bluuebunny/crossref_metadata_2025_split huggingface dataset:
EFFECTS OF HIGH‐DOSE AND LOW‐DOSE NALOXONE ON PLASMA ACTH IN PATIENTS WITH ACTH HYPERSECRETION
Authors: DEUSS U. , ALLOLIO B. , KAULEN D. , FISCHER H. , WINKELMANN W. 
Published: March 2008

SUMMARYThe effect of a high (5–4 mg/h) and a low (0–8 mg/h) dose of naloxone (i.v. over a period of 90 min) on ACTH secretion was compared with placebo in patients with Addison's disease, congenital adrenal hyperplasia, Cushing's disease or Nelson's syndrome. In seven patients with primary adrenal insufficiency the high dose of naloxone provoked a significant increase of plasma ACTH concentrations (P<0.02) whereas the low dose of naloxone failed to influence ACTH secretion. In six patients with ACTH dependent Cushing's disease or Nelson's syndrome both doses failed to alter plasma ACTH levels. These results support the concept of inhibitory δ‐or k‐opiate receptors in the regulation of ACTH secretion. In patients with Cushing's disease or Nelson's syndrome ACTH secretion is insensitive to naloxone, presumably because of an autonomous pituitary adenoma or hypothalamic derangement.
EFFECT OF A SINGLE BOLUS OF ETOMIDATE UPON EIGHT MAJOR CORTICOSTEROID HORMONES AND PLASMA ACTH
Authors: ALLOLIO B. , DÖRR H. , STUTTMANN R. , KNORR D. , ENGELHARDT D. , WINKELMANN W. 
Published: March 2008

SUMMARYIn a prospective controlled trial we investigated the effect of an induction dose of etomidate (0.26 mg/kg i.v.) on plasma ACTH, progesterone, 17αOH‐progesterone, 11‐deoxycortisol, cortisol, cortisone, corticosterone, 11‐deoxycorticosterone, and aldosterone in seven males undergoing general anaesthesia. Seven other male patients receiving thiopentone at induction (5.0 mg/kg i.v.) served as controls. Plasma ACTH concentrations rose higher in the etomidate group (346 ± 124 vs. 117 ± 74 pg/ml, mean ± SEM), but the difference was not significant. After etomidate we found a clear suppression of plasma cortisol (P<0.01), cortisone (P<0.01), corticosterone (P<0.01), and aldosterone (P<0.05) compared to corticosteroid levels after induction with thiopentone. Plasma 11‐deoxycortisol and 11‐deoxycorticosterone concentrations were grossly elevated 210 min after etomidate (91 ± 28 nmol/1 and 7.04 ± 0.47 nmol/1, respectively, P<0.01) demonstrating inhibition of 11β‐hydroxylation of both glucocorticoid and mineralocorticoid intermediates. In contrast, no significant difference in plasma progesterone and 17α‐OH‐progesterone levels was found between the two groups indicating that the cholesterol‐side‐chain cleavage enzyme is less sensitive to etomidate than 11β‐hydroxylase. Our results suggest that after induction of anaesthesia with a single bolus of etomidate, inhibition of other enzymes in the corticosteroid‐synthetic pathway (e.g. cholesterol‐side‐ chain cleavage enzyme) is of little clinical relevance.
THYROTROPHIN BLOCKING ANTIBODIES IN THE SERA OF MOTHERS WITH CONGENITALLY HYPOTHYROID INFANTS
Authors: GINSBERG JODY , WALFISH P. G. , RAFTER D. J. , VON WESTARP C. , EHRLICH R. M. 
Published: March 2008

