5-year-old female with Chief complaint and HPI HPI, continued 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, -  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 present 134 93 25  Hyperinsulinemia  Idiopathic Ketotic 52 ◦ Congenital hypoglycemia 4.4 17 0.45 ◦ Beta- adenoma  IEMs EVALUATION? ◦ Reactive hypoglycemia  GH deficiency  Anion gap: 24 ◦ Medication  deficiency  Day PTA Urine ketones: 40, glc: neg ◦ Munchhausen by proxy  Ingestions (alcohol,  DOA Urine ketones: 150, glc: neg salicylates)  , 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 kinetics during 45 3.8 15 0.4 young children fasting in 12 children with a h/o KH.  Hypoglycemia and uniformly  Assessed glucoregulatory ,  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 diet  Cortisol: 43.2  Assessed rates of endogenous glucose  GH: could not be added  Characteristic inability to respond to after brief fast production (EGP), glucose uptake, ,  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 and cortisol levels duringfasting hypoglycemia for the diagnosis of adequate glucose production related to deficiency and . 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