Publications by authors named "Kate Millington"

15 Publications

  • Page 1 of 1

Hyperglycemia during induction therapy for acute lymphoblastic leukemia is temporally linked to pegaspargase administration.

Pediatr Blood Cancer 2021 Dec 21:e29505. Epub 2021 Dec 21.

Division of Endocrinology, Boston Children's Hospital, Boston, Massachusetts, USA.

Background: Chemotherapy regimens containing glucocorticoids and pegaspargase are associated with hyperglycemia; however, the pattern and underlying risk factors are not well characterized. We determined the pattern of hyperglycemia and associated factors in children with acute lymphoblastic leukemia (ALL) receiving glucocorticoids and pegaspargase during induction.

Methods: Retrospective analysis of patients treated between 2010 and 2020 at a single institution. Pretreatment data, glucose values, and insulin regimens were abstracted from the record. Hyperglycemia was defined as two or more random glucose measurements ≥200 mg/dl. Analyses of demographic and clinical factors were conducted with logistic regression.

Results: Two hundred thirteen patients, median age 6 years (range 1.0-18.9 years), 47% female, were included. The prevalence of hyperglycemia was 23% (n = 48). Mean glucose levels peaked 3 days following administration of pegaspargase. In multivariable analysis, age ≥10 years (odds ratio [OR] 6.2, 95% confidence interval [CI]: 2.9-13.4), female sex (OR 2.7, 95% CI: 1.2-6.2), and family history of diabetes (OR 3.2, 95% CI: 1.4-7.3) were predictive of hyperglycemia. Age ≥10 years (OR 19.4, 95% CI: 5.5-68.4), family history of diabetes (OR 8.2, 95% CI: 2.7-25.3), and higher body mass index (BMI) (OR 1.8, 95% CI: 1.1-2.9) were associated with insulin treatment.

Conclusions: Onset of hyperglycemia in children receiving induction chemotherapy for ALL is temporally linked to administration of pegaspargase. Older age, female sex, and family history of diabetes are predictive of hyperglycemia during induction; older age, family history of diabetes, and higher BMI are associated with insulin treatment. Frequent glucose monitoring is indicated during induction therapy for ALL.
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http://dx.doi.org/10.1002/pbc.29505DOI Listing
December 2021

The Medical Implications of Banning Transgender Youth From Sport Participation.

JAMA Pediatr 2021 Dec 6. Epub 2021 Dec 6.

Division of Endocrinology, Boston Children's Hospital, Boston, Massachusetts.

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http://dx.doi.org/10.1001/jamapediatrics.2021.4597DOI Listing
December 2021

Severe Hypernatremia in an Adolescent With Anorexia Nervosa.

Clin Pediatr (Phila) 2021 12 27;60(14):586-590. Epub 2021 Oct 27.

Boston Children's Hospital, Boston, MA, USA.

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http://dx.doi.org/10.1177/00099228211055283DOI Listing
December 2021

Lipoprotein subtypes after testosterone therapy in transmasculine adolescents.

J Clin Lipidol 2021 Nov-Dec;15(6):840-844. Epub 2021 Oct 2.

Division of Endocrinology, Boston Children's Hospital, Boston, Massachusetts, United States; Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, United States.

Differences in lipoprotein-particle subclasses between men and women start in puberty and narrow after menopause, suggesting a role for sex steroids. In this cross-sectional cohort study, we examined lipoprotein subtype profiles in transmasculine adolescents treated with testosterone. Transmasculine adolescents (n = 17) had lipoprotein profiles that were similar to those of cisgender males (n = 33) and more atherogenic than those of cisgender females (n = 32), with higher concentrations of small low-density lipoprotein (LDL) particles (435 ± 222 nmol/L vs. 244 ± 163 nmol/L, p = 0.008) and lower concentrations of large high-density lipoprotein (HDL) particles (1.5 ± 1.3 μmol/L vs 2.7 ± 1.2 μmol/L, p = 0.003) when compared to cisgender females. Thus, testosterone appears to be a major contributor to differences in lipoprotein profiles, a surrogate for cardiovascular disease risk, between cisgender women and both transgender and cisgender men.
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http://dx.doi.org/10.1016/j.jacl.2021.09.051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8742606PMC
October 2021

Growth in Transgender/Gender-Diverse Youth in the First Year of Treatment With Gonadotropin-Releasing Hormone Agonists.

