Download Therapie benigner/maligner Skeletterkrankungen

“Nichts ist so überflüssig wie ein Kropf!“
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 Selenomethionin  Abfall der TPO-Ak um 46%/3 Mon. bzw.
56%/6 Mon.
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   SDAutodestruktion (?)
• nur bei starkem Se-Mangel  Dejodase-Aktivität 
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 
Selenoproteine sind beteiligt am
• Knochenstoffwechsel
• Endokrinen Pankreas
• Nebennieren
Ausreichende Selenversorgung wichtig für
Spermatogenese.
Selenüberversorgung beeinträchtigt Ovarfunktion.
Selen und Schilddrüse – Zukunft?
abhängig vom Ergebnis einer
primären Endpunktstudie (Hypothyreose) bei
Patienten mit AIT
The effect of selenium on thyroid status in a
population with marginal selenium and iodine status
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.
Thomson et al., Br J Nutr 94:962-8, 2005
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, D10117 Berlin, Germany. [email protected] 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 SePPknockout 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 Sedependent 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]
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. [email protected] 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.
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. [email protected]
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