[Hormone changes induced by administration of clomiphene in amenorrheic women].
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Biomedical subjects
Publications and source records attributed to G Faglia.
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Plasma and urinary GH responses following acute physical exercise were evaluated in 19 short-statured children (12 males, 7 females, median age: 11.4 yr, age range: 6.1-14.5 yr, Tanner stage I-III, height < or = 3rd centile for age; 7 with familial short stature, FSS; 8 with constitutional growth delay, CGD; 4 with GH deficiency, GHD) and 7 normally growing, age- and sex-matched control children (4 males, 3 females, median age 11.0 yr, range: 7.2-13.1 yr, Tanner stage I-III). All patients and controls underwent a standardized exercise protocol (consisting of jogging up and down a corridor for 15 min, strongly encouraged to produce the maximum possible effort, corresponding to 70-80% of the maximal heart rate) after an overnight fasting. Samples for plasma GH determinations were drawn at 0 time (baseline), at 20 min (5 min after the end of exercise) and at 35 min (after 20 min of rest); urine samples were collected before (0 time) and at 40, 80 and 120 min after exercise. The distance covered by children with GHD during the test was significantly lower (p<0.05) than in the other groups of patients and controls. No differences in the pattern of plasma GH responses after physical exercise were found between children with FSS, CGD and healthy controls, the maximum percent increase (vs baseline) being evident at 20 min (median, FSS: +1125%; CGD: +1271%; controls: +571%). Children with GHD showed a smaller percent increase (+94%) of plasma GH, significantly lower (p<0.01) than those recorded in the other groups. A significant percent increase (p<0.01) of baseline urinary GH following exercise was found in children with FSS (median: +34%), CGD (+18%) and controls (+44%). Children with FSS and CGD showed a gradual increase of urinary GH, reaching the maximum at 80 min, while healthy controls had a more evident and precocious increase (maximum at 40 min). Urinary median GH levels did not change following physical exercise in children with GHD (-5%, not significant). A significant correlation was found between the maximal percent increase (vs baseline) of plasma and urinary GH following physical exercise (r=0.7, p<0.001). In conclusion, our results show that: 1) plasma and urinary GH responses (as well as the distance covered and the number of steps, i.e. the physical performance) to a standardized exercise protocol are similar in children with FSS, CGD and in normal-statured controls, being unable to differentiate among the "normal variants" of growth; 2) children with GHD, unable to accomplish the same performance of the other three groups, show significantly reduced plasma and urinary GH responses following physical exercise. Although the determination of GH responses to pharmacological stimuli remains the definitive tool for the diagnosis of GHD, these preliminary results seem to suggest a potential role of urinary (and plasma) GH response to a standardized exercise protocol as a safe, acceptable first screening test for GH sufficiency also in children, as previously reported in adults.
Measurements of total body fat (BF) and fat free mass (FFM) obtained by anthropometry, using the Durnin and Womersley (DW) equations, and by total body dual energy x-ray absorptiometry (DXA) were compared in 8 adults with childhood-onset GH deficiency (GHD) and in 9 healthy subjects. The sensitivity of these two methods in detecting the changes in body composition produced by six months of GH therapy in patients with GHD was also compared. Anthropometric determination of percent BF was calculated from the sum of biceps, triceps, subscapular and suprailiac skinfolds, using the appropriate DW and Siri equations for body density and percent fat estimation. FFM was calculated by subtracting BF from body mass (BM). BF and FFM were also determined by DXA (QDR 1000/W, Hologic Inc). The data obtained from the GHD patients were compared with those recorded in a control group of healthy males, matched for sex, age and physical activity. Body composition obtained by anthropometry: before GH treatment, significant differences existed between patients and controls in terms of BM (mean +/- SD: 45.8 +/- 10.0 vs 71.7 +/- 6.6 kg), percent BF (21.0 +/- 3.2 vs 17.1 +/- 3.7%) and FFM (36.0 +/- 6.5 vs 59.3 +/- 3.7 kg), while body mass index (BMI, kg/m2) values were similar in the two groups. Six months of GH therapy did not change BM and BMI, but caused a significant reduction of percent BF (from 21.0 +/- 3.2 to 18.6 +/- 4.0%) and a rise of FFM (from 36.0 +/- 6.5 to 38.0 +/- 6.7 kg). After treatment, no significant differences were found between percent BF values of patients and controls. Body composition obtained by DXA: BF (22.0 +/- 3.9%) and FFM (37.2 +/- 8.0 kg) of patients significantly differed from those of controls (16.8 +/- 3.7% and 59.8 +/- 3.7 kg) before treatment; after GH treatment, percent BF values (17.7 +/- 4.9%) of patients were similar to those of controls. Anthropometry vs DXA: high correlation (p < 0.001-0.0001, R2 = 0.784-0.988) was found between the percent BF and FFM determined by anthropometry and by DXA for both patients, before and after treatment, and controls. It is noteworthy that, for both BF and FFM, most values were evenly distributed along the identity line, showing no systematic overestimation or underestimation by anthropometry. The relation between DXA and anthropometry was maintained even after GH treatment. These results indicate that body fat and FFM assessment by anthropometry are comparable to those by DXA. GH-induced changes in body composition in hypopituitary adults are detected with the same level of accuracy by the two techniques. The reliability, practicality and low cost of anthropometry favour its use for the assessment of body composition even in GHD patients.
