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1.
Pediatr Diabetes ; 23(4): 499-506, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35138695

RESUMO

AIM: To investigate the oral health of children and adolescents with type 1 diabetes (T1D) and its associations with diabetes-related and lifestyle factors. DESIGN: Cross-sectional study at a large tertiary hospital pediatric diabetes clinic. Oral examination determined dental caries experience and gingival health. Secondary outcome measures included salivary characteristics, oral hygiene and dietary practices, and diabetes-related factors. RESULTS: Eighty children and adolescents with T1D participated; mean (SD) age and HbA1c were 13.4(2.6) years and 7.7(0.9)%, respectively. Forty-seven (59%) participants had one or more decayed, missing or filled teeth; 75 (94%) participants had gingivitis. Half (50%) reported ≥3 hypoglycemic episodes necessitating rapid-acting carbohydrate in the previous week. Sixty-two participants (78%) had normal saliva flow, however, 42 (52%) had reduced salivary buffering capacity. Glycemic control (HbA1c ) was not associated with caries experience, gingival health or salivary characteristics. Increased frequency of tooth brushing (OR, 0.11; 95%CI 0.01-0.97, p = 0.05) and interdental flossing (OR, 0.31; 95%CI 0.12-0.81, p = 0.02) were associated with lower caries experience. Interdental flossing (OR, 0.31; 95% CI 0.12-0.80, p = 0.02) and good oral hygiene (OR, 0.06; 95% CI 0.01-0.22, p < 0.001) were associated with less gingivitis. CONCLUSION: Poor oral health is common in children with T1D, regardless of HbA1c. Given potential implications for short- and long-term systemic health, this study demonstrates the need for targeted strategies to improve oral health in children with T1D.


Assuntos
Cárie Dentária , Diabetes Mellitus Tipo 1 , Gengivite , Adolescente , Criança , Estudos Transversais , Índice CPO , Cárie Dentária/epidemiologia , Cárie Dentária/etiologia , Cárie Dentária/prevenção & controle , Suscetibilidade à Cárie Dentária , Diabetes Mellitus Tipo 1/complicações , Gengivite/epidemiologia , Gengivite/etiologia , Humanos , Prevalência
2.
J Paediatr Child Health ; 58(1): 104-109, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34323325

RESUMO

AIM: To investigate the effectiveness of inpatient and outpatient interventions in attaining improved glycaemic control in children/adolescents with type 1 diabetes mellitus and persistently high/deteriorating HbA1c. METHODS: A retrospective study at a tertiary paediatric centre. Admitted individuals who had prior attempts at ambulatory stabilisation were matched with intervention naïve controls who underwent outpatient intervention. The mean age was 14.6 years in the admitted group and 14.7 years in the ambulatory group. Mean duration of diabetes was 6.1 years in the admitted group and 7.3 years in the ambulatory group. Change in HbA1c from baseline was assessed to 12 months. RESULTS: Mean baseline HbA1c was 11.3% (100 mmol/mol), with 11.4% in the admitted group and 11.2% in the ambulatory group. Sustained reduction in HbA1c at 12 months was seen in both groups (n = 35 in each): mean (standard deviation) 10.1% (1.5) in admitted (mean reduction in HbA1c 1.4%) and 9.7% (1.4) in ambulatory (mean reduction in HbA1c 1.5%). Proportions achieving delta HbA1c ≥2% (22 mmol/mol) at 12 months were 25 and 31% in admitted and ambulatory groups, respectively. A sustained reduction in HbA1c of ≥2% (22 mmol/mol) after 12 months was more likely in those who attained this reduction by 6 months (17/24 who achieved this at 6 months vs. 3/41 who had not). CONCLUSIONS: Both inpatient and outpatient stabilisation strategies achieved sustained improvements in HbA1c. We recommend an individualised approach to stabilisation, with review of the intervention's success at 6 months with further intensification as needed.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Adolescente , Glicemia , Criança , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hemoglobinas Glicadas/análise , Controle Glicêmico , Humanos , Pacientes Internados , Estudos Retrospectivos
3.
J Paediatr Child Health ; 57(9): 1402-1407, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33928709

