bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gsα and Gi2α mutations in clinically non‐functioning pituitary tumours
Authors: Williamson Elizabeth A. , Daniels Mark , Foster Sally , Kelly William F. , Kendall‐Taylor Pat , Harris Philip E. 
Published: March 2008

SummaryBACKGROUND AND OBJECTIVE Activating mutations of Gsα (gsp) and Gi2α (gip) have been described in various endocrine neoplastic conditions. The objective of this study was to assess the prevalence of gsp and gip mutations in clinically non‐functioning pituitary tumours (NFTs) and to compare the clinical phenotypic characteristics of tumours bearing G protein gene mutations with wild‐type tumours.DESIGN Twenty‐two NFTs and 20 normal anterior pituitary glands screened for G protein gene mutations.PATIENTS Twenty‐two patients; 14 female (median age 59 years, range 19–76) and 8 males (median age 66·5 years, range 50–77).MEASUREMENTS Site‐directed hybridization or direct sequencing of polymerase chain reaction amplified Gsα and Gi2α DNA.RESULTS G protein gene mutations were identified in 3/22 (13%) of NFTs. Two tumours demonstrated gsp mutations, one at codon 201 arginine to cysteine, and the second at codon 227 giutamine to arginine. Three tumours demonstrated gip mutations at codon 205 giutamine to arginine. Two tumours with gsp mutations also harboured gip mutations. All tumours with G protein gene mutations demonstrated local bone infiltration into the surrounding structures.CONCLUSIONS G protein gene mutations have been demonstrated in a proportion of non‐functioning pituitary tumours. The presence of dual gsp and gip mutations in two tumours suggests the possibility of multiple hits in a stepwise pathogenesis of pituitary neoplasia.
Plasma 18‐oxocortisol levels in the patients with adrenocortical disorders
Authors: Yamakita Noriyoshi , Mune Tomoatsu , Morita Hiroyuki , Yasuda Keigo , Miura Kiyoshi , Gomez‐Sanchez Celso E. 
Published: March 2008

OBJECTIVES 18‐Oxocortisol (18oxoF) shares structural characteristics with cortisol and aldosterone and is secreted from the adrenal cortex. It has been reported that 18oxoF has weak gluco and mineralo‐corticoid activities and increases blood pressure when administered to animals. We tried to clarify the characteristics of the production of 18oxoF in patients with adrenocortical disorders compared with the control subjects.DESIGN AND PATIENTS In patients with primary aldosteronism due to aldosterone producing adenoma (APA) (n= 21) and Cushing's disease or syndrome (Cushing's disease n= 13; adrenocortