Taylor_Speroff's Clinical Gynecologic Endocrinology and Infe

288 Section II • Clinical Endocrinology

45,XX/46,XY (Chimerism) Chimerism is the term used to describe one body derived from the fusion of cells from both twins of a dizygotic pair. All chimeras are, by definition, mosaics but are derived from two distinct zygotes rather than from a single zygote. 564 Chimeras are not visibly different unless a developmental anomaly in one of the cell lines or sex discordance between the cell lines causes a visibly abnormal phenotype. Most known chimeras are discovered in one of two ways. One is random chance, when people with normal phenotypes are genotyped (e.g., as prospective transplant donors or recipients) and found to carry three or four alleles at multiple loci, instead of one or two. 565–568 Most of the other known chimeras are recognized because of a sex difference between their cell lines, resulting in anomalies of sexual anatomy, maturation, or function that spur the search for an explanation, leading to discovery of mixed cell lines. 569,570 Consequently, a predominance of abnor mal sexual development can be expected in chimeras, due to ascertainment bias. The disturbance in sexual development presumably results from conflicting directions generated by sexually distinct gonadal cells during embryogenesis. A newborn infant with ambiguous external genitalia pres ents a major diagnostic challenge and a social and medical emergency. The physicians involved must make an impor tant decision regarding the sex of rearing. The evaluation must be organized and efficient to ensure that the appro priate gender is assigned, that potential life-threatening conditions are recognized, and that the necessary medical, surgical, and psychological interventions begin promptly. A multidisciplinary approach is essential, drawing on the expertise of specialists in neonatology, endocrinology, urol ogy, genetics, psychology, and, if available, medical ethics. 571 Diagnostic procedures may delay the decision, but a period of delay is far better than a later reversal of sex assignment. Naming the child should be delayed until a gender is firmly assigned. Open communication with the parents and fam ily is key, emphasizing initially that the team will work with them to make the best possible decisions and that the child can become a well-adjusted, functional member of society. Ideally, one member of the team should be designated to conduct discussions with the family. 572 Parental education, guidance, support, and ongoing communication with the family’s primary care physician are essential. 573,574 Diagnostic Evaluation The initial evaluation of an infant with ambiguous genitalia should include a thorough history, complete physical exami nation, abdominal/pelvic ultrasonography, a karyotype and FISH for SRY , and endocrine studies of adrenal and gonadal steroid secretion. DIAGNOSIS AND MANAGEMENT OF AMBIGUOUS GENITALIA

History and Physical Examination The history should focus on identifying any prenatal exposure to androgens or medications that might act as endocrine disrup tors, maternal virilization during pregnancy, and any previously affected relatives, unexplained infant death, or consanguinity. A careful physical examination cannot establish a diag nosis but can provide useful clues. The presence or absence of dysmorphic features or other anomalies should be noted because the finding usually excludes most forms of CAH and suggests a broader pattern of malformations character istic of a trisomy (trisomy 21, 18, or 13) or a specific syn drome. Hyperpigmentation suggests high levels of ACTH as in CAH. A systematic examination of the genitalia should answer each of the following questions: ● ● Are gonads palpable? Palpation of the genital and ingui nal regions is perhaps the most important part of the physical examination. Gonads in the inguinal regions or in scrotal folds are almost certainly testes. 575 Asymmetry of the gonads or genitalia suggests gonadal dysgenesis or the presence of both testis and ovary (ovotesticular DSD). Gonads that are not palpable may be in the abdomen and can be ovaries or testes, but virilizing CAH must be excluded specifically. ● ● What is the length and diameter of the phallus? Careful examination of the phallus may help differentiate between a penis and a clitoris. Whereas the penis has a midline ventral frenulum, the clitoris has two folds extending from its lateral aspects to the labia minora. The phallus should be measured from the pubic ramus (compress ing any suprapubic fat) to the tip of the glans (exclud ing any excess foreskin) after stretching to the point of resistance; diameter should be measured at the midpoint. Measurements should be compared to established norms, which are adjusted for gestational age. In a term infant, normal penile length is 2.5 cm or greater and normal diameter is 0.9 cm or greater. 576 In normal neonates, clito ral length ranges between 2 and 6 mm and measurements greater than 9 mm are unusual. 577,578 Micropenis that is not accompanied by hypospadias can be caused by decreased testosterone production in utero or by growth hormone or gonadotropin deficiency. Clitoromegaly resulting from androgen exposure can be caused by maternal androgen exposure, CAH, or ovotesticular DSD.

● ● What is the position of the urethral meatus? The urethral meatus may be found anywhere along the ventral surface of the phallus or on the perineum. Hypospadias is almost always accompanied by chordee, which is a ventral curva ture of the phallus resulting from a shortened urethra. A single opening at the base of the phallus can represent either an incompletely fused penile urethra (hypospadias) or a virilized urogenital sinus. In either case, the findings must be confirmed radiologically or by cystoscopy/vaginoscopy. ● ● Are the labioscrotal folds fused? The findings can range widely from the unfused labia majora of a normal female, to varying degrees of posterior fusion, to a bifid scrotum, Copyright © 2019 Wolters Kluwer, Inc. Unauthorized reproduction of the content is prohibited.