Download PDF
Nuklearmedizin 2005; 44(02): 56-61
DOI: 10.1055/s-0038-1623926
Original Article
Schattauer GmbH

Where does subclinical hypothyroidism start?

Implications for the definition of the upper reference limit for thyroid stimulating hormoneWo beginnt die subklinische Hypothyreose?Implikationen zur Definition der oberen Referenzgrenze für Thyreotropin
K. Zöphel
1   Klinik für Nuklearmedizin (Direktor: Prof. Dr. med. Hans Döge), Klinikum Chemnitz gGmbH, Chemnitz
2   Klinik und Poliklinik für Nuklearmedizin (Direktor: Prof. Dr. med. Jörg Kotzerke), Universitätsklinikum Carl Gustav Carus der Technischen Universität Dresden, Deutschland
,
G. Wunderlich
1   Klinik für Nuklearmedizin (Direktor: Prof. Dr. med. Hans Döge), Klinikum Chemnitz gGmbH, Chemnitz
,
Th. Grüning
4   Department of Nuclear Medicine, Derriford Hospital, Plymouth, United Kingdom
,
R. Koch
3   Institut für Medizinische Informatik und Biometrie (Direktor: Prof. Dr. med. Hildebrand Kunath), Universitätsklinikum Carl Gustav Carus der Technischen Universität Dresden, Deutschland
,
H. Döge
1   Klinik für Nuklearmedizin (Direktor: Prof. Dr. med. Hans Döge), Klinikum Chemnitz gGmbH, Chemnitz
,
J. Kotzerke
2   Klinik und Poliklinik für Nuklearmedizin (Direktor: Prof. Dr. med. Jörg Kotzerke), Universitätsklinikum Carl Gustav Carus der Technischen Universität Dresden, Deutschland
› Author Affiliations
Further Information

Publication History

Eingegangen: 15 September 2004

11 October 2004

Publication Date:
11 January 2018 (online)

Also available at
    Permissions and Reprints

Summary

The upper limit of the TSH reference range is currently under discussion. In its recent guidelines, the National Academy of Clinical Biochemistry (NACB) recommended the use of ~2.5 mIU/L, rather than ~4 mIU/L, due to the fact that reference populations, on which the definition of the reference range is based, contain persons undergoing an initial phase of autoimmune thyroid disease. This will skew the upper reference limit of TSH. Ultrasonography, in addition to measurement of thyroid autoantibodies, should be used to exclude these persons. Objective: The present study investigates whether the NACB recommendation also applies for a region of mild iodine deficiency. Methods: According to NACB criteria, a reference population (713 persons) was defined out of a total study population of 1442. The TSH reference range was calculated in this reference group and in further subgroups by percentiles. The results were compared with the total study population and the NACB recommendation. All assays used were provided by BRAHMS Diagnostica AG, Hennigsdorf, Germany. Results: As expected, all median TSH values, excluding the median of the group with a hypoechogenic thyroid were close to 1.2 mIU/L. The 97.5th percentile in the reference population was 3.35 mIU/L. However, there was no difference compared to the total study population. Conclusion: The upper reference limit for TSH based on a reference population according to NACB criteria came down to 3.35 mIU/L, but not to ~2.5 mIU/L. Interestingly, there is no difference compared to the total study population.

Zusammenfassung

Über die obere Grenze des Referenzbereichs für TSH wird lebhaft diskutiert. Die National Academy of Clinical Biochemistry (NACB) empfiehlt in ihren aktuellen Richtlinien die Absenkung derselben von derzeit ~4 mIU/l auf ~2,5 mIU/l mit der Begründung, dass die Referenzpopulationen, die der Referenzbereichsbestimmung zugrunde liegen, Personen enthalten, die bereits ein initiales Stadium einer Autoimmunthyreopathie durchlaufen. Dies verschiebt die obere Grenze des TSH-Referenzbereichs. Die Sonographie soll deshalb neben der Autoantikörperbestimmung zum Ausschluss solcher Personen herangezogen werden. Ziel: Diese Untersuchung soll klären, ob diese Empfehlung der NACB auf eine Region mit milder Ioddefizienz übertragbar ist. Methoden: Aus einem Gesamtkollektiv von 1442 Personen wurde eine Referenzpopulation (713 Personen) nach den NACB-Kriterien definiert. In diesem Referenzkollektiv und in weiteren Subgruppen erfolgte dann die Bestimmung des TSH-Referenzbereichs über Perzentilen. Diese wurden untereinander, mit dem Gesamtkollektiv und der NACB-Empfehlung verglichen. Alle Assays stammten von der Firma BRAHMS Diagnostica AG, Hennigsdorf. Ergebnisse: Erwartungsgemäß lagen alle medianen TSH-Werte, bis auf den der Gruppe mit sonographisch echoarmer Schilddrüse (1,78 mIU/l), um 1,2 mIU/l. Die 97,5. Perzentile in der Referenzpopulation wurde mit 3,35 mIU/l bestimmt. Allerdings unterschied sich dieser Wert nicht von dem des Gesamtkollektivs. Schlussfolgerung: Die obere Grenze des TSH-Referenzbereichs wird in einem nach den Kriterien der NACB definierten Referenzkollektiv mit 3,35 mIU/l zwar niedriger, jedoch nicht bei ~2,5 mIU/l, gefunden. Interessanterweise findet sich diesbezüglich kein Unterschied zwischen Referenz- und Gesamtkollektiv.

