Comparative results of a 4-year study on cardiovascular parameters, lipid metabolism, body composition and bone mass between untreated and treated adult growth hormone deficient patients.

OBJECTIVE: To evaluate the long-term evolution of cardiovascular parameters, lipid metabolism, body composition and bone mass in untreated and treated adult growth hormone deficient patients (AGHD) comparing the differences between the two groups and within each group. DESIGN: Seventy-one AGHD-patients were enrolled; 48 received growth hormone (GH) therapy: treated group (TG) and 23 received no GH therapy: control group (CG). In the TG, 22 were childhood-onset (CO) GH-deficient patients, 18-44 years (12 males) and 26 were adult-onset (AO) GH-deficient patients, 27-66 years (10 males). In the CG, 10 patients were AGHD-CO, 20-43 years (8 males) and 13 were AGHD-AO, 25-70 years (8 males). For patients in the TG, GH was administered at a starting dose of 0.1mg/day, adjusted to maintain IGF-I levels between 0 and 2 SDS for gender and age. At baseline and during the 4th year of replacement therapy or follow-up, the following parameters were evaluated: body mass index, waist circumference, blood glucose, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, total cholesterol/HDL-cholesterol ratio, systolic and diastolic blood pressure, 2-D echocardiogram with mitral Doppler, bone mineral density (total body, lumbar spine, and femoral neck), bone mineral content (BMC) and body composition. RESULTS: In the TG, there was a decrease in diastolic blood pressure (-4.0+/-1.8 mmHg, p<0.035) and an increase in blood glucose levels (0.58+/-0.19 mmol/L, p<0.025), bone mineral content (0.2+/-0.0 kg, p<0.015) and bone mineral density of lumbar spine (0.3+/-0.1 SDS, p<0.015) and femoral neck (0.4+/-0.1 SDS, p<0.001). All other variables did not show significant changes in any of the two groups. At year 4, changes (delta) differed between patients in the TG and those in the CG with regard to cholesterol levels (TG: -0.27+/-0.16 mmol/L, CG: 0.34+/-0.23 mmol/L, p<0.045), blood glucose (TG: 0.58+/-0.19 mmol/L, CG: -0.12+/-0.19 mmol/L, p<0.025) and BMC (TG: 0.2+/-0.0 g, CG: 0.0+/-0.0 g, p<0.015). An assessment of the changes in variables over time, with and without therapy, considering CO and AO separately, revealed a significant difference in total cholesterol levels during year 4 in CO patients CO (TG: -0.28+/-0.25 mmol/L and CG: 0.84+/-0.25 mmol/L, p<0.015). No differences related to the time of onset of GHD were found in changes in the remaining variables studied. There were no differences related to gender, GHD etiology or the presence of other pituitary hormone deficiencies in the evolution of the parameters analyzed. CONCLUSIONS: Our 4-year study in GH deficient adults showed significant beneficial effects on some cardiovascular risk parameters and BMC in treated patients. However, there are still unsettled issues regarding long-term benefits and these patients should be carefully monitored.

Controversies in the evolution of paediatric-adolescent varicocele: clinical, biochemical and histological studies.

OBJECTIVE: To study hormonal and histological parameters of paediatric-adolescent varicocele in order to know certain aspects of its natural history, in an attempt to find prognostic markers of testicular damage. DESIGN AND METHODS: In a prospective cross-sectional study, we evaluated 93 children and adolescents with left unilateral varicocele and 29 healthy males as control group. All of them were classified according to Tanner stage. Scrotal Doppler in both testes and GnRH and human chorionic gonadotrophin (hCG) tests were performed in all subjects. Surgery was performed in 28 patients and homolateral testicular biopsy in 18. RESULTS: Hormonal measurements of patients with varicocele were compared with a control group for each Tanner stage. Testicular biopsy specimens were analysed by light and electron microscopy. We only observed statistical differences in Tanner III patients in basal FSH (median and range) controls=1.70 (1.10-3.70) IU/l vs varicocele=4.20 (1.00-7.50) IU/l, P<0.05 and in Tanner IV patients in LH post-GnRH: controls=11.0 (7.50-15.0) IU/l vs varicocele=18.0 (5.10-29.0) IU/l, P<0.05 and in testosterone post-hCG: controls=9.50 (7.7-10.0) ng/ml vs varicocele=12.0 (6.2-23.0) ng/ml, P<0.01. No correlation was found between the various clinical grades of varicocele and hormonal measurements for each Tanner stage. No statistically significant differences were found between pre- and post-operative hormonal findings, either in basal levels or in maximal responses. On the other hand, no morphological abnormalities were observed by electron microscopy in germ cells, tubular wall and interstice. CONCLUSIONS: There appears to be no reliable biochemical marker in children and adolescents that may predict impaired testicular function. A significant size discrepancy between both testes, testicular pain and a hyperresponse to GnRH stimulation should continue to be, for the time being, the indications for surgery.

Reproducibility and variability of the arginine test in normal adults. Comparison between sexes.

