Dr. Stafford specializes in Pediatric Endocrinology with special interest in disorders of puberty and Prader-Willi syndrome (PWS). Her research interests include in medical education curriculum development, faculty development and endocrine dysfunction in PWS.
- Pediatric Endocrinology
- Prader-Willi syndrome
- Disorders of puberty
Clinical Professor, Pediatrics - Endocrinology and Diabetes
Associate Program Director, Division of Endocrinology and Diabetes (2018 - Present)
Associate Chief, Division of Endocrinology and Diabetes (2018 - Present)
Honors & Awards
Best of Boston, Best Pediatric Endocrinologists, Boston Magazine (2015-2018)
Visiting Medical Educator, Human Resources for Health, Rwanda (2013, 2016, 2017)
Rabkin Fellowship in Medical Education, Beth Israel Deaconess Medical Center, Boston, MA (2011-2012)
Boards, Advisory Committees, Professional Organizations
Co-Chair, Nominating Committee, Pediatric Endocrine Society (2018 - Present)
Member, Training Council, Pediatric Endocrine Society (2010 - Present)
Member, International Relations Committee, Pediatric Endocrine Society (2015 - Present)
Chair, Training Council and Program Directors Committee, Pediatric Endocrine Society (2014 - 2017)
Medical Education:University of Connecticut School of Medicine Registrar (1992) CT
Residency:Lucile Packard Children's Hospital at Stanford University Medical Center (1995) CA
Fellowship:Boston Children's Hospital (1999) MA
Board Certification: Pediatric Endocrinology, American Board of Pediatrics (1999)
Community and International Work
Human Resources for Health, Rwanda, Kigali, Rwanda
Ministry of Health, Rwanda
Pediatric Residency Program,
Opportunities for Student Involvement
A Study of Diazoxide Choline in Patients With Prader-Willi Syndrome
The purpose of this is study is to evaluate the effects of DCCR (diazoxide choline controlled release tablets) in children and adults with Prader-Willi syndrome.
Stanford is currently not accepting patients for this trial. For more information, please contact Alicia Harnett, 650-723-0441.
Graduate and Fellowship Programs
Pediatric Endocrinology (Fellowship Program)
Measuring change in knowledge acquisition of Rwandan residents: using the American Board of Pediatrics International In-Training Examination (I-ITE) as an independent tool to monitor individual and departmental improvements during the Human Resources for Health program: an observational study.
BMC medical education
2019; 19 (1): 217
BACKGROUND: Rwanda is the only African country to use the pediatric International In-Training Examination (I-ITE). The objectives of this study were to use the scores from the I-ITE to outline the baseline level of knowledge of Rwandan residents entering the pediatric residency and the trends in knowledge acquisition from 2012 to 2018, during the Human Resources for Health (HRH) Program, an education partnership between the Rwanda Ministry of Health and a consortium of US universities.METHODS: A retrospective descriptive analysis of the I-ITE exam scores, taken by all Rwandan pediatric residents for five of the six academic years of the study period. Individual resident scores were weighted using the non-Rwandan I-ITE sites to minimise confounding from annual variations in exam difficulty. Statistical analysis included descriptives with ANOVA to compare variation in annual mean scores.RESULTS: Eighty-four residents took 213 I-ITE exam sittings over the five exam cycles. The mean weighted I-ITE score of all residents increased from 34% in 2013 to 49% (p<0.001) in 2018. The 32-point gap between the mean US-ITE and Rwandan I-ITE score in 2012-2013 was reduced to a 16-point gap in 2017-2018. First year resident (PG1) scores, which likely reflect the knowledge level of undergraduate medical students entering the residency program, increased from 34.8 to 44.3% (p=0.002) between 2013 and 2018.CONCLUSIONS: The I-ITE is an independent, robust tool, measuring both learners and the institutional factors supporting residents. This is the first study to demonstrate that the I-ITE can be used to monitor resident knowledge acquisition in resource-limited settings, where assessment of resident knowledge can be a major challenge facing the academic medicine community. The significant increase in I-ITE scores between 2012 and 18 reflects the substantial curricular reorganisation accomplished through collaboration between Rwandan and US embedded faculty and supports the theory that programs such as HRH are highly effective at improving the quality of residency programs and undergraduate medical education.
