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Book: Pediatric endocrinology and inborn errors of metabolism

Sarafoglou, Kyriakie

2009

Author's details	ed. by Kyriakie Sarafoglou
Keywords	Endocrine System Diseases ; Metabolism, Inborn Errors ; Child
Language	English
Size	XIII, 949 S. : zahlr. Ill., graph. Darst.
Publisher	McGraw-Hill Med
Publishing place	New York u.a.
Publishing country	United States
Document type	Book
HBZ-ID	HT014499156
ISBN	0-07-143915-3 ; 978-0-07-143915-2
Database	Catalogue ZB MED Medicine, Health

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Article: Case Report: Anastrozole as a monotherapy for pre-pubertal children with non-classic congenital adrenal hyperplasia.

Liu, Sandy C / Suresh, Malavika / Jaber, Mutaz / Mercado Munoz, Yesica / Sarafoglou, Kyriakie

Frontiers in endocrinology

2023 Volume 14, Page(s) 1101843

Abstract: Most children with non-classic congenital adrenal hyperplasia (NC-CAH) due to 21-hydroxylase deficiency are asymptomatic and do not require cortisol replacement therapy unless they develop symptoms of hyperandrogenemia. The current practice is to treat ... ...

Abstract	Most children with non-classic congenital adrenal hyperplasia (NC-CAH) due to 21-hydroxylase deficiency are asymptomatic and do not require cortisol replacement therapy unless they develop symptoms of hyperandrogenemia. The current practice is to treat symptomatic children with hydrocortisone aimed at suppressing excess adrenal androgen production irrespective of the child's level of endogenous cortisol production. Once on hydrocortisone therapy, even children with normal cortisol production require stress dosing. Some children with NC-CAH may present with premature adrenarche, growth acceleration, and advanced bone age, but with no signs of genital virilization and normal endogenous cortisol production. In these cases, an alternative therapy to hydrocortisone treatment that does not impact the hypothalamic-pituitary-adrenal axis, but targets increased estrogen production and its effects on bone maturation, could be considered. Aromatase inhibitors (AIs), which block the aromatization of androgen to estrogen, have been used off-label in men with short stature to delay bone maturation and as an adjunct therapy in children with classic CAH. The use of AI as a monotherapy for children with NC-CAH has never been reported. We present three pre-pubertal female children with a diagnosis of NC-CAH treated with anastrozole monotherapy after presenting with advanced bone age, early adrenarche, no signs of genital virilization, and normal peak cortisol in response to ACTH stimulation testing. Bone age z-scores normalized, and all three reached or exceeded their target heights. Monotherapy with anastrozole can be an effective alternative in slowing down bone maturation and improving height outcomes in children with NC-CAH and normal adrenal cortisol production.
MeSH term(s)	Child ; Female ; Humans ; Adrenal Hyperplasia, Congenital/complications ; Adrenal Hyperplasia, Congenital/drug therapy ; Adrenal Hyperplasia, Congenital/diagnosis ; Anastrozole ; Androgens ; Estrogens ; Hydrocortisone ; Hypothalamo-Hypophyseal System ; Pituitary-Adrenal System ; Virilism
Chemical Substances	Anastrozole (2Z07MYW1AZ) ; Androgens ; Estrogens ; Hydrocortisone (WI4X0X7BPJ)
Language	English
Publishing date	2023-03-02
Publishing country	Switzerland
Document type	Case Reports ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2023.1101843
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Article: Depressive and anxiety disorders and antidepressant prescriptions among insured children and young adults with congenital adrenal hyperplasia in the United States.

Harasymiw, Lauren A / Grosse, Scott D / Cullen, Kathryn R / Bitsko, Rebecca H / Perou, Ruth / Sarafoglou, Kyriakie

Frontiers in endocrinology

2023 Volume 14, Page(s) 1129584

Abstract: Background: Dysfunction in the hypothalamic-pituitary-adrenal axis has been associated with depressive and anxiety disorders. Little is known about the risk for these disorders among individuals with congenital adrenal hyperplasia (CAH), a form of ... ...

Abstract	Background: Dysfunction in the hypothalamic-pituitary-adrenal axis has been associated with depressive and anxiety disorders. Little is known about the risk for these disorders among individuals with congenital adrenal hyperplasia (CAH), a form of primary adrenal insufficiency. Objective: We investigated the prevalence of depressive and anxiety disorders and antidepressant prescriptions in two large healthcare databases of insured children, adolescents, and young adults with CAH in the United States. Methods: We conducted a retrospective cohort study using administrative data from October 2015 through December 2019 for individuals aged 4-25 years enrolled in employer-sponsored or Medicaid health plans. Results: Adjusting for age, the prevalence of depressive disorders [adjusted prevalence ratio (aPR) = 1.7, 95% confidence interval (CI): 1.4-2.0, p<0.001], anxiety disorders [aPR = 1.7, 95% CI: 1.4-1.9, p<0.001], and filled antidepressant prescriptions [aPR = 1.7, 95% CI: 1.4-2.0, p<0.001] was higher among privately insured youth with CAH as compared to their non-CAH peers. Prevalence estimates were also higher among publicly insured youth with CAH for depressive disorders [aPR = 2.3, 95% CI: 1.9-2.9, p<0.001], anxiety disorders [aPR = 2.0, 95% CI: 1.6-2.5, p<0.001], and filled antidepressant prescriptions [aPR = 2.5, 95% CI: 1.9-3.1, p<0.001] as compared to their non-CAH peers. Conclusions: The elevated prevalence of depressive and anxiety disorders and antidepressant prescriptions among youth with CAH suggests that screening for symptoms of depression and anxiety among this population might be warranted.
MeSH term(s)	United States/epidemiology ; Adolescent ; Humans ; Child ; Young Adult ; Adrenal Hyperplasia, Congenital/drug therapy ; Adrenal Hyperplasia, Congenital/epidemiology ; Hypothalamo-Hypophyseal System ; Retrospective Studies ; Pituitary-Adrenal System ; Anxiety Disorders/drug therapy ; Anxiety Disorders/epidemiology ; Antidepressive Agents/therapeutic use ; Prescriptions
Chemical Substances	Antidepressive Agents
Language	English
Publishing date	2023-08-17
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2023.1129584
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Article ; Online: Development of Tanner Stage-Age Adjusted CDC Height Curves for Research and Clinical Applications.

Miller, Bradley S / Sarafoglou, Kyriakie / Addo, O Yaw

Journal of the Endocrine Society

2020 Volume 4, Issue 9, Page(s) bvaa098

Abstract: Background and objective: Variations in normal pubertal development, pubertal disorders, and race/ethnicity can lead to differences in growth patterns and timing that are not captured by the Centers for Disease Control and Prevention (CDC) height-for- ... ...

Abstract	Background and objective: Variations in normal pubertal development, pubertal disorders, and race/ethnicity can lead to differences in growth patterns and timing that are not captured by the Centers for Disease Control and Prevention (CDC) height-for-chronological age (CA Study design: Population-based Tanner staging and anthropometric data for 13 358 children age 8 to 18 years from 3 large US national surveys: National Health Examination Surveys (NHES cycle III); the Hispanic Health and Nutrition Examination Surveys (HHANES) and the third National Health and Nutrition Examination Surveys (NHANES III) were analyzed. TSA Results: As expected, the TSA Conclusions: TSA
Language	English
Publishing date	2020-07-17
Publishing country	United States
Document type	Journal Article
ISSN	2472-1972
ISSN (online)	2472-1972
DOI	10.1210/jendso/bvaa098
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Article ; Online: Attention-Deficit/Hyperactivity Disorder Among US Children and Adolescents With Congenital Adrenal Hyperplasia.

Harasymiw, Lauren A / Grosse, Scott D / Sarafoglou, Kyriakie

Journal of the Endocrine Society

2020 Volume 4, Issue 12, Page(s) bvaa152

Abstract: Background: Little is known regarding risk for co-occurring mental health conditions among pediatric patients with congenital adrenal hyperplasia (CAH). The objective of the current study was to investigate the prevalence of medically managed attention- ... ...

Abstract	Background: Little is known regarding risk for co-occurring mental health conditions among pediatric patients with congenital adrenal hyperplasia (CAH). The objective of the current study was to investigate the prevalence of medically managed attention-deficit/hyperactivity disorder (ADHD) in 2 large administrative samples of insured children and adolescents with and without CAH in the United States. Methods: We assessed the prevalence of CAH and of medically managed ADHD using algorithms defined from diagnosis codes and filled prescriptions data using the IBM MarketScan Commercial and Multi-State Medicaid claims databases. We evaluated subjects who were continuously enrolled for ≥ 12 months with a first claim during October 2015 through December 2017 when they were 5 to 18 years old. Results: The administrative prevalence of CAH in the Commercial (N = 3 685 127) and Medicaid (N = 3 434 472) samples was 10.1 per 100 000 (n = 372) and 7.2 per 100 000 (n = 247), respectively. The prevalence of medically managed ADHD in the non-CAH population was 8.4% in the Commercial sample and 15.1% in the Medicaid sample. Among children with CAH, there was no increased prevalence of ADHD in the Commercial (9.2%, prevalence ratio [PR] = 1.1; 95% confidence interval [CI], 0.82-1.54; Conclusions: Using 2 large samples of insured children and adolescents in the United States, we found similar prevalence of medically managed ADHD among those with CAH and the general population. Future research to assess the validity of our claims algorithm for identifying pediatric CAH cases is warranted.
Language	English
Publishing date	2020-10-14
Publishing country	United States
Document type	Journal Article
ISSN	2472-1972
ISSN (online)	2472-1972
DOI	10.1210/jendso/bvaa152
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Article: Application of Deep Neural Networks as a Prescreening Tool to Assign Individualized Absorption Models in Pharmacokinetic Analysis.

Jaber, Mutaz M / Yaman, Burhaneddin / Sarafoglou, Kyriakie / Brundage, Richard C

Pharmaceutics

2021 Volume 13, Issue 6

Abstract: A specific model for drug absorption is necessarily assumed in pharmacokinetic (PK) analyses following extravascular dosing. Unfortunately, an inappropriate absorption model may force other model parameters to be poorly estimated. An added complexity ... ...

Abstract	A specific model for drug absorption is necessarily assumed in pharmacokinetic (PK) analyses following extravascular dosing. Unfortunately, an inappropriate absorption model may force other model parameters to be poorly estimated. An added complexity arises in population PK analyses when different individuals appear to have different absorption patterns. The aim of this study is to demonstrate that a deep neural network (DNN) can be used to prescreen data and assign an individualized absorption model consistent with either a first-order, Erlang, or split-peak process. Ten thousand profiles were simulated for each of the three aforementioned shapes and used for training the DNN algorithm with a 30% hold-out validation set. During the training phase, a 99.7% accuracy was attained, with 99.4% accuracy during in the validation process. In testing the algorithm classification performance with external patient data, a 93.7% accuracy was reached. This algorithm was developed to prescreen individual data and assign a particular absorption model prior to a population PK analysis. We envision it being used as an efficient prescreening tool in other situations that involve a model component that appears to be variable across subjects. It has the potential to reduce the time needed to perform a manual visual assignment and eliminate inter-assessor variability and bias in assigning a sub-model.
Language	English
Publishing date	2021-05-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics13060797
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Article ; Online: Reply.

Bomberg, Eric Morris / Addo, Oppong Yaw / Sarafoglou, Kyriakie / Miller, Bradley Scott

The Journal of pediatrics

2021 Volume 236, Page(s) 329–331

Language	English
Publishing date	2021-06-12
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	3102-1
ISSN	1097-6833 ; 0022-3476
ISSN (online)	1097-6833
ISSN	0022-3476
DOI	10.1016/j.jpeds.2021.06.013
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Article ; Online: Adjusting for Pubertal Status Reduces Overweight and Obesity Prevalence in the United States.

Bomberg, Eric Morris / Addo, Oppong Yaw / Sarafoglou, Kyriakie / Miller, Bradley Scott

The Journal of pediatrics

2021 Volume 231, Page(s) 200–206.e1

Abstract: Objective: To compare pediatric overweight and obesity prevalence among non-Hispanic white, Mexican American, and non-Hispanic black US youths before and after adjusting body mass index (BMI) for pubertal status, as assessed by Tanner stage.: Study ... ...

Abstract	Objective: To compare pediatric overweight and obesity prevalence among non-Hispanic white, Mexican American, and non-Hispanic black US youths before and after adjusting body mass index (BMI) for pubertal status, as assessed by Tanner stage. Study design: We analyzed cross-sectional anthropometric and pubertal data from non-Hispanic white, Mexican American, and non-Hispanic black youths in the National Health and Nutrition Examination Survey (NHANES) III. We developed specialized Tanner stage and chronological age-adjusted models to establish Tanner-stage adjusted BMI z-scores, which were then used to determine adjusted overweight/obesity prevalence. We compared pediatric overweight/obesity prevalence before and after pubertal status adjustment. Results: Among 3206 youths aged 8-18 years (50% male; 26% non-Hispanic white, 35% Mexican American, 39% non-Hispanic black), adjusting BMI for Tanner stage significantly reduced overweight (males, from 29% to 21%; females, from 29% to 17%) and obesity (males, from 14% to 7%; females, from 11% to 5%) prevalence across all races/ethnicities. The obesity prevalence reduction was more pronounced in Mexican Americans (males, 11% reduction; females, 9% reduction) and non-Hispanic blacks (males and females, 10% reduction) compared with non-Hispanic whites (males, 6% reduction; females, 5% reduction). Similar patterns were seen in overweight prevalence. Conclusions: Adjusting for pubertal status reduced the prevalence of overweight/obesity in non-Hispanic white, Mexican American, and non-Hispanic black youth. This suggests that adjusting for puberty incorporates changes otherwise not captured when only considering the age of a child. Adjusting BMI for pubertal status may be important when interpreting a youth's weight status and consideration for obesity management, as well as when interpreting pediatric overweight/obesity prevalence data.
MeSH term(s)	Adolescent ; African Americans/statistics & numerical data ; Body Mass Index ; Child ; Cross-Sectional Studies ; Female ; Humans ; Male ; Mexican Americans/statistics & numerical data ; Pediatric Obesity/epidemiology ; Prevalence ; Puberty ; United States/epidemiology ; Whites/statistics & numerical data
Language	English
Publishing date	2021-01-16
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3102-1
ISSN	1097-6833 ; 0022-3476
ISSN (online)	1097-6833
ISSN	0022-3476
DOI	10.1016/j.jpeds.2020.12.038
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Article ; Online: Interpretation of Steroid Biomarkers in 21-Hydroxylase Deficiency and Their Use in Disease Management.

Sarafoglou, Kyriakie / Merke, Deborah P / Reisch, Nicole / Claahsen-van der Grinten, Hedi / Falhammar, Henrik / Auchus, Richard J

The Journal of clinical endocrinology and metabolism

2023 Volume 108, Issue 9, Page(s) 2154–2175

Abstract: The most common form of congenital adrenal hyperplasia is 21-hydroxylase deficiency (21OHD), which in the classic (severe) form occurs in roughly 1:16 000 newborns worldwide. Lifelong treatment consists of replacing cortisol and aldosterone deficiencies, ...

Abstract	The most common form of congenital adrenal hyperplasia is 21-hydroxylase deficiency (21OHD), which in the classic (severe) form occurs in roughly 1:16 000 newborns worldwide. Lifelong treatment consists of replacing cortisol and aldosterone deficiencies, and supraphysiological dosing schedules are typically employed to simultaneously attenuate production of adrenal-derived androgens. Glucocorticoid titration in 21OHD is challenging as it must balance the consequences of androgen excess vs those from chronic high glucocorticoid exposure, which are further complicated by interindividual variability in cortisol kinetics and glucocorticoid sensitivity. Clinical assessment and biochemical parameters are both used to guide therapy, but the specific purpose and goals of each biomarker vary with age and clinical context. Here we review the approach to medication titration for children and adults with classic 21OHD, with an emphasis on how to interpret adrenal biomarker values in guiding this process. In parallel, we illustrate how an understanding of the pathophysiologic and pharmacologic principles can be used to avoid and to correct complications of this disease and consequences of its management using existing treatment options.
MeSH term(s)	Child ; Adult ; Humans ; Infant, Newborn ; Adrenal Hyperplasia, Congenital/diagnosis ; Adrenal Hyperplasia, Congenital/drug therapy ; Glucocorticoids/therapeutic use ; Hydrocortisone/therapeutic use ; Steroids ; Biomarkers ; Disease Management ; Steroid 21-Hydroxylase
Chemical Substances	Glucocorticoids ; Hydrocortisone (WI4X0X7BPJ) ; Steroids ; Biomarkers ; Steroid 21-Hydroxylase (EC 1.14.14.16)
Language	English
Publishing date	2023-03-24
Publishing country	United States
Document type	Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/clinem/dgad134
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Article: Sex non-specific growth charts and potential clinical implications in the care of transgender youth.

Bomberg, Eric Morris / Miller, Bradley Scott / Addo, Oppong Yaw / Rogol, Alan David / Jaber, Mutaz M / Sarafoglou, Kyriakie

Frontiers in endocrinology

2023 Volume 14, Page(s) 1227886

Abstract: Introduction: The Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) created separate growth charts for girls and boys because growth patterns and rates differ between sexes. However, scenarios exist in which this ... ...

Abstract	Introduction: The Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) created separate growth charts for girls and boys because growth patterns and rates differ between sexes. However, scenarios exist in which this dichotomizing "girls versus boys" approach may not be ideal, including the care of non-binary youth or transgender youth undergoing transitions consistent with their gender identity. There is therefore a need for growth charts that age smooth differences in pubertal timing between sexes to determine how youth are growing as "children" versus "girls or boys" (e.g., age- and sex-neutral, compared to age- and sex-specific, growth charts). Methods: Employing similar statistical techniques and datasets used to create the CDC 2000 growth charts, we developed age-adjusted, sex non-specific growth charts for height, weight, and body mass index (BMI), and z-score calculators for these parameters. Specifically, these were created using anthropometric data from five US cross-sectional studies including National Health Examination Surveys II-III and National Health and Nutrition Examination Surveys I-III. To illustrate contemporary clinical practice, we overlaid our charts on CDC 2000 girls and boys growth charts. Results: 39,119 youth 2-20 years old (49.5% female; 66.7% non-Hispanic White; 21.7% non-Hispanic Black) were included in the development of our growth charts, reference ranges, and z-score calculators. Respective curves were largely superimposable through around 10 years of age after which, coinciding with pubertal onset timing, differences became more apparent. Discussion: We conclude that age-adjusted, sex non-specific growth charts may be used in clinical situations such as transgender youth in which standard "girls versus boys" growth charts are not ideal. Until longitudinal auxological data are available in these populations, our growth charts may help to assess a transgender youth's growth trajectory and weight classification, and expectations surrounding these.
MeSH term(s)	United States/epidemiology ; Humans ; Female ; Adolescent ; Male ; Child, Preschool ; Child ; Young Adult ; Adult ; Gender Identity ; Transgender Persons ; Cross-Sectional Studies ; Growth Charts ; Sexual Behavior
Language	English
Publishing date	2023-08-11
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2023.1227886
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