Therapie benigner/maligner Skeletterkrankungen

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Nichts ist so überflüssig wie ein Kropf!
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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.

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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 ?

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Selen

• Selen insbes. in Fisch Fleisch
• geringe therapeutische Breite (max. 400 µg
  Na-Selenit oder Selenomethionin)
• SelenintoxikationVeränderungen der
  FingernägelHaar- und Nagelverlustmetallischer
  Geschmack im Mundknoblauchartiger Geruch der
  AusatmungsluftErbrechen, DurchfällePTT ? Leuko ?

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Selenoproteine sind beteiligt am

• Knochenstoffwechsel
• Endokrinen Pankreas
• Nebennieren
• Ausreichende Selenversorgung wichtig für
  Spermatogenese.
• Selenüberversorgung beeinträchtigt Ovarfunktion.

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Selen und Schilddrüse Zukunft?
abhängig vom Ergebnis einer primären
Endpunktstudie (Hypothyreose) bei Patienten mit
AIT
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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 (P0.009). 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 (P0.0045).
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 94962-8, 2005
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1 Endocrinology. 2006 Mar147(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-Universitae
tsmedizin Berlin, Schumannstrasse 20/21, D-10117
Berlin, Germany. lutz.schomburg_at_charite.de 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
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1 Endocr Rev. 2005 Dec26(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.
josef.koehrle_at_charite.de 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.
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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.
a.avenell_at_abdn.ac.uk 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.