View details for DOI 10.1186/s12909-019-1617-8
View details for PubMedID 31208418
- Making the Consult Interaction More Than a Transaction: Helping Fellows Be Better Teachers and Residents Be Better Learners. The Journal of pediatrics 2019; 209: 3
Creating the Subspecialty Pediatrics Investigator Network (vol 192, pg 3, 2018)
JOURNAL OF PEDIATRICS
2019; 207: 269
View details for Web of Science ID 000462161200064
Pediatric Endocrinology Trainees' Education and Knowledge About Insulin Pumps and Continuous Glucose Monitors.
Diabetes technology & therapeutics
2019; 21 (3): 105–9
Recent data demonstrating a lack of improvement in average hemoglobin A1c levels despite the increased use of insulin pumps and continuous glucose monitors (CGMs) suggest that patients are not using these technologies optimally. Suboptimal provider understanding of these devices may be a contributing factor.We sought to assess fellows' knowledge, attitudes, and practices regarding insulin pumps and CGMs using a mixed-methods survey. We polled 42 pediatric endocrinology fellows and 69 attending physicians in pediatric endocrinology using items on a five-point Likert scale.Perceived fellow knowledge of insulin pumps and CGMs was only 3.6 ± 1.0 and 3.6 ± 0.9, respectively. Despite consensus about the need for pediatric endocrinologists to understand these technologies, only 14.7% of fellows reported the presence of a formal curriculum about these technologies at their institutions. Potential gaps identified in fellows' knowledge include general use and troubleshooting, advanced insulin pump features, infusion sets and dermatological complications, systematic approach to data, interpretation and application of CGM data, and keeping pace with technological advances.Our data suggest suboptimal fellow knowledge and understanding of insulin pumps and CGMs in pediatric type 1 diabetes management, which is likely attributable to inadequate education in fellowship training programs. The development of formal educational curricula targeting areas of weakness identified in this survey may improve clinician knowledge of these technologies and ultimately impact patient education and care.
View details for DOI 10.1089/dia.2018.0331
View details for PubMedID 30681363
View details for PubMedCentralID PMC6434593
Undernutrition and growth in the developing world.
Current opinion in endocrinology, diabetes, and obesity
PURPOSE OF REVIEW: Despite targeted interventions, an estimated 150.8 million children under 5 years globally are still stunted, of which more than half live in Asia and more than one-third live in Africa. This review summarizes our current knowledge regarding how longitudinal bone growth is regulated by nutritional intake in the developing world. Dietary macronutrients and micronutrients necessary for growth are also briefly reviewed.RECENT FINDINGS: Recent advances include investigations of nutritionally sensitive regulators of growth as well as prospective evaluations of the role of specific dietary components on growth in order to better assess their impact.SUMMARY: Further investigation is required to understand how nutrition impacts growth, the mechanisms underlying stunting and to optimize therapeutic strategies for children who are at risk for growth attenuation or are stunted in low and middle-income countries (LMICs).
View details for DOI 10.1097/MED.0000000000000461
View details for PubMedID 30507697
Effects of MetAP2 inhibition on hyperphagia and body weight in Prader-Willi syndrome: A randomized, double-blind, placebo-controlled trial.
