Minipuberty consists of activation of the hypothalamic-pituitary-gonadal (HPG) axis during the neonatal period, resulting in high gonadotropin and sex steroid levels, and occurs mainly in the first 3–6 months of life in both sexes. The rise in the levels of these hormones allows for the maturation of the sexual organs. In boys, the peak testosterone level is associated with penile and testicular growth and the proliferation of gonadic cells. In girls, the oestradiol levels stimulate breast tissue, but exhibit considerable fluctuations that probably reflect the cycles of maturation and atrophy of the ovarian follicles. Minipuberty allows for the development of the genital organs and creates the basis for future fertility, but further studies are necessary to understand its exact role, especially in girls. Nevertheless, no scientific study has yet elucidated how the HPG axis turns itself off and remains dormant until puberty. Additional future studies may identify clinical implications of minipuberty in selected cohorts of patients, such as premature and small for gestational age infants. Finally, minipuberty provides a fundamental 6-month window of the possibility of making early diagnoses in patients with suspected sexual reproductive disorders to enable the prompt initiation of treatment rather than delaying treatment until pubertal failure.

BackgroundHuman growth is a complex mechanism that depends on genetic, environmental, nutritional and hormonal factors. The main hormone involved in growth at each stage of development is growth hormone (GH) and its mediator, insulin-like growth factor 1 (IGF-1). In contrast, vitamin D is involved in the processes of bone growth and mineralization through the regulation of calcium and phosphorus metabolism. Nevertheless, no scientific study has yet elucidated how they interact with one another, especially as a dysfunction in which one influences the other, even if numerous biochemical and clinical studies confirm the presence of a close relationship.Main bodyWe reviewed and analyzed the clinical studies that have considered the relationship between vitamin D and the GH/IGF-1 axis in pediatric populations. We found two main areas of interest: the vitamin D deficiency status in patients affected by GH deficit (GHD) and the relationship between serum vitamin D metabolites and IGF-1. Although limited by some bias, from the analysis of the studies presented in the scientific literature, it is possible to hypothesize a greater frequency of hypovitaminosis D in the subjects affected by GHD, a reduced possibility of its correction with only substitution treatment with recombinant growth hormone (rGH) and an improvement of IGF-1 levels after supplementation treatment with vitamin D.ConclusionsThese results could be followed by preventive interventions aimed at reducing the vitamin D deficit in pediatric age. In addition, further research is needed to fully understand how vitamin D and growth are intertwined.

Complete androgen insensitivity syndrome (CAIS) is an X-linked recessive genetic disorder resulting from maternally inherited or de novo mutations involving the androgen receptor gene, situated in the Xq11-q12 region. The diagnosis is based on the presence of female external genitalia in a 46, XY human individual, with normally developed but undescended testes and complete unresponsiveness of target tissues to androgens. Subsequently, pelvic ultrasound or magnetic resonance imaging (MRI) could be helpful in confirming the absence of Mullerian structures, revealing the presence of a blind-ending vagina and identifying testes. CAIS management still represents a unique challenge throughout childhood and adolescence, particularly regarding timing of gonadectomy, type of hormonal therapy, and psychological concerns. Indeed this condition is associated with an increased risk of testicular germ cell tumour (TGCT), although TGCT results less frequently than in other disorders of sex development (DSD). Furthermore, the majority of detected tumoral lesions are non-invasive and with a low probability of progression into aggressive forms. Therefore, histological, epidemiological, and prognostic features of testicular cancer in CAIS allow postponing of the gonadectomy until after pubertal age in order to guarantee the initial spontaneous pubertal development and avoid the necessity of hormonal replacement therapy (HRT) induction. However, HRT is necessary after gonadectomy in order to prevent symptoms of hypoestrogenism and to maintain secondary sexual features. This article presents differential clinical presentations and management in patients with CAIS to emphasize the continued importance of standardizing the clinical and surgical approach to this disorder.

Hashimoto's thyroiditis (HT) is the most common cause of thyroid disease in children and adolescents. Along with significant modifications of thyroid function, HT in pediatric age can be accompanied by relevant thyroid structural alterations. Over time, benign thyroid nodules, carcinoma and, rarely, primary non-Hodgkin lymphoma can develop. However, the relationships between HT and neoplasms are poorly defined. The main aim of this paper is to discuss what is presently known regarding the coexistence of HT and thyroid tumors. Moreover, we attempt to define the pathogenesis of cancer development in children with HT. Literature analysis showed that despite its rarity and relatively promising prognosis, thyroid cancer is associated with HT. Although not all reasons for the coexistence of these diseases are clearly defined, children with HT should be considered at higher risk for thyroid cancer development. Strict correlations between high levels of serum TSH and anti-thyroid antibodies with cancer must be remembered. The same is true for the presence of nodules, especially if multiple nodules are present and ultrasonography and thyroid fine needle aspiration cytology should be promptly used in uncertain cases.

