Development
Conditions
Keywords
adolescents, puberty, androgens, hyperandrogenemia
Brief summary
In girls with elevated androgens the precise source of androgen excess throughout puberty and early adolescence has not been carefully examined. The investigators propose to examine whether the adrenal gland produces the majority of androgens during puberty by studying the differences in androgen responses to adrenocorticotropin hormone (ACTH) administration in normal weight (NW) and obese (OB) girls ages 7-18. The investigators' analyses will compare steroid changes before and 60 min after ACTH administration in NW and OB girls.
Detailed description
Subjects will have blood drawn at 1900 hr for baseline hormone measurements. At 2200 hr each subject will take a single oral dose of dexamethasone at 2200 hr. At 0700 hr the following day, subjects will have a blood sample drawn for hormone measurements. After this blood sample, 0.25 mg adrenocorticotropin hormone (ACTH) will be administered as an iv bolus. At 30 and 60 minutes after Cosyntropin, blood samples will be obtained for repeat hormone measurements.
Interventions
Subjects will have blood drawn at 1900 hr for baseline hormone measurements. At 2200 hr each subject will take a single oral dose of dexamethasone at 2200 hr. At 0700 hr the following day, subjects will have a blood sample drawn for hormone measurements. After this blood sample, adrenocorticotropin (ACTH) will be administered as an iv bolus. At 30 and 60 minutes after Cosyntropin, blood samples will be obtained for repeat hormone measurements.
DRUGDexamethasone
Subjects will have blood drawn at 1900 hr for baseline hormone measurements. At 2200 hr each subject will take a single oral dose of dexamethasone at 2200 hr. At 0700 hr the following day, subjects will have a blood sample drawn for hormone measurements. After this blood sample, 0.25 mg adrenocorticotropin (ACTH) will be administered as an iv bolus. At 30 and 60 minutes after Cosyntropin, blood samples will be obtained for repeat hormone measurements.
Sponsors
University of California, San Diego
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
7 Years to 18 Years
Healthy volunteers
Yes
Inclusion criteria
* Normal CBC (Hemoglobin must be at least 11mg/dl) * Normal renal and liver function tests (AST& ALT 10-45 IU/L; Albumin 3.3-5 g/dL; Alk phos 30-130 IU/L; * direct bili \<0.2 mg/dL; * total bili \<1.2 mg/dL; total protein 6.0-8.0 g/dL) Normal vital signs including normal blood pressure (pulse 60-100/min, respirations 12-20/min, BP 80/60-130/80)
Exclusion criteria
* Pregnancy * On oral contraceptives * On insulin lowering drugs * On anti-androgens (i.e., spironolactone, flutamide, finasteride, etc) * On medications that will influence androgen metabolism or clearance * On medications that will inhibit the cytochrome P450 enzyme system (cimetidine, ketoconazole, etc) * Subjects with morning cortisol\<5 ug/dL will be excluded and asked to see their primary care physician. * Subjects with 17-OHP\>250 ng/dL) will be excluded and asked to see their primary care physician. * Subject with a history of Cushing syndrome or adrenal insufficiency will be excluded
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 17-hydroxyprogesterone Response to ACTH | 0 and 60 minutes after ACTH administration | 17-hyrooxyprogesterone levels before and after ACTH |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Free Testosterone Response to ACTH | 0 and 60 min after ACTH administration | Free Testosteorne levels before and after ACTH |
| Androstenedione Response to ACTH | 0 and 60 min after ACTH administration | Androstenedione levels before and after ACTH |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Early Puberty Group Subjects were subdivided into normal weight and overweight groups. Subjects will have blood drawn at 1900 hr for baseline measurements. At 2200 hr each subject will take dexamethasone. At 0700 hr the following day, subjects will have a blood drawn for hormone measurements. After this adrenocorticotropin (ACTH) will be administered as an iv bolus. At 30 and 60 minutes after ACTH, blood will be obtained for repeat hormone measurements.
Adrenocorticotropin: Subjects will have blood drawn at 1900 hr for baseline hormone measurements. At 2200 hr each subject will take a oral dose of dexamethasone at 2200 hr. At 0700 hr the following day, subjects will have a blood drawn for hormone measurements. After this, adrenocorticotropin (ACTH) will be administered. At 30 and 60 minutes after Cosyntropin, blood samples will be obtained for repeat hormone measurements.
