Cosecretion of glycosylated prolactin and non-glycosylated prolactin from childhood to the end of puberty.

BACKGROUND: Glycosylated prolactin (G-PRL) is considered as the major post-translational modification of prolactin (PRL) showing reduced lactotropic and mitogenic activities compared to non-glycosylated prolactin (NG-PRL). AIM: To evaluate the evolution of G-PRL in normoprolactinemic children and adolescents and to analyze possible variations in glycosylated/total prolactin (T-PRL) ratios. METHODS: T-PRL, G-PRL and NG-PRL were evaluated in 111 healthy female and male children and adolescents (4.1-18 years), classified as group 1 (Tanner I), group 2 (Tanner II-III) and group 3 (Tanner IV-V). G-PRL and NG-PRL were identified by chromatography on concanavalin-A-Sepharose. RESULTS: G-PRL/T-PRL (median-range): females, group 1: 0.59 (0.17-0.77), group 2: 0.56 (0.31-0.78), group 3: 0.60 (0.38-0.79); males, group 1: 0.64 (0.39-0.80), group 2: 0.61 (0.24-0.79), group 3: 0.62 (0.35-0.90); the p value is not significant among the different groups in both genders. G-PRL/T-PRL ratios do not change when comparing low (first quartile) versus high (third quartile) T-PRL levels in the different groups. CONCLUSION: Our study would appear to support cosecretion of G-PRL and NG-PRL from childhood to the end of puberty. Such cosecretion would not be dependent on sex steroid levels. It is important to point out that puberty does not change the proportions of G-PRL and NG-PRL.

Prolactinoma in children and adolescents.

The evolution of prolactinomas in children and adolescents continues to be controversial. Girls have more prevalence of microprolactinomas and their signs and symptoms are related to hyperprolactinemia and the resulting hypogonadotrophic hypogonadism. In males, the greater incidence of macroadenomas results in the presence of neuro-ophthalmologic signs. The larger prevalence of macroadenomas in males is consistent with findings in adults and would not be related to a later diagnosis. In patients with asymptomatic hyperprolactinemia, the presence of altered proportions of PRL isoforms should be evaluated. The diagnosis of prolactinoma requires both radiographic evidence of pituitary adenoma and laboratory analysis documenting the presence of sustained hyperprolactinemia. Because of their effectiveness and tolerance, dopaminergic agonists are the initial therapy of choice in pediatric age patients. Finally, molecular biology and genetic studies have brought new insights into the pathogenesis, clinical behavior and different therapeutic responses.

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.

Medium and long-term outcome of growth hormone therapy in growth hormone deficient adults

We evaluated long-term replacement therapy outcomes in various subsets of patients with adult growth hormone (GH) deficiency (AGHD) as well as the patients' susceptibility to adverse events. Fifty-nine patients with AGHD were evaluated, 27 with childhood onset (CO) (18-44 years old, 12 females) and 32 with adult onset (AO) (27-70 years, 18 females). A significant improvement in HDL-cholesterol was observed in AGHD-AO males (basal: 41.3 +/- 12.9 mg/dl, intratreatment: 47.5 +/- 13.2 mg/dl, p = 0.009). However, individual analyses showed that total cholesterol decreased below 240 mg/dl in 33% of AGHD-CO patients and in 50% of AGHD-AO patients, and below 200 mg/dl in 67% of AGHD-CO patients and in 29% of AGHD-AO patients; in the AGHD-AO group, normalization of LDL-cholesterol (< or = 160 mg/dl) and triglycerides (< or = 200 mg/dl) was found in 100% and 50% of patients, respectively; the total cholesterol/HDL ratio decreased below 4.5 in 20% of AGHD-CO patients and in 25% of AGHD-AO patients. The cardiological evaluation showed a significant intra- and interindividual heterogeneity, but cardiac mass improved in patients with a baseline cardiac mass index below 60 g/m2. Markers of bone apposition increased significantly, while bone resorption markers were found to remain unchanged during treatment. A correlation was found between increased bone mineral content and lean body mass (p = 0.0009). Susceptibility to adverse events was not found to be dependent on gender or on the time of onset of the deficiency. Our findings would appear to confirm that a more severe metabolic impairment is correlated with a better therapeutic outcome.

Medium and long-term outcome of growth hormone therapy in growth hormone deficient adults

We evaluated long-term replacement therapy outcomes in various subsets of patients with adult growth hormone (GH) deficiency (AGHD) as well as the patients susceptibility to adverse events. Fifty-nine patients with AGHD were evaluated, 27 with childhood onset (CO) (18-44 years old, 12 females) and 32 with adult onset (AO) (27-70 years, 18 females). A significant improvement in HDL-cholesterol was observed in AGHD-AO males (basal: 41.3 +/- 12.9 mg/dl, intratreatment: 47.5 +/- 13.2 mg/dl, p = 0.009). However, individual analyses showed that total cholesterol decreased below 240 mg/dl in 33% of AGHD-CO patients and in 50% of AGHD-AO patients, and below 200 mg/dl in 67% of AGHD-CO patients and in 29% of AGHD-AO patients; in the AGHD-AO group, normalization of LDL-cholesterol (< or = 160 mg/dl) and triglycerides (< or = 200 mg/dl) was found in 100% and 50% of patients, respectively; the total cholesterol/HDL ratio decreased below 4.5 in 20% of AGHD-CO patients and in 25% of AGHD-AO patients. The cardiological evaluation showed a significant intra- and interindividual heterogeneity, but cardiac mass improved in patients with a baseline cardiac mass index below 60 g/m2. Markers of bone apposition increased significantly, while bone resorption markers were found to remain unchanged during treatment. A correlation was found between increased bone mineral content and lean body mass (p = 0.0009). Susceptibility to adverse events was not found to be dependent on gender or on the time of onset of the deficiency. Our findings would appear to confirm that a more severe metabolic impairment is correlated with a better therapeutic outcome.(AU)

Medium and long-term outcome of growth hormone therapy in growth hormone deficient adults

We evaluated long-term replacement therapy outcomes in various subsets of patients with adult growth hormone (GH) deficiency (AGHD) as well as the patients susceptibility to adverse events. Fifty-nine patients with AGHD were evaluated, 27 with childhood onset (CO) (18-44 years old, 12 females) and 32 with adult onset (AO) (27-70 years, 18 females). A significant improvement in HDL-cholesterol was observed in AGHD-AO males (basal: 41.3 +/- 12.9 mg/dl, intratreatment: 47.5 +/- 13.2 mg/dl, p = 0.009). However, individual analyses showed that total cholesterol decreased below 240 mg/dl in 33% of AGHD-CO patients and in 50% of AGHD-AO patients, and below 200 mg/dl in 67% of AGHD-CO patients and in 29% of AGHD-AO patients; in the AGHD-AO group, normalization of LDL-cholesterol (< or = 160 mg/dl) and triglycerides (< or = 200 mg/dl) was found in 100% and 50% of patients, respectively; the total cholesterol/HDL ratio decreased below 4.5 in 20% of AGHD-CO patients and in 25% of AGHD-AO patients. The cardiological evaluation showed a significant intra- and interindividual heterogeneity, but cardiac mass improved in patients with a baseline cardiac mass index below 60 g/m2. Markers of bone apposition increased significantly, while bone resorption markers were found to remain unchanged during treatment. A correlation was found between increased bone mineral content and lean body mass (p = 0.0009). Susceptibility to adverse events was not found to be dependent on gender or on the time of onset of the deficiency. Our findings would appear to confirm that a more severe metabolic impairment is correlated with a better therapeutic outcome.(AU)

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.

Macroprolactinemia in childhood and adolescence: a cause of asymptomatic hyperprolactinemia.

Asymptomatic hyperprolactinemias associated with altered proportions of molecular forms of circulating prolactin (PRL) have been reported in adults. The scarce references available in children and adolescents prompted us to report our experience in the evaluation and follow-up of patients with macroprolactinemia. We studied 5 patients (1 male and 4 females) aged 11.6-18 years with incidentally discovered asymptomatic hyperprolactinemia. Patients underwent repeated evaluations for a period of 3 months to 8 years, and their PRL levels remained elevated (34.4-516 ng/ml). Structural variants of PRL >/=45 kD ranged between 58.9 and 78.6%. Chromatographic profiles showed increases in Big Big PRL in the 5 cases, ranging between 40 and 72% (normal: 9-21%), and in Big PRL in 3 cases, ranging between 30.0 and 32.6% (normal: 5-25%). Little PRL was decreased in all cases, ranging between 20.6 and 41.1% (normal: 50-90%). In conclusion, upon detection of hyperprolactinemia with no clinical manifestations and no alteration of the remaining endocrine functions, macroprolactinemia should be considered as a possible diagnosis. The confirmed absence of functional alterations during the follow-up would favor a no-treatment approach and at the same time avoid repeating imaging studies.

Peripubertal prolactinomas: clinical presentation and long-term outcome with different therapeutic approaches.

UNLABELLED: The evolution of prolactinomas in children and adolescents continues to be controversial. We report on the long-term evolution (2-20 yr) of prolactinomas in 40 patients (29 F, 11 M). In females, the age for the onset of symptoms ranged between 8 and 16 yr and the age at which diagnosis was made ranged from 15 to 19 yr; in males, ages ranged from 8 to 17 yr and from 13.8 to 19 yr, respectively. In females, there was predominance of microprolactinomas (22/ 29) and the symptomatology resulted from functional disorders, whereas in males there was predominance of macroprolactinomas (8/11) and symptoms were caused by tumor mass disorders. Surgery was used as primary therapy in nine patients and as supplemental therapy in six patients. Twenty-four patients were treated primarily with bromocriptine and seven with cabergoline. Of the nine patients treated primarily with surgery, only one achieved gonadotropic axis restoration; in 25/31 patients receiving drug therapy gonadotropic function was restored to normal. Fifteen patients showed complete resolution or substantial shrinkage of tumor. CONCLUSION: In pediatric and adolescent age, there seem to be age- and sex-dependent differences in the clinical presentation of prolactinomas that cannot be accounted for only in terms of time of evolution. Drug therapy can control the disease, normalize prolactin levels and achieve gonadotropic axis restoration in most patients.

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.

[Treatment of hyperprolactinemic amenorrhea with cabergoline]. / Tratamiento de amenorreas hiperprolactinémicas con cabergolina.

Cabergoline (CAB) is a long-acting dopamine agonist. In the first national study with CAB--as part of an international multicentric study--39 adult and adolescent females (16 to 44 years old) with hyperprolactinemic amenorrhea (18 microadenomas and 21 idiopathic hyperprolactinemias) were evaluated. CAB or bromocriptine (BEC) was administered for 24 weeks: over 8 weeks, treatment was given under double-blind conditions, and over the remaining 16 weeks (open period) 18 patients received CAB and 21 received BEC as a result of a random distribution. Maximum dosage: CAB = 1.5 mg in 2 or 3 weekly doses; BEC = up to 10 mg in 2 daily doses. Prolactin was measured at base line and 2, 4, 6, 8, 12, 14, 16, 20 and 24 weeks after the initiation of treatment. When vaginal bleeding was restored, progesterone was measured as an ovulation sign. The 4 adolescents continued with CAB treatment for 1 more year. Prolactin was statistically evaluated according to Man Whitney Test (general population) or Wilcoxon Test (adolescents). There were no significant differences between basal levels of prolactin (ng/ml) in patients treated with BEC or CAB: (173.86 +/- 28.23 and 152.11 +/- 14.06 respectively); at the fourth week of treatment the decrease was smaller (p = 0.005) in patients treated with BEC (36.36 +/- 5.71) than in those treated with CAB (14.06 +/- 3.60) and at 24 weeks differences disappeared: BEC = 19.88 +/- 4.48 and CAB = 9.63 +/- 2.62 (p = NS). The adolescents showed a marked decrease in prolactin with no significant differences between BEC and CAB: basal levels = 168.17 +/- 75.47 and 213 +/- 96.99 (p = NS); 4 weeks = 48.00 +/- 8.72 and 35.00 +/- 12.58 (p = NS); 24 weeks = 34.33 +/- 10.17 and 21.75 +/- 7.23 respectively. At 48 weeks (23.25 +/- 11.23) levels remained the same as those of week 24 (p = NS). Some patients treated with BEC had nausea, vomits and epigastralgia; these symptoms were not observed with CAB. All patients resumed menstrual cycles, except one treated with BEC; 6 patients treated with CAB became pregnant, and the 5 patients who continued under our control gave birth to healthy infants. It is concluded that CAB is a useful therapy. This is specially true for adolescents (an age group difficult to manage) because of its easy administration and the almost complete absence of side effects.