Many scientific studies have revealed a trend towards an earlier onset of puberty and have disclosed an increasing number of children that display precocious puberty. As an explanation, some authors have considered the global socio-economic improvement across different populations, and other authors have considered the action of endocrine disrupting chemicals (EDCs). Among these, bisphenol A (BPA), an aromatic compound largely used worldwide as a precursor of some plastics and chemical additives, is well known for its molecular oestrogen-like and obesogenic actions. We reviewed the medical literature of the previous 20 years that examined associations between BPA exposure and the age of puberty in humans, considering only those referring to clinical or epidemiological data. Of 19 studies, only 7 showed a correlation between BPA and puberty. In particular, the possible disruptive role of BPA on puberty may be seen in those with central precocious puberty or isolated premature breast development aged 2 months to 4 years old, even if the mechanism is undefined. Some studies also found a close relationship between urinary BPA, body weight, and early puberty, which can be explained by the obesogenic effect of BPA itself. The currently available data do not allow establishment of a clear role for BPA in pubertal development because of the conflicting results among all clinical and epidemiological studies examined. Further research is needed to fully understand the potential role of exposure to EDCs and their adverse endocrine health outcomes.

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Rationale: Splenic cysts (SCs) are rare findings in children, particularly the youngest. Here, we discuss a case that is useful for the differential diagnosis and treatment of SCs. Patient concerns: A 9-year-old Albanian boy was admitted for severe abdominal pain localized mainly in the left hypochondrium for approximately 24 hours. His medical history was without significant clinical problems. Diagnosis: Splenomegaly was diagnosed during the first clinical examination, and laboratory tests showed an increase in CA 125 and CA19-9. Abdominal ultrasonography showed splenomegaly with a large hypoechoic oval formation with well-defined margins and the presence of internal fine suspension spots; abdominal magnetic resonance imaging revealed a well-defined SC. The cystic lesion caused major effects on the neighboring organs, shifting them from their normal sites. Interventions: Considering the mass's volume, an open splenectomy was performed. Upon histopathological examination, the lesion was characterized by a stratified squamous keratinized thick lining and brownish liquid contents consisting of lymphocytes, erythrocytes, and hemosiderin-rich macrophages. These features informed the diagnosis of a giant epidermoid SC. Outcomes: No complications occurred in the post-operative period, and blood exams revealed the quick normalization of CA 19.9 and CA 125 levels. The boy was discharged on the eighth post-operative day. No complaints were documented during the regular follow-up. Lessons: This case shows that modern imaging techniques are useful for the differential diagnosis between epithelial mass and SCs of different origins. Open splenectomy has been the treatment of choice for years, but future studies should clarify whether more conservative methods are associated with positive long-term outcomes and if they can also be used for large SCs.

Background: Clinically relevant neurological manifestations in children with celiac disease (CD) are unusual, especially when they are considered as signs of the onset of the disease. In this paper, a case of Guillain-Barrè syndrome (GBS) as the first manifestation of CD in a 23-month-old child is reported. Case presentation: We describe a case of CD onset with peripheral neuropathy in a 23-month-old Bulgarian boy presenting with a sudden refusal to walk and absence of deep tendon reflexes in both lower limbs. Neurological symptoms were preceded by two months of gastrointestinal symptoms such as vomiting, abdominal distention, and clear signs of malnutrition and weight loss. When we evaluated the child six months after the onset of the symptoms, clinical and laboratory findings showed clear signs of peripheral neuropathy associated with malnutrition. Serum deamidated gliadin and tissue transglutaminase antibodies were therefore measured. The anti-gliadin levels were more than sixteen times higher than normal and the IgA anti-transglutaminase levels were four times higher than normal. Anti-endomysium antibodies were positive, and human leukocyte antigens (HLA) II typing confirmed a genetic predisposition to CD (DQ2 positive and DQ8 negative). Given the association between the clinical evidence of the disease and the results of the celiac screening tests, a diagnosis of CD was made without biopsy confirmation of the enteropathy. The child began a restricted gluten-free diet that led to complete recovery of the peripheral neuropathy, walking, reflexes, and overall improvement after three months on the diet. Conclusion: Our case underlines the rare but possible associations between CD and peripheral neuropathy in children as an onset symptom, even in the absence of gastrointestinal manifestations, thus suggesting that CD should always be considered in the differential diagnosis of peripheral neuropathy in children. A good knowledge of the extra-intestinal manifestations of CD is essential for the rapid introduction of a gluten-free diet that could be useful for the resolution of the neurological symptoms.