PMID- 22486586
OWN - NLM
STAT- MEDLINE
DCOM- 20121113
LR  - 20171116
IS  - 1365-2265 (Electronic)
IS  - 0300-0664 (Linking)
VI  - 77
IP  - 2
DP  - 2012 Aug
TI  - Is there sufficient evidence to consider the use of 11beta-hydroxysteroid 
      dehydrogenase type 1 inhibition in children?
PG  - 159-68
LID - 10.1111/j.1365-2265.2012.04406.x [doi]
AB  - Manifestations of the metabolic syndrome [obesity, dyslipidaemia, hypertension, 
      blood glucose derangements including prediabetes or type 2 diabetes mellitus 
      (T2DM)] in juvenile populations are becoming increasingly prevalent throughout 
      the world and are at the point of being a global public health concern. 
      Derangements in cortisol regeneration seem to be involved in the pathophysiology. 
      Treatment with selective 11beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1) inhibitors 
      could be a therapeutic strategy in paediatric patients with manifestations of the 
      metabolic syndrome. Based on preclinical and clinical data regarding development 
      of the 11beta-HSD1 enzyme, it appears that maturation occurs within the first year 
      of life. Different changes in biomarkers for assessing the efficacy and safety of 
      11beta-HSD1 inhibitors are to be expected in paediatric patients compared to adults, 
      reflecting differences in metabolism. The effect of 11beta-HSD1 treatment in 
      children on bone differentiation and development as well as adrenocorticotropic 
      hormone (ACTH), circulating and local cortisol tissue concentrations, androgens 
      and respective stress response is not yet known. Based on current literature, the 
      concept of inhibition of 11beta-HSD1 is considered a potentially effective mean to 
      regulate local cortisol levels in the paediatric population, and 11beta-HSD1 
      inhibitors may provide a valuable target and treatment option for the metabolic 
      syndrome in paediatric patients. However, the uncertainty over effects on the 
      developing skeleton combined with mild increases in adrenal androgen levels 
      raises potential concerns regarding growth as well as onset of puberty as to 
      their future use in children. Future clinical studies are needed to thoroughly 
      assess the risks and benefits of this new class of drugs in the paediatric 
      population.
CI  - (c) 2012 Blackwell Publishing Ltd.
FAU - Furst-Recktenwald, Sabine
AU  - Furst-Recktenwald S
AD  - F. Hoffmann-La Roche Ltd, Basel, Switzerland. sabine.fuerst-recktenwald@roche.com
FAU - Dorr, Helmuth G
AU  - Dorr HG
FAU - Quinkler, Marcus
AU  - Quinkler M
FAU - Dotsch, Jorg
AU  - Dotsch J
FAU - Stewart, Paul M
AU  - Stewart PM
LA  - eng
PT  - Journal Article
PT  - Review
PL  - England
TA  - Clin Endocrinol (Oxf)
JT  - Clinical endocrinology
JID - 0346653
RN  - 0 (Enzyme Inhibitors)
RN  - EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenase Type 1)
RN  - WI4X0X7BPJ (Hydrocortisone)
SB  - IM
MH  - 11-beta-Hydroxysteroid Dehydrogenase Type 1/antagonists & inhibitors/*metabolism
MH  - Adipose Tissue/metabolism
MH  - Adolescent
MH  - Child
MH  - Enzyme Inhibitors/therapeutic use
MH  - Humans
MH  - Hydrocortisone/blood
MH  - Liver/metabolism
MH  - Metabolic Syndrome/blood/drug therapy/metabolism
EDAT- 2012/04/11 06:00
MHDA- 2012/11/14 06:00
CRDT- 2012/04/11 06:00
PHST- 2012/04/11 06:00 [entrez]
PHST- 2012/04/11 06:00 [pubmed]
PHST- 2012/11/14 06:00 [medline]
AID - 10.1111/j.1365-2265.2012.04406.x [doi]
PST - ppublish
SO  - Clin Endocrinol (Oxf). 2012 Aug;77(2):159-68. doi: 
      10.1111/j.1365-2265.2012.04406.x.