Diabetes, obesity & metabolism
2017; 19 (12): 1751–61
There are no treatments for the extreme hyperphagia and obesity in Prader-Willi syndrome (PWS). The bestPWS clinical trial assessed the efficacy, safety and tolerability of the methionine aminopeptidase 2 (MetAP2) inhibitor, beloranib.Participants with PWS (12-65 years old) were randomly assigned (1:1:1) to biweekly placebo, 1.8 mg beloranib or 2.4 mg beloranib injection for 26 weeks at 15 US sites. Co-primary endpoints were the changes in hyperphagia [measured by Hyperphagia Questionnaire for Clinical Trials (HQ-CT); possible score 0-36] and weight by intention-to-treat. ClinicalTrials.gov registration: NCT02179151.One-hundred and seven participants were included in the intention-to-treat analysis: placebo (n = 34); 1.8 mg beloranib (n = 36); or 2.4 mg beloranib (n = 37). Improvement (reduction) in HQ-CT total score was greater in the 1.8 mg (mean difference -6.3, 95% CI -9.6 to -3.0; P = .0003) and 2.4 mg beloranib groups (-7.0, 95% CI -10.5 to -3.6; P = .0001) vs placebo. Compared with placebo, weight change was greater with 1.8 mg (mean difference - 8.2%, 95% CI -10.8 to -5.6; P < .0001) and 2.4 mg beloranib (-9.5%, 95% CI -12.1 to -6.8; P < .0001). Injection site bruising was the most frequent adverse event with beloranib. Dosing was stopped early due to an imbalance in venous thrombotic events in beloranib-treated participants (2 fatal events of pulmonary embolism and 2 events of deep vein thrombosis) compared with placebo.MetAP2 inhibition with beloranib produced statistically significant and clinically meaningful improvements in hyperphagia-related behaviours and weight loss in participants with PWS. Although investigation of beloranib has ceased, inhibition of MetAP2 is a novel mechanism for treating hyperphagia and obesity.
View details for PubMedID 28556449
Transcranial direct current stimulation reduces food-craving and measures of hyperphagia behavior in participants with Prader-Willi syndrome.
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
2016; 171B (2): 266–75
Prader-Willi syndrome (PWS) is a neurodevelopmental genetic disorder characterized by intellectual disabilities and insatiable appetite with compulsive eating leading to severe obesity with detrimental health consequences. Transcranial direct current stimulation (tDCS) has been shown to modulate decision-making and cue-induced food craving in healthy adults. We conducted a pilot double blind, sham-controlled, multicenter study of tDCS modulation of food drive and craving in 10 adult PWS participants, 11 adult obese (OB) and 11 adult healthy-weight control (HWC) subjects. PWS and OB subjects received five consecutive daily sessions of active or sham tDCS over the right dorsolateral prefrontal cortex (DLPFC), while HWC received a single sham and active tDCS in a crossover design. Standardized psychometric instruments assessed food craving, drive and hyperphagia by self-report and caregiver assessment over 30 days. Robust baseline differences were observed in severity scores for the Three-Factor Eating Questionnaire (TFEQ) and Dykens Hyperphagia Questionnaire (DHQ) for PWS compared to HWC while obese participants were more similar to HWC. Active tDCS stimulation in PWS was associated with a significant change from baseline in TFEQ Disinhibition (Factor II) (Ƶ = 1.9, P < 0.05, 30 days) and Total Scores (Ƶ = 2.3, P < 0.02, 30 days), and participant ratings of the DHQ Severity (Ƶ = 1.8, P < 0.06, 5 days) and Total Scores (Ƶ = 1.9, P < 0.05, 15 days). These findings support sustained neuromodulatory effects and efficacy of tDCS to reduce food drive and behaviors impacting hyperphagia in PWS. Transcranial direct current stimulation may represent a straight-forward, low risk and low cost method to improve care, management and quality of life in PWS.
View details for DOI 10.1002/ajmg.b.32401
View details for PubMedID 26590516
Fellows as Teachers: Raising the Educational Bar.
Annals of the American Thoracic Society
2016; 13 (4): 465–68
Fellows are expected to educate trainees, peers, and patients, during and long after fellowship. However, there has been relatively little emphasis on the acquisition of teaching skills in fellowship programs. Challenges to teaching by fellows during subspecialty training include demanding clinical duties, their limited knowledge base in the field, brief contact time with learners during consultative roles, and, for new fellows, personal unfamiliarity with the learners and hospital culture. Fellows' teaching skills can be improved by formal curricula addressing teaching, and by direct observation and feedback of teaching akin to what is provided for learning clinical care. Further expansion of fellow-as-teacher programs will allow in-depth training for fellows seeking careers as medical educators. Even without such dedicated programs, emphasis on honing teaching skills during fellowship will telegraph the importance of teaching and help evolve divisional culture. Such efforts can have a positive impact on patients and learners, and enhance the teaching skills of future faculty.
View details for DOI 10.1513/AnnalsATS.201601-026PS
View details for PubMedID 26835749
The High Direct Medical Costs of Prader-Willi Syndrome.
