Birth weight in different etiologies of disorders of sex development

Context: It is well established that boys are heavier than girls at birth. Although the cause of birth weight (BW) difference is unknown, it has been proposed that it could be generated from prenatal androgen action. Objective: The aim of the current study was to determine the BW of children with disorders of sex development (DSD) of different etiologies and to evaluate the effects of androgen action on BW. Methods: Data regarding diagnosis, BW, gestational age, karyotype, and concomitant conditions were collected from the InternationalDisorders of SexDevelopment (I-DSD) Registry (www.i-dsd).BWstandard deviation score was calculated according to gestational age. Cases were evaluated according to disorder classification in I-DSD (i.e., disorders of gonadal development, androgen excess, androgen synthesis, androgen action, nonspecific disorder of undermasculinization groups, and Leydig cell defect). Results: A total of 533 cases were available; 400 (75%) cases were 46,XY, and 133 (25%) cases were 46,XX. Eighty cases (15%) were born small for gestational age (SGA). Frequency of SGA was higher in the 46,XY group (17.8%) than in the 46,XX (6.7%) group (P = 0.001). Mean BW standard deviation scores of cases with androgen excess and androgen deficiency [in disorders of gonadal development, androgen synthesis, and Leydig cell defect groups and androgen receptor gene (AR)mutation-positive cases in disorders of androgen action groups]were similar to normal childrenwith the same karyotype. SGA birth frequency was higher in the AR mutation-negative cases in disorders of androgen action group and in the nonspecific disorders of the undermasculinization group. Conclusions: BWdimorphism is unlikely to be explained by fetal androgen action per se. 46,XY DSDs due to nonspecific disorders of undermasculinizationare more frequently associatedwithfetal growth restriction, SGA, and concomitant conditions

The current landscape of European registries for rare endocrine conditions

Objective To identify cross-border international registries for rare endocrine conditions that are led from Europe and to understand the extent of engagement with these registries within a network of reference centres (RCs) for rare endocrine conditions. Methods Database search of international registries and a survey of RCs in the European Reference Network for rare endocrine conditions (Endo-ERN) with an overall response rate of 82%. Results Of the 42 conditions with orphacodes currently covered within Endo-ERN, international registries exist for 32 (76%). Of 27 registries identified in the Orphanet and RD-Connect databases, Endo-ERN RCs were aware of 11 (41%). Of 21 registries identified by the RC, RD-Connect and Orphanet did not have a record of 10 (48%). Of the 29 glucose RCs, the awareness and participation rate in an international registry was highest for rare diabetes at 75 and 56% respectively. Of the 37 sex development RCs, the corresponding rates were highest for disorders of sex development at 70 and 52%. Of the 33 adrenal RCs, the rates were highest for adrenocortical tumours at 68 and 43%. Of the 43 pituitary RCs, the rates were highest for pituitary adenomas at 43 and 29%. Of the 31 genetic tumour RCs, the rates were highest for MEN1 at 26 and 9%. For the remaining conditions, awareness and participation in registries was less than 25%. Conclusion Although there is a need to develop new registries for rare endocrine conditions, there is a more immediate need to improve the awareness and participation in existing registries.This publication is part of the project ‘777215/EuRRECa’ which has received funding from the European Union’s Health Programme (2014–2020)

Eucalcemic Parathyroid Hormone Elevation After Parathyroidectomy for Primary Sporadic Hyperparathyroidism: Risk Factors, Trend, and Outcome