RESUMO

AIM: Management of children with differences/disorders of sex development (DSD) is complex with limited evidence to guide clinical decisions. Regular multidisciplinary team meetings were set up in Sydney and Melbourne paediatric hospitals to enable systematic peer review of complex decision-making. We aim to describe the workload and role of these meetings. METHODS: The multidisciplinary team forum includes invited representatives from endocrinology, urology, gynaecology, genetics, psychology, social work, clinical ethics, laboratory and hospital executive and meetings occur 1-3 times monthly. Descriptive data were collected from de-identified meeting referrals and minutes between August 2012 to August 2018 (Sydney) and January 2014 to August 2018 (Melbourne). RESULTS: A total of 192 referrals (142 new and 50 follow-ups) aged 1 week to 17 years were discussed across the two sites. 46, XY DSD (n = 81) was the most common sub-classification. Consideration of surgical options and optimal management of gonads with malignant potential were amongst the common reasons for referral to the multidisciplinary team meetings. Surgical interventions were considered but not recommended after review for 38 of 154 (24.7%) procedures. Gonad retention to allow potential functional benefit was recommended in 15/46 (32.6%) referrals. Evidence of premalignant or malignant changes was found in 20/57 (35%) gonads removed, with dysgenetic features and atrophy/streak features in 6 (10.5%) and 27 (47.4%) gonads respectively. CONCLUSION: Formal DSD multidisciplinary team meetings provide a framework and opportunity for multi and interdisciplinary discussions amongst representatives from several specialities to help make complex decision-making.


Assuntos
Transtornos do Desenvolvimento Sexual , Equipe de Assistência ao Paciente , Adolescente , Criança , Transtornos do Desenvolvimento Sexual/terapia , Humanos , Encaminhamento e Consulta , Desenvolvimento Sexual
4.
J Assist Reprod Genet ; 38(10): 2735-2743, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34424432

RESUMO

PURPOSE: Increasing numbers of transgender adolescents are receiving gender-affirming treatments (GAT). Given GAT can impair reproductive function, clinical guidelines advise prior counselling regarding fertility preservation (FP). For transgender adults assigned male at birth, FP is usually achieved via a masturbatory sample and sperm cryopreservation. This is less straightforward in transgender adolescents, since they may not be developmentally ready to masturbate and/or masturbation may cause unacceptable gender dysphoria. Testicular biopsy represents an alternative method for sperm retrieval in these adolescents, but for those in early/mid puberty, it is difficult to predict whether sperm will be found. The purpose of this study was therefore to identify factors that predict successful sperm retrieval for cryopreservation via testicular biopsy. METHODS: A retrospective cohort study was undertaken at a tertiary-referral pediatric gender service. Subjects were included if they'd received a testicular biopsy in association with the commencement of GAT between 2010 and 2019. The primary outcome measure was successful sperm retrieval, and potential predictors included age, testicular volume and serum testosterone, LH and FSH levels. RESULTS: Of 25 subjects who received a biopsy prior to starting any GAT, 17 had successful sperm retrieval. While age, testosterone, LH and FSH levels showed minimal differences, testicular volume was significantly higher in those with successful sperm retrieval, and a threshold of ≥ 10 mL showed 92% sensitivity and 71% specificity in predicting successful retrieval. An additional 6 patients received a biopsy after starting puberty suppression and before commencement of oestrogen, and one of these individuals had sperm successfully retrieved despite > 2 years of regular puberty suppression. CONCLUSION: These findings suggest that testicular volume is most useful in predicting successful sperm retrieval following testicular biopsy in transgender adolescents and are likely to be of relevance to other young people undertaking FP, including those with cancer.


Assuntos
Criopreservação/métodos , Preservação da Fertilidade/métodos , Recuperação Espermática/estatística & dados numéricos , Testículo/cirurgia , Pessoas Transgênero/estatística & dados numéricos , Adolescente , Biópsia , Humanos , Masculino , Estudos Retrospectivos
5.
Pediatr Diabetes ; 21(7): 1292-1300, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32829528

RESUMO

INTRODUCTION: In 2017, the Australian Federal Government fully subsidized continuous glucose monitoring (CGM) devices for patients under 21 years of age with T1D with the aim of reducing rates of severe hypoglycaemia (SH) and improving metabolic control. The aim of this study was to reports on metabolic outcomes in youth from a single tertiary centre. METHODS: The study design was observational. Data were obtained on youth who commenced CGM between May 2017 and December 2019. RESULTS: Three hundred and forty one youth who commenced CGM and had clinical outcome data for a minimum of 4 months. 301, 261, 216, 172, and 125 had outcome data out to 8, 12, 16, 20, and 24 months, respectively. Cessation occurred between 27.9% and 32.8% of patients 12 to 24 months after CGM commencement. HbA1c did not change in patients who continued to use CGM. In the 12 months prior to starting CGM the rate of severe hypoglycaemia events were 5.0 per 100 patient years. The rates of severe hypoglycaemia in those continuing to use CGM at 4, 8, 12, 16, 20, and 24 months, were 5.2, 5.1, 1.6, 6.1, 2.4, and 0 per 100 patient years, respectively. DISCUSSION: Our experience of patients either ceasing or underusing CGM is less than reported in other cohorts but is nonetheless still high. There may have been a reduction in rates of severe hypoglycaemia over the 24 months follow up period; however, the absolute numbers of events were so low as to preclude meaningful statistical analysis.


Assuntos
Automonitorização da Glicemia/instrumentação , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Financiamento Governamental , Hipoglicemia/prevenção & controle , Adolescente , Austrália , Glicemia/metabolismo , Automonitorização da Glicemia/economia , Criança , Diabetes Mellitus Tipo 1/complicações , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemia/sangue , Hipoglicemia/etiologia , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Masculino , Atenção Terciária à Saúde
6.
Pediatr Diabetes ; 19(4): 832-839, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29573084

RESUMO

OBJECTIVE: The purpose of this study was to estimate clinician qualities that influence metabolic outcomes in youth with type 1 diabetes. RESEARCH DESIGN AND METHODS: Data were gathered over two 3 month periods in a large tertiary diabetes center (1500 patients, 8 clinicians) from patients with type 1 diabetes who received continuous care from each clinician. Data included sex, age, diabetes duration, insulin regimen, body mass index (BMI), insulin dose and episodes of severe hypoglycemia. Clinician data included target blood glucose levels, target glycated hemoglobin (HbA1c), Diabetes Attitude Scale and Big 5 Personality Inventory Scale. Mean HbA1c per clinician was the primary outcome variable. RESULTS: The 8 clinicians saw a total of 464 patients during the first time period, and 603 in the second time period. Lowest to highest mean HbA1c per clinician varied by 0.7%. There were small but statistically significant differences between clinicians with their patients' age at diagnosis, duration of diabetes, age, gender, treatment type and BMI SD score. After controlling for these differences, the clinician characteristics that were associated with lower mean HbA1c were having no lower limit in target HbA1c and being self-reportedly "less agreeable." The impact of these clinician attitudinal traits was equivalent to the combined effects of patient characteristics and treatment type. CONCLUSIONS: There was a significant variation in metabolic outcomes between treating clinicians. After controlling for patient clinical differences, clinician mean HbA1c was associated with lower limit in target HbA1c and being "less agreeable." Clinicians who were more demanding and dogmatic appeared to have better outcomes.


Assuntos
Atitude do Pessoal de Saúde , Diabetes Mellitus Tipo 1/terapia , Personalidade/fisiologia , Papel do Médico , Relações Médico-Paciente , Adolescente , Glicemia/metabolismo , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/epidemiologia , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Lactente , Recém-Nascido , Masculino , Papel do Médico/psicologia , Prognóstico , Inquéritos e Questionários , Resultado do Tratamento
7.
Med J Aust ; 206(9): 398-401, 2017 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-28490305

RESUMO

OBJECTIVES: To determine the relationship between glycaemic control trajectory and the long term risk of severe complications in people with type 1 diabetes mellitus, as well as the effects of paediatric and adult HbA1c levels. DESIGN, SETTING, PARTICIPANTS: Data linkage study of data for adults with childhood-onset type 1 diabetes (diagnosed during 1975-2010) who had transitioned from paediatric diabetes care at the Royal Children's Hospital (Melbourne) to adult diabetes care at the Royal Melbourne Hospital during 1992-2013. MAIN OUTCOME MEASURES: Severe complications were categorised as severe diabetic retinopathy (SDR), chronic kidney disease, ulceration or amputation, and death. Mean HbA1c levels were calculated for the paediatric and adult periods. Four glycaemic control trajectories were defined according to mean paediatric and adult HbA1c levels: stable low (paediatric and adult HbA1c ≤ 66 mmol/mol); improving (paediatric HbA1c > 66 mmol/mol, adult HbA1c ≤ 66 mmol/mol); worsening (paediatric HbA1c ≤ 66 mmol/mol, adult HbA1c > 66 mmol/mol); and stable high (paediatric and adult HbA1c > 66 mmol/mol). RESULTS: 503 eligible participants (253 men) were identified, 26 (5.2%) of whom had at least one severe complication, including 16 with SDR (3.2%). No-one in the stable low group, but 4% of the improving, 1% of the worsening, and 7% of the stable high groups developed SDR. Higher mean paediatric (per 10.9 mmol/mol increase: odds ratio [OR], 2.9; 95% CI, 1.9-4.3; P < 0.01) or adult HbA1c levels (OR, 2.1; 95% CI, 1.4-3.1; P < 0.01) were associated with increased risk of SDR, as was longer duration of type 1 diabetes (per additional year: OR, 1.3; 95% CI, 1.2-1.5; P < 0.01). CONCLUSION: SDR was associated with higher paediatric HbA1c levels, independent of glycaemic control during adulthood; it was not documented in patients with a stable low glycaemic control trajectory.


Assuntos
Diabetes Mellitus Tipo 1/complicações , Retinopatia Diabética/epidemiologia , Hemoglobinas Glicadas/análise , Nefropatias/epidemiologia , Adolescente , Adulto , Glicemia/análise , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Armazenamento e Recuperação da Informação , Modelos Logísticos , Masculino , Análise Multivariada , Estudos Retrospectivos , Fatores de Risco , Transição para Assistência do Adulto , Vitória , Adulto Jovem
9.
Pediatr Diabetes ; 17(3): 174-83, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-25643603

RESUMO

BACKGROUND AND OBJECTIVE: Controversy exists regarding which individuals will benefit most from commencement of diabetes technologies such as continuous subcutaneous insulin infusion (CSII) or continuous glucose monitoring systems (CGMS), such as 'real-time' sensor-augmented pumping (SAP). Because higher usage correlates with haemoglobin A1c (HbA1c) achieved, we aimed to predict future usage of technologies using a questionnaire-based tool. SUBJECTS: The tool was distributed to two groups of youth with type 1 diabetes; group A (n = 50; mean age 12 ± 2.5 yr) which subsequently commenced 'real-time' CGMS and group B (n = 47; mean age 13 ± 3 yr) which commenced CSII utilisation. METHODS: For the CGMS group, recommended usage was ≥5 days (70%) per week [≥70% = high usage (HU); <70% = low usage (LU)], assessed at 3 months. In the CSII group, HU was quantified as entering ≥5 blood sugars per day to the pump and LU as <5 blood sugars per day, at 6 months from initiation. Binary logistic regression with forward stepwise conditional was used to utilise tool scales and calculate an applied formula. RESULTS: Of the CGMS group, using gender, baseline HbA1c, and two subscales of the tool generated a formula which predicted both high and low usage with 92% accuracy. Twelve (24%) showed HU vs. 38 who exhibited LU at 3 months. Of the CSII group, 32 (68%) exhibited HU vs. 15 who exhibited LU at 6 months. Four tool items plus gender predicted HU/LU with 95% accuracy. CONCLUSIONS: This pilot study resulted in successful prediction of individuals who will and those who will not go on to show recommended usage of CSII and CGMS.