J Adolesc Health 2022 Jan 24;70(1):108-113. Epub 2021 Jul 24.

Division of Pediatric Endocrinology, University of California at San Francisco, San Francisco, California.

Purpose: Transgender/gender-diverse (TGD) youth are treated with gonadotropin-releasing hormone agonists (GnRHas) to halt endogenous puberty and prevent the development of secondary sex characteristics discordant with their gender identity. This treatment may have significant impact on growth and height velocity (HV).

Methods: Participants were recruited prior to GnRHa initiation from four gender specialty clinics in the U.S. Anthropometric, laboratory, and Tanner-stage data were abstracted from medical records.

Results: Fifty-five TGD youth (47% designated male at birth) with a mean ± standard deviation age of 11.5 ± 1.2 years were included in the analysis. HV in the first year of GnRHa use was median (interquartile range) 5.1 (3.7-5.6) cm/year. Later Tanner stage at GnRHa initiation was associated with lower HV: 5.3 (4.4-5.6) cm/year for Tanner stage II, 4.4 (3.3-6.0) cm/year for Tanner stage III, and 1.6 (1.5-2.9) cm/year for Tanner stage IV (p = .001). When controlled for age, there was not a significant difference in mean HV between TGD youth and prepubertal youth; however, when stratified by Tanner stage individuals starting GnRHa at Tanner stage IV had an HV below that of prepubertal youth, 1.6 (1.5-2.9) versus 6.1 (4.3-6.5) cm/year, p = .006.

Conclusions: Overall, TGD youth treated with GnRHa have HV similar to that of prepubertal children, but TGD youth who start GnRHa later in puberty have an HV below the prepubertal range. Ongoing follow-up of this cohort will determine the impact of GnRHa treatment on adult height.
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http://dx.doi.org/10.1016/j.jadohealth.2021.06.022DOI Listing
January 2022

Greater Than Expected Prevalence of Type 1 Diabetes Mellitus Found in an Urban Gender Program.

Transgend Health 2021 Feb 15;6(1):57-60. Epub 2021 Feb 15.

Division of Endocrinology, Boston Children's Hospital, Boston, Massachusetts, USA.

The prevalence of type 1 diabetes mellitus among transgender and gender diverse (TGD) youth is nearly five times higher than in the general pediatric population (9.9 per 1000 people vs. 1.93 per 1000 people). We hypothesize that minority stress experienced by TGD youth may lead to a higher prevalence of diabetes.
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http://dx.doi.org/10.1089/trgh.2020.0027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906220PMC
February 2021

A serous borderline ovarian tumour in a transgender male adolescent.

Br J Cancer 2021 02 27;124(3):567-569. Epub 2020 Oct 27.

Dana-Farber Cancer Institute, Boston Children's Hospital, Boston, MA, USA.

Here we present a transgender male adolescent with an androgen receptor-positive serous borderline ovarian tumour in the setting of testosterone treatment for medical gender transition. To our knowledge, this is the second report of borderline tumour in a transgender individual and the first in an adolescent, an age group in which borderline tumours are extremely rare. We discuss the specific considerations of treating ovarian tumours in the transgender male population, the incompletely understood role of androgens in the genesis of ovarian epithelial neoplasia, and an emphasis on assessing cancer risk in transgender patients based on patient anatomy.
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http://dx.doi.org/10.1038/s41416-020-01129-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851115PMC
February 2021

Physiological and Metabolic Characteristics of a Cohort of Transgender and Gender-Diverse Youth in the United States.

J Adolesc Health 2020 09 14;67(3):376-383. Epub 2020 May 14.

Division of Endocrinology, Boston Children's Hospital, Boston, Massachusetts.

Purpose: The purpose of this study was to describe baseline physical and laboratory characteristics of participants in the largest prospective study of transgender and gender-diverse (TGD) youth in the United States.

Methods: Participants were recruited from four clinics which specialize in the care of TGD youth before starting either GnRH analogs for pubertal suppression or gender-affirming hormone treatment. Anthropometric and laboratory measurements were abstracted from the medical chart. Baseline characteristics including height, weight, body mass index, blood pressure, and laboratory measurements were compared with those of age-matched National Health and Nutritional Examination Survey comparison group.

