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Nichts ist so überflüssig wie ein Kropf!. Selen und Schilddrüse 1987: Assoziation Selenmangel mit Hypothyreose 1990: Identifikation der 5-Dejodase als.

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Presentation on theme: "Nichts ist so überflüssig wie ein Kropf!. Selen und Schilddrüse 1987: Assoziation Selenmangel mit Hypothyreose 1990: Identifikation der 5-Dejodase als."— Presentation transcript:

1 Nichts ist so überflüssig wie ein Kropf!

2 Selen und Schilddrüse 1987: Assoziation Selenmangel mit Hypothyreose 1990: Identifikation der 5-Dejodase als Selenoenzym 1992: in ehem. Belgisch-Kongo häufig Hypothyreose + kleine echoarme SD; nur J + Se erhielt die SD-Fkt. 2002: 70 hypothyreote Pat. mit florider AIT 200µg Na-Selenit für 3 Mon. Abfall der TPO-Ak um 36%, nach Absetzen Wiederanstieg innerhalb von 3 Mon. 2003: 70 Pat. mit florider AIT 200µg Seleno- methionin Abfall der TPO-Ak um 46%/3 Mon. bzw. 56%/6 Mon.

3 Selen und Schilddrüse wichigstes Selenoenzym: Glutathion-Peroxidase (GPx) alle 3 bekannten Dejodasen sind Selenoenzyme SD gehört zu den Organen mit dem höchsten Selengehalt in SD entstehen bei SD-Hormonsynthese vermehrt freie Radikale leichter/mäßiger Se-Mangel GPx SD- Autodestruktion (?) nur bei starkem Se-Mangel Dejodase-Aktivität

4 Selen Selen insbes. in Fisch + Fleisch geringe therapeutische Breite (max. 400 µg Na-Selenit oder Selenomethionin) Selenintoxikation: Veränderungen der Fingernägel Haar- und Nagelverlust metallischer Geschmack im Mund knoblauchartiger Geruch der Ausatmungsluft Erbrechen, Durchfälle PTT Leuko

5 Knochenstoffwechsel Endokrinen Pankreas Nebennieren Ausreichende Selenversorgung wichtig für Spermatogenese. Selenüberversorgung beeinträchtigt Ovarfunktion. Selenoproteine sind beteiligt am

6 Selen und Schilddrüse – Zukunft? abhängig vom Ergebnis einer primären Endpunktstudie (Hypothyreose) bei Patienten mit AIT

7 Investigation of (a) the relationship between Se and thyroid status, and (b) the effect of Se supplementation on thyroid status. (a) no significant correlations between Se status and measures of thyroid status plasma thyroxine (T4) was lower in males with higher plasma Se levels (P=0.009). Se supplementation increased plasma Se and GPx activity, but produced only small changes in plasma T4 and triiodothyronine (T3):T4 ratio. (b) there was a significant reduction in plasma T4 (P=0.0045). Data suggest that Se status in New Zealand is close to adequate for the optimal function of deiodinases. Adequate plasma Se may be approximately 0.82-0.90 µmol/l, compared with 1.00-1.14 µmol/l for maximal GPx activities. The effect of selenium on thyroid status in a population with marginal selenium and iodine status. Thomson et al., Br J Nutr 94:962-8, 2005

8 1: Endocrinology. 2006 Mar;147(3):1306-13. Epub 2005 Dec 1. Synthesis and metabolism of thyroid hormones is preferentially maintained in selenium-deficient transgenic mice. Schomburg L, Riese C, Michaelis M, Griebert E, Klein MO, Sapin R, Schweizer U, Kohrle J. Institut fur Experimentelle Endokrinologie, Charite-Universitaetsmedizin Berlin, Schumannstrasse 20/21, D- 10117 Berlin, Germany. The thyroid gland is rich in selenium (Se) and expresses a variety of selenoproteins that are involved in antioxidative defense and metabolism of thyroid hormones (TH). Se deficiency impairs regular synthesis of selenoproteins and adequate TH metabolism. We recently generated mice that lack the plasma Se carrier, selenoprotein P (SePP). SePP-knockout mice display decreased serum Se levels and manifest growth defects and neurological abnormalities partly reminiscent of thyroid gland dysfunction or profound hypothyroidism. Thus, we probed the TH axis in developing and adult SePP-knockout mice. Surprisingly, expression of Se-dependent 5'-deiodinase type 1 was only slightly altered in liver, kidney, or thyroid at postnatal d 60, and 5'-deiodinase type 2 activity in brain was normal in SePP- knockout mice. Thyroid gland morphology, thyroid glutathione peroxidase activity, thyroid Se concentration, and serum levels of TSH, T4, or T3 were within normal range. Pituitary TSHbeta transcripts and hepatic 5'-deiodinase type 1 mRNA levels were unchanged, indicating regular T3 bioactivity in thyrotropes and hepatocytes. Cerebellar granule cell migration as a sensitive indicator of local T3 action during development was undisturbed. Collectively, these findings demonstrate that low levels of serum Se or SePP in the absence of other challenges do not necessarily interfere with regular functioning of the TH axis. 5'-deiodinase isozymes are preferentially supplied, and Se- dependent enzymes in the thyroid are even less-dependent on serum levels of Se or SePP than in brain. This indicates a top priority of the thyroid gland and its selenoenzymes with respect to the hierarchical Se supply within the organism. PMID: 16322066 [PubMed - indexed for MEDLINE]

