ABBOTT LABORATORIES BECKMAN COULTER …

1 The 9th EFCC Continuous Postgraduate Course in Clinical Chemistry Under the Auspices of IFCC NEW TRENDS IN CLASSIFICATION, DIAGNOSIS AND MANAGEMENT OF THYROID DISEASES Handbook Edited by Prof. Ana-Maria imundi , Prof. Victor Blaton, Barbara Mo ina, Reviewed by Prof. Elizabeta Topi , Organizers Croatian Society of Medical Biochemists Slovenian Association for Clinical Chemistry European Federation of Clinical Chemistry and Laboratory Medicine Dubrovnik, October 24-25, 2009 The organizers would like to thank ABBOTT LABORATORIES BECKMAN COULTER ROCHE DIAGNOSTICS MINISTRY OF SCIENCE, EDUCATION AND SPORTS Table of contents EDITIORIAL 1. THYROID HORMONE synthesis , STORAGE AND RELEASE .. 1 Prof. Vesna Barac-Latas, Department of Physiology and Immunology, Medical Faculty, University of Rijeka, Croatia 2.

2 THYROID DISEASES: EPIDEMIOLOGY, PATHOPHYSIOLOGY AND CLASSIFICATION .. 11 Academician Zvonko Kusi ; Tomislav Juki , , ; Marta Bori , Department of oncology and nuclear medicine - Referral Center for Thyroid Diseases of the Ministry of Health, "Sestre milosrdnice" University Hospital, Zagreb, Croatia 3. 19 Assist. Prof. Simona Gaber ek, , Department of Nuclear Medicine, University Medical Centre Ljubljana, Slovenia 4. HYPOTHYROIDISM .. 29 Prof. Sergej Hojker University Medical Center Ljubljana, Ljubljana, Slovenija 5. THYROID 37 Assoc. Prof. Nikola Be i , , Department of Surgical Oncology, Institute of Oncology, Ljubljana, Slovenia 6. CELL SIGNALING IN CARCINOMA CELLS DIFFERENCES BETWEEN HEALTHY CELLS AND TRANSFORMED CELLS .. 43 Sanda Jelisavac osi , University Hospital Centre Zagreb, Department of Pathophysiology and Scientific Research, Zagreb, Croatia 7.

3 BASIC CONCEPTS AND MISCONCEPTS IN CLINICAL AND DIAGNOSTIC ENDOCRINOLOGY .. 55 Prof. Gabor L. Kovacs, , Institute of Laboratory Medicine, University of Pecs, Hungary 8. INAPPROPRIATE TSH 65 Emese Mezosi, , Ist Department of Internal Medicine, University Medical School of Pecs, Hungary 9. THYROID DISEASES AND OBESITY .. 73 Jo o-Tiago Guimar es, , Biochemistry Department, Faculty of Medicine, University of Porto & Clinical Pathology Service, S o Jo o Hospital, Porto, Portugal 10. THYROID (DYS)FUNCTION AND PREGNANCY .. 77 Prof. Paolo Beck-Peccoz, , Department of Medical Sciences, University of Milan, Endocrinology and Diabetology Unit, Fondazione Policlinico IRCCS, Milan, Italy 11. REPORTS ON THYROID DISEASES: TRUTHS, MYTHS AND PITFALLS .. 81 Prof. Mladen Petrove ki, , Department of Medical Informatics, Rijeka University School of Medicine, Rijeka, and Department of Clinical Laboratory Diagnosis, Dubrava University Hospital, Zagreb, Croatia 12.

4 PREANALYTICAL AND ANALYTICAL ERRORS IN THYROID ASSAYS .. 89 Tam s K szegi, , , medHabil University of P cs, Institute of Laboratory Medicine, P cs, Hungary 13. BIOLOGICAL VARIATION OF THYROID AUTOANTIBODIES AND THYROGLOBULIN .. 99 Esther Jensen1,, Per Hyltoft Petersen2, Ole Blaabjerg1, Laszlo Heged s3 1 Department of Clinical Biochemistry, Hiller d Hospital, Hiller d, Denmark, 2 NOKLUS, Norwegian quality improvement of primary care LABORATORIES , Division for General Practice, University of Bergen, Bergen, Norway, 3 Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark 14. NATIONAL ACADEMY OF CLINICAL BIOCHEMISTRY LABORATORY SUPPORT FOR THE DIAGNOSIS AND MONITORING OF THYROID DISEASE: A PERSONAL SUMMARY .. 105 Prof. Pierre Carayon, , Department of Biochemistry and Molecular Biology, Marseille Medical School and Mediterranean University Hospital, Marseille, France Editorial The Eight EFCC Continuous Postgraduate Course in Clinical Chemistry: New Trends in Classification, Diagnosis and Management of Thyroid Diseases The Croatian Society of Medical Biochemists and Slovenian Association for Clinical Chemistry, together with the European Federation of Clinical Chemistry and Laboratory Medicine (EFCC), have again organized this ninth postgraduate weekend course under the auspices of IFCC.

