Hypogonadism may be suspected if puberty is delayed. Pubertal delay may be caused by a normal physiological variant, by primary ovarian insufficiency (Turner syndrome), or reflect congenital hypogonadotropic hypogonadism (HH; genetic) or acquired HH (brain lesions). Any underlying chronic disease like inflammatory bowel disease, celiac disease, malnutrition (anorexia or orthorexia), or excessive physical activity may also result in functional HH. Thus, girls with delayed puberty should be evaluated for an underlying pathology before any treatment, including oral contraception, is initiated. Estrogen replacement is important and natural 17β-estradiol, preferably transdermally, is the preferred choice, whereas the oral route can be used as an alternative depending on patient preference and compliance. Sexual activity is often delayed in the hypogonadal adolescent girl. In the adolescent hypogonadal girl, hormone replacement therapy (HRT) most likely has been initiated at the time she becomes sexually active. If a risk of unwanted pregnancy cannot be ruled out, there is a need to consider contraception. This consideration does not contradict the principles of HRT but can be included as a part of the substitution, e.g. oral contraceptives containing 17β-estradiol or a progestogen intrauterine device combined with continuous 17β-estradiol (transdermal or oral).

Passage from childhood to adult life involves biological changes culminating in full reproductive capacity as well as psychosocial development. For patients with congenital hypogonadotropic hypogonadism (CHH), this can be an emotionally challenging time as their pubertal failure results in striking physical differences from their peers. CHH is difficult to differentiate from common disorders of puberty such as constitutional delay of growth and puberty. As such, delays in diagnosis are frequent, and it is a common source of stress and frustration for these adolescents. While effective treatments are available for inducing puberty and attaining fertility is possible in most cases, patients may find it difficult to cope with living with CHH. A critical issue for adolescents with CHH is the risk for being lost to follow-up during the transition from pediatric-centered care to adult care. This article will review the state of the art in diagnosis and treatment of patients with CHH with a particular focus on supporting an effective transition from pediatric-centered care to adult-oriented endocrine services. A synthesis of best practices is offered to help guide clinicians in supporting patients and families during this challenging period of care.

Hypothalamic obesity (HO) is a rare and serious disease of various origins: tumor, traumatism, radiotherapy, vascular, genetic, or even psychotropic drug use. HO usually begins in childhood with eating disorders and progresses with an aggregate of severe comorbidities. Transition from pediatric to adult health care is a critical period to assure weight stability and a good management of comorbidities. In case of loss to follow-up, there is an increased risk of major weight gain and long-term complications with severe obesity. To minimize this risk, pediatric and adult specialists must work together to prepare, supervise, and monitor transition. Transition ideally involves the patient, parents, and care providers with a good communication between pediatric and adult teams from expert centers. Maintaining a diet and physical activity management plan, acquisition of autonomy for hormone replacement therapy and management of psychosocial consequences of obesity are fundamental issues in patients with HO. Patient associations and specialized diet center weight loss programs can help as well as group approaches.

Recent advances in fertility preservation (FP) techniques have led to a wide spread of indications. FP should now be discussed not only for young girls having to receive gonadotoxic treatments for cancer, but also for those with genetic or endocrine disorders, as well as benign ovarian diseases at risk of premature ovarian insufficiency. For premenarchal girls, ovarian tissue cryopreservation is still the only available technique. Oocyte cryopreservation after ovarian stimulation could be offered to postmenarchal girls. Whenever possible, the parents and the young patient should be informed of the benefits to be expected, as well as of the risks and limits of FP for children.

Girls with Turner syndrome (TS) require special consideration during transition from childhood to adult care. During the transition years, treatment for short stature will be completed and sexual development induced in parallel with the peer group. The timing of sexual development may have later repercussions with respect to psychosocial development and partnership status. Late presentation of TS, which is so common, can result in additional difficulties with the transition process.

Adolescence and young adulthood are times of multiple developmental changes, including physiological, social, emotional, cognitive, and behavioral transformations. The adolescent or young adult living with type 1 or type 2 diabetes must navigate the vicissitudes of these developmental stages while managing the rigors and self-care demands of these conditions. Diabetes in children is managed by adults, mainly by parents. As the child matures, diabetes management tasks transition from parents to the developing teen. This transition in care is a process that generally begins in early adolescence and culminates when the older teen successfully accepts and manages diabetes self-care tasks. Along with the transitions in diabetes management tasks, older teens and young adults must be prepared for transfer from the pediatric diabetes care team to an adult-focused health care team. Numerous publications have described the challenges associated with both the process of transition and the act of transfer. Lack of preparation during transition followed by unsuccessful transfer often results in gaps in diabetes care exceeding 6 months, deterioration in glycemic control, increase in emergency room use and hospitalization, and emergence of diabetes complications among older teens and young adults. There is need for ongoing research internationally to address these deficiencies in order to improve the short- and long-term health of young persons with diabetes.

