bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of the new dopaminergic agonist CV 205–502 on plasma prolactin levels and tumour size in bromocriptine‐resistant prolactinomas
Authors: Duranteau L. , Chanson P. , Lavoinne A. , Horlait S. , Lubetzki J. , Kuhn J. M. 
Published: March 2008

SUMMARYBromocriptine is currently and successfully used for the treatment of pituitary prolactinomas. However, bromocriptine appears unable to normalize plasma prolactin levels in about 10|X% and to reduce tumour size in one‐third of cases. The lack of normalization of plasma prolactin levels in spite of a daily dose of bromocriptine equal to or higher than 15 mg suggests a bromocriptine resistance. We compared the long‐term effects of bromocriptine and CV 205–502 (a non‐ergot derivative D2 dopamine agonist) on plasma prolactin levels and tumour size in seven bromocriptine‐resistant prolactinomas. Bromocriptine reduced significantly (P > 0.001) plasma prolactln levels (from 2307 |Mp 518 to 568 |Mp 279 μg/I) (conversion to SI units: 1 μg/I = 20 mU/I). Visual field defects observed in five patients Improved in four. However, CT scan analysis showed a decrease in tumour size in only three patients. Except for transient and minor side‐effects at the beginning of the treatment, CV 205–502 was well tolerated In five of seven patients. In the remaining two patients nausea and vertigo occurred with high dosages of CV 205–502 and it was necessary to reduce the daily dose. CV 205–502 lowered plasma prolactin to levels similar to those obtained after bromocriptine therapy in four cases. In the three remaining patients, CV 205–502 was more potent than bromocriptine as demonstrated by the further 90|X% reduction in plasma levels obtained in one case and by the normalization of plasma prolactin levels in the two other cases. One woman became pregnant during CV 205–502 treatment. However, no further change in visual disturbance or in tumour size was observed during the treatment with CV 205–502. These results show that CV 205–502 appears to be more potent than bromocriptine in reducing plasma prolactin levels in some bromocriptine‐resistant prolactinomas and suggest that different mechanisms may be Involved In such a resistance.
TRIAC (3,5,3′‐triiodothyroacetic acid) has parallel effects at the pituitary and peripheral tissue levels in thyroid cancer patients treated with l‐thyroxine
Authors: Mechelany C. , Schlumberger M. , Challeton C. , Comoy E. , Parmentier C. 
Published: March 2008

Summary. objective To investigate whether the addition of 3,5,3′‐ triiodothyroacetic acid (TRIAC) to thyroxine (T4) treatment can suppress TSH secretion without inducing thyrotoxicosis at the periphery.design Thyroid cancer patients were studied with different treatment modalities: T4 at supraphysiologic dose (2.5±0.3 μg/kg/day) and after reduction to a physiologic dose (1.8±0.3 μg/kg/day); then with the addition of TRIAC 500 or 1000 μg/day to the physiologic T4 treatment dose. PATIENTS Twenty‐two patients who had total thyroid ablation for differentiated thyroid carcinoma.measurementsClinical and biological parameters of thyroid hormone action studied included heart rate, serum creatine phosphokinase, testosterone‐oestradiol binding globulin, procollagen III and osteocalcin levels.resultsThe addition of TRIAC induced a significant and dose‐dependent decrease in serum TSH levels and parallel effects on peripheral tissues. Compared to the suppressive T4 treatment dose, the addition of TRIAC to the physiologic T4 dose resulted in greater Inhibition of TSH secretion in only 50% of the patients. The effects at the periphery of both treatment modalities were similar for a comparable level of TSH suppression.conclusionsEven at low dose and when combined with T4, TRIAC has parallel effects on the pituitary and peripheral tissues. There is no justification for the use of TRIAC as suppressive treatment in thyroid cancer patients.
Isolated ACTH deficiency
Authors: Orme S. M. , Belchetz P. E. 
Published: March 2008

Summary. Isolated ACTH deficiency is a rare disorder. We report four cases of this disease which presented to the Department of Endocrinology at Leeds General Infirmary over a one‐year period. The diagnostic clinical and biochemical features of each case are discussed and the pertinent literature is reviewed. The clinical investigations vary somewhat between cases as the four patients presented in markedly different ways. Well validated dynamic endocrine investigations were employed including glucagon stimulation test (GST) and the corticotrophin releasing hormone (CRH) test (using 100 μg of human CRH with samples for ACTH and cortisol). Two patients probably had CRH deficiency and two had ACTH deficiency. All the cases are instructive, illustrating different features of this heterogeneous condition.We conclude that the diagnosis of this condition may be difficult due to the varied clinical presentation. We suggest that it is commoner than previously thought and that the precision of diagnosis can be improved using the CRH test.
The assay of urinary growth hormone in normal and acromegalic adults
Authors: Evans A. J. , Willis D. S. , Wood P. J. 
Published: March 2008

Summary.objectivesTo establish a normal range for urinary growth hormone in adults and to investigate the urinary growth hormone levels in patients with acromegaly, comparing these with the serum growth hormone results of a glucose tolerance test. We also studied the molecular Identity of the growth hormone recognized by our assay method.design Overnight urine samples and, in some cases, timed urine samples taken during the day were obtained from healthy volunteers and acromegalic patients. A standard glucose tolerance test with serum growth hormone measurements was performed on the acromegalic patients.patients One hundred and thirty‐five normal adults and 33 acromegalic patients were studied.measurementsUrinary growth hormone was measured using a sensitive and precise assay developed previously. RESULTS in healthy volunteers overnight urinary growth hormone values fell gradually with increasing age, but there was no significant difference between men and women in any decade or between smokers and non‐smokers. Sexual intercourse had no detectable effect on the values, but there was a large increase following strenuous exercise. Studies of the diurnal patterns in normal and abnormal adults suggested that it might be possible to diagnose acromegaly on a random urine sample. Gel filtration studies on a urine sample from an acromegalic patient showed a single peak of molecular weight 22000. Using overnight collections there was clear discrimination between the values given by the normal adults and the acromegalic patients and an excellent correlation between urinary growth hormone levels in acromegatlc patients and the mean serum growth hormone in a glucose tolerance test.conclusions in contrast to some other groups we conclude that urinary growth hormone provides a useful, non‐invasive screening test for acromegaly, but this conclusion depends crucially on the assay being sensitive and precise at low values.
Growth characteristics and response to growth hormone therapy in patients with hypochondroplasia: genetic linkage of the insulin‐like growth factor I gene at chromosome 12q23 to the disease in a subgroup of these patients
Authors: Mullis P. E. , Patel M. S. , Brlckell P. M. , Hindmarsh P. C. , Brook C. G. D. 
Published: March 2008

SummaryHypochondroplasia, a heterogeneous and usually mild form of chondrodystrophy, is a common cause of short stature. It often goes unrecognized in childhood and is diagnosed in adult life when disproportionate short stature becomes obvious.We performed restriction enzyme analysis of the Insulinlike growth factor I (IGF‐I) gene on the families of 20 white British Caucasian children with short stature attributed to hypochondroplasia by radiological and clinical criteria, who were undergoing human growth hormone (r‐hGH) treatment, in 60 children with Isolated growth hormone deficiency and in SO normal Individuals. The frequency of the heterozygous pattern (Hind III: 8.2, 5.2, 4.8, 3.2 kb fragments, Pvu: 8.4, 5.1, 4.7, 2.5 kb fragments) in children with hypochondroplasia was significantly higher (X2:P<0.05) than in the control groups. The hypochondro‐plastic children whose response to r‐hGH treatment was characterized by a proportionate Increase in both spinal and sublschial leg length were all heterozygous for two co‐inherited IGF‐I gene restriction fragment length polymorphism (RFLP) alleles (Hind III: 5 2,4 8 kb; Pvu II: 5 1,47 kb). Children whose response was characterized by accentuation of the body disproportion by r‐hGH treatment were all homozygous for these alleles (Hind III: 4 8,4 8 kb; Pvu II: 4.7, 4.7 kb). Their response to r‐hGH treatment is significantly different (P<0.01). Studies of the families of the heterozygous affected children demonstrated strong linkage (lod score 3 311 at zero recombination) of the IGF‐I gene locus at chromosome 12q23 to this subgroup of hypochondroplasia. The 5 2 kb Hind III and 51 kb Pvu II alleles are in strong linkage disequilibrium with this trait. These data indicate that IGF‐I gene may be a candidate gene for involvement in the aetiology of short stature presenting with hypochondroplastic features and a proportionate response to r‐hGH treatment; they also provide support for the concept of genetic heterogeneity in chondrodystrophy.
Inter‐relations between growth hormone, insulin, insulin‐like growth factor‐l (IGF‐I), IGF‐binding protein‐1 (IGFBP‐1) and sex hormone‐binding globulin in acromegaly
Authors: Holly J. M. P. , Cotterlll A. M. , Jemmott R. C. , Shears D. , Al‐Othman S. , Chard T. , Wasa J. A. H. 
Published: March 2008

