Prader-Willi syndrome (PWS) is a rare genetic disorder resulting from lack of expression of the paternally derived chromosome 15q11-13, associated with several complications, including pubertal disorders, short stature, hyperphagia, obesity, glucose metabolism abnormalities, scoliosis, obstructive sleep apnea syndrome (OSAS) and behavioral problems. We report the case of a girl affected by PWS who presented at the age of 5.9 with premature pubarche, accelerated linear growth and advanced bone age (BA). She was subsequently diagnosed with non-classic congenital adrenal hyperplasia (CAH) confirmed by genetic analysis. Considering the clinical, biochemical, and genetic findings, hydrocortisone therapy was started to prevent rapid BA acceleration and severe compromission of final height. During infancy, short stature and low levels of insulin-like growth factor-1 (IGF-1) for age and gender led to suspicion of growth hormone deficiency (GHD), confirmed by stimulation testing (arginine and clonidine). rhGH therapy was administered and continued until final height was reached. During endocrinological follow up she developed impaired glucose tolerance with positive markers of β-cell autoimmunity (anti-glutamic acid decarboxylase antibodies, GAD Ab), which evolved over time into type 1 diabetes mellitus and insulin therapy with a basal-bolus scheme and an appropriate diet were needed.

The possession of permanent, adipose breasts in women is a uniquely human trait that develops during puberty, well in advance of the first pregnancy. The adaptive role and developmental pattern of this breast morphology, unusual among primates, remains an unresolved conundrum. The evolutionary origins of this trait have been the focus of many hypotheses, which variously suggest that breasts are a product of sexual selection or of natural selection due to their putative role in assisting in nursing or as a thermoregulatory organ. Alternative hypotheses assume that permanent breasts are a by-product of other evolutionary changes. We review and evaluate these hypotheses in the light of recent literature on breast morphology, physiology, phylogeny, ontogeny, sex differences, and genetics in order to highlight their strengths and flaws and to propose a coherent perspective and a new hypothesis on the evolutionary origins of perennially enlarged breasts in women. We propose that breasts appeared as early as Homo ergaster, originally as a by-product of other coincident evolutionary processes of adaptive significance. These included an increase in subcutaneous fat tissue (SFT) in response to the demands of thermoregulatory and energy storage, and of the ontogenetic development of the evolving brain. An increase in SFT triggered an increase in oestradiol levels (E2). An increase in meat in the diet of early Homo allowed for further hormonal changes, such as greater dehydroepiandrosterone (DHEA/S) synthesis, which were crucial for brain evolution. DHEA/S is also easily converted to E2 in E2-sensitive body parts, such as breasts and gluteofemoral regions, causing fat accumulation in these regions, enabling the evolution of perennially enlarged breasts. Furthermore, it is also plausible that after enlarged breasts appeared, they were co-opted for other functions, such as attracting mates and indicating biological condition. Finally, we argue that the multifold adaptive benefits of SFT increase and hormonal changes outweighed the possible costs of perennially enlarged breasts, enabling their further development.

Substantial hormonal and neurobiological changes occur during puberty, and are widely argued to render this period of life a sensitive period in terms of risk for mental health problems. However, there is a paucity of research focusing on adrenarche, the earlier phase of pubertal development. Furthermore, there is a limited understanding of the association between adrenarche and neural development during this phase of life. We systematically reviewed research examining human adrenarcheal development as operationalized by hormonal levels of DHEA and DHEA-S, in relation to indices of mental health (Systematic Review 1). We then reviewed the limited amount of literature that has examined the association between adrenarcheal development and brain structure or function (Systematic Review 2). In general, studies showed that earlier timing of adrenarche was associated with greater mental health symptoms, and there is emerging support that brain development plays a role in this relationship. However, several methodological inconsistencies were noted. We propose that future research in this area test a theoretical model of adrenarche as a sensitive period of neurobiological development, whereby timing of exposure to hormones interacts with brain development, biological sex, and psychosocial stress to influence environmental sensitivity and risk for mental health problems through adolescence.

BACKGROUND: Juvenile granulosa cell tumors (JGCT) are rare ovarian tumors that frequently present with precocious puberty. Presentation in infants less than a year of age is also rare.
METHODS: We describe a 10-month-old infant who presented with both premature thelarche and adrenarche due to JGCT. Laboratory evaluation revealed classic elevation of estradiol and inhibin B, and less classic elevation of total and free testosterone. Oophorectomy and staging resulted in a diagnosis of Stage IA JGCT.
CONCLUSIONS: Survival rates are >95% among patients diagnosed under 10 years of age. Tumor recurrence is rare but can occur as late as 48 months. Therefore, tumor surveillance is warranted for patients with even a Stage IA JGCT and involves monitoring serial inhibin B levels along with intermittent imaging.

BACKGROUND: Polycystic ovary syndrome (PCOS) appears to arise as a complex trait with contributions from both heritable and nonheritable factors. Polygenic influences appear to account for about 70% of the variance in pathogenesis. In view of this evidence for congenital contributions to the syndrome, childhood manifestations may be expected.
OBJECTIVE: The objective has been to review the evidence that risk factors for PCOS can be recognized in childhood.
METHODS: This study consisted of screening of the PCOS literature for articles pertaining to potential childhood and adolescent antecedents.
RESULTS: Congenital virilizing disorders; above average or low birth weight for gestational age; premature adrenarche, particularly exaggerated adrenarche; atypical sexual precocity; or intractable obesity with acanthosis nigricans, metabolic syndrome, and pseudo-Cushing syndrome or pseudo-acromegaly in early childhood have been identified as independent prepubertal risk factors for the development of PCOS. During adolescence, PCOS may masquerade as physiological adolescent anovulation. Asymptomatic adolescents with a polycystic ovary occasionally (8%) have subclinical PCOS but often (42%) have a subclinical PCOS type of ovarian dysfunction, the prognosis for which is unclear.
CONCLUSIONS: Identifying children at risk for PCOS offers the prospect of eventually preventing some of the long-term complications associated with this syndrome once our understanding of the basis of the disorder improves.

Previously used standards for the diagnosis of precocious puberty in girls no longer appear to be appropriate in the USA, in that a significant number of girls are being seen in paediatricians\' offices with breast budding before 8 years of age. The timing of menarche, however, has changed little over the past few decades. Early maturing girls are more likely to become obese in adolescence and adulthood than normal or late maturing girls. Early maturing white girls are heavier at the onset of puberty, but this is not the case for African-American girls or boys of either race. Boys and girls with premature pubarche may be more hyperinsulinaemic than normal children, and girls with premature pubarche more likely to develop functional ovarian and adrenal hyperandrogenism. Early menarche is preceded by prepubertal hyperinsulinaemia. It is proposed that pubertal onset, although not necessarily the tempo of puberty, is influenced by hyperinsulinaemia and insulin resistance. If this hypothesis is correct, insulin resistance may be more prevalent in US children than previously recognized. An advance in timing of onset of puberty has not been noted in other countries, although it is likely that this phenomenon may become more prevalent as other countries adopt a more American lifestyle and diet.