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Division of Pediatric Endocrinology

Â鶹´«Ã½'s Division of Endocrinology in the Department of Pediatrics is dedicated to improving the health of children through clinical care, teaching and research.

Our division faculty is comprised of five pediatric endocrinologists and a pediatric nurse practitioner, who is also a Certified Diabetes Educator. Two clinical nurses perform specialized endocrine function testing and provide education in endocrine disorders. Four clinical nurses and one APN clinical nurse specialist, three of whom are Certified Diabetes Educators, provide in- and outpatient diabetes education, instruct patients in intensive insulin regimens including CSII and CGM, and maintain a high level of inpatient diabetic care through education of the hospital nursing staff. In addition, two dietitians, a social worker and a child psychologist are available to offer nutritional guidance and psychosocial evaluation and advice.

Pediatric Endocrinology Training

Our teaching programs are closely intertwined with both the Department of Pediatrics and the Division of Endocrinology in the Department of Internal Medicine. In addition to departmental conferences, division faculty give lectures in the Academic Half Day lecture series for residents and a series of lectures for third-year medical students. Popular electives are offered to residents and fourth-year medical students, and third- and fourth-year medical students are supervised in the outpatient clinics. Finally, the division assists in the training of fellows from the Division of Endocrinology in Internal Medicine by its supervision of fellows in a one-month rotation and its participation in a combined case conference.

Clinical Services

The division offers clinical care for infants, children, and adolescents with growth disorders, complex endocrine system disorders, diabetes, and metabolic bone disease is comprehensive and state-of-the-art. Division members participate in several multi-disciplinary clinics, including the Lipid Disorders, Turner Syndrome, and Prader-Willi Syndrome clinics. We have also recently developed a highly successful program to transition adolescents with diabetes to adult care. One faculty member is responsible for patient care on the inpatient service. Most newly-diagnosed diabetic children are hospitalized for a brief period to initiate therapy and education. Consultations to assess and assist in the management of complex inpatients are also provided, as requested by other services.

Research

TODAY (Treatment Options for type 2 Diabetes in Adolescents and Youth)

Â鶹´«Ã½ was one of 15 sites in the NIH-funded, multi-center TODAY (Treatment Options for type 2 Diabetes in Adolescents and Youth) Study (Sherida E. Tollefsen, PI) and is participating in TODAYPhase 2. Division members are participating in ELLIPSE, a Novo Nordisk trial to compare the safety and efficacy of liraglutide with metformin vs metformin monotherapy on glycemic control in children and adolescents with type 2 diabetes, and in a Zafgen-funded phase 3 trial of subcutaneous beloranib in obese subjects with Prader-Willi syndrome.

The research protocol was designed to evaluate the efficacy of three treatment regimens (metformin alone, metformin plus rosiglitazone, and metformin plus intensive lifestyle intervention) on time to treatment failure based on glycemic control. Nationwide, 699 subjects were randomized into one of the treatment regimens and were treated for at least two years.

At the SLU site, 39 subjects were randomized, and 35 subjects have been retained to date. Of the 699 randomly-assigned participants (mean duration of diagnosed type 2 diabetes, 7.8 months), 319 (45.6 percent) reached the primary outcome over an average follow-up of 3.86 years. Rates of failure were 51.7 percent, 38.6 percent, and 46.6 percent for metformin alone, metformin plus rosiglitazone, and metformin plus lifestyle intervention, respectively. Metformin plus rosiglitazone was superior to metformin alone (P = 0.006); metformin plus lifestyle intervention was intermediate but not significantly different from metformin alone or metformin plus rosiglitazone. Pre-specified analyses according to sex and race or ethnic group showed differences in sustained effectiveness, with metformin alone least effective in non-Hispanic black participants and metformin plus rosiglitazone most effective in girls.

Serious adverse events were reported in 19.2 percent of participants. Long-term observation of these participants is ongoing in two phases - phase 1 from 3/1/11 through 2/28/14 and phase 2 [RFA-DK-14-502 - Limited Competition: Continuation of Treatment Options for type 2 Diabetes in Adolescents and Youth], which is funded through 4/30/21.

