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Increased abdominal adiposity in adolescents with classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency

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Increased abdominal adiposity in adolescents with classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency

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Content

Master

of Science in Clinical, Biomedical, and Translational
Investigations

Department of Preventive Medicine, Keck School of Medicine of USC

Increased Abdominal Adiposity in Adolescents with Classical
Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

Master of Science Candidate: Mimi S. Kim
December, 2014

This thesis is dedicated to my mentors,
who have allowed me to stand on their shoulders to reach for the stars.

This thesis is also dedicated to John and Liam Engelke.

Table of Contents

Page 1 …………………………………………. Body of Text
Page 13 …………………………………………. References
Page 17 …………………………………………. Table 1
Page 18 …………………………………………. Table 2
Page 19 …………………………………………. Table 3
Page 20 …………………………………………. Figure

Title Page Picture: Single-slice cross-sectional computed tomography image of
abdominal adiposity in an adolescent with congenital adrenal
hyperplasia.

Introduction
Obesity rates in youth with classical congenital adrenal hyperplasia (CAH) due to
21-hydroxylase deficiency exceed the alarmingly high rates seen in children and
adolescents today (1-4). Sixteen percent of youth are obese in the U.S. (5), and an
even greater percentage of CAH children and adolescents are obese. Since obesity is a
key risk factor for cardiovascular disease (CVD), the heightened prevalence of obesity
in CAH youth could result in increased rates of metabolic sequelae and CVD in
adulthood in this population. Studies have suggested specific hormonal imbalances
inherent in classical CAH as likely to contribute to obesity and the CVD risk in these
patients, including hyperandrogenism, and life-long glucocorticoid therapy often at
supraphysiological doses to suppress adrenal androgen production (1, 6, 7). As well,
circulating concentrations of the adipokine leptin are abnormally elevated in both CAH
and obese individuals, and are important in the modulation of food intake, insulin
sensitivity, and energy homeostasis through central and peripheral pathways. It is
important to better understand the role of these select hormonal imbalances in the
development of obesity in CAH. In addition, CAH could potentially serve as a model to
better understand classical sex differences in the prevalence of CVD in the general
population.
Studies thus far have found increased fat mass in CAH youth, using simple skin-
fold thickness and bioelectrical impedance analysis measures (4, 8). It has been shown
that this increase in fat develops progressively during childhood (4), even in children
under good hormonal control. This increase in fat mass has also been found in young
adults with CAH by using whole-body dual-energy x-ray absorptiometry (WB DXA) to
1

more precisely quantify fat distribution (9). These fundamental studies of fat mass allow
us to now further explore what the role of fat could be in the development of CVD risk in
CAH.
Once thought of as a storage depot for energy, adipose tissue is now seen as an
endocrine organ with multiple metabolic functions (10). We now also know that the
specific location of the fat depot is more important than total body fat. Abdominal
adiposity has come to represent a key contributing factor in the risks conferred by
obesity, and is positively associated with increased risk for metabolic disease,
independent of total body adiposity (11). Visceral adipose tissue (VAT) is of particular
concern because it is highly inflamed in individuals with obesity and metabolic
syndrome (12), and may produce inflammatory substances associated with CVD.
Currently, little is known about the metabolic role of abdominal adipose tissue in CAH
patients, and imaging studies of specific fat depots have yet to be performed in this at-
risk cohort.
Therefore, we sought to study abdominal adiposity in adolescents with classical
CAH, with a focus on characterizing visceral and subcutaneous adipose tissue (SAT)
with computed tomography (CT) imaging. We hypothesized that abdominal adiposity
would be increased in adolescents with CAH, compared to controls matched for
variables known to affect adiposity. To address implications in CAH, we measured
metabolic and inflammatory markers in adolescents with CAH. To address the
relationship between hyperandrogenism and abdominal adiposity, we also quantified
androgens and hormonal control in adolescents with CAH.

2

Participants and Methods
The study was cross-sectional and approved by the Children’s Hospital Los
Angeles Institutional Review Board (IRB). Patients 18 years or older and parents of
participating children gave written informed consent, and all minors at least 7 years of
age gave assent.
We studied 28 adolescents with CAH recruited from the Pediatric Endocrinology
clinic, and rigorously matched for age, sex, ethnicity, and body mass index (BMI) to
healthy controls (other than overweight/obesity). Controls were recruited from the
General Pediatric and Endocrinology clinics at our center. Anthropometric measures of
height (cm) and weight (kg) were obtained in all participants. Waist circumference (WC)
was measured from CT images using Synedra View (Synedra Information
Technologies, Innsbruck, Austria). Abnormal WC was defined using the CDC criteria of
> 90
th
percentile if < 20 years old (13), >102 cm for adult males, and > 88 cm for adult
females (14). BMI (kg/m
2
) and waist-to-height ratios (WHtR) were calculated. WHtR is
emerging as an important measure of abdominal obesity, with a strong predictive value
for metabolic syndrome and CVD risk (15) and an abnormal WHtR was defined as > 0.5
(16).
CT imaging
A single, cross-sectional CT slice (CT HiLight Advantage, GE Medical Systems,
Milwaukee, WI) was used to quantify VAT and SAT at the level of the umbilicus. Studies
were obtained using the following settings: 80 kVp, 70 mA, 2 s, 1-cm slice thickness,
and a required time of 5–10 min. Analyses were performed using a graphical interface
created with Matlab (The Mathworks, Natick, MA). VAT and SAT were defined as
3

previously described (17), and determined by measuring voxels in the area with
negative Hounsfield units, after manually excluding bowel for VAT analyses. Intra- and
inter-coefficients of variation for repeated measurements ranged from 1-3% (18).
Visceral-to-subcutaneous fat ratio (VAT:SAT) was calculated.
CAH adolescents: Additional measures
After an overnight (12 h) fast, and prior to routine morning CAH medications,
CAH adolescents had their blood drawn at the Clinical Trials Unit for genotyping and
measurement of analytes. Analytes were measured at Quest Diagnostics Nichols
Institute (San Juan Capistrano, CA) as follows: leptin by electrochemiluminescence;
insulin, sex hormone binding globulin (SHBG), and plasminogen activator inhibitor-1
(PAI-1) by radioimmunoassay; 17-hydroxyprogesterone (17-OHP), androstenedione,
plasma renin activity (PRA), and total and free testosterone by liquid chromatography
tandem mass spectrometry; high-sensitivity C-reactive protein (hs-CRP) by
nephelometry; and plasma catecholamines by high-performance liquid chromatography.
Glucose and lipids [total cholesterol, low-density lipoprotein (LDL), high-density
lipoprotein (HDL), very low density lipoprotein (VLDL), and triglycerides] were analyzed
at the Children’s Hospital Los Angeles Laboratory (Los Angeles, CA).CYP21A2
mutations were determined by Multiplex Ligation Probe Analysis (Esoterix Laboratory
Services, Calabasas Hills, CA). Insulin sensitivity was quantified by calculated
homeostasis model assessment of insulin resistance [HOMA-IR; (fasting insulin µIU/mL
x fasting glucose mmol/L)/22.5]. Elevated HOMA-IR index was defined as > 3.16 in
adolescents (19) and > 2.5 in adults.
4

Blood pressure was determined from the average of three separate
measurements. For youth < 20 years old, prehypertensive was classified as SBP or
DBP 90-94
th
percentile, and hypertensive as SBP or DBP ≥ 95
th
percentile. For adults ≥
20 years old, prehypertensive was classified as SBP 120-140 mmHg or DBP 80-90
mmHg, and hypertensive as SBP ≥ 140 or DBP ≥ 90 mmHg. WB DXA (Hologic Delphi
W, Bedford, MA) was used to assess total fat mass and regional body fat distribution
(e.g. trunk and arm fat). Metabolic syndrome was assessed using International Diabetes
Federation criteria (20).
Glucocorticoid dose equivalencies for longer-acting formulations were calculated
based on their growth-suppressing effects compared to hydrocortisone: prednisone
dose was multiplied by 5 and dexamethasone dose was multiplied by 80 (21). Medical
history and family history pertaining to CVD, hypertension, type 2 diabetes, and
smoking were obtained.
Statistical analyses
Measures of paired-samples t-tests and Wilcoxon signed rank tests were used to
determine whether there were statistically significant differences between CAH and
matched controls. Bivariate associations such as Pearson's product-moment
correlations and Spearman's rank-order correlations were performed to assess various
relationships within the CAH group. Data are reported as mean ±SD. Analyses were
performed using SPSS (V.21, IBM Corp., Armonk, NY). All P-values have been
adjusted using the Benjamini-Hochberg false discovery rate controlling procedure to
address false positive results that may arise from performing multiple statistical
comparisons (22, 23). Nominal P-values associated with the entire set of comparisons
5

