bluuebunny/crossref_metadata_2025_split huggingface dataset:
CYPROTERONE ACETATE, AN ALTERNATIVE GESTAGEN IN POSTMENOPAUSAL OESTROGEN/GESTAGEN THERAPY
Authors: RIIS B. J. , JENSEN J. , CHRISTIANSEN C. 
Published: March 2008

SUMMARYSeventy‐six healthy, early postmenopausal women (aged 45–54 years) were allocated to 2 years of treatment with a cyclic combination of 2 mg oestradiol valerate (21 d) and 1 mg cyproterone acetate (11 d) or placebo. Sixty‐five women (86%) completed the study. In the placebo group the bone mineral content in the forearms (measured by single photon absorptiometry) and the bone mineral content in the lumbar spine and total skeleton (measured by dual photon absorptiometry) decreased significantly and at the same magnitude (P < 0001), whereas all bone mass measurements remained unchanged in the hormone‐treated group. In the hormone‐treated group there was a significant decrease in biochemical estimates of bone turnover (serum alkaline phosphatase, serum phosphate, fasting urinary calcium and hydroxyproline), whereas these values were unchanged in the placebo treated group. We conclude that treatment with a cyclic combination of 2 mg oestradiol valerate and 1 mg cyproterone acetate is effective as prophylaxis of postmenopausal bone loss.
THE PLASMA ARGININE VASOPRESSIN RESPONSE TO INSULIN‐INDUCED HYPOGLYCAEMIA IN CHILDREN WITH SHORT STATURE IS RELATED TO AGE AND THE ONSET OF PUBERTY
Authors: SECKL J. R. , DUNGER D. B. , HUEN K. , LIGHTMAN S. L. 
Published: March 2008

SUMMARYThe plasma arginine vasopressin (AVP) response to insulin‐induced hypoglycaemia was investigated in 27 children with short stature. None had diabetes insipidus. Six patients were excluded from further analysis because of hypothalamo‐pituitary dysfunction. Of the remainder, 14 were prepubertal (Tanner 1) and seven were pubertal (Tanner 2–4). Both groups had similar height velocity retardation. There was a significant rise of AVP of 3.4±1.3 pmol/1 at 30 min in the pubertal group (P < 0.05) but no significant change in prepubertal patients. There was a significant relationship between chronological age and AVP response 30 min after insulin (r= 0.45, P < 0.05) and a closer correlation between bone age and AVP response (r= 0.62, P < 0.01). The data suggest that insulin‐induced hypoglycaemia does not reliably stimulate AVP secretion in children and that this response is related to age and pubertal stage.
EVIDENCE FOR GONADAL DESENSITIZATION AFTER PULSATILE THERAPY IN WOMEN WITH AMENORRHOEA?
Authors: GLASIER A. , BAIRD D. T. , McNEILLY A. S. 
Published: March 2008

SUMMARYSixteen women with primary and secondary amenorrhoea were treated with pulsatile GnRH administered subcutaneously. Ovulation was successfully induced in 6/8 women with hypogonadotrophic hypogonadism; and in 2/2 women with idiopathic hyperprolactinaemia; but in only 3/6 women with amenorrhoea associated with an elevated LH:FSH ratio. Using serial blood sampling, we were unable to demonstrate the establishment of a physiological pattern of gonadotrophin secretion in the presence of an apparently normal menstrual cycle. Nor did we observe a consistent relationship between injection of GnRH and the resultant gonadotrophin response. A reduction or total cessation of both pituitary and gonadal sensitivity to GnRH was observed in four women. Possible reasons for these findings are discussed.
INCOMPLETE MASCULINIZATION DUE TO A DEFICIENCY OF 17β‐HYDROXYSTEROID DEHYDROGENASE: COMPARISON OF PREPUBERTAL AND PERIPUBERTAL SIBLINGS
Authors: WILSON S. C. , HODGINS M. B. , SCOTT J. S. 
Published: March 2008