Results: Seventy-eight TGD youth with a median age of 11 years (range 8-14 years) were recruited before pubertal suppression, of whom 41 (53%) were designated male at birth, and 296 participants with a median age of 16 years (range 12-20 years) were recruited before beginning gender-affirming hormones, of whom 99 (33%) were designated male at birth. The mean high-density lipoprotein cholesterol was lower in the study participants when compared with that of National Health and Nutritional Examination Survey participants (50.6 ± 12.3 mg/dL vs. 53.3 ± 13.3 mg/dL, p = .001). Otherwise, the study cohorts were similar in terms of body mass index, proportion of overweight and obesity, blood pressure, and baseline laboratory variables.

Conclusions: Before starting gender-affirming treatment, TGD youth are physiologically similar to the general population of children and adolescents in the United States, with the exception of slightly lower high-density lipoprotein cholesterol. Evaluation of this cohort over time will define the physiological effects of pubertal blockade and gender-affirming hormone treatment.
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http://dx.doi.org/10.1016/j.jadohealth.2020.03.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483238PMC
September 2020

Plasma β-Hydroxybutyrate for the Diagnosis of Diabetic Ketoacidosis in the Emergency Department.

Pediatr Emerg Care 2021 Dec;37(12):e1345-e1350

From the Divisions of Endocrinology.

Objective: Diabetic ketoacidosis (DKA) is a common emergency department presentation of both new-onset and established diabetes mellitus (DM). β-Hydroxybutyrate (BOHB) provides a direct measure of the pathophysiologic derangement in DKA as compared with the nonspecific measurements of blood pH and bicarbonate. Our objective was to characterize the relationship between BOHB and DKA.

Methods: This is a cross-sectional retrospective study of pediatric patients with DM presenting to an urban pediatric emergency department between January 1, 2016, and September 30, 2018. Analyses were performed on each patient's initial, simultaneous BOHB and pH. Diagnostic test characteristics of BOHB were calculated, and logistic regression was performed to investigate the effects of age and other key clinical factors.

Results: Among 594 patients with DM, with median age of 12.3 years (interquartile range, 8.7-15.9 years), 176 (29.6%) presented with DKA. The inclusion of age, transfer status, and new-onset in the statistical model did not improve the prediction of DKA beyond BOHB alone. β-Hydroxybutyrate demonstrated strong discrimination for DKA, with an area under the curve of 0.95 (95% confidence interval, 0.93-0.97). A BOHB value of 5.3 mmol/L predicted DKA with optimal accuracy (90.6% of patients were correctly classified). The sensitivity, specificity, and positive and negative predictive values of this cut point were 76.7% (95% confidence interval, 69.8%-82.7%), 96.4% (94.2%-98.0%), 90.0% (84.0%-94.3%), and 90.8% (87.7%-93.3%), respectively.

Conclusions: β-Hydroxybutyrate accurately predicts DKA in children and adolescents. More importantly, because plasma BOHB is the ideal biochemical marker of DKA, BOHB may provide a more optimal definition of DKA for management decisions and treatment targets.
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http://dx.doi.org/10.1097/PEC.0000000000002035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7394730PMC
December 2021

Case Series: Minocycline-Associated Thyroiditis.

Horm Res Paediatr 2019 18;92(4):276-283. Epub 2019 Sep 18.

Division of Endocrinology, Boston Children's Hospital, Boston, Massachusetts, USA.

Introduction: Minocycline, a member of the tetracycline class of antibiotics, has been associated with benign thyroid pigmentation but reports of thyroid dysfunction are sparse.

Methods: Cases were selected via an inquiry of the electronic medical records for patients with thyroid dysfunction and the use of a tetracycline antibiotic. Non-autoimmune thyroiditis was defined as abnormally low or suppressed thyroid-stimulating hormone (TSH, <0.3 µIU/mL), elevated free thyroxine or total thyroxine, and undetectable antithyroid antibodies.

Results: Nine cases of thyroiditis without autoimmunity were identified out of 423 reviewed patients. Cases of thyroiditis occurred in adolescents ages 14-17 years who had been taking minocycline for 6 months to 4 years. In all cases, minocycline was prescribed for the treatment of acne. Four of the 9 received treatment for thyrotoxicosis with a β-blocker (in 3 cases) and/or antithyroid drug (in 2 cases). Thyroiditis was symptomatic in all but one individual who presented with painless goiter. All thyroiditis was transient and resolved after a median of 4.5 months (range 2-5 months). In one case, thyroiditis was followed by transient hypothyroidism.

Discussion: Minocycline is known to cause thyroid abnormalities, although it has not been definitively linked to thyroid dysfunction. Here, we report 9 cases of non-autoimmune thyroiditis in adolescents receiving minocycline for acne. We recommend that minocycline exposure be considered in the differential diagnosis for thyroiditis and that patients receiving minocycline be counseled regarding the risk of thyroid dysfunction.
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http://dx.doi.org/10.1159/000502843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078063PMC
May 2020

The Utility of Potassium Monitoring in Gender-Diverse Adolescents Taking Spironolactone.

J Endocr Soc 2019 May 4;3(5):1031-1038. Epub 2019 Apr 4.

Division of Endocrinology, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts.

Context: Current guidelines recommend close monitoring of electrolytes in transgender patients using spironolactone given the risk of hyperkalemia from mineralocorticoid antagonism. In patients taking spironolactone for other conditions, the rate of hyperkalemia is low, and the utility of frequent monitoring has been questioned.

Objective: We hypothesized that the rate of hyperkalemia in gender-diverse adolescents taking spironolactone is low and, when present, clinically insignificant.

Design And Outcomes: A retrospective chart review of adolescents seen in a specialty gender clinic at a tertiary care pediatric hospital over 10 years identified patients prescribed spironolactone for gender transition. Study outcomes were the incidence of hyperkalemia, defined as serum potassium concentration >5.0 mmol/L, and the relationship between potassium levels and spironolactone dose and duration.

Results: Records were reviewed for 85 subjects with a mean ± SD age of 16.6 ± 1.7 years. There were a total of 269 potassium measurements (80 prior to spironolactone initiation and 189 during spironolactone treatment). Six potassium measurements in five subjects were >5.0 mmol/L, indicating a rate of hyperkalemia of 2.2%. None of the subjects had symptoms of hyperkalemia, and all elevated measurements were normal when repeated. Only one subject discontinued spironolactone after an elevated potassium measurement. There was no relationship between hyperkalemia and spironolactone dose. Potassium measurements decreased with increasing treatment duration.

Conclusions: Hyperkalemia in patients taking spironolactone for gender transition is rare and when present is transient and asymptomatic. In the absence of other medical comorbidities, routine electrolyte monitoring in this population may be unnecessary.
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http://dx.doi.org/10.1210/js.2019-00030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497918PMC
May 2019

11-year old boy with facial hair, acne and deepened voice.

BMJ Case Rep 2019 Mar 20;12(3). Epub 2019 Mar 20.

Instructor in Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.

11-year old twin boy found to have idiopathic precocious puberty after routine well-child examination revealed discordant pubertal growth between the two brothers.
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http://dx.doi.org/10.1136/bcr-2018-226600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6453341PMC
March 2019

Patient and parent perceptions of the diagnosis and management of cystic fibrosis-related diabetes.

J Clin Transl Endocrinol 2014 Sep 11;1(3):100-107. Epub 2014 Jul 11.

Division of Endocrinology & Diabetes, The Children's Hospital of Philadelphia, Department of Pediatrics, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA 19104, USA.

Background: Cystic Fibrosis Related Diabetes (CFRD) is an increasingly common complication in CF. CFRD introduces an additional complex chronic disease to individuals already attending to demanding treatment regimens. An improved understanding of the reaction to and coping mechanisms surrounding CFRD may facilitate management of CFRD.

Methods: Semi-structured interviews completed by 10 children with CFRD, 10 adults with CFRD and 10 parents of children with CFRD in a single large CF Care Center were analyzed utilizing phenomenological analysis.

Results: Patients and families reported having limited knowledge of CFRD prior to diagnosis. CFRD was considered an extension of their underlying CF and successful management depended upon integration into existing routines.

Conclusions: Health care professionals caring for patients with CFRD should be informed of the specific challenges that arise in CFRD. Education in advance of CFRD diagnosis may facilitate management.
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http://dx.doi.org/10.1016/j.jcte.2014.07.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5685035PMC
September 2014
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