bluuebunny/crossref_metadata_2025_split huggingface dataset:
CLINICAL AND BIOCHEMICAL EFFECTS OF INCREMENTAL DOSES OF THE LONG‐ACTING SOMATOSTATIN ANALOGUE SMS 201‐995 IN TEN ACROMEGALIC PATIENTS
Authors: SHI Y. F. , HARRIS A. G. , ZHU X. F. , DENG J. Y. 
Published: March 2008

SUMMARYTen patients (seven women, three men) with active acromegaly, five previously treated and five newly diagnosed, were included in an open‐label prospective trial of 3 daily subcutaneous injections of the long‐acting somatostatin analogue SMS 201‐995 (Sandostatin) at increasing doses in order to obtain maximum growth hormone (GH) suppression. Four patients had received surgery, radiotherapy or bromocriptine. SMS 201‐995 doses were increased in a stepwise fashion from 100 μg every 8 h (three times daily) to 200, 300 and finally 500 μg three times daily at monthly intervals if mean serum GH values failed to decrease to undetectable levels in over 75% of the samples. The optimal dose was maintained for up to 28 months. Significant clinical improvement of headache, soft tissue swelling, facial features, hyperhidrosis and paraesthesia occurred in all patients. Mean 12‐h GH levels were significantly suppressed in four patients and fell to normal values in four. Suppression of GH levels was not achieved in two patients. Comparison of the mean interindividual GH values shows that the optimal efficacious dose is 100 μg t. i. d. in 7/10 patients. Somatomedin‐C (SM‐C) was also significantly reduced to below 50% of pretreatment levels in nine patients in whom it was measured. The subsequent increments of SMS 201‐995 up to 500 μg three times daily did not produce further clinically relevant GH or SM‐C suppression. Pituitary tumour shrinkage occurred in five patients. Thyroid function remained normal. Impaired glucose tolerance occurred in four patients. Side‐effects (diarrhoea, abdominal discomfort) were mild and transient. Asymptomatic gallstones occurred in three patients on 1500 μg/day and one patient on 600 μg/day after 6‐12 months treatment. This dose‐finding study shows that 100 μg three times daily SMS 201‐995 is an effective therapy for most of the acromegalic patients we treated.
FAMILIAL ACROMEGALY: STUDIES IN THREE FAMILIES
Authors: McCARTHY M. I. , NOONAN K. , WASS J. A. H. , MONSON J. P. 
Published: March 2008

SUMMARYAcromegaly is usually regarded as a disease which arises sporadically except on those rare occasions in which it occurs as one component of an inherited pluriglandular syndrome. Familial acromegaly occurring in isolation has been reported only rarely. We have studied three families in each of which two first‐degree relatives have developed acromegaly without clinical evidence of other endocrinopathies, in order to clarify the relationship of familial acromegaly to multiple endocrine neoplasia, type 1 (MEN 1). No further subclinical cases of acromegaly have been detected in those first‐degree relatives of the index cases who were screened. In two of the families, we have found no evidence of abnormal pancreatic or parathyroid function either in the acromegalic index cases or their asymptomatic relatives: a diagnosis of MEN 1 is therefore effectively excluded. In the third family, the presence of multiple subcutaneous lipomata in several members of the family and elevations of PTH levels in two (normocalcaemic) acromegalic index cases, might indicate a highly atypical presentation of MEN 1. None of the six acromegalic index cases had elevations of circulating growth hormone releasing hormone levels. We conclude that isolated familial acromegaly may be more common than has hitherto been realized and that, in these families at least, ectopic production of growth hormone releasing hormone is not responsible.
THE APPLICATION OF DECONVOLUTION ANALYSIS TO ELUCIDATE THE PULSATILE NATURE OF GROWTH HORMONE SECRETION USING A VARIABLE HALF‐LIFE OF GROWTH HORMONE
Authors: HINDMARSH P. C. , MATTHEWS D. R. , BRAIN C. , PRINGLE P. J. , BROOK C. G. D. 
Published: March 2008

SUMMARYA deconvolution analysis model to calculate pituitary growth hormone (GH) secretion rate from measured serum GH concentration has been developed. This uses an iterative method of‘curve‐stripping’based on an estimate of the half‐life. The model has been applied to serum GH profiles and demonstrates that GH secretion occurs in discrete bursts with quiescent periods between secretory episodes, an‘on‐off’phenomenon. The model can clearly dissect complicated concentration profiles such as the serum GH concentration response to growth hormone releasing hormone. The estimate was derived from calculating the half‐life of serum GH in 10 subjects following an intravenous bolus injection of 50 mU of biosynthetic human growth hormone (b‐hGH) and following infusions of the exogenous hormone (3 mU/kg/h) for 15, 30, 60 and 180 min. Endogenous GH secretion was suppressed by a continuous infusion of somatostatin (1‐14). An asymptotic relationship between the duration of GH infusion and the GH half‐life was established. A half‐life of 15.3 min was achieved after exposure to GH for 60 min and a maximum half‐life of 15.7 min after 180 min exposure.
ARGININE POTENTIATES THE GHRH‐ BUT NOT THE PYRIDOSTIGMINE‐INDUCED GH SECRETION IN NORMAL SHORT CHILDREN. FURTHER EVIDENCE FOR A SOMATOSTATIN SUPPRESSING EFFECT OF ARGININE
Authors: GHIGO EZIO , BELLONE JAELE , MAZZA ENRICO , IMPERIALE ELISEO , PROCOPIO MASSIMO , VALENTE FRANCESCA , LALA ROBERTO , DE SANCTIS CARLO , CAMANNI FRANCO 
Published: March 2008

SUMMARYTo investigate the mechanism underlying the GH‐releasing effect of arginine (ARG), we studied the interactions of ARG (0.5 g/kg infused i. v. over 30 min) with GHRH (1 μg/kg i. v.) and with pyridostigmine (PD, 60 mg orally) on GH secretion in 15 children and adolescents with familial short stature (5.1‐15.4 years). In a group of eight subjects ARG induced a GH increase not statistically different to that observed after GHRH (peak, mean±SEM: 38.0±10.4 vs 64.0±14.4 mU/1). The combined administration of ARG and GHRH led to GH levels (101±15.2 mU/1) higher than those observed after GHRH (P < 0.025) or ARG alone (P < 0.001) and overlapping with those recorded after combined PD and GHRH administration (111±22.4 mU/1). In the other seven subjects, ARG and PD administration induced a similar GH response either when administered alone (25.2±13.6 and 27.8±4.0 mU/1, respectively) or in combination (33.8±5.4 mU/1). In conclusion, our results show that in children ARG administration potentiates GHRH‐ but not PD‐induced GH increase. These findings agree with the hypothesis that the GH‐releasing effect of both ARG and PD is mediated via the same mechanism, namely, by suppression of endogeneous somatostatin release. Combined administration of either ARG or PD with GHRH has a similar striking GH‐releasing effect which is clearly higher than that of GHRH alone.
THE EFFECTS OF IMPROVED BLOOD GLUCOSE ON GROWTH HORMONE AND CORTISOL SECRETION IN INSULIN‐DEPENDENT DIABETES MELLITUS
Authors: WÜRZBURGER M. I. , PRELEVIC G. M. , SÖNKSEN P. H. , PERIC L. A. , TILL S. , MORRIS R. W. 
Published: March 2008

