Natural History Study of Patients With Excess Androgen
Natural History Study of Patients With Excess Androgen
This study will evaluate and gather information in patients with genetic causes of too much
 androgen (male-like hormone) in order to better understand the effects of too much androgen
 and describe problems associated with it. Too much androgen in childhood, if untreated,
 results in rapid growth and early puberty with early cessation of growth and short stature in
 adulthood. Too much androgen in adulthood may result in infertility, and women may have
 excess facial hair, acne and a more male-like appearance. Excess androgen may also affect
 mood and behavior and possibly the secretion of other hormones, such as insulin. Two genetic
 diseases that result in early childhood androgen excess are congenital adrenal hyperplasia
 (CAH) and familial male-limited precocious puberty (FMPP).

 Patients with known or suspected CAH due to 21-hydroxylase deficiency, 11- hydroxylase
 deficiency, or 3-beta-hydroxysteroid dehydrogenase deficiency and males with known or
 suspected FMPP may be eligible for this study. Patients with both classic and non-classic CAH
 are eligible, and patients with androgen excess of unknown cause may be eligible.

 Participants undergo the following procedures:

 -  Medical history and physical examination.

 -  Fasting blood tests for analysis of hormones, blood chemistries including blood sugar
 and cardiovascular risk factors such as lipids.

 -  Oral glucose tolerance test for patients with elevated insulin levels. For this test, a
 catheter (plastic tube) is placed in a vein in the patient's arm. The patient drinks a
 sugar-containing fluid and blood samples are collected through the catheter at intervals
 starting with drinking the solution, and then 30, 60 and 120 minutes after drinking the
 solution.

 -  24-hour urine collection to measure hormone levels in the urine.

 -  DNA testing for patients with 21-hydroxylase deficiency to help identify the type of
 genetic mutation responsible for the disease.

 -  X-ray of the left hand to measure bone age in growing children. The x-ray is used to
 determine how far into puberty the child is and how much growth potential is left in the
 bones.

 -  A pelvic ultrasound in females and testicular ultrasound in males to evaluate the size
 and development of the gonads (ovaries in females and testes in males).

 -  Cognitive and psychological tests, including an IQ test and evaluation of memory,
 achievement and behavior.

 -  Other tests and evaluations based on medical need.

 The schedule for these procedures varies. In a part of the study involving only patients with
 CAH, growing children are evaluated twice (once in childhood and once after reaching adult
 height), and adults are evaluated once. In another part of the study involving patients with
 CAH and FMPP, growing children are seen twice a year, and adults and children who have
 reached adult height may be seen annually. Additional visits may be scheduled if medically
 indicated. In this part of the study, females are asked to keep a record of their periods
 after their first menstrual cycle.
Androgen excess in childhood results in pseudoprecocious puberty, accelerated childhood
 growth with premature epiphyseal fusion, adult short stature, and unknown metabolic and
 psychological perturbations. Congenital adrenal hyperplasia (CAH) and familial male-limited
 precocious puberty (FMPP) are two genetic diseases that result in early childhood androgen
 excess, and CAH due to 21-hydroxylase deficiency is the most common cause of hyperandrogenism
 in childhood. This protocol will elucidate a comprehensive phenotypic profile for patients
 with CAH and FMPP. Data will be collected in a large cohort of patients regarding growth and
 development, hormonal and metabolic factors and psychological characteristics. This protocol
 will allow investigators to compare patients with androgen excess of different etiologies,
 elucidate androgen-mediated and disease-specific phenotypic characterizations, and allow the
 investigators to acquire further knowledge for use in the design of future therapeutic
 interventions.
-  INCLUSION CRITERIA:

 1. Males, ages 0 - 99 with known or suspected FMPP or

 2. Patients (males and females, ages 0 - 99) with known or suspected (based on
 hormonal, clinical and/or genetic testing) CAH of any type.

 3. Patients with excess androgen of unknown etiology or

 4. Relatives of patients in this protocol.

 EXCLUSION CRITERIA:

 1. Females with isolated polycystic ovary syndrome. If, following a diagnostic work-up, a
 patient is determined to have PCOS as the only cause of her hyperandrogenism; she will
 no longer be followed on this protocol.

 2. Patients with significant non-endocrine medical conditions.

 3. Females who are pregnant at the time of initial enrollment.