Transition has been defined as "the purposeful, planned movement of adolescents and young adults with chronic physical and medical conditions from child-centered to adult-oriented health care systems." We will here describe the challenges of such a process: challenges coming from the pediatrician, from the adolescent, linked to the disease itself, and those from the parents. We will outline how to overcome those fears and challenges to provide a successful transition process. A key factor to underline that process is that a relationship based on confidence should be established between the pediatrician and the physician for adults, in order for that relationship, based on trust, to be the basis for the transfer of the adolescent from the pediatric system of care to the adult one.

Deficiency of the 21-hydroxylase enzyme is the most common form of congenital adrenal hyperplasia (CAH), accounting for more than 95% of the cases. With the advent of newborn screening and hormone replacement therapy, most children with CAH survive into adulthood. Adolescents and adults with CAH experience a number of complications, including short stature, obesity, infertility, impaired bone mineral density, and reduced quality of life. Transition from pediatric to adult care and management of long-term complications are challenging for both patients and practitioners. In adulthood, the aims of the medical treatment are to substitute cortisol and, when necessary, aldosterone deficiency, to ensure normal fertility, and to avoid the long-term consequences of glucocorticoid use on bone, metabolism, and cardiovascular risk. Recent data suggest that poor health status is likely to begin in adolescence and persist into adulthood, highlighting the importance of this time period in a patient's endocrine care. During transition from pediatric to adult specific care, a shift in treatment goals is thus needed. Successful transition from pediatric to adult health care requires a regular follow-up of patients by a multidisciplinary team including pediatric endocrinologists, urologists, gynecologists, psychiatrists, and adult endocrinologists. All of this could be included in a specific therapeutic education program regarding transition and/or CAH.

Spermatozoa have occasionally been identified in ejaculate of adult Klinefelter syndrome (KS) patients but very exceptionally in KS adolescents. Spermatozoa can also be retrieved in testicular tissue of KS adolescents. The testis may also harbor spermatogonia and noncompletely differentiated germ cells. Neither clinical features nor hormonal parameters could predict germ cell recovery in KS adults or adolescents. No predictive factors can actually demonstrate that early diagnosis of KS would allow increasing the chance of sperm retrieval even if it has been suggested that semen quality may decline with age in KS patients. Leydig cell dysfunction may also be another factor that might affect the spermatogenesis process in XXY adolescents. Fertility preservation might be preferentially proposed in KS adolescents when semen sampling is possible, when the patient is able to consider alternative options to become a father, and to accept germ cell retrieval failure. However, precocious diagnosis of KS has also to be considered because it might not solely improve the possibility of fertility preservation after the onset of puberty, but also the medical care and the quality of life of these patients.

Growth hormone (GH) is essential not only for normal growth during childhood, but also for the acquisition of bone mass and muscle strength in both sexes. This process is completed after the achievement of adult height in the phase of transition from adolescence to adulthood. Adolescents with childhood onset GH deficiency (GHD) show reduction of bone mineral density, decrease in lean body mass, increase in fat mass, and deterioration of the lipid profile. For this reason, continuation of GH replacement therapy in the transition age is recommended in all patients with a confirmed diagnosis of GHD. To confirm the diagnosis of GHD, GH treatment should be discontinued for at least 1 month after the attainment of adult height, and the patient should be re-evaluated for GH secretion. Current guidelines indicate that retesting is not required for those with a transcription factor mutation, more than 3 pituitary hormone deficits, or isolated GHD associated with an identified mutation. The key predictors of persistent GHD are its severity, the presence of additional pituitary hormone deficits, low insulin-like growth factor I (IGF-I) concentration, and the presence of structural hypothalamic-pituitary abnormalities Treatment should be initiated with a low dose (0.2-0.5 mg/day s.c.) and then adjusted according to IGF-I concentrations.

