bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular heterogeneity of serum follicle‐stimulating hormone in hypogonadal patients before and during androgen replacement therapy and in normal men
Authors: Harsch Igor A. , Simoni Manuela , Nieschlag Eberhard 
Published: March 2008

SummaryOBJECTIVE The present study was performed to characterize the molecular heterogeneity of serum FSH in normal males and to investigate the possible influence of testosterone on serum FSH in androgen‐deficient men before and during testosterone administration.DESIGN AND PATIENTS Serum samples were taken at 10‐minute intervals between 0730 and 0830 h from nine healthy, eugonadal men and from eight men with primary hypogonadism (Klinefelter's syndrome). In the hypogonadal patients, sampling was performed before treatment (n= 8), 4‐5 days after the first and the third injection of 250 mg testosterone enanthate given intramuscularly at three‐weekly intervals (n= 6), as well as 3 months after the onset of therapy (n= 3). Sampling was repeated 7 days apart in two of the nine healthy volunteers.MEASUREMENTS Aliquots from the individual serum samples were pooled and fractionated by chromatofocusing in the pH range 6‐3. Immunoreactive FSH was measured by immunofluorimetric assay (IFMA) in each fraction and the individual serum samples. In each serum pool, bioactive FSH was determined by in‐vitro bioassay (rat Sertoli cell aromatase bioassay), testosterone by RIA and LH by IFMA.RESULTS After grouping the percentage of immunoreactive FSH recovered in the individual fractions into intervals of 0 5 pH units, significant differences between controls and patients were observed in the pH regions 4‐4.5, 5.5‐6 and 6‐6.5. No statistically significant changes in the isoform distribution of FSH were detected during therapy in the Klinefelter patients. A high degree of variability, which did not follow a common pattern, was observed in the isoform distribution of FSH within the same individuals, both in the hypogonadal patients during treatment and in the two normal men whose blood samples were taken on two different occasions.CONCLUSIONS Serum FSH is highly heterogeneous in normal and hypogonadal men. There is a spontaneous intra‐individual variability in the relative abundance of the different FSH isoforms in serum that may most probably be related to metabolic deglycosylation of FSH. Minor but significant differences in the molecular heterogeneity of serum FSH could be demonstrated in Klinefelter patients compared to normal men. These differences are not modified by administration of testosterone enanthate at doses achieving normal androgenization, suggesting that factors different from testosterone may modulate FSH pleomorphism.
Evening administration of melatonin enhances the pulsatile secretion of prolactin but not of LH and TSH in normally cycling women
Authors: Terzolo Massimo , Revelli Alberto , Guidetti Daniela , Piovesan Alessandro , Cassoni Paola , Paccotti Piero , Angeli Alberto , Massobrio Marco 
Published: March 2008

SummaryOBJECTIVE The aim of the study was to evaluate the effects of exogenous melatonin on the spontaneous pulsatile release of PRL, TSH and LH in normal women.DESIGN A double blind placebo‐controlled protocol was designed to study seven subjects in the mid follicular phase of two non‐consecutive cycles. Two mg of exogenous melatonin or placebo were given at 1600 and 2000 h, and blood samples were collected every 10 minutes from 1800 to 2400 h for hormone determination.RESULTS Melatonin treatment caused a significant upward resetting of the pulsatile pattern of PRL in six out of seven subjects. Average maximal peak height was significantly increased (median 716 mlU/l (range 198‐1433) on melatonin vs 324 mlU/l (212‐688) on placebo, P<0.001), nadir value (572 mlU/l (148‐1084) vs 216 mlU/l (54‐580), P < 0 001) and area under the peak (26352 mlU/l min (5904‐93672) vs 12096 mlU/l min (2340‐33552), P<0 001), whereas peak number, amplitude and interpeak interval did not change significantly. TSH pulsatility was unaffected by melatonin administration in four out of six subjects. Distribution of LH patterns after melatonin was inhomoge‐neous: level of pulsatility was higher in two cases and reduced in three; group analysis did not therefore show significant variation of pulsatility parameters.CONCLUSIONS Exogenous melatonin has a stimulatory effect on PRL release without affecting the temporal pattern of its pulsatile secretion in normal women. Melatonin has minor, if any, effect on TSH secretion whereas the effect on LH may depend on individual sensitivity.
Enhanced prolactin responsiveness to galanin in patients with Cushing's disease
Authors: Invitti C. , Giraldi F. Pecori , Tagliaferri A. , Scacchi M. , Dubini A. , Cavagnini F. 
Published: March 2008

SummaryOBJECTIVE Galanin is believed to play a role in the control of prolactin (PRL) secretion in the rat. Such a role is uncertain in humans where the neuropeptide is expressed by the corticotrophs. However, in clinical conditions of enhanced ACTH secretion, increased PRL levels are often observed. Therefore, we evaluated the effect of galanin infusion on serum PRL levels in patients with Cushing's disease and in control subjects. For comparison, the PRL responses to TRH and metoclopramide were also investigated in the same patients.DESIGN Four tests were performed: (a) 40‐minute infusion of 0–3 μg/kg/min of galanin; (b) infusion of normal saline only; (c) metoclopramide test (10 mg as i.v. bolus); (d) TRH test (200 mg as i.v. bolus).PATIENTS Twenty‐four normal subjects and nine patients suffering from active Cushing's disease were investigated.MEASUREMENTS Serum concentrations of PRL were measured by radioimmunoassay on blood samples collected before and for 90 minutes after drug or saline administration.RESULTS Serum baseline PRL levels were superimposable in normal subjects and in patients with Cushing's disease. In normal subjects, infusion of galanin induced a distinct PRL increase compared to saline (mean ±SEM incremental areas 6514 ±2572 vs 540 ±571 μ/l/90 min, P= 005, respectively).In patients with Cushing's disease, galanin evoked a remarkable PRL rise with hormone levels which were significantly greater (P < 0.001) than those observed in the same patients after infusion of saline (21908 ± 4180 vs 534 ± 1556 mU/l/90 min) or after galanin administration in controls (P<0.01). The PRL response to TRH and, much more so, to metoclopramide was significantly lower in patients with Cushing's disease than in normal subjects (42125± 8000 vs 73181 ± 7246 mU/l/90 min, P<0.01 after TRH and 79095 ± 27265 vs 229049 ± 10602 mU/l/90 min, P < 001 after metoclopramide).CONCLUSIONS Galanin appears to be a specific, though weak, PRL secretagogue in normal subjects. The galanin‐induced PRL release was significantly increased in patients with Cushing's disease. A number of hypothetical mechanisms may underlie the enhanced PRL reactivity to galanin in Cushing's disease. This finding together with the impaired PRL responsiveness to TRH and metoclopramide, also observed in this study, is a further example of a dysregulation of PRL secretion in patients with Cushing's disease.
Protein intake during aggressive calorie restriction in obesity determines growth hormone response to growth hormone‐releasing hormone after weight loss
Authors: Megia Ana , Herranz Lucrecia , Luna Reyes , Gómez‐Candela Carmen , Pallardo Felipe , Gonzalez‐Gancedo Pilar 
Published: March 2008

SummaryOBJECTIVE We evaluated the influence of two types of calorie restriction, total fast or very low calorie diet, on GH responsiveness to GHRH in severely obese patients.DESIGN Twenty patients with massive obesity underwent one of two types of calorie restriction, total fast (10 patients) or very low calorie diet (10 patients).MEASUREMENTS Fasting GH, IGF‐I, glucose, insulin and GH secretion after GHRH (100 ug i.v.) were assessed in all patients before and after diet therapy.RESULTS Both types of diet produced similar weight reduction (total fast, 5.6 ± 1.6 kg/m2vs very low calorie diet, 5.6 ± 1.5 kg/m2 mean ± SD). A significant increase in the integrated GH secretion was observed after weight‐loss with very low calorie diet (17 ± 9 vs27 ± 12mU/l min; P < 0.05). However, no change was found in GH response after weight loss with total fast (13 ± 5 vs 15 ± 7 μ/l min). Glucose, insulin and IGF‐I levels showed a significant decrease with weight reduction which was similar for both groups.CONCLUSION These findings suggest that the type of dietary manipulation during calorie restriction in obese patients may influence the changes in GH response to GHRH after weight loss.
Relationships between insulin‐like growth factor‐1 levels and growth hormone concentrations during diurnal profiles and following oral glucose in acromegaly
Authors: Dobrashian R. D. , O'Halloran D. J. , Hunt A. , Beardwell C. G. , Shalet S. M. 
Published: March 2008

SummaryOBJECTIVE The aim of this study was to refine the biochemical definition of disease activity in acromegaly by comparing serum growth hormone (GH) measurements during a 10‐hour day profile with serum GH values during an oral glucose tolerance test.DESIGN Using plasma insulin‐like growth factor‐1 (IGF‐1) levels as a measure of disease activity, serum GH data from a day profile and from an oral glucose tolerance test were compared.PATIENTS Thirty‐five acromegalic patients were studied, 13 of whom had serum GH measured during a day profile and 22 during an oral glucose tolerance test. In addition, basal plasma IGF‐1 levels were estimated in all acromegalic patients, and in 24 normal subjects.MEASUREMENTS Following acid‐ethanol extraction of the plasma samples, IGF‐1 levels were measured by radioimmunoassay using a polyclonal antibody. In a day profile, six to eight blood samples for serum GH estimation were taken at hourly intervals during the day; during an oral glucose tolerance test samples for serum GH estimation were taken in the fasting state and every 30 minutes for 2 hours and measured by a two‐site IRMA for GH. RESULTS Ninety‐four per cent of acromegalic patients with raised plasma IGF‐1 levels had serum GH concentrations <10 mU/l whilst 98% of acromegalic patients with plasma IGF‐1 levels in the normal range had serum GH concentrations lt;6 mU/l. A highly significant positive correlation was found between the mean serum GH concentrations (r=0 67), the minimum serum GH concentration (r = 0 65) and the area under the GH curve (r = 0–66) estimated during an oral glucose tolerance test and plasma IGF‐1 concentrations. The relations between identical indices of serum GH concentration measured during a day profile and plasma IGF‐1 levels, although significant, show a less powerful correlation. The relation between serum GH and plasma IGF‐1 levels describes a curvilinear model, plasma IGF‐1 levels exhibiting a plateau at serum GH concentrations >40 mU/l but maintaining a linear relationship with serum GH levels <20 mU/l.CONCLUSIONS A highly significant correlation exists between plasma IGF‐1 levels and various parameters of serum GH levels in acromegalic patients. Hormonal assessment of disease activity in acromegaly is more accurately reflected by the serum GH concentration during an oral glucose tolerance test rather than by the serum GH level during a day profile. Normalization of plasma IGF‐1 levels is rarely achieved unless the mean serum GH level is reduced to <6 mU/l.
High prolactin levels in patients with Cushing's disease without pathological evidence of pituitary adenoma
Authors: Comtois Ronald , Beauregard Hugues , Hardy Jules , Robert Françoise , Somma Maurice 
Published: March 2008

SummaryOBJECTIVE This study was designed to compare the clinical and biochemical features of patients with Cushing's disease without pathological evidence of pituitary adenoma (n= 11) to those in whom a pituitary ACTH adenoma was documented (n= 11).DESIGN The clinical and biochemical features of 11 patients with Cushing's disease without pathological evidence of pituitary adenomas were compared to 11 subjects with ACTH‐secreting adenomas. The patients underwent transsphenoidal microsurgery between 1979 and 1989. During surgery, when an adenoma was not visualized, a partial hypophysectomy of the central mucoid wedge was performed.MEASUREMENTS Cushing's disease was established by the clinical features of hypercortisolism and the high levels of 24‐hour free urinary Cortisol with no suppression in response to low, but with suppression in response to high, doses of dexamethasone. Basal and post TRH‐GnRH plasma prolactin, FSH and LH levels were assessed in each patient before transsphenoidal microsurgery.RESULTS Similar results were observed in patients with and without ACTH‐secreting adenomas regarding cure rate, and free urinary Cortisol levels both basal and after 2 days of dexamethasone, 8 mg daily. After surgery, plasma Cortisol levels in cured patients were lower in subjects with ACTH‐secreting adenomas than in those without pituitary tumours (P &lt 0.05). Areas under the curve of PRL (P<0.002) and LH (P< 0.04) were significantly higher in patients without pituitary adenoma after TRH‐GnRH administration. Compared to controls, the peak prolactin level after TRH‐GnRH administration was higher in patients without pituitary adenoma (P < 0005) and lower in those with ACTH adenoma (P< 0.05). Furthermore, a peak prolactin level equal to or greater than 1410 mU/l during the TRH‐GnRH test was found in 11/11 patients without ACTH adenoma and 3/11 patients in the other group (P < 0 001), while the CT‐scan findings were suggestive of pituitary adenoma in six patients of each group. CONCLUSION This study suggests that patients with Cushing's disease without pituitary adenomas can be distinguished from those with ACTH‐secreting adenomas by their high prolactin levels after TRH‐GnRH administration.
Roles of LH and insulin resistance in lean and obese polycystic ovary syndrome
Authors: Grulet H. , Hecart A.C. , Delemer B. , Gross A. , Sulmont V. , Leutenegger M. , Caron J. 
Published: March 2008

