Systematic thyroid screening in myotonic dystrophy: link between thyroid volume and insulin resistance.

BACKGROUND: Myotonic dystrophy (DM1), a neuromuscular disease related to DMPK gene mutations, is associated to endocrine disorders and cancer. A routine endocrine work-up, including thyroid ultrasound (US), was conducted in 115 genetically-proven DM1 patients in a neuromuscular reference center. The aim of this study was to determine the prevalence and the causes of US thyroid abnormalities in DM1. RESULTS: In the whole population (age 45.1 ± 12.2 years, 61.7% female), palpable nodules or goiters were present in 29.2%. The percentage of US goiter (thyroid volume > 18 mL) and US nodules were, respectively, 38.3 and 60.9%. Sixteen of the 115 patients had a thyroidectomy, after 22 fine-needle aspiration cytology guided by thyroid imaging reporting and data system (TIRADS) classification. Six micro- (1/6 pT3) and 3 macro-papillary thyroid carcinoma (PTCs) (2/3 intermediate risk) were diagnosed (7.9% of 115). Thyroid US led to the diagnosis of 4 multifocal and 2 unifocal (including 1 macro-PTC) non-palpable PTCs. Ultrasound thyroid volume was positively correlated to body mass index (BMI) (p = 0.015) and parity (p = 0.036), and was inversely correlated to TSH (p < 0.001) and vitamin D levels (p = 0.023). The BMI, the frequencies of glucose intolerance and PTC were significantly higher in UsGoiter versus non-UsGoiter groups. CONCLUSION: In this systematically screened DM1 cohort, the frequency of UsGoiter, mainly associated to BMI, was about 40%, US nodules 60%, thyroidectomies 13-14%, and PTCs 8%, two-thirds of them being micro-PTCs with good prognosis. Therefore, a systematic screening remains debatable. A targeted US screening in case of clinical abnormality or high BMI seems more appropriate.

[Atrial natriuretic hormones and metabolic syndrome: recent advances]. / Hormones natriurétiques et syndrome métabolique : mise au point.

Natriuretic peptides are a group of hormones including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C type (CNP), urodilatin and guanilyn. ANP (half-life: 2-4 min), is secreted by the atrium, BNP (half-life: 20 min) by the ventricle, CNP by the vascular endothelium, urodilatin by the kidney and guanylin by the intestine. These natriuretic peptides prevent water and salt retention through renal action, vasodilatation and hormonal inhibition of aldosterone, vasopressin and cortisol. These peptides also have a recently demonstrated metabolic effect through an increase of lipolysis, thermogenesis, beta cell proliferation and muscular sensitivity to insulin. Blood levels of these natriuretic peptides depend on "active NPR-A receptors/clearance NPR-C receptors", the last ones being abundant on adipocytes. Therefore, natriuretic peptides act as adipose tissue regulator and constitute a link between blood pressure and metabolic syndrome. They are used as markers and treatment of cardiac failure. Other applications are on going. BNP and NT-proBNP (inactive portion de la pro-hormone) are used as markers of cardiac failure since they have a longer half-life than ANP. BNP decrease is quicker and more important than that one of NT-ProBNP in case of improvement of cardiac failure. Chronic renal insufficiency and beta-blockers increase BNP levels. BNP measurement is useless under treatment with neprilysine inhibitors such as sacubitril, one of the neutral endopeptidases involved in catabolism of natriuretic peptides. The association sacubitril/valsartan is a new treatment of chronic cardiac failure, acting through the decrease of ANP catabolism.

Hyperparathyroidism complicating CYP 24A1 mutations.

CYP24A1 gene mutations induce infantile hypercalcemia, with high 1,25(OH)2D contrasting with low PTH levels. The adult phenotype is not well known. Two unrelated adult patients were referred for nephrolithiasis, hypertension, hypercalcemia, hypercalciuria, normal 25-OHD levels, and inappropriate PTH levels (22 to 92pg/mL;N: 15-68) suggesting primary hyperparathyroidism, leading to surgery. Hypercalciuria improved despite persistent hypercalcemia, treated with cinacalcet. The ratio 25-OHD3/24-25-(OH)2D3>100 (N<25) suggested the diagnosis of CYP24A1 mutations which were confirmed through Sanger sequencing. In conclusion, the adult phenotype associated with CYP24A1 mutations can evolve over time from hypercalcemia with suppressed PTH towards hyperparathyroidism with moderately increased PTH level, adenoma and/or slightly increased parathyroid glands. Surgery decreased calciuria and improved kidney function. Cinacalcet was partially effective on hypercalcemia since PTH was inappropriate. This novel phenotype, a phenocopy of hyperparathyroidism, might evolve in few cases towards hyperparathyroidism despite random association of the 2 diseases cannot be excluded.