Effect of Short Term Adrenal Suppression on Androgen Overproduction in Overweight Girls With Androgen Excess

This study will test whether short-term suppression of adrenal function can ameliorate androgen (male hormone) overproduction in overweight girls with androgen excess. The investigators hypothesize that one month of oral hydrocortisone administration will improve androgen levels in girls with adrenal androgen overproduction. Specifically, this intervention will improve androgen levels after adrenal stimulation testing with adrenocorticotropin hormone (ACTH).

• Hydrocortisone (Drug), also known as Cortef: 10 mg/m2/per day PO at bedtime (X4 weeks)

Primary outcomes

• Changes in free testosterone after ACTH administration before and after hydrocortisone administration for 4 weeks [30 and 60 minutes after ACTH, baseline, and after 4 weeks of hydrocortisone administration]

Secondary outcomes

• Changes in adrenal steroid precursors after ACTH, baseline, and after 4 weeks of hydrocortisone administration [30 and 60 minutes after ACTH, baseline, and after 4 weeks of hydrocortisone administration]

Sex: Female, ages: 7 Years to 18 Years

Inclusion Criteria:

* Overweight(>85th BMI%) females
* Early to late puberty (expected age range 7-18)
* Hyperandrogenemic (free testosterone greater than 2.5 standard deviations above the mean for normal control subjects of the same Tanner Stage)
* 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 luteinizing hormone (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
* History of Cushing's syndrome or adrenal insufficiency
* Pregnant

• Christine M. Burt Solorzano, MD, Principal investigator, University of Virginia