Antonella Lonero

Prolactin May Be Increased in Newly Diagnosed Celiac Children and Adolescents and Decreases after 6 Months of Gluten-Free Diet

Background/Aims: Prolactin (PRL) is produced by the anterior pituitary gland. It exerts its role on the breast gland but also plays a modulatory role in autoimmune mechanisms. Celiac disease (CD) is a gluten-sensitive autoimmune enteropathy sometimes associated with autoimmune endocrinopathies. No data on PRL levels in CD patients are available at diagnosis, and no conclusive data are reported. Methods: We aimed to evaluate PRL secretion in newly diagnosed CD pediatric patients and, in the case of hyperprolactinemia, any changes in its levels while the patients were on a gluten-free diet (GFD). We recruited 67 patients and 39 healthy controls. Results: PRL was statistically higher in the CD patients (13.5 ± 9.2 ng/ml) than in the controls (8.5 ± 5.0 ng/ml). In the CD group, PRL was inversely correlated with the age at diagnosis (r = -0.326; p = 0.007). In patients with hyperprolactinemia at diagnosis, PRL decreased after 6 months of GFD. Conclusion: This paper confirms that PRL may be increased at diagnosis of CD and shows, for the first time, that it decreases after a short course of GFD. Changes in the levels of inflammatory cytokines in CD may account for changes in PRL levels. Younger patients seem more prone to develop hyperprolactinemia than older ones.

Metabolic Outcomes, Bone Health, and Risk of Polycystic Ovary Syndrome in Girls with Idiopathic Central Precocious Puberty Treated with Gonadotropin-Releasing Hormone Analogues

Background/Aims: Gonadotropin-releasing hormone analogues (GnRHa) represent the gold standard treatment for central precocious puberty (CPP). We aimed to assess the effects of GnRHa treatment on metabolic outcomes, bone status, and polycystic ovary syndrome (PCOS) prevalence in young girls with idiopathic CPP (ICPP). Methods: We enrolled 94 ICPP girls who were at least 2 years after menarche and had already attained adult height at the time of the study: 56 previously treated with depot triptorelin (3.4 ± 0.6 years) and 38 untreated. Auxological parameters, lipid profile, homeostatic model assessment of insulin resistance (HOMA-IR), bone state, and prevalence of PCOS were assessed. Results: The 2 groups were similar for body mass index (BMI) and waist circumference. HOMA-IR, dehydroepiandrosterone sulfate, and Δ4-androstenedione were higher in the treated than in the untreated subjects (p < 0.001). Significant differences were found for amplitude-dependent speed of sound (p < 0.03) and bone transmission time z-scores (p < 0.01). The prevalence of PCOS was higher in the treated than in the untreated subjects (p < 0.04). Conclusion: GnRHa therapy is associated with hyperandrogenism and an increase in insulin resistance and PCOS prevalence, but not with increased BMI or lipid profile alterations. Long-term evaluations at the time of expected peak bone mass achievement are needed to understand the persistent or transient nature of subtle bone abnormalities.

Body Mass Index in Children and Their Parents: A Cross-Sectional Study in aStudy Population of Children from Southern Italy

The prevalence of overweight and obesity has increased over the last decades. Parental obesity plays an important role in determining childhood obesity. We aimed to evaluate the relationship between parental and offspring’ weight status in a population of children from South of Italy, as no data have ever been published from this area. We recruited 636 children (5.7 ± 1.5 years old) and their parents. Seventy-three (11.5%) and sixteen (2.5%) children were overweight and obese, respectively. Offspring weight status was significantly associated with parents’ weight status. The linear regression analysis showed that offspring BMI was more affected by paternal than by maternal BMI. Our data confirmed that parents’ weight status plays an important role on children’s BMI. Interestingly, in our study, parents’ height and weight were measured and not reported as in most of the previous papers, strengthening our conclusions. We suggest that intensive nutritional education and preventive programs should be performed in children with overweight / obese parents rather than in children with normal weight parent. Furthermore, nutritional education should be performed also for overweight parents to modify preventable risk factor for pediatric obesity.

