title: Is there sufficient evidence to consider the use of 11β-hydroxysteroid dehydrogenase type 1 inhibition in children?
abstract: 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 11β-hydroxysteroid dehydrogenase 1 (11β-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 11β-HSD1 enzyme, it appears that maturation occurs within the first year of life. Different changes in biomarkers for assessing the efficacy and safety of 11β-HSD1 inhibitors are to be expected in paediatric patients compared to adults, reflecting differences in metabolism. The effect of 11β-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 11β-HSD1 is considered a potentially effective mean to regulate local cortisol levels in the paediatric population, and 11β-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.
authors.affiliation: F. Hoffmann-La Roche Ltd, Basel, Switzerland. sabine.fuerst-recktenwald@roche.com
authors.forename: Sabine
authors.initials: S
authors.lastname: Fürst-Recktenwald
authors.forename: Helmuth G
authors.initials: HG
authors.lastname: Dörr
authors.forename: Marcus
authors.initials: M
authors.lastname: Quinkler
authors.forename: Jörg
authors.initials: J
authors.lastname: Dötsch
authors.forename: Paul M
authors.initials: PM
authors.lastname: Stewart
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism; D000293:Adolescent; D002648:Child; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008099:Liver / Q000378:metabolism; D024821:Metabolic Syndrome / Q000097:blood / Q000188:drug therapy / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D006854:Hydrocortisone