We assess the severity and frequency of diabetic ketoacidosis (DKA) in new-onset type 1 diabetes mellitus (T1D) patients and in patients with previous diagnosis of T1D in a referral Brazilian university hospital in the first five months of the COVID-19 pandemic. We also compare the data with data from pre-pandemic periods. Forty-three new-onset T1D patients were diagnosed between April and August of the years 2017, 2018, 2019, and 2020. During the COVID-19 pandemic, the number of newonset T1D was over twice the number of new-onset T1D in the same period in the three previous years. All the 43 patients survived and are now on outpatient follow-up. We also compared the characteristics of the T1D patients hospitalized between April and August of the years 2017, 2018, and 2019 (32 hospitalizations) to the characteristics of the T1D patients hospitalized between April and August/2020 (35 hospitalizations; 1 patient was hospitalized twice in this period). Fourteen of the 34 patients admitted during the pandemic presented with COVID-19-related symptoms (any respiratory symptom, fever, nausea, vomiting, and diarrhea), but only one had positive SARS-CoV-2 RT-PCR test. Samples from 32 out of these 34 patients were assayed for SARS-CoV-2 antibodies, and four patients were positive for total antibodies (IgM and IgG). In agreement with recent reports from European countries, we observed increased frequency of DKA and severe DKA in new-onset and previously diagnosed T1D children and adolescents in a large referral public hospital in Brazil in the first five months of the COVID-19 pandemic. The reasons for this outcome might have been fear of SARS-CoV-2 infection in emergency settings, the more limited availability of primary healthcare, and the lack of school personnel's attention toward children's general well-being.
The aim of the study was to clarify the relationship and the time of aldosterone and renin recoveries at immediate and long-term follow-up in aldosterone-producing adenoma (APA) patients who underwent adrenalectomy. Prospective and longitudinal protocol in a cohort of APA patients was followed in a single center. Among 43 patients with primary aldosteronism (PA), thirteen APA patients were enrolled in this study. Blood was collected for aldosterone, renin, potassium, creatinine, cortisol, and ACTH before and 1, 3, 5, 7, 15, 30, 60, 90, 120, 180, 270, 360 days after adrenalectomy. At diagnosis, most patients (84%) had hypokalemia and high median aldosterone levels (54.8; 24.0–103 ng/dl) that decreased to undetectable (<2.2) or very low (<3.0) levels between fifth to seventh days after surgery; then, between 3–12 months, its levels gradually increased to the lower normal range. The suppressed renin (2.3; 2.3–2.3 mU/l) became detectable between the fifteen and thirty days after surgery, remaining normal throughout the study. The aldosterone took longer than renin to recover (60 vs.15 days; p<0.002) and patients with higher aldosterone had later recovery (p=0.03). The cortisol/ACTH levels remained normal despite the presence of a post-operative hypoaldosteronism. Blood pressure and antihypertensive requirement decreased after adrenalectomy. In conclusion, our prospective study shows the borderline persistent post-operative hypoaldosteronism in the presence of early renin recovery indicating incapability of the zona glomerulosa of the remaining adrenal gland to produce aldosterone. These findings contribute to the comprehension of differences in renin and aldosterone regulation in APA patients, although both are part of the same interconnected system.
BackgroundDistinct genome-wide methylation patterns have consistently clustered pituitary neuroendocrine tumors (PT) into molecular groups associated with specific clinicopathological features. Here we aim to identify, characterize and validate the methylation signatures that objectively classify PT into those molecular groups.MethodsCombining in-house and publicly available data, we conducted an analysis of the methylome profile of a comprehensive cohort of 177 tumor and 20 non-tumor specimens from the pituitary gland. We also retrieved methylome data from an independent pituitary tumor (PT) cohort (N=86) to validate our findings.ResultsWe identified three methylation clusters associated with functional status and adenohypophyseal cell lineages using an unsupervised approach. We also identified signatures based on differentially methylated CpG probes (DMP), some of which overlapped with pituitary-specific transcription factors genes (SF1 and Tpit), that significantly distinguished pairs of clusters related to functional status and adenohypophyseal cell lineage. These findings were reproduced in an independent cohort, validating these methylation signatures. The DMPs were mainly annotated in enhancer regions associated with pathways and genes involved in cell identity and tumorigenesis.ConclusionsWe identified and validated methylation signatures that distinguished PT by distinct functional status and adenohypophyseal cell lineages. These signatures, annotated in enhancer regions, indicate the importance of these elements in pituitary tumorigenesis. They also provide an unbiased approach to classify pituitary tumors according to the most recent classification recommended by the WHO 2017 using methylation profiling.Key-pointsDistinct methylation landscapes define PT groups with specific functional status/subtypes and adenohypophyseal lineages subtypes.Methylation abnormalities in each cluster mainly occur in CpG annotated in distal regions overlapping predicted enhancers regions associated with pathways and genes involved in cell identity and tumorigenesis.DNA methylation signatures provide an unbiased approach to classify PT.Importance of the studyThis study harnessed the largest methylome data to date from a comprehensive cohort of pituitary specimens obtained from four different institutions. We identified and validated methylation signatures that distinguished pituitary tumors into molecular groups that reflect the functionality and adenohypophyseal cell lineages of these tumors. These signatures, mainly located in enhancers, are associated with pathways and genes involved in cell identity and tumorigenesis. Our results show that methylome profiling provides an objective approach to classify PT according to the most recent classification of PT recommended by the 2017 WHO.
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