Omar Villaroel

Cardiovascular risk of young growth-hormone-deficient adolescents. Differences in growth-hormone-treated and untreated patients.

Objective: To determine whether postprandial lipids, coagulation factors and homocysteine levels are abnormal in young growth hormone (GH)-deficient (GHD) adolescents. Methods: Fifteen GHD adolescents on GH replacement were studied. Ten untreated GHD adolescents and 15 healthy subjects served as controls. Fasting lipids, lipoprotein(a), fibrinogen, plasminogen activator inhibitor-1, homocysteine, folate and vitamin B12 levels were measured. Cholesterol and triglycerides were measured 4 h after a high fat meal. Results: Fasting and postprandial triglycerides and homocysteine levels of untreated GHD patients were increased compared to those of GH-treated GHD subjects and healthy controls; fibrinogen concentrations were elevated in both treated and untreated adolescents. Conclusions: GHD adolescents present an abnormal fasting and postprandial lipid profile. In addition, the increased fibrinogen and homocysteine levels are suggestive of the accumulation of cardiovascular risk factors early on in life.

Decreased bone mass despite long-term estrogen replacement therapy in young women with Turner’s syndrome and previously normal bone density

OBJECTIVE To determine whether young women with Turners syndrome who had normal bone mineral density (BMD) before the induction of puberty maintain normal BMD in young adulthood. DESIGN Controlled clinical study. SETTING A private hospital clinical research setting. PATIENTS Young women with Turners syndrome in Tanner stage V of puberty with previously normal BMD. INTERVENTIONS Oral conjugated estrogens and progesterone acetate were administered continuously for a mean (+/-SD) of 4.1+/-1.0 years. Bone mineral densities and blood samples were evaluated. MAIN OUTCOME MEASURE(S) The BMD of the lumbar spine and the femoral neck was determined during young adulthood. The change in BMD over the previous 6 years also was evaluated. Serum concentrations of the carboxy-terminal propeptide of type 1 collagen and of the carboxy-terminal cross-linked telopeptide of type 1 collagen were measured. RESULT(S) The BMD of the lumbar spine was reduced significantly in our patients. There was no change in the BMD of the femoral neck or lumbar spine over a period of 6.1 years. Concentrations of the carboxy-terminal propeptide of type 1 collagen were decreased, whereas concentrations of the carboxy-terminal cross-linked telopeptide of type 1 collagen were increased. CONCLUSION(S) Young women with Turners syndrome do not attain normal peak bone mass even when estrogen replacement therapy is begun in adolescence. Their low BMD seems to be due to decreased bone formation and increased bone resorption.

Serum lipids, lipoprotein Ip(a), and plasminogen activator inhibitor-1 in patients with Turner's syndrome before and during growth hormone and estrogen therapy

OBJECTIVE To evaluate whether girls with Turners syndrome have an increased risk for cardiovascular disease due to alterations in their lipoprotein metabolism. DESIGN Controlled clinical study. SETTING Private academic hospital. PATIENT(S) Fifteen untreated girls with Turners syndrome were studied initially; 11 of these patients were evaluated further while on therapy. INTERVENTION(S) Serum lipids, lipoprotein lp(a), and plasminogen activator (PA) inhibitor-1 were measured before and during 6 months of either GH or estrogen (E) treatment. MAIN OUTCOME MEASURE(S) Serum lipids, lipoprotein lp(a), and PA inhibitor-1 (PAI-1). RESULT(S) Total and low-density lipoprotein (LDL) cholesterol, triglycerides, lipoprotein lp(a), and PA inhibitor-1 levels were normal in Turners syndrome patients compared with age-matched controls; HDL cholesterol was increased. During GH treatment, a significant decrease in total and LDL cholesterol was noted, whereas lipids, lipoprotein(a), and PA inhibitor-1 levels did not change with E therapy. CONCLUSION(S) The normal lipoproteins of untreated adolescents with Turners syndrome, as well as the further decrease of total and LDL cholesterol during GH treatment, would seem to indicate that lipoproteins do not increase the cardiovascular risk of these girls.

Effectiveness and limitations of the use of the gonadotropin-releasing hormone agonist leuprolide acetate in the diagnosis of delayed puberty in males.

In order to evaluate the effectiveness of the gonadotropin-releasing hormone agonist leuprolide acetate in distinguishing gonadotropin deficiency from delayed puberty, a single subcutaneous dose of 20 micrograms/kg of leuprolide acetate was administered at 07.00 h to 14 patients with constitutionally delayed puberty and to 8 gonadotropin-deficient subjects, and serum gonadotropin and testosterone levels were determined at baseline and 1,2,3,6,12, and 24 h thereafter. The increase in gonadotropin and testosterone levels was significant in patients with delayed puberty, so that the mean peak luteinizing hormone and to a lesser degree the mean peak testosterone levels clearly differentiated normally delayed from gonadotropin-deficient puberty. However, when the peak gonadotropin and testosterone concentrations were analyzed individually, there was a considerable overlap between the two groups of males, limiting the usefulness of this test.

Circulating levels of high-sensitivity C-reactive protein and soluble markers of vascular endothelial cell activation in growth hormone-deficient adolescents.

