Health-related quality of life and binge eating among adolescent girls with PCOS

Publisher Copyright: Copyright: © 2022 The Author(s).Background: Polycystic ovary syndrome (PCOS) affects 3–8% of adolescents. It is characterized by hyperandrogenism and oligoovulation/anovulation. PCOS has a negative impact on health-related quality of life (HRQoL). However, the extents to which factors influence total HRQoL of adolescents are not known. Adult PCOS patients have a higher incidence of binge eating than the general reproductive-age female population. Limited data on binge eating in adolescents with PCOS are available. Aim of this study was to investigate how PCOS and its associated factors, including binge eating, affect the HRQoL of adolescent girls. Methods: This case-control study recruited 63 adolescent girls 13–18 years of age with PCOS and 66 age-matched healthy controls. The PCOS health-related quality of life questionnaire (PCOSQ) and Binge Eating Scale (BES) were used. Multiple linear regression was executed to establish exact predictors and their effect on total HRQoL. Results: HRQoL was significantly lower in adolescents with PCOS than controls (4.9 (interquartile range (IQR) 1.5) vs. 5.8 (IQR 0.9) points). The lowest scores were found in the body hair and weight domains. BES results were not significantly higher in the PCOS group than in the control group (p = 0.727). The main predictors for total HRQoL were PCOS diagnosis per se (β = –1.002; p < 0.001), BES score (β = –0.27; p = 0.004) and body mass index (BMI) percentile (β = –0.007; p = 0.013). Conclusions: The lower HRQoL in adolescents with PCOS is attributable to the diagnosis of PCOS, BES score and BMI percentile, confirming the importance of tailoring clinical interventions and counselling to address the domains (i.e., symptoms of hirsutism and weight concerns) causing distress and lowering HRQoL. Further implementation research is required to evaluate the impact of targeted interventions on the HRQoL of adolescent girls with PCOS.publishersversionPeer reviewe

Graves’ disease as a manifestation of immune reconstitution inflammatory syndrome in an HIV-1-infected adolescent patient : A case report

Funding Information: Paediatric Endocrinology Department staff, Children's Clinical University Hospital; Outpatient Department of the Latvian Centre of Infectious Diseases; Rare Diseases Centre, Children's Clinical University Hospital. Publisher Copyright: © 2022 The AuthorsIntroduction: Although Graves' disease (GD) is the most common cause of hyperthyroidism in adolescents, it is very rare for it to result from the production of thyroid-stimulating hormone (TSH) receptor autoantibodies due to Graves' immune reconstitution inflammatory syndrome (IRIS). Especially for paediatric patients, very little is known about the aetiology and complete pathogenesis of Graves’ IRIS. Furthermore, details of a valid treatment plan are severely lacking. The case report presented here is only the third for paediatric patients worldwide. Case presentation: We report on a Caucasian female adolescent who initially presented with non-specific complaints about discomfort and tightness in the anterior part of the neck and thyroid enlargement. Based on clinical, laboratory and thyroid ultrasound findings, she was diagnosed with GD. However, after several months of outpatient treatment, the patient's GD could still not be fully managed with conservative therapy alone. Only when the patient was hospitalized for the third time was it discovered that she had previously been diagnosed with human immunodeficiency virus infection and had received highly active antiretroviral therapy (HAART) for the previous 29 months. Consequently, the production of autoantibodies to TSH receptors and abnormal changes in thyroid hormones had led to the development of GD and her final diagnosis was established as Graves' IRIS. Ultimately, a total thyroidectomy was performed. Discussion/conclusion: This case report demonstrates how fundamentally important it is to have full access to a patient's complete anamnesis and results of all previous investigations. Clinicians should be made aware of the potential existence of thyroid dysfunction and other autoimmune or infectious processes in paediatric patients initiating or reinitiating HAART. Further research is needed to optimize the treatment for such paediatric patients.publishersversionPeer reviewe

Two Cases of Leigh Syndrome in One Family : Diagnostic Challenges and Clinical Management Experience in Latvia

Publisher Copyright: © 2021 Arta Katkevica et al.Leigh syndrome is a neurodegenerative disorder with an incidence of 1: 40,000 live births. The clinical presentation of LS is highly variable with heterogeneity in the disease-associated symptoms of cerebellar, motor, and extrapyramidal dysfunction and common infections. There is no effective treatment for this condition; as such, the prognosis of this condition is very poor with death occurring within the first few years of life. In this study, we report the first LS case in Latvia with SURF1 pathogenic variants in two siblings. The difficulties encountered establishing a diagnosis for the first proband and the effective prenatal diagnosis for the second offspring that led to termination of the pregnancy are discussed.publishersversionPeer reviewe

The genetic diagnosis of rare endocrine disorders of sex development and maturation : a survey among Endo-ERN centres