SUMMARYGrowth hormone and cortisol secretion were studied in 25 patients with insulin‐dependent diabetes before (Study 1) and 2 weeks after improved glucoregulation (Study 2). Blood samples for serum growth hormone (GH) and blood glucose determination were collected at hourly intervals whilst blood samples for cortisol and C‐peptide were collected every 6 h during the 24‐h period in Study 1 and Study 2. Glycaemic control was significantly improved in Study 2 compared to that in Study 1 (8.5 vs 13.3 mmol/1; P <0.001). With improved control, growth hormone levels rose by 21% (5.7 vs 4.7 mU/1; P < 0.05). Throughout both study periods growth hormone levels were higher in patients with no residual C‐peptide secretion (10 CpN patients) compared with patients with residual beta‐cell function (15 CpP patients) (7.1 vs 3.2 mU/1 in Study 1; 8‐9 vs 4.2 mU/1 in Study 2; P < 0.001). Characteristic shapes of the 24‐h blood glucose profile curves during both study periods were significantly different between the CpN and CpP group. Plasma cortisol decreased in both groups with improved metabolic control (P < 0.001) but the observed different diurnal pattern did not change. These results demonstrate the importance of residual endogenous insulin secretion in determining growth hormone secretion in insulin‐dependent diabetes and have important implications for glycaemic control and risk of microvascular complications.
OVARIAN SENSITIVITY TO GONADOTROPHINS IN PATIENTS WITH PCO IS UNAFFECTED BY SUPPRESSION OF LH
Authors: FLEMING R. , HAMILTON M. P. R. , CONAGHAN C. , BLACK W. P. , COUTTS J. R. T. 
Published: March 2008

SUMMARYInfertile women with oligomenorrhoea and elevated LH concentrations (presumed polycystic ovary disease, PCO) were treated with exogenous gonadotrophins, HMG and HCG, for induction of follicular growth and ovulation, respectively. This was effected in the absence or presence of a gonadotrophin releasing hormone analogue (GnRH‐A) to suppress basal LH and the positive feedback surge of LH. Analyses of the duration of HMG therapy required to attain the degree of stimulation for HCG to be administered showed no difference between those with and without LH suppression. Analyses of the ultrasound estimations of rates of follicle growth and continued recruitment during the course of HMG also failed to show any effect of LH suppression. These data show that the high sensitivity of these patients to HMG is not related to the circulating LH concentrations.
SERUM INHIBIN LEVELS DURING THE PERIOVULATORY INTERVAL IN NORMAL WOMEN: RELATIONSHIPS WITH SEX STEROID AND GONADOTROPHIN LEVELS
Authors: MCLACHLAN ROBERT I. , COHEN NANCY L. , DAHL KRISTINE D. , BREMNER WILLIAM J. , SOULES MICHAEL R. 
Published: March 2008

SUMMARYInhibin is a gonadal glycoprotein believed to be important in the regulation of pituitary FSH secretion and/or to function as a paracrine factor within the ovary and testis. We studied serum levels of inhibin, oestradiol (E2), progesterone (P), FSH and LH during the periovulatory interval in order to determine whether there is differential control of sex steroid and inhibin secretion by the mature follicle and the emerging corpus luteum. Seven normal cyclic women were admitted 3–4 days prior to midcycle and blood samples drawn every 3 h for 5–7 days. Serum E2, P, FSH, LH and inhibin were measured by radioimmunoassay. Data were normalized around the peak LH value (0 h). Serum E2 and inhibin rose in parallel (r = 0.92, P < 0.001) between – 69 and – 18 h, E2 reached a peak of 1296 ± 154 (mean±SEM) pmol/1 at −18 h, then fell to 1050± 139 pmol/1 at 0 h. Serum inhibin, on the other hand, continued to rise to a peak of 837±95U/lat – 6 h, fell to 455±48 U/lat +45 h, then rose again. On average, the peak inhibin level occurred 10.4± 5.1 h after the peak E2 (P < 0.05). Inhibin levels were positively correlated with both serum LH and FSH between – 24 and +24 h (P<0.01). Serum E2 was negatively correlated with LH, FSH and inhibin between – 24 and 0 h (P < 0.01). Serum P levels increased from 1.8 ± 0.3 nmol/1 at – 24 h to 14.3 ± 1.0 nmol/1 at +60 h. Serum inhibin was positively correlated with serum P from −24 to 0 h (P<0.01) and +45 to +60 h (P < 0.01), but was inversely correlated from 0 to +45 h(P< 0.01). We conclude that the maturing follicle secretes both E2 and inhibin in parallel until – 18 h, at which time the process of luteinization is initiated by the onset of the midcycle LH surge, as evidenced by the rise in P. E2 secretion then falls while inhibin secretion rises, indicating different regulation of secretion of these two hormones by the maturing follicle. Furthermore, the close positive correlation between inhibin and gonadotrophin levels around midcycle suggests that FSH and/or LH stimulate inhibin secretion and that the presumed negative feedback effect of inhibin on FSH secretion is overcome at this time. After midcycle, inhibin secretion initially falls, then rises, while P rises progressively. This transient divergence of P and inhibin secretion may occur during the transformation of the preovulatory follicle into the corpus luteum.
EFFECT OF OCTAPEPTIDE SOMATOSTATIN ANALOGUE (SMS 201‐995) ON PLASMA 7B2 (A NEUROENDOCRINE POLYPEPTIDE) LEVELS IN PATIENTS WITH ACROMEGALY
Authors: NATORI SHOICHI , IGUCHI HARUO , OHASHI MASAO , NAKAO RYUSUKE , BLOOM STEPHEN R. , NAWATA HAJIME 
Published: March 2008

