Mitchell E Geffner

University of Southern California | USC · Department of Pediatrics

Context Low bone mineral density (BMD) has been reported in children and adolescents living with perinatally-acquired HIV (PHIV). Little is known about their bone accrual through puberty compared to an uninfected healthy cohort. Objective To compare bone accrual in PHIV and healthy children. Design PHIV children aged 7-16 years had dual energy X-...

Turner syndrome affects 50 per 100,000 females, affects multiple organs through all stages of life, necessitating multidisciplinary care. This guideline extends previous ones and includes important new advances, within diagnostics and genetics, estrogen treatment, fertility, co-morbidities, and neurocognition and neuropsychology. Exploratory meetin...

Introduction: Studies of gonadotropin-releasing hormone analogues (intramuscular [IM] leuprolide acetate [LA] and triptorelin) for treatment monitoring of central precocious puberty (CPP) demonstrate this approach is effective for confirming pubertal hormone suppression. Herein, we provide new data using subcutaneous LA (SC LA), suggesting similar...

The relationships between alterations in the intestinal barrier, and bacterial translocation with the development of metabolic complications in youth with perinatally-acquired HIV (YPHIV) have not been investigated. The PHACS Adolescent Master Protocol enrolled YPHIV across 15 U.S. sites, including Puerto Rico, from 2007-2009. For this analysis, we...

Background There are little data on changes in insulin sensitivity during the first few years of life following in utero human immunodeficiency virus (HIV) and antiretroviral (ARV) exposure. Methods The Tshilo Dikotla study enrolled pregnant persons with HIV (PWH) (receiving tenofovir/emtricitabine or lamivudine plus dolutegravir or efavirenz) and...

The Kabi International Growth Study (KIGS) was first established in 1987 and is the largest pharmaco-epidemiological study of recombinant human growth hormone (rhGH). KIGS is aimed at evaluating long-term safety and treatment outcomes in pediatric subjects who received Genotropin rhGH therapy (Pfizer, New York, NY, USA) as prescribed by physicians...

Introduction: Patients with classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency exhibit an increased prevalence of obesity from childhood including central adiposity and inflammation. There is also an emerging affected brain phenotype in CAH, with decreased cortico-limbic gray matter volumes and white matter abnormaliti...

Background: In the last 15 years, the care provided for individuals born with differences of sex development (DSD) has evolved, with a strong emphasis on interdisciplinary approaches. However, these developments have not convinced some stakeholders to embrace the current model of care. This care model has also paid insufficient attention to socio-c...

A Pediatric Endocrine Society (PES) Drugs and Therapeutics Committee workgroup sought to determine the prescribing practices of pediatric endocrinologists when treating children <10 years of age with congenital adrenal hyperplasia (CAH). Our workgroup administered a 32-question online survey to PES members. There were 187 respondents (88.9% attendi...

Background The role of body fat on metabolic complications remains poorly understood in young people living with perinatally acquired HIV (YPHIV). Objective Our objective was to assess the association of changes in adiposity over 2 years with metabolic outcomes in YPHIV. Methods The PHACS Adolescent Master Protocol (AMP) study enrolled YPHIV from...

Disclosure: A. Larkin: None. C. Capparelli: None. B.S. Miller: Advisory Board Member; Self; Abbvie, Vertice, Ascendis, Bristol-Myers Squibb, Biomarin, Tolmar, Novo Nordisk, Pfizer, Inc. Research Investigator; Self; Abbvie, Amicus, Aeterna Zentaris, Amgen Inc, OPKO, Alexion Pharmaceuticals, Inc., Lumos, Novo Nordisk, Lysogene, Pfizer, Inc. M.E. Geff...

Screening for congenital adrenal hyperplasia (CAH) remains heterogenous across geographies—we sought to determine the proportion of non-classical CAH (NCAH) detection by one vs. two newborn screens (NBS) in two U.S. regions. Data were collected at tertiary centers in Houston (HOU) and Los Angeles (LA) on 35 patients with NCAH, comparing patients id...

Aims: To examine the impact of pregnancy on microvascular and cardiovascular measures in women with youth-onset T2D. Methods: Microvascular and cardiovascular measures were compared in in a cohort of 116 women who experienced a pregnancy of ≥ 20 weeks gestation and 291 women who did not among women in the Treatment Options for Type 2 Diabetes in...

Context: Congenital adrenal hyperplasia (CAH) is a genetic disorder which results in hormonal imbalances and decreased brain volumes in regions important for emotional processing. Objective: To examine whether emotion perception differs between youth with CAH and control youth, and if these differences relate to brain volumes. Design: Cross-se...

Introduction: Patients with classical congenital adrenal hyperplasia (CAH) have prenatal and postnatal hormonal imbalances. To characterize the ontogeny of reported brain and behavior changes in older children with CAH, we aimed to study brain structure in infants with CAH compared to healthy controls. Methods: We performed neuroimaging in 16 in...

Background: Testicular adrenal rest tumors (TARTs) increase the risk of infertility in males with classic congenital adrenal hyperplasia (CAH). There is no consensus regarding at what age screening testicular ultrasounds should begin and how often they should be repeated. Furthermore, it is unknown whether patients and parents are aware of the sig...

Objective: Infants and toddlers with classical congenital adrenal hyperplasia (CAH) are at high risk for morbidity/mortality arising from life-threatening adrenal crisis. Management of acute illnesses in CAH requires an understanding of factors leading to emergency department (ED) visits and hospitalizations in the first few years of life. We, the...

Background The role of obesity on long-term metabolic complications remains poorly understood in youth living with perinatally-acquired HIV (YPHIV). Methods The PHACS Adolescent Master Protocol (AMP) study enrolled YPHIV from 2007-2009 across 15 U.S. sites, including Puerto Rico. We included YPHIV aged 7-19 yr with body composition data assessed b...

Context Early initiation of growth hormone (GH) therapy is recommended for short children born small for gestational age (SGA); however, real-world data indicate that treatment is often delayed. Objective To assess the impact of patient age at GH therapy initiation on long-term growth outcomes and safety in short children born SGA. Methods Analys...

Objective: Prenatal exposures, including undernutrition, overnutrition, and parental diabetes, are recognized risk factors for future cardiometabolic disease. There are currently no data on effects of parental diabetes on disease progression or complications in youth-onset type 2 diabetes (T2D). We analyzed effects of parental diabetes history on...

Introduction: The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) trial examined the effects of three treatment arms in a group of racially and ethnically diverse adolescents and youth with type 2 diabetes mellitus. TODAY2 was an observational follow-up study reporting outcomes and complications in these participants after h...

Background Children with growth hormone deficiency (GHD) are treated with recombinant human growth hormone (rhGH), usually administered as a daily subcutaneous injection. Long-acting hGH (LAGH) treatments (approved and in development) have the potential to improve adherence and treatment outcomes. Somatrogon is a LAGH currently being developed as a...

Here we present the design and early findings from CAH-300 /NCT05101902, a prescreening protocol to identify participants who are potentially eligible for the CAH-301 Phase 1/2 treatment trial with BBP-631, an AAV5-based gene therapy for classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD). The CYP21A2 gene encodes...

Noonan, Turner, and Prader-Willi syndromes are classical genetic disorders that are marked by short stature. Each disorder has been recognized for several decades and is backed by extensive published literature describing its features, genetic origins, and optimal treatment strategies. These disorders are accompanied by a multitude of comorbidities...

Background: Few data exist on early-life metabolic perturbations in newborns with perinatal HIV and antiretroviral (ARV) exposure (HEU) but uninfected compared to those without perinatal HIV exposure (HUU). Methods: We enrolled pregnant persons living with HIV (PLHIV) [receiving tenofovir (TDF)/emtricitabine or lamivudine (XTC) plus dolutegravir...

Gonadotropin-releasing hormone agonists (GnRHa's) are the standard treatment for children with central precocious puberty (CPP). We aim to present data on available GnRHa options with an easy-to-review table and discuss factors that influence treatment selection. Five GnRHa's are currently FDA-approved and prescribed in the US and published data su...

Context KIGS is a large, international database (1987-2012) of children treated with recombinant human growth hormone (rhGH) in real-world settings. Objective To evaluate the safety and efficacy of rhGH from the full KIGS cohort Design, Patients, Setting, and Intervention Data were collected by investigators from children with growth disorders tr...

Background: Congenital adrenal hyperplasia (CAH) is a group of genetic disorders that affects the adrenal glands and is the most common cause of primary adrenal insufficiency in children. In the past few decades, magnetic resonance imaging (MRI) has been implemented to investigate how the brain may be affected by CAH. A systematic review was condu...

We report a case of a fetus with a prenatal diagnosis of classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Although CAH is typically assessed postnatally, this fetal case had multiple prenatal clinical assessments made feasible by an interdisciplinary CAH center. The approach facilitated the development and delivery o...

This analysis compared microvascular and cardiac outcomes from women in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study, originally diagnosed with youth-onset Type 2 diabetes between the ages of 10-17 yrs, who experienced a pregnancy lasting 20 wks during the course of the study vs. those without. Pregnancy informat...

Introduction To describe experiences of clitoromegaly in women with congenial adrenal hyperplasia (CAH). Methods CAH females (46XX, >=16 years old) from the United States and Canada were eligible for a cross-sectional online survey (2019-2020) if reporting clitoromegaly (life-long: “growing up with a larger than average clitoris,” secondary: “clit...

Classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is the most common primary adrenal insufficiency in children, involving cortisol deficiency, hyperandrogenism, and cardiometabolic risk. Prior studies have reported that youth with classical CAH have a higher prevalence of the components of metabolic syndrome: obesity,...

Background The association between gut dysfunction and body fat composition in youth living with perinatal HIV infection (YPHIV) has not been investigated. Methods We included YPHIV aged 7-19 years from the Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol with plasma available within 6 months of baseline whole-body dual energy x-ray abso...

Background In persons living with HIV, mitochondrial disease (MD) is difficult to diagnose, as clinical signs are non-specific with inconsistent patterns. Fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) are mitokines elevated in MD patients without HIV, and associated with cardiometabolic comorbidities in adults liv...

Purpose of review: With the rapidly increasing incidence of type 2 diabetes mellitus (T2DM) in youth (as in adults), it is critical to recognize phenotypic markers that can help predict and potentially prevent its onset, and reduce the associated burden of the disease for patients, families, and society. In this review, we summarize the most recen...

Objective: To compare long-term growth between HIV-exposed uninfected children (CHEU) born to women with perinatally-acquired HIV (CHEU-PHIV) and CHEU born to women with non-perinatally-acquired HIV (CHEU-NPHIV). Design: Longitudinal analysis of anthropometric measurements from a U.S.-based multisite prospective cohort study enrolling CHEU and t...

L’hormone de croissance (GH) est indiquée pour le traitement de la petite taille chez les enfants nés petits pour l’âge gestationnel (SGA). Cette analyse a étudié l’effet de l’âge au début de la GH sur l’efficacité et la sécurité à long terme chez les enfants nés SGA. Les enfants nés SGA dans les programmes NordiNet IOS et ANSWER qui étaient prépub...

In individuals with intact thirst and adequate fluid intake, the identification of diabetes insipidus may be challenging due to normal serum sodium levels and normal serum osmolality. In such cases, a water deprivation test can prove critical in indirectly assessing the activity of anti-diuretic hormone within the body. Lack of urinary concentratio...

We investigated the association of metabolic syndrome (MetS) and its components [abdominal obesity, elevated triglycerides (TG), low HDL cholesterol, elevated blood pressure (BP), and impaired fasting glycemia (IFG)] with neurocognitive impairment in youth with perinatally acquired HIV (YPHIV) or who are perinatally HIV-exposed uninfected (YPHEU)....

Youth with classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency exhibit an increased prevalence of obesity, early adiposity rebound, and increased abdominal adiposity compared to unaffected youth. Current obesity management in CAH largely focuses on lifestyle modifications. There is evidence that topiramate therapy is eff...

Context Youth with classical congenital adrenal hyperplasia (CAH) exhibit abnormal adrenomedullary function with decreased epinephrine levels noted in newborns and young infants. Little is known about how this relates to morbidity during the first year of life. Objective To study plasma epinephrine levels in infants with classical CAH and examine...

Background: Few weight management interventions target young children with obesity from low-income minority families. Objective: To conduct a nonrandomized, pragmatic, pilot study of an adapted, evidence-based, weight management program (Kids N Fitness [KNF]) customized for children ages 3-7 years (Kids N Fitness Jr. [KNF-JR]) on changes in adiposi...

Background: Early-life metabolic derangements in HIV-exposed uninfected (HEU) infants have been reported. Methods: Pregnant women with HIV and HIV-uninfected pregnant women were enrolled with their newborns in a US cohort from 2011 to 2015. We measured cord insulin, C-peptide, and metabolic cytokines of HEU and HIV-unexposed uninfected (HUU) new...

Context Gray matter morphology in the prefrontal cortex and subcortical regions, including the hippocampus and amygdala, are affected in youth with classical congenital adrenal hyperplasia (CAH). It remains unclear if white matter connecting these aforementioned brain regions is compromised in youth with CAH. Objective To examine brain white matte...