The Journal of pediatrics
2016; 175: 137–43
To assess medical resource utilization associated with Prader-Willi syndrome (PWS) in the US, hypothesized to be greater relative to a matched control group without PWS.We used a retrospective case-matched control design and longitudinal US administrative claims data (MarketScan) during a 5-year enrollment period (2009-2014). Patients with PWS were identified by Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code 759.81. Controls were matched on age, sex, and payer type. Outcomes included total, outpatient, inpatient and prescription costs.After matching and application of inclusion/exclusion criteria, we identified 2030 patients with PWS (1161 commercial, 38 Medicare supplemental, and 831 Medicaid). Commercially insured patients with PWS (median age 10 years) had 8.8-times greater total annual direct medical costs than their counterparts without PWS (median age 10 years: median costs $14 907 vs $819; P < .0001; mean costs: $28 712 vs $3246). Outpatient care comprised the largest portion of medical resource utilization for enrollees with and without PWS (median $5605 vs $675; P < .0001; mean $11 032 vs $1804), followed by mean annual inpatient and medication costs, which were $10 879 vs $1015 (P < .001) and $6801 vs $428 (P < .001), respectively. Total annual direct medical costs were ∼42% greater for Medicaid-insured patients with PWS than their commercially insured counterparts, an increase partly explained by claims for Medicaid Waiver day and residential habilitation.Direct medical resource utilization was considerably greater among patients with PWS than members without the condition. This study provides a first step toward quantifying the financial burden of PWS posed to individuals, families, and society.
View details for DOI 10.1016/j.jpeds.2016.05.018
View details for PubMedID 27283463
- The International Olympic Committee Consensus statement on age determination in high-level young athletes. British journal of sports medicine 2010; 44 (7): 476–84
Isolated lymphocytic infiltration of pituitary stalk preceding the diagnosis of germinoma in 2 prepubertal children treated with growth hormone.
2009; 72 (1): 57–62
We report the clinical course of 2 patients with central diabetes insipidus and evolving to panyhypopituitarism which prompted the diagnosis of an isolated pituitary stalk thickening (PST). In both patients, all etiological investigations were normal and the first biopsy revealed an isolated lymphocytic infiltrate with no sign of malignancy. Close clinical follow-up accompanied by serial brain MRIs was proposed to determine a precise diagnosis and for early detection and treatment of neoplastic disease. In our first case, the diagnosis of germinoma was made 9 months after the PST diagnosis owing to tumor progression. In the second case, the time course was even longer with the diagnosis of germinoma 6 years following initial presentation. In these cases, it is speculated that the lymphocytic infiltrates represent the first sign of a host reaction to an occult germinoma. To our knowledge, this is the third case reported of lymphocytic infiltrates preceding a germinoma in a prepubertal girl, and the only case reported in a prepubertal boy. These cases underline the difficulties in establishing the diagnosis of germinoma in a patient with isolated PST.
View details for DOI 10.1159/000224342
View details for PubMedID 19571561
Altered hypothalamic-pituitary-ovarian axis function in young female athletes: implications and recommendations for management.
Treatments in endocrinology
2005; 4 (3): 147–54
Young women have become increasingly active in athletics during the 20th century. Those involved in sports that emphasize lean body type are at high risk for the development of menstrual dysfunction, including amenorrhea. This is mediated by an alteration in function of the hypothalamic-pituitary-ovarian (HPO) axis, with loss of normal secretion of luteinizing hormone, and subsequent lack of estrogen production. Disruption of the HPO axis appears to be dependent on the body's recognition of an energy imbalance, which may be due to a lack of compensatory caloric intake in the face of significant energy expenditure. Other pituitary hormones, such as triiodothyronine, growth hormone, and insulin-like growth factor-1 may also be affected. These metabolic changes have an impact on bone mineralization during a critical period in the development of bone mass. Recognition by physicians of the so-called 'female athlete triad', consisting of disordered eating, amenorrhea, and osteoporosis, may allow therapeutic intervention. Diagnosis of eating disorders and decreased bone mineral density can have significant impact on the health of the young athlete. Treatment is aimed at restoring normal menstrual function by increasing caloric intake to balance the increased energy demands of athletic participation. Concurrent treatment of the hypoestrogenemic state using estrogen replacement is controversial, but may aid in alleviating further loss of bone mass.
