Demographic, Healthcare Access, and Dietary Factors Associated With Thyroid Hormone Treatments for Hypothyroidism.

CONTEXT: Clinical guidelines have recommended a trial of liothyronine (LT3) with levothyroxine (LT4) in select patients with hypothyroidism. However, little is known about the real-world use of LT3 and desiccated thyroid extract (DTE) and the characteristics of patients treated with LT3 and DTE. OBJECTIVES: (1) Determine national trends of new LT4, LT3, and DTE prescriptions in the United States; (2) determine whether sociodemographic, healthcare access, and dietary factors are associated with different thyroid hormone (TH) therapies. METHODS: Parallel cross-sectional studies were conducted using 2 datasets: (1) a national patient claims dataset (2010-2020) and (2) the National Health and Nutrition Examination Study (NHANES) dataset (1999-2016). Included participants had a diagnosis of primary or subclinical hypothyroidism. Study outcomes included the impact of demographics and healthcare access on differences in the proportion of TH therapies consisting of LT4, LT3, and DTE (patient claims) and differences in dietary behaviors between DTE-treated participants and LT4-treated matched controls (NHANES). RESULTS: On an average annual basis, 47 711 adults received at least 1 new TH prescription, with 88.3% receiving LT4 monotherapy, 2.0% receiving LT3 therapy, and 9.4% receiving DTE therapy. The proportion receiving DTE therapy increased from 5.4% in 2010 to 10.2% in 2020. In the analysis between states, high primary care and endocrinology physician densities were associated with increased use of LT4 monotherapy (odds ratio 2.51, P < .001 and odds ratio 2.71, P < .001). DTE-treated NHANES participants (n = 73) consumed more dietary supplements compared to LT4-treated participants (n = 146) (4.7 vs 2.1, P < .001). CONCLUSIONS: The proportion of new TH therapies containing DTE for hypothyroidism doubled since 2010 while LT3 therapies remained stable. DTE treatment was associated with decreased physician density and increased dietary supplement use.

Peptide-based urinary monitoring of fibrotic nonalcoholic steatohepatitis by mass-barcoded activity-based sensors.

Noninvasive detection of nonalcoholic steatohepatitis (NASH), the progressive form of nonalcoholic fatty liver disease, promises to improve patient screening, accelerate drug trials, and reduce health care costs. On the basis of protease dysregulation of the biological pathways of fibrotic NASH, we developed the Glympse Bio Test System (GBTS) for multiplexed quantification of liver protease activity. GBTS-NASH comprises a mixture of 19 mass-barcoded PEGylated peptides that is administered intravenously and senses liver protease activity by releasing mass-barcoded reporters into urine for analysis by mass spectrometry. To identify a protease signature of NASH, transcriptomic analysis of 355 human liver biopsies identified a 13-protease panel that discriminated clinically relevant NASH ≥F2 fibrosis from F0-F1 with high classification accuracy across two independent patient datasets. We screened 159 candidate substrates to identify a panel of 19 peptides that exhibited high activity for our 13-protease panel. In the choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) mouse model, binary classifiers trained on urine samples discriminated fibrotic NASH from simple steatosis and healthy controls across a range of nondisease conditions and indicated disease regression upon diet change [area under receiver operating characteristics (AUROCs) > 0.97]. Using a hepatoprotective triple combination treatment (FXR agonist, ACC and ASK1 inhibitors) in a rat model of NASH, urinary classification distinguished F0-F1 from ≥F2 animals and indicated therapeutic response as early as 1 week on treatment (AUROCs >0.91). Our results support GBTS-NASH to diagnose fibrotic NASH via an infusion of peptides, monitor changes in disease severity, and indicate early treatment response.