The Adrenal Contribution to Androgen Production in Girls During Puberty

Study Overview
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Brief Summary
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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
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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.

Official Title
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The Adrenal Contribution to Androgen Production in Girls During Puberty

Conditions
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Development

Intervention / Treatment
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* Drug: Adrenocorticotropin
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Obese group<br>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 ACTH, blood samples will be obtained for repeat hormone measurements. | Drug: Adrenocorticotropin<br>* 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.<br>* Other names: ACTH;Drug: Dexamethasone<br>* 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.<br>* Other names: dex;|
| Experimental: Nonobese group<br>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 ACTH, blood samples will be obtained for repeat hormone measurements. | Drug: Adrenocorticotropin<br>* 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.<br>* Other names: ACTH;Drug: Dexamethasone<br>* 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.<br>* Other names: dex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 17-hydroxyprogesterone Response to ACTH | 17-hyrooxyprogesterone levels before and after ACTH | 0 and 60 minutes after ACTH administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Free Testosterone Response to ACTH | Free Testosteorne levels before and after ACTH | 0 and 60 min after ACTH administration | 
| Androstenedione Response to ACTH | Androstenedione levels before and after ACTH | 0 and 60 min after ACTH administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adolescents, puberty, androgens, hyperandrogenemia