Pittock, Siobhán T.

Abstract Background In 2017, Mayo Clinic Laboratories commenced offering a comprehensive type 1 diabetes mellitus (T1DM) autoantibody (Ab) evaluation including 4 known Abs targeting glutamic acid decarboxylase (GAD65), protein tyrosine phosphatase-like islet antigen 2 (IA2), insulin (IAA), and zinc transporter 8 protein (ZnT8) antigens. Methods The objective of this study was to evaluate real-time data on the frequency and patterns of all 4 Abs stratified by age and sex from 6044 unique consecutive adult and pediatric patients undergoing evaluation for suspected diabetes. Results At least one Ab was found in 3370 (56%) of all samples: 67% of children (aged 0–17), 49% of young adults (aged 18–35), and 41% for both middle-aged (aged 36–55) and older (aged >55) adults (P ≤ 0.0001). GAD65-Abs were the most common in all age groups, followed by ZnT8-Ab in those <36 years, or IAA-Ab in those ≥36. Frequencies of IA2- and ZnT8-Abs drop significantly with increasing age. Clusters of 3 or 4 Abs were more frequently encountered in younger patients (41% of children vs 12% in middle- and 13% in older age groups, P ≤ 0.0001). Conclusions Children undergoing serological evaluation for T1DM were more commonly positive for autoantibodies than older age groups. The frequency of ZnT8- and IA2-Abs decreases, and IAA-Ab frequency increases with increasing age, and clusters of 2 to 4 autoantibodies are more common in children. In clinical practice, comprehensive testing for diabetes autoantibodies resulted in a switch in diagnosis to T1DM for patients previously classified as type 2 diabetes mellitus.

Abstract The practice of maternal-fetal surgery (MFS) has expanded from lethal fetal conditions to conditions which are significantly disabling but not a lethal fetal abnormality. The inclusion of myelomeningocele within the scope of MFS in the 1990s sparked a renewed debate over the ethics of MFS. While demonstrating increasing efficacy and range of application, MFS continues to be ethically fraught due to the inherent tension between maternal and fetal interests. Ethical issues central to MFS include the patienthood of the fetus; the balance of risks and benefits between the woman and fetus; informed consent for experimental procedures; and determination of conditions that meet ethical qualifications for MFS intervention. These concerns are likely to persist and evolve as perinatal medicine continues to advance. Here we summarize the current state of MFS ethics, highlighting the major positions in the literature thus far as well as examine future directions. It is essential robust discussions of these important issues continue both to ensure ethical medical practice and to provide support to clinicians, pregnant women, and their families.

Mutations in the hepatocyte nuclear factor‐1‐beta (HNF1B) gene cause a variety of diseases in different organ systems. Mutations have been described as causing neonatal cholestasis, maturity‐onset diabetes of the young (type 5), cortical renal cysts, urogenital abnormalities, liver dysfunction, and atrophy of the pancreas. We describe a male patient who presented with cholestatic liver disease in infancy which progressed by age 14 to end‐stage liver disease due to HNF1B disease. He subsequently underwent liver transplantation at age 15 and then developed diabetes requiring insulin which did not resolve after cessation of corticosteroids. To our knowledge, this is the first case reported of liver transplantation for decompensated cirrhosis secondary to HNF1B disease.

AbstractRationale, aims, and objectivesWaist circumference (WC) and waist‐to‐height ratio (WHtR) are superior surrogate markers of central obesity than body mass index. However, WC is not measured routinely in paediatric clinics. The objective of this study was to implement measurement of WC during routine assessment of children in an ambulatory outpatient clinic setting and subsequent dissemination of cardiometabolic risk counselling in children with central obesity (defined as WHtR ≥0.5).MethodProspective cohort of patients aged 6 to 20 years. Study period was divided into three phases: baseline (3 months), process improvement (2 months), and implementation (6 months). Define‐Measure‐Analyse‐Improve‐Control (DMAIC) strategy was applied. Measurement of WC was implemented as a component of the physical examination in patients. Outcome measures were (1) improvement in frequency of WC measurement and (2) utilization of WHtR in cardiometabolic risk counselling.ResultsWaist circumference was not measured in any patient during baseline phase (n = 551). During process improvement phase, of the total 347 patients, WC was measured in 35% vs target of 30%. In the implementation phase, WC was measured in 37% patients (365 out of 964). Of these 365 patients, 175 (48%) had elevated WHtR, and 73% of them (n = 128) were counselled about their increased cardiometabolic risk.ConclusionsApplication of an evidence‐based DMAIC protocol led to significant improvement in assessment for central obesity in an ambulatory clinic practice and appropriate counselling regarding cardiometabolic risk reduction in children and adolescents with central obesity over an 8‐month period. Meticulous planning and execution, frequent reinforcement, and integrating feedback from the involved multi‐disciplinary team were important factors in successful implementation of this quality improvement project.

AbstractIntroductionThyroid cancer is the most common paediatric endocrine cancer; accurate diagnosis and prompt management of paediatric thyroid nodules is critical. The McGill Thyroid Nodule Score (MTNS), based upon clinical, ultrasound (US) and cytology criteria, has recently been modified and studied in a pilot paediatric group with good results. We aim to describe the diagnostic accuracy of the paediatric modified MTNS (PMTNS) in a large paediatric cohort.MethodsWe utilized an established retrospective cohort between 1996 and 2015 of 99 patients ≤21 years old with 131 thyroid nodules. Two experienced paediatric radiologists, blinded to pathology and radiology reports, reviewed US features. We abstracted cytology, histology and laboratory results, assigning each nodule a PMTNS. PMTNS performance was compared to FNA and histology.ResultsApproximately 33% of nodules were malignant. The cohort was predominantly adolescent (mean age 15.4 ± 3.8 years). The average PMTNS for malignant and benign nodules, based on final histology, was 12.7 ± 4.3 and 1.7 ± 2.9, respectively. A PMTNS ≥8 resulted in a 93.2% sensitivity and 93.1% specificity for detecting malignancy, while a PMTNS ≥9 resulted in a 90.9% sensitivity and 96.6% specificity. However, Bethesda cytology category ≥4 independently had a 97.7% sensitivity and 94.0% specificity for detecting malignancy. The PMTNS had diminishing diagnostic accuracy in younger children compared with older children.ConclusionPaediatric modified McGill Thyroid Nodule Score predicts malignancy, perhaps due to the score's emphasis on cytology results; however, the score is less accurate in younger patients. While cytology results remain reliable, further work is needed to develop a non‐invasive scoring system to predict malignancy in children.

Abstract Background: A thyroid storm (TS) is a rare, but life-threatening condition in hyperthyroid patients. Mortality in adult TS patients may be as high as 10%. Typically, a trigger precipitates the storm in hyperthyroid patients. Case presentation: We report the case of an adolescent girl with untreated hyperthyroidism who developed fulminant TS after a significant choking episode. Initially, she was found to have neck swelling and tachycardia leading providers to suspect infection. She deteriorated after a CAT Scan (CT) was performed with iodine contrast, potentially worsening storm symptoms. Here, we describe the case, the treatment strategy and propose a treatment modification for pediatric patients. Conclusions: While many children are found to have minor abnormalities in thyroid studies, this case highlights the critical importance of prompt medical attention for any child with significantly elevated free thyroxine (FT4) levels as morbidity can occur when left untreated.