Thyroid Function Anomalies in Children with Down Syndrome: Early TSH Alteration can Predict Future Hypothyroidism Development?

Background: Subclinical hypothyroidism is a common finding in Down syndrome (DS) patients and transition towards overt hypothyroidism can occur, but there are no predictor factors to identify patients that will need replacement therapy later in life. Objective and hypotheses: This is a retrospective cohort study on a population of DS paediatric patients. This study was designed to evaluate possible early predictive features of hypothyroidism development. Methods: We retrospectively evaluated 49 paediatric DS patients (31 males and 18 females). Median (IQR) age at first evaluation was 3.47 (0.5 \u2013 15.7) years and follow-up 4.3 years (1\u20139). Thyroid function was described as normal (TSH 0.31\u20135.00 mUI/ml), subclinical hypothyroidism (TSH 5.10\u201310.00 mUI/ml, normal fT4 and fT3) or overt hypothyroidism (TSH O 10.00 mUI/ml). Autoimmune etiology was investigated through auto-antibodies positivity (AbTPO, AbTG; TRAb). Statistical analysis was performed using logistic regression and ROC curves, Mann- Whitney test, chisquare test and Odd ratio. The statistical significance was set at P!0.05. Results: In our study 38.8% of patients (19/49) showed subclinical hypothyroidism during followup. Therapy with L-thyroxine was initiated in 8 patients (16.3%), who were diagnosed with overt hypothyroidism (4/8 have autoimmune thyroiditis). We found that a TSH cut-off value of 5.07 mUI/ml at first evaluation was significantly predictive of overt hypothyroidism development during follow-up (sensibility 100%, specificity 43.9%). Moreover, patients who started replacement therapy during follow-up, had significantly increased thyrotropin values at first evaluation (P!.01). Also anti-thyroid antibodies positivity resulted to be predictive of thyroid disease (P!.002). Finally, we observed that TSH O 5.07 associated with anti-thyroid antibodies positivity increased the risk of hypothyroidism of 12.6 time. Conclusion: Our study showed that an early increase of TSH value, using as cut-off 5.07 mUI/ml, associated with auto-antibodies positivity can identify DS patients who need a more careful followup, since the risk of hypothyroidism seems to be higher

Enhanced platelet release of superoxide anion in systemic hypertension: Role of AT1 receptors

BACKGROUND: Enhanced oxidative stress has been observed in hypertension, but the underlying mechanism has not been fully clarified. OBJECTIVE: To study the relationship between oxygen free radicals and hypertension, using platelets as a tool to measure the cellular production of superoxide anion (O2). DESIGN: Forty patients with hypertension were allocated randomly to groups to receive either irbesartan, an inhibitor of angiotensin II type 1 (AT1) receptors (n = 20), or a diuretic (hydrochlorothiazide) (n = 20). In each patient, collagen-induced production of O2 by platelets was studied before and after 4 weeks of treatment. Forty sex- and age-matched healthy individuals were studied as controls. METHODS: Platelet-produced O2 was measured using lucigenin chemiluminescence and hydroethidine cytofluorimetric analysis. RESULTS: Compared with healthy individuals, patients with hypertension showed a greater production of O2 by platelets (P < 0.001); there was no correlation between blood pressure and platelet O2 production. After treatment, no changes in platelet O2 formation were observed in patients receiving hydrochlorothiazide; conversely, those treated with irbesartan showed a significant (P < 0.001) decrease in platelet O2 production. At the end of the treatment, no differences in blood pressures were observed between the two groups. In-vitro incubation of platelets with angiotensin II elicited a significant increase in O2 (P < 0.001) that was dose-dependently inhibited by irbesartan and diphenylene iodonium, an inhibitor of NADPH oxidase. CONCLUSION: Patients with hypertension showed an enhanced formation of O2 in platelets that was not dependent on blood pressure but could be mediated by AT1 receptors via NADPH oxidase activation

Autonomic cardiovascular control and diastolic dysfunction in hypertensive subjects

Background: Early hypertension is associated with left ventricular diastolic dysfunction due to increased end-diastolic pressure. This increase, through the cardiopulmonary reflexes, can influence autonomic cardiovascular control. Methods: We assessed autonomic nervous system modulation of cardiovascular signals by power spectral analysis of RR interval and systolic arterial pressure variabilities in subjects with recently diagnosed hypertension with or without diastolic dysfunction and in normotensive control subjects. Results: Both hypertensive groups had higher low-frequency (LF) power expressed in nortualized units (NUs) than normotensive controls (p < 0.05;p < 0.001) during controlled breathing at rest. The LF spectral index measured after tilt was greater in hypertensive subjects with diastolic dysfunction than in those without (p < 0.05). LF NUs measured at rest correlated significantly with the E/Awave ratio and after tilt with the E-wave deceleration time. Conclusions: These results seem to indicate that in subjects with recently diagnosed hypertension sympathetic modulation of the sinus node prevails. During tilt, a maneuver designed to stimulate systemic arterial and cardiopulmonary baroreceptor reflexes, hypertensive subjects with diastolic dysfunction, who presumably also have higher end-diastolic pressures, seem to have greater sympathetic modulation of the sinus node than hypertensive subjects without diastolic dysfunction. (c) 2005 Elsevier Ireland Ltd. All rights reserved