Differences of sex development and maturation (SDM) represent a heterogeneous puzzle of rare conditions with a large genetic component whose management and treatment could be improved by an accurate classification of underlying molecular conditions, and next-generation sequencing (NGS) should represent the most appropriate approach. Therefore, we conducted a survey dedicated to the use and potential outcomes of NGS for SDM disorders diagnosis among the 53 health care providers (HCP) of the European Reference Network for rare endocrine conditions. The response rate was 49% with a total of 26 HCPs from 13 countries. All HCPs, except 1, performed NGS investigations for SDM disorders on 6720 patients, 3764 (56%) with differences of sex development (DSD), including 811 unexplained primary ovarian insufficiency, and 2956 (44%) with congenital hypogonadotropic hypogonadism (CHH). The approaches varied from targeted analysis of custom gene panels (range: 11-490 genes) in 81.5% of cases or whole exome sequencing with the extraction of a virtual panel in the remaining cases. These analyses were performed for diagnostic purposes in 21 HCPs, supported by the National Health Systems in 16 cases. The likelihood of finding a variant ranged between 7 and 60%, mainly depending upon the number of analysed genes or criteria used for reporting, most HCPs also reporting variants of uncertain significance. These data illustrate the status of genetic diagnosis of DSD and CHH across Europe. In most countries, these analyses are performed for diagnostic purposes, yielding highly variable results, thus suggesting the need for harmonization and general improvements of NGS approaches.publishersversionPeer reviewe

Long-term prognosis of patients with pediatric pheochromocytoma

A third of patients with paraganglial tumors, pheochromocytoma, and paraganglioma, carry germline mutations in one of the susceptibility genes, RET, VHL, NF1, SDHAF2, SDHA, SDHB, SDHC, SDHD, TMEM127, and MAX. Despite increasing importance, data for long-term prognosis are scarce in pediatric presentations. The European-American-Pheochromocytoma-Paraganglioma-Registry, with a total of 2001 patients with confirmed paraganglial tumors, was the platform for this study. Molecular genetic and phenotypic classification and assessment of gene-specific long-term outcome with second and/or malignant paraganglial tumors and life expectancy were performed in patients diagnosed at <18 years. Of 177 eligible registrants, 80% had mutations, 49% VHL, 15% SDHB, 10% SDHD, 4%NF1, and one patient each in RET, SDHA, and SDHC. A second primary paraganglial tumor developed in 38% with increasing frequency over time, reaching 50% at 30 years after initial diagnosis. Their prevalence was associated with hereditary disease (P=0.001), particularly in VHL and SDHD mutation carriers (VHL vs others, P=0.001 and SDHD vs others, P=0.042). A total of 16 (9%) patients with hereditary disease had malignant tumors, ten at initial diagnosis and another six during follow-up. The highest prevalence was associated with SDHB (SDHB vs others, P<0.001). Eight patients died (5%), all of whom had germline mutations. Mean life expectancy was 62 years with hereditary disease. Hereditary disease and the underlying germline mutation define the long-term prognosis of pediatric patients in terms of prevalence and time of second primaries, malignant transformation, and survival. Based on these data, gene-adjusted, specific surveillance guidelines can help effective preventive medicine.publishersversionPeer reviewe

Role of Single Nucleotide Variants in the YAP1 Gene in Adolescents with Polycystic Ovary Syndrome

Background: Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in women. It can manifest in adolescence, affecting up to 8% of adolescents. Long-term health consequences characteristic of PCOS are impaired fertility, increased risk of type 2 diabetes, metabolic disorders and cardiovascular disease. All of these sequelae are exacerbated by increased body weight, a major feature of PCOS. The protein encoded by the YAP1 gene plays a key role in one of the pivotal mechanisms that govern cellular/organismal metabolism and contributes to the pathogenesis of metabolic diseases. Aim: To compare the prevalence of single nucleotide variants (SNVs) in the YAP1 gene among adolescents with PCOS, adolescents at risk of PCOS development and healthy adolescents, and assess their association with the clinical characteristics of PCOS. Results: The frequencies of the five investigated YAP1 gene SNVs (rs11225161, rs11225166, rs3858420, rs11225138 and rs79981660) were not significantly different among adolescents with PCOS, risk group patients and healthy controls. Furthermore, none of the SNVs contributed to the clinical characteristics of adolescents with PCOS and adolescents at risk of PCOS development. Conclusions: No significant associations were found between PCOS in adolescents and the five investigated SNVs in the YAP1 gene

Non-classical congenital adrenal hyperplasia-causing alleles in adolescent girls with pcos and in risk group for pcos development