were ordered, adjusted critical values based on the ordered position of the test were
computed, and the nominal P-values were compared to the adjusted critical values to
ascertain statistical significance. Using this procedure, three comparisons previously
considered to be significant at P<0.05 (correlations between VAT and HDL cholesterol,
catecholamine, and Vitamin D levels) were excluded after adjustment for multiple
comparisons. Adjusted significance levels are presented in the text and tables.
Results
Baseline characteristics
Baseline characteristics of CAH and control adolescents are shown in Table 1.
The CAH group was confirmed to have 21-hydroxylase deficiency by genotype. It was
comprised of 71% salt-wasting type and 29% simple-virilizing type, as determined by
genotype for 90.5% of the cohort; six subjects with multiple heterozygous mutations
identified on PCR analysis were classified based on clinical phenotype. Of the CAH
subjects, 60.7% were overweight or obese, and 53% had an abnormal WHtR. Seventy-
five percent of CAH youth < 20 years old were normotensive, 11% were
prehypertensive, and 14% were hypertensive. The four young adults with CAH ( ≥ 20
years old) had normal blood pressures. Only one CAH adolescent had metabolic
syndrome.
The mean glucocorticoid dose was 19.5 ±5.4 mg/m
2
/d of hydrocortisone
equivalents with nine patients on a longer-acting glucocorticoid (eight were on
dexamethasone). The average fludrocortisone dose was 0.1 ±0.05 mg/d, with four
simple-virilizing patients not on this treatment. CAH males had a mean 17-OHP level of
9725.2 ±9844 ng/dL (SI unit conversion x 0.0302 =nmol/L), androstenedione 284.2
6

±261.1 ng/dL (SI unit conversion x 0.0349 =nmol/L), testosterone 405.9 ±211.5 ng/dL
(SI unit conversion x 0.0347 =nmol/L), free testosterone 63.6 ±34.8 pg/mL (SI unit
conversion x 3.47 =pmol/L), and SHBG 35.7 ±13 nmol/L. CAH females had a mean 17-
OHP level of 2169.1 ±2447.5 ng/dL, androstenedione 124.6 ±79.6 ng/dL, testosterone
21.7 ±14.5 ng/dL, free testosterone 4.1 ±3.7 pg/mL, and SHBG 28.3 ±16.2 nmol/L.
Subjects had a mean PRA 5.42 ±4.74 ng/mL/h (SI unit conversion x 1.0 =mcg/L/h).
Abdominal Adiposity
The main finding of this study was significantly increased abdominal adiposity in
adolescents with CAH compared to controls, for both VAT (Figure 1A; CAH 43.8 ±45.5
vs. controls 26.4 ±29.6 cm
2
) and SAT (Figure 1B; CAH 288.1 ±206.5 vs. controls 226.3
±157.5 cm
2
). The VAT:SAT was also significantly higher in CAH than controls (Figure
1C; CAH 0.154 ±0.067 vs. controls 0.118 ±0.064).
Within the CAH group, additional measures of obesity and body composition
correlated positively with both VAT and SAT, including BMI percentile, WHtR, and trunk
and total body fat mass (Table 2). Arm fat had the same correlations as trunk and total
body fat (data not shown). In terms of circulating metabolic markers, leptin correlated
positively with VAT and SAT (Table 2). Of note, 50% of the CAH cohort had elevated
leptin levels, which were significantly higher in obese (29.2 ±18.9) compared to non-
obese adolescents (9.4 ±7.3; P<0.05) without CAH, and correlated strongly with
measures of obesity [BMI percentile, P<0.05, WHtR, P<0.001, and total fat mass,
P<0.001]. HOMA-IR index was elevated in 18% of patients, and correlated positively
with VAT and SAT (Table 2). Fasting lipids (total cholesterol, LDL, VLDL, and
triglycerides) correlated positively with both VAT and SAT as well (Table 2). There were
7

no significant mean differences between hypertension categories, when comparing with
adominal adiposity. Family history for CVD, or CVD risk factors such as smoking,
hypertension, and type 2 diabetes did not show any correlations with abdominal
adiposity.
We found positive correlations between abdominal adipose tissue amount and
inflammatory markers in CAH youth. Both VAT and SAT showed positive correlations
with the adipokine PAI-1 and with hs-CRP which is known to correlate with CVD risk in
adults [Table 2; (24)]. Vitamin D levels, which play a role in reducing inflammation, did
not show significant correlations with VAT and SAT. Twenty-seven percent of CAH
adolescents were Vitamin D deficient.
Among adolescents with CAH, we found no sex difference in VAT (males 47.2
±60.1 vs. females 40.8 ±29.5 cm
2
) or SAT (males 246 ±198.1 vs. females 324.6 ±213.4
cm
2
). We also did not find a sex difference in our controls for VAT (males 25.4 ±33.8 vs.
females 27.4 ±26.5 cm
2
) or SAT (males 180.5 ±134.7 vs. females 265.9 ±169.3 cm
2
).
Although serum androgen levels did not show significant correlations with abdominal
adiposity in CAH, there was a negative correlation between SHBG and both VAT and
SAT (Table 3). There were no correlations between other markers of hormonal control
(17-OHP), or glucocorticoid dose with VAT or SAT in the CAH group. Total
catecholamines were only measured in six subjects, and so statistical associations
between catecholamines and adiposity were not significant.
Family history for CVD or CVD risk factors including smoking, hypertension, and
type 2 diabetes did not show any positive correlations with abdominal adipose tissue.

8

Discussion
This study demonstrates that adolescents with CAH have significantly increased
amounts of both visceral and subcutaneous adipose tissue compared to matched
controls, increasing their risk for CVD as they enter adulthood. We already see an
increased prevalence of obesity in adolescents with CAH, above the epidemic rates
seen in normal children, and now we see that CAH adolescents have more unfavorable
fat distribution for the same degree of obesity. This places CAH youth at even greater
risk for harmful metabolic sequelae from obesity. It is probable that a combination of
hormone imbalances inherent in CAH contributes to the abnormal development of
adipose tissue and its function.
Over the past two decades, there has been an increasing focus in obese
individuals on specific regions of fat accumulation, in particular VAT (11), and adipose
tissue is now regarded as an active endocrine organ. Rich in macrophages, and
producing adipokines such as PAI-1, VAT is well-known to play a harmful role in obesity
and actively promotes inflammation in the body (24). The strong correlations between
VAT and several adipokines/inflammatory markers (leptin, PAI-1, and hs-CRP) in our
CAH youth support this potentially pathological role of VAT. The implications of
increased abdominal adipose tissue in CAH include: 1) an association with insulin
resistance and metabolic syndrome in youth (25); 2) adipokines can act centrally and
stimulate regions of the brain regulating appetite; and 3) inflammation is a CVD risk
factor itself (24) and it is possible that adolescents with CAH have similar systemic low-
grade inflammation as obese adolescents without CAH (25). Furthermore, our
adolescents with CAH exhibit a higher VAT:SAT than controls, which is concerning
9

given that the increased proportion of VAT to SAT is known to be a particularly adverse
metabolic phenotype in obese adolescents (25). Although only one CAH adolescent in
our study had metabolic syndrome, we found strong correlations between VAT and the
main components of the metabolic syndrome in our CAH cohort, including obesity,
insulin resistance, and LDL levels.
Patients with CAH have several reasons to develop elevated levels of the
adipokine, leptin, including epinephrine deficiency (26) and an altered leptin axis due to
decreased soluble leptin receptor (27). Our classical CAH cohort exhibited elevated
leptin levels, with a predominance in obese adolescents, similar to other CAH studies
(1, 26, 27). However, it may be the dysregulation of leptin suppression seen in CAH (28)
that is important in the development of obesity in this population. Leptin has already
been implicated with insulin resistance in CAH (26) and acts centrally as a key regulator
of food intake and energy balance. We confirmed that leptin levels correlate with
abdominal adipose tissue, more strongly in SAT, similar to studies of adiposity in
individuals without CAH (29). More study is needed to understand the exact role of
leptin, and related neuroendocrine pathways between abdominal adipose tissue and the
brain, in the development of metabolic sequelae in individuals with CAH.
The inherent hormonal imbalances in CAH of hyperandrogenism and
glucocorticoid deficiency are important to consider in the pathophysiology of obesity in
this cohort, with evidence of crosstalk between androgens and glucocorticoids at the
neuroendocrine and peripheral levels, and functional hyperandrogenism associated with
increased abdominal adiposity in adult women (30). An interesting finding in this study
was the lack of sex differences in CAH adolescents, with regard to abdominal adipose
10

tissue. This finding could suggest a propensity towards an ‘android’ phenotype of
abdominal obesity in females with CAH, secondary to exposure to elevated androgens
over a lifetime. Although our cohort of controls did not show a difference in VAT
between males and females regardless of BMI, normative data show increased VAT in
males compared to females as of late adolescence (15) , with typical sex differences in
body composition primarily attributable to sex steroids (31). It is well known that adult
men have twice the visceral fat of women (17), and there is a known association
between abdominal adiposity and functional hyperandrogenism in women (30) that is
relevant to females with CAH. There could be either a pathological role for excess
androgens or a lack of protective effect from estrogen (6). We did not see significant
correlations between either androstenedione or testosterone with abdominal adipose
tissue in our adolescents with CAH. However, a strong negative correlation between
abdominal adiposity and SHBG was noted in our CAH adolescents, with known
associations between low SHBG levels and higher free testosterone, insulin resistance,
obesity, and dyslipidemia in adults (32, 33). Understanding the mechanisms by which
androgens could potentially equalize sex differences between females and males in
CAH could help understand typical sex differences in CVD. However, untreated CAH
patients would need to be studied in order to better assess the relationship between
hyperandrogenism and adiposity, which would not be ethically possible in classical
CAH. Hormonal control or treatment was not a modulating factor in these patients, with
no correlations between 17-OHP or glucocorticoid doses and abdominal adipose tissue,
despite our patients being on relatively high mean glucocorticoid doses overall.
However, it is known that patients with much higher glucocorticoid levels in Cushing
11

Syndrome have increased visceral adipose tissue and obesity (34), and the contribution
of chronic, supraphysiological glucocorticoid replacement over a lifetime to the
development of CVD risk in CAH needs to be further evaluated.Serum 17-OHP levels
did not correlate with the amount of abdominal adipose tissue, suggesting that hormonal
control was not a modulating factor in these patients.
A limitation of our study was the lack of dietary intake information at the time of
the study visit, and the cross-sectional design. Additionally, we do not have plasma
catecholamine levels for all CAH cases studied. The association between total
catecholamines and abdominal adiposity merits further study in CAH youth, with
implications in the regulation of leptin and lipolysis, in the development of increased
abdominal adiposity in CAH youth.
We conclude that adolescents with CAH exhibit a concerning and likely
pathological tendency towards visceral adiposity.
The combination of pro-inflammatory VAT, hormonal imbalances inherent in
CAH, and increased propensity towards obesity is concerning in these youth. More
studies are necessary to elucidate underlying mechanisms of obesity in CAH, including
neuroendocrine pathways, and the role of catecholamine deficiency in patients with
classical CAH. In the clinical setting, adolescents with classical CAH should be
evaluated for central abdominal obesity, with a simple obesity measure such as WHtR
highly correlating with VAT. We can then target these at-risk individuals for preventive
weight loss and therapeutics to decrease long-term adverse outcomes in CAH.

12

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16

TABLE 1. Clinical Characteristics of Adolescents with CAH Due to 21-Hydroxylase Deficiency
and Matched Controls

CAH (N = 28) Control (N = 28)
Gender (Female) 15 15
Age (years)
†
15.6 ± 3.2 16.7 ± 2.3
Ethnicity
†

19 (68%) Hispanic
5 (18%) Non-Hispanic
white
3 (11%) Asian
1 (3%) African-American
19 (68%) Hispanic
5 (18%) Non-Hispanic
white
3 (11%) Asian
1 (3%) African-American
Weight (kg) 67.5 ± 17.7 74 ± 18.6
Height (cm) 156.5 ± 10.5 164.8 ± 8.3 **
Body Mass Index (BMI; kg/m
2
)
†
27.8 ± 8.2 27.2 ± 6.7
Waist Circumference (cm) 84.80 ± 15.29 90.68 ± 15.32
Waist-to-Height 0.55 ± 0.11 0.55 ± 0.10
Glucocorticoid Dose (mg/m
2
/d) 19.5 ±5.4 N/A
Fludrocortisone Dose (mg/d) 0.1 ±0.05 (N = 24) N/A
†
Matching criteria. Mean ± SD
** P < 0.01
17

TABLE 2. Abdominal Fat: Correlations with Body Composition, and Metabolic and
Inflammatory Markers in Adolescents with CAH due to 21-Hydroxylase Deficiency
VAT SAT
Body Composition
BMI Percentile 0.44 * 0.92 ***
WC 0.82 ** 0.95 ***
WHtR 0.84 ** 0.96 ***
Trunk Fat Mass 0.75 *** 0.94 ***
Total Fat Mass 0.75 *** 0.96 ***
Metabolic
Leptin 0.43 * 0.73 ***
HOMA-IR 0.54 * 0.52 *
Total Cholesterol 0.61 ** 0.60 **
HDL 0.39 0.16

LDL 0.50 * 0.58 **
VLDL 0.53 * 0.47 *
TG 0.52 * 0.47 *
Inflammatory
PAI-1 0.56 ** 0.48 *
hs-CRP 0.42 * 0.63 **
25-hydroxy Vitamin D -0.39 * -0.50 **
* P < 0.05; ** P < 0.01; *** P < 0.001
VAT, visceral adipose tissue; SAT, subcutaneous adipose tissue; BMI, body mass index; WC,
waist circumference; WHtR, waist-to-height; HOMA-IR, homeostasis model assessment of
insulin resistance; HDL, high-density lipoprotein; LDL, low-density lipoprotein; VLDL, very low
density lipoprotein; TG, triglycerides; PAI-1, plasminogen activator inhibitor-1; hs-CRP, high-
sensitivity C-reactive protein.

18

TABLE 3. Abdominal Fat Correlations with Androgens and Hormonal Control in
Adolescents with CAH due to 21-Hydroxylase Deficiency

VAT SAT
Sex hormone binding globulin -0.45* -0.56**
Testosterone -0.07 -0.17
Androstenedione -0.20 -0.29
17-hydroxyprogesterone -0.14 -0.17
Glucocorticoid Dose 0.07 0.004

* P < 0.05; ** P < 0.01

19

Figure 1. Abdominal adiposity in adolescents with classical CAH and matched controls.
A. Visceral adipose tissue (VAT) is higher in adolescents with CAH compared to
controls (P < 0.001). B. Subcutaneous adipose tissue (SAT) is higher in adolescents
with CAH compared to controls (P = 0.001). C. Visceral-to-subcutaneous adipose tissue
ratio (VAT:SAT) is higher in adolescents with CAH compared to controls (P = 0.01).
A
B
CAH Control
0
20
40
60
Mean Visceral Fat (cm
2
)

CAH Control
0
100
200
300
400
Mean Subcutaneous Fat (cm
2
)

*
*
20

C
CAH Control
0.00
0.05
0.10
0.15
0.20
VAT:SAT

*
21

Abstract (if available)

Abstract Context: Childhood obesity rates in congenital adrenal hyperplasia (CAH) exceed the high rates seen in normal children, potentially increasing their risk of cardiovascular disease (CVD). Abdominal adiposity, in particular visceral adipose tissue (VAT), is strongly associated with metabolic syndrome and CVD. However, it remains unknown whether VAT is increased in CAH youth. ❧ Objective: To determine if adolescents with classical CAH have more VAT and subcutaneous adipose tissue (SAT) than matched controls. Also, to determine whether VAT and SAT are associated with biomarkers of metabolic syndrome, inflammation, and hyperandrogenism in CAH. ❧ Design/Setting: Cross-sectional study at a tertiary center. ❧ Participants: CAH adolescents (N = 28

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Asset Metadata

Creator Kim, Mimi S. (author)

Core Title Increased abdominal adiposity in adolescents with classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency

School Keck School of Medicine

Degree Master of Science

Degree Program Clinical, Biomedical and Translational Investigations

Publication Date 10/31/2014

Defense Date 10/30/2014

Publisher University of Southern California (original), University of Southern California. Libraries (digital)

Tag 21-hydroxylase,adiposity,androgens,cardiovascular disease,congenital adrenal hyperplasia,OAI-PMH Harvest,obesity

Format application/pdf (imt)

Language English

Contributor Electronically uploaded by the author (provenance)

Advisor Azen, Stanley P. (committee chair), Geffner, Mitchell (committee chair), Mittelman, Steven D. (committee member)

Creator Email mimikim09@gmail.com,mskim@chla.usc.edu

Permanent Link (DOI) https://doi.org/10.25549/usctheses-c3-510753

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Legacy Identifier etd-KimMimiS-3049.pdf

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Document Type Thesis

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Rights Kim, Mimi S.

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Source University of Southern California (contributing entity), University of Southern California Dissertations and Theses (collection)

Access Conditions The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the a...

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