Documenti di Didattica
Documenti di Professioni
Documenti di Cultura
Cortisolo
Il cortisolo (denominato anche idrocortisone) sintetizzato
dalla zona fascicolata/reticolare della corticale del surrene
La biosintesi e la liberazione indotta dallormone
adrenocorticotropo (ACTH), rilasciato dallipofisi, a sua
volta sotto il controllo dellipotalamo via CRH
(corticotropin-releasing hormone).
LACTH
1) aumenta la traslocazione del substrato (colesterolo) nella
membrana interna dei mitocondri, dove sono localizzati gli
enzimi biosintetici.
2) aumenta la trascrizione genica degli enzimi biosintetici
Cortisolo
La sua sintesi e secrezione sensibile al retrocontrollo
negativo esercitato dal cortisolo circolante o dai
glucorticoidi di sintesi.
Secrezione giornaliera
Cortisolo
Aldosterone
10 mg/die
0.125 mg/die
6-24 mg/100ml
0.01 mg/100 ml
Concentrazione siero
Ore 8
Ore 22
1.5-8 mg/100ml
0.01 mg/100 ml
Glucocorticoids
Glucocorticoid
Receptors
GR dimer
DNA binding
Trans-activation
Anti-inflammatory
Anti-inflammatory
proteins
proteins
Side-effects
Side-effects
(metabolic,
(metabolic,
endocrine)
endocrine)
GR monomer
Inflammatory
Inflammatoryproteins
proteins
cytokines,
cytokines,enzymes,
enzymes,
adhesion
adhesion
molecules
molecules
Repressione della
trascrizione
genica glucocorticoide
mediata
Dopo
le infezioni;
Ritenzione idrosalina ed ipertensione (per effetto
mineralcorticoide di alcune molecole, aumento epatico della
sintesi di angiotensinogeno e aumento delle risposte pressorie
catecolaminergiche);
Ritardo della crescita nei bambini;
Dopo trattamento prolungato, inibizione e soppressione dellasse
ipotalamo-ipofisi-surrene ed atrofia surrenalica.
Ulcere peptiche;
Iperglicemia e diabete mellito iatrogeno;
(diminuzione masse
muscolari per riduzione della sintesi proteica ed aumento della degradazione proteica,
assottigliamento cute, bilancio negativo azoto)
Agli
Harvey William
Cushing
(1869-1933)
American physician
and neurosurgeon
sostitutiva dellinsufficienza
surrenalica acuta e cronica primaria e
secondaria
(Linsufficienza corticosurrenale cronica definita morbo di
Addison)
Bone Density/Osteoporosis
Is There a Reduction of Bone Density
in Children With Asthma Using ICS?
Conclusion: ICS use is not associated
with a reduction in bone density in
children with asthma
Leone et al., Chest, 124, 2329-2340, 2003
Bone Density/Osteoporosis
Is There a Reduction of Bone Density in Adults
With Asthma Using ICS?
Conclusion: Adult asthma patients generally do
not sustain a significant reduction in BMD in
response to ICS treatment, although the effect
may become clinically important in patients
receiving high-dose ICSs for many
years.
Leone et al., Chest, 124, 2329-2340, 2003
Cataracts
Is There an Elevated Risk of Developing Cataracts
Associated With the Use of ICS?
Conclusion: The risk of subcapsular and
nuclear cataracts associated with ICS use is
negligible in young asthma patients, however, it
may be elevated in older patients.
Conclusion: The dose-effect relationship
between ICS use and cataract formation is
poorly understood
Leone et al., Chest, 124, 2329-2340, 2003
Glaucoma
Is There an Elevated Risk of Glaucoma Associated
With ICS Use?
Conclusion: The risk of glaucoma associated
with ICS use is likely to be small, however,
further study is warranted.
Conclusion: There is an apparent, although
poorly studied, dose-effect relationship between
ICS use and glaucoma.
Leone et al., Chest, 124, 2329-2340, 2003
Growth
Does ICS Therapy Affect the Rate
of Growth in Asthmatic Children?
Conclusion: Therapy with ICSs is associated
with a decrease in short-term growth rates in
children, but the overall effect is small
Conclusion: The adult height attained by
asthmatic children treated with ICSs is not
different from that of nonasthmatic adults.
Leone et al., Chest, 124, 2329-2340, 2003