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Objective: Patients with congenital hypothyroidism (CH) display subclinical abnormalities of the cardiovascular system that are related to unphysiological fluctuations of TSH levels and occur despite careful replacement therapy., Design: The aim of the present case-control study was to evaluate the effects of long-term levothyroxine (l-T(4)) replacement therapy on the vascular district in CH patients by assessing endothelial function with flow-mediated dilation (FMD) and brachial artery distensibility with the measurement of the coefficient of distensibility (DC)., Methods: Thirty-two young adults with CH aged 18.9+/-0.2 years and 32 age- and sex-matched controls underwent brachial Doppler ultrasound examination to measure FMD and DC at the time of the study. Hypothyroidism was diagnosed by neonatal screening, and l-T(4) treatment was initiated within the first month of life., Results: Compared to healthy controls, CH patients had significantly reduced brachial artery reactivity with lower FMD values (8.9+/-5.7 vs 14.1+/-5.1% P=0.003) and decreased vascular distensibility (24.6+/-1.6 vs 27.3+/-3 kPa(-1)x10(-3), P<0.0002). Linear regression analysis revealed that both total and pubertal mean TSH and number of episodes of undertreatment were independent determinants of FMD and DC. Pubertal mean TSH was the best predictor of both FMD and DC (r=0.81 and r=0.87 respectively, P<0.001)., Conclusions: Young adults with CH treated with long-term l-T(4) replacement therapy may have significant impairment of both FMD and DC. Our data suggest that high TSH levels, inadequately corrected by l-T(4) replacement therapy in CH patients especially during puberty, can exert significant effects on the elastic and functional vessel properties.

Background: Iodide transport defects (ITDs), rare causes of congenital hypothyroidism (CH), have been shown to arise from abnormalities of the sodium/iodide symporter (NIS). We describe a 16-year-old girl with CH caused by an ITD resulting from a novel mutation of NIS., Summary: A 16-year-old girl with CH diagnosed by a neonatal screening program received early treatment with L-thyroxine replacement therapy. A (123)I scan had failed to reveal any iodide uptake by the thyroid and salivary glands; thus, thyroid agenesis was diagnosed. Thyroglobulin (Tg) was not measured when she was a neonate or infant. Unexpectedly, at the age of 14.5 years, a nodular goiter and high serum Tg concentrations (303 ng/mL; normal, <50) were identified. Her thyroid radioactive iodine uptake was very low as was the saliva to plasma iodide ratio (0.5). Analysis of her NIS gene revealed an in-frame six-nucleotide deletion of the coding sequence (1206-1211delGTCGGC) corresponding to the deletion of amino acids 287 and 288 of the human NIS protein located at the beginning of the VIII transmembrane segment. The proband was homozygous for this deletion, whereas both unrelated parents and her brother were heterozygous. COS-7 cells transfected with the mutant NIS failed to concentrate iodide, confirming that the mutation was the direct cause of the ITD in this patient., Conclusions: We describe a patient with CH caused by a previously not described mutation of the NIS gene that was inherited from her parents. We therefore recommend that thyroid ultrasonography be performed in CH patients with low radioactive iodine uptake and elevated serum Tg.

Background: GH-deficient (GHD) children have reduced left ventricular (LV) mass, but impairment of cardiac function has never been documented., Aim: The aim of the study was to evaluate effects of GHD and GH therapy on cardiac function using load-dependent and load-independent indices of myocardial contractility., Patients and Methods: Echocardiography was performed in 24 GHD children at baseline and 1 and 2 yr after GH therapy and in 24 controls., Results: Compared with controls, GHD children at baseline had lower LV mass (LV mass/BSA 50.6 +/- 1.8 vs. 60.5 +/- 2.4 g/m(2); P < 0.002, and LV mass/H(2.7) 28.7 +/- 1.2 vs. 33.6 +/- 1.3 g/m(2.7); P < 0.009). Global systolic function was normal, with only a trend toward slight impairment of the fractional shortening (34.9 +/- 1.5 vs. 37.6 +/- 1.1%). However, subtle LV dysfunction was revealed by load-dependent and load-independent indices of myocardial contractility. In fact, GHD patients compared with controls showed lower rate-corrected mean velocity of circumferential fiber shortening (1.0 +/- 0.03 vs. 1.18 +/- 0.03 circ/sec; P = 0.0001) and stress shortening index (0.10 +/- 0.02 vs. 0.18 +/- 0.02; P < 0.007) and higher end-systolic stress (49.2 +/- 1.4 vs. 45.7 +/- 1.0 g/cm(2); P < 0.05). One year of GH treatment was associated with a significant improvement of cardiac size (LV mass/BSA 67.8 +/- 2.9 g/m(2); LV mass/H(2.7) 38.2 +/- 2.0 g/m(2.7); P < 0.0001 and P = 0.0003, respectively) and myocardial contractility (mean velocity of circumferential fiber shortening 1.2 +/- 0.04 circ/sec; P < 0.0002; stress shortening index 0.19 +/- 0.02; P < 0.003) and reduced afterload (end-systolic stress 43.9 +/- 1.4 g/cm(2); P < 0.03)., Conclusions: Our data indicate that GH deficiency is associated with abnormalities in morphology and function in not only adults but also children and further supports the beneficial effect of GH on the heart.