Noonan syndrome is a common autosomal dominant disorder associated with an increased risk of malignancy. We report a 16-year-old female with Noonan syndrome (KRAS gene variant, Q22R) and diffuse-type tenosynovial giant cell tumor, a proliferative disorder that has been rarely reported in this population. These tumors may represent a complication of...

Introduction: In the randomized "Toddler Turner" study, girls who received growth hormone (GH) starting at ages 9 months to 4 years (early-treated [ET] group) had marked catch-up growth and were 1.6 ± 0.6 SD taller than untreated (early-untreated [EUT]) control girls after 2 years. However, whether the early catch-up growth would result in greater...

Background: Prenatal exposures, including parental nutrition and diabetes (DM) status, are increasingly viewed as risk factors for future cardiometabolic health. There are currently no data on effects of parental DM on disease progression or complications in youth-onset T2D. Aims: To analyze effects of parental history of DM on glycemic outcomes an...

Background There are few data on the prevalence of gestational diabetes (GDM) in pregnant women living with HIV (WLHIV) in sub‐Saharan Africa, particularly those using integrase strand transfer inhibitors such as dolutegravir (DTG). Methods We prospectively enrolled pregnant WLHIV and pregnant women without HIV ≥18 years old in Gaborone, Botswana,...

Background: Youth with congenital adrenal hyperplasia (CAH) have a higher prevalence of obesity, early adiposity rebound, and increased fat mass. Unsuccessful dietary self-control could contribute to obesity, and understanding food-seeking behavior could therefore guide prevention. Dietary decision-making involves key brain regions such as the limb...

The CYP21A2 gene, which encodes the 21-hydroxylase enzyme, plays a critical role in glucocorticoid (GC) and mineralocorticoid synthesis by the adrenal cortex. CYP21A2 pathogenic variants cause 21-hydroxylase deficiency (21OHD), the most common type of CAH, characterized by variable degrees of adrenal insufficiency and androgen excess. Standard trea...

Background: Growth hormone (GH) is indicated for the treatment of short stature in children born small for gestational age (SGA) who fail to show catch-up growth. In pilot studies, early initiation of GH has been associated with favorable growth responses in short SGA children. However, few studies have examined the short- and long-term effects of...

Objective: We assessed differences in mitochondrial function between youth living with perinatal HIV (YPHIV) and youth perinatally HIV-exposed but uninfected (YPHEU). Design: Cross-sectional analysis. Methods: We measured lactate and pyruvate values, as well as mitochondrial Complex I and Complex IV activity in peripheral blood mononuclear cel...

Introduction: Youth with classical congenital adrenal hyperplasia (CAH) have higher prevalence of cardiometabolic risk factors such as obesity, abdominal adiposity, and hypertension. Patients with CAH also exhibit an earlier adiposity rebound (AR) compared to normative populations. However, the predictive relationship between AR and cardiometaboli...

The second-to-fourth digit ratio (2D:4D) has been associated with sexual dimorphism, with a lower 2D:4D in males. A large body of research has relied on the 2D:4D as a proxy for prenatal androgen exposure, and includes reports of relationships between 2D:4D and a wide range of human traits. Here, we examine the validity of the 2D:4D proxy by studyi...

Importance Congenital adrenal hyperplasia (CAH) is the most common primary adrenal insufficiency in children, involving excess androgens secondary to disrupted steroidogenesis as early as the seventh gestational week of life. Although structural brain abnormalities are seen in CAH, little is known about facial morphology. Objective To investigate...

Objective To identify risk factors for glycemic failure in youth with type 2 diabetes (T2D). Methods A retrospective review of HbA1c, anthropomorphic measures, medication records, and laboratory studies was performed using registry data from a dedicated pediatric type 2 diabetes clinic. Latent profile analysis (LPA) was performed to model longitud...

Mitochondrial dysfunction (MD) is linked to cardiometabolic complications, such as obesity and insulin resistance (IR), the frequencies of which are higher in adults living with HIV infection and receiving combination antiretroviral therapies (ARV). ARV-treated youth living with perinatally-acquired HIV infection (YLPHIV) may be especially suscepti...

Background Across numerous settings, bone mineral density for age and sex is lower in children/adolescents living with perinatally-acquired HIV (PHIV) compared to uninfected peers. We assessed incidences of any fracture/any long bone fracture, and osteoporosis prevalence in PHIV and HIV-exposed uninfected (PHEU) participants in the Pediatric HIV/AI...

Purpose: Youth with classical Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency have an increased prevalence of obesity, abdominal adiposity, and fat mass compared to unaffected youth. As well, CAH youth in the United Kingdom (UK) have been found to have an earlier adiposity rebound (AR; rise in BMI corresponding to increased ad...