SUMMARYWe examined IgG from 15 mothers of infants with congenital hypothyroidism for their ability to block TSH‐stimulated iodine organification in vitro. Only one out of 15 of these IgGs exhibited TSH‐blocking activity. This IgG could inhibit TSH action by 30–50%. It could not block radiolabelled TSH from binding to its receptor but did inhibit dibutyryl cyclic AMP stimulation of iodine organification implying a unique effect on post‐receptor processes via a membrane binding site distant from the TSH binding site. Interestingly, there was no evidence of autoimmune thyroid disease in the mother. These results suggest that the transplacental passage of TSH‐blocking antibodies plays little, if any, role in the development of congenital hypothyroidism.
THE SENSITIVITY OF GROWTH HORMONE AND PROLACTIN SECRETION TO THE SOMATOSTATIN ANALOGUE SMS 201–995 IN PATIENTS WITH PROLACTINOMAS AND ACROMEGALY
Authors: LAMBERTS S. W. J. , ZWEENS M. , KLIJN J. G. M. , VAN VROONHOVEN C. C. J. , STEFANKO S. Z. , DEL POZO E. 
Published: March 2008

SUMMARYThe somatostatin analogue SMS 201–995 has recently been shown to be effective in suppressing GH secretion in most acromegalic patients. In the present study it was investigated whether PRL release in prolactinoma and acromegalic patients might also be sensitive to SMS 201–995 and whether co‐secretion of PRL in acromegaly plays a role in determining the sensitivity of GH secretion to SMS 201–995. The S.C. administration of 50 μg SMS 201–995 did not affect high plasma PRL levels in four microprolactinoma patients. Therapy of one of these patients for 3 d with 50 μg three times a day also did not affect PRL levels. The single administration of 50 μg SMS 201–995 in 22 acromegalic patients lowered plasma GH levels for 2–6 h to less than 5 μg/l in 14 patients and to less than 50% of control values in 16 patients. In 18 of these 22 patients the immunohistochemical picture of the pituitary tumour was known. Eleven patients had pure GH‐containing tumours and in seven patients there were mixed GH/PRL‐containing tumours. In two of these latter patients there was evidence for GH and PRL being secreted by the same tumour cells. The sensitivity of GH secretion to SMS 201–995 did not differ between the patients with pure GH or mixed GH/PRL‐containing adenomas. Plasma PRL levels were not affected by SMS 201–995 in the patients with pure GH‐secreting tumours, but were significantly suppressed in four of the seven patients with mixed GH/PRL containing tumours. Chronic treatment for 16 weeks of one patient with a mixed GH/PRL‐containing tumour with SMS 201–995 (100 μg three times a day) resulted in normalization of both the increased GH and PRL levels. It is concluded that SMS 201–995 does not affect tumorous PRL secretion in patients with pure prolactinomas. In acromegalic patients with mixed GH/PRL‐containing tumours PRL secretion in some patients is sensitive to SMS 201–995, making these patients good candidates for chronic treatment with the analogue. The simultaneous presence of PRL in the GH‐secreting pituitary tumour or the presence of hyperprolactinaemia in acromegalics does not play a role in the sensitivity of GH secretion to the somatostatin analogue.
TALL STATURE: A CLINICAL, ENDOCRINOLOGICAL AND RADIOLOGICAL STUDY
Authors: HINDMARSH P. C. , STANHOPE R. , KENDALL B.E. , BROOK C. G. D. 
Published: March 2008

SUMMARYWe have studied GH secretory dynamics in 38 (25 F, 13 M) children referred for investigation and treatment of tall stature (Height SD score (SDS)< 1·8). Five children had elevated basal GH levels (mean 20·4 mU/l) and a further four had abnormal GH responses to exogenous TRH. Two other children had paradoxical GH responses to oral glucose loading. Although one of these was receiving high dose testosterone to limit final height. All these children were pubertal and did not show concordance between peak GH concentration observed after insulin‐induced hypoglycaemia and during stage IV sleep. Twenty‐four hour GH profiles revealed increased GH pulse amplitude and area under the pulse during puberty. Morning GH secretion was also regularly observed and it is possible that the paradoxical responses seen by us and reported by others reflect this increased physiological secretion. Pituitary radiology revealed morphological abnormalities suggestive of microadenomata in 17 patients but these were all in late puberty and these changes may be related more to the effects of sex hormones than to somatotroph pathology. ‘Abnormal’ endocrinology and radiology are seen in tall children in puberty and must be interpreted with caution.
A RE‐EVALUATION OF DOPAMINE EXCRETION IN PHAEOCHROMOCYTOMA
Authors: TIPPETT P. A. , McEWAN A. J. , ACKERY D. M. 
Published: March 2008