SummaryAcromegaly is characterized by a hypersecretion of GH, which in turn results in an excess of IGF‐I, an important mediator of its actions. IGF‐I itself is intimately related to insulin both in structure and function. IGF‐I circulates associated with specific binding proteins which appear to have Important effects on its activity. We have examined the inter‐relations between GH, prolactin, insulin, IGF‐I and one of the binding proteins, IGFBP‐1, in 62 patients with acromegaly of varying activity. Serum IGF‐I levels were closely related to the logarithm of mean GH levels (r = 0.76; n = 62; P < 0.001) but multiple regression analysis suggested that, after accounting for the variation due to GH, insulin accounted for some of the additional variation of IGF‐I. IGF‐I concentrations were independent of prolactin. Fasting Insulin levels were high and unrelated to mean GH levels but correlated with those of IGF‐I (r = 0.542; n = 57; P<0.001). This correlation coefficient was further improved by also accounting for variations in IGFBP‐1 (r = 0.684; n = 57; P< 0.001). Even In subjects whose acromegaly was well controlled or cured, as indicated by GH levels of <1 mU/l or IGF‐I levels of <2 U/ml, fasting insulin levels remained significantly elevated in some individuals. The reason for this persistent abnormality is not clear. Fasting IGFBP‐1 levels were low and unrelated to mean GH but were Inversely related to fasting insulin levels (r=−0.593; n = 57; P<0.001). We propose that a cascade of events occurs In acromegaly. GH hypersecretion causes chronic elevation of IGF‐I levels which In turn could lead to increased pancreatic insulin production. This raised insulin could then have additional effects, raising IGF‐I levels further and lowering IGFBP‐1; the latter could then result in accentuated IGF‐activity.
Effect of growth hormone on human sleep energy
Authors: Aström Christina , Trojaborg Werner 
Published: March 2008

SUMMARY objective We wished, by means of power spectrum EEC analysis, to examine REM and delta sleep energy in adults with high and normal plasma growth hormone (GH) concentration design After a 3‐day regular sleep/wake schedule, all‐night polysomnographic recordings were performed on two consecutive nights before as well as one year after treatment for acromegaly by adenomectomy. The sleep energy was calculated by power spectrum analysis patients We studied nine patients aged 24–45 years with untreated active acromegaly. The same patients were reexamined one year after adenomectomy when plasma GH concentrations were normal measurements The acromegaly was verified biochemically by measuring basal plasma GH concentration and plasma GH during hyperglycaemia as well as Insulin‐like growth factor. Cerebral computer tomography (CT) and magnetic resonance (MR) scans revealed an intrasellar adenoma in all patients. The resulting sleep records obtained before and after adenomectomy were subjected to power spectrum analysis and a manually blinded sleep scoring results The power spectrum analysis showed that when circulating GH was elevated the energy In the REM sleep per minute was significantly higher compared to the REM energy/mm after surgery when GH concentration had normalized. A similar relation was found for delta sleep (stage 3 + 4, deep sleep) where the energy per minute was higher before treatment than after conclusions The study demonstrates that plasma GH concentration was correlated to sleep energy. During high GH concentration the REM and delta sleep energy were high and normalization of plasma GH was followed by normalization of REM and delta sleep energy per time unlt
Human chorionic gonadotrophin contributes to the bioactivity of Pergonal
Authors: Rodgers M. , Mitchell R. , Lambert A. , Peers N. , Robertson W. R. 
Published: March 2008

