PMID- 26903552
OWN - NLM
STAT- MEDLINE
DCOM- 20160809
LR  - 20191210
IS  - 1479-683X (Electronic)
IS  - 0804-4643 (Linking)
VI  - 174
IP  - 5
DP  - 2016 May
TI  - Is safety of childhood growth hormone therapy related to dose? Data from a large 
      observational study.
PG  - 681-91
LID - 10.1530/EJE-15-1017 [doi]
AB  - OBJECTIVE: Concerns have been raised of increased mortality risk in adulthood in 
      certain patients who received growth hormone treatment during childhood. This 
      study evaluated the safety of growth hormone treatment in childhood in everyday 
      practice. DESIGN: NordiNet((R)) International Outcome Study (IOS) is a 
      noninterventional, observational study evaluating safety and effectiveness of 
      Norditropin((R)) (somatropin; Novo Nordisk A/S, Bagsvaerd, Denmark). METHODS: 
      Long-term safety data (1998-2013) were collected on 13 834 growth hormone treated 
      pediatric patients with short stature. Incidence rates (IRs) of adverse events 
      (AEs) defined as adverse drug reactions (ADRs), serious ADRs (SADRs), and serious 
      AEs (SAEs) were calculated by mortality risk group (low/intermediate/high). The 
      effect of growth hormone dose on IRs and the occurrence of cerebrovascular AEs 
      were investigated by the risk group. RESULTS: We found that 61.0% of patients 
      were classified as low-risk, 33.9% intermediate-risk, and 5.1% high-risk. Three 
      hundred and two AEs were reported in 261 (1.9%) patients during a mean (s.d.) 
      treatment duration of 3.9 (2.8) years. IRs were significantly higher in the high- 
      vs the low-risk group (high risk vs low risk-ADR: 9.11 vs 3.14; SAE: 13.66 vs 
      1.85; SADR: 4.97 vs 0.73 events/1000 patient-years of exposure; P < 0.0001 for 
      all). Except for SAEs in the intermediate-risk group (P = 0.0486) in which an 
      inverse relationship was observed, no association between IRs and growth hormone 
      dose was found. No cerebrovascular events were reported. CONCLUSIONS: We conclude 
      that safety data from NordiNet((R)) IOS do not reveal any new safety signals and 
      confirm a favorable overall safety profile in accordance with other pediatric 
      observational studies. No association between growth hormone dose and the 
      incidence of AEs during growth hormone treatment in childhood was found.
CI  - (c) 2016 European Society of Endocrinology.
FAU - Savendahl, Lars
AU  - Savendahl L
AD  - Department of Women's and Children's HealthKarolinska Institutet and Pediatric 
      Endocrinology Unit, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
FAU - Pournara, Effie
AU  - Pournara E
AD  - Global Medical AffairsNovo Nordisk Health Care AG, 8050 Zurich, Switzerland.
FAU - Pedersen, Birgitte Tonnes
AU  - Pedersen BT
AD  - Epidemiology, Novo Nordisk A/S2860 Soborg, Denmark.
FAU - Blankenstein, Oliver
AU  - Blankenstein O
AD  - Institute for Experimental Pediatric EndocrinologyCharite-University Medicine 
      Berlin, 13353 Berlin, Germany.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Observational Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20160222
PL  - England
TA  - Eur J Endocrinol
JT  - European journal of endocrinology
JID - 9423848
RN  - 12629-01-5 (Human Growth Hormone)
SB  - IM
MH  - Child
MH  - Drug-Related Side Effects and Adverse Reactions/*epidemiology/mortality
MH  - Dwarfism/*drug therapy/epidemiology
MH  - Female
MH  - Human Growth Hormone/administration & dosage/*adverse effects/pharmacology
MH  - Humans
MH  - Incidence
MH  - Male
MH  - Outcome Assessment, Health Care/*statistics & numerical data
MH  - Risk
EDAT- 2016/02/24 06:00
MHDA- 2016/08/10 06:00
CRDT- 2016/02/24 06:00
PHST- 2015/10/14 00:00 [received]
PHST- 2016/02/22 00:00 [accepted]
PHST- 2016/02/24 06:00 [entrez]
PHST- 2016/02/24 06:00 [pubmed]
PHST- 2016/08/10 06:00 [medline]
AID - EJE-15-1017 [pii]
AID - 10.1530/EJE-15-1017 [doi]
PST - ppublish
SO  - Eur J Endocrinol. 2016 May;174(5):681-91. doi: 10.1530/EJE-15-1017. Epub 2016 Feb 
      22.