The second-to-fourth digit ratio (2D:4D) has been associated with sexual dimorphism, with a lower 2D:4D in males. A large body of research has relied on the 2D:4D as a proxy for prenatal androgen exposure, and includes reports of relationships between 2D:4D and a wide range of human traits. Here, we examine the validity of the 2D:4D proxy by studyi...

Purpose: Classical Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency affects 1:15,000 newborns and involves adrenal insufficiency and androgen excess. These hormone abnormalities are evident as early as 7 weeks’ gestation and persist throughout pregnancy. Structural brain abnormalities are also known to occur in CAH, with abnorm...

Objective: In TODAY, 4.5% of obese youth clinically diagnosed with T2D had genetic variants consistent with MODY diagnosis. The course of IS and β-cell function in obese youth with MODY remains unknown. In this secondary analysis we examined IS and β-cell function in MODY vs. non-MODY obese youth at randomization and over time. Methods: Genetic...

Context Classical Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency results in hormone imbalances present both prenatally and postnatally that may impact the developing brain. Objective To characterize gray matter morphology in the prefrontal cortex and subregion volumes of the amygdala and hippocampus in youth with CAH, compar...

Introduction: Testicular adrenal rest tumors (TART) are a known consequence for males with classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. TART are associated with potential infertility in adults. However, little is known about TART in very young males with CAH. Objective: We assessed the presence of TART in newb...

Context: Classical Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency results in hormone imbalances present both prenatally and postnatally that may impact the developing brain. Objective: To characterize gray matter morphology in the prefrontal cortex and subregion volumes of the amygdala and hippocampus in youth with CAH, compa...

INTRODUCTION: Testicular adrenal rest tumors (TART) are a known consequence for males with classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. TART are associated with potential infertility in adults. However, little is known about TART in very young males with CAH. OBJECTIVE: We assessed the prevalence of TART in newbo...

Purpose: Infants and toddlers with classical congenital adrenal hyperplasia (CAH) are at high risk for adrenal crisis and associated sequelae. To better understand acute illness at this early age, we determined the frequency and severity of acute illness and hospitalizations between 0-4 years of age, both within CAH and compared to controls. We als...

Objective: To understand the factors associated with glycemic control after starting insulin in youth with type 2 diabetes following glycemic failure (persistent HbA1c ≥8%) with metformin alone, metformin+rosiglitazone or metformin+lifestyle in the TODAY study. Methods: Change in HbA1c after add-on insulin therapy and the factors predictive of g...

Objective: In the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study, metformin plus rosiglitazone (M + R) maintained glycemic control better than metformin alone (M) or metformin plus lifestyle (M + L) in youth with type 2 diabetes (T2D). We hypothesized that changes in visceral adipose tissue (VAT) and subcutaneous adip...

Background: Youth with classical congenital adrenal hyperplasia (CAH) exhibit up to double the prevalence of obesity, earlier adiposity rebound, and increased abdominal adiposity and total fat mass compared to unaffected individuals. Lifestyle modification often results in suboptimal body mass index (BMI) reduction. Therefore, more aggressive inter...

Adrenal insufficiency (AI) remains a significant cause of morbidity and mortality in children with 1 in 200 episodes of adrenal crisis resulting in death. The goal of this working group of the Pediatric Endocrine Society Drug and Therapeutics Committee was to raise awareness on the importance of early recognition of AI, to advocate for the availabi...

Background: Metabolic perturbations in HIV-exposed uninfected (HEU) obese youth may differ from those in the general obese pediatric population. Methods: Metabolic parameters of obese (Body Mass Index Z-score >95 percentile) HEU youth in the Pediatric HIV/AIDS Cohort Study (PHACS) Surveillance Monitoring of ART Toxicities (SMARTT) study were com...

Individuals with Turner syndrome (TS) have a higher morbidity and mortality compared to the general population. Diabetes and cardiovascular disease are the major contributors to this burden. Precursors to diabetes and cardiovascular disease make up what is known as metabolic syndrome, including abdominal obesity, hypertension, dyslipidemia, and ele...

Background: Disordered bone mineral metabolism and low vitamin D concentrations are associated with cardiovascular abnormalities; few studies have evaluated this relationship in HIV-infected youth. Setting: The Adolescent Master Protocol is a Pediatric HIV/AIDS Cohort Study network study conducted across 14 US sites. Methods: Among perinatally...

Number: 1941 Abstract Type: General Abstract Authors: