title: Sirolimus therapy in infants with severe hyperinsulinemic hypoglycemia.
abstract: Hyperinsulinemic hypoglycemia is the most common cause of severe, persistent neonatal hypoglycemia. The treatment of hyperinsulinemic hypoglycemia that is unresponsive to diazoxide is subtotal pancreatectomy. We examined the effectiveness of the mammalian target of rapamycin (mTOR) inhibitor sirolimus in four infants with severe hyperinsulinemic hypoglycemia that had been unresponsive to maximal doses of diazoxide (20 mg per kilogram of body weight per day) and octreotide (35 μg per kilogram per day). All the patients had a clear glycemic response to sirolimus, although one patient required a small dose of octreotide to maintain normoglycemia. There were no major adverse events during 1 year of follow-up.
authors.affiliation: From the Developmental Endocrinology Research Group, Clinical and Molecular Genetics Unit, Institute of Child Health, University College London (S.S., P.S., V.A., K.H.), and the Departments of Paediatric Endocrinology (S.S., P.S., V.A., K.H.) and Histopathology (D.P., M.A.), Great Ormond Street Hospital for Children, London, and the Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter (S.F., S.E.) - all in the United Kingdom; the Department of Pathology, University of California, San Francisco, San Francisco (S.A.); and the Department of Pathology and Laboratory Medicine, University of Texas Medical School at Houston, Houston (N.T., R.E.B.).
authors.forename: Senthil
authors.initials: S
authors.lastname: Senniappan
authors.forename: Sanda
authors.initials: S
authors.lastname: Alexandrescu
authors.forename: Nina
authors.initials: N
authors.lastname: Tatevian
authors.forename: Pratik
authors.initials: P
authors.lastname: Shah
authors.forename: Ved
authors.initials: V
authors.lastname: Arya
authors.forename: Sarah
authors.initials: S
authors.lastname: Flanagan
authors.forename: Sian
authors.initials: S
authors.lastname: Ellard
authors.forename: Dyanne
authors.initials: D
authors.lastname: Rampling
authors.forename: Michael
authors.initials: M
authors.lastname: Ashworth
authors.forename: Robert E
authors.initials: RE
authors.lastname: Brown
authors.forename: Khalid
authors.initials: K
authors.lastname: Hussain
mesh_terms: D001786:Blood Glucose / Q000032:analysis; D044903:Congenital Hyperinsulinism / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D001786:Blood Glucose; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus