.2 Methodologic Sensitivity;144
10.2.3;7.2.3 Interferences;145
10.3;7.3 TgAb Measurements Used as a Surrogate Tumor Marker;147
10.4;7.4 Tg mRNA as a Tumor Marker;148
10.5;7.5 The Clinical Utility of Tg Measurement when TgAb Is Present;148
10.6;7.6 The Clinical Utility of Tg Measurement when TgAb Is Absent;150
10.6.1;7.6.1 Factors Influencing Circulating Tg Concentrations;150
10.6.2;7.6.2 Serum Tg Reference Range;151
10.6.3;7.6.3 Serum Tg Measurements for Nonmalignant Thyroid Conditions;152
10.6.4;7.6.4 Tg Measurement for Differentiated Thyroid Cancer;154
10.7;References;157
11;Thyroid Function Testing in Ambulatory Practice;169
11.1;8.1 Choice of Tests in Thyroid Function Testing;170
11.2;8.2 Evaluation of the Symptomatic Patient;171
11.2.1;8.2.1 Suspected Thyrotoxicosis;172
11.2.2;8.2.2 Suspected Hypothyroidism;173
11.2.3;8.2.3 Nodular Goiter;174
11.3;8.3 Use of Thyroid Function Tests to Monitor Treated Thyroid Dysfunction;175
11.3.1;8.3.1 Monitoring Hypothyroidism;175
11.3.2;8.3.2 Monitoring Hyperthyroidism;176
11.4;8.4 Screening of the General Population for Thyroid Dysfunction;177
11.5;8.5 Screening of Targeted Populations;178
11.5.1;8.5.1 Women of Childbearing Age, Pregnant Women, and Lactating Women;178
11.5.2;8.5.2 Elderly;179
11.5.3;8.5.3 Patients with Specific Comorbidities;180
11.6;8.6 Conclusions;181
11.7;References;181
12;Assessing Thyroid Function in Infants and Children;186
12.1;9.1 Introduction;186
12.2;9.2 Infants;187
12.2.1;9.2.1 Hypothyroidism;187
12.2.2;9.2.2 Hypothyroxinemia in the Preterm Infant;191
12.2.3;9.2.3 Hyperthyroidism;192
12.3;9.3 Children;193
12.3.1;9.3.1 Hypothyroidism;193
12.3.2;9.3.2 Hyperthyroidism;195
12.4;References;197
13;Assessing Thyroid Function in Hospitalized Patients;199
13.1;10.1 Introduction;199
13.2;10.2 Low T3 State;201
13.3;10.3 Low T3/T4 State;204
13.4;10.4 Measurement of Thyroid Hormones in Illness;205
13.5;10.5 TSH Regulation in the Low T3 and Low T3/T4 States;206
13.6;10.6 Interpretation of Thyroid Tests in the Hospitalized Patient;207
13.7;10.7 Drugs that Affect Thyroid Function Tests;210
13.7.1;10.7.1 Glucocorticoids;210
13.7.2;10.7.2 Dopamine;210
13.7.3;10.7.3 Amiodarone;212
13.7.4;10.7.4 Heparin and Low Molecular Weight Heparins;212
13.7.5;10.7.5 Diphenylhydantoin;213
13.8;10.8 Variants of Nonthyroidal Illness;213
13.8.1;10.8.1 HIV and Thyroid Function;213
13.8.2;10.8.2 Liver Disease and Thyroid Function;214
13.8.3;10.8.3 Hyperemesis Gravidarum;214
13.8.4;10.8.4 Psychiatric Illness and Thyroid Function;215
13.9;10.9 Concluding Remarks;215
13.10;References;216
14;Assessing Thyroid Function in Pregnancy;220
14.1;11.1 Importance of Thyroid Status in Pregnancy;220
14.1.1;11.1.1 Thyroid Physiology in Pregnancy;220
14.2;11.2 Human Chorionic Gonadotrophin;222
14.3;11.3 Clinical Relevance of Assessing Thyroid Function in Pregnancy;224
14.3.1;11.3.1 Hyperthyroidism;224
14.3.2;11.3.2 Hypothyroidism;225
14.4;11.4 Maternal Thyroid Disease in Pregnancy: Effect on Child Development;225
14.5;11.5 Clinical Implications of Thyroid Antibodies in Gestation;226
14.6;11.6 Methods for Measuring Thyroid Function in Pregnancy;226
14.6.1;11.6.1 Total and Free Thyroid Hormone Measurements in Pregnancy;227
14.6.2;11.6.2 TSH Tests in Pregnancy;228
14.6.3;11.6.3 Free Thyroid Hormone Testing in Pregnancy;234
14.7;11.7 Development of Reference Intervals for Thyroid Hormones in Pregnancy;234
14.7.1;11.7.1 Trimester-Specif ic Method-Specif ic Reference Intervals;235
14.7.2;11.7.2 Trimester-Specific Thyroid Function Tests;235
14.8;11.8 Screening for Thyroid Function in Pregnancy;237
14.9;11.9 Conclusions;239
14.10;References;239
15;Assessing Thyroid Function in the Elderly;245
15.1;12.1 Changes in Normal Thyroid Function with Aging;245
15.2;12.2 Hypothyroidism in the Elderly;246
15.2.1;12.2.1 Prevalence;246
15.2.2;12.2.2 Etiology;247
15.2.3;12.2.3 Clinical Manifestations;247
15.2.4;12.2.4 Diagnosis;249
15.2.5;12.2.5 Treatment;249
15.3;12.3 Hyperthyroidism in the Elderly;250
15.3.1;12.3.1 Prevalence;250
15.3.2;12.3.2 Etiology;251
15.3.3;12.3.3 Clinical Manifestations;251
15.3.4;12.3.4 Diagnosis;253
15.3.5;12.3.5 Treatment;253
15.4;12.4 Thyroid Nodules and Cancer;255
15.5;12.5 Challenges in Assessing Thyroid Function in the Elderly;255
15.5.1;12.5.1 What is the Normal TSH Range in the Elderly?;255
15.5.2;12.5.2 Altered Presentation of Thyroid Disease in the Elderly;257
15.5.3;12.5.3 The Effects of Comorbid Conditions and Drugs on Thyroid Function in the Elderly;257
15.5.4;12.5.4 Risks of Treatment in the Elderly;257
15.6;References;258
16;Influence of Drugs on Thyroid Function Tests;261
16.1;13.1 Introduction;261
16.2;13.2 Alterations of Thyroid Hormone Secretion;261
16.2.1;13.2.1 Thionamides;261
16.2.2;13.2.2 Lithium;263
16.2.3;13.2.3 Iodides;263
16.2.4;13.2.4 Other Medications that Decrease Thyroid Hormone Secretion;265
16.3;13.3 Changes in T4 and T3 Serum Transport Proteins;265
16.3.1;13.3.1 Medications that Increase TBG;266
16.3.2;13.3.2 Medications that Decrease TBG;267
16.3.3;13.3.3 Competition with T4 and T3 Binding Sites on Thyroid Hormone Binding Proteins;268
16.4;13.4 Metabolism of Thyroid Hormones;269
16.4.1;13.4.1 Hepatic Metabolism;269
16.4.2;13.4.2 Deiodination;270
16.5;13.5 Central TSH Suppression;271
16.6;13.6 Medications with Multiple Effects;272
16.6.1;13.6.1 Glucocorticoids;272
16.6.2;13.6.2 Amiodarone;273
16.6.3;13.6.3 Bexarotene;275
16.6.4;13.6.4 Cytokines;275
16.6.5;13.6.5 Other Medications with Effects on Thyroid Function Tests;276
16.7;13.7 Levothyroxine Absorption;277
16.8;13.8 Conclusions;278
16.9;References;278
17;Index;288