BACKGROUND: Patients with eucalcemic parathyroid hormone elevation (ePTH) after parathyroidectomy for primary hyperparathyroidism (HPT) may be at risk of recurrence. We aimed to examine risk factors, trend of PTH level, and outcome of patients with ePTH 6 months after parathyroidectomy. METHODS: A total of 161 primary HPT were analyzed. The 6-month postoperative calcium and PTH levels were obtained. ePTH was defined as an elevated PTH level in the presence of normocalcemia. At 6 months, 98 had eucalcemic normal PTH and 63 (39.1%) had ePTH. Perioperative variables, PTH trend, and outcome were compared between 2 groups. Multivariable analyses were performed to identify independent preoperative and operative/postoperative risk factors for ePTH. RESULTS: Among preoperative factors, advanced age (odds ratio [OR] = 1.042, P = .027) and low 25-hydroxyvitamin D(3) (25OHD(3)) (OR = 1.043, P = .009) were independently associated with ePTH, whereas among operative/postoperative factors, high 10-min intraoperative PTH level (OR = 1.015, P = .040) and high postoperative 3-month PTH (OR = 1.048, P < .001) were independently associated with ePTH. After a mean follow-up of 38.7 months, recurrence rate was similar between the 2 groups (P = 1.00). In the first 2 postoperative years, 75 (46.6%) had ePTH on at least 1 occasion and 8 (5.0%) had persistently ePTH on every occasion. CONCLUSIONS: Advanced age, low 25OHD(3), high 10-min intraoperative PTH, and high postoperative 3-month PTH were independently associated with ePTH at 6-month. Although 39.1% of patients had ePTH at 6 months, more than 50% had at least 1 ePTH within the first 2 years of follow-up. Recurrence appeared similar between those with or without ePTH at 6 months.published_or_final_versionSpringer Open Choice, 21 Feb 201

Myths and misconceptions about hypnosis and suggestion: Separating fact and fiction

We present 21 prominent myths and misconceptions about hypnosis in order to promulgate accurate information and to highlight questions for future research. We argue that these myths and misconceptions have (a) fostered a skewed and stereotyped view of hypnosis among the lay public, (b) discouraged participant involvement in potentially helpful hypnotic interventions, and (c) impeded the exploration and application of hypnosis in scientific and practitioner communities. Myths reviewed span the view that hypnosis produces a trance or special state of consciousness and allied myths on topics related to hypnotic interventions; hypnotic responsiveness and the modification of hypnotic suggestibility; inducing hypnosis; and hypnosis and memory, awareness, and the experience of nonvolition. By demarcating myth from mystery and fact from fiction, and by highlighting what is known as well as what remains to be discovered, the science and practice of hypnosis can be advanced and grounded on a firmer empirical footing

Novel H6PDH mutations in two girls with premature adrenarche: 'apparent' and 'true' CRD can be differentiated by urinary steroid profiling.

Inactivating mutations in the enzyme hexose-6-phosphate dehydrogenase (H6PDH, encoded by H6PD) cause apparent cortisone reductase deficiency (ACRD). H6PDH generates cofactor NADPH for 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1, encoded by HSD11B1) oxo-reductase activity, converting cortisone to cortisol. Inactivating mutations in HSD11B1 cause true cortisone reductase deficiency (CRD). Both ACRD and CRD present with hypothalamic-pituitary-adrenal (HPA) axis activation and adrenal hyperandrogenism. To describe the clinical, biochemical and molecular characteristics of two additional female children with ACRD and to illustrate the diagnostic value of urinary steroid profiling in identifying and differentiating a total of six ACRD and four CRD cases. Clinical, biochemical and genetic assessment of two female patients presenting during childhood. In addition, results of urinary steroid profiling in a total of ten ACRD/CRD patients were compared to identify distinguishing characteristics. Case 1 was compound heterozygous for R109AfsX3 and a novel P146L missense mutation in H6PD. Case 2 was compound heterozygous for novel nonsense mutations Q325X and Y446X in H6PD. Mutant expression studies confirmed loss of H6PDH activity in both cases. Urinary steroid metabolite profiling by gas chromatography/mass spectrometry suggested ACRD in both cases. In addition, we were able to establish a steroid metabolite signature differentiating ACRD and CRD, providing a basis for genetic diagnosis and future individualised management. Steroid profile analysis of a 24-h urine collection provides a diagnostic method for discriminating between ACRD and CRD. This will provide a useful tool in stratifying unresolved adrenal hyperandrogenism in children with premature adrenarche and adult females with polycystic ovary syndrome (PCOS)

