Sleep-wake Changes of Luteinizing Hormone Frequency in Pubertal Girls With and Without High Testosterone (CRM005)

Community sample and patients from local clinics

Inclusion Criteria:

• Early to midpubertal girls (late Tanner 1 [i.e., estradiol > 20 pg/ml] to Tanner 3)
• Premenarcheal
• Approximate ages, 8-15 years

Exclusion Criteria:

• BMI-for-age < 5th percentile
• Inability to comprehend what will be done during the study or why it will be done
• Being a study of GnRH pulse regulation in adolescent girls with and without HA, boys are excluded
• Obesity associated with a diagnosed (genetic) syndrome (e.g., Prader-Willi syndrome, leptin deficiency), obesity related to medications (e.g., glucocorticoids), etc.
• Pregnancy or lactation
• Virilization
• Total testosterone > 150 ng/dl (confirmed on repeat)
• DHEAS > upper limit of age-appropriate normal range (confirmed on repeat) (mild elevations may be seen in adolescent HA, and elevations < 1.5 times the age-appropriate upper limit of normal will be accepted in such girls)
• Follicular phase 17-hydroxyprogesterone > 250 ng/dl (for girls < 12 years old) or > 300 ng/dl (for girls 12 and older) (confirmed on repeat), which suggests the possibility of congenital adrenal hyperplasia. NOTE: If an elevated follicular 17-hydroxyprogesterone is confirmed on repeat testing, an ACTH stimulated 17-hydroxyprogesterone < 1000 ng/dl will be required for study participation
• History of premature adrenarche (i.e., appearance of pubic and/or axillary hair before age 8)
• A previous diagnosis of diabetes
• Fasting glucose ≥ 126 mg/dl, or a hemoglobin A1c > 6.5% (confirmed on repeat)
• Abnormal TSH (confirmed on repeat) (subjects with adequately treated hypothyroidism, reflected by normal TSH values, will not be excluded)
• Abnormal prolactin (confirmed on repeat) (mild elevations may be seen in HA girls, and elevations < 1.5 times the upper limit of normal will be accepted in this group)
• Evidence of Cushing's syndrome by history or physical exam (e.g., history of impaired growth in children, striae)
• Hematocrit < 36% and hemoglobin < 12 g/dl (confirmed on repeat)
• Significant history of cardiac or pulmonary dysfunction (e.g., known or suspected congestive heart failure; asthma requiring intermittent systemic corticosteroids; etc.)
• Persistent liver test abnormalities (confirmed on repeat), with the exception that mild bilirubin elevations will be accepted in the setting of known Gilbert's syndrome
• Persistently abnormal sodium, potassium, or elevated creatinine concentration (confirmed on repeat)
• Bicarbonate concentrations < 20 or > 30 (confirmed on repeat)

• No medications known to affect the reproductive system, glucose metabolism, lipid metabolism, or blood pressure can be taken in the 3 months prior to the first inpatient GCRC study (or in the 2 months prior to screening)

  • Such medications include oral contraceptive pills, progestins, metformin, glucocorticoids, psychotropics, and sympathomimetics/stimulants (e.g., methylphenidate)
  • Patients taking restricted medications will be excluded unless written permission (for the subjects to discontinue the medication) is received from the subject's physician
• Weight < 22 kg is an absolute exclusion criterion (to ensure safe blood withdrawal)