Assuntos
Automonitorização da Glicemia/estatística & dados numéricos , Diabetes Mellitus Tipo 1/terapia , Sistemas de Infusão de Insulina/estatística & dados numéricos , Cooperação do Paciente/estatística & dados numéricos , Adolescente , Criança , Feminino , Humanos , Masculino , Projetos Piloto , Inquéritos e Questionários
12.
Int J Transgend Health ; 25(1): 10-18, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38323021

RESUMO

Background: Pelvic pain is a common complaint among individuals assigned female at birth. However, few studies have explored pelvic pain among transmasculine patients on gender-affirming testosterone treatment, and most of these were performed in adult populations. Aims: The aim of our study was to investigate the prevalence, risk factors, nature and treatment of pelvic pain among trans adolescents on testosterone. Methods: A retrospective cohort study was performed on all trans adolescents started on gender-affirming testosterone treatment at our institution between 2007 and 2020. Results: Among 158 trans adolescents who were started on testosterone therapy and followed-up for at least six months, 37 (23.4%) reported pelvic pain, with a median interval between testosterone initiation and reported onset of pain of 1.6 months (range 0.3-6.4). The prevalence of pelvic pain was higher in patients who were receiving menstrual suppression (n = 36, 26.3%) compared to those who were not (n = 1, 4.8%), giving a risk difference of 21.5% (95% CI 9.8% to 33.2%, p = 0.028). The most common descriptive terms were "cramps" (n = 17, 45.9%) and "similar to previous period pain" (n = 8, 21.6%). A range of different pharmacological strategies were employed, including paracetamol, NSAIDs, danazol, norethisterone, medroxyprogesterone, etonogestrel implant, intra-uterine device, goserelin and pelvic floor physiotherapy, with variable outcomes. Conclusion: In conclusion, we report here - in what is to our knowledge the first time - the prevalence rate of pelvic pain in trans adolescents on gender-affirming testosterone treatment, and observe that a quarter of them described pelvic pain. Limitations of our study include its retrospective nature, which is likely to be associated with under-reporting of pelvic pain, and the limited documentation of the nature and likely causes of this pain within the medical records. Prospective longitudinal studies to better understand the nature, etiology and optimal management of testosterone-associated pelvic pain are therefore warranted.

