bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE PITUITARY‐ADRENAL RESPONSE TO CRF‐41 IS UNALTERED BY INTRAVENOUS SOMATOSTATIN IN NORMAL SUBJECTS
Authors: STAFFORD P. J. , KOPELMAN P. G. , DAVIDSON KATHERINE , McLOUGHLIN LORRAINE , WHITE A. , REES L. H. , BESSER G. M. , COY D. H. , GROSSMAN A. 
Published: March 2008

SUMMARYWe have previously reported that the hypothalamo‐pituitary‐adrenal response to insulin‐induced hypoglycaemia is normal while the cortisol release to pituitary stimulation by corticotrophin releasing factor (CRF‐41) is reduced in obesity. Impaired growth hormone (GH) secretion is also found in obesity which may result from altered central levels of somatostatin (SMS). We have investigated, by giving a simultaneous infusion of SMS to six volunteer normal weight men during a CRF test, whether it is possible for SMS to modify pituitary‐adrenal function. Each subject received intravenous CRF‐41 (0.5 μg/ kg) on two occasions during an infusion of isotonic saline or SMS (4 μg/min) in a randomized double‐blind study. Plasma GH, cortisol, ACTH and SMS were measured. Three subjects demonstrated GH peaks during saline infusion but no peaks were seen in any subject during SMS infusion. No significant difference was found between peak cortisol responses during saline or SMS infusion (SMS cortisol 443 ± 61 nmol/l, saline cortisol 485 ± 52 nmol/l); neither was there any difference in the ACTH responses. We conclude that SMS does not alter the pituitary response to CRF in normal weight men and is thus less likely to be responsible for the altered pituitary‐adrenal function seen in obesity. Further studies of alternative mechanisms are required to explain the cause of this abnormality.
PERIFUSION STUDIES OF BROMOCRIPTINE‐TREATED AND UNTREATED MACROPROLACTINOMAS: EFFECTS OF DOPAMINE, BROMOCRIPTINE AND TRH
Authors: BEVAN J. S. , BURKE C. W. 
Published: March 2008

SUMMARYThere have been no detailed in‐vitro studies of PRL secretion by human macroprolactinoma cells exposed to bromocriptine (BC) to within a few days of surgical removal. We have studied cells from four such tumours (serum PRL 7.05–247 U/l) and six untreated tumours (serum PRL 4–80.35 U/l) using a perifusion technique. The BC‐treated tumours had shown tumour shrinkage and were treated until 40–96 h before surgery, but in one patient serum PRL had not suppressed below 15 U/l despite chronic treatment. Pretreatment serum PRL responses to TRH were blunted in all 10 patients. During perifusion with dopamine (DA, 5 μmol/l) untreated prolactinomas had a higher PRL secretion rate (19.3 ± 2.7 μU/mg tissue/min, mean ± SEM) than BC‐treated (3.9 ± 0.7, P= 0.005). When DA was removed, PRL secretion from untreated tumours increased to 129.7 ± 18.7 μU/mg/min, but in three of the BC‐treated, little increase occurred. In the fourth (from the patient whose serum PRL had not fully suppressed) PRL secretion increased from 4.4 to 25.6 μU/mg/min after DA withdrawal, and DA and BC dose‐related inhibition of PRL was similar to that observed in untreated tumours. TRH (10 ng/ml), without DA, provoked increased PRL release from both untreated (266% basal secretion, n= 3) and BC‐treated (298%, n= 3) tumours; this effect was completely inhibited by DA (5 μmol/l). The absence of hormones other than PRL following potassium (55 mmol/l) excluded contaminating normal pituitary. We conclude: (1) The effects of BC on prolactinoma PRL secretion may persist for at least 4 days; (2) partial in‐vivo BC resistance can be due to factors other than DA receptor malfunction; (3) the apparent discrepancy between in‐vivo and in‐vitro TRH responses was consistent with the presence of increased hypothalamic DA tone in vivo; and (4) BC may have differential effects on TRH and DA‐controlled PRL pools in the tumourous lactotroph.
QUANTIFICATION OF URINARY GROWTH HORMONE (GH) EXCRETION BY CENTRIFUGAL ULTRAFILTRATION AND RADIOIMMUNOASSAY: APPRAISAL OF THE RELATIONSHIP BETWEEN 24 H URINARY GH AND MEAN 24 H SERUM GH LEVELS IN NORMAL AND ABNORMAL STATES OF GH SECRETION
Authors: WEISSBERGER A. J. , HO K. Y. , STUART M. C. 
Published: March 2008

