AVP deficiency (central diabetes insipidus) following immunization with anti-COVID-19 BNT162b2 Comirnaty vaccine in adolescents: A case report

IntroductionThe coronavirus disease 19 (COVID-19) pandemic has prompted the development of new vaccines to reduce the morbidity and mortality associated with this disease. Recognition and report of potential adverse effects of these novel vaccines (especially the urgent and life-threatening ones) is therefore essential. Case presentationA 16-year-old boy presented to the Paediatric Emergency Department with polyuria, polydipsia and weight loss over the last four months. His past medical history was unremarkable. Onset of symptoms was referred to be few days after first dose of anti-COVID-19 BNT162b2 Comirnaty vaccine and then worsened after the second dose. The physical exam was normal, without neurological abnormalities. Auxological parameters were within normal limits. Daily fluid balance monitoring confirmed polyuria and polydipsia. Biochemistry laboratory analysis and urine culture were normal. Serum osmolality was 297 mOsm/Kg H2O (285-305), whereas urine osmolality was 80 mOsm/Kg H2O (100-1100), suggesting diabetes insipidus. Anterior pituitary function was preserved. Since parents refused to give consent to water deprivation test, treatment with Desmopressin was administered and confirmed ex juvantibus diagnosis of AVP deficiency (or central diabetes insipidus). Brain MRI revealed pituitary stalk thickening (4 mm) with contrast enhancement, and loss of posterior pituitary bright spot on T1 weighted imaging. Those signs were consistent with neuroinfundibulohypophysitis. Immunoglobulin levels were normal. Low doses of oral Desmopressin were sufficient to control patient's symptoms, normalizing serum and urinary osmolality values and daily fluid balance at discharge. Brain MRI after 2 months showed stable thicken pituitary stalk and still undetectable posterior pituitary. Due to persistence of polyuria and polydipsia, therapy with Desmopressin was adjusted by increasing dosage and number of daily administrations. Clinical and neuroradiological follow-up is still ongoing. ConclusionHypophysitis is a rare disorder characterized by lymphocytic, granulomatous, plasmacytic, or xanthomatous infiltration of the pituitary gland and stalk. Common manifestations are headache, hypopituitarism, and diabetes insipidus. To date, only time correlation between SARS-CoV-2 infection and development of hypophysitis and subsequent hypopituitarism has been reported. Further studies will be needed to deepen a possible causal link between anti-COVID-19 vaccine and AVP deficiency

Case Report: Liraglutide for Weight Management in Beckwith-Wiedemann Syndromic Obesity

Genetic obesity, including syndromic and non-syndromic forms, represents a minority of cases compared to essential obesity but gene dysregulations lead to complex clinical conditions that make their management particularly difficult. Among them, Beckwith-Wiedemann syndrome (BWS) is a multisystem human genomic imprinting disorder characterized by overgrowth. We describe the first case of liraglutide treatment in an 18-year-old boy patient affected by BWS complicated by macroglossia, cryptorchidism, nephroblastoma, organomegaly, microscopic lymphocytic colitis, pharmacologically treated arterial hypertension, obesity, and obstructive sleep apnea syndrome. He presented a normal cognitive development. Body mass index at the time of first transition visit in the adult endocrinology department at the age of 18-years-old was 40.6 kg/m2 without glucose metabolism impairment. Lifestyle interventions failed because of poor compliance. During 20 months of 3.0 mg liraglutide treatment, a weight loss of 19 kg (−13.3%) and BMI reduction of 6.8 points were registered without side effects. To date, liraglutide treatment was effective on obesity in 7 subjects with Prader Willy Syndrome and 14 with melanocortin-4 receptor mutations. The efficacy of liraglutide in BWS could be related to a crosstalk among glucagon-like peptide (GLP)-1 system, mechanisms related to the cyclin-dependent kinase inhibitor 1C (CDKN1C), and dopamine mesolimbic circuit. Clinical trials aiming at a tailored medicine in genetic obesity are needed

Endocrine disorders in childhood and adolescence. Natural history of subclinical hypothyroidism in children and adolescents and potential effects of replacement therapy: a review.