SummaryOBJECTIVE We examined batch variation in the LH‐like bioactive content of Pergonal and determined whether hCG contributes to this.DESIGN Random selection of three batches of Pergonal, consisting of three ampoules in each batch.MEASUREMENTS The LH content in each ampoule was determined by radioimmunoassay (R‐LH), immunoradio‐metric assay (l‐LH) andin vitroLeydig cell bioassay (B‐LH) using the urinary hMG International Standard 70/45. Human chorionic gonadotrophin was determined by immunoradiometric assay (I‐hCG) using the hCG IRP 75/537. The isohormone content of each batch was examined by chromatofocussing over the range pH 4.5– 7.0 and the fractions collected were assayed for LH and hCG content. The variability in potency between batches was assessed by single factor analysis of variance.RESULTS THE GONADOTROPHIN CONTENT OF EACH BATCH (IU/AMPOULE, MEAN ± SEM,N=3 AMPOULES) WAS R‐LH (40.9 ± 0.5, 40.8 ± 0.2, 39.3 ± 0 7,P<0.15), I‐LH (39.0 ± 1.5, 28.3 ± 0.8, 36.9 ± 3.3,P< 0.001), B‐LH (27.3 ± 0.3,12.0 ± 0.9, 19.3 ± 0.9,P< 0001) AND I‐HCG (16.4 ± 0.7, 11.7 ± 0.2, 10.5 ± 0.5,P< 0.001). THE CHROMATOFOCUSSING RECOVERIES BELOW PH 5.5 EXPRESSED AS A PERCENTAGE OF THE TOTAL AMOUNT OF ANALYTE ELUTED FROM THE COLUMN AND COLLATED FOR ALL THREE BATCHES OF PERGONAL WERE (MEAN %± SD,N= 3 BATCHES) R‐LH (58.4 ± 4.0), I‐LH (41.3 ± 7.5), B‐LH (81.4 ± 2.8) AND I‐HCG (87.8 ± 3.7).CONCLUSIONS There was significant batch variation in the I‐LH, B‐LH and I‐hCG (P< 0.001) but not the R‐LH (P> 0.15) content of Pergonal. More than 80% of the total B‐LHrecoverychromatofocussed below pH 5.5 and corresponded to the region of highest I‐hCG (>87%) and lowest I‐LH (< 42%) recovery. This was highly suggestive of hCG contributing to the LH‐like bioactivity of Pergonal.
Differential effects of arginine on growth hormone releasing hormone and insulin induced growth hormone secretion
Authors: Koppeschaar H. P. F. , ten Horn C. D. , Thljssen J. H. H. , Page M. D. , Dieguez C. , Scanion M. F. 
Published: March 2008

OBJECTIVE We wished to investigate the interaction of arginine, GHRH and insulin stress on GH secretion.DESIGN Six healthy, non‐obese volunteers underwent seven separate studes in random order. They received (1) insulin alone at 0 minutes; (2) GHRH alone at 15 minutes; (3) arginine alone at 0–30 minutes; (4) arginine at 0–30 minutes and GHRH at 15 minutes; (5) insulin at 0 minutes and arginine at 0–30 minutes; (6) Insulin at 0 minutes, GHRH at 15 minutes and arginine at 0–30 minutes; (7) Insulin at 0 minutes and GHRH at 15 minutes.MEASUREMENTS GH and PRL were measured from —30 to 150 minutes at Intervals of 15 minutes.RESULTS Arginine increased GH responses to GHRH and decreased GH responses to hypoglycaemia, but this inhibitory effect of arginine was reversed by GHRH.CONCLUSIONS The findings suggest that arglnine‐Induced GH release is mainly mediated by a decrease In somatostatinergic tone, while GH responses to insulin stress are probably mediated by both an increase in hypothalamic GHRH release and Inhlbition of somatostatin.
Effect of menopause and hormone replacement therapy on urinary excretion of pyridinium cross‐links: a longitudinal and cross‐sectional study
Authors: Hassager C. , Colwell A. , Assiri A. M. A. , Eastell R. , Russell R. G. G. , Christiansen C. 
Published: March 2008

OBJECTIVE To study longitudinally the effect of the menopause and hormone replacement therapy on the new markers of bone resorption: urinary excretion of pyridinoline and deoxypyridinoline.DESIGN AND PATIENTS Urinary pyridinoline and deoxypyridinoline were measured every 3 months for 2–3 years in 15 healthy women aged 45–54 years. Nine remained premenopausal and six became post‐menopausal during the study. Urinary pyridinoline and deoxypyridinoline were also measured before and after 3 months of either placebo or hormone replacement therapy in 65 postmenopausal women, aged 45–54 years, who were participating in a double‐blind study.MEASUREMENTS Urinary pyridinoline and deoxypyridinoline were measured in fasting urine samples by spectrofluorometry after high performance liquid chromatography and corrected for creatinine excretion.RESULTS Urinary pyridinoline and deoxypyridinoline remained almost constant during the premenopausal period. Both started to increase 6 months after the last menstrual bleeding and the mean post‐menopausal values were 30–50% higher than the premenopausal values in the same subjects (values in nmol/mmol creatinine given as mean ± SEM: urinary pyridinoline (premenopausal) = 29 ± 2 vs urinary pyridinoline (post‐menopausal) = 38 ± 6, P <0.05; urinary deoxypyridinoline (premenopausal) = 8 ± 1 vs urinary deoxypyridinoline (post‐menopausal) = 12 ± 1, P <0.05). Three months of post‐menopausal hormone replacement therapy decreased (P <0.001) both to premenopausal levels.CONCLUSION Urinary pyridinoline and deoxypyridinoline, new markers of bone resorption, remain fairly constant in the years before the menopause and start to increase about 6 months after the last menstrual bleeding. This increase is reversed by hormone replacement therapy.
Interleukin‐6, a growth promoting cytokine, is present in human pituitary adenomas: an immunocytochemical study
Authors: Tsagarakis S. , Kontogeorgos G. , Glannou P. , Thalassinos N. , Woolley J. , Besser G. M. , Grossman A. 
Published: March 2008