SummaryOBJECTIVE The relationship between insulin resistance and hyperandrogenism led us to study insulin resistance in polycystic ovary syndrome (PCOS) in order to determine its prevalence and pathogenesis. DESIGN Blood samples were taken on the 8th day after menses commenced.PATIENTS Sixty‐one women with PCOS, 30 with normal weight (BMK25 kg/m2) (group 1) and 31 with obesity (BMI<26 kg/m2) (group 2) were studied. They were divided also according to LH level: group A, low or normal LH (n==23) and group B, high LH (n= 38). Twenty lean control women and 16 obese control women were studied.MEASUREMENTS Serum LH, testosterone, free testosterone, dehydroepiandrosterone, sex‐hormone binding globulin, androstenedione, and fasting insulin were measured. Insulin sensitivity was explored by the insulin tolerance test (ITT). ITT was performed by bolus i.v. insulin of 0 1 IU/kg. Blood glucose was measured before (– 5, 0) and after injection (3, 5, 7, 10, 15 minutes). Insulin sensitivity was given by the ratio of glycaemic variation to initial blood glucose (AG/G index).RESULTS ΔG/G was correlated with other insulin resistance parameters, particularly fasting insulin r=–0.40, P<0.01. The PCOS groups had the following insulin resistances (mean ± SEM) compared to matched groups: ΔG/G lean PCOS vs lead controls: 0.45 ± 0.02 vs 0.61 ± 0.01, P< 0.001; ΔG/G obese PCOS vs obese controls: 0.32 ± 0.02 vs 0.40 ± 0.01, P<0.02. Insulin resistance was higher in group A than in group B: ΔG/G 0 29 ± 002 vs 0 45 ± 0 02, P < 0.001. The prevalence of insulin resistance was 63% in lean PCOS and 51% in obese PCOS. Positive correlations between AG/G index and LH were found in group 1 and 2, respectively r= 0.45, P<0.01 and r= 0.55, P<0.01.CONCLUSION PCOS was associated with a significant decrease of insulin sensitivity, independent of obesity. The correlation between LH and insulin sensitivity suggests a complementary action in PCOS.
Effect of long‐term administration of progestogen on post‐menopausal bone loss: result of a two‐year, controlled randomized study
Authors: Trémollières F. , Pouilles J. M. , Ribot C. 
Published: March 2008

SummaryOBJECTIVE We determined whether a progestogen given alone to post‐menopausal women may prevent bone loss.STUDY DESIGN Thirty‐five early post‐menopausal women who had not received any form of treatment to prevent bone loss were randomly assigned to a 2‐year regimen of 500 μ g/day of a gestagen derived from 19‐norprogester‐one (Promegestone) or a placebo for 21 days out of a 28‐day treatment cycle. Bone mineral density of the spine was measured by dual photon absorptiometry.RESULTS After 2 years of treatment bone mineral density decreased significantly in the placebo group by a mean of 4.5%. In the gestagen group, the rate of bone change was significantly lower as compared to the placebo group (‐1.3%± 1.2% vs −4.5%± 2% (mean ± SEM), P & lt; 0.05). There were no changes in the biochemical bone turnover parameters in the placebo group but in the gestagen group a significant decrease was observed in the urinary calcium excretion after 2 years.CONCLUSION The results suggest that a gestagen with no androgenic action can partly counteract early post‐menopausal bone loss.
Effects of 17 months treatment using recombinant insulin‐like growth factor‐I in two children with growth hormone insensitivity (Laron) syndrome
Authors: Heinrichs C. , Vis H. L. , Bergmann P. , Wilton P. , Bourguignon J. P. 
Published: March 2008

SummaryOBJECTIVE With the availability of recombinant insulin‐like growth factor‐I (recIGF‐I), it was possible to study whether this peptide could promote growth without noticeable side‐effects in patients with growth hormone insensitivity syndrome (Laron syndrome). We report data obtained before and during 17 months treatment using recIGF‐I, 40 μg/kg s.c. twice a day, in two Lebanese siblings.PATIENTS The boy and the girl showed very short stature (‐6.8 and −6.1 SDS), high GH (79 and 147 IU/I), low plasma IGF‐I (0.12 and 0.18 U/ml) and undetectable GH‐binding protein. Height velocities were 4.3 and 3.8 cm/year before treatment which started at 8.4 and 6.8 years of age, respectively.RESULTS After 1–8 weeks of therapy, biological evidence of IGF‐I effect was obtained from reduction in serum GH and increase in procollagen‐I. During the first 6 months of treatment, height velocity increased to 7.8 and 8.4 cm/year without any clinical evidence of side‐effects. Between 6 and 12 months, growth response decreased to 6.6 and 6.3 cm/year. Between 12 and 17 months, growth rate returned to pretreatment values. Changes in bone mineral density paralleled growth response and bone maturation increased by 1 5 and 2 0 years during the first 12 months of treatment. Daily assessment of blood sugar showed asymptomatic low values (< 2 8 mM/I) in 11/730 and 22/730 measurements in the boy and the girl, respectively.CONCLUSIONS Treatment of two patients with growth hormone insensitivity syndrome using 40 μ g/kg of IGF‐I twice a day resulted in increased linear bone growth and bone mineralization as well as increased bone maturation without remarkable adverse events. After 1 year of therapy, growth response could no longer be observed in these two patients.
Documentation of parathyroid carcinoma fifteen years after resection of a parathyroid ‘adenoma’
Authors: Ebner Susana , Emerson Charles H. 
Published: March 2008

SummaryThis report describes a 40‐year‐old man in whom the diagnosis of parathyroid carcinoma was made almost 15 years after resection of the primary lesion. The case emphasizes the importance of recognizing pre and intraoperative factors that differentiate between parathyroid adenoma and carcinoma and illustrates that surgical palliation is feasible in selected patients with parathyroid carcinoma.
The importance of thyroid microsomal antibodies in the development of elevated serum TSH in middle‐aged women: associations with serum lipids
Authors: Geul K. W. , van Sluisveld I. L. L. , Grobbee D. E. , Docter R. , de Bruyn A. M. , Hooykaas H. , van der Merwe J. P. , van Hemert A. M. , Krenning E. P. , Hennemann G. , Weber R. F. A. 
Published: March 2008

SummaryOBJECTIVE We assessed the relative risk of both serum TSH and antithyroid antibody concentrations with regard to progression of thyroid failure and studied the lipid profiles of individuals with elevated TSH levels.DESIGN, PATIENTS AND MEASUREMENTS In a randomly selected group of 427 women aged 40–60 (mean 55) years volunteering in an epidemiological survey in Zoetermeer, TSH and thyroid microsomal antibodies (TMA) were determined. Ten years after the initial survey only TSH was measured and the lipid profiles of the individuals with elevated serum TSH levels were studied and compared with a reference group.RESULTS During follow‐up, four of 427 women were treated with thyroxine. Seventeen of 423 women initially had elevated serum concentrations of TSH (> 4 2 mU/l), 11 of whom were TMA positive. In the group of 406 women with initially a normal TSH, nine out of 37 (24%) TMA‐positive women developed elevated serum levels of TSH over 10 years. In contrast only 10 of 369 (3%) TMA‐negative women had elevated serum TSH levels 10 years after the initial survey (P < 0.001). Altogether, at the end of the observation period, 40% of TMA‐positive subjects had elevated serum TSH concentrations, compared to 3% in the TMA‐negative group (P < 0.01). TSH levels in the upper part of the normal range also appeared to have a predictive value: if those both with TSH levels between 2.0 and 4.2 and with a positive TMA status were contrasted with those without antibodies and low TSH, the crude relative risk was 71.5 (31.0–164.3), whereas the crude relative risk of presence versus absence of TMA was only 36.3 (18.8–70.3). Women with elevated TSH levels did not show changes in serum concentrations of total cholesterol (7 4 ± 1.1 mmol/l), apo‐A, (4.7 ± 1.0 mmol/l) and apo‐B (3.1 ± 0.7 mmol/l) lipoproteins, compared with control individuals (7.2 ± 1.3, 4.7 ± 0.8 and 3.0 ± 0.7 mmol/l, respectively).CONCLUSIONS The determination of serum TMA in middle‐aged women can identify an important group of women at risk of developing an elevated serum TSH. TMA measurement is of potential use in the prevention of cardiovascular disease. An elevated serum TSH, however, in our study‐group does not seem to be accompanied by an abnormal lipid profile, as reported by others.