The goal of this study is to test whether the hormone kisspeptin has the potential to prospectively diagnose adolescents with self-resolving or permanent delayed puberty. Some children with delayed puberty will eventually enter puberty on their own. However, some children with delayed puberty have a permanent condition and require medical treatment to undergo puberty. Right now, there is no reliable diagnostic tool to tell whether a child's delayed puberty will be self-resolving or permanent. The hormone kisspeptin has the potential to prospectively diagnose adolescents with self-resolving or permanent delayed puberty.

The investigators are seeking boys (ages 13.5-17 years) and girls (ages 12-17) years with a diagnosis of delayed puberty. Study participation involves 2 outpatient visits and two hospital admissions (one 11-hour, overnight admission and one 6-hour day admission) when subjects will receive two investigational drugs, the naturally occurring hormones kisspeptin and gonadotropin-releasing hormone (GnRH). Subjects will then be followed every 6 months until they reach 18 years of age to determine if their pubertal delay was self-resolved or permanent.

Inclusion Criteria:

Adolescent Boys

• ages 13.5-17 years
• testicular volume <4 mL OR 4-8 ml with no change in the past 6 months by Prader orchidometer
• first morning (before 9AM) LH <2 mIU/mL and testosterone <50 ng/dL

Adolescent Girls

• ages 12-17 years
• Tanner stage I OR II breast development with no change in the past 6 months
• first morning (before 9AM) LH <2 mIU/mL and estradiol <20 pg/ml

All Subjects:

• bone age less than chronological age
• weight ≥ 28 kg
• body mass index >10th percentile and <+3 SDS for bone age
• blood pressure >5th percentile and <95th percentile for bone age and height
• white blood cell counts, platelet counts, electrolytes, thyroid stimulating hormone (TSH), free thyroxine (T4) within reference range for age
• erythrocyte sedimentation rate <2X the upper limit of the reference range for age
• hemoglobin within reference range for girls of the same chronological age
• blood urea nitrogen (BUN), creatinine, prolactin not elevated
• aspartate aminotransferase (AST) and alanine aminotransferase (ALT) no more than 2X the upper limit of the reference range
• Insulin-like growth factor 1 (IGF-1) within reference range for bone age

Exclusion Criteria:

All Subjects:

• history or presence of underlying condition that could cause delayed puberty (chronic illness, weight loss, abnormal cranial magnetic resonance imaging (MRI))
• history of an allergic drug reaction