13.
Arch Dis Child ; 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38237958

RESUMO

AIMS: Improved behaviour, mood, cognition and HbA1c have been reported with short-term use of continuous subcutaneous insulin infusion (CSII) in youth with type 1 diabetes (T1D). We sought to re-examine these findings in a randomised controlled trial (RCT), with longitudinal follow-up. METHODS: RCT of youth aged 7-15 years with T1D, at two tertiary paediatric centres. Participants were randomised to commence CSII or continue multiple daily injections (MDI). Behaviour, mood, cognition and HbA1c were assessed. Primary outcome was difference in parent-reported behaviour (BASC-2) at 4 months. After the 4-month RCT, MDI participants commenced CSII; outcomes were reassessed at +2 years. RESULTS: Participating youth (n=101) were randomised to CSII (n=56) or MDI (n=45). Significant differences favouring CSII were found at 4 months in parent-reported behaviour problems (Cohen's d 0.41 (95% CI 0.004 to 0.795); p=0.048) and HbA1c (mean (95% CI) difference: 7 (2.3 to 11.7) mmol/mol (0.6% (0.2 to 1.0%); p=0.001)). Improvements from baseline were documented in mood and cognitive outcomes in both study groups over the 4-month RCT; however, no between-group differences were evident at 4 months. Sixteen of 76 (21%) participants completing assessments at +2 years had discontinued CSII. In n=60 still using CSII, measurements of behaviour, mood and HbA1c were comparable to baseline. CONCLUSIONS: Parent-reported behaviour problems and HbA1c, but not mood or neurocognitive outcomes, were clinically significantly lower with CSII, relative to MDI, after 4 months. Observational follow-up indicated no impact of treatment modality at +2 years, relative to baseline levels. Taken together, these data indicate that use of CSII alone does not comprehensively benefit neuropsychological outcomes in childhood T1D.

14.
Diabetes Metab Res Rev ; 29(4): 257-72, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23364787

RESUMO

Optimal use of recent technological advances in insulin delivery and glucose monitoring remain limited by the impact of behaviour on self-care. In recent years, there has been a resurgence of interest in psychosocial methods of optimizing care in youth with type 1 diabetes. We therefore sought to examine the literature for demographic, interpersonal and intrapersonal correlates of self-care and/or metabolic control. Studies for this systematic review were obtained via an electronic search of Medline, Embase, Cumulative Index to Nursing and Allied Health Literature and PsycINFO databases. Seventy studies fulfilled the inclusion criteria. These studies have indicated that identifiable individual characteristics in each domain are robustly associated with metabolic control and/or self-care in children and adolescents. We present these characteristics and propose a theoretical model of their interactions and effect on diabetes outcomes. There is currently no consensus regarding patient selection for insulin pump therapy. In this era of scarce healthcare resources, it may be prudent to identify youth requiring increased psychosocial support prior to regimen intensification. The importance of this review lies in its potential to create a framework for rationally utilizing resources by stratifying costly therapeutic options to those who, in the first instance, will be most likely to benefit from them.


Assuntos
Atitude Frente a Saúde , Automonitorização da Glicemia/psicologia , Demografia , Diabetes Mellitus Tipo 1/psicologia , Autocuidado/psicologia , Adolescente , Diabetes Mellitus Tipo 1/terapia , Humanos , Seleção de Pacientes , Psicoterapia
15.
Proc Natl Acad Sci U S A ; 107(7): 3105-10, 2010 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-20133622

RESUMO

Heterozygous coding mutations in the INS gene that encodes preproinsulin were recently shown to be an important cause of permanent neonatal diabetes. These dominantly acting mutations prevent normal folding of proinsulin, which leads to beta-cell death through endoplasmic reticulum stress and apoptosis. We now report 10 different recessive INS mutations in 15 probands with neonatal diabetes. Functional studies showed that recessive mutations resulted in diabetes because of decreased insulin biosynthesis through distinct mechanisms, including gene deletion, lack of the translation initiation signal, and altered mRNA stability because of the disruption of a polyadenylation signal. A subset of recessive mutations caused abnormal INS transcription, including the deletion of the C1 and E1 cis regulatory elements, or three different single base-pair substitutions in a CC dinucleotide sequence located between E1 and A1 elements. In keeping with an earlier and more severe beta-cell defect, patients with recessive INS mutations had a lower birth weight (-3.2 SD score vs. -2.0 SD score) and were diagnosed earlier (median 1 week vs. 10 weeks) compared to those with dominant INS mutations. Mutations in the insulin gene can therefore result in neonatal diabetes as a result of two contrasting pathogenic mechanisms. Moreover, the recessively inherited mutations provide a genetic demonstration of the essential role of multiple sequence elements that regulate the biosynthesis of insulin in man.