Prader-Willi syndrome (PWS)

Susan E. Myers, M.D., in the Division of Pediatric Endocrinology and her collaborator, Barbara Whitman, Ph.D., continue to contribute significantly to our understanding of children and adults with Prader-Willi syndrome (PWS). They participated in a randomized, double-blind, placebo-controlled, phase 3 trial of ZGN-440 (subcutaneous beloranib in suspension) in obese subjects with PWS.

An abstract showing statistically and clinically significant weight loss and improvement in hyperphagia in patients with PWS has been presented by the study group; in addition, a second abstract showed that ~90% of weight loss with beloranib was due to loss of body fat, indicating preferential loss of fat with minimal change in lean mass. The majority of adverse events (AEs) were consistent with patient population characteristics and AEs observed in prior beloranib clinical trials.

ELLIPSE Trial
Margaret Siska, M.D., is the principal investigator for a Novo Nordisk trial entitled ELLIPSE (efficacy and safety of liraglutide with metformin versus metformin monotherapy on glycemic control in children and adolescents with type 2 diabetes), and one patient has completed and other patients are being screened for this study. Drs. Tollefsen and Siska have also joined the Pediatric Diabetes Consortium, a consortium of academic institutions participating in clinical research for type 2 diabetes treatment options in pediatric patients.

Grants/Contracts

New
  • National Institutes of Health (NIDDK)
  • SE Tollefsen, PI, Â鶹´«Ã½ site
  • RFA-DK-14-502 - Limited Competition: Continuation of Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) Study
Continuing
  • Novo Nordisk
    MK Siska, PI, NN2211-3659 - Efficacy and Safety of Liraglutide in Combination with Metformin versus Metformin Monotherapy on Glycemic Control in Children and Adolescents with Type 2 Diabetes (ELLIPSE)
  • National Institutes of Health (NIDDK)
    SE Tollefsen, PI, Â鶹´«Ã½ site
  • Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY)
    TODAY, TODAY ARRA, T2P1, T2P2

Publications

  1. Kapadia CR, Nebesio TD, Myers SE, Willi S, Miller BS, Allen DB, Jacobson-Dickman E. Endocrine effects of inhaled corticosteroids in children. JAMA Pediatrics 2015; 170(2):163-170.
  2. McCandles SE, Yanovski JA, Miller J, Fu C, Bird LM, Salehi P, Chan CL, Stafford D, Abuzzahab MJ, Viskochill D, Barlow SE, Anglo M, Myers SE, Whitman BY, Styne D, Roof E, Dykens EM, Scheimann AO, Malloy J, Zhuang D, Taylor K, Hughes T, Kim DD, Butler MG. Effects fo MetAP2 inhibition on hyperphagia and body weight in Prader-Willi syndrome: A randomized, double-blind, placebo-controlled trial. Diabetes Obes Metab 2017;1-11
  3. Finkle A, Zavertnik S, Myers S, Cormier D, Heithaus JL, Augustyn M. Growing up fast: managing Autism Spectrum Disorder and precocious puberty. Challenging Case August 2020. J Dev Behav Pediatr. Publish Ahead of Print, September 22, 2020.

As members of the TODAY Study Group, SE Tollefsen and DP Dempsher were cited in the following publications:

  1. Levers-Landis CE, Walders-Abramson N, Amodei N, Drews KL, Kaplan J, Levitt Katz LE, Lavietes S, Saletsky R, Seidman D, Yasuda P for the TODAY Study Group. Longitudinal correlates of health risk behaviors in children and adolescents with type 2 diabetes. Journal of Pediatrics 2015; 166(5):1258-1264.
  2. Larkin ME, Walders-Abramson N, Hirst K, Keady J, Ievers-Landis CE, Venditti EM, Yasuda PM. Effects of comorbid conditions on health related quality of life in youth with type 2 diabetes: the TODAY clinical trial. Diabetes Management 2015; 5(6):431-439.
  3. Zeitler P, Hirst K, Copeland KC, El ghormli L, Katz LL, Levitsky LL, Linder B, McGuigan P, White NH, Wilfley D for the TODAY Study Group. HbA1c after a short period of monotherapy with metformin identifies durable glycemic control among adolescents with type 2 diabetes. Diabetes Care 2015; 38:2285-2292.
  4. Tryggestad JB, Willi SM. Complications and comorbidities of T2DM in adolescents: findings from the TODAY clinical trial. Journal of Diabetes and Its Complications 2015; 29(2):307-312.
  5. Walders-Abramson N, Anderson B, Larkin ME, Chang N, Venditti E, Bzdick S, Tryggestad JB, Tan K, Geffner ME, Hirst K. Benefits and barriers to participating in longitudinal research of youth-onset type 2 diabetes: results from the TODAY retention survey. Clinical Trials 2016; 13(2):240-243.
  6. Chernausek SD, Arslanian S, Caprio S, Copeland KC, El ghormli L, Kelsey MM, Koontz MB, Orsi CM, Wilfley D. Relationship between parental diabetes and presentation of metabolic and glycemic function in youth with type 2 diabetes: baseline findings from the TODAY trial. Diabetes Care 2016; 39(1):110-117.
  7. Klingensmith GJ, Pyle L, Nadeau KJ, Barbour LA, Goland RS, Willi SM, Linder B, White NH for the TODAY Study Group. Pregnancy outcomes in youth with type 2 diabetes: the TODAY study experience. Diabetes Care 2016; 39:122-129.
  8. Kelsey MM, Geffner ME, Guandalini C, Pyle L, Tamborlane WV, Zeitler PS, White NH for the TODAY Study Group. Presentation and effectiveness of early treatment of type 2 diabetes in youth: lessons from the TODAY study. Pediatric Diabetes 2016; 17(3):212-221.

Presentations

  • Dempsher, DP: "Hyperinsulinism" Division of Neonatology noon conference, SSM Cardinal Glennon Children's Hospital. St. Louis, MO, 8/3/15.
  • Dempsher, DP: "Diabetic Ketoacidosis" PL1 Introductory Lectures, Department of Pediatrics, SSM Cardinal Glennon Children's Hospital. St. Louis, MO, 8/12/15.
  • Eddy, MC: "A Curious Case of a Newborn Metabolic Screen" Pediatric Science Days, Department of Pediatrics, SSM Cardinal Glennon Children's Hospital. St. Louis, MO, 4/21/16.
  • Myers, SE: "Perioperative Management of Children with Endocrine Disorders" Pediatric Surgery Grand Rounds, SSM Cardinal Glennon Children's Hospital. St. Louis, MO, 3/16/16.
  • Yanovski JA, Myers S, et al.: "Improvement in Hyperphagia and Weight Loss in Adolescent Patients: Results from bestPWS, a Phase 3, Randomized, Placebo-Controlled, Clinical Trial of Beloranib in Prader-Willi Syndrome" 2016 Pediatric Academic Societies meeting. Baltimore, MD, 5/1/16.
  • Butler MG, Myers S, et al.: "Weight Loss and Improvement in Body Composition: Results from bestPWS, a Phase 3, Randomized, Placebo-Controlled, Clinical Trial of Beloranib in Prader-Willi Syndrome" 2016 Endocrine Society meeting. Boston, MA, 4/3/16.
  • In addition to monthly resident PL1 and Core Curriculum lectures and the second- and third-year medical student lectures, Division faculty members have given the following presentations at the combined case conference with the Division of Endocrinology in the Department of Internal Medicine:
    • Dempsher, DP
      Disorders of Puberty (7/25/17)
    • Myers, SE
      Growth Disorders (8/29/17)
    • Dempsher, DP
      A Case of Congenital Hypothyroidism from Iodine deficiency (9/26/17)
    • Siska, MK
      Premature Ovarian Failure in a 15yr old girl 10/31/17
    • Eddy, MC 12yr old boy with hypocalcemia 11/28/17
    • Jackson, KE 17 alpha-hydroxylase deficiency CAH 1/30/18
    • Myers, SE
      Hypothalamic Obesity 2/27/18
    • Dempsher, DP
      15 year old w/acute testicular swelling 3/27/18
    • Siska, MK
      A Case of 46,XY DSD 4/24/18
    • Eddy, MC
      Empty Sella Wyndrome