Evaluation of Adrenal Androgens in Normal and Obese Girls After Suppression and Stimulation

Evaluation of Adrenal Androgens in Normal and Obese Girls After Suppression and Stimulation (JCM022)

Women with polycystic ovary syndrome (PCOS) often have irregular menstrual periods, too much facial and body hair, and weight gain. Women with PCOS also have a hard time becoming pregnant. Girls with high levels of the male hormone testosterone often develop PCOS as adults. Some girls with high levels of male hormone will develop normal hormone levels as they grow up, but most girls continue to have high levels of male hormone as adults. The purpose of this study is to understand where the male and female hormones come from in girls as they get older. The investigators think the adrenal gland, makes most of the hormones in young girls and that the ovary and the adrenal gland make these hormones in older girls. The investigators would like to find out whether an overactive adrenal gland makes these hormones higher in girls who are overweight, compared to those who are not overweight.

Study Overview

• Status: Active, not recruiting
• Conditions: Obesity; Polycystic Ovary Syndrome; Hyperandrogenemia
• Intervention / Treatment: Drug: Dexamethasone; Drug: Cortrosyn

Detailed Description

We propose that the adrenal gland is the predominant source of the early morning rise in progesterone and testosterone which is more marked in early puberty. Specifically, we hypothesize that dexamethasone administration at 22:00 will be associated with a dampened progesterone and testosterone rise the subsequent morning in normal girls. We also propose that the adrenal gland is the source of the excess androgen production in young obese girls, and that dexamethasone will decrease their early morning testosterone and progesterone levels. We will explore the hypothesis that functional adrenal hyperandrogenism, or ACTH hyperresponsiveness, is one mechanism underlying this excess adrenal androgen production seen in obesity.

• Study Type: Interventional
• Enrollment (Estimated): 84
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Charlottesville, Virginia, United States, 22902
      • University of Virginia Center for Research in Reproduction

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Normal and obese (>95th BMI%) females
• Weight of 24 kg or more
• Early to late puberty (expected age range 7-18)
• Screening labs within age-appropriate normal range, with the exception of a mildly low hematocrit (see below) and the hormonal abnormalities inherent in obesity which could include mildly elevated LH, lipids, testosterone, prolactin, DHEAS, E2, glucose, and insulin; and decreased follicle-stimulating hormone (FSH) and/or sex hormone-binding globulin (SHBG)

Exclusion Criteria:

• Screening labs outside of age-appropriate normal range
• Hemoglobin <12 mg/dL and hematocrit<36% (Subjects will be offered the opportunity to take iron supplementation for 60 days if their hematocrit is slightly low (33-36%) (suggestive of iron deficiency anemia) and will then return for retesting of their hemoglobin/hematocrit. If still <36%, they will be excluded.)
• Morning Cortisol <5 g/dL
• 17-hydroxyprogesterone >295 ng/dL
• Weight<24 kg
• History of Cushing's syndrome or adrenal insufficiency
• Pregnant (self reported)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dexamethasone, Cortrosyn; Dexamethasone given 1 mg PO Cortrosyn given single IV bolus 0f 0.25 mg	Drug: Dexamethasone; 1 mg PO; Drug: Cortrosyn; single IV bolus of 0.25 mg will be administered; Other Names: ACTH

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in progesterone concentrations from the 2100-2300 time block to the 0500-0700 time block in normal weight girls compared to overweight girls.	A primary endpoint for analysis in this study is the change in progesterone concentrations from the 2100-2300 time block to the 0500-0700 time block in normal weight girls compared to overweight girls.	Time frame for the study will be 14 hours (Sampling begins at 1900 hrs and proceeds through 0800 hours the following morning).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overnight changes in male and female hormones in response to ACTH suppression	Secondary endpoints will include overnight changes in testosterone, estradiol, cortisol, dehydroepiandrosterone (DHEA), and luteinizing hormone (LH) pulse patterns in response to adrenocorticotropic hormone (ACTH) suppression. These secondary endpoints will be evaluated in a similar manner to the primary endpoint.	14 hours (Sampling begins at 1900 hours and proceeds through 0800 the following morning)
Response to ACTH stimulation in normal weight and overweight girls	Examine the differences in hormone responses to ACTH in normal weight and overweight girls.	14 hours (1900 - 0800 hrs)

Collaborators and Investigators

• Sponsor: University of Virginia
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); University of California, San Diego
• Investigators: Principal Investigator: Christine Burt Solorzano, MD, University of Virginia

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2006
• Primary Completion (Estimated): August 27, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: August 19, 2011
• First Submitted That Met QC Criteria: August 22, 2011
• First Posted (Estimated): August 23, 2011

Study Record Updates

• Last Update Posted (Actual): October 27, 2023
• Last Update Submitted That Met QC Criteria: October 25, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Endocrine System Diseases; Ovarian Cysts; Cysts; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Polycystic Ovary Syndrome; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone; Cosyntropin
• Other Study ID Numbers: 12702 (Other Identifier: University of Virginia Institutional Review Board for Health Sciences Research); U54HD028934-18 (U.S. NIH Grant/Contract); JCM022 (Other Identifier: University of Virginia)