SUMMARYIncomplete masculinization due to a deficiency of 17β‐hydroxysteroid dehydrogenase (17β‐HSD) was investigated in siblings aged 4 years (Case 1) and 12 years (Case 2). Diagnosis was based on increased ratios of androstenedione (A) to testosterone (T) in blood, and impaired reduction of A to T by 17β‐HSD in vitro in the testes. Impairment was total in Case 2 but partial in Case 1. Case 2 also showed deficient conversion of dehydroepiandrosterone (DHA) to androstenediol and of oestrone to oestradiol by 17β‐HSD which were normal in Case 1. Oxidation of T to A by 17β‐HSD and conversion of 17α‐hydroxyprogesterone to A by 17,20 desmolase were normal in the testes of both siblings. 3β‐HSD conversion of DHA to A was normal in Case 1, but markedly increased in Case 2. In contrast to testicular findings, 17β‐HSD reduction of A to T in genital skin fibroblasts from Case 2 was normal and diagnosis would not have been possible from studies of measurements of this enzyme in skin. The severity of the testicular 17β‐HSD deficiency in the peripubertal compared with the prepubertal sibling suggests either considerable intra‐familial variation in the extent of the enzyme defect or that puberty may aggravate this disorder. The normal reductive action of 17β‐HSD in skin, despite impaired action in testes, suggests involvement of more than one iso‐enzyme.
INTRINSIC PULSATILITY OF ACTH RELEASE FROM THE HUMAN PITUITARY IN VITRO
Authors: GAMBACCIANI M. , LIU J. H. , SWARTZ W. H. , TUEROS V. S. , RASMUSSEN D. D. , YEN S. S. C. 
Published: March 2008

SUMMARYAn in‐vitro perifusion system was used to investigate spontaneous ACTH release from human fetal (21–23 weeks gestation) and adult pituitaries. The pattern of ACTH release from fetal pituitaries (n= 7) exhibited a remarkable pulsatile character with a mean (± SEM) pulse interval of 11.3 ± 0.8 min. The mean pulse amplitude was 49.7 ± 6.3 pg, with a nadir to peak increment of 90.7 ± 10.4%. The mean ACTH release rate was 87.2±13.3 pg/2 min. Addition of the calcium chelator EGTA (4 nM) to the perifusion medium induced a significant (p±0.01) decrease in both ACTH release rate (from 102.0 ± 8.5 to 52.0 ± 9.9 pg/2 min) and ACTH pulse amplitude (from 57.7 ± 2.8 to 31.3 ± 4.6 pg) (n= 3). Administration of either 2 nM corticotrophin releasing factor (CRF) or 56 mM KCl induced 10‐ and 2‐fold increases in ACTH secretion, respectively (n= 2). Quarters of adult human pituitaries (n– 6) also secreted ACTH in a pulsatile fashion, with a pulse interval of 14.8±1.7 min, pulse amplitude of 86.7± 10.0 pg, nadir to peak increment of 84.5 ± 9.8%, and overall release rate of 167.2 ± 8.8 pg/2 min. These studies demonstrate that ACTH release from the isolated human pituitary in vitro is characterized by high frequency/low amplitude pulses, independent of hypothalamic stimulation. Accordingly, this spontaneous calcium‐dependent pulsatile ACTH release apparently reflects the activity of an intrinsic intrapituitary pulse‐generating mechanism.
ROLE OF GONADAL STEROIDS IN THE SEROTONINERGIC CONTROL OF PROLACTIN SECRETION IN MEN
Authors: FORESTA C. , INDINO M. , SCANDELLARI C. 
Published: March 2008

SUMMARYThe physiological regulation of PRL secretion seems to involve the central serotonin system, since plasma PRL levels are enhanced by serotoninergic agonists and serotonin re‐uptake blockers. The aim of this study was to evaluate whether the influence of oestrogens on PRL is mediated by the hypothalamic serotonin system. The PRL response to fenfluramine, a serotonin agonist that releases the amine and inhibits its re‐uptake, was assessed in 10 normal men (aged 18–25 years) and in six castrated men (aged 18–24 years). In both groups, the effect of fenfluramine on PRL secretion was also evaluated on the sixth day after receiving clomiphene citrate, an oestrogen antagonist and partial agonist. In castrated men, fenfluramine administration was also performed on the seventh day after the last dose of testosterone enanthate (200 mg i.m. every 3 weeks for 4 months). Our results demonstrate that in normal men fenfluramine treatment significantly enhances plasma PRL levels, and clomiphene citrate treatment significantly reduces this effect. In castrated men, fenfluramine is also able to enhance PRL secretion but to a lesser extent; after clomiphene citrate treatment the increase of plasma PRL levels induced by fenfluramine rises to the normal range. We therefore suggest that in man oestrogens and aromatizable androgens influence PRL secretion at least in part by involving the activation of the hypothalamic serotonin system.
KINETICS OF INSULIN DISAPPEARANCE FROM PLASMA IN CORTISONE‐TREATED NORMAL SUBJECTS
Authors: ELLEMANN K. , THORSTEINSSON B. , FUGLEBERG S. , FELDT‐RASMUSSEN B. , ANDERSEN O. O. , GRÖNBÆK P. , BINDER C. 
Published: March 2008