Keywords

Thyroid stimulating hormone - subclinical hypothyroidism - TSH reference range - thyroid gland

Schlüsselwörter

Thyreotropin - TSH-Referenzbereich - subklinische Hypothyreose - Schilddrüse
 

  • Literatur

  • 1 Bergoglio LM, Vilchez PE, Fatemi S. et al. TPOAb Assay Limitations may be responsible for the skew in the upper reference limit. Latin American Thyroid Society 2003 Cordoba, Argentina: Abstract # 123.
    PubMedSearch in Google Scholar
  • 2 Col NF, Surks MI, Daniels GH. Subclinical thyroid disease – clinical applications. JAMA 2004; 291: 239-43.
    CrossrefPubMedSearch in Google Scholar
  • 3 Demers LM, Spencer CA. Laboratory medicine practice guidelines: laboratory support for the diagnosis and monitoring of thyroid disease. Thyroid 2003; 13: 45-56.
    CrossrefSearch in Google Scholar
  • 4 Dietlein M, Dressler J, Farahati J. et al. Procedure guideline for radioiodine therapy of differentiated thyroid cancer (version 2). Nuklearmedizin 2004; 43: 115-20.
    Thieme ConnectPubMedSearch in Google Scholar
  • 5 Dietlein M, Schober O, Schicha H. Overtherapy or undertherapy for papillary thyroid micro-carcinoma?. Nuklearmedizin 2004; 43: 107-14.
    Thieme ConnectPubMedSearch in Google Scholar
  • 6 Dietlein M, Dressler J, Grünwald F. et al. Guideline for in vivo- and in vitro procedures for thyroid diseases (version 2). Nuklearmedizin 2003; 42: 109-15.
    Thieme ConnectPubMedSearch in Google Scholar
  • 7 Dietlein M, Dressler J, Eschner W. et al. Procedure guideline for radioiodine test (version 2). Nuklearmedizin 2003; 42: 116-9.
    Thieme ConnectPubMedSearch in Google Scholar
  • 8 Dietlein M, Dressler J, Eschner W. et al. Procedure guideline for thyroid scintigraphy (version 2). Nuklearmedizin 2003; 42: 120-2.
    Thieme ConnectPubMedSearch in Google Scholar
  • 9 Dietlein M, Dressler J, Eschner W. et al. Procedure guideline for iodine-131 whole-body scintigraphy for differentiated thyroid cancer (version 2). Nuklearmedizin 2003; 42: 123-5.
    Thieme ConnectPubMedSearch in Google Scholar
  • 10 Dietlein M, Moka D, Schmidt M. et al. Prevention, screening and therapy of thyroid diseases and their cost-effectiveness. Nuklearmedizin 2003; 42: 181-9.
    Thieme ConnectPubMedSearch in Google Scholar
  • 11 Görges R, Brandt-Mainz K, Freudenberg L. et al. Continously increasing sensitivity in thyroid cancer aftercare in the course of three generations of thyroglobulin IMAs. Nuklearmedizin 2003; 43: 157-66.
    Thieme ConnectSearch in Google Scholar
  • 12 Hollowell JG, Staehling NW, Hannon WH. et al. Serum thyrotropin, thyroxine, and thyroid antibodies in the United States population (1988 to 1994): NHANES III. J Clin Endocrinol Metab 2002; 87: 489-99.
    CrossrefPubMedSearch in Google Scholar
  • 13 Imaizumi M, Akahoshi M, Ichimaru S. et al. Risk for ischemic heart disease and all-cause mortality in subclinical hypothyroidism. J Clin Endocrinol Metab 2004; 89: 3365-70.
    CrossrefPubMedSearch in Google Scholar
  • 14 King C, Ilic A, Koelsch K. et al. Homeostatic expansion of T cells during immune insufficiency generates autoimmunity. Cell 2004; 117: 265-77.
    CrossrefPubMedSearch in Google Scholar
  • 15 Löffler M, Weckesser M, Franzius C. et al. Iodine excretion during stimulation with rhTSH in differentiated thyroid carcinoma. Nuklearmedizin 2003; 42: 240-3.
    Thieme ConnectPubMedSearch in Google Scholar
  • 16 Pedersen OM, Aardal NP, Larssen TB. et al. The value of ultrasonography in predicting autoimmune thyroid disease. Thyroid 2000; 10: 251-9.
    CrossrefPubMedSearch in Google Scholar
  • 17 Pirnat E, Zaletel K, Gaberscek S. et al. Early changes of thyroid hormone concentrations after 131I therapy in Graves’ patients pretreated or not with methimazole. Nuklearmedizin 2004; 43: 129-34.
