Comparative Analysis of Extracellular Vesicles in Polycystic Ovary Syndrome (PCOS), Congenital Adrenal Hyperplasia (CAH), and Premature Adrenarche (PA)
Erica Eugster, MD
Primary Investigator
Manahil Mustafa
Primary Investigator
Brief description of study
What is the purpose of this study?
Extracellular vesicles (EVs) are double-membrane particles that transport proteins, microRNAs (miRNAs), and lipids, playing a crucial role in cell-to-cell communication and reflecting the cellular environment. Recent research has highlighted their potential as biomarkers and therapeutic agents in various adult conditions, yet their role in pediatric endocrine disorders remains largely unexplored. This study aims to investigate the miRNA profiles within EVs from girls with hyperandrogenism due to polycystic ovary syndrome (PCOS), congenital adrenal hyperplasia (CAH), and premature adrenarche (PA) compared with age-matched healthy controls. We hypothesize that EV-derived miRNA in peripheral blood will exhibit distinct profiles unique to each of these conditions that will correlate with clinical and biochemical features such as amenorrhea and hormone concentrations. Our findings could significantly enhance the understanding of EV biology in pediatric conditions and explore the potential for miRNAs to serve as novel biomarkers that could ultimately aid in disease risk assessment and diagnosis.
Detailed description of study
What will happen during the study?
The study will employ a multi-faceted approach to achieve its specific aims, incorporating both quantitative and qualitative methodologies. We will recruit a total of 60 participants, including girls with PCOS (10), CAH (20), and PA (10), along with age-matched healthy controls (20). Blood samples will be collected to isolate EVs and analyze their miRNA content. The overall strategy will include the following key components:
STUDY DESIGN AND METHODS
1. Participant Recruitment: We aim to recruit a total of 60 participants from our Pediatric Endocrine Clinic. Two groups will be established:
o Group 1: 10 girls diagnosed with PCOS, 10 age-matched girls with classic CAH, and 10 healthy age-matched controls.
o Group 2: 10 girls with PA, 10 age-matched girls with classic CAH, and 10 healthy age-matched controls.
Eligibility of study
You may be eligible for this study if you meet the following criteria:
- Conditions: Polycystic Ovary Syndrome, PCOS, Congenital Adrenal Hyperplasia, CAH, Premature Adrenarche, Riley
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Age: 3 years - 18 years
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Gender: Female
Inclusion and exclusion criteria for group 1
Inclusion criteria
• Girls with PCOS or CAH age 12 < 18 years
• Healthy control girls aged 12 18 years.
• Confirmed diagnosis of PCOS by the presence of clinical and/or biochemical hyperandrogenism (elevated free testosterone)
• Confirmed diagnosis of classic CAH and followed in the Riley pediatric endocrine clinic.
• English speaking
Exclusion criteria
• Girls age <12 or >18 years
• Presence of other causes of anovulation and androgen excess such as non-classical congenital adrenal hyperplasia (NC-CAH), Cushing syndrome, androgen-secreting tumors, hyperprolactinemia, thyroid disease, and drug-induced.
• Boys.
• Pregnant girls
• Non-English speaking.
Inclusion and exclusion criteria for group 1
Inclusion Criteria
• Girls with PA or CAH ages 3 to 9 years
• Healthy controls girls ages 3 to 10 years.
• Confirmed diagnosis of PA defined as early (<8 years) onset of adult body odor, pubic hair or axillary hair) in addition to elevated DHEAs level.
• Diagnosis of classic CAH and followed in the Riley pediatric endocrine clinic.
• English speaking.
Exclusion Criteria
• Girls age <3 or >10.
• Girls with evidence of central precocious puberty
• Other causes of early puberty (such as adrenal tumors, non-classic congenital adrenal hyperplasia, or exposure to androgens)
• Boys
• Non-English speaking.