Funding Information: Funding: The study was financially supported by a Riga Stradins University internal research grant. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Background: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women. Depending on the diagnostic criteria applied, it occurs in up to 16.6% of the general female population. Congenital adrenal hyperplasia includes a group of autosomal recessive disorders, the most common of which is non-classical congenital adrenal hyperplasia (NCAH) caused by mutations in the CYP21A2 gene. PCOS and NCAH have similar clinical manifestations (hyperandrogenemia, i.e., hirsutism, acne, alopecia, and increased androgen levels in the blood) and potential impact on long-term health (infertility, increased risk of type 2 diabetes, and cardiovascular disease. Consequently, it is thought that NCAH mutations in the heterozygous state may play a role in PCOS development and phenotypic expression. Objective: To determine the prevalence of the most common pathogenic alleles of the CYP21A2 gene in adolescents with PCOS and adolescents at risk of PCOS development, and to compare the results with healthy adolescents matched for gynecological age. Methods: A cross-sectional study was conducted with 55 PCOS patients, 23 risk patients (with hyperandrogenism but a normal menstrual cycle), and 49 healthy adolescents. Genetic variations in the CYP21A2 gene were analyzed using a standard Multiplex Ligation-dependent Probe Amplification test (SALSA MLPA Probemix P050-C1 CAH; MRC Holland). Results: No significant differences were found among the three groups regarding the frequency of carriers of NCAH variations in the heterozygous state. It was found that the I172N carrier in the PCOS group had a significantly higher Global Acne Grading Scale score than PCOS patients without this variation (p = 0.038). Within the control group of healthy adolescents, compound heterozygous carriers (IVS2-12A > G and-113G > A) had a significantly higher body mass index than non-carriers (p = 0.036). Conclusion: We found no differences in the incidence of NCAH-causing variations in the heterozygous state in adolescent PCOS patients, risk adolescents (with hirsutism but normal menstruation), and healthy adolescents. Future studies of larger cohorts and rarer pathogenic CYP21A2 gene variations are required.publishersversionPeer reviewe

The european registry for rare bone and mineral conditions (EuRR-Bone): results of a survey on osteogenesis imperfecta and fibrous dysplasia McCune-Albright síndrome

Introduction: EuRR-Bone offers an electronic reporting system (e REC) that captures the occurrence of rare conditions within reference networks such as ERN BOND and Endo-ERN. Secondary surveys following the reported cases in e-REC collect a brief amount of data for understanding the clinical presentation of the reported condition. Osteogenesis Imperfecta (OI) and Fibrous Dysplasia/McCune-Albright Syndrome (FD/MAS) are two rare conditions that require expert care but the extent of variation in care delivery across expert centres is unclear. Methods: Between May 2020 and May 2021, 80 FD/MAS and 76 OI cases were reported in e-REC. Reporters were invited to complete a secure online questionnaire. The questionnaire was completed in 123/ 156 cases (68%) by 12 centres from eight countries. Results: The median age at presentation for FD/MAS was 20 years (range, 0, 72) and 3 years (range 0, 47) for OI. History, clinical findings and imaging were collected in the diagnosis of both conditions. Of 58 confirmed cases of FD/MAS 8 (14%) had genetic testing; 30/31 confirmed cases of OI had genetic testing (97%). Of 58 FD/MAS cases, endocrinopathies were tested in 38 (65%), Gonadotropin-Independent precocious puberty was the commonest pathology (24%) followed by GH excess and Hyperprolactinemia (both 8%). Mobility was assessed in 16/ 31 (51%) OI cases, using clinical data in 43%, and a 6-minute walk test in 25%. Cardiovascular morbidity was investigated in 17/31 (52%) OI cases, pulmonary problems were reported in 1/31 (3%). Quality of life was assessed in 41% of FD/MAS cases (5/25 pediatric and 20/33 adult cases) and 32% of OI cases (10/30 pediatric patients). Validated questionnaires (e.g.EQ5D, BPI) were used only in FD/MAS patients. Conclusion: Although the clinical care of OI and FD/MAS at expert centres is variable, there are some outcomes that are collected routinely by the majority and may represent the core dataset that should be used as a minimum to unify data collection across centres

The genetic diagnosis of rare endocrine disorders of sex development and maturation: a survey among Endo-ERN centres

Differences of sex development and maturation (SDM) represent a heterogeneous puzzle of rare conditions with a large genetic component whose management and treatment could be improved by an accurate classification of underlying molecular conditions, and next-generation sequencing (NGS) should represent the most appropriate approach. Therefore, we conducted a survey dedicated to the use and potential outcomes of NGS for SDM disorders diagnosis among the 53 health care providers (HCP) of the European Reference Network for rare endocrine conditions. The response rate was 49% with a total of 26 HCPs from 13 countries. All HCPs, except 1, performed NGS investigations for SDM disorders on 6720 patients, 3764 (56%) with differences of sex development (DSD), including 811 unexplained primary ovarian insufficiency, and 2956 (44%) with congenital hypogonadotropic hypogonadism (CHH). The approaches varied from targeted analysis of custom gene panels (range: 11–490 genes) in 81.5% of cases or whole exome sequencing with the extraction of a virtual panel in the remaining cases. These analyses were performed for diagnostic purposes in 21 HCPs, supported by the National Health Systems in 16 cases. The likelihood of finding a variant ranged between 7 and 60%, mainly depending upon the number of analysed genes or criteria used for reporting, most HCPs also reporting variants of uncertain significance. These data illustrate the status of genetic diagnosis of DSD and CHH across Europe. In most countries, these analyses are performed for diagnostic purposes, yielding highly variable results, thus suggesting the need for harmonization and general improvements of NGS approaches