ABSTRACT
A total of 198 subjects were randomized to either high-dose (0.05 mg/kg.d) or low-dose (0.025 mg/kg.d) GH for 7 d; the alternate dose was then received after a 2-wk washout period. Groups included in the study were: normal, GH-insensitive (GHI; homozygous for the E180 splice mutation); heterozygous GHI (carriers of the E180 splice mutation); GH-deficient; and idiopathic short stature. Serum IGF binding protein-3 (IGFBP-3) concentrations (collected on d 1, 5, and 8 of treatment weeks) were GH-dependent, with significant elevation by d 5 of treatment, regardless of dose, in all normal subjects. GHI subjects had low baseline IGFBP-3 and poor or no response to either low- or high-dose GH. Heterozygous subjects, however, did not differ from age-matched normals with regard to IGFBP-3 generation. All GH-deficient subjects had subnormal baseline concentrations of IGFBP-3; most, but not all, were able to generate levels into normal ranges by 8 d of therapy. Children with idiopathic short stature showed a better response in IGFBP-3 generation compared with that previously observed with IGF-I, reaching concentrations in normal range with either dose of GH, suggesting that any GHI in this group is relatively limited to IGF-I production. For the diagnosis of GHI, the highest sensitivity (100%) and specificity (92%) was found on d 8 of the high-dose GH-IGFBP-3 generation test. Failure to raise both IGF-I and IGFBP-3 lowered sensitivity to 82-86% with low-dose GH, and 86-91% with high-dose GH.
Subject(s)
Drug Resistance , Human Growth Hormone/administration & dosage , Insulin-Like Growth Factor Binding Protein 3/blood , Adolescent , Adult , Body Height , Child , Female , Heterozygote , Human Growth Hormone/deficiency , Humans , Insulin-Like Growth Factor I/metabolism , Kinetics , Male , Mutation , RNA Splicing/genetics , Receptors, Somatotropin/genetics , Sensitivity and SpecificityABSTRACT
Olanzapine (Zyprexa) is an atypical neuroleptic used in adult and pediatric patients for the management of schizophrenia. Common side effects include increased appetite and weight gain. An uncommon but severe adverse effect is the development of diabetic ketoacidosis, reported until now only in adults. We report a case of acute onset diabetic ketoacidosis presenting in a 16-year-old girl during olanzapine therapy.