SUMMARYWe studied the sequential changes of plasma levels of immunoreactive ‘7B2’(IR‐7B2), a neuroendocrine polypeptide, after a subcutaneous injection of 50 μg of synthetic octapeptide somatostatin analogue (SMS 201‐995) in seven patients with acromegaly due to GH‐producing pituitary adenoma. Compared to the basal levels, mean plasma IR‐7B2 and GH levels significantly decreased, until 5 and 10 h respectively after the administration of SMS 201‐995. The mean (±SEM) nadir levels of plasma IR‐7B2 and GH were 68.1 ± 101 and 13.1 ±6.9%, respectively, compared to mean plasma levels before treatment (100%). Plasma IR‐7B2 as well as GH levels did not change significantly when saline was administered subcutaneously to three acromegalic patients. In addition, plasma IR‐7B2 levels did not change significantly after the administration of SMS 201.995 in normal subjects or in patients with primary hypothyroidism in whom SMS 201.995 induced a decrease of plasma TSH levels. These results strongly suggest that SMS 201‐995 has an unequivocal suppressive effect on the synthesis and/or the secretion of 7B2 in human somatotroph adenoma cells.
OESTROGEN AND PROGESTERONE RECEPTORS IN MEN WITH BILATERAL OR UNILATERAL PUBERTAL MACROMASTIA
Authors: LEE KOK‐ONN , CHUA DIXIE Y. F. , CHEAH JIN‐SENG 
Published: March 2008

SUMMARYAbnormalities at the tissue receptor level may be important in the pathophysiology of pubertal macromastia, which may be unilateral or bilateral. We studied breast tissue removed from seven boys of age 16–17 years, five with bilateral and two with unilateral gynaecomastia. We confirmed that their physical features, karyotype, and plasma concentrations of testosterone, oestradiol, LH, FSH, and prolactin were all normal for adolescent males. Oestrogen and progesterone receptors were measured with a steroid binding (dextran coated charcoal) assay which was used for breast cancer receptor studies. Oestrogen receptors were not detectable in any of the 12 breasts studied. Progesterone receptors were detectable at a low level in two patients with bilateral gynaecomastia, one breast from each patient. We conclude that although the development of bilateral or unilateral male macromastia in puberty may yet be mediated by a local tissue receptor abnormality, this disorder is probably not mediated by an abnormal increase in oestrogen receptor number.
SUPEROVULATION INDUCTION IN WOMEN SUPPRESSES LUTEINIZING HORMONE SECRETION AT THE PITUITARY LEVEL
Authors: MESSINIS IOANNIS E. , TEMPLETON ALLAN 
Published: March 2008

SUMMARYIn superovulated women the pituitary response to GnRH is markedly attenuated by an unspecified ovarian factor(s). To examine the site of attenuation, the response of the pituitary to GnRH was investigated in five normally ovulating women during the late follicular phase of 3 cycles, i.e. a spontaneous (control) cycle, a cycle treated with ‘pure’ FSH, and a cycle treated with a combination of ‘pure’ FSH and pulsatile GnRH, via a pump (15 νg/ pulse). The oestradiol levels (mean ± SEM) at the time of the GnRH challenge were respectively 646 ±35, 1692 ±282 and 5976±1129 pmol/1. The size of the leading follicle was similar in all groups. Serum LH levels during treatment with FSH decreased significantly, while during treatment with FSH plus GnRH they increased initially and then decreased progressively. The response of pituitary LH to GnRH was significantly attenuated during treatment with FSH and FSH plus GnRH, as compared to the spontaneous cycles, but was not abolished. The attenuation was significantly greater in the FSH plus GnRH cycles (94%) than in the FSH cycles (59%). We conclude that in superovulated cycles, the attenuation of the pituitary response to GnRH increases with the degree of ovarian hyperstimulation. It is suggested that the responsible unspecified ovarian factor(s) exerts its effects at least at the pituitary level.
PATTERNS OF ACTH AND CORTISOL PULSATILITY OVER TWENTY‐FOUR HOURS IN NORMAL MALES AND FEMALES
Authors: HORROCKS P. M. , JONES A. F. , RATCLIFFE W. A. , HOLDER G. , WHITE A. , HOLDER R. , RATCLIFFE J. G. , LONDON D. R. 
Published: March 2008

SUMMARYPatterns of plasma ACTH and Cortisol concentrations were studied in 10 healthy subjects (five male, five female in the early follicular phase, overall age range 21–32 years) by sampling through an indwelling cannula every 15 min for 24 h. The subjects were in hospital, ambulant, and taking normal meals. Plasma ACTH was measured by a two‐site immunoradiometric assay with a detection limit of 3.9 ng/1 (0.9 pmol/1). Pulses were identified by the method of Clayton et al. (1987) using stringent criteria to minimize false positive peaks. All subjects showed a circadian rhythm of ACTH, the acrophase occurring between 0615 and 0920 h in all but one subject and the mesor value was between 9.2 and 18.6 ng/1 (2.0 and 4.1 pmol/I). There were significantly fewer pulses between 1800 and 2400 h compared with the other three 6‐h periods. The pattern of ACTH differed between males and females in several respects: more pulses (18 vs 10), greater mean peak amplitude (16.8 vs 10.3 ng/1), greater area under the 24‐h profile (350.9 vs 206.6 ng/1 h) and higher mean level (14.7 vs 8.6 ng/1) in the males. In contrast, the Cortisol pattern did not show statistically different sex differences. The sex differences suggest greater sensitivity to, or availability of, ACTH to the female adrenal cortex, or different set points in Cortisol feedback.
Allgrove syndrome: an autosomal recessive syndrome of ACTH insensitivity, achalasia and alacrima
Authors: Moore P. S. J. , Couch R. M. , Perry Y. S. , Shuckett E. P. , Winter J. S. D. 
Published: March 2008

SummaryAllgrove syndrome (Isolated glucocorticoid deficiency, achalasia and alacrima) was found in eight members of an inbred French Canadian/North American Indian pedigree. The high degree of consanguinity supports an autosomal recessive mode of inheritance for this disorder. Six patients presented with hypoglycaemia and other evidence of cortisol deficiency between 2·5 and 8 years of age; however, two others became cortisol deficient after Initial testing showed normal cortisol responses to ACTH, evidence that the glucocorticoid Insufficiency of this syndrome may not be congenital, but may develop as late as the third decade. No evidence of mineralocorticoid deficiency has been found during 65 patient‐years of follow‐up. Aiacrima was the earliest and most consistent clinical sign of Allgrove syndrome. Other manifestations of peripheral or autonomic neuropathy were found in four patients. The patients showed similar facial features, and three had significant veto‐pharyngeal Incompetence. Ail showed oesophageal dysmotility even in the absence of symptomatic dysphagia. In‐vitro studies of lymphocyte ACTH binding showed no differences from normal controls. If such lymphocyte binding, as has been suggested, reflects adrenal ACTH receptor activity, these data would suggest that the glucocorticoid deficiency of Allgrove syndrome is not the result of a defect in that receptor. However, the observation that ACTH does not elicit increased adenylate cyclase activity even in normal lymphocytes casts considerable doubt on the physiological significance of ACTH binding to lymphocytes. It seems likely, therefore, that true ACTH receptors are not expressed on peripheral lymphocytes, and any conclusions regarding a possible receptor defect in Allgrove syndrome must await studies of receptor expression on adrenal cell membranes
Metabolic effects of pharmacological adrenergic blockade in phaeochromocytoma
Authors: Krentz Andrew J. , Hale Peter J. , Horrocks Peter M. , Heslop Kirsten E. , Johnston Desmond G. , Wright Alex D. , Nattrass Malcolm 
Published: March 2008