SUMMARYThe effect of glucocorticoid excess on insulin disappearance from plasma was examined in eight normal men during cortisone treatment (50 mg orally twice daily for 4 d) and in the absence of any medication (control) in random order. Constant infusion of insulin (1–5 mU/kg/min) was used to achieve different levels of steady state plasma insulin concentrations; normoglycaemia was preserved by a glucose clamp technique. The experimentally determined data were compared using a previously validated model of saturation kinetics. The amount of glucose required to maintain normoglycaemia during the insulin infusions was significantly less in the cortisone study than in the control study, while the parameter estimates for the kinetics of insulin disappearance from plasma were unaffected by cortisone. Thus, insulin action and insulin kinetics in the steady state are dissociated in normal subjects rendered insulin resistant by short‐term cortisone treatment.
FOOD‐INDUCED CORTISOL SECRETION IS MEDIATED BY CENTRAL ALPHA‐1 ADRENOCEPTOR MODULATION OF PITUITARY ACTH SECRETION
Authors: AL‐DAMLUJI S. , IVESON T. , THOMAS J. M. , PENDLEBURY D. J. , REES L. H. , BESSER G. M. 
Published: March 2008

SUMMARYFood ingestion stimulates Cortisol secretion in man, but the mechanism of this effect is unknown. We have investigated the possible role of adrenoceptors in the mediation of this effect. Six normal males were given continuous 3 h i.v. infusions of normal saline, methoxamine (alpha‐1 adrenoceptor agonist) and thymoxamine (alpha‐1 adrenoceptor antagonist). Methoxamine enhanced and thymoxamine attenuated the ACTH and Cortisol responses to a standard meal given 60 min after commencement of the infusion. The drugs had no effect on nutrient absorption. Four patients with recent onset of pituitary ACTH deficiency and normally responsive adrenal glands showed no ACTH or Cortisol rises after the standard meal, demonstrating that postprandial Cortisol secretion is mediated by pituitary rather than gut ACTH. Our previous investigations have demonstrated that alpha‐1 adrenoceptors stimulate pituitary ACTH secretion in man by an action within the blood brain barrier. We therefore conclude that postprandial Cortisol secretion is mediated by central stimulant alpha‐1 adrenoceptors modulating pituitary ACTH secretion.
REMISSION OF HYPOPARATHYROIDISM DURING LACTATION: EVIDENCE FOR A PHYSIOLOGICAL ROLE FOR PROLACTIN IN THE REGULATION OF VITAMIN D METABOLISM
Authors: CUNDY T. , HAINING S. A. , GUILLAND‐CUMMING D. F. , BUTLER J. , KANIS J. A. 
Published: March 2008

SUMMARYWe studied a young woman with surgical hypoparathyroidism who, on her usual maintenance dose of calcitriol, developed hypercalcaemia 9 d postpartum when lactation was established. Serum values of 1,25‐dihydroxyvitamin D3 (1,25(OH)2D3) values were very high (127 pg/ml). The patient remained without exogenous calcitriol treatment for 40 d, during which time serum 1,25(OH)2D3 levels remained within the normal range and serum calcium fell with a half‐time of 27 d. The requirements for calcitriol increased to antepartum levels when lactation had ceased. There was a close negative correlation between requirements for calcitriol and serum PRL values. After weaning, an episode of hypercalcaemia was induced by increasing the dose of calcitriol. On stopping calcitriol the serum 1,25(OH)2D3 fell to low values (4 pg/ml) within 2 d and serum calcium fell with a half‐time of 3 d, necessitating the early reintroduction of calcitriol. We conclude that in hypoparathyroidism exogenous vitamin D requirements fall during lactation because of enhanced endogenous production of 1,25(OH)2D3. The lactation‐associated increase in circulating 1,25(OH)2D3 concentrations thus results from a parathyroid hormone‐independent mechanism, possibly by an effect of PRL on the la‐hydroxylase.
ACID THYROGLOBULIN PROTEASE ACTIVITIES IN HUMAN DISEASED THYROID GLANDS
Authors: YOSHINARI M. , OKAMURA K. , SHIROOZU A. , NAKASHIMA T. , INOUE K. , FUJISHIMA M. 
Published: March 2008

SUMMARYThe lysosomal acid protease is thought to be a main enzyme in hydrolysis of thyroglobulin. The protease activity of lysosome‐rich fractions of various diseased thyroid glands were assayed by the sensitive and reproducible method developed in our laboratory. They included 78 diseased thyroid glands; 37 thyrotoxic goitres, five irradiated thyroids, five Hashimoto's thyroiditis, one granulomatous thyroiditis, six multinodular goitres, 14‘cold’ adenomas, four‘hot’ adenomas with three paranodular tissues, and six carcinomas. Fifteen paranodular tissues of cold and solitary thyroid nodules were served as controls. The protease activities were significantly increased in thyroid tissues of thyrotoxic goitres, Hashimoto's thyroiditis, adenomas and adenocarcinomas. In thyrotoxic goitres, the protease activity correlated well with the mean area size of colloid follicles. The‘hot’ adenomas had higher protease activity than‘cold’ ones. The protease activity of multinodular goitres was nearly normal. Only the irradiated thyroid glands had low protease activities. Therefore the high protease activities in hyperfunctioning goitres seem to reflect hormone secretory activities. On the other hand, cold neoplastic goitres seem to have lysosomal protease activities which are not associated with thyroidal secretory process. The assay of acid protease activity will be useful to understand the pathophysiology of lysosomal system in diseased thyroid glands.
THE DEFINITION OF TRUE RECURRENCE OF PITUITARY‐DEPENDENT CUSHING'S SYNDROME AFTER TRANSSPHENOIDAL OPERATION
Authors: LAMBERTS S. W. J. , KLIJN J. G. M. , de JONG F. H. 
Published: March 2008

SUMMARYTwo patients are described with pituitary‐dependent Cushing's syndrome who had successful transsphenoidal selective removal of basophil microadenomas. After a period of adrenal insufficiency the clinical signs and the Cortisol secretion rate became normal after 12–18 months, together with the return of a normal feedback response to glucocorticoids (dexcamethasone suppression), a normal diurnal rhythm of plasma Cortisol, and a normal response to stress (increase of plasma Cortisol to insulin‐induced hypoglycaemia). However, pituitary‐dependent Cushing's syndrome recurred 38 and 56 months after operation. This was preceded by gradual changes of the results of the dexamethasone tests, disappearance of the diurnal rhythm of Cortisol, and of the responses of plasma Cortisol to hypoglycaemia.‘True recurrence’ should be defined as the return of the clinical and biochemical characteristics of Cushing's syndrome after a successful transsphenoidal operation, with a normal hypothalamic‐pituitary‐adrenal axis as evidenced by a normal response to dexamethasone, a normal diurnal rhythm of Cortisol and a normal increase of plasma Cortisol with insulin‐induced hypoglycaemia.
CLINICAL USEFULNESS OF A HIGHLY SENSITIVE ENZYME‐IMMUNOASSAY OF TSH
Authors: MORI T. , IMURA H. , BITO S. , IKEKUBO K. , INOUE S. , HASHIDA S. , ISHIKAWA E. , OGAWA H. 
Published: March 2008