Assuntos
Diabetes Mellitus/genética , Insulina/biossíntese , Mutação/genética , Precursores de Proteínas/genética , Análise Mutacional de DNA , Primers do DNA/genética , Dosagem de Genes , Genes Recessivos/genética , Humanos , Recém-Nascido , Insulina/genética , Masculino , Sondas de Oligonucleotídeos
16.
Horm Res Paediatr ; 96(2): 128-143, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-34781289

RESUMO

BACKGROUND: Despite distinct underlying aetiologies, the clinical phenotypes and hormonal profiles of children with various differences of sex development (DSD) are often similar, which presents challenges to ascertaining an accurate diagnosis on clinical grounds alone. Associated features and important clinical outcomes can, however, vary significantly in different DSD, thus establishing an accurate molecular diagnosis may have important implications for decision-making and management planning in a given individual. SUMMARY: The wider availability of next-generation sequencing techniques in recent years has led to recommendations for earlier integration of genetic testing in the diagnostic pathway of children with DSD. This review provides a practical overview of the clinical applications, advantages, and limitations of the more commonly available diagnostic genetic tests and outlines a suggested approach to testing. The potential clinical implications of a confirmed genetic diagnosis, subsequent management pathways for individuals with DSD, and challenges that remain to be addressed are also outlined. KEY MESSAGES: Despite significant improvements in our understanding of the complex genetic pathways that underlie DSD, an accurate diagnosis still eludes many affected individuals. Establishing a molecular diagnosis provides aetiological certainty, enabling improved information for families and individualized clinical management, including monitoring or prophylactic intervention where additional health risks exist. A stepwise approach to genomic testing is recommended to afford highest diagnostic yield from available resources. Looking forward, collaborative multicentre prospective studies will be required to assess the true impact of a genetic diagnosis on improving clinical care pathways and health, well-being and patient-reported outcomes for individuals with DSD.


Assuntos
Transtornos do Desenvolvimento Sexual , Humanos , Criança , Transtornos do Desenvolvimento Sexual/diagnóstico , Transtornos do Desenvolvimento Sexual/genética , Estudos Prospectivos , Testes Genéticos , Fenótipo , Biologia Molecular , Desenvolvimento Sexual/genética
17.
Obstet Gynecol ; 142(5): 1096-1104, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37562053

RESUMO

OBJECTIVE: To investigate the prevalence, nature, and effectiveness of menstrual suppression in transgender and gender-diverse (TGD) adolescents, and to explore whether there is an association between menstrual suppression and mental health in this population. METHODS: A cross-sectional study was performed of TGD adolescents assigned female at birth attending their first appointment at a specialist pediatric gender service between February 2017 and December 2021. Demographic and mental health data were collected using a questionnaire at the time of first visit, and information regarding menstrual suppression at this time was retrieved from the medical record. RESULTS: A total of 530 TGD individuals were included; 131 (24.7%) were on menstrual suppression at their initial visit, mainly to help alleviate gender dysphoria. Combined oral contraceptive pills were the most common agent used (n=61, 46.6%), followed by norethindrone (n=39, 29.8%) and intramuscular medroxyprogesterone (n=19, 14.5%). Rates of effectiveness (in stopping menstruation) and patient satisfaction were high. Among the 399 individuals not on menstrual suppression, there was strong interest in starting this treatment. No differences in the risk of gender dysphoria, depression, or anxiety were observed between those who were receiving menstrual suppression and those who were not. CONCLUSION: Effectiveness of and satisfaction with menstrual suppression were high in TGD adolescents receiving this treatment. These findings support the routine exploration and management of menstrual health in TGD adolescents. However, menstrual suppression was not associated with any difference in gender dysphoria, depression, or anxiety symptoms in this cross-sectional study, and longitudinal studies are required to better investigate this.