Introduction: Lysinuric protein intolerance (LPI; MIM 222700) is a rare, autosomal recessive metabolic disorder caused by mutations in the SLC7A7 gene, which encodes the light chain of the cationic amino acids (CAA) transporter y+. The clinical presentation of LPI includes gastrointestinal symptoms, failure to thrive, episodes of coma, hepatosplenomegaly and osteoporosis. However, other findings have also been reported, and these suggest a multisystem involvement., Discussion: We report a girl with confirmed LPI who presented with severe short stature that was unresponsive to adequate LPI treatment. The girl was found to have a classic growth hormone deficiency (GHD) and responded well to growth hormone (GH) replacement therapy., Conclusion: While it is not known whether the mechanisms involved in the GHD of our patient are related to LPI, this case suggests that GH/IGF-I axis should be investigated in LPI children with persistent growth failure.

Objective: This open, prospective study was designed to evaluate the effect of growth hormone deficiency (GHD) and GH replacement therapy on serum homocysteine (Hcy) concentration in children with GHD., Subjects: Seventeen prepubertal children with GHD (11 boys and six girls) aged 8.6 +/- 1.9 years were studied before and after 12 months of GH replacement therapy at a dose of GH of 30 microg/kg/day. Seventeen healthy children acted as controls and were matched for age, sex and body mass index (BMI)., Methods: At study entry, height, weight, blood pressure, serum Hcy, serum IGF-I, total-low density lipoprotein (LDL)- and high density lipoprotein (HDL) cholesterol, triglycerides, free T4, free T3, vitamin B12, folate, glucose and creatinine were measured in all subjects. The atherogenic index (AI) was also calculated as the ratio of total cholesterol/HDL cholesterol (T/HDL). In GHD children these parameters were also revaluated after 12 months of GH therapy., Results: At study entry height and serum IGF-I were significantly lower, as expected, in GHD patients than in controls (P < 0.0001 and P < 0.007, respectively). Serum Hcy levels were significantly higher in GHD patients than in healthy children (8.4 +/- 2.9 vs. 6.0 +/- 2.9 micromol/l; P < 0.03), although the absolute values were within the normal values for age and sex. There were no significant differences at baseline with respect to blood pressure, serum vitamin B12, folate, fT3, fT4, lipid profile, creatinine and glucose levels. After 12 months of GH replacement therapy height and serum IGF-I increased significantly compared to pretreatment values (P < 0.0001); serum Hcy levels decreased significantly (6.0 +/- 3.3 micromol/l; P < 0.002) compared to baseline values, becoming similar to control values. Total cholesterol (3.5 +/- 0.6 mmol/l) and the AI (2.5 +/- 0.8) decreased significantly with respect to both pretreatment (4.2 +/- 1.0 mmol/l; P < 0.0002 and 3.4 +/- 0.8; < 0.002, respectively) and control values (4.2 +/- 0.4 mmol/l; P < 0.0005 and 3.3 +/- 1.1; P = 0.02, respectively)., Conclusions: GHD in children is associated with higher serum levels of Hcy compared to controls, without significantly affecting the lipid profile. GH replacement for 12 months significantly decreased the Hcy levels and improved the lipid profile with a decrease of total cholesterol and the total/HDL cholesterol ratio, compared to pretreatment values. Given the small number of patients, further larger studies are needed to clarify whether these results may have significant effects in the prevention of cardiovascular disease in adulthood.