Tiago Da Silva Santos

Introduction: MODY probability calculator (MPC) represents an easy‐to‐use tool developed by Exeter University to help clinicians prioritize which individuals should be oriented to genetic testing. We aimed to assess the utility of MPC in a Portuguese cohort with early‐onset monogenic diabetes.Methods: This single‐centre retrospective study enrolled 132 participants submitted to genetic testing between 2015 and 2020. Automatic sequencing and, in case of initial negative results, generation sequencing were performed. MODY probability was calculated using the probability calculator available online. Positive and negative predictive values (PPV and NPV, respectively), accuracy, sensitivity and specificity of the calculator were determined for this cohort.Results: Seventy‐three individuals were included according to inclusion criteria: 20 glucokinase (GCK‐MODY); 16 hepatocyte nuclear factor 1A (HNF1A‐MODY); 2 hepatocyte nuclear factor 4A (HNF4A‐MODY) and 35 DM individuals with no monogenic mutations found. The median probability score of MODY was significantly higher in monogenic diabetes‐positive subgroup (75.5% vs. 24.2%, p < .001). The discriminative accuracy of the calculator, as expressed by area under the curve, was 75% (95% CI: 64%–85%). In our cohort, the best cut‐off value for the MODY calculator was found to be 36%, with a PPV of 74.4%, NPV of 73.5% and corresponding sensitivity and specificity of 76.2% and 71.4%, respectively.Conclusions: In a highly pre‐selected group of probands qualified for genetic testing, the Exeter MODY probability calculator provided a useful tool in individuals' selection for genetic testing, with good discrimination ability under an optimal probability cut‐off of 36%. Further geographical and population adjustments are warranted for general use.

Background: Adrenal insufficiency (AI) is a life-threatening condition caused by an impaired secretion of the adrenal glucocorticoid and mineralocorticoid hormones. It comprises a heterogeneous group of primary, secondary and acquired disorders. Presentation differs according to the child’s age, but it usually presents with nonspecific and insidious symptoms and signs. The main purpose of this study was to describe and compare patients with primary or secondary AI. Methods: Retrospective analysis of all patients with adrenal insufficiency followed at the Pediatric Endocrinology Unit in a tertiary care Portuguese hospital over the last 30 years. Data on family history, age at the first manifestation and at etiological diagnosis, and clinical presentation (symptoms, signs and laboratory evaluation) was gathered for all patients. Results: Twenty-eight patients with AI were included; 67.9% were male, with a median (25th–75th percentile, P25–P75) age of 1 (0.5–36) month at the first presentation. The principal diagnostic categories were panhypopituitarism (42.9%) and congenital adrenal hyperplasia (25%). The most frequent manifestations (75%) were vomiting and weight loss. They were followed for a median (P25–P75) period of 3.5 (0.6–15.5) years. In respect to neurodevelopmental delay and learning difficulties, they were more common in the secondary AI group. Conclusions: Despite medical advances, the diagnosis and management of AI remains a challenge, particularly in the pediatric population, and clinicians must have a high index of suspicion. An early identification of AI can prevent a potential lethal outcome, which may result from severe cardiovascular and hemodynamic instability.

Gestational trophoblastic disease (GTD) represents a heterogeneous group of disorders within placental trophoblastic cells that are rather rare in perimenopausal ages. One of its complications is the development of secondary clinical hyperthyroidism, which can be potentially complicated if not properly and early recognized. We report the case of a 50-year-old perimenopausal woman, gravida 2 para 2, who presented to the emergency department with severe acute lower abdominal pain and abnormal uterine bleeding for one month. She also reported abnormal sweating and palpitation for a one-week duration and amenorrhea for the previous three months. Abdominal examination showed a pelvic mass resembling a 15-week sized uterus. Serum β-hCG levels were strongly increased, and abdomen ultrasound displayed an enlarged uterus with “snow-storm” features, compatible with the diagnosis of GTD. Laboratory data revealed suppressed TSH levels and high free thyroxine and free triiodothyronine levels (4 and 1.5 times above the upper limit of normality, respectively). Thyrotropin-receptor antibodies (TRAb) levels were negative, and thyroid ultrasound excluded major structural disease. She was managed with anti-thyroid drugs, Lugol’s iodine, beta-blockers, and steroids during preoperative care. Thereafter, she underwent surgery, being diagnosed with a hydatidiform mole postoperatively. Her thyroid function returned to normal after three months, without the further need for antithyroid drugs. This case highlights the importance of considering GTD as an aetiology for thyrotoxicosis in perimenopausal women, especially in the absence of findings suggesting primary thyroid disease.

Introduction: Thyroid-stimulatory antibody (TSAb) assays have been recently optimized, potentially allowing to determine thyrotropin receptor antibodies' (TRAbs) functionality in routine clinical practice. We aimed to determine TSAb's predictive role of relapse at antithyroid drug (ATD) withdrawal in Graves’ disease (GD). Methods: Retrospective study of GD patients with stable normal thyroid function under low ATD doses that were proposed for withdrawal. Thyroid function tests and TRAb and TSAb levels were obtained at ATD suspension and every three to six months after that, for a minimum of 16 months. Clinical factors associated with GD relapse, such as age at diagnosis, sex, smoking status, thyroid volume, and presence of orbitopathy, were also evaluated. Results: Thirty-five patients with GD were included for analysis, with a median follow-up period of 24 months, during which 14 patients (40%) relapsed. Relapse was more common in patients with positive TSAb than patients with negative TSAb at ATD withdrawal (79% vs. 33%, p=0.01). Relapse-free survival was shorter in TSAb-positive patients (p=0.01). There were no differences in relapse rates according to TRAb positivity at ATD withdrawal (42.9% vs. 36.4%, p=0.74). We also did not find any differences in relapse rate regarding age, sex, smoking status, thyroid volume, or presence of Graves’ orbitopathy. On multivariate analysis, only TSAb positivity at ATD withdrawal was independently associated with relapse (hazard ratio [HR] 6.63, 95% confidence interval [CI], 1.30-33.7, p=0.02). Conclusion: At ATD withdrawal, TSAb-positive patients demonstrated a higher risk for GD relapse. Measuring TSAb before ATD suspension, instead of TRAbs, could become an important tool for the clinical management of these patients.

Evidence Associated with the Use of Oxazolidinones in the Treatment of Skin and Skin Structure Infections: A Retrospective Study