The effects of long-term total parenteral nutrition on gut mucosal immunity in children with short bowel syndrome: a systematic review

BACKGROUND: Short bowel syndrome (SBS) is defined as the malabsorptive state that often follows massive resection of the small intestine. Most cases originate in the newborn period and result from congenital anomalies. It is associated with a high morbidity, is potentially lethal and often requires months, sometimes years, in the hospital and home on total parenteral nutrition (TPN). Long-term survival without parenteral nutrition depends upon establishing enteral nutrition and the process of intestinal adaptation through which the remaining small bowel gradually increases its absorptive capacity. The purpose of this article is to perform a descriptive systematic review of the published articles on the effects of TPN on the intestinal immune system investigating whether long-term TPN induces bacterial translocation, decreases secretory immunoglobulin A (S-IgA), impairs intestinal immunity, and changes mucosal architecture in children with SBS. METHODS: The databases of OVID, such as MEDLINE and CINAHL, Cochran Library, and Evidence-Based Medicine were searched for articles published from 1990 to 2001. Search terms were total parenteral nutrition, children, bacterial translocation, small bowel syndrome, short gut syndrome, intestinal immunity, gut permeability, sepsis, hyperglycemia, immunonutrition, glutamine, enteral tube feeding, and systematic reviews. The goal was to include all clinical studies conducted in children directly addressing the effects of TPN on gut immunity. RESULTS: A total of 13 studies were identified. These 13 studies included a total of 414 infants and children between the ages approximately 4 months to 17 years old, and 16 healthy adults as controls; and they varied in design and were conducted in several disciplines. The results were integrated into common themes. Five themes were identified: 1) sepsis, 2) impaired immune functions: In vitro studies, 3) mortality, 4) villous atrophy, 5) duration of dependency on TPN after bowel resection. CONCLUSION: Based on this exhaustive literature review, there is no direct evidence suggesting that TPN promotes bacterial overgrowth, impairs neutrophil functions, inhibits blood's bactericidal effect, causes villous atrophy, or causes to death in human model. The hypothesis relating negative effects of TPN on gut immunity remains attractive, but unproven. Enteral nutrition is cheaper, but no safer than TPN. Based on the current evidence, TPN seems to be safe and a life saving solution

Gonadectomy in conditions affecting sex development: a registry-based cohort study

Objectives To determine trends in clinical practice for individuals with DSD requiring gonadectomy. Design Retrospective cohort study. Methods Information regarding age at gonadectomy according to diagnosis; reported sex; time of presentation to specialist centre; and location of centre from cases reported to the International DSD Registry and who were over 16 years old in January 2019. Results Data regarding gonadectomy were available in 668 (88%) individuals from 44 centres. Of these, 248 (37%) (median age (range) 24 (17, 75) years) were male and 420 (63%) (median age (range) 26 (16, 86) years) were female. Gonadectomy was reported from 36 centres in 351/668 cases (53%). Females were more likely to undergo gonadectomy (n = 311, P < 0.0001). The indication for gonadectomy was reported in 268 (76%). The most common indication was mitigation of tumour risk in 172 (64%). Variations in the practice of gonadectomy were observed; of the 351 cases from 36 centres, 17 (5%) at 9 centres had undergone gonadectomy before their first presentation to the specialist centre. Median age at gonadectomy of cases from high-income countries and low-/middle-income countries (LMIC) was 13.0 years (0.1, 68) years and 16.5 years (1, 28), respectively (P < 0.0001) with the likelihood of long-term retention of gonads being higher in LMIC countries. Conclusions The likelihood of gonadectomy depends on the underlying diagnosis, sex of rearing and the geographical setting. Clinical benchmarks, which can be studied across all forms of DSD will allow a better understanding of the variation in the practice of gonadectomy