Varicocele in prepubertal boys. Evaluation of clinical Doppler and hormonal findings.

Hormonal, clinical and scrotal Doppler findings were assessed in 16 prepubertal patients having unilateral varicocele. As already described in pubertal patients, Doppler studies made it possible to detect patterns of prolonged, intermittent or permanent reflux. An LH-RH test and an hCG test measuring LH, FSH and testosterone (T) were performed in all cases. Patients with varicocele showed (median and range): LH B (mlU/ml): 0.40 (0.40-2.1); LH Mx.: 3.7 (1.1-15); FSH B (mlU/ml): 1.95 (0.40-4.5); FSH Mx.: 4.9 (3.1-10); T B (ng/ml): 0.2 (0.1-1.5); T Post.: 2.25 (0.82-11.5). The control group showed: LH B (mlU/ml): 0.40 (0.4-0.85); LH Mx.: 2.15 (0.63-12) FSH B (mlU/ml): 1.45 (0.4-3); FSH Mx.: 4.25 (2.6-5.9); T B (ng/ml): 0.1 (0.1-0.3); T Post.: 3.26 (1.0-5.6). No significant differences were found between the hormonal results of the different groups classified according to the scrotal findings. Basal LH and FSH in grade 3 varicoceles were found to be significantly higher (p < 0.05) than those of the control group. Basal T, as well as the maximal response of both gonadotropins to LH-RH, and T response to hCG showed no significant differences with reference to the control group. Our findings provide indirect support to the notion that the gonadal damage would become detectable from puberty onwards.

Growth hormone neurosecretory disfunction in major depressive illness.

Neurotransmitter impairments in MDI can also affect hormonal neuroregulation. Therefore, we decided to study the integrated concentration of growth hormone (IC-GH) and its 24-h secretory profile in this pathology. Ten women with major depressive illness (MDI) (three premenopausal and seven postmenopausal) and four normal matched controls (one premenopausal and three postmenopausal) were evaluated. Samples were obtained every 30 min using a constant withdrawal pump. Growth hormone (GH) pulses were analysed by Cluster System. Twenty-four hour IC-GH was evaluated as area under the curve (AUC) and the following results were found: depressed (D) = 429.15 +/- 367.9 vs. controls (C) = 1281.07 +/- 379.77 (p < .008); nocturnal IC-GH: D = 220 +/- 274.0 vs. C = 739.52 +/- 378.15 (p < .02). No statistically significant differences were found between D and C in diurnal IC-GH or in the number of nocturnal or diurnal pulses. Adrenal (cortisol at 0800h, 2300h and post-suppression with 1 mg of dexamethasone) and thyroid (T3, T4, 0800h and 1700h TSH) evaluations did not show statistically significant differences between D and C women. In conclusion, patients with MDI present a decrease in total GH secretion at the expense of the nocturnal period, probably due to changes in the neurotransmitters that would be involved in depression.

[Variability of growth hormone response to repeated stimulation tests in children of normal height]. / Variabilidad de respuesta de hormona de crecimiento a pruebas de estímulo reiteradas en niños de talla normal.

The presence of false negatives in the evaluation of patients with short stature and the variability of 24 hour growth hormone (GH) physiological studies in the normal population are well known. Therefore the reproducibility of two widely used pharmacological test was studied in normal children. Forty prepuberal children were evaluated (34 boys and 6 girls), with chronological ages ranging from 2 years 11 months to 12 years 11 months (mean: 9 years 1 month), bone ages from 3 years 2 months to 12 years 6 months (mean: 8 years 4 months) and with normal stature and growth velocity (SDS > -2) and normal body mass index (BMI < 25). Clonidine test was performed (100 micrograms/m2 surface) measuring GH (ng/ml) 0,06 and 90 min in 20 patients (Group I). Exercise-Propranolol test was performed (0,5 mg/kg weight) with basal and post-exercise GH measurements in 20 patients (Groups II). The tests were repeated at one week intervals and each child was his own control. Group I showed (mean +/- SD): 1st test: B = 1.78 +/- 1.59, Max Resp = 13.16 +/- 8.34; 2nd test: B = 1.17 +/- 0.51, Max Resp = 15.12 +/- 8.09. Group II showed (mean +/- SD): 1st test: B = 1.38 +/- 0.58, Max Resp 16.97 +/- 9.69; 2nd test: B = 1.54 +/- 1.16, Max Resp = 13.49 +/- 7.81. Wilcoxon's test did not show significant differences when comparing B vs B and Max Resp vs Max Resp in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunoradiometric assay of thyrotropin during the first six months of life.

The aim of this preliminary study was to assess variation in thyrotropin (thyroid-stimulating hormone; TSH) levels using an immunoradiometric assay during the first 6 months of life of normal infants. One hundred and five normal newborns (59 females, 46 males) were evaluated for TSH, triiodothyronine and thyroxine at 48 h of life, and TSH was additionally determined at 15 days (n = 42), 30 days (n = 38), 60 days (n = 24), 90 days (n = 28), and 180 days (n = 30). Complete determinations during the total period of the study were obtained in 17 infants. Samples corresponding to the 48-hour period did not exhibit a normal distribution. In this group, percentile 3 corresponded to 0.9 mU/l, the median to 4.2 mU/l and percentile 97 to 17.7 mU/l. Levels of TSH similar to those of the normal adult population were reached between 30 and 60 days of life. Nevertheless, TSH levels of some of the children remained at higher values for a longer period. In summary, our results suggest that high TSH levels might not always indicate an underlying pathology. A critical evaluation of the normality criteria could avoid unnecessary studies and treatments.

Variabilidad de respuesta de hormona de crecimiento a pruebas de estímulo reiteradas en niños de talla normal. / [Variability of growth hormone response to repeated stimulation tests in children of normal height]

The presence of false negatives in the evaluation of patients with short stature and the variability of 24 hour growth hormone (GH) physiological studies in the normal population are well known. Therefore the reproducibility of two widely used pharmacological test was studied in normal children. Forty prepuberal children were evaluated (34 boys and 6 girls), with chronological ages ranging from 2 years 11 months to 12 years 11 months (mean: 9 years 1 month), bone ages from 3 years 2 months to 12 years 6 months (mean: 8 years 4 months) and with normal stature and growth velocity (SDS > -2) and normal body mass index (BMI < 25). Clonidine test was performed (100 micrograms/m2 surface) measuring GH (ng/ml) 0,06 and 90 min in 20 patients (Group I). Exercise-Propranolol test was performed (0,5 mg/kg weight) with basal and post-exercise GH measurements in 20 patients (Groups II). The tests were repeated at one week intervals and each child was his own control. Group I showed (mean +/- SD): 1st test: B = 1.78 +/- 1.59, Max Resp = 13.16 +/- 8.34; 2nd test: B = 1.17 +/- 0.51, Max Resp = 15.12 +/- 8.09. Group II showed (mean +/- SD): 1st test: B = 1.38 +/- 0.58, Max Resp 16.97 +/- 9.69; 2nd test: B = 1.54 +/- 1.16, Max Resp = 13.49 +/- 7.81. Wilcoxons test did not show significant differences when comparing B vs B and Max Resp vs Max Resp in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Variabilidad de respuesta de hormona de crescimento a pruebas de estimulo reiteradas en niños de talla normal / Variability of growth hormone response to repeated stimulation tests in children of normal stature