Dex | 10 |
| Late Puberty Group Subjects were further subdivided into normal weight and overweight groups. Subjects will have blood drawn at 1900 hr for baseline measurements. At 2200 hr each subject will take dexamethasone. At 0700 hr the following day, subjects will have a blood drawn for hormone measurements. After this, adrenocorticotropin (ACTH) will be administered. At 30 and 60 minutes after ACTH, blood will be obtained for repeat hormone measurements.
Adrenocorticotropin: Subjects will have blood drawn at 1900 hr for baseline hormone measurements. At 2200 hr each subject will take dexamethasone at 2200 hr. At 0700 hr the following day, subjects will have a blood drawn for hormone measurements. After this, adrenocorticotropin (ACTH) will be administered as an iv bolus. At 30 and 60 minutes after Cosyntropin, blood samples will be obtained for repeat hormone measurements.
Dex | 40 |
| Total | 50 |
Baseline characteristics
| Characteristic | Early Puberty Group | Late Puberty Group | Total |
|---|---|---|---|
| Age, Continuous Normal Wieght | 9.8 years STANDARD_DEVIATION 1 | 13.9 years STANDARD_DEVIATION 0.9 | 12.1 years STANDARD_DEVIATION 1 |
| Age, Continuous Overweight | 9.4 years STANDARD_DEVIATION 0.7 | 14.9 years STANDARD_DEVIATION 0.4 | 12.4 years STANDARD_DEVIATION 0.6 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 10 Participants | 40 Participants | 50 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 40 |
| other Total, other adverse events | 0 / 10 | 0 / 40 |
| serious Total, serious adverse events | 0 / 10 | 0 / 40 |
Outcome results
Primary
17-hydroxyprogesterone Response to ACTH
17-hyrooxyprogesterone levels before and after ACTH
Time frame: 0 and 60 minutes after ACTH administration
Population: Analysis is performed on a normal weight group comprised of 4 early puberty and 10 late puberty girls and an overweight group of 6 early puberty and 30 late puberty girls
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Early Puberty Group | 17-hydroxyprogesterone Response to ACTH | Normal Weight | 2.4 ng/mL | Standard Error 0.5 |
| Early Puberty Group | 17-hydroxyprogesterone Response to ACTH | Over Weight | 2.9 ng/mL | Standard Error 0.4 |
| Late Puberty Group | 17-hydroxyprogesterone Response to ACTH | Normal Weight | 3.7 ng/mL | Standard Error 0.8 |
| Late Puberty Group | 17-hydroxyprogesterone Response to ACTH | Over Weight | 3.1 ng/mL | Standard Error 0.7 |
| Total Number | 17-hydroxyprogesterone Response to ACTH | Normal Weight | 3.1 ng/mL | Standard Error 0.6 |
| Total Number | 17-hydroxyprogesterone Response to ACTH | Over Weight | 3.0 ng/mL | Standard Error 0.6 |
Secondary
Androstenedione Response to ACTH
Androstenedione levels before and after ACTH
Time frame: 0 and 60 min after ACTH administration
Population: Analysis is performed on a normal weight group comprised of 4 early puberty and 10 late puberty girls and an overweight group of 6 early puberty and 30 late puberty girls
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Early Puberty Group | Androstenedione Response to ACTH | Normal Wieght | 0.5 ng/mL | Standard Error 0.1 |
| Early Puberty Group | Androstenedione Response to ACTH | Overweight | 0.6 ng/mL | Standard Error 0.2 |
| Late Puberty Group | Androstenedione Response to ACTH | Normal Wieght | 1.6 ng/mL | Standard Error 0.3 |
| Late Puberty Group | Androstenedione Response to ACTH | Overweight | 3.1 ng/mL | Standard Error 0.7 |
Secondary
Free Testosterone Response to ACTH
Free Testosteorne levels before and after ACTH
Time frame: 0 and 60 min after ACTH administration
Population: Analysis is performed on a normal weight group comprised of 4 early puberty and 10 late puberty girls and an overweight group of 6 early puberty and 30 late puberty girls
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Early Puberty Group | Free Testosterone Response to ACTH | Normal weight | 2 pmol/L | Standard Error 0.3 |
| Early Puberty Group | Free Testosterone Response to ACTH | Overweight | 3.5 pmol/L | Standard Error 0.4 |
| Late Puberty Group | Free Testosterone Response to ACTH | Normal weight | 7 pmol/L | Standard Error 1 |
| Late Puberty Group | Free Testosterone Response to ACTH | Overweight | 32 pmol/L | Standard Error 3 |