SUMMARYIn a re‐evaluation of the use of dopamine as a prognostic factor in phaeochromocytoma, a series of 34 patients was imaged with iodine‐131‐meta‐iodobenzyl‐guanidine, a radiopharmaceutical specifically localized in chromaffin tumours. Fourteen patients were found to have malignant disease. Increased dopamine excretion was found in 9 (64%) of these patients, including all four with primary intra‐adrenal tumours, and this was associated with a poor prognosis. Of the five patients in the malignant group with normal dopamine excretion on referral, the disease extent was minimal and in four the primary tumour had been resected. Twenty patients appeared to have benign phaeochromocytoma from the imaging results. Of these, 16 were intra‐adrenal and four were extra‐adrenal. In 19 the dopamine excretion was within the control range but in one it was marginally increased. From these observations it would seem that dopamine excretion may be a useful prognostic factor when combined with imaging to determine the extent of the disease.
THE USE OF AN LHRH AGONIST, BUSERELIN, IN THE LONG‐TERM MANAGEMENT OF PREMENSTRUAL SYNDROMES
Authors: BANCROFT J. , BOYLE H. , And P. WARNER , FRASER H. M. 
Published: March 2008

SUMMARYBuserelin, an LHRH agonist, was given by nasal spray to 20 women with premenstrual syndrome. In 10 women benefits were such that they continued treatment for periods varying from 5 to 15 months. There were significant improvements in mood and physical symptoms, and side‐effects such as hot flushes were mild. The remaining 10 women were all made worse by the spray and stopped it within 2 months. Ovulation was blocked in all women though six showed evidence of ovulation during the first treatment month, and two women later in treatment. Of the long‐term group, six eventually became amenorrhoeic, and four continued to menstruate. There was a significant improvement in symptoms during treatment in the long‐term group. Physical symptoms continued to be worse before any menstrual bleeding. Mood change lost its relationship to menstruation. The adverse effects in the short‐term group were sometimes severe and it is necessary to identify the characteristics of the woman who are likely to show such reactions before recommending this treatment for more general use.
CIRCULATING BRADYKININ‐LIKE IMMUNOREACTIVITY AND THE PENTAGASTRIN‐INDUCED CARCINOID FLUSH
Authors: BALKS H. J. , CONLON J. M. , CREUTZFELDT W. , STÖCKMANN F. 
Published: March 2008

SUMMARYBradykinin and structurally related peptides are potent vasodilators and a role for these kinins in the aetiology of the carcinoid flush has been proposed. Using an antiserum directed against the COOH‐terminal region of bradykinin in radioimmunoassay, the concentrations of bradykinin‐like immunoreactivity in extracts of peripheral blood were compared in patients with carcinoid syndrome (n = 11) and healthy subjects (n = 6). In the fasted state, the concentrations of bradykinin‐like immunoreactivity in the patients (10 ± 5 ng/l) were not significantly different from the concentrations in healthy subjects (6 ± 3 ng/l). An intravenous injection of pentagastrin (0.6 μg/kg) provoked a flush of differing degrees of severity in all patients. In four patients, the flush was concurrent with large rises (277‐, 26‐, 11‐ and 10‐fold over mean basal values) in bradykinin‐like immunoreactivity that was resolved by high performance liquid chromatography into lysyl‐bradykinin and bradykinin (approximate ratio 1:2). In two patients, small rises in immunoreactivity (2.4‐ and 1.7‐fold) occurred after the flush and in the remaining five patients no rise in bradykinin‐like immunoreactivity was measured. In the healthy subjects, the pentagastrin injection did not provoke a flush and no rises in bradykinin‐like immunoreactivity were observed. The data support earlier results obtained using bioassays that the carcinoid flush in some patients is associated with the appearance in blood of bradykinin‐related peptides. It has been shown, however, that these kinins cannot be the sole causative agent of the flush. It is suggested, therefore, that the aetiology of the flush is probably multi‐factorial.
DEXAMETHASONE‐SUPPRESSIBLEHYPERALDOSTERONISM: STUDIES ON OVERPRODUCTION OF 18‐HYDROXYCORTISOL IN THREE AFFECTED FAMILY MEMBERS
Authors: DAVIS J. R. E. , BURT D. , CORRIE J. E. T. , EDWARDS C. R. W. , SHEPPARD M. C. 
Published: March 2008

SUMMARYWe report a newly diagnosed family in which a father and his two sons were found to be hypertensive and to have the rare familial condition dexametha‐sone‐suppressible hyperaldosteronism (DSH). All three patients became normotensive on dexamethasone treatment alone and have been successfully maintained on low doses of the drug for 6 months since diagnosis. Each of the patients had extremely high plasma and urinary concentrations of the recently discovered steroid 18‐hydroxycortisol, which were more than ten times higher than the upper normal limit. Plasma levels were readily suppressed by dexamethasone treatment. The hypothesis that 18‐hydroxycortisol might derive from 18‐hydroxylation of recirculating Cortisol was tested by measuring plasma 18‐hydroxycortisol levels during low‐dose and high‐dose hydrocortisone infusions, in a normal subject and in one of the patients with DSH. During the high‐dose infusions (with plasma Cortisol levels of 3000‐5000 nmol/1) there was net production of 18‐hydroxycortisol within 8 h, but this was not observed during the low‐dose infusions (plasma Cortisol levels 300‐400 nmol/1). The origin of 18‐hydroxycortisol remains uncertain: these findings do not support the recirculation theory, but lend weight to the alternative hypothesis that 18‐hydroxycortisol is produced in transitional adrenocortical tissue. This steroid is of considerable value in the differential diagnosis of primary hyperaldosteronism and may also be important as a marker of transitional adrenal cell function.
THE COMBINED USE OF SODIUM VALPROATE AND METYRAPONE IN THE TREATMENT OF CUSHING'S SYNDROME
Authors: NUSSEY S. S. , PRICE P. , JENKINS J. S. , ALTAHER A. R. H. , GILLHAM B. , JONES M. T. 
Published: March 2008

SUMMARYWe have investigated the combined use of metyrapone and sodium valproate in the treatment of five cases of dexamethasone‐suppressible Cushing's disease and one case with dexamethasone non‐suppressible disease. Metyrapone alone reduced 24 h urinary free cortisol (UFC) and plasma cortisol concentrations. Addition of sodium valproate to metyrapone produced a further reduction in these values in five of six patients with a reduction in plasma ACTH in three of five patients who had dexamethasone‐suppressible disease. Plasma 11‐deoxy‐cortisol increased markedly on metyrapone. However, addition of valproate produced a further rise in 11‐deoxycortisoi values in four of five patients including the patient with dexamethasone non‐suppressible disease. The results suggest that valproate may be a useful addition to metyrapone in the medical treatment of some patients with Cushing's syndrome and that it may have an action both at the hypothalamus and peripherally.
EFFECTS OF LUGOL'S SOLUTION ON THYROID FUNCTION IN NORMALS AND PATIENTS WITH UNTREATED THYROTOXICOSIS
Authors: TAN T. T. , MORAT P. , NG M. L. , KHALID B. A. K. 
Published: March 2008

SUMMARYThirty‐eight normal volunteers and 10 patients with untreated thyrotoxicosis were each given 0.5 ml of Lugol's solution daily for 10 days. On days 0, 5, 10, 15 and 20, serum levels of T4, free T4, T3 and TSH (by sensitive immunoradiometric assay) were measured. In normal subjects, the serum concentrations of free T4 declined significantly at day 10 while TSH levels were significantly increased at days 5, 10 and 15. Serum levels of T4 and T3 did not change significantly. All the observed changes took place within the limits of normal ranges for the hormones mentioned. In contrast, in the thyrotoxic subjects, both T4 and T3 were significantly decreased at days 5 and 10, while serum TSH remained below detection limit (0.14 mU/l) throughout the study. Short exposure to excessive iodide in normal subjects affects T4 and T3 release and this effect could be partially overcome by compensatory increase in TSH. In thyrotoxicosis, lack of compensatory increase in TSH results in rapid decreases in T4 and T3 levels. The integrity of the hypothalamo‐pituitary‐thyroidal axis may be effectively assessed by measuring TSH response to iodide suppression, using a highly sensitive immunoradiometric assay.
CIRCULATING SEX HORMONE‐BINDING GLOBULIN AND TESTOSTERONE IN NEWBORNS AND INFANTS
Authors: BOLTON N. J. , TAPANAINEN J. , KOIVISTO M. , VIHKO R. 
Published: March 2008

SUMMARYThe concentrations of sex hormone‐binding globulin (SHBG) and testosterone (T) were measured in the cord blood of full‐term newborns (14 boys, 15 girls) and pre‐term newborns (10 boys, 5 girls), and in the venous circulation of 100 full‐term infants aged 1‐204 days. The ratio of T to SHBG (the‘free androgen index’, FAI) was calculated to reflect the level of unbound T (the free, biologically active fraction). In boys’umbilical cord sera, T concentrations were significantly greater in arterial than in venous sera, while there was no such difference in the concentration of SHBG. Levels of SHBG in cord sera were considerably lower than those seen in the maternal circulation at term, but they were significantly greater in boys’than in girls’cord sera. Levels of T, and the FAI, were significantly greater in boys’arterial cord sera than in girls'. In early infancy, SHBG concentrations rose in both sexes, the highest values being seen in girls. In infant girls, levels of T and the FAI were constantly low. In infant boys, the expected peak in serum T concentrations was observed at 1‐3 months the values approaching those seen in men. In contrast, values of the FAI at this age were relatively low, similar to those seen in women. This suggests that the elevation of male serum T during the first months of life lacks biological significance. However, it is important to realise that the FAI in male infants is about one order of magnitude larger than that in female infants at this time.
THE BIOACTIVITY OF IMMUNOREACTIVE ADRENOCORTICOTROPHIN IN HUMAN BLOOD IS DEPENDENT ON THE SECRETORY STATE OF THE PITUITARY GLAND
Authors: GOVERDE HENNY J. M. , PESMAN GERARD J. , SMALS ANTHONY G. H. 
Published: March 2008

SUMMARYA highly sensitive bioassay, using preincubated purified isolated rat adrenal cells, has been developed for measuring plasma ACTH. This bioassay enables detection of ACTH in plasma of about 0.9 pmol/1. Bioactive ACTH (B‐ACTH) plasma levels were determined during insulin‐induced hypoglycaemia in 12 female subjects and the values were compared with immunoreactive ACTH (I‐ACTH) levels. The mean (|Mp SD) basal B‐ACTH level amounted to 1·7 ± 0·8 pmol/1, the mean I‐ACTH to 2·9 ± 1·4 pmol/1. The highest mean B‐ACTH plasma value was found 30 min after insulin injection: 14·7 ± 15·7 pmol/1 (I‐ACTH: 12·8 ± 9·9 pmol/1). By 90 min the B‐ACTH level had returned to baseline (1·6 ± 0·8 pmol/1), whereas the I‐ACTH level was still significantly higher (5·4 ± 2·7 pmol/1) than at time zero. Remarkably, the B‐ACTH to I‐ACTH ratio (B/I ratio) showed a biphasic profile during the insulin tolerance test, the ratio increasing from 0·60 ± 0·77 at time zero to 1·08 ± 0·35 at the ACTH peak, and decreasing after that to a lower value of 0·33 ± 0·11 at 90 min.From these results it is concluded: (1) in the morning hours a considerable amount of circulating I‐ACTH has no steroidogenic activity; (2) the B/I ratio temporarily increases immediately after insulin injection but gradually decreases afterwards to values half the baseline level at 90 min. Whereas this decrease at 90 min can be explained by differences in disappearance rates, the increase of B‐ACTH relative to I‐ACTH at 30 min indicates that estimations of immunoreactive ACTH reflect the biological activity of newly released ACTH with greater precision than at steady state level. Thus, the B/I‐ACTH ratio can be used as a tool for measuring the state of the pituitary releasing activity.
BASAL AND SALINE‐STIMULATED LEVELS OF PLASMA ATRIAL NATRIURETIC FACTOR IN ACROMEGALY
Authors: McKNIGHT JOHN A. , McCANCE DAVID R. , HADDEN DAVID R. , KENNEDY LAURENCE , ROBERTS GERALDINE , SHERIDAN BRIAN , ATKINSON A. BREW 
Published: March 2008