    Thieme ConnectPubMedSearch in Google Scholar
  • 18 Prummel MF, Strieder T, Wiersinga WM. The environment and autoimmune thyroid diseases. Eur J Endocrinol 2004; 150: 605-18.
    CrossrefPubMedSearch in Google Scholar
  • 19 Prummel MF, Wiersinga WM. Thyroid autoimmunity and miscarriage. Eur J Endocrinol 2004; 751-5.
    PubMedSearch in Google Scholar
  • 20 Reinhardt M, Schümichen C, Schächtele S. et al. Assessment of basal and stimulated TSH in overt and subclinical hyperthyroidism. Nuklearmedizin 1995; 34: 61-5.
    Thieme ConnectPubMedSearch in Google Scholar
  • 21 Roden M, Nowotny P, Vierhapper H. et al. Diagnostic relevance of suppressed basal concentrations of TSH compared with the negative TRH test in detection and exclusion of hyperthyroidism. Acta Endocrinol 1991; 124: 136-42.
    Search in Google Scholar
  • 22 Sahlmann CO, Siefker U, Lehmann K. et al. Quantitative thyroid scintigraphy for the differentiation of Graves’ disease and hyperthyroid autoimmune thyroiditis. Nuklearmedizin 2004; 43: 124-8.
    Thieme ConnectPubMedSearch in Google Scholar
  • 23 Schicha H, Reiners Chr, Moser E. et al. Subclinical thyroid disease. Nuklearmedizin 2004; 43: 69-71.
    Thieme ConnectPubMedSearch in Google Scholar
  • 24 Sharp D. Whose normal thyroid function is better – yours or mine?. Lancet 2002; 360: 353-4.
    CrossrefPubMedSearch in Google Scholar
  • 25 Spencer CA. Subclinical Hypothyroidism and TSH – New Aspects on TSH Reference Values. Guest Lecture anlässlich der Tagung Schilddrüse Heidelberg 2003; Berlin: De Gruyter; 2004
    Search in Google Scholar
  • 26 Spencer CA. National Academy of Clinical Biochemistry. Consensus Guidelines. 2003: Guideline 22 and; 27
  • 27 Spencer CA, Takeuchi M, Kazarosyan M. Current status and performance goals for serum thyrotropin (TSH) assays. Clin Chem 1996; 42: 140-5.
    PubMedSearch in Google Scholar
  • 28 Spencer CA, Takeuchi M, Kazarosyan M. et al. Interlaboratory/intermethod differences in functional sensitivity of immunometric assays of thyrotropin (TSH) and impact on reliability of measurement of subnormal concentrations of TSH. Clin Chem 1995; 41: 367-74.
    PubMedSearch in Google Scholar
  • 29 Spencer CA, Schwarzbein D, Guttler RB. et al. Thyrotropin (TSH)-releasing hormone stimulation test responses employing third and fourth generation TSH assays. J Clin Endocrinol Metab 1993; 76: 494-8.
    PubMedSearch in Google Scholar
  • 30 Surks MI, Ortiz E, Daniels GH. et al. Subclinical thyroid disease – scientific review and guidelines for diagnostic and management. JAMA 2004; 291: 228-38.
    CrossrefPubMedSearch in Google Scholar
  • 31 Taimela E, Taehtelae R, Koskinen P. et al. Ability of two new thyrotropin (TSH) assays to separate hyperthyroid patients from euthyroid patients with low TSH. Clin Chem 1994; 40: 101-5.
    PubMedSearch in Google Scholar
  • 32 Zöphel K, Saller B, Wunderlich G. et al. Auto-antibodies to Thyroperoxidase (TPOAb) in a Large Population of Euthyroid Subjects: Implications for the Definition of TPOAb Reference Intervals. Clin Lab 2003; 49: 591-600.
    PubMedSearch in Google Scholar
  • 33 Zöphel K, Wunderlich G, Kopprasch C. et al. Predictive value of thyrotropin receptor antibodies (TRAb) using the second generation TRAb human assay after radioiodine treatment in Graves‘ disease. Nuklearmedizin 2003; 42: 63-70.
    Thieme ConnectPubMedSearch in Google Scholar
  • 34 Zöphel K, Pinkert J, Wunderlich G. et al. Can immunoradiometric measurement of Serum Thyrotropin (TSH) compete with a luminometric assay?. Nuklearmedizin 1999; 38: 150-5.
    Thieme ConnectPubMedSearch in Google Scholar