Summary Twelve‐hour hormonal and metabolic profiles were performed in a 68‐year‐old woman with a benign adrenal phaeochromocytoma (a) prior to adrenergic blockade, (b) after the establishment of pharmacological alpha‐blockade with phenoxybenzamine, (c) after combined alpha and beta‐blockade with phenoxybenzamine and propranolol, and (d) after successful surgery and withdrawal of medication. Pretreatment, (a) vs (d), significant elevations (12‐h mean ± SD) were observed In the concentrations of noradrenaline (44·9 ± 14 ± 4 vs 2·3 ± 0.7 nmol/l, p > 0·01), glucose (6·9 ± 1·9 vs 5·0 ± 1·0 mmol/l, p > 0·05), glycerol (0·22 ± 0.02 vs 0·07 ± 0·01 mmol/l, p > 0·01), non‐esterifled fatty acids (0·71 ± 0·28 vs 0·34 ± 0·08 mmol/l, p>0·01), and total ketone bodies (0·08 ± 0·03 vs 0·03 ± 0·02 mmol/l, p > 0·01). Alpha‐blockade, (b) vs (a), was associated with an increase in noradrenaline levels (P > 0·01) but not with any significant alterations in intermediary metabolite concentrations. Following the establishment of combined alpha and beta‐blockade, (c) vs (b), plasma noradrenaline returned to its pretreatment level while the concentrations of glycerol, fatty acids and ketone bodies were normalized. A completely physiological 12‐h blood glucose profile, however, was observed only post‐operatively. No significant differences were observed in mean plasma insulin levels between the four studies. These results indicate impaired regulation of multiple aspects of carbohydrate, lipid and ketone body metabolism in our patient. Alpha‐blockade did not ameliorate the abnormalities in any aspect of intermediary metabolism and was associated with an increase in noradrenaline levels. Combined alpha and beta‐blockade effectively normalized lipolysis and ketone body metabolism but did not fully correct the abnormality in glucose metabolism.
Heterogeneity of circulating TSH‐receptor antibodies in thyroid disease demonstrated directly by chromatography
Authors: Worthington J. , Byfield P. G. H. , Hlmsworth R. L. 
Published: March 2008

SummaryThe heterogeneity of circulating TSH‐receptor antibodies (TRAb) has been demonstrated directly by affinity chromatography on the dye Remazol Yellow‐GGL. The technique resolved these antibodies Into discrete peaks within the general serum Immunoglobulln background. Peaks were detected initially by a binding (radioreceptor) assay and then characterized by their ability to stimulate the uptake of iodine‐125 Into FRTL‐5 cells. Thirteen subjects with high serum levels of TRAb were studied. The two hypothyrold patients each produced a single peak of TRAb activity with no ability to stimulate uptake of iodine‐125 into cultured cells. The remaining 11 patients had Graves’ disease; their sera produced a range of elution profiles after chromatography with TRAb activity resolved Into as many as five peaks. Considerable differences were seen in the relative abilities of the resolved TRAb components to bind to receptors and to stimulate cellular uptake of Iodine‐125 both between and within individual samples. No two patients produced components which chromatographed in the same position on the gradients employed for elution from the dye