9 1: Endocr Rev. 2005 Dec;26(7):944-84. Epub 2005 Sep 20. Selenium, the thyroid, and the endocrine system. Kohrle J, Jakob F, Contempre B, Dumont JE. Institut fur Experimentelle Endokrinologie, Charite, Humboldt Universitat zu Berlin, Schumannstrasse 20/21, D-10098 Berlin, Germany. Recent identification of new selenocysteine-containing proteins has revealed relationships between the two trace elements selenium (Se) and iodine and the hormone network. Several selenoproteins participate in the protection of thyrocytes from damage by H(2)O(2) produced for thyroid hormone biosynthesis. Iodothyronine deiodinases are selenoproteins contributing to systemic or local thyroid hormone homeostasis. The Se content in endocrine tissues (thyroid, adrenals, pituitary, testes, ovary) is higher than in many other organs. Nutritional Se depletion results in retention, whereas Se repletion is followed by a rapid accumulation of Se in endocrine tissues, reproductive organs, and the brain. Selenoproteins such as thioredoxin reductases constitute the link between the Se metabolism and the regulation of transcription by redox sensitive ligand-modulated nuclear hormone receptors. Hormones and growth factors regulate the expression of selenoproteins and, conversely, Se supply modulates hormone actions. Selenoproteins are involved in bone metabolism as well as functions of the endocrine pancreas and adrenal glands. Furthermore, spermatogenesis depends on adequate Se supply, whereas Se excess may impair ovarian function. Comparative analysis of the genomes of several life forms reveals that higher mammals contain a limited number of identical genes encoding newly detected selenocysteine-containing proteins.

10 1: Cochrane Database Syst Rev. 2004 Oct 18;(4):CD003703. Selenium supplementation for critically ill adults. Avenell A, Noble DW, Barr J, Engelhardt T. Health Services Research Unit, University of Aberdeen, Polwarth Building, Foresterhill, Aberdeen, Scotland, UK, AB25 2ZD. BACKGROUND: Selenium is a trace mineral essential to human health, which has an important role in the immune response, defence against tissue damage and thyroid function. Improving selenium status could help protect against overwhelming tissue damage and infection in critically ill adults. OBJECTIVES: This review assessed the effects of selenium supplementation including the selenium-containing compound, ebselen, on adults recovering from critical illness. SEARCH STRATEGY: We searched CENTRAL (The Cochrane Library, Issue 2, 2003), MEDLINE, (1966 to July 2003), EMBASE (1980 to Week 30 2003),CAB NAR (1973 to March 2003), BIOSIS (1985 to July 2003), CINAHL (1982 to July 2003), HEALTHSTAR (1975 to September 2002), Current Controlled Trials, and reference lists. We contacted investigators, and handsearched four journals. Date of the most recent search: December 2003. SELECTION CRITERIA: Randomized trials of selenium or ebselen supplementation by any route, in adults with critical illness (including burns, head injury, brain haemorrhage, cerebrovascular accident and surgery). DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. We sought additional information as required from trialists. We also undertook pooling of data for outcomes and selected exploratory analyses were undertaken. MAIN RESULTS: Seven randomized trials involving813participants were included. The quality of trials, as reported, was poor, particularly for allocation concealment. The availability of outcome data was limited and trials involving selenium supplementation, were small. Thus the results must be interpreted with caution. Because of heterogeneity, results are presented for the random effects models.Four selenium trials showed no statistically significant difference in mortality (relative risk (RR) 0.52, 95% confidence interval (CI) 0.20 to 1.34). Three trials of ebselen also showed no statistically significant difference in mortality (RR 0.83, 95% CI 0.51 to 1.35).One trial of selenium found no statistically significant difference between groups for participants developing infection (RR 1.33, 95% CI 0.55 to 3.24). Three trials of ebselen provided data for participants developing infections (pyrexia, respiratory infections or meningitis), which was not statistically significant (RR 0.60, 95% CI 0.36 to 1.02).No clear evidence emerged for the benefits of selenium or ebselen supplementation for the outcomes of days on a ventilator, length of intensive care unit stay, length of hospital stay or quality of life. REVIEWERS' CONCLUSIONS: There is insufficient evidence to recommend supplementation of critically ill patients with selenium or ebselen. Trials are required which overcome the defects of the reviewed studies, particularly inadequate size and methodology. This review will be updated when four ongoing trials are completed.

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