Background: Bariatric surgery (BS) is effective for achieving significant weight loss. However, weight regain (WR) is an emerging problem. Objective: To assess the prognostic value of morning serum cortisol, a 1 mg dexamethasone suppression test (DST), 24 h urinary free cortisol (UFC) and late-night salivary cortisol (LNSC) in a cohort of patients with severe obesity (pwSO) undergoing BS in terms of weight loss and WR. Methods: Patients scheduled for BS underwent the following procedures at baseline, 12 months and 24 months after BS: medical history, anthropometric data, blood analysis and cortisol tests. We evaluated total weight loss (TWL) ≥ 30% at 1 year and WR after 2 years as an increase of ≥10% of the maximum weight lost. Results: In total, 142 subjects were included; 101 (71.1%) were females and the mean age was 45.9 ± 9.2 years. Up to 76.8% of subjects achieved ≥30% TWL, without statistically significant differences in DST results or morning serum cortisol, UFC or LNSC levels. However, a higher pre-surgery morning serum cortisol level was a significant predictor of a WR ≥ 10% (cortisol 17.8 [IQR 13.1–18.5] vs. 12.0 [IQR 8.8–15.8] μg/dL; p < 0.01); OR of 1.216 (95% CI 1.069–1.384); AUC [0.761, CI: (0.616–0.906); p < 0.01]. A cut-off value of cortisol > 13.0 μg/dL was predictive of a WR ≥ 10% (sensitivity 0.71; specificity 0.63). Conclusions: No cortisol test was useful in predicting weight loss; however, the pre-surgery morning serum cortisol level was able to predict a WR ≥ 10% in a cohort of pwSO 2 years after BS. A cut-off value of cortisol > 13 μg/dL might be an easy tool to identify patients at higher risk of WR, enabling healthcare providers to implement tailored, long-term strategies to minimize this outcome.

Background: This study aimed to investigate whether A1AT (α‐1 antitrypsin) bloodstream levels, measured acutely after ischemic stroke, can predict the outcome of patients with stroke. Methods and Results: Two cohorts of patients with stroke were studied independently and retrospectively: a pilot cohort of 59 patients and a larger replicative study with 527 patients. Blood samples were drawn at hospital admission (2 a poor outcome). Association studies between A1AT levels and functional outcomes were conducted. We also evaluated the added value of A1AT as a prognostic biomarker over the clinical model (sex, age, premorbid modified Rankin Scale and National Institutes of Health Stroke Scale scores) with the likelihood ratio test. In both studies, the levels of A1AT were higher in patients who had worse outcomes, were older, and had higher National Institutes of Health Stroke Scale scores at admission. In the pilot study, higher levels of A1AT were also associated with death at discharge and at 3 months after stroke ( P =0.035 and P =0.023, respectively). The addition of A1AT to the clinical model did not show enough evidence of increasing the fit of the model to the data in either cohort. Conclusions: Based on our data, we cannot claim that A1AT is an independent biomarker of ischemic stroke. Nevertheless, A1AT is potentially involved in stroke outcomes and might be explored as a potential therapeutic target.

Genetic tests have led to the discovery of many novel genetic variants related to growth failure, but the clinical significance of some results is not always easy to establish. The aim of this report is to describe both clinical phenotype and genetic characteristics in an adult patient with short stature associated with a homozygous variant in disintegrin and metalloproteinase with thrombospondin motifs type 17 gene (ADAMTS17) combined with a homozygous variant in the GH secretagogue receptor (GHS-R). The index case had severe short stature (SS) (−3.0 SD), small hands and feet, associated with eye disturbances. Genetic tests revealed homozygous compounds for ADAMTS17 responsible for Weill–Marchesani-like syndrome but a homozygous variant in GHS-R was also detected. Dynamic stimulation with an insulin tolerance test showed a normal elevation of GH, while the GH response to macimorelin stimulus was totally flattened. We show the implication of the GHS-R variant and review the molecular mechanisms of both entities. These results allowed us to better interpret the phenotypic spectrum, associated co-morbidities, its implications in dynamic tests, genetic counselling and treatment options not only to the index case but also for her relatives.

Marina Giralt, M.S., Roser Ferrer, Ph.D., Noelia Díaz-Troyano, Ph.D., Belén Vega, M.S., Manuel Luque-Ramírez, Ph.D., Sílvia Martínez, M.S., Bárbara Fernández, Ph.D., Irene Martínez, M.S., Aleix Fabregat, Ph.D., Eulalia Urgell, Ph.D., Ignacio Cardona, M.S., Gregori Casals, Ph.D., and Héctor F. Escobar-Morreale, Ph.D.. Ann Lab Med -0001;0:. https://doi.org/10.3343/alm.2024.0362

Introduction: This case illustrates the challenges in the diagnosis of a rare disease with an intricate orientation. The definitive genetic diagnosis was carried out after establishing crucial correlations between the preliminary clinical indications and the laboratory findings. Case Presentation: The initial presentation was myoclonic jerks. This was a direct consequence of hyperinsulinaemic hypoglycaemia (HH), and not a phenotypic characteristic described in previous case reports. Linking this to glycaemia led to the evaluation of response to fasting, where inadequate insulin suppression resulted in hypoketotic hypoglycaemia. The diagnosis of chronic kidney dysfunction associated with atypical Fanconi renal tubulopathy syndrome type 4 (FRTS4) was indicated on the basis of a decreased estimated glomerular filtration rate, nephrocalcinosis, millimetric lithiasis, rickets, and complex proximal tubulopathy. This indicated atypical FRTS4 as associated with HH and necessitated further molecular genetic testing. Conclusion: The patient was identified as a carrier of the c.187C>T (p.Arg63Trp) variant in the HNF4A gene, which is a heterozygous missense variant classified as pathogenic. This entity is rare, and the published literature reporting HNF4A gene variants associated with atypical FRTS and HH is limited. It is therefore important to report such cases to contribute to the growing body of evidence and help identify pathogenic HNF4A variants and their implications.