Considering the patient's transition from child to adolescent to adult and its psychological aspects in endocrinology and diabetology, it is necessary to recall the child's psycho-affective development when he enters adolescence. Indeed, adolescence appears paradigmatic of the "child-adult" transition; it is a specific and decisive psychic process which allows the child to become an adult, that is to say autonomous and subject to his desire. In our paper, we study the resonance of a chronic disease in young people; type 1 diabetes is chosen.

Gut bacteria exert a variety of metabolic functions unavailable to the host and are increasingly seen as a virtual organ located inside our gastrointestinal tract. Scattered in our intestinal epithelium, enteroendocrine cells (EECs) regulate several aspects of the host's physiology and translate signals coming from the gut microbiota through their hormonal secretions. In this chapter, we will assess the interplay between the gut microbiota and EEC and its consequences for the physiology of the host. We will first describe alterations of different populations of EEC in germ-free animals. The role of mediators of this interaction, such as microbial metabolites and their receptors will also be discussed. Finally, different strategies harnessing host-microbe crosstalk for therapeutic purposes will be presented with an emphasis on obesity and related disorders.

The physiological studies by British physiologists William Maddock Bayliss and Ernest Henry Starling, at the beginning of the last century, demonstrated the existence of specific messenger molecules (hormones) circulating in the blood that regulate the organ function and physiological mechanisms. These findings led to the concept of endocrinology. The first 2 hormones were secretin, discovered in 1902, and gastrin, discovered in 1905. Both hormones that have been described are produced in the gut. This chapter summarizes the history around the discovery of these 2 hormones, which is perceived as the birth of endocrinology. It is noteworthy that after the discovery of these 2 gastrointestinal hormones, many other hormones were detected outside the gut, and thereafter gut hormones faded from both the clinical and scientific spotlight. Only recently, the clinical importance of the gut as the body's largest endocrine organ producing a large variety of hormones has been realized. Gastrointestinal hormones are essential regulators of metabolism, growth, development and behavior and are therefore the focus of a modern pediatric endocrinologist.

Obesity and its comorbidities such as type 2 diabetes constitute major worldwide health threats, and the identification of an effective medical intervention has emerged as a global priority. The limited effectiveness of historical, anti-obesity treatments is commonly attributed to the complexity of the disease and the redundancy of metabolic regulatory mechanisms that sustain body weight. At the forefront of obesity research is the development of combinational drug therapies that simultaneously target multiple regulatory pathways, which promote dysfunctional metabolism. Recently, molecularly crafted unimolecular "multi-agonism" of balanced activity at 3 key receptors involved in metabolism and specifically the glucagon-like peptide (GLP)-1 receptor, glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon receptor was reported as superior to conventional monoagonist therapy. These mixed peptide agonists are designed to pharmacologically integrate the insulinotropic and anorexigenic effects of GLP-1, the thermogenic and lipolytic activities of glucagon, and the insulinotropic and insulin sensitizing properties of GIP. The molecular mechanism of these purposefully promiscuous ligands is not completely understood, however, recent studies in pancreatic beta cells point to the prospect of a complex signaling network that can magnify the signaling of multi-agonist ligands. The activation of this signalosome might explain the additional therapeutic benefit inherent to simultaneous cellular activation through multiple metabolic receptors.

The long-lasting weight-reducing effect of bariatric surgical procedures cannot simply be explained by the malabsorption of nutrients and the subsequent energy deficit due to this malabsorption. Clinical studies have shown that the reorganization of the anatomy of the gut and the subsequent alterations of gastrointestinal physiology have a large impact on the secretion and function of gastrointestinal hormones, which regulate hunger and satiety. These changes have been named the BRAVE effect: <under>b</under>ile flow alteration, <under>r</under>eduction of gastric size, <under>a</under>natomical gut rearrangement and altered flow of nutrients, <under>v</under>agal manipulation, and <under>e</under>nteric gut modulation. In addition, the metabolic improvements, for example, increased insulin secretion and improved glucose sensitivity after bariatric surgery cannot simply be explained by the weight loss achieved by the operation. Several metabolic improvements occur directly after bariatric surgery even before significant weight loss has occurred. Clinical studies revealed that the altered gastrointestinal physiology and the postoperative profile of gastrointestinal hormones are responsible for these metabolic alterations. Further insights into the changes of gastrointestinal hormone profiles before and after bariatric surgery may open new ways to prevent the surgical procedure and probably obtain equivalent results by nutraceuticals.