Predictors of surgical complications in boys with hypospadias: data from an internationa registry.

Background: Complications are frequently reported after hypospadias repair and there is a need to understand the factors that influence their occurrence. Methods: Data from boys with hypospadias born between 2000 and 2020 were obtained from the International Disorders of Sex Development (I-DSD) Registry. Logistic regressions, fisher's exact tests and spearman's correlation tests were performed on the data to assess associations between clinical factors and complication rates. Results: Of the 551 eligible boys, data were available on 160 (29%). Within the cohort, the median (range) External Masculinization Score (EMS) was 6 (2, 9). All presented with one or more additional genital malformation and 61 (38%) presented with additional extragenital malformations. Disorders of androgen action, androgen synthesis and gonadal development were diagnosed in 28 (18%), 22 (14%) and 9 (6%) boys, respectively. The remaining 101 (62%) patients were diagnosed as having non-specific 46,XY Disorders of Sex Development. Eighty (50%) boys had evidence of abnormal biochemistry, and gene variants were identified in 42 (26%). Median age at first hypospadias surgery was 2 years (0, 9), and median length of follow-up was 5 years (0, 17). Postsurgical complications were noted in 102 (64%) boys. There were no significant associations with postsurgical complications. Conclusions: Boys with proximal hypospadias in the I-DSD Registry have high rates of additional comorbidities and a high risk of postoperative complications. No clinical factors were significantly associated with complication rates. High complication rates with no observable cause suggest the involvement of other factors which need investigation.

Copeptin: Utility in Paediatric Patients with Hyponatraemia.

INTRODUCTION: Copeptin concentrations are a useful component of the diagnostic workup of paediatric patients with polyuria and polydipsia, but the value of measuring copeptin in patients with hyponatraemia is less clear. CASE REPORTS: We report 5 children with hyponatraemia in the context of different underlying pathologies. Copeptin concentrations were elevated in 4 cases (13.7, 14.4, 26.1, and 233 pmol/L; reference range 2.4-8.6 pmol/L), suggesting that non-osmoregulated vasopressin release (syndrome of inappropriate antidiuretic hormone) was the underlying mechanism for low sodium levels. In one of the patients, there was an underlying diagnosis of Schaaf-Yang syndrome (MAGEL2 gene mutation) with a clinical picture suggestive of dysregulated vasopressin production with inappropriately high and then low copeptin release. In one hyponatraemic patient, low copeptin concentrations indicated that non-osmoregulated arginine vasopressin release was not the cause of hyponatraemia and oliguria. DISCUSSION: Copeptin measurement did not influence management acutely but helped to clarify the mechanism leading to hyponatraemia when the result was available. Relatively high and low copeptin concentrations in association with hypo- and hypernatraemia indicate dysregulated vasopressin production in Schaaf-Yang syndrome.

Height as a Clinical Biomarker of Disease Burden in Adult Mitochondrial Disease.

CONTEXT: Abnormal growth and short stature are observed in patients with mitochondrial disease, but it is unclear whether there is a relationship between final adult height and disease severity. OBJECTIVE: To determine whether patients with genetically confirmed mitochondrial disease are shorter than their peers and whether stature is related to disease severity. DESIGN: Analysis of final adult height in relation to disease severity as determined by the Newcastle Mitochondrial Disease Adult Scale (NMDAS). SETTING: UK Mitochondrial Disease Patient Cohort (Mito Cohort). PATIENTS: 575 patients were identified with recorded height, weight, and molecular genetic diagnosis of mitochondrial disease within the Mito Cohort. MAIN OUTCOME MEASURES: Adult height, body mass index (BMI), and their association with genetic subgroup and disease severity. RESULTS: Adults with mitochondrial disease were short, with a mean height of -0.49 SD (95% CI, -0.58 to -0.39; n = 575) compared with UK reference data. Patients were overweight, with a BMI SD of 0.52 (95% CI, 0.37 to 0.67; n = 472). The most common genetic subgroup (m.3243A>G mutation) had a height SD of -0.70 (95% CI, -0.85 to -0.54; n = 234) and a BMI SD of 0.12 (95% CI, -0.10 to 0.34; n = 212). NMDAS scores were negatively correlated with height SD (r = -0.25; 95% CI, -0.33 to -0.17; P < 0.001, n = 533). Rate of disease progression also correlated negatively with adult height (P < 0.001). CONCLUSION: Final height in mitochondrial disease reflects disease severity and rate of disease progression. Mitochondrial dysfunction and associated subclinical comorbidities affect growth plate physiology.