INFERIOR PETROSAL SINUS SAMPLING IN THE DIAGNOSIS OF CUSHING'S SYNDROME

Introduction: 15% of ACTH-dependent Cushing´s syndrome is due to ectopic ACTH-secreting tumor. Radiological and biochemical techniques have been developed to assist distinguish the source of the hormone: ectopic or pituitary gland. Objective: Case report of an ACTH-dependent Cushing´s syndrome whose diagnostic definition was conducted by bilateral inferior petrosal sinus sampling. Case Report: A 47 years old female, presenting with amenorrhea, weight gain, weakness, hypertension, osteoporosis, mood disorder. On examination, moon facies, dorsal hump, abdominal purple striae 1.5 cm of width, lower limb edema. Laboratory findings demonstrated ACTH-dependent hypercortisolism. Suppression test with dexamethasone 16 mg suggested ectopic ACTH production. However, imaging did not detect lesions in the CNS or elsewhere responsible for hormone excess. The patient was referred to another service to perform inferior petrosal sinus sampling, which showed no gradient between the ACTH levels measured close to the gland compared to the periphery, confirming the ectopic source of ACTH. New imaging tests showed tumor in the thymus. Patient underwent thoracoscopy with excision of the lesion and was discharged on the 10th postoperative with normalization of cortisol and ACTH. Conclusion: The bilateral inferior petrosal sinus sampling is the test that provides greater sensitivity and specificity in differentiating pituitary and ectopic ACTH production. Once the initial imaging tests showed no tumor, this test was instrumental in confirming the etiology of ectopic ACTH, which led to new research and, consequently, diagnosis and treatment.Introdução: 15% dos casos de síndrome de Cushing ACTH-dependente devem-se a tumor ectópico. Técnicas bioquímicas e radiológicas têm sido desenvolvidas para ajudar na distinção entre produção ectópica ou hipofisária de ACTH. Objetivo: Relato de síndrome de Cushing ACTH-dependente, cuja definição diagnóstica foi realizada por cateterização bilateral de seio petroso inferior. Relato de caso: Mulher, 47 anos, com amenorreia, ganho de peso, fraqueza, hipertensão arterial, osteoporose e transtorno de humor. Ao exame, fácies em lua cheia e giba dorsal, estrias violáceas abdominais de 1,5 cm, membros inferiores com edema. A investigação laboratorial detectou hipercortisolismo ACTH-dependente. Teste de supressão com dexametasona (16 mg) sugeriu produção ectópica de ACTH. Entretanto, exames de imagem não detectaram lesões no sistema nervoso central ou fora dele responsáveis pelo excesso hormonal. A paciente foi encaminhada a outro serviço para realização de cateterização de seio petroso inferior, que não evidenciou gradiente entre os níveis de ACTH dosados próximo à glândula comparados à periferia, confirmando a origem ectópica do ACTH. Novos exames de imagem evidenciaram tumor em timo. Paciente foi submetida à videotoracoscopia com exérese da lesão, recebendo alta no 10º pós operatório com normalização dos níveis de cortisol e ACTH. Conclusão: A cateterização bilateral de seio petroso inferior é o teste que oferece maior sensibilidade e especificidade na diferenciação entre produção hipofisária e ectópica de ACTH. Uma vez que os exames de imagem iniciais não evidenciaram tumor, esse teste foi essencial na confirmação da etiologia ectópica do ACTH, o que motivou nova investigação e, consequente, diagnóstico e tratamento

Families\u27 healthcare experiences for children with inherited metabolic diseases: Protocol for a mixed methods cohort study

Introduction Children with inherited metabolic diseases (IMDs) often have complex and intensive healthcare needs and their families face challenges in receiving high-quality, family centred health services. Improvement in care requires complex interventions involving multiple components and stakeholders, customised to specific care contexts. This study aims to comprehensively understand the healthcare experiences of children with IMDs and their families across Canada. Methods and analysis A two-stage explanatory sequential mixed methods design will be used. Stage 1: quantitative data on healthcare networks and encounter experiences will be collected from 100 parent/guardians through a care map, 2 baseline questionnaires and 17 weekly diaries over 5-7 months. Care networks will be analysed using social network analysis. Relationships between demographic or clinical variables and ratings of healthcare experiences across a range of family centred care dimensions will be analysed using generalised linear regression. Other quantitative data related to family experiences and healthcare experiences will be summarised descriptively. Ongoing analysis of quantitative data and purposive, maximum variation sampling will inform sample selection for stage 2: a subset of stage 1 participants will participate in one-on-one videoconference interviews to elaborate on the quantitative data regarding care networks and healthcare experiences. Interview data will be analysed thematically. Qualitative and quantitative data will be merged during analysis to arrive at an enhanced understanding of care experiences. Quantitative and qualitative data will be combined and presented narratively using a weaving approach (jointly on a theme-by-theme basis) and visually in a side-by-side joint display. Ethics and dissemination The study protocol and procedures were approved by the Children\u27s Hospital of Eastern Ontario\u27s Research Ethics Board, the University of Ottawa Research Ethics Board and the research ethics boards of each participating study centre. Findings will be published in peer-reviewed journals and presented at scientific conferences

Outcomes in pediatric studies of medium-chain acyl-coA dehydrogenase (MCAD) deficiency and phenylketonuria (PKU): a review.

BACKGROUND: Inherited metabolic diseases (IMDs) are a group of individually rare single-gene diseases. For many IMDs, there is a paucity of high-quality evidence that evaluates the effectiveness of clinical interventions. Clinical effectiveness trials of IMD interventions could be supported through the development of core outcome sets (COSs), a recommended minimum set of standardized, high-quality outcomes and associated outcome measurement instruments to be incorporated by all trials in an area of study. We began the process of establishing pediatric COSs for two IMDs, medium-chain acyl-CoA dehydrogenase (MCAD) deficiency and phenylketonuria (PKU), by reviewing published literature to describe outcomes reported by authors, identify heterogeneity in outcomes across studies, and assemble a candidate list of outcomes. METHODS: We used a comprehensive search strategy to identify primary studies and guidelines relevant to children with MCAD deficiency and PKU, extracting study characteristics and outcome information from eligible studies including outcome measurement instruments for select outcomes. Informed by an established framework and a previously published pediatric COS, outcomes were grouped into five, mutually-exclusive, a priori core areas: growth and development, life impact, pathophysiological manifestations, resource use, and death. RESULTS: For MCAD deficiency, we identified 83 outcomes from 52 articles. The most frequently represented core area was pathophysiological manifestations, with 33 outcomes reported in 29/52 articles (56%). Death was the most frequently reported outcome. One-third of outcomes were reported by a single study. The most diversely measured outcome was cognition and intelligence/IQ for which eight unique measurement instruments were reported among 14 articles. For PKU, we identified 97 outcomes from 343 articles. The most frequently represented core area was pathophysiological manifestations with 31 outcomes reported in 281/343 articles (82%). Phenylalanine concentration was the most frequently reported outcome. Sixteen percent of outcomes were reported by a single study. Similar to MCAD deficiency, the most diversely measured PKU outcome was cognition and intelligence/IQ with 39 different instruments reported among 82 articles. CONCLUSIONS: Heterogeneity of reported outcomes and outcome measurement instruments across published studies for both MCAD deficiency and PKU highlights the need for COSs for these diseases, to promote the use of meaningful outcomes and facilitate comparisons across studies

Patient and family engagement in the development of core outcome sets for two rare chronic diseases in children