Background/Aims: Significant endothelial dysfunction as determined by lower flow-mediated vasodilation of the brachial artery was recently reported by us in growth hormone-deficient (GHD) adolescents. The circulating concentrations of markers of vascular endothelial cell and platelet activation and their relationship to inflammatory markers have not been previously evaluated in this group of patients. Objective: To assess the relationship between circulating levels of high-sensitivity C-reactive protein (CRP) and soluble markers of vascular endothelial cell activation in GHD adolescents. Design/Methods: Twenty-eight GHD children on GH treatment with a chronological age of 15.7 ± 2.6 years and 16 untreated GHD adolescents with a chronological age of 16.6 ± 3.3 years were studied. Concentrations of CRP, as an inflammatory marker, were measured in all patients and the association between CRP and the fasting soluble markers of vascular endothelial cell activation intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin and P-selectin levels was evaluated. Sixteen healthy adolescents with a mean chronological age of 15.1 ± 2.2 years served as controls. Results: CRP and P-selectin levels were significantly higher in untreated GHD adolescents than in treated GHD subjects or in healthy controls (p < 0.02), while VCAM-1 concentrations were increased in both untreated and treated GHD adolescents when compared to controls (p < 0.007). E-selectin and ICAM-1 levels were similar in all three groups. CRP was found to be associated with BMI (r: 0.62; p < 0.001), P-selectin (r: 0.43; p < 0.01), E-selectin (r: 0.27; p < 0.03), ICAM-1 (r: 0.23; p < 0.05) and VCAM-1 (r: 0.40; p < 0.001) concentrations in untreated GHD adolescents and with P-selectin (r: 0.88; p < 0.001) and E-selectin (r: 0.29; p < 0.01) in treated GHD subjects. A weak inverse association was observed in a subgroup of patients between brachial artery endothelium-dependent dilation and P-selectin (r: –0.56; p < 0.07). Conclusions: Low-grade inflammation as manifested by increased circulating levels of CRP seems to be associated with the early activation of vascular endothelial cells in GHD adolescents

Short- and long-term effect of oral salbutamol on growth hormone secretion in prepubertal asthmatic children☆

Salbutamol, a beta 2-adrenergic agonist, is being extensively used in Venezuela as a brochodilator in the treatment of asthma in children. Previous reports have shown oral salbutamol either to inhibit or not to affect growth hormone (GH) secretion. We evaluated the effect of oral salbutamol (0.1 mg/kg every 6 hours for 3 months) on GH secretion in eight prepubertal short children with mild asthma. Levels of GH during sleep (samples taken every 30 minutes from 9 PM to 6 AM) and after GH-releasing hormone ([GHRH] 1 microgram/kg intravenously [IV]) were measured before, at 24 hours, and at 3 months of salbutamol treatment. Overnight integrated concentrations of GH and peak GH levels following GHRH diminished significantly after 24 hours of salbutamol therapy (from 4.5 +/- 1.3 to 3.4 +/- 0.8 micrograms/L and from 46.6 +/- 47.3 to 16.2 +/- 7.9 micrograms/L, respectively, P < .05). However, GH levels after 3 months of salbutamol were not different from basal levels (4.5 +/- 1.3 v 5.1 +/- 5.1 +/- 2.9 micrograms/L during the overnight studies and 46.6 +/- 47.3 v 37.8 +/- 30.4 micrograms/L after GHRH). Our data suggest an inhibition of both spontaneous and stimulated GH secretion following short-term oral salbutamol ingestion, but this suppressive effect is not maintained with its long-term use.

Acknowledgements to Reviewers

Badenhoop, K., Frankfurt am Main Bang, P., Stockholm Baron, J., Bethesda, Md. Barreca, A., Genoa Barrios, V., Madrid Bartalena, L., Varese Bartrons, R., L’Hospitalet Baudin, E., Villejuif Bauer, K., Hannover Baumgartner, A., Berlin Baxter, R., St. Leonards Beauvillain, J.C., Lille Beck, M., Mainz Beck-Peccoz, P., Milan Ben-Shlomo, A., Los Angeles, Calif. Bettendorf, M., Heidelberg Bianchi, G., Bologna Bland, M.L., San Francisco, Calif. Blasi Cabus, J.M., Barcelona Böhm, B., Ulm Brabant, G., Hannover Brain, C.F., London Brämswig, J.H., Münster Breckwoldt, M., Freiburg i. Br. Brucker, C., Ulm Buchanan, C., London Burbach, J.P., Utrecht Buyse, M., Paris Buyukgebiz, A.B., Izmir Carel, J.-C., Paris Chaussain, J.-L., Paris Chiarelli, F., Chieti Chrousos, G.P., Bethesda, Md. Clark, A.J.L., London Coerper, S., Tübingen Cohen, L.E., Boston, Mass. Cohen, M.M., Halifax Cole, T.J., London Corry, D.B., Sylmar, Calif. Cowell, C.T., Westmead Crofton, P.M., Edinburgh Cutfield, W., Auckland Czernichow, P., Paris

Contents Vol. 60, 2003

Anne Marcovich: Quelles missions pour les médecins de campagne du XIX siècle français? Soigner, éduquer, civiliser. Le rapport d’un médecin cantonal du Haut-Rhin (Alsace) en 1849 [Which Tasks for Countryside Physicians in 19th Century France? To Heal, to Educate, to Civilise the People.A Country Physician’s Report from the French Department of the Haut-Rhin in 1849] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 170