ABSTRACT
BACKGROUND: The rate of autoimmune thyroiditis in children with celiac disease (CD) is high relative to the normal population. Since the majority of these patients are also euthyroid, thyroid imaging methods are gaining significance in diagnosis and follow-up. This study examines the effectiveness of thyroid ultrasonography (US) and thyroid shear wave elastography (SWE) in diagnosing thyroid disease in children with CD. MATERIALS AND METHODS: This cross-sectional controlled study analyzed thyroid US, SWE, serum thyroid function tests, and thyroid autoimmune antibodies of 106 CD patients and 103 control patients without CD. An Aplio 500 ultrasound device with a linear array transducer and elastography software was used for thyroid US and SWE measurement of all patients. RESULTS: Right lobe thyroid volume, left lobe thyroid volume, total thyroid volume, thyroid mean elasticity (m/s), right lobe elasticity (kPa), left lobe elasticity (kPa), and mean thyroid elasticity (kPa) levels of the CD group were higher than those of the control group (p < 0.001). The relationships between thyroid US and thyroid mean elasticity (m/s), thyroid mean elasticity (kPa), anti-thyroid peroxidase antibody, and thyroid-stimulating hormone were positive and moderate, respectively (r = 0.612, 0.612, 0.636, and 0.565, respectively; p < 0.001). CONCLUSION: In this study, SWE findings were compatible with laboratory findings, as they constituted a sensitive and useful method in the diagnosis and follow-up of autoimmune thyroid disease in children with CD.
Subject(s)
Celiac Disease , Elasticity Imaging Techniques , Celiac Disease/diagnostic imaging , Child , Cross-Sectional Studies , Elasticity Imaging Techniques/methods , Humans , Thyroid Gland/diagnostic imaging , UltrasonographyABSTRACT
BACKGROUND & AIMS: Congenital diarrheal disorders are rare inherited intestinal disorders characterized by intractable, sometimes life-threatening, diarrhea and nutrient malabsorption; some have been associated with mutations in diacylglycerol-acyltransferase 1 (DGAT1), which catalyzes formation of triacylglycerol from diacylglycerol and acyl-CoA. We investigated the mechanisms by which DGAT1 deficiency contributes to intestinal failure using patient-derived organoids. METHODS: We collected blood samples from 10 patients, from 6 unrelated pedigrees, who presented with early-onset severe diarrhea and/or vomiting, hypoalbuminemia, and/or (fatal) protein-losing enteropathy with intestinal failure; we performed next-generation sequencing analysis of DNA from 8 patients. Organoids were generated from duodenal biopsies from 3 patients and 3 healthy individuals (controls). Caco-2 cells and patient-derived dermal fibroblasts were transfected or transduced with vectors that express full-length or mutant forms of DGAT1 or full-length DGAT2. We performed CRISPR/Cas9-guided disruption of DGAT1 in control intestinal organoids. Cells and organoids were analyzed by immunoblot, immunofluorescence, flow cytometry, chromatography, quantitative real-time polymerase chain reaction, and for the activity of caspases 3 and 7. RESULTS: In the 10 patients, we identified 5 bi-allelic loss-of-function mutations in DGAT1. In patient-derived fibroblasts and organoids, the mutations reduced expression of DGAT1 protein and altered triacylglycerol metabolism, resulting in decreased lipid droplet formation after oleic acid addition. Expression of full-length DGAT2 in patient-derived fibroblasts restored formation of lipid droplets. Organoids derived from patients with DGAT1 mutations were more susceptible to lipid-induced cell death than control organoids. CONCLUSIONS: We identified a large cohort of patients with congenital diarrheal disorders with mutations in DGAT1 that reduced expression of its product; dermal fibroblasts and intestinal organoids derived from these patients had altered lipid metabolism and were susceptible to lipid-induced cell death. Expression of full-length wildtype DGAT1 or DGAT2 restored normal lipid metabolism in these cells. These findings indicate the importance of DGAT1 in fat metabolism and lipotoxicity in the intestinal epithelium. A fat-free diet might serve as the first line of therapy for patients with reduced DGAT1 expression. It is important to identify genetic variants associated with congenital diarrheal disorders for proper diagnosis and selection of treatment strategies.