Assuntos
Menstruação , Pessoas Transgênero , Transexualidade , Adolescente , Criança , Feminino , Humanos , Recém-Nascido , Estudos Transversais , Identidade de Gênero , Saúde Mental , Pessoas Transgênero/psicologia
18.
Int J Neonatal Screen ; 9(4)2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37873849

RESUMO

There are mixed reports on the inclusion and use of 21 deoxycortisol (21DF) as the primary decision marker for classical 21-hydroxylase deficiency. We hypothesize that this may be due to insufficient recognition of the presence and chromatographic separation of isomeric steroids. The aim of this study was to determine the comparative utility of 21DF for screening and diagnosis of CAH due to classical 21-hydroxylase deficiency using a second-tier LC-MS/MS method that included the separation of isomeric steroids to 17OHP and 21DF. For each baby sample, one 3.2 mm dried blood spot was eluted in a methanolic solution containing isotopically matched internal standards. Data were interrogated by univariate and receiver operator characteristic analysis. Steroid profile results were generated for 924 non-CAH baby samples (median gestational age 37 weeks, range 22 to 43 weeks) and 17 babies with 21-hydroxylase deficiency. The ROC curves demonstrated 21DF to have the best sensitivity and specificity for the diagnosis of classical 21-hydroxylase deficiency with an AUC = 1.0. The heatmap showed the very strong correlation (r = 0.83) between 17OHP and 21DF. Our data support 21DF as a robust marker for CAH due to 21-hydroxylase deficiency. We recommend that 21DF be incorporated into routine newborn screening panels as part of the second-tier LC-MS/MS method, follow-up plasma steroid panels, and external quality assurance material.

19.
Sex Dev ; 17(1): 8-15, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36724755

RESUMO

INTRODUCTION: Steroid 5-alpha reductase deficiency (5α-R2D) is a rare condition caused by genetic variants that reduce the activity of the enzyme that converts testosterone into dihydrotestosterone. The clinical spectrum of 5α-R2D is known to overlap with other 46,XY differences of sex development (DSD) such as androgen insensitivity or gonadal dysgenesis. However, the clinical trajectories of the aetiologies can differ, with 5α-R2D presenting its own challenges. METHODS: In this study, we have collated clinical information for five individuals with variants in SRD5A2 identified using research genetic testing in an Australian paediatric setting. RESULTS: We describe how a genetic finding resolved or confirmed a diagnosis for these individuals and how it guided clinical management and family counselling. CONCLUSION: This work highlights the importance of early genetic testing in children born with 46,XY DSD where it complements traditional first-line testing.


Assuntos
Transtorno 46,XY do Desenvolvimento Sexual , Testes Genéticos , Masculino , Humanos , Criança , Mutação , Austrália , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/genética , Transtorno 46,XY do Desenvolvimento Sexual/genética , Transtorno 46,XY do Desenvolvimento Sexual/patologia , Testosterona , Proteínas de Membrana/genética
20.
J Clin Endocrinol Metab ; 107(1): 241-257, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34476487

RESUMO

Internationally, increasing numbers of children and adolescents with gender dysphoria are presenting for care. In response, gender-affirming therapeutic interventions that seek to align bodily characteristics with an individual's gender identity are more commonly being used. Depending on a young person's circumstances and goals, hormonal interventions may aim to achieve full pubertal suppression, modulation of endogenous pubertal sex hormone effects, and/or development of secondary sex characteristics congruent with their affirmed gender. This is a relatively novel therapeutic area and, although short-term outcomes are encouraging, longer term data from prospective longitudinal adolescent cohorts are still lacking, which may create clinical and ethical decision-making challenges. Here, we review current treatment options, reported outcomes, and clinical challenges in the pharmacological management of trans and gender-diverse adolescents.


Assuntos
Disforia de Gênero/tratamento farmacológico , Terapia de Reposição Hormonal/métodos , Procedimentos de Readequação Sexual/métodos , Adolescente , Criança , Feminino , Disforia de Gênero/diagnóstico , Disforia de Gênero/psicologia , Humanos , Masculino , Pessoas Transgênero/psicologia , Resultado do Tratamento
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