Leseproben

"Chapter 7 Thyroglobulin Measurement Carole Spencer and Ivana Petrovic (p. 125-126)

7.1 Tg Biosynthesis and Metabolic Clearance

The thyroglobulin (Tg) gene is encoded by human chromosome 8q24.2–8q24.3 in a 8.5 kb coding sequence covering 48 exons. As illustrated in Fig. 7. , transcription of the 330 kDa Tg monomeric protein is regulated by a number of transcription factors that include TTF- , TTF-2, and Pax-8 [ –3]. Posttranslational processing is complex and necessitates multiple molecular chaperones to control the glycosylation, appropriate folding, dimerization, and trafficking of the mature protein to the apical membrane where thyroid peroxidase catalyses the iodination of the hormonogenic sites [ , 3–6].

Comparisons between Tg derived from papillary cancers versus normal thyroid tissue show differences in carbohydrate, iodine content, sulfation, charge, and immunological properties [7– 3]. These differences likely result from defective posttranslational processing of tumor-derived Tg leading to the secretion of Tg molecules with an abnormal tertiary structure. Because Tg epitopes are conformational, any alteration in the tertiary structure of the molecule has the potential to disrupt the immunological interaction(s) with the assay reagents [7, 0, , 4– 6].

The half-life of Tg in serum approximates 3 days and is determined by the terminal sialic acid content of the molecule [ 7]. Both the sialic acid and iodine content of the Tg derived from papillary tumors tend to be lower than normal, suggesting the possibility for differences in the metabolic clearance of Tg protein secreted by different tumors [8, 7– 9].

An accelerated metabolic clearance of tumor-derived Tg could be the reason why serum Tg can be paradoxically low or even undetectable in some patients with a significant tumor burden [ , 2, 20–24]. 7.2 Tg Assay Methodology: Technical Issues Tg measurement still remains technically challenging. Most laboratories favor automated immunometric assay (IMA) methods because they are nonisotopic, require shorter incubations than radioimmunoassay (RIA; hours vs. days), and can be automated.

Manufacturers are beginning to use a two-step approach to overcome the “hook” problems that plague tumor-marker IMAs, wherein high antigen concentrations exceed the binding capacity of the capture antibody and cause inappropriately low results [25–28]. Unfortunately, Tg IMA methodology appears to have a greater propensity for interference, both from human anti-mouse antibodies (HAMA; see Sect. 7.2.3. ) and Tg autoantibodies (TgAb; see Sect. 7.2.3.2) as compared with RIA [ 6]. RIA is not influenced by HAMA; however TgAb has the potential to interfere and cause false low or high RIA values depending on the specificity of the RIA reagents employed [26, 29–33]."