bluuebunny/crossref_metadata_2025_split huggingface dataset:
VALUE OF BASAL PLASMA CORTISOL ASSAYS IN THE ASSESSMENT OF PITUITARY‐ADRENAL INSUFFICIENCY
Authors: HÄGG E. , ASPLUND K. , LITHNER F. 
Published: March 2008

SUMMARYA basal plasma Cortisol value taken in a physically unstressed state in 68 patients with or without hypothalamic‐pituitary‐adrenocortical disease was compared with the maximal plasma Cortisol concentration during an insulin tolerance test. There was a strong positive correlation between the values. Basal Cortisol levels above 300 nmol/1 (RIA method) almost excluded ACTH‐cortisol insufficiency and those below 100 nmol/1 strongly suggested dysfunction. A repeated basal Cortisol estimation within a month was especially valuable in categorizing patients with levels between 100 and 200 nmol/1. We suggest that a basal Cortisol measurement may be used as a first laboratory test in patients evaluated for possible hypothalamic‐pituitary‐adrenocortical insufficiency; in many patients, this approach obviates more sophisticated and expensive testing.
DETERMINANTS OF THYROID VOLUME AS MEASURED BY ULTRASONOGRAPHY IN HEALTHY ADULTS IN A NON‐IODINE DEFICIENT AREA
Authors: BERGHOUT A. , WIERSINGA W. M. , SMITS N. J. , TOUBER J. L. 
Published: March 2008

SUMMARYThyroid volume was measured by ultrasonography in 50 healthy adults (25 males, 25 females, age 20‐70 years) living in the non‐iodine deficient area of Amsterdam. Thyroid volume was 10‐7 ± 4–6 ml (mean ± SD, range 2.7‐20.4 ml). No relation was found between thyroid volume and any of the following parameters: plasma TSH, T4, T3, thyroglobulin (Tg), urinary iodine excretion, tobacco and alcohol consumption. Thyroid volume in males (12.7 ± 4.4 ml) was greater than in females (8.7 ± 3.9 ml, p = 0.0014), but no sex difference was observed in the ratio of thyroid volume to body weight (males, 0.16 ± 005 ml/ kg; females 013 ± 0.06 ml/kg; NS). Thyroid volume was positively related to body weight, but not to age. We conclude that the sex difference in thyroid volume is due to the difference in body weight between males and females. Lean body mass is presumably the most important physiological determinant of thyroid size in subjects living in a non‐iodine deficient area.
COMPARISON OF INTESTINAL CALCIUM ABSORPTION AND CIRCULATING 1,25‐DIHYDROXYVITAMIN D LEVELS IN MALIGNANCY‐ASSOCIATED HYPERCALCAEMIA AND PRIMARY HYPERPARATHYROIDISM
Authors: RALSTON S. H. , COWAN R. A. , GARDNER M. D. , FRASER W. D. , MARSHALL E. , BOYLE I. T. 
Published: March 2008

SUMMARYThe relation between circulating 1,25‐dihydroxyvitamin D (l,25(OH)2D) levels and intestinal calcium absorption–as determined by an oral calcium load test–was studied in 16 patients with hypercalcaemia of malignancy (HM) and 16 with hypercalcaemic primary parathyroidism (HPT). In the HPT group serum calcium rose significantly after the oral calcium load and the increment correlated significantly with 1,25(OH)2D levels. While 1,25(OH)2D levels were raised to within the hyperparathyroid range in a number of HM patients, there was no correlation between change in serum calcium and 1,25(OH)2D level in the HM group and serum calcium did not rise significantly after the oral calcium load. HM patients with detectable or raised 1,25(OH)2D levels typically had few, or no, bone metastases in association with squamous lung cancers. A high proportion of these patients exhibited other aspects of hyperparathyroid‐like activity such as increased renal tubular calcium reabsorption, depressed renal tubular phosphate reabsorption and elevated urinary cyclic AMP excretion. Conversely, HM patients with undetectable 1,25(OH)2D levels typically had extensive metastatic bone disease in association with breast carcinoma and were less likely to exhibit other hyperparathyroid‐like features. It is postulated that in the former, the ‘inappropriately’ detectable or raised 1,25(OH)2D levels may have been due to enhanced renal la‐hydroxylase activity stimulated by the parathyroid hormone (PTH)‐like effect of a non‐PTH ectopic humoral mediator. In the latter the suppressed 1,25(OH)2D levels would be the predicted result of a non humorally mediated hypercalcaemia. It is currently unclear why intestinal calcium absorption was depressed in all HM patients when 1,25(OH)2D levels were normal or raised in some cases. It is possible, however, that in HM there is ‘end organ’ resistance to the effects of 1,25(OH)zD due to a generalized malabsorptive process.
IgG SUBCLASS DISTRIBUTION OF THYROID AUTOANTIBODIES: A ‘FINGERPRINT’ OF AN INDIVIDUAL'S RESPONSE TO THYROGLOBULIN AND THYROID MICROSOMAL ANTIGEN
Authors: McLACHLAN S. M. , FELDT‐RASMUSSEN U. , YOUNG E. T. , MIDDLETON S. L. , BLICHERT‐TOFT M. , SIERSBOEK‐NIELSEN K. , DATE J. , CLARK F. , SMITH B. REES 
Published: March 2008

SUMMARYThe IgG subclass distribution of autoantibodies to thyroglobulin and thyroid microsomal antigen was studied in 21 patients with Graves' disease during fluctuations in total IgG class autoantibody levels induced by various forms of therapy. In addition, changes in autoantibody subclass distributions were investigated during the natural course of Hashimoto's disease in seven patients taking thyroxine. The autoantibodies were principally of subclasses IgGl and/or IgG4 in Graves' patients although IgG2 contributed significantly to thyroglobulin antibodies in 5/7 Hashimoto sera. In Graves' disease the distribution of microsomal and thyroglobulin antibodies among the IgG subclasses remained essentially unchanged over periods of 6 months‐2 years whether autoantibody levels decreased during carbimazole therapy or increased transiently following 13lIodine treatment or subtotal thyroidectomy. Similar observations were made for thyroglobulin antibodies in Hashimoto patients studied over 2½‐4 years; furthermore, the IgG subclass distribution of microsomal antibodies was usually different from that of thyroglobulin antibodies in the same patient. These observations suggest that the microsomal and/or thyroglobulin antibody subclass distribution is characteristic for a particular individual and may be regarded as the ‘fingerprint’ of an individual's response to these thyroid autoantigens.
CHOLINERGIC MUSCARINIC RECEPTOR BLOCKADE WITH PIRENZEPINE ABOLISHES SLOW WAVE SLEEP‐RELATED GROWTH HORMONE RELEASE IN YOUNG PATIENTS WITH INSULIN‐DEPENDENT DIABETES MELLITUS
Authors: PAGE M. D. , KOPPESCHAAR H. P. F. , DIEGUEZ C. , GIBBS J. T. , HALL R. , PETERS J. R. , SCANLON M. F. 
Published: March 2008

SUMMARYCholinergic receptor blockade has been shown to abolish GH secretion in a variety of physiological and pharmacological situations in normal subjects. We have investigated the effect of pirenzepine on nocturnal GH secretion in young adult patients with Type I insulin‐dependent diabetes mellitus. Five patients (three male, two female; aged 20‐27 years) were studied in a randomized order on two days separated by at least 1 week. All patients showed episodes of slow wave sleep on each occasion and this was followed by peaks of GH release when placebo alone was administered (range of GH peaks 6–115 mU/1). In contrast, cholinergic muscarinic receptor blockade with pirenzepine (100 mg orally at 2200 and 2400 h) completely abolished nocturnal GH release in each individual without altering the occurrence of slow wave sleep itself. Mean plasma glucose levels at each sampling time between each study did not differ significantly. The ability to abolish nocturnal GH secretion may be important in the field of diabetes, since excess GH secretion is implicated in several acute metabolic and chronic microvascular complications of the disease.
EFFECT OF SMS 201–995, A LONG‐ACTING SOMATOSTATIN ANALOGUE, ON THE SECRETION AND MORPHOLOGY OF A PITUITARY GROWTH HORMONE CELL ADENOMA
Authors: GEORGE S. R. , KOVACS K. , ASA S. L. , HORVATH E. , CROSS E. G. , BURROW G. N. 
Published: March 2008

SUMMARYThe present study reports the effects of SMS 201–995, a long‐acting somatostatin analogue, on blood GH levels, glucose tolerance and tumour morphology in a 36‐year‐old, previously untreated acromegalic woman. Treatment (50 μg s.c, 8‐hourly) resulted in marked suppression of GH concentration and an improvement in glucose tolerance. After 10 d of treatment, the tumour was removed by transsphenoidal surgery and studied by histology, immunohisto‐chemistry, transmission electron microscopy and morphometry. Histologically, the tumour was an acidophilic adenoma which contained immunoreactive GH in many adenoma cells. By electron microscopy, the tumour was composed of densely granulated somatotrophs containing numerous large secretory granules and many lysosomes showing crinophagy. No cell necrosis or vascular impairment were evident. Using morphometry, the tumour was compared with 10 densely granulated somatotroph adenomas, removed from acromegalic patients not treated with somatostatin. The nuclear and cytoplasmic areas of the adenoma subjected to SMS 201–995 treatment were smaller, and the lysosomes occupied more of the cytoplasmic volume than those of controls. The nuclear/ cytoplasmic ratio, cytoplasmic volume densities of endoplasmic reticulum, Golgi apparatus, mitochondria, secretory granules and secretory granule diameters were within the range of control adenomas. In vitro, treated adenoma cells secreted GH and retained responsiveness to both GRH stimulation and somatostatin suppression. The morphologic findings after SMS 201–995 treatment, are consistent with suppression of GH release. There is no evidence that somatostatin has any direct cytotoxic or vasotoxic effects. It appears that SMS 201–995 represents a potent and promising drug in the medical treatment of acromegaly, however, more is needed to elucidate the mechanism of somatostatin suppression and to provide evidence for adenoma shrinkage.
THE EFFECTS OF DITHIOTHREITOL ON THYROID STIMULATION IN VITRO
Authors: GINSBERG J. , RAFTER D. J. , von WESTARP C. , MURRAY P. G. 
Published: March 2008

SUMMARYThere is evidence that the porcine TSH receptor contains essential disulphide bridge(s) which can be disrupted by dithiothreitol (DTT). The aim of the present study was to determine whether exposure of intact thyroid cells to DTT leads to altered thyroid stimulation. TSH‐stimulated iodine organification in cultured porcine thyroid cells was studied following short‐term DTT exposure; a dose‐dependent inhibition was observed with DTT but not oxidized DTT. Cell viability, follicle formation, and total protein synthesis were preserved. A minimum of 30 min incubation with DTT was required for inhibition. However, under identical conditions, DTT had no effect on TSH or forskolin‐stimulated cyclic AMP (cAMP) production. These results suggest that DTT inhibition of organification is mediated by post‐receptor mechanisms likely involving thyroid peroxidase. The effects of DTT on thyroid stimulation in vitro does not appear to involve disruption of the disulphide bridge(s) in the TSH receptor.
EFFECT OF ORAL FRUSEMIDE ON DIAGNOSTIC INDICES OF THYROID FUNCTION
Authors: NEWNHAM H. H. , HAMBLIN P. S. , LONG F. , LIM C‐F. , TOPLISS D. J. , STOCKIGT J. R. 
Published: March 2008