It is well established that children with extreme short stature, secondary to GH deficiency (GHD) or achondroplasia, face a disability that may affect their adult psychosocial outcome, while contrasting data are reported for short normal children. In our hands, adults with GHD have shown an unsatisfactory psychosocial adjustment due to the low adult height and hypothetically to the persistent GHD. This study has been carried out to evaluate the influence of growth in height on the social outcome in 45 adults with constitutional growth delay (CGD). Interviews with subjects and parents were used for assessment. Data obtained were compared with those found in an age, sex and social matched control group of adults with normal height. Some issues were also compared with the data we previously found in adults with GHD. Present mean age of the patients is 24 +/- 2 yr. A high percentage (32.8%) of unemployment or underemployment (part-time work) was found. Four patients (8.8%) were married, while 84.4% lived with their parents or relatives, confirming the notion of prolonged economic dependency on the family. The patients preferred single sporting activities, avoiding team work. Surprisingly, scholastic achievement was in general similar to that observed in controls. Similar findings have been previously observed in patients with GHD. Since no defect in GH secretion has been documented in CGD, the presence of a negative psychosocial outcome more probably seems to be due to the final unsatisfactory height rather than to a GH defect.(ABSTRACT TRUNCATED AT 250 WORDS)
Circulating TSH bioactivity may vary in several clinical and experimental conditions. Since the reliability of the current methods for the measurement of TSH bioactivity is limited, a new bioassay based on cAMP accumulation in Chinese Hamster Ovary cells transfected with recombinant human TSH receptor (CHO-R) was set up. The sensitivity was 0.3 +/- 0.1, 0.4 +/- 0.1 and 0.01 +/- 0.01 micrograms/L for TSH IRP 80/558, recombinant human TSH and bovine TSH, respectively. Standard curves were parallel, and the intra- and inter-assay coefficients of variation were 13 +/- 1.1% and 22 +/- 1.9%, respectively. LH, FSH, CG and TSH subunits did not stimulate cAMP accumulation up to high concentrations. Circulating TSH was partially purified by immunoaffinity separation and concentrated before being bioassayed. However, plain sera with high TSH levels, such as those from primary hypothyroid patients (PH), could be directly tested in CHO-R bioassay, provided that sera were added at concentrations lower than 10%. TSH from 6 normal subjects had biological to immunological ratio (B/I) ranging from 0.6 to 2.1 (mean +/- SD = 1.4 +/- 0.5). TSH from 6 patients with PH showed bioactivity significantly lower than in normals (B/I = 0.6 +/- 0.3; p < 0.001; range = 0.3-1.1). TSH from 5 patients with central hypothyroidism of hypothalamic origin (CH) had undetectable basal bioactivity (B/I < 0.2), which normalized in only one patient after acute TRH and in all patients after chronic TRH administration. In conclusion, CHO-R cells provide an excellent tool for evaluating TSH bioactivity, owing to high sensitivity, specificity, reproducibility and feasibility of the assay.(ABSTRACT TRUNCATED AT 250 WORDS)
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We studied the hypothalamic-pituitary-gonadal system in 33 men with PRL-secreting tumors to determine at which level(s) high PRL levels interfere with testicular function. In basal conditions serum PRL levels ranged between 24-4500 ng/ml, serum LH and FSH concentrations were lower than normal in 61% and 39% of patients; low testosterone (T) levels and sexual impotence appeared more common (85% and 88%) than that we expected on the basis of gonadotropin deficiency. Mean T increase after hCG in 14 patients with prolactinomas was significantly less than in normals (3.3 +/- 0.7) ng/Ml vs 7.3 +/- 0.5 ng/ml; p less than 0.025); a significantly higher T response to hCG was obtained in 5 cases retested after PRL levels had been reduced by therapy. GnRH test induced a normal LH rise in 45% of patients, Mean serum LH increase after clomiphene administration did not differ from that in normals, though 4 out of 10 patients showed an impared response. Metoclopramide injection did not cause a rise of LH in 11 patients so tested. These data, while not excluding a central influence of PRL on LHRH, suggest that in men the antigonadotropic effects of PRL are mainly exerted at the gonadal levels.
