Higher prevalence of incidental findings identified upon coronary calcium score assessment in type 2 and type 3 diabetes versus type 1 diabetes.

AIM: Noninvasive assessment of infraclinic coronary atherosclerosis by coronary artery calcium score (CAC) measurement leads to the identification of incidental findings. The aim of this study was to determine the prevalence of incidental findings following systematic CAC assessment in diabetic patients with high cardiovascular risk, to identify the determinants, and to assess the midterm consequences of these findings in patient care. METHODS: 732 consecutive asymptomatic patients (187 type 1 diabetes (TD1), 482 type 2 diabetes (TD2) and 63 type 3 diabetes (TD3)) aged 60.6±0.7 years who had a CAC assessment by Multiple Detector Computed Tomography between 2015 and 2017 were systematically included. Clinical and biological data were collected from medical electronic files. RESULTS: 117/732 diabetic patients (16.0%) had incidental findings of which 105 (14.3%) were unknown. Incidental findings were more frequent in TD3 (23.8%) and TD2 (17.0%) than in TD1 (10.7%) (p = 0.05). 76 diabetic patients (10.4%) had lung abnormalities, mainly pulmonary nodules (31 patients, 4.2%). The other incidental finding were pericardial (1.5%), vascular (1.2%), thymic (0.7%) and digestive diseases (0.5%). 42.6% of patients with incidental findings had an additional TDM and 56.8% a specialized medical advice. In 10 patients (9.3% of incidental findings), the identification of incidental finding led to a specific treatment of the underlying disease. In multivariate analysis, microalbuminuria, type of diabetes (TD2/TD3 vs TD1) and smoking were significantly associated with incidental findings (p = 0.003; p = 0.026; p = 0.050 respectively). CONCLUSIONS: Incidental findings are not rare in diabetic patients upon CAC assessment. A fraction of them are accessible to specific treatment. These findings raise the question if a systematic low dose chest TDM should be conducted in TD2 or TD3 patients and in any diabetic smokers by enlarging the window used for CAC assessment.

NNT mutations: a cause of primary adrenal insufficiency, oxidative stress and extra-adrenal defects.

OBJECTIVE: Nicotinamide nucleotide transhydrogenase (NNT), one of the several genes recently discovered in familial glucocorticoid deficiencies (FGD), is involved in reactive oxygen species detoxification, suggesting that extra-adrenal manifestations may occur, due to the sensitivity to oxidative stress of other organs rich in mitochondria. Here, we sought to identify NNT mutations in a large cohort of patients with primary congenital adrenal insufficiency without molecular etiology and evaluate the degree of adrenal insufficiency and onset of extra-adrenal damages. METHODS: Sanger or massive parallel sequencing of NNT and patient monitoring. RESULTS: Homozygous or compound heterozygous NNT mutations occurred frequently (26%, 13 unrelated families, 18 patients) in our cohort. Seven new mutations were identified: p.Met337Val, p.Ala863Glu, c.3G>A (p.Met1?), p.Arg129*, p.Arg379*, p.Val665Profs*29 and p.Ala704Serfs*19. The most frequent mutation, p.Arg129*, was found recurrently in patients from Algeria. Most patients were diagnosed belatedly (8-18 months) after presenting severe hypoglycemia; others experiencing stress conditions were diagnosed earlier. Five patients also had mineralocorticoid deficiency at onset. One patient had congenital hypothyroidism and two cryptorchidism. In follow-up, we noticed gonadotropic and genitalia impairments (precocious puberty, testicular inclusions, interstitial Leydig cell adenoma, azoospermia), hypothyroidism and hypertrophic cardiomyopathy. Intrafamilial phenotype heterogeneity was also observed. CONCLUSIONS: NNT should be sequenced, not only in FGD, but also in all primary adrenal insufficiencies for which the most frequent etiologies have been ruled out. As NNT is involved in oxidative stress, careful follow-up is needed to evaluate mineralocorticoid biosynthesis extent, and gonadal, heart and thyroid function.