SUMMARYUsing a recently developed sensitive enzyme immunoassay (EIA) for TSH, serum TSH levels in normal subjects and patients with various thyroid disorders were measured. The minimum detectable concentration was less than 0.005 mU/l. An excellent correlation was observed between TSH values measured by EIA and by sensitive radioimmunoassay (r= 0.932). In 26 normal subjects, serum TSH ranged from 0.30 to 2‐65 mU/l (geometric mean 0.97 raU/l). In 27 untreated hyperthyroid Graves' patients, serum TSH was detected in all but one, ranging from 0.005 to 0.19 mU/l (geometric mean 0.040). These values were proved to be specific for human TSH by absorption, recovery, cross‐reactivity and dilution studies; non‐specific serum effects were also ruled out. In 10 patients with destructive thyroiditis, similar TSH values (0.005‐0.20 mU/l, mean 0.032) were observed. However, no significant correlations between TSH and circulating thyroid hormone levels were observed in these thyrotoxic conditions. Furthermore, 9 untreated Graves' patients did not respond to a single i.v. injection of TRH. In 13 hypothyroid patients with hypothalamopituitary disorders, 10 had basal TSH levels of less than 0.4 mU/l, and TRH tests in five gave peak TSH values of more than 0.8 mU/l, which were associated with significant increases in serum T3. In three patients with Sheehan's syndrome, elevated basal TSH levels were observed. Two of them responded to TRH, but these TSH elevations were not associated with T3 increases. In conclusion, this sensitive EIA could measure TSH levels in most patients with thyrotoxicosis and central hypothyroidism. However, the true significance of these measured values needs to be elucidated by future studies.The conventional radioimmunoassay (RIA) for TSH cannot fully discriminate low TSH levels from those of euthyroid subjects, but recently developed sensitive RIA and immunoradiometric assay (IRMA) have been reported to be able to discriminate between them (Pekary et al., 1975; Smith et al., 1979; Mori et al., 1983; Seth et al., 1984). However, even these assays cannot detect serum TSH in patients with thyrotoxicosis. Detectable amounts of TSH have been observed in the pituitary of hyperthyroid Graves' patients (Kumahara et al., 1967; Mori, 1973). We could expect them, therefore, to secrete some TSH into the circulation, but to detect low TSH levels, it is necessary to apply a very sensitive assay. Cytochemical bioassay of TSH has been reported to be of sufficient sensitivity (Bitensky et al., 1974). However, the assay is not suitable for routine use, and is known to be interfered with by certain non‐specific serum effects (Condliffe & Weintraub, 1979).We have recently reported the development of a highly sensitive enzyme immunoassay (EIA) for TSH which could detect 0.005 mU/l or even less (Inoue et al., 1986). This paper deals with clinical application of the EIA, and discusses the significance of TSH values measured in cases of decreased TSH secretion.
ORBITAL COBALT IRRADIATION COMBINED WITH RETROBULBAR OR SYSTEMIC CORTICOSTEROIDS FOR GRAVES' OPHTHALMOPATHY: A COMPARATIVE STUDY
Authors: MARCOCCI C. , BARTALENA L. , PANICUCCI M. , MARCONCINI C. , CARTEI F. , CAVALLACCI G. , LADDAGA M. , CAMPOBASSO G. , BASCHIERI L. , PINCHERA A. 
Published: March 2008

