Advice on the management of ambiguous genitalia to a young endocrinologist from experienced clinicians.

The birth of a child with ambiguous genitalia is a challenging and distressing event for the family and physician and one with life-long consequences. Most disorders of sexual differentiation (DSD) associated with ambiguous genitalia are the result either of inappropriate virilization of girls or incomplete virilization of boys. It is important to establish a diagnosis as soon as possible, for psychological, social, and medical reasons, particularly for recognizing accompanying life-threatening disorders such as the salt-losing form of congenital adrenal hyperplasia.

Reflections on future research in adolescent reproductive health.

A group of basic scientists, clinicians, clinical investigators, psychologists, patient advocacy groups, and representatives from professional societies and governmental agencies met at the National Institutes of Health in October, 2007 with the long-term goal of having the menstrual cycle accepted and understood as a marker of general health in adolescent girls. An equally important goal was to develop a research agenda for this area of investigation. This chapter comprises the highlights of discussions throughout that meeting, with an emphasis on ideas generated during a final session led by an internationally renowned physician-scientist, in which reports from four breakout groups were presented.

Mutations in the synthesis and action of estrogen: the critical role in the male of estrogen on pubertal growth, skeletal maturation, and bone mass.

The discovery of males with mutations in CYP19, the gene that encodes aromatase, the enzyme catalyzing the final step in the conversion of androgen to estrogen, and of a man with a mutation in the estrogen receptor alpha gene has led to increasing recognition of the critical role of estrogen in the male. The diverse roles of estrogen in the male, both circulating and locally synthesized, is supported by extensive studies in male mice generated with disruption of the aromatase gene or the genes encoding the alpha- and beta-estrogen receptor. This presentation focuses on the crucial role of estradiol in the human male on the pubertal growth spurt, skeletal maturation and the cessation of linear growth, and the accrual of bone mass.

A window of opportunity: the diagnosis of gonadotropin deficiency in the male infant.

A common cause of micropenis is congenital hypogonadotropic hypogonadism, whether isolated or associated with multiple pituitary hormone deficiencies. The postnatal surge in FSH, LH, and testosterone in the male infant as a consequence of the continued function of the fetal GnRH pulse generator provides a 6-month window of opportunity to establish the diagnosis of hypogonadotropic hypogonadism and alert the clinician to the possibility of its association with multiple pituitary hormone deficiencies. When ACTH or GH deficiency or both deficiencies are present, hypoglycemia and cortisol deficiency can lead to neonatal and infantile death or increased morbidity.

Management of the clinically inapparent adrenal mass ("incidentaloma").

The National Institutes of Health Consensus Development Program convened surgeons, endocrinologists, pathologists, biostatisticians, radiologists, oncologists, and other health care professionals, as well as members of the general public, to address the causes, prevalence, and natural history of clinically inapparent adrenal masses, or "incidentalomas"; the appropriate evaluation and treatment of such masses; and directions for future research. Improvements in abdominal imaging techniques have increased detection of adrenal incidentalomas, and because the prevalence of these masses increases with age, appropriate management of adrenal tumors will be a growing challenge in our aging society. To address six predetermined questions, the 12-member nonfederal, nonadvocate state-of-the-science panel heard presentations from 21 experts in adrenal incidentalomas and consulted a systematic review of medical literature on the topic provided by the Agency for Healthcare Research and Quality and an extensive bibliography developed by the National Library of Medicine.

The neuroendocrinology of human puberty revisited.

The fundamental aspects of the hypothalamic luteinizing hormone-releasing hormone (LHRH)(1) [1]pulse generator-pituitary gonadotrophin-gonadal apparatus in mammals have striking commonalities. There are, however, critical, substantive differences in the neuroendocrinology of puberty among species. The onset of puberty in the human is marked by an increase in the amplitude of LH pulses, an indirect indicator of the increase in amplitude of LHRH pulses.