Treatment of osteoporosis in children with glucocorticoid-treated diseases

Glucocorticoid induced osteoporosis (GIO) is the most frequent form of drug induced osteoporosis. Glucocorticoids affect osteoblastogenesis, osteoclastogenesis and promote the apoptosis of osteoblasts and osteocytes. A decrease of bone mineral density has been described in several pediatric diseases that require glucocorticoids, both as long-term replacement therapy, such as Congenital Adrenal Hyperplasia, and as treatment of acute phase or relapses, such as asthma, juvenile rheumatoid arthritis, inflammatory bowel diseases, systemic lupus erythematosus, organ transplantation and Steroid Sensitive Nephrotic Syndrome. The increasing number of children with GIO and at risk of fractures reflects the complex nature of this condition, and the need of development of anti-osteoporotic drugs. In this review, we focus on the mechanisms of GIO in some pediatric diseases and on treatment of osteoporosis. We also report data on new signaling pathways as potential targets for future anti-osteoporotic drugs.

A novel OTX2 gene frameshift mutation in a child with microphthalmia, ectopic pituitary and growth hormone deficiency

Abstract OTX2 mutations are reported in patients with eye maldevelopment and in some cases with brain or pituitary abnormalities. We describe a child carrying a novel OTX2 heterozygous mutation. She presented microphthalmia, absence of retinal vascularization, vitreal spots and optic nerve hypoplasia in the right eye and mild macular dystrophy in the left eye. Midline brain structures and cerebral parenchyma were normal, except for the ectopic posterior pituitary gland. OTX2 sequencing showed a heterozygous c.402del mutation. Most of OTX2 mutations are nonsense or frameshift introducing a premature termination codon and resulting in a truncated protein. More rarely missense mutations occur. Our novel OTX2 mutation (c.402del) is a frameshift mutation (p.S135Lfs*43), never reported before, causing a premature codon stop 43 amino-acids downstream, which is predicted to generate a premature truncation. The mutation was associated with microphthalmia and ectopic posterior pituitary.

A Novel OTX2 Gene Mutation in a Child with Growth Hormone Deficiency

Conclusions Among medically resistant cases, 17/26 patients (65,4%) had KATP genes mutations, of which 9 were paternally inherited and represent focal HI, what was confirmed histologically and 8 had diffuse disease (4 heterozygous denovo mutations and 4 homozygous and compound heterozygous mutations); 1 patient (3,8%) had severe GCK mutation; 8/26 patients had wild type genes. Among medically responsive cases, 11/64 patients (17 %) had mutations in KATP genes, interestingly 2 of them (both with heterozygous intronic mutations) spontaneously resolved during 6 months after diagnosis; 2/64 (3,1%) – in GCK, 3/64 (4,6%) – in GLUD1 and 1/64 (1,5%) – in HADH gene.

Low Bone Mineral Density is Associated to Poor Glycemic Control and Increased Dickkopf-1 (DKK-1) Serum Levels in Children and Adolescents with Type 1 Diabetes

Conclusions Among medically resistant cases, 17/26 patients (65,4%) had KATP genes mutations, of which 9 were paternally inherited and represent focal HI, what was confirmed histologically and 8 had diffuse disease (4 heterozygous denovo mutations and 4 homozygous and compound heterozygous mutations); 1 patient (3,8%) had severe GCK mutation; 8/26 patients had wild type genes. Among medically responsive cases, 11/64 patients (17 %) had mutations in KATP genes, interestingly 2 of them (both with heterozygous intronic mutations) spontaneously resolved during 6 months after diagnosis; 2/64 (3,1%) – in GCK, 3/64 (4,6%) – in GLUD1 and 1/64 (1,5%) – in HADH gene.