The biochemical diagnosis of growth hormone deficiency in adults (AGHD) remains controversial, mainly as regards stimulation tests and suggested cut-off lines. The insulin tolerance test proved to be the most effective growth hormone (GH) secretagogue in normal males, but a poor intra-individual reproducibility has been reported. Given the safety of the arginine test (AST), we decided to evaluate the incidence of false negatives (non responder normal subjects), its reproducibility and variability. Twenty five healthy non-obese volunteers (16 males, 9 females) with a chronological age range between 19 and 40 years, (mean: 29.8) were evaluated. AST was performed (0.5 g/kg i.v. infusion for 30 min), measuring GH (IRMA) at baseline (B), 30, 60 and 90 minutes, and it was repeated in the same subject 7 to 30 days later; in females both tests were performed in the early follicular phase. Results (median and range) were: 1st test B: 0.61 (0.35-22.60) micrograms/L; maximal response (Mx Resp) 10.00 (0.48-48.80) micrograms/L. 2nd test B: 0.50 (0.38-27.0) micrograms/L; Mx Resp 11.00 (0.50-47.70) micrograms/L. The statistical evaluation (Wilcoxon signed rank test) showed no differences between B vs. B and Mx Resp vs Mx Resp. Separated by sex, males showed: 1st test: B 0.45 (0.35-4.30) micrograms/L; Mx Resp 6.30 (0.48-48.80) micrograms/L. 2nd test B 0.46 (0.38-8.80) micrograms/L; Mx Resp 10.90 (0.50-47.70) micrograms/L, while females showed 1st test: B 5.20 (0.50-22.60) micrograms/L; mx Resp 14.00 (3.50-36.70) micrograms/L. 2nd test B 3.60 (0.75-27.00) micrograms/L; Mx Resp 13.00 (3.70-28.10) micrograms/L. The statistical comparison (Mann Whitney test) showed significant differences between both sexes in basal values of the first and second test (p < 0.001), and in the maximal response of the first test (p < 0.03). The statistical analysis did not show significant differences in delta increases between males and females, neither in the first AST nor in the second one. Considering GH values > or = 3 micrograms/L as a positive response, 4 males exhibited insufficient responses in both tests and other 2 males showed discordant results between tests 1 and 2. All females evaluated produced responses above 3 micrograms/L in both tests. The results of the present study demonstrate that, particularly in men, AST has no clear limit of normality while it shows good intra-individual reproducibility. In conclusion, at present the biochemical diagnosis of AGHD requires a clear and precise standardization which includes all variables that can modify the GH response to the stimulus used.

Reproducibility and variability of the arginine test in normal adults. Comparison between sexes.

The biochemical diagnosis of growth hormone deficiency in adults (AGHD) remains controversial, mainly as regards stimulation tests and suggested cut-off lines. The insulin tolerance test proved to be the most effective growth hormone (GH) secretagogue in normal males, but a poor intra-individual reproducibility has been reported. Given the safety of the arginine test (AST), we decided to evaluate the incidence of false negatives (non responder normal subjects), its reproducibility and variability. Twenty five healthy non-obese volunteers (16 males, 9 females) with a chronological age range between 19 and 40 years, (mean: 29.8) were evaluated. AST was performed (0.5 g/kg i.v. infusion for 30 min), measuring GH (IRMA) at baseline (B), 30, 60 and 90 minutes, and it was repeated in the same subject 7 to 30 days later; in females both tests were performed in the early follicular phase. Results (median and range) were: 1st test B: 0.61 (0.35-22.60) micrograms/L; maximal response (Mx Resp) 10.00 (0.48-48.80) micrograms/L. 2nd test B: 0.50 (0.38-27.0) micrograms/L; Mx Resp 11.00 (0.50-47.70) micrograms/L. The statistical evaluation (Wilcoxon signed rank test) showed no differences between B vs. B and Mx Resp vs Mx Resp. Separated by sex, males showed: 1st test: B 0.45 (0.35-4.30) micrograms/L; Mx Resp 6.30 (0.48-48.80) micrograms/L. 2nd test B 0.46 (0.38-8.80) micrograms/L; Mx Resp 10.90 (0.50-47.70) micrograms/L, while females showed 1st test: B 5.20 (0.50-22.60) micrograms/L; mx Resp 14.00 (3.50-36.70) micrograms/L. 2nd test B 3.60 (0.75-27.00) micrograms/L; Mx Resp 13.00 (3.70-28.10) micrograms/L. The statistical comparison (Mann Whitney test) showed significant differences between both sexes in basal values of the first and second test (p < 0.001), and in the maximal response of the first test (p < 0.03). The statistical analysis did not show significant differences in delta increases between males and females, neither in the first AST nor in the second one. Considering GH values > or = 3 micrograms/L as a positive response, 4 males exhibited insufficient responses in both tests and other 2 males showed discordant results between tests 1 and 2. All females evaluated produced responses above 3 micrograms/L in both tests. The results of the present study demonstrate that, particularly in men, AST has no clear limit of normality while it shows good intra-individual reproducibility. In conclusion, at present the biochemical diagnosis of AGHD requires a clear and precise standardization which includes all variables that can modify the GH response to the stimulus used.