Prader
Prader - - Willi Willi
S. Bernasconi S. Bernasconi
Dipartimento Età Evolutiva Dipartimento Età Evolutiva
Università di Parma Università di Parma
Tabarka
Tabarka 20062006
Growth
Growth hormonehormone improvesimproves mobilitymobility and body and body compositioncomposition
in infantsin infants and and toddlerstoddlers withwith PraderPrader-Willi-Willi syndromesyndrome
J. CarrelJ. Carrel etetal J. Pediatral J. Pediatr.2004.2004
AgeAge--relatedrelated comparisonscomparisons of changeof change in in mobilitymobility
scores
scores over 12 monthsover 12 months revealed
revealed a a significantsignificant effect
effect forfor GH forGH for infantsinfants whowho beganbegan GH GH beforebefore 18 18 months
months of of ageage, , anan effecteffect thatthat waswas notnot observedobserved in in toddlers
toddlers whowho beganbegan GH GH after 18
after 18 monthsmonths of ageof age..
GH GH therapy therapy and and mortality mortality
Approval
Approval of GH treatment of GH treatment was was obtained
obtained in 2000 in 2000 by by P&U, and the P&U, and the safety
safety surveillance surveillance database database registered
registered 675 PWS 675 PWS patients patients treated treated with with GH up GH up until until 2003 2003 . . However
However , , fatal fatal events events after the start after the start of GH
of GH therapy therapy have have been been recently recently reported
reported ( ( within within 6 6 months months ). ).
GH GH therapy therapy and and mortality mortality
yesyes 6.26.2++4.94.9
mm 44
Pharmacia
Pharmacia, 2003, 2003
yesyes 6.56.5
mm 11
Eiholzer
Eiholzer, 2002, 2002
nono 0.70.7
mm 11
Nordmann
Nordmann, 2002, 2002
obesity obesity ageage ((yryr))
sexsex nn
GH GH therapy therapy and and mortality mortality
yesyes 6.3/3.8
6.3/3.8 m/fm/f
22 Grugni, 2005
Grugni, 2005
yesyes 4.7/9.3
4.7/9.3 ff
22 Riedl
Riedl, 2005, 2005
yesyes 3.93.9
mm 11
Sacco, 2005 Sacco, 2005
yesyes 4.54.5
mm 11
VanVan Vliet, 2004Vliet, 2004
yesyes 6.26.2++4.94.9
mm 44
Pharmacia
Pharmacia, 2003, 2003
yesyes 6.56.5
mm 11
Eiholzer
Eiholzer, 2002, 2002
nono 0.70.7
mm 11
Nordmann
Nordmann, 2002, 2002
obesity obesity ageage ((yryr))
sexsex nn
GH GH therapy therapy and and mortality mortality
Possible
Possible mechanism mechanism (s) (s) by by which which GH GH treatment
treatment might might contribute contribute to to this this outcome
outcome in at in at - - risk risk children children include: include:
ÆÆ
Promotion of Promotion of fluid fluid retention retention leading
leading to to right right heart heart failure failure ; ;
ÆÆ
Promotion of Promotion of growth growth of of lymphoid lymphoid tissue
tissue in the in the posterior posterior pharynx pharynx resulting
resulting in in airway airway obstruction obstruction . .
GH GH therapy therapy and and mortality mortality
RISK FACTORS RISK FACTORS
zz
Severe Severe obesity obesity
zz
History History of of respiratory respiratory impairment impairment
zz
Sleep Sleep apnea apnea
zz
Respiratory Respiratory infection infection
zz
Gender (M:F= 3:1) Gender (M:F= 3:1)
GH GH therapy therapy and and mortality mortality
According
According to to thesethese data, data, itit hashas beenbeen recommended
recommended: :
ÆÆ to perform polysomnography and ENT to perform polysomnography and ENT examination
examination beforebefore and 6and 6--8 8 weeksweeks after after starting
starting of GH of GH therapytherapy;;
ÆÆ in the case of hyperplasia of lymphoid in the case of hyperplasia of lymphoid tissue, adenoidectomy + tonsillectomy tissue, adenoidectomy + tonsillectomy
should be taken into
should be taken into considerationconsideration, , eithereither before
before or or duringduring GH GH administrationadministration;;
GH GH therapy therapy and and mortality mortality
ÆÆ GH GH therapytherapy mightmight start start withwith a a lowerlower dose, and
dose, and dosagedosage couldcould bebe increasedincreased gradually
gradually on the on the basisbasis of of clinicalclinical response
response and and instrumentalinstrumental assessmentassessment;;
ÆÆ in the case of in the case of respiratoryrespiratory infectioninfection, GH , GH treatment
treatment shouldshould bebe interruptedinterrupted and and aggressive
aggressive therapytherapy of the of the infectioninfection isis mandatory
mandatory;;
ÆÆ a a closeclose cardiologiccardiologic evaluationevaluation shouldshould bebe performedperformed beforebefore and and duringduring GH GH
therapy therapy..
PRADER
PRADER - - WILLI SYNDROME WILLI SYNDROME
~17 obese PWS
~17 obese PWS childrenchildren receivingreceiving rhGHrhGH havehave beenbeen dieddied : : howeverhowever mortalitymortality in in
PWS PWS treatedtreated withwith rhGHrhGH (0,4%) (0,4%) isis likelylikely no no more and
more and maymay eveneven bebe lessless frequentfrequent thanthan in in anan untreateduntreated PWS PWS populationpopulation ((~ 2,6%)~ 2,6%)
LeeLee P GGH 22-P GGH 22-1717--20062006
Short
Short--TermTerm EffectsEffects of Growthof Growth HormoneHormone on Sleepon Sleep Abnormalities
Abnormalities in Praderin Prader--WilliWilli Syndrome Syndrome
J MillerJ Miller, J , J SilverseinSilversein, J , J ShusterShuster, DJ. , DJ. DriscollDriscoll, M Wagner, M Wagner
J J ClinClinEndocrinolEndocrinolMetabMetab.2006.2006
Conclusions
Conclusions:: MostMost of of ourour PWS patientsPWS patients hadhad improvementimprovement after after short
short--termterm GH treatment, GH treatment, butbut 32% 32% hadhad worseningworsening of of sleepsleep disturbance
disturbance. A subset of PWS . A subset of PWS patientspatients are at are at riskrisk duringduring thisthis window window of vulnerabilityof vulnerability shortlyshortly after initiationafter initiation of GH. of GH.
Because
Because itit isis difficultdifficult to predictto predict whowho willwill worsenworsen withwith GH, patientsGH, patients withwith PWS shouldPWS should havehave PSA PSA beforebefore and after and after startingstarting GH and shouldGH and should bebe monitoredmonitored forfor sleepsleep apnea withapnea with upper respiratoryupper respiratory tracttract infections. infections. Otorhinolaryngological
Otorhinolaryngological evaluationevaluation isis warrantedwarranted ifif sleepsleep apnea apnea worsens
worsens on GH. on GH.
IGF-IGF-I I levelslevels shouldshould bebe monitored, monitored, withwith the goal beingthe goal being physiological physiological levels
levels. .