OBJECTIVE: Subclinical hypothyroidism (SH) is quite common in children and adolescents. The natural history of this condition and the potential effects of replacement therapy need to be known to properly manage SH. The aim of this review is to analyse: 1) the spontaneous evolution of SH, in terms of the rate of reversion to euthyroidism the persistence of SH or the progression to over hypothyroidism; 2) the effects of replacement therapy, with respects to auxological data, thyroid volume and neuropsychological functions. Methods: We systematically searched PubMed, Cochrane and EMBASE (1990 to 2012) and identified 39 potentially relevant articles of which only 15 articles were suitable to be included. Results and Conclusions: SH in children is a remitting process with a low risk of evolution toward overt hypothyroidism. Most of the subjects reverted to euthyroidism or remained SH, with a rate of evolution toward overt hypothyroidism ranging between 0% to 28.8%, being 50% in only one study (9 articles). The initial presence of goiter and elevated thyroglobulin-antibodies, the presence of coeliac disease and a progressive increase in thyroperoxidase-antibodies and TSH value predict a progression toward overt hypothyroidism. Replacement therapy is not justified in children with SH but with TSH 5-10 mIU/L, no goiter and negative anti-thyroid antibodies. An increased growth velocity was shown in children treated with levothyroxine (2 articles). Levothyroxine reduced thyroid volume in 25% to 100% of children with SH and autoimmune thyroiditis (2 studies). No effects on neuropsychological functions (one study) and post-treatment evolution of SH (one study) were reported

Pediatric obesity and vitamin D deficiency: a proteomic approach identifies multimeric adiponectin as a key link between these conditions.

Key circulating molecules that link vitamin D (VD) to pediatric obesity and its co-morbidities remain unclear. Using a proteomic approach, our objective was to identify key molecules in obese children dichotomized according to 25OH-vitamin D (25OHD) levels. A total of 42 obese children (M/F = 18/24) were divided according to their 25OHD3 levels into 25OHD3 deficient (VDD; n = 18; 25OHD<15 ng/ml) or normal subjects (NVD; n = 24; >30 ng/ml). Plasma proteomic analyses by two dimensional (2D)-electrophoresis were performed at baseline in all subjects. VDD subjects underwent a 12mo treatment with 3000 IU vitamin D3 once a week to confirm the proteomic analyses. The proteomic analyses identified 53 "spots" that differed between VDD and NVD (p<0.05), amongst which adiponectin was identified. Adiponectin was selected for confirmational studies due to its tight association with obesity and diabetes mellitus. Western Immunoblot (WIB) analyses of 2D-gels demonstrated a downregulation of adiponectin in VDD subjects, which was confirmed in the plasma from VDD with respect to NVD subjects (p<0.035) and increased following 12mo vitamin D3 supplementation in VDD subjects (p<0.02). High molecular weight (HMW) adiponectin, a surrogate indicator of insulin sensitivity, was significantly lower in VDD subjects (p<0.02) and improved with vitamin D3 supplementation (p<0.042). A direct effect in vitro of 1α,25-(OH)2D3 on adipocyte adiponectin synthesis was demonstrated, with adiponectin and its multimeric forms upregulated, even at low pharmacological doses (10(-9) M) of 1α,25-(OH)2D3. This upregulation was paralleled by the adiponectin interactive protein, DsbA-L, suggesting that the VD regulation of adiponectin involves post-transciptional events. Using a proteomic approach, multimeric adiponectin has been identified as a key plasma protein that links VDD to pediatric obesity

Co-occurrence of genomic imbalances on Xp22.1 in the SHOX region and 15q25.2 in a girl with short stature, precocious puberty, urogenital malformations and bone anomalies

BACKGROUND: Mutations of SHOX represent the most frequent monogenic cause of short stature and related syndromes. The genetic alterations include point mutations and deletions/duplications spanning both SHOX and its regulatory regions, although microrearrangements are confined to either the downstream or upstream enhancers in many patients. Mutations in the heterozygous state have been identified in up to 60-80% of Leri-Weill Dyschondrosteosis (LWD; MIM #127300) and approximately 4-5% of Idiopathic Short Stature (ISS; MIM#300582) patients. Homozygous or compound heterozygous mutations as well as biallelic deletions of SHOX and/or the enhancer regions result in a more severe phenotype, which is known as Langer Mesomelic Dysplasia (LMD; MIM #249700). CASE PRESENTATION: A 17 year old girl, presented with severe short stature, growth hormone deficiency (GHD), precocious puberty, dorsal scoliosis, dysmorphisms and urogenital malformations. She was born with agenesis of the right tibia and fibula, as well as with a supernumerary digit on the left foot. Array comparative genomic hybridization (aCGH) analysis detected the presence of two distinct duplications on Xp22.1 flanking the SHOX coding sequence and involving its regulatory regions. An additional duplication of 1.6-2.5 Mb on 15q25.2 that included 13 genes was also identified. The girl was adopted and the parent's DNA was not available to establish the origin of the chromosome imbalances. CONCLUSIONS: The complex phenotype observed in our patient is probably the result of the co-occurrence of rearrangements on chromosomes Xp22.1 and 15q25.2. The duplicated region on 15q25.2 region is likely to contain dosage-sensitive genes responsible for some of the clinical features observed in this patient, whereas the extreme short stature and the skeletal anomalies are likely attributable to the comorbidity of GHD and copy number variants in the SHOX region

