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Context: Small adjustments in levothyroxine (LT4) dose do not appear to provide clinical benefit despite changes in thyrotropin (TSH) levels within the reference range. We hypothesize that the accompanying changes in serum total triiodothyronine (T3) levels do not reflect the magnitude of the changes in serum TSH., Objective: This work aims to characterize the relationships of serum free thyroxine (FT4) vs T3, FT4 vs TSH, and FT4 vs the T3/FT4 ratio., Methods: This cross-sectional, observational study comprised 9850 participants aged 18 years and older treated with LT4 from a large clinical database from January 1, 2009, to December 31, 2019. Patients had been treated with LT4, subdivided by serum FT4 level. Main outcome measures included model fitting of the relationships between serum FT4 vs TSH, FT4 vs T3, and FT4 vs T3/FT4. Mean and median values of TSH, T3, and T3/FT4 were calculated., Results: The relationships T3 vs FT4 and TSH vs FT4 were both complex and best represented by distinct, segmented regression models. Increasing FT4 levels were linearly associated with T3 levels until an inflection point at an FT4 level of 0.7 ng/dL, after which a flattening of the slope was observed following a convex quadratic curve. In contrast, increasing FT4 levels were associated with steep declines in TSH following 2 negative sigmoid curves. The FT4 vs T3/FT4 relationship was fit to an asymptotic regression curve supporting less T4 to T3 activation at higher FT4 levels., Conclusion: In LT4-treated patients, the relationships between serum FT4 vs TSH and FT4 vs T3 across a range of FT4 levels are disproportionate. As a result, dose changes in LT4 that robustly modify serum FT4 and TSH values may only minimally affect serum T3 levels and result in no significant clinical benefit., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The Complete Blood Count (CBC) is a commonly used low-cost test that measures white blood cells, red blood cells, and platelets in a person's blood. It is a useful tool to support medical decisions, as intrinsic variations of each analyte bring relevant insights regarding potential diseases. In this study, we aimed at developing machine learning models for COVID-19 diagnosis through CBCs, unlocking the predictive power of non-linear relationships between multiple blood analytes., Methods: We collected 809,254 CBCs and 1,088,385 RT-PCR tests for SARS-Cov-2, of which 21% (234,466) were positive, from 900,220 unique individuals. To properly screen COVID-19, we also collected 120,807 CBCs of 16,940 individuals who tested positive for other respiratory viruses. We proposed an ensemble procedure that combines machine learning models for different respiratory infections and analyzed the results in both the first and second waves of COVID-19 cases in Brazil., Results: We obtain a high-performance AUROC of 90 + % for validations in both scenarios. We show that models built solely of SARS-Cov-2 data are biased, performing poorly in the presence of infections due to other RNA respiratory viruses., Conclusions: We demonstrate the potential of a novel machine learning approach for COVID-19 diagnosis based on a CBC and show that aggregating information about other respiratory diseases was essential to guarantee robustness in the results. Given its versatile nature, low cost, and speed, we believe that our tool can be particularly useful in a variety of scenarios-both during the pandemic and after., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2022.)

In recent years the immunomodulatory actions of vitamin D, a steroid hormone, have been extensively studied. In 2020, due to the COVID-19 pandemic, the question arose as to 25(OH)D status would be related to susceptibility to SARS-CoV-2 infection, since several studies pointed out a higher prevalence and severity of the disease in populations with low levels of 25(OH)D. Thus, we investigated the 25(OH)D levels in adults "Detected" positive for SARS CoV-2 by RT-PCR (reverse transcriptase polymerase chain reaction) test, and in negative controls, "not Detected", using the Fleury Group's examination database, in Sao Paulo, Brazil. Of a total of 14.692 people with recent assessments of 25(OH)D and RT-PCR tests for COVID-19, 2.345 were positive and 11.585 were negative for the infection. The groups did not differ in the percentage of men and women, or in the age distribution. There were no differences in the distribution of 25(OH)D between the two groups (p = 0.08); mean 25(OH)D of 28.8 ± 21.4 ng/mL and 29.6 ± 18.1 ng/mL, respectively. In the specific population studied, clinical, environmental, socioeconomic and cultural factors should have greater relevance than 25(OH)D in determining the susceptibility to COVID-19.

Context: Treatment with levothyroxine (LT4) that normalize serum thyrotropin (TSH) is expected to restore lipid metabolism., Objective: To assess statin utilization in LT4-treated patients through an observational drug utilization study., Methods: Three sites were involved: (1) 10 723 outpatients placed on LT4 during 2006-2019 identified from the Clinical Research Data Warehouse of the University of Chicago; (2) ~1.4 million LT4 prescriptions prepared by primary care physicians during January-December 2018, identified from the IQVIA™ database of medical prescriptions in Brazil; (30 ~5.4 million patient interviews during 2009-2019, including ~0.32 million patients on LT4, identified from the Fleury Group database in Brazil., Results: On site 1, initiation of therapy with LT4 increased the frequency of statin utilization (19.1% vs 24.6%), which occurred ~1.5 years later (median 76 weeks) and, among those patients that were on statins, increased intensity of treatment by 33%, despite normalization of serum TSH levels; on site 2, after matching for sex and age, the frequency of statins prescription was higher for those patients using LT4: females, 2.1 vs 3.4% (odds ratio [OR] 1.656 [1.639-1.673]); males, 3.1 vs 4.4% (OR 1.435 [1.409-1.462]); and, on site 3, after matching for sex and age, the frequency of statin utilization was higher in those patients using LT4: females, 10 vs 18% (OR 2.02 [2.00-2.04]); males, 15 vs 25% (OR 1.92 [1.88-1.96]); all P values were <.0001., Conclusion: Prescription and utilization of statins were higher in patients taking LT4. The reasons for this association should be addressed in future studies., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)