SUMMARYWe studied the acute effect of standard therapeutic doses of oral frusemide on indices of thyroid function in 34 hospital in‐patients with congestive cardiac failure. A transient decrease in total T4, elevation in the T3 resin uptake and consequent increase in the free T4 index (FT4I) were seen 2–5 h after ingestion of frusemide at a chronic morning dosage of 80,120 or 250 mg. The FT4I pre‐ vs post‐frusemide values after 250 mg of drug were 109 ± 12 vs 129 ± 18 (P < 0.05) after 120mg 92 ± 14vs 119 ± 12 (P < 001), and after 80 mg 102 ± 6 vs 112 ± 4 (P < 0.01) (mean ± SEM). Similar increases in apparent free T4 measured by an analogue tracer assay (free T4 RIA sol, Henning, Berlin) were seen after frusemide. In a time course study, the major change in the T3 uptake 120 min after frusemide ingestion correlated with the change in serum frusemide concentration. When frusemide was added to serum in vitro its influence was greatest in methods that involved least dilution of serum. In two of the patients difficulty in clinical assessment of thyroid status was compounded by the effect of oral frusemide on FT41. We conclude that oral frusemide may influence biochemical assessments of thyroid function in patients with congestive cardiac failure. It is necessary to consider the time interval between ingestion of high doses of oral frusemide and blood sampling in evaluating such results.
AN EVALUATION OF ANTI‐INSULIN RADIOIMMUNODETECTION IN PATIENTS WITH SUSPECTED INSULINOMA
Authors: CHAPMAN C. E. , FAIRWEATHER D. S. , KEELING A. A. , CHANDLER S. T. , ANDERSON P. , DYKES P. W. , BRADWELL A. R. 
Published: March 2008

SUMMARYNine patients with suspected insulinoma were scanned with iodine‐131 labelled anti‐insulin. The clinical diagnosis was subsequently confirmed at laparotomy in eight patients, two of whom had liver metastases. The primary insulinoma was accurately localized by anti‐insulin scanning in four patients and these tumours ranged from 1 to 3 cm in diameter. Both computerized axial tomography (CT) scanning and pancreatic angiography had given false negative results in one of these patients. Hepatic metastases were correctly identified in one of two patients. No hepatic false positive reports occurred. Positive scan areas were graded as definite, probable or possible. All four of the pancreatic positive results graded as definite or probable positive were correct. Three false positive results occurred in the region of the pancreatic body, all had been graded as possible. Anti‐insulin scanning failed to detect four subsequently proven insulinomata (3 mm‐2 cm in diameter). Pelvic uptake of anti‐insulin occurred in a patient who was found to have a para‐ovarian tumour. An homogenate of this tumour also reacted with anti‐insulin in a radioimmunoassay. A true negative pancreatic scan was obtained in this patient. We conclude that this technique is insufficiently accurate for routine clinical use.
FACTORS IN THE OUTCOME OF TRANSSPHENOIDAL SURGERY FOR PROLACTINOMA AND NON‐FUNCTIONING PITUITARY TUMOUR, INCLUDING PREOPERATIVE BROMOCRIPTINE THERAPY
Authors: BEVAN J. S. , ADAMS C. B. T. , BURKE C. W. , MORTON K. E. , MOLYNEUX A. J. , MOORE R. A. , ESIRI M. M. 
Published: March 2008

SUMMARYRadical transsphenoidal surgery in 58 patients with large non‐functioning pituitary tumours relieved pressure symptoms and disconnection hyperprolacti‐naemia without loss of pituitary function, and verified the diagnosis. Preoperative bromocriptine did not cause any shrinkage of non‐functioning tumours (n= 8), even up to 48 weeks. Thirty‐two patients not given postoperative radiotherapy are being followed‐up, and although two show minor CT scan evidence of tumour regrowth, for the others the delay in radiotherapy is enabling reproduction where required. In 20 patients with non‐invasive macroprolactinomas radical sugery caused no loss of pituitary function but cured eight, of whom one has relapsed; none of eight invasive prolactinomas was cured by surgery. Pre‐operative bromocriptine caused marked size reduction in seven of seven macroprolactinomas, but if continued beyond 6 weeks induced tumour fibrosis and uneven shrinkage which made surgery dangerous and unproductive. Selective transsphenoidal surgery relieved hyper‐prolactinaemia in 70% of patients with meso‐ (n= 15) or microprolactinoma (n= 24) usually without loss of pituitary function: the relapse rate was 1 per 88 patient years of follow‐up. Invasive prolactinomas, and macroprolactinomas showing uneven shrinkage with a short (up to 4 weeks) course of bromocriptine should have radiotherapy rather than surgery, while the patients most suited to surgery are those with mesoprolactinomas, or some macroprolactinomas with compact intrasellar shrinkage after short‐term bromocriptine. Microprolacti‐nomas generally did not benefit from surgery as compared to conservative therapy. In none of the tumour groups were the surgical findings an accurate predictor of postoperative pituitary function.
LACK OF VEGETATIVE AND ENDOCRINE ORCADIAN RHYTHMS IN FATAL FAMILIAL THALAMIC DEGENERATION
Authors: LUGARESI A. , BARUZZI A. , CACCIARI E. , CORTELLI P. , MEDORI R. , MONTAGNA P. , TINUPER P. , ZUCCONI M. , ROITER I. , LUGARESI E. 
Published: March 2008

SUMMARYA total lack of neuroendocrine and vegetative circadian rhythms was observed in a patient with a familial degeneration of the anterior and dorso‐medial thalamic nuclei. Our findings support the role of the thalamus in regulating the periodicity of endocrine and vegetative functions.
MALIGNANT SOMATOSTATINOMA PRESENTING WITH DIABETIC KETOACIDOSIS
Authors: JACKSON J. A. , RAJU B. U. , FACHNIE J. D. , MELLINGER R. C. , JANAKIRAMAN N. , LLOYD R. V. , VINIK A. I. 
Published: March 2008

SUMMARYHigh circulating levels of somatostatin (SRIF) were detected in a patient with a metastatic tumour after development of diabetic ketoacidosis (DKA). Fasting insulin and C‐peptide levels were markedly suppressed, but plasma glucagon was not suppressed below normal. Progressive cachexia ensued; at autopsy a poorly differentiated non‐small cell neuroendocrine carcinoma metastatic to liver was found. Small gallstones were noted. Electron microscopy of tumour tissue showed neurosecretory granules and tonofilament bundles. Immunohis‐tochemical staining of tumour cells was diffusely positive for carcinoembryonic antigen, bombesin‐like immunoreactivity, and calcitonin with focal immuno‐reactivity for SRIF, serotonin, neuron‐specific enolase, chromogranin, and epithelial membrane antigen. Column chromatography of plasma and tumour extract revealed five or more peaks of material with SRIF‐like immunoreactivity (SRIF‐LI): predominantly SRIF‐28 and intermediates in tumour extract, and SRIF‐14 and an intermediate between SRIF‐28 and SRIF‐14 in plasma. DKA in this case of somatostatinoma syndrome may reflect differential effects of tumour production of larger molecular weight SRIF forms on insulin and glucagon secretion.
REDUCTION OF HUMAN AND RAT TESTICULAR FOLLICLE STIMULATING HORMONE RECEPTORS BY HUMAN MENOPAUSAL GONADOTROPHIN IN VIVO AND IN VITRO
Authors: NAMIKI M. , NAKAMURA M. , OKUYAMA A. , SONODA T. , ITATANI H. , SUGAO H. , SAKURAI T. , NISHIMUNE Y. , MATSUMOTO K. 
Published: March 2008

SUMMARYReduction of human and rat testicular FSH receptors by hMG was studied in vivo and in vitro. After a single injection of hMG, the number of high affinity FSH receptors were significantly reduced for 5 and 3 d in human and rat testes, respectively, without affecting their affinity. FSH receptor numbers recovered to pretreatment values by 14 d after the injection. Radioactivity in rat testes found 48 h after a s.c. injection of 125I‐labelled human FSH was less than 10% of the maximum found 10 h after the injection, showing that the prolonged reduction of FSH receptors after hMG injection was not due to occupancy of the binding sites. Occupied FSH receptors measured in rat testes accounted for about 15% of all receptors on the day after an injection of hMG and for less than 5% after the third day. In experiments in vitro using organ culture techniques, an exposure to hMG for 24 h induced a dose‐related significant loss of the specific FSH binding sites for 7 and 5 d in human and rat testes, respectively. Thereafter, the loss was gradually recovered. These findings suggest that the reduction in FSH receptors in human and rat testes by hMG is mainly due to down‐regulation of the binding sites and that the testicular organ culture method used in the present study is useful to study hormonal regulation of testicular function, especially in human testes.
FAMILIAL HYPOCALCIURIC HYPERCALCAEMIA III: BONE MINERAL METABOLISM
Authors: KRISTIANSEN J. H. , RØDBRO P. , CHRISTIANSEN C. , JOHANSEN J. , JENSEN J. T. 
Published: March 2008

SUMMARYBone mineral metabolism was studied in 10 subjects with familial hypocalciuric hypercalcaemia (FHH) and 10 age‐, sex‐ and surface area matched healthy controls. Bone turnover was estimated by urinary calcium and hydroxyproline excretions relative to creatinine (Ca/Creat and OHPr/Creat, respectively), serum bone Gla‐protein (S‐BGP) and serum alkaline phosphatase (S‐ALP). Bone status was evaluated by measurement of bone mineral content (BMC) on both forearms and X‐ray examinations of the hands. Ca/Creat and OHPr/Creat (indices of bone resorption) were both significantly higher in the FHH group than in the controls. S‐BGP and S‐ALP (indices of bone formation) tended towards a higher level in the FHH subjects, but the differences were not significant. The BMC values were similar in the two study groups and did not change with time. We conclude that these patients with FHH might have a bone turnover higher than normal, and that the increased bone resorption must be paralleled by an increased bone formation.
A COMPARISON BETWEEN THE EFFECTS OF SMS 201–995, BROMOCRIPTINE AND A COMBINATION OF BOTH DRUGS ON HORMONE RELEASE BY THE CULTURED PITUITARY TUMOUR CELLS OF ACROMEGALIC PATIENTS
Authors: LAMBERTS S. W. J. , VERLEUN T. , HOFLAND L. , DEL POZO E. 
Published: March 2008

SUMMARYThe in‐vivo reaction of the plasma GH concentration to the administration of the somatostatin analogue SMS 201‐995, bromocriptine and their combination were compared with the in‐vitro effects of both compounds and their combination on GH release and the GH tumour cell content of 9 acromegalic patients. Exposure of cultured GH‐secreting pituitary tumour cells for 4–96 h to SMS 201‐995 showed a variable, but in all instances during longer incubations statistically significant inhibition of GH release, which paralleled the sensitivity of GH secretion to the drug in vivo. This inhibitory effect on GH release was in two of the eight tumours accompanied by a decrease in the GH tumour cell content after 24‐72 h of culture. These changes either reflect an inhibition of GH synthesis and/or an increase in intracellular breakdown (crinophagy) of GH and might be the basis for the tumour shrinkage which has been observed in about half of the acromegalic patients during long‐term SMS 201‐995 therapy. The inhibitory effects of bromocriptine on GH secretion were antagonized by haloperidol, while the inhibitory effect of SMS 201‐995 was not affected by the dopamine receptor antagonist. This suggests that the effects of SMS 201‐995 and bromocriptine are mediated via separate mechanisms involving different receptors. Additive but no potentiating inhibitory effects of both drugs on GH release were observed in a group of six patients in vivo and in three of six tumours in vitro.