The use of Complementary and Alternative Medicine (CAM) among Italian children: A cross-sectional survey.

OBJECTIVE: To examine prevalence and modalities of CAM use in children living in Novara, a northern Italian city, and to estimate the prescription rate from paediatricians. METHOD: We administered a phone questionnaire to the parents of a sample of 147 children, asking questions about CAM use, children's health profile, parental socio-economic status, use modalities, effectiveness perceptions, and motivations. A parallel survey was conducted by e-mail by investigating family paediatricians attitudes about CAM. RESULTS: Among 147 children whose families responded to our survey 48.3% was treated with CAM at least once in life and 38,1% during the previous year. Children treated with CAM were on average younger than those who were not. The types of CAM used were herbal medicine and homeopathy. Parents who choose CAM for their children were more skeptical about vaccinations. CAM were most frequently used to treat pathologies of ear, nose and throat. 85.9% of parents was willing to use CAM in future, 78.9% would pass to conventional medicine if CAM failed. Among paediatricians 81.5% prescribed CAM at least once, but only 13.6% received specific CAM training. CONCLUSION: The prevalence of children using CAM in Novara is high, in line with investigations conducted in Northern European countries. The distribution of pathologies treated with CAM, parental socio-economic status and general scepticism towards vaccination are consistent with the literature. Physicians should keep themselves up-to-date also about evidence-based CAM therapies and, most importantly, should have an open dialogue about CAM with their patients

Discordant biochemical parameters of acromegaly remission do not influence the prevalence or aggressiveness of metabolic comorbidities: a single-center study

Purpose: The discrepancy between the biomarkers of disease's activity in acromegalic patients (GH and IGF-1) is almost frequent representing a challenge for the development of comorbidities in the long term. The aim of this study was to evaluate the prevalence and severity of metabolic comorbidities (diabetes, hypertension, and dyslipidemia) in surgically treated acromegalic patients with disease control and discordant GH and/or IGF-1 levels compared with those with concordant values.Patients and methods: Retrospective monocentric observational study on acromegalic surgically treated patients with biochemical remission (group A) or mild discordant GH or IGF-1 levels (group B). Metabolic complications and medical therapy were assessed at diagnosis and at the last follow-up visit. Severity of the disease was set for drug titration or shift to another molecule or more than before.Results: There were 18 patients that met the inclusion criteria [group A: nine patients; group B: nine patients, follow-up 7 years (IQR 5.0;11.25)]. The prevalence of female patients was significantly higher in the remission group compared with the discordant group (p < 0.02). Considering metabolic complications, at the last follow-up, 61.1% was affected by hypertension, 33.3% by diabetes, and 61.1% by dyslipidemia, without differences between groups. Drug characteristics (dose, shift, number) during the follow-up did not differ significantly between groups.Conclusion: Metabolic complications, mainly dyslipidemia, are frequent in cured acromegalic patients, but GH/IGF-1 discrepancy does not seem to represent a risk factor for their presence or persistence. More extended studies are needed to confirm our results in a long-term period

Principali test di stimolo e di inibizione per la patologia antero-ipofisaria: avvertenze per l'uso nella popolazione di età superiore ai 65 anni

SommarioLa fisiopatologia dell'invecchiamento non è ancora stata del tutto chiarita sebbene numerosi filoni di ricerca siano attivi in questo ambito in considerazione dell'aumento della vita media della popolazione generale. Il sistema endocrino riveste un ruolo critico in questo contesto in quanto, durante l'invecchiamento, avvengono importanti modifiche nel pattern secretorio dell'asse ipotalamo-ipofisi e nella sua sensibilità ai meccanismi di feedback. Risulta pertanto evidente come, nell'ambito della quotidiana pratica clinica, sia necessaria un'interpretazione critica dei principali test endocrinologi per lo studio delle patologie ipofisarie nella popolazione over 65, per la quale spesso non esistono cut-off età-specifici