SUMMARYWe have applied a simple method for the quantification of 24 h urinary GH excretion (24 h UGH), combining centrifugal ultrafiltration and radio‐immunoassay (RIA), to an appraisal of the relationship between 24 h UGH and mean 24 h serum GH levels in normal and abnormal states of GH secretion. Forty‐four subjects, comprising 13 normal adults, 12 short‐statured subjects and 19 subjects with active acromegaly, underwent blood sampling at 20‐min intervals and concurrent urine collection for 24 h. Mean 24 h serum GH and 24 h UGH were also determined in four post‐menopausal women before and during cyclical oestrogen replacement therapy, and 24 h UGH was measured in six normal men prior to and following the subcutaneous administration of biosynthetic GH (0.2 IU/kg).Each subject's mean 24 h serum GH level was determined by assaying a ‘pooled’ sample, derived from equal aliquots of the 73 serum samples obtained during the 24 h study. The method for quantification of 24 h UGH employs centrifugal microconcentrators, and involves a 50‐fold concentration of urine, followed by dialysis and RIA. Surface adsorptive hormone loss during sample collection and ultrafiltration is minimized by the prior addition of bovine serum albumin to the urine collection container. Immunoreactive GH in ultrafiltered urine dilutes in parallel with the RIA standard curve. GH is stable in urine stored at −20°C for at least 12 months.There was a highly significant correlation between 24 h UGH and mean 24 h serum GH values obtained from the combined population of normal adults (including the post‐menopausal women during oestrogen therapy) and short‐statured subjects (r=0.69,P> 0.0001). A significant correlation was also found in short‐statured subjects alone (r= 0.63,P> 0.05). In contrast, there was no significant correlation between 24 h UGH and mean 24 h serum GH in subjects with active acromegaly, and their 24 h UGH values were not distinguishable from those of the ‘non‐acromegalic’ subjects. A significant increase in 24 h UGH occurred in the post‐menopausal women given cyclical oestrogen replacement therapy (9.7 ± 2.6 (mean ± SE) to 24.6 ± 1.0 μIU/mmol creatinine,P> 0.02), reflecting the increase in their mean 24 h serum GH levels (0.8 ± 0.3 to 5.3 ± 0.7 mIU/l,P> 0.01). Twenty‐four hour UGH increased from 4.6 ± 0.6 to 17.1 ± 2.1 μIU/mmol creatinine (P> 0.002) in the men given biosynthetic GH. Twenty‐four hour UGH measurements reflect mean 24 h serum GH levels in normal adults and short‐statured subjects. While the measurement of 24 h UGH shows promise as an investigative tool, our results cast doubt on its use in the diagnosis of acromegaly.
EFFECTS OF INTRANASAL CALCITONIN ADMINISTRATION ON PITUITARY GH RESPONSE TO hGHRH (1–29)NH2 IN NORMAL ADULT SUBJECTS
Authors: GIUSTINA ANDREA , ROMANELLI GIUSEPPE , DOGA MAURO , PIZZOCOLO GIUSEPPE , GIUSTINA GIANNI 
Published: March 2008

SUMMARYStudies in man demonstrated that intramuscular salmon (s) calcitonin (CT) administration blunted pituitary GH response to hypothalamic stimuli such as arginine infusion and insulin‐induced hypoglycaemia. However, the mechanisms underlying this inhibiting action of CT are still unclear. The aim of our study was to investigate the effects of intranasal (i.n.) and i.m. sCT administration on GH secretion elicited by direct pituitary stimulation in man with human GH‐releasing hormone (GHRH) (1–29)NH2. Seven healthy non‐obese volunteers (five men, two women; mean age ± SDM 25 ± 2) underwent a bolus intravenous injection of GHRH, 100 pg, alone or associated with sCT, administered either i.n., 300 IU, or i.m., 100 IU. Our data demonstrate a significant decrease in GH secretion after GHRH when either i.n. or i.m. sCT is administered. GH peak (mean ± SDM); GHRH alone 22.9 ± 2.5 is GHRH plus i.n. sCT, 8.9 ± 1.5 μg/l, P > 0.001; or vs GHRH plus i.m. sCT 12.3 ± 2.5 μg/l, P > 0.001. Area under the curve of GH secretion: GHRH alone 1211 ± 196 vs GHRH plus i.n. sCT 551 ± 116 μg 120 min/l, P > 0.001; or vs GHRH plus i.m. sCT 700 ± 167 μg 120 min/l, P > 0.001. We conclude that sCT is able to inhibit GHRH‐stimulated GH secretion in man.
INSULIN‐LIKE GROWTH FACTOR 1 AND BONE TURNOVER IN GLUCOCORTICOID‐TREATED AND CONTROL SUBJECTS
Authors: REID I. R. , GLUCKMAN P. D. , IBBERTSON H. K. 
Published: March 2008

SUMMARYThe role of the growth hormone‐somatomedin axis in the genesis of steroid osteoporosis has been studied by measuring circulating insulin‐like growth factor I (IGF‐1) levels in asthmatic subjects either receiving or not receiving therapy with oral glucocorticoids. There was no difference in IGF‐1 levels between the two groups (60.6 μg/l (95% confidence interval 47.3–77.8) in the control subjects vs 69.1 μg/l (49.3–96.9) in the steroid‐treated group). IGF‐1 declined with age in the control subjects but not in those taking steroids. When IGF‐1 levels were correlated with biochemical indices of bone turnover, a significant relationship was found with urine hydroxyproline in the control subjects (r=0.55, P<0.02) but not in those taking steroids. It is concluded that glucocorticoid therapy does not alter mean circulating levels of IGF‐1 but that the growth hormone‐somatomedin axis may influence bone turnover in normal subjects. Interference by glucocorticoids with the normal regulation of IGF‐1 and its influence on bone turnover is suggested.
THE EFFECT OF THYROID DISEASE ON PROINSULIN AND C‐PEPTIDE LEVELS
Authors: BEER S. F. , PARR J. H. , TEMPLE R. C. , HALES C. N. 
Published: March 2008

SUMMARYC‐peptide and proinsulin levels were studied in hyper and hypothyroidism both pre and post‐treatment and in comparison to matched normals. Fasting C‐peptide was reduced in untreated hyperthyroidism (0.4 ± 0.2 (mean ± SEM) vs 0.7 ± 0.2 nmol/l, P<0.05) but returned to normal levels following treatment. Fasting proinsulin was elevated in untreated hyperthyroidism (3.6 ± 0.7 vs 2.4 ± 0.5 pmol/l, P<0.05) also returning to normal after treatment. A similar pattern was seen after oral glucose. The increased proinsulin and reduced C‐peptide suggest there may be a defect of proinsulin processing in hyperthyroidism.Fasting C‐peptide was reduced in untreated hypothyroidism (0.4 ± 0.1 vs 0.7 ± 0.1 nmol/l, P<0.05) and also returned to normal after treatment. Fasting proinsulin did not differ significantly from controls. However, proinsulin was reduced after oral glucose (4.7 ± 0.7 vs. 7.9 ± 2.0 pmol/l, P<0.05) as was C‐peptide (0.9 ± 0.2 vs 2.6 ± 0.3 nmol/l, P<0.05). Both returned to normal after treatment. These findings suggest there are abnormalities of proinsulin and C‐peptide levels in both hyper and hypothyroidism.
RESISTANCE OF METASTATIC PANCREATIC ENDOCRINE TUMOURS AFTER LONG‐TERM TREATMENT WITH THE SOMATOSTATIN ANALOGUE OCTREOTIDE (SMS 201–995)
Authors: WYNICK D. , ANDERSON J. V. , WILLIAMS S. J. , BLOOM S. R. 
Published: March 2008

SUMMARYTen patients with metastatic pancreatic endocrine tumours were treated with the long‐acting somatostatin analogue octreotide (SMS 201–995). Three patients showed no response, clinically or biochemically, and treatment was therefore withdrawn. The seven remaining patients continued treatment for a median period of 28 months (range 13–54 months). Treatment was initially effective, symptoms improved and the concentrations of tumour‐related hormones were reduced.Worsening of symptoms and rising levels of tumour‐related hormone concentrations occurred a median of 5 months (range 1–6 months) after the start of therapy and were initially reversed by increasing the dose of octreotide over a median of 10 months (range 6–16 months). However, after a median of 13 months (range 5–34 months) at the maximum dosage, symptoms recurred and were no longer responsive to a further increase in dosage of octreotide or other therapeutic measures. All patients died within a period of 5 months once this resistant phase of their illness had been reached.
SPONTANEOUS GROWTH HORMONE (GH) PULSATILITY IS THE MAJOR DETERMINANT OF GH RELEASE AFTER THYROTROPHIN‐RELEASING HORMONE IN ADOLESCENT DIABETICS
Authors: EDGE J. A. , HUMAN D. H. , MATTHEWS D. R. , DUNGER D. B. 
Published: March 2008

SUMMARYGH release is abnormally regulated in insulin‐dependent diabetes (IDDM), and paradoxical stimulation of GH release after TRH has been reported. However, overnight GH pulsatility is increased in IDDM, and it may be difficult to distinguish TRH‐stimulated release from spontaneous secretory episodes. To resolve this question, we carried out two overnight GH profiles followed by either TRH or saline control tests in six adolescents with IDDM; ages 11.4–14.7 years, duration IDDM 2.4–6.7 years.A rise in GH was seen in four of six following TRH, but with no consistent pattern. A rise was also seen in four of six following saline. Peak GH levels were similar after TRH and saline (19.3 ± 4.4 vs 25.8 ± 5.5 mU/l; mean ± SEM). Mean blood glucose was no different during TRH and saline tests (9.5 ± 1.6 vs 7.5 ± 0.6 mmol/l).The two subjects who had an early GH peak after TRH were those in whom GH levels had already begun to rise, suggesting the coincident occurrence of a spontaneous GH pulse. The timing of the next GH pulse could be predicted equally well after TRH and saline from the overnight secretory profile using autocorrelation.Paradoxical GH stimulation after TRH is not seen in adolescents with IDDM, but apparent responses may be due to timing coincident with the increased spontaneous pulsatility.
EFFECT OF MORPHINE ON CORTISOL AND PROLACTIN SECRETION IN ANOREXIA NERVOSA AND DEPRESSION
Authors: ZIS ATHANASIOS P. , REMICK RONALD A. , CLARK CAMPBELL M. , GOLDNER ELLIOT , KELLY GRANT B. E. , BROWN GREGORY M. 
Published: March 2008

SUMMARYEndogenous opioid peptides are involved in feeding regulation, and alterations in opioidergic regulation have been implicated in the pathophysiology of eating disorders. To investigate further this hypothesis, we conducted a placebo‐controlled study of the effect of the opiate alkaloid morphine on cortisol and prolactin secretion in six patients with anorexia nervosa and six age‐matched healthy volunteers, and compared the results with those obtained in nine depressed patients. Basal cortisol but not basal prolactin levels were elevated in patients with anorexia nervosa and patients with depression. Following the administration of morphine plasma concentrations of cortisol levels declined progressively and at a similar rate in all three groups. The prolactin response to morphine was attenuated significantly in patients with depression. Neither the cortisol and prolactin response to morphine in the anorectic patients nor the cortisol response in the depressed patients we observed in this study suggests altered opiate receptor sensitivity. However, the decreased prolactin response to morphine in depressed patients remains compatible with this hypothesis.
NASAL CALCITONIN FOR TREATMENT OF ESTABLISHED OSTEOPOROSIS
Authors: OVERGAARD K. , RIIS B. J. , CHRISTIANSEN C. , PØADENPHANT J. , JOHANSEN J. S. 
Published: March 2008

SUMMARYThirty‐seven women with established osteoporosis completed a one‐year double‐blind, placebo‐controlled study with the primary aim of examining the effect of nasal salmon calcitonin (200 IU daily) on bone and calcium metabolism. All the women received a daily calcium supplement of 500 mg. For comparison we also report data from an age‐matched group of healthy women who did not receive calcium supplementation. The bone mineral measured in the forearm (single photon absorptiometry) and spine (dual photon absorptiometry) showed a similar pattern during treatment. The calcitonin group (n = 17) did not lose bone mineral in comparison with the placebo (n= 20) and the control groups (n= 19) (P< 0.01). The biochemical estimates of both bone resorption and bone formation decreased highly significantly in the calcitonin group (P< 0.001) and were unchanged in the control group, whereas the placebo (calcium) group showed intermediate values. Neither subjective nor objective side‐effects occurred in any of the groups. We conclude that nasal calcitonin is a realistic treatment of established osteoporosis.
HETEROGENEITY OF THE POLYCYSTIC OVARY SYNDROME: CLINICAL, ENDOCRINE AND ULTRASOUND FEATURES IN 556 PATIENTS
Authors: CONWAY G. S. , HONOUR J. W. , JACOBS H. S. 
Published: March 2008

SUMMARYThis paper reports an analysis of the clinical, endocrine and ultrasound data within a population of 556 patients with ultrasound‐diagnosed polycystic ovaries. Compared with those not so affected, hirsutism was associated with a higher mean serum testosterone concentration, infertility was associated with higher mean gonadotrophin concentrations, obesity was associated with a higher mean serum testosterone concentration, hyperprolactinaemia was associated with a lower mean serum testosterone concentration and smaller ovaries, alopecia was associated with lower mean serum LH and testosterone concentrations, and acanthosis nigricans was associated with obesity and a raised mean serum testosterone concentration. The heterogeneity illustrates the limitations in the use of specific clinical or endocrine criteria as requirements for the diagnosis of the polycystic ovary syndrome.
VARIABLE EFFECTS OF RU 486 ON ENDOMETRIAL MAINTENANCE IN THE LUTEAL PHASE EXTENDED BY EXOGENOUS hCG
Authors: CROXATTO HORACIO B. , SALVATIERRA ANA MARIA , CROXATTO HECTOR D. , SPITZ IRVING M. 
Published: March 2008

SUMMARYThis study was designed to assess the features and conditions for endometrial bleeding induction with the synthetic antiprogestin and antiglucocorticoid RU 486 during hCG‐induced prolongation of the luteal phase. Eighteen healthy, surgically sterilized women and another five women with an intrauterine contraceptive device (IUD) participated. All subjects received hCG which was injected daily in increasing doses (500 to 15 000 IU) from day 9 to day 15 of the luteal phase. Ten subjects received hCG alone, and groups of three to 16 subjects received hCG combined with RU 486 (25, 50, 100,200 or 400 mg/day). RU 486 administration was commenced on day 12 following the LH surge and given either for 1, 4 or 7 consecutive days. In certain cycles, tamoxifen (20 mg/day) was given for 4 consecutive days with hCG, or with hCG and RU 486. All treatment cycles were separated by one or two resting cycles. Frequent blood samples were taken to monitor the endocrine response.Treatment with hCG alone or with the various combinations of RU 486 produced similar serum levels of oestradiol and progesterone which were equivalent to those observed during early pregnancy. With hCG alone, the onset of bleeding was on day 21–24 after the LH surge, coinciding with the drop in oestradiol and progesterone. With RU 486 doses of 50 mg/day or more, an early bleeding episode almost invariably occurred on day 14–17 after the LH surge in the presence of high circulating steroid levels. In contrast, 25 mg/day RU 486 for 4 days failed to induce this early onset of bleeding in three out of six cases. Tamoxifen did not cause early bleeding and failed to potentiate the effect of RU 486. In 43% of the cycles treated with RU 486, a second bleeding episode occurred on days 22–24 after the LH surge coincident with the drop of steroids. This late bleeding was less frequent (17%) in the subgroup receiving a total dose of 700 or 800 mg RU 486. In those cycles that exhibited a second bleeding episode coincident with the fall in progesterone, endometrial biopsies, taken shortly after the initial early bleeding had stopped, showed a mixed proliferative and secretory endometrium, suggestive of incomplete shedding. In contrast, only proliferative endometrium, compatible with complete shedding, was evident in cycles characterized by the absence of a second bleeding episode. It is concluded that during maintenance of corpus luteum function with exogenous hCG, RU 486 can induce endometrial bleeding despite high circulating progesterone and oestradiol levels. With the lower doses of RU 486 this bleeding is often accompanied by incomplete sloughing of the endometrium leading to a second bleeding episode at the time of corpus luteum demise.
IS OLEIC ACID THE THYROXINE BINDING INHIBITOR IN THE SERUM OF ILL PATIENTS?
Authors: HAYNES I. G. , LOCKETT S. J. , FARMER M. J. , FITCH N. J. , BRADWELL A. R. , SHEPPARD M. C. , RAMSDEN D. B. 
Published: March 2008

SUMMARYThe possibility that oleic acid is the thyroxine binding inhibitor in the serum of seriously ill patients was investigated. 3H‐Oleic acid was shown to bind directly to human thyroxine‐binding globulin (TBG) by the techniques of one and two‐dimensional immunoelectrophoresis in combination with autoradiography. However, no correlation was seen between serum thyroxine concentration and oleic acid concentration in two groups of patients, one of which underwent routine cholecystectomy, whilst the other group was admitted to an intensive therapy unit (mortality 75%). No correlation was seen between serum total thyroxine concentration and either stearic, palmitic, linoleic or arachidonic acid concentrations in these groups. Therefore, it was concluded that oleic acid was unlikely to be the circulating inhibitor of thyroxine binding.
HEPATIC MICROSOMAL ENZYME INDUCTION AND ADRENAL CRISIS DUE TO o,p’DDD THERAPY FOR METASTATIC ADRENOCORTICAL CARCINOMA
Authors: HAGUE R. V. , MAY W. , CULLEN D. R. 
Published: March 2008

SUMMARYTwo cases are described in which metastatic adrenocortical carcinoma associated with Cushing's syndrome was treated with mitotane (o,p'DDD). The first patient had initially been treated by bilateral adrenalectomy and, whilst responding to mitotane biochemically and by remission of metastases, experienced repeated episodes of adrenal crisis requiring a substantial increase in steroid therapy. The second patient failed to respond to the drug, but evidence of hepatic enzyme induction was noted during its administration. It is suggested that hepatic microsomal enzyme induction can occur in association with treatment with mitotane and that this can lead to an increased destruction of exogenous steroid with clinical consequences.
PERSISTENT HYPERINSULINAEMIC HYPOGLYCAEMIA OF INFANCY: LONG‐TERM TREATMENT WITH THE SOMATOSTATIN ANALOGUE SANDOSTATIN†
Authors: GLASER BENJAMIN , LANDAU HEDDY , And ADINA SMILOVICI , NESHER RAFAEL 
Published: March 2008

SUMMARYSix infants with severe, persistent hyperinsulinaemic hypoglycaemia were treated with the long‐acting somatostatin analogue SMS 201–995 (Sandostatin, Sandoz, Basle, Switzerland). Effective control of hypoglycaemia without the need for parenteral glucose was achieved in five of the six cases with doses ranging from 10 to 40 μg/kg day given either by four S.C. injections per day, or by continuous subcutaneous infusion (CSI). One has been well controlled on SMS 10 μg/kg day for 17 months as an out‐patient without requiring surgery, while the five others underwent sub‐total pancreatectomy after receiving short courses of the drug. In two patients where hypoglycaemia persisted after sub‐total pancreatectomy SMS was effective in inhibiting insulin secretion and preventing hypoglycaemia. Plasma somatomedin concentrations and linear growth were not suppressed in any patient. It is concluded that Sandostatin is useful in the pre and post‐operative management of most infants with this syndrome. In selected cases this analogue of somatostatin may also be a long‐term treatment option in place of pancreatectomy.