SUMMARYCombined therapy with systemic corticosteroids and orbital cobalt radiotherapy has been shown to be an effective treatment of severe Graves' ophthalmopathy. The potentially serious side‐effects of large doses of systemic corticosteroids prompted us to evaluate the use of retrobulbar corticosteroids instead of systemic corticosteroids. Forty‐four patients with active Graves' ophthalmopathy were given orbital cobalt irradiation (total dose 2000 rads) and retrobulbar methylprednisolone acetate (14 bilateral injections at 20‐30 d intervals). The degree of ocular involvement and responses to treatment were evaluated by numerical scoring (ophthalmopathy index, OI) and clinical assessment. Excellent or good responses were observed in 11 out of 44 patients (25%), 24 (55%) showed slight responses, and no change was found in 9 patients (20%). The initial OI mean score was 5‐9; the final score was 3‐2, with a change of ‐ 2.7 (P< 0001). Regression or partial improvement was observed in most cases (35/44, 80%) with soft tissue changes, and in all 9 cases with sight loss due to optic neuropathy. Proptosis, corneal lesions and extra‐ocular muscle involvement were less responsive, since regression or partial improvement was observed in 39% (12/31), 50% (8/16) and 31% (13/42), respectively. No major side‐effects were observed. The effects of this type of therapy and those obtained by combined therapy with systemic corticosteroids and orbital radiotherapy were compared in two groups of 30 patients each, randomly assigned to either treatment. The results obtained in the group receiving systemic corticosteroids were more satisfactory both clinically (excellent and good responses being observed in 60% vs 30% of cases) and in terms of changes of the OI (mean decrease 3.5 vs 2.6, P<0.02). In conclusion, the combination of orbital irradiation with retrobulbar corticosteroids may be used in the treatment of severe Graves' ophthalmopathy, but appears to be less effective than orbital irradiation used with systemic corticosteroids. Thus, the use of retrobulbar corticosteroids should be limited to patients with contra‐indications to systemic steroids.
NEW FINDINGS IN APPARENT MINERALOCORTICOID EXCESS
Authors: DIMARTINO‐NARDI J. , STONER E. , MARTIN K. , BALFE J. W. , JOSE P. A. , NEW M. I. 
Published: March 2008

SUMMARYWe report two female siblings (ages 4 and 9 years) and one 8‐year‐old male with the syndrome of apparent mineralocorticoid excess (AME) presenting with low renin hypertension and hypoaldosteronism. The deficiency of 11β‐hydroxysteroid dehydrogenase results in a defect of the peripheral metabolism of Cortisol (F) to cortisone (E). As a result, the serum Cortisol half‐life (T½) is prolonged, ACTH is suppressed, and serum F is normal. The specific diagnosis of the disorder was made by the decreased ratio of the urinary metabolites of E (tetrahydrocortisone, THE) and F (tetrahydrocortisol, THF). Continuous i.v. hydrocortisone administration caused an increase in blood pressure and decrease in serum potassium demonstrating the abnormal mineralocorticoid activity of Cortisol in these patients. Addition of spironolactone resulted in a decrease in blood pressure, rise in serum potassium and a gradual increase in plasma renin activity. These studies suggest that an abnormality in Cortisol action or metabolism results in Cortisol behaving as a potent mineralocorticoid and causing the syndrome of AME.
THE RELATIONSHIPS BETWEEN SERUM T3 INDEX, THYROID VOLUME, AND THYROID STIMULATING, TSH RECEPTOR BINDING AND THYROID GROWTH STIMULATING ANTIBODIES IN UNTREATED GRAVES' DISEASE
Authors: BLIDDAL H. , HEGEDÜS L. , HANSEN J. M. , BECH K. , VAN DER GAAG R. , DREXHAGE H. A. 
Published: March 2008

SUMMARYThis study represents an international double‐blind collaborative study of abnormal immunoglobulin activity in untreated Graves' disease. Laboratories in two countries participated in a comparison of thyrotrophin binding inhibiting (TBII), thyroid stimulating (TSAb), and growth stimulating (TGI) immunoglobulins with clinical data, including ultrasonically measured thyroid size. The correlation between TGI and thyroid volume (n= 25, Rs= 0.54, P < 0‐05) and the fact that 9 of 10 patients with high range TGI values had large goitres establish the relationship between TGI and goitre, confirming that the in‐vitro activity of these antibodies is related to an in‐vivo action. In addition, both TBII and TSAb correlated with serum free T3 indices (TBII: n= 60, Rs= 0.46, P < 0.001, and TSAb: n= 60, Rs= 0.64, P<0001). Moreover, both TBII and TSAb correlated with thyroid volume (TBII: n= 60, Rs= 0.37, P< 0.01, and TSAb: n= 60, Rs= 0.41, P < 0001) suggesting that these antibodies are also important in development of goitre in Graves' disease. Finally, some correlation between the antibodies was observed. TBII correlated with TSAb (n= 60, Rs= 0.47, P < 0.001), and in the 16 patients with positive TGI results, this activity correlated with TBII (Rs= 0.54, P <0.05), but not with TSAb. Also some cases were found with corresponding high range TBII and TGI, while negative for TSAb, suggesting a close relationship between the in‐vitro measurement of TSH binding and TGI.