View details for PubMedID 15898820
Adolescent androgen abnormalities.
Current opinion in obstetrics & gynecology
2002; 14 (5): 445–51
Polycystic ovary syndrome is one of the most common endocrinopathies affecting premenopausal women. This review focuses on this major cause of hyperandrogenism in adolescents and young women, highlighting new diagnostic and therapeutic strategies that are under investigation. The pathophysiologic role in the disorder are the subject of several recent reports.Recent studies have found a 33% prevalence of abnormal glucose tolerance in a cohort of affected adolescents, higher fasting insulin levels and lower insulin sensitivity, and that glucose tolerance testing appears to be necessary for routine screening. The effects of hyperinsulinism may be counteracted by insulin sensitizing agents. In adult women with polycystic ovary syndrome, metformin treatment reduced hyperinsulinemia and hyperandrogenemia. In some obese adolescents, metformin therapy resulted in declines in body mass index, insulin, and glucose. Restoration of regular menses may also occur after metformin treatment. Thus, data is accumulating that insulin-sensitizing agents may be helpful in decreasing the pathophysiologic effects of hyperinsulinism and insulin resistance associated with polycystic ovary syndrome. Other hormonal alterations in polycystic ovary syndrome have also been the subject of recent reports. Leptin secretion was found to be markedly irregular in these women. Elevated LH secretion may be secondary to accelerated gonadotropin-releasing hormone pulse generator activity, although the etiology of the pulse alterations is unclear.Although polycystic ovary syndrome is the most common endocrine disorder affecting young women, it is one of the least understood, reflected by the wealth of research in this area. One area of focus has been the pathophysiologic link between insulin resistance and this disorder, including the effects of promising new agents to counteract these effects.
View details for PubMedID 12401970
Calcium-stimulated insulin secretion in diffuse and focal forms of congenital hyperinsulinism.
The Journal of pediatrics
2000; 137 (2): 239–46
To identify infants with hyperinsulinism caused by defects of the beta-cell adenosine triphosphate-dependent potassium channel complex and to distinguish focal and diffuse forms of hyperinsulinism caused by these mutations.The acute insulin response to intravenous calcium stimulation (CaAIR) was determined in 9 patients <20 years with diffuse hyperinsulinism caused by defective beta-cell sulfonylurea receptor (SUR1(-/-)), 3 patients with focal congenital hyperinsulinism (6 weeks to 18 months), a 10-year-old with insulinoma, 5 with hyperinsulinism/hyperammonemia syndrome caused by defective glutamate dehydrogenase (6 months to 28 years), 4 SUR1(+/-) heterozygotes with no symptoms, and 9 normal adults. Three infants with congenital focal disease, 1 with diffuse hyperinsulinism, and the child with insulinoma underwent selective pancreatic intra-arterial calcium stimulation with hepatic venous sampling.Children with diffuse SUR1(-/-) disease and infants with congenital focal hyperinsulinism responded to CaAIR, whereas the normal control group, patients with hyperinsulinism/hyperammonemia syndrome, and SUR1(+/-) carriers did not. Selective arterial calcium stimulation of the pancreas with hepatic venous sampling revealed selective, significant step-ups in insulin secretion that correlated anatomically with the location of solitary lesions confirmed surgically in 2 of 3 infants with congenital focal disease and in the child with insulinoma. Selective arterial calcium stimulation of the pancreas with hepatic venous sampling demonstrated markedly elevated baseline insulin levels throughout the pancreas of the infant with diffuse hyperinsulinism.The intravenous CaAIR is a safe and simple test for identifying infants with diffuse SUR1(-/-) hyperinsulinism or with focal congenital hyperinsulinism. Preoperative selective arterial calcium stimulation of the pancreas with hepatic venous sampling can localize focal lesions causing hyperinsulinism in children. The combination of these calcium stimulation tests may help distinguish focal lesions suitable for cure by local surgical resection.
View details for DOI 10.1067/mpd.2000.107386
View details for PubMedID 10931418
View details for PubMedCentralID PMC4151173