Background: Core outcome sets (COS) are lists of consensus-determined outcomes to be measured and reported in all clinical research studies within a disease area. While including patients and families in COS development to improve their relevance and applicability to patient values is key, there is limited literature documenting practical barriers and facilitators to successful patient engagement in COS development. In this paper, as researchers and patient partners, we provide a resource for COS developers to meaningfully and effectively engage patients and families. Main body: To establish a consensus-based COS for children with two inherited metabolic diseases (medium-chain acyl-CoA dehydrogenase deficiency and phenylketonuria), we conducted an evidence review, Delphi survey, and workshop. Two adult patient partner co-investigators co-developed the study protocol, co-designed strategies to address challenges with incorporating patient perspectives, and led all patient engagement activities, including communication with a group of family advisors. Seven adult family advisors received training about COS development and subsequently contributed to Delphi survey development, outcome definitions, the consensus workshop, and selection of outcome measurement instruments. Patient partner co-investigators and family advisors were essential to the successful design, conduct, and completion of the two COS. Patient partner co-investigators supported the understanding, inclusion and engagement of family advisors, and helped develop accessible tools to determine patient-oriented outcome measurement instruments. Patient partner co-investigators and family advisors collaborated with the study team to co-develop surveys, modify technical language, and recruit participants to the study. Together, we addressed challenges to patient engagement in COS development such as unfamiliarity with study methods, comprehensibility of materials and ongoing engagement, and power imbalances between team members. Conclusion: Our approach to patient and family engagement in COS development for two rare conditions for children was feasible and considered valuable by all study team members, including patients and family members, in improving the relevance of the deliverable to patients. This approach to patient engagement in developing COS can be applied to other paediatric disease contexts, allowing patient and family perspectives to influence the direction of future studies to develop COS.Medicine, Faculty ofNon UBCPediatrics, Department ofReviewedFacultyResearche

Youth and family involvement in the development of a plain language trial results communication tool: CommuniKIDS

Abstract Background Pediatric trials are possible through voluntary participation of children, youth (age ≤ 18 years), and their families. Despite important arguments for trialists to provide trial progress or results, and evidence that participants desire it, this information remains rarely shared with youth and their families. Little guidance exists on how trialists can best communicate trial results back to participants and their families. Guided by Liabo et al.’s framework, we describe how we developed a pediatric-specific, “plain language summary” clinical trial results template called CommuniKIDS with an adult patient partner, family partner (parent), youth advisors, and parent advisors, taking into account their unique knowledge needs and preferences. Main text Patient and Public Involvement (PPI) was integrated in the development of the CommuniKIDS template. In collaboration with Clinical Trials Ontario, we used a generic trial results template as a starting point. The core project leadership team included a patient partner and a family partner from project inception to completion. Five youth (ages 13–18 years) and eight parent advisors were consulted at each point of the development process through three virtual workshops conducted separately; youth workshops were led by a youth facilitator. During these workshops, advisors agreed on the importance and value of sharing trial results, and expressed their preferences on content, format, and timing of sharing trial results. PPI-led improvements included the addition of three new sections to the CommuniKIDS template: “at a glance,” “side effects,” and “next steps.” We reflect on our PPI strategy in the context of five “values” and six “practicalities” identified as good PPI principles, and summarize lessons learned when collaborating with youth and families from this project. Conclusion Involvement of a patient partner, a family partner, youth advisors, and parent advisors in the development of CommuniKIDS was critical to create a clinical trial results template that is useful and relevant to its end-users. To our knowledge, CommuniKIDS is the first to meaningfully engage youth and parents as advisors and partners in developing a plain language summary results template for pediatric trial participants and their families. Our experience of co-developing CommuniKIDS demonstrates that meaningful PPI can be achieved in trial results communication and knowledge translation practices. This report provides resources for those seeking to involve youth and families in their initiatives and in meaningfully sharing trial results

Additional file 1: of Establishing core outcome sets for phenylketonuria (PKU) and medium-chain Acyl-CoA dehydrogenase (MCAD) deficiency in children: study protocol for systematic reviews and Delphi surveys

Additional details on the methods for the rapid review and evidence map. (PDF 174 kb