Evaluation

developmental problem. Due to the vast differential diagnosis of delayed puberty, every effort should be made to elicit a detailed medical history, neonatal/pediatric history, as well as family history, including the age of puberty in parents, and/or any family members with a history of delayed puberty. Medical history should include questions about systemic diseases, including autoimmune diseases, as well as any CNS trauma, surgery or symptoms such as headaches, dizziness, or visual changes. Pertinent neonatal and pediatric exposures to chemoradiation should be noted. Patients and their parents should be asked about history of eating disorders, excessive exercise, and psycho-social functioning. Dysmorphic features or delayed cognitive development may indicate an underlying genetic syndrome.

Physical examination should include current and previous height, weight, body mass index (BMI), and linear growth velocity, which can be determined from growth charts. Clinicians should note any midline facial defects, neurologic de cits, including anosmia, and any signs of androgen excess. Features of Turner’s syndrome such as short height, broad chest, webbed neck, and low hairline should be documented, if present. Tanner staging should be performed. Most often, examination of external genitalia may suf ce; however, when needed, pelvic ultrasonography may be performed to evaluate internal pelvic structures.

Laboratory Investigation and Imaging

Every effort should be made to rule out other forms of delayed puberty before achieving the diagnosis of CDGP. A basic initial evaluation of delayed puberty includes measurements of FSH, LH, E2, and a single radiograph of the left hand and wrist to determine bone age. LH and E2 levels of >0.3 mIU/mL and 20 pg/mL, respectively, suggest onset of puberty. Young girls with CDGP can have a bone age that is delayed by about 2 years compared to chronological age. It may be challenging to distinguish between CDGP and IHH in routine testing as both are due to de ciency of FSH and LH secretion. In fact, there is considerable overlap of FSH and LH values in girls with CGDP and IHH. The GnRH stimulation test has limited value in such situations, given signi cant variability in response, and the lack of a commonly accepted cut-off value. However, a history of delayed puberty in a parent or sibling followed by spontaneous onset of puberty supports a diagnosis of CDGP. In contrast, IHH leads to permanent pubertal delay due to the absence of GnRH secretion. In such cases, a family history of pubertal development with exogenous sex steroids can support the diagnosis of IHH.

Advanced laboratory testing or imaging is dictated by the patient’s history, physical examination or FSH, LH, and E2 levels. For example, CNS symptoms or headaches may warrant magnetic resonance imaging (MRI) of the brain and/or pituitary. History of unintentional weight loss may require evaluation of thyroid function tests