5 The Course entitled New Trends in Classification, Diagnosis and Management of Thyroid Diseases promotes continuing postgraduate education of professionals in clinical chemistry and laboratory medicine, and ensures the laboratory knowledge harmonization. In this Course the state-of-the-art on thyroid physiology, pathophysiology as well as new approach to diagnosis and management will be presented by well-known experts. The integrated knowledge of the authors and the material prepared by these experts especially for this course, is intended to provide updated information of supreme quality to the reader. Renowned experts in different fields have tried to cover the clinical and laboratory aspects of thyroid diseases. We hope that all those attending the Course, will have an excellent opportunity to acquire new knowledge and exchange experience in the field.

6 Ana-Maria imundi Zagreb, October 2009 Barac-Latas V. Thyroid hormone synthesis , storage and release 1 1. THYROID HORMONE synthesis , STORAGE AND RELEASE Prof. Vesna Barac-Latas, Department of Physiology and Immunology, Medical Faculty, University of Rijeka, Croatia Thyroid gland The thyroid gland consists of two lobes (left and right) connected by a thin, median isthmus forming a "butterfly" shape. It is located in the neck, in front of the trachea, just below the larynx, weighs 15-20g in the adult. This is highly vascularized organ with blood flow about 5mL/g/min of tissue. Although the thyroid represents about of body weight it accounts for 2% of total blood flow. The gland receives fibers from both sympathetic and parasympathetic divisions of the autonomic nervous system.

7 The sympathetic fibers are derived from the cervical ganglia and enter the gland along the blood vessels. The parasympathetic fibers are derived from the vagus and reach the gland by branches of the laryngeal nerves. Figure Structure of the thyroid gland. The gland consists of thousands of follicles, each a spheroidal sac of epithelial cells (thyrocytes) surrounding a lumen containing colloid, a depot of thyroid hormone precursor, thyroglobulin. The average diameter of follicle is 300 microns. The epithelium of the normal gland is usually described as cuboidal, with the apical plasma membrane (facing the follicle lumen) and the basolateral plasma membrane on opposite site. The most conspicuous structural difference between the apical and basolateral cell surface is that only former is furnished with microvili (pseudopods).

8 Cytochemical studies show differences in enzyme components between the two domains, presence of peroxidase, aminopeptidase and H2O2-genereting activity only at the apical surface and Na+/K+ ATPase only at the basolateral surface. Barac-Latas V. Thyroid hormone synthesis , storage and release 2 The thyroid gland secretes three hormones: thyroxine (T4) and triiodothyronine (T3), both of which are iodinated derivatives of tyrosine, and calcitonin, a polypeptide hormone. T4 and T3 are produced by the follicular cells but calcitonin is secreted by the C (parafolicular) cells, which are of separate embryological origin. Calcitonin is functionally unrelated to the other thyroid hormones. It has a minor role in calcium homeostasis. Biological actions of thyroid hormones Thyroid hormones (THs) are essential for normal growth and development and stimulate metabolism in most tissues (adult brain is a conspicuous exception).

9 THs increase mitochondrial oxidative phosphorylation and maintain amino acid and electrolyte transport into cells. They increase calorigenesis and oxygen consumption in most tissues. THs stimulate the synthesis of proteins that can be structural proteins or enzymes. They regulate carbohydrate metabolism, accelerating insulin degradation and increasing gluconeogenesis. Stimulation of lipid metabolism leads to a fall cholesterol concentration in plasma. THs also increase the sensitivity of the cardiovascular and nervous system to catecholamines, the former leading to increases in heart rate and cardiac output, and the latter to increased arousal. Most of the actions of THs are exerted through modulation of gene expression.

10 They enter into the cells and act by binding to specific receptors in the nuclei, where they stimulate the synthesis of a variety of species of mRNA, thus stimulating the synthesis of proteins, including enzymes and hormones. T3 exerts its effects through interaction with nuclear thyroid receptors (TR) that have a high affinity and high specificity for T3. These receptors belong to the family of ligand-regulated transcription factors that are associated with chromatin. The formation of the T3-TR/DNA complex and subsequent recruitment of a variety of transcriptional coactivators leads to activation of the target genes, giving increased mRNA and protein production. synthesis , storage and release of thyroid hormones The thyroid gland produces two related hormones, 3,5,3',5'-tetraiodothyronine (thyroxine; T4) and 3,5,3'-triiodothyronine (T3).