Over the past 20 years, a clear secular trend toward the earlier onset of puberty has been described. A better knowledge should help clinicians attempting to define both precocious and delayed puberty (PP and DP, respectively). The definition of PP for girls is the appearance of secondary sex characteristics development before the age of 8 years, while DP is based on the absence of thelarche at the age of 13 years. Regarding PP, one should clinically distinguish between true precocious puberty, i.e., complete or central PP, and incomplete PP, which refers to premature thelarche, premature pubarche, and isolated menarche. Evaluation of girls of PP requires careful examination of the clinical expression, a GnRH test, and imaging of the central neurosystem. GnRH analog is considered the gold standard treatment of central precocious puberty. Peripheral PP should be managed according to the underlying causes. DP is suspected in girls with no breast development by the age of 13 years, or absence of menarche at 15 years with secondary sex characteristics. The clinical examination along with endocrine, radiological, and genetic investigation should be able to identify girls with permanent hypogonadism as opposed to those with transitory hypogonadism, who undergo spontaneous but DP. Estrogen therapy should be discussed according to the causes of DP. In all cases, emotional and psychosocial disorders should be considered for these girls with disorders of puberty.

Ambiguous genitalia in the newborn need immediate and rational management. This complex situation requires a strategy of clinical, hormonal, genetic, molecular, and radiographic investigation to determine the etiology of the intersex state and orient the therapeutic approach. Physical examination is key to diagnosis. Careful palpation to locate gonads at the genital folds or in the inguinal region provides the first element for diagnostic orientation. If gonads are absent, a diagnosis of female pseudohermaphroditism seems advisable; if gonads are palpated, a diagnosis of male pseudohermaphroditism is more appropriate. Karyotyping is systematic while polymerase chain reaction (PCR) analysis of the SRY gene provides information about the presence of a Y chromosome within 1 day. Hormonal investigation should be based on clinical and genetic orientation. Substantially elevated plasma 17-OH progesterone will confirm the diagnosis of congenital adrenal hyperplasia due to deficiency in 21-hydroxylase. Testicular stimulation with human chorionic gonadotropin (hCG) will determine the functional value of testicular tissue. Exploration of the genitourinary axis is principally carried out by ultrasound and genitography. By the end of these investigations, the medical team should be able to give a precise diagnosis. Female pseudohermaphroditism may be due to excess fetal androgens (congenital adrenal hyperplasia), increased androgen production of maternal origin, or placental androgen excess. In male pseudohermaphroditism, if testosterone rises normally after hCG stimulation, androgen resistance is indicated. If it does not rise after this test, either testicular dysgenesis or disturbance in testosterone biosynthesis may be responsible. The assignment of sex for rearing must be guided by the etiology of the genital malformation, the anatomic condition, and family considerations. In cases of female pseudohermaphroditism, the newborn should always be declared to be of female sex at birth. In cases of male pseudohermaphroditism, great care should be taken in the declaration of male sex: the potential for reconstructive surgery and the pubertal "programmed" response of the external genitalia to endogenous and exogenous testosterone are determinant. Management of ambiguous genitalia in the newborn requires an entire multidisciplinary team in every step of the diagnostic procedure, the choice of sex assignment, and the treatment strategy.

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The diagnosis of Frasier syndrome is based on the association of male pseudohermaphroditism (as a result of gonadal dysgenesis), with steroid-resistant nephrotic syndrome due to focal and segmental glomerular sclerosis (FSGS), which progresses to end-stage renal failure (ESRF) during adolescence or adulthood. Frasier syndrome results from mutations in the Wilms' tumour suppressor gene WT1, which is responsible for alterations in male genital development and podocyte dysfunction. We describe the case of a 7-year-old girl who was referred to the paediatric emergency department with ESRF. Haemodialysis was started immediately because of severe hypertension and hyperkalaemia. In view of the fact that our patient had a past medical history of pseudohermaphroditism, we suspected that the acute presentation in ESRF may be related to a new diagnosis of Frasier syndrome. Our hypothesis was confirmed on examination of the medical records. There had been no medical follow-up for several years and, in particular, no renal imaging or functional assessment had ever been performed. This lack of surveillance explains why our patient presented with ESRF much earlier in this disease than expected and subsequently had to undergo kidney transplantation at a very young age.