Gonadotropin secretion was investigated in 10 healthy volunteers (5 men and 5 women in the early follicular phase of cycle) by the following procedures: i) infusion of saline over 4 1/2 h period; ii) infusion of dopamine (DA) 4 microgram/kg bw/min over 4 h period; iii) oral administration of L-dopa (D) 100 mg plus carbidopa (C) 35 mg after 24 h pretreatment with C 50 mg every 6 h. This last pharmacological approach selectively enhances the central dopaminergic tonus. Blood samples were withdrawn every 15 min over 4 1/2 h period. No ultradian periodicity in LH and FSH secretion was observed. No significant modification in serum FSH levels was induced by any treatment at any time, while a significant decrease in serum LH concentration was observed from 45 to 240 min during DA infusion (-46.8%; p less than 0.005) and from 60 to 240 min after D + C administration -41.5%; p less than 0.05). These data demonstrate that, in humans, acute dopaminergic stimuli have an inhibitory action on LH release and suggest that this inhibition is exerted at the central level.
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Serum osteocalcin and alkaline phosphatase levels, as indexes of bone formation, and urinary calcium and hydroxyproline excretions relative to creatinine, as indexes of bone resorption, were measured in 10 obese women before and after two months of hypocaloric diet. In basal condition, serum osteocalcin, but not alkaline phosphatase levels, were higher in obese than in controls (7 +/- 0.4 vs 5.3 +/- 0.2 ng/ml). Urinary calcium/creatinine and hydroxyproline/creatinine ratios were also significantly higher than those in normals (0.37 +/- 0.05 vs 0.2 +/- 0.01 and 0.035 +/- 0.004 vs 0.02 +/- 0.002, respectively). After weight loss, serum osteocalcin significantly increased (9.5 +/- 0.5 ng/ml), while urinary calcium/creatinine and hydroxyproline/creatinine ratios fell to the normal values (0.23 +/- 0.03 and 0.026 +/- 0.001). In conclusion, it appears that obesity, at least in young women, is associated with a high bone turnover, which seems to be reversible with weight loss.
Octreotide, an analog of somatostatin, is a valid tool for the cure of acromegalic disease. This compound has a prolonged half-life and is more selective than native somatostatin in suppressing growth hormone (GH) secretion. Octreotide, 100 micrograms tid sc, decreases GH levels and improves clinical symptoms in about 85% of acromegalic patients, lowering GH to below 5 ng/ml in 45% and to below 2 ng/ml in 17-21%. Octreotide normalizes somatomedin-C (IGF-I) levels in 36-50% of patients. The increase of dosage up to 1500 micrograms/day does not appear useful in poor responsive patients. No adverse effects on other endocrine functions submitted to hypothalamus-pituitary control have been observed. A slight shrinkage of the pituitary tumor is observed in 30-50% of cases. Octreotide therapy is well tolerated and side effects are usually mild. However the possibility of colelithiasis, liver damage and diabetes mellitus in patients with glucose intolerance must be taken into account. In conclusion octreotide is a useful complement to therapeutic means now used for the treatment of acromegaly.
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