Es conocida la existencia de falsos negativos en la evaluacion de pacientes con déficit de talla, así como la variabilidad de los estudios fisiológicos de la hormona de crecimiento (GH) en 24 hs en la población normal. Por tal motivo, decidimos investigar, en niños normales, la reproductibilidad de dos pruebas farmacológicas de uso habitual, aplicadas al mismo individuo. Se evaluaron 40 niños prepuberales (34 niños, 6 niñas), con edades cronológicas comprendidas entre 2 y 12 años (media = 9 años) y edades óseas entre 3 y 12 años (media = 8 años), quienes presentaban talla y velocidad de crecimiento normales y normopeso. Se efectuó prueba de clonidina (100 Ag/m² superficie corporal) dosando (GH (ng/ml) 0, 60 y 90 min. em 20 pacientes (Grupo I). Se realizó prueba de ejercicio más propranolol (0,5 mg/Kg peso) con dosajes de GH basal y post-ejercicio en 20 pacientes (Grupo II). Las pruebas se repitieron con una semana de diferencia y cada niño fue testigo de sí mismo. En el Grupo I se observó (media ñ DS): 1er prueba: B = (1,78 ñ 1,59, Resp. Max. = 13,16 ñ 8,34; 2da prueba: B = 1,17 ñ 0,51, Resp. Max. = 15,12 ñ 8,09. En el Grupo II se observó (media ñ DS): 1er prueba: B = 1,38 ñ 0,58, Resp Max. = 16,97 ñ 9,69; 2da. prueba: B = 1,54 ñ 1,16, Resp Max. = 13,49 ñ 7,81. El test de Wilcoxon no mostró diferencias significativas al comparar B vs B y Resp. Max. vs Resp. Max. en ambos grupos. Al analizar las pruebas individuales y considerar respuesta positiva un valor de GH ò ng/ml, se observó un 30 por ciento de respuestas disímiles en el Grupo I y un 18 por ciento en el Grupo II...(AU)

Variabilidad de respuesta de hormona de crescimento a pruebas de estimulo reiteradas en niños de talla normal / Variability of growth hormone response to repeated stimulation tests in children of normal stature

Es conocida la existencia de falsos negativos en la evaluacion de pacientes con déficit de talla, así como la variabilidad de los estudios fisiológicos de la hormona de crecimiento (GH) en 24 hs en la población normal. Por tal motivo, decidimos investigar, en niños normales, la reproductibilidad de dos pruebas farmacológicas de uso habitual, aplicadas al mismo individuo. Se evaluaron 40 niños prepuberales (34 niños, 6 niñas), con edades cronológicas comprendidas entre 2 y 12 años (media = 9 años) y edades óseas entre 3 y 12 años (media = 8 años), quienes presentaban talla y velocidad de crecimiento normales y normopeso. Se efectuó prueba de clonidina (100 µg/m² superficie corporal) dosando (GH (ng/ml) 0, 60 y 90 min. em 20 pacientes (Grupo I). Se realizó prueba de ejercicio más propranolol (0,5 mg/Kg peso) con dosajes de GH basal y post-ejercicio en 20 pacientes (Grupo II). Las pruebas se repitieron con una semana de diferencia y cada niño fue testigo de sí mismo. En el Grupo I se observó (media ñ DS): 1er prueba: B = (1,78 ñ 1,59, Resp. Max. = 13,16 ñ 8,34; 2da prueba: B = 1,17 ñ 0,51, Resp. Max. = 15,12 ñ 8,09. En el Grupo II se observó (media ñ DS): 1er prueba: B = 1,38 ñ 0,58, Resp Max. = 16,97 ñ 9,69; 2da. prueba: B = 1,54 ñ 1,16, Resp Max. = 13,49 ñ 7,81. El test de Wilcoxon no mostró diferencias significativas al comparar B vs B y Resp. Max. vs Resp. Max. en ambos grupos. Al analizar las pruebas individuales y considerar respuesta positiva un valor de GH ò ng/ml, se observó un 30 por ciento de respuestas disímiles en el Grupo I y un 18 por ciento en el Grupo II...