OBJECTIVE The aim of this study was to investigate the presence of interleukin‐6 (IL‐6) in human pituitary adenomas.DESIGN Immunocytochemistry was performed in 15 cases of pituitary adenomas obtained at transsphenoldal surgery.PATIENTS Fifteen cases of pituitary adenomas were examined; these included five GH‐secreting adenomas, four prolactinomas, four ACTH‐secreting adenomas and two null‐cell (‘functionless’) adenomas.MEASUREMENTS Each tumour was stained for the presence of IL‐6 by means of the avidin‐blotin‐peroxidase complex (ABC) technique, and was also stained for GH, prolactin, ACTH and α‐subunit by conventional immunocytochemistry.RESULTS Fourteen of the 15 tumours examined, excepting one GH‐secreting tumour, demonstrated clusters of IL‐6 positively stained cells; the specificity of the staining was established by a significant decrease in staining in parallel sections of all tumours studied when the anti IL‐6 antibody was preabsorbed with recombinant human IL‐6. CONCLUSIONS It is concluded that IL‐6 immunoreactivity is present in human pituitary tumours, and is independent of the specific secretory cell product. The role of this cytokine in the pathogenesis of such tumours requires further investigation.
Analysis of trough serum growth hormone concentrations: comparison of an immunoradiometric assay and a sensitive ELISA for growth hormone
Authors: Pringle P. J. , Silvio L. Di , Hindmarsh P. C. , Matthews D. R. , Kurtz A. B. , Brook C. G. D. 
Published: March 2008

OBJECTIVES We compared a sensitive assay for GH (ELISA) with a conventional immunoradiometric (IRMA) assay with particular reference to the oscillatory activity detected by Fourier transformation and the estimation of trough concentrations using occupancy analysis.DESIGN Eight healthy adult male volunteers underwent 24‐hour profiles during which samples were drawn at 20‐minute intervals. Samples were analysed by an ELISA and an IRMA system.MEASUREMENTS The 24‐hour serum GH concentration profiles were subjected to Fourier transformation and to occupancy analysis.RESULTS No additional GH periodicities could be determined in the ELISA data other than the well documented 180–200‐minute periodicity. Median observed concentrations (OC) at 5% occupancy were 0.035 mU/l (range 0.004–0.22) for the ELISA and 0.035 mU/l (range 0.001–0.50) for the IRMA. For all OC parameters, 5,50 and 95%, there was a good correlation between the ELISA and IRMA systems. The mean difference (bias) between the ELISA and IRMA were ‐ 0.05, ‐ 0.28 and ‐1.40 mU/l at OC values of 5, 50 and 95% respectively and the standard deviations of the difference at the same OC values were 0.10, 0.50 and 1.61 mU/l.CONCLUSION Although there is a qualitative improvement on visual inspection of individual 24‐hour serum GH profiles obtained using the ELISA system, there is little additional information gained in terms of pulse periodicity or occupancy analysis.
A case of multiple endocrine neoplasia: hyperparathyroidism, insulinoma, GRF‐oma, hypercalcitoninaemia and intractable peptic ulceration
Authors: Price David E. , Absalom Stephen R. , Davidson Katharine , Bolia Amman , Bell Peter R. F. , Howlett Trevor A. 
Published: March 2008

A 42‐year‐old woman with a family history of multiple endocrine neoplasia type 1 (MEN 1) presented with symptomatic hypoglycaemia and peptic ulceration. Investigation revealed an insulinoma, hyperparathyroidism, hypercalcitoninaemia with a positive pentagastrin stimulation test, acromegaly due to a GRF‐oma, hyperprolacti‐naemia and normal serum gastrin levels. Five pancreatic tumours were removed at laparotomy and immuno‐staining was positive for insulin, calcitonin, somatostatin and glucagon. Post‐operatively she developed elevated serum gastrin levels and gross peptic ulceration, despite H2‐blockers, and died of gastro‐intestinal haemorrhage suggesting that removal of the somatostatinoma may have allowed increased gastrin secretion from a gastrinoma.This case emphasizes the importance of measuring a wide variety of tumour marker peptides in MEN 1 and suggests that caution is required in interpretation of the pentagastrin stimulation test in such cases. Patients with MEN 1 and known peptic ulceration may require peri‐operative omeprazole treatment even if serum gastrin levels are normal.