5-year-old female with Chief complaint and HPI HPI, continued hypoglycemia hypoglycemia 5-year-old female transferred from OSH Exam consistent with moderate-severe Endorama to PICU with lethargy, dehydration, and dehydration January 19, 2012 low blood sugar Cont’d lethargy after total 40 ml/kg IVF Rochelle Naylor, MD USOH until 2 days PTA bolus N/V, no po intake except small amounts Labs significant for serum BG of 52 of water Rcv’d D10 (2 ml/kg), placed on D5NS at To OSH ER day PTA- dx’d w/ UTI, d/c’d 1500 ml/m2/d prior to txfer to Comer home w/ Abx ICU DOA cont’d n/v, lethargic taken to ED OSH labs Hospital Course Past Medical History Continued on IVF in PICU w/ FT, NSVD, no complications 12.1 134 93 25 Autism spectrum disorder 8.11 330 52 improvement 35.8 4.4 17 0.45 GERD IVFs d/c’d; transferred to floor HD #2 UTIs x3 Tolerated small po intake x1 Pneumonia x2 Head CT- negative Previous episodes of lethargy HD#3- emesis of water and lethargy Urine toxicology screen- negative ◦ During illnesses w/ poor po intake ◦ POC BG= 44 ◦ 2 years old- after refusal to eat in the care of her GP x ◦ Serum BG= 45 ~16 hours IVFs of D5NS resumed, Peds Endo Medications- None consulted for hypoglycemia Allergies: Azithromycin- delerium Physical Examination FAMILY HISTORY REVIEW OF SYSTEMS Wt: 20 kg (75th); Ht: 102.8 cm (15th) Negative for DM Nausea, vomiting- Gen: WD, WN; NAD DIFFERENTIAL Negative for now resolved HEENT: W/o dysmorphic features; PERRL; DIAGNOSIS FOR hypoglycemia Appetite improved, MMM; NL thyroid examination; neck supple tolerating po intake HYPOGLYCEMIA IN A CV: RRR, NL S1, S2, no murmurs No concern for Pulm: CTA b/l CHILD? SOCIAL HISTORY ingestions Abd: Soft, NT, ND, no masses No access to LAHW parents GU: Tanner I hypoglycemic agents MSK: NL ROM, No edema, TD, deformity Neuro: Nonfocal, 2+ DTRs DDx of hypoglycemia in children OSH labs Ketones absent Ketones present 134 93 25 Hyperinsulinemia Idiopathic Ketotic 52 ◦ Congenital hypoglycemia 4.4 17 0.45 ◦ Beta-cell adenoma IEMs EVALUATION? ◦ Reactive hypoglycemia GH deficiency Anion gap: 24 ◦ Medication Cortisol deficiency Day PTA Urine ketones: 40, glc: neg ◦ Munchhausen by proxy Ingestions (alcohol, DOA Urine ketones: 150, glc: neg salicylates) Fatty acid, organic acid oxidation defects Laboratory evaluation Idiopathic ketotic hypoglycemia Mechanism of IKH-Huidekoper, et al 139 98 16 Most common form of hypoglycemia in Study looked at glucose kinetics during 45 3.8 15 0.4 young children fasting in 12 children with a h/o KH. Hypoglycemia and ketosis uniformly Assessed glucoregulatory hormones, Beta-hydroxybutyrate: 6.84 provoked by a brief fast after hypocaloric plasma ketones, FFA, alanine Lactic acid: 1.1 (later that day w/ BG-146, bicarb 20) high fat, low carbohydrate diet Cortisol: 43.2 Assessed rates of endogenous glucose GH: could not be added Characteristic inability to respond to glucagon after brief fast production (EGP), glucose uptake, gluconeogenesis, glycogenolysis HbA1c: 5.1 Usually appears between the first and POC BGs: 91-154 throughout the remainder of the hospitalization third years of life, and remits 5/12 became hypoglycemic spontaneously by age 6-8 ◦ Youngest of subjects (2.5-3.9 years) Mechanism of IKH Mechanism of IKH Mechanism of IKH Alanine levels significantly lower at the Hypoglycemic Normoglycemic IKH is caused by the inability to sustain an end of the test in hypoglycemic subjects EGP: -31.9% EGP: -17.9% adequate EGP during fasting, possibly Ketones, FFA levels were WNL during GGL: -66.2% GGL: -50.8% because of a limitation in the supply of duration of fasting in all subjects GNG: 6.8% GNG: 19.5% alanine Mechanism of IKH-Pagliara, et al Objective: determine if the primary defect in IKH is a deficiency of gluconeogenic precursors or an abnormality in the hepatic gluconeogenic enzyme system 8 children with IKH and 7 age-matched controls Utility of GH and cortisol values during hypoglycemia Study aim: To determine if GH and 70% had GH and cortisol levels below cortisol obtained during fasting “normal” thresholds hypoglycemia can identify children with deficiencies Retrospective chart review of all Conclusion: A deficiency in gluconeogenic precursor diagnostic fasting tests (n=151) (alanine) rather than a defect in the hepatic Hypoglycemia defined as SBG ≤50 mg/dL gluconeogenic enzyme apparatus is the most NL GH level defined as ≥7.5 ng/mL likely etiology of IKH NL cortisol level defined as ≥18 mcg/dL Summary References H H Huidekoper, M Duran, M Turkenburg, et al. Fasting adaptation in Idiopathic ketotic hypoglycemia is the idiopathic ketotic hypoglycemia: a mismatch between glucose production most common form of hypoglycemia in and demand. Eur J Pediatr. 2008; 167(8):859-65. AS Pagliara, IE Kari, DC De Vivo et al. Hypoalaninemia: a concomitant of young children ketotic hypoglycemia. J Clin Invest. 1972; 51(6):1440-9. A Kelly, R Tang, S Becker, CA Stanley. Poor specificity of low growth IKH is caused by the inability to sustain hormone and cortisol levels duringfasting hypoglycemia for the diagnosis of adequate glucose production related to growth hormone deficiency and adrenal insufficiency. Pediatrics. 2008;122 (3):e522-8. decreased alanine supply CJ Elder, VJ Wright, NP Wright. Time to end the routine testing of growth hormone and cortisol on hypoglycemia screens? Arch Dis Child. While GH and cortisol deficiency need to 2009;94 (12):1000-1. DON’T HAVE ARTICLE be ruled out, the utility of assessment at the time of hypoglycemia is questionable.