SUMMARYWe have studied plasma ANF before and after a 4‐h intravenous infusion of normal saline in eight subjects with active acromegaly and in eight age and sex‐matched control subjects. Plasma ANF, serum aldosterone and blood pressure were measured basally and after 2 and 4 h and plasma renin activity basally and after 4 h. Basal plasma ANF was similar in each group (4.4 |Mp 1.5 pmol/1 (mean |Mp SEM) in acromegalic subjects and 5.3 ± 0.7 pmol/1 in controls NS). Plasma ANF did not rise significantly after saline in the acromegalic group (2‐h value, 5.9 ± 0.9; 4‐h value, 5.1 ± 0.9 pmo1/1) but did rise significantly in the control group (2‐h value, 8.9 ± 1.9; 4‐h value 9.5 ± 1.3 pmo1/1, both values P < 0.05 vs basal level). The 4‐h ANF value was significantly higher in the control group than in the acromegalic group (P < 0.05). Basal and stimulated serum aldosterone values were similar in the two groups. Plasma renin activity suppressed to a lesser extent in the acromegalic group after 4 h. The facts that basal plasma ANF was not raised in acromegalic subjects and did not respond to saline stimulation demonstrate that an abnormality of ANF control may be an important factor in the aetiology of the expanded sodium status of patients with acromegaly and hence may contribute to the hypertension seen in patients with growth hormone excess.
HORMONAL RESPONSE TO BLOOD VOLUME EXPANSION IN DIABETIC SUBJECTS WITH AND WITHOUT AUTONOMIC NEUROPATHY
Authors: O'HARE J. P. , ANDERSON J. V. , MILLAR N. D. , DALTON N. , TYMMS D. J. , BLOOM S. R. , CORRALL R. J. M. 
Published: March 2008

SUMMARYThe hormonal and renal response to volume expansion, produced by water immersion for 4 h, was studied in 14 insulin‐dependent diabetic subjects (seven without complications, seven with autonomic neuropathy) and in 14 age‐and‐sex‐matched normal control subjects. The diabetic subjects showed an impaired natriuretic response to volume expansion (total amount of sodium excreted 21 mmol compared to 39 mmol in normals, P > 0.01) but the response did not differ in those with and without autonomic neuropathy. There was no significant difference in the suppression of plasma renin or aldosterone during immersion in either group. Plasma catecholamines suppressed on immersion in all groups. Basal values were lowest in the group with autonomic involvement. Atrial natriuretic peptide levels showed a twofold rise (from 4.8 to 9.6 pmol/l, P > 0.01) on immersion. There was no significant difference in the levels of this hormone between diabetic patients and normal subjects or between those diabetics with and those without autonomic neuropathy. The present study confirms that diabetic subjects retain sodium avidly during volume expansion. This enhancement cannot be ascribed to any measurable difference in the levels of circulating hormones known to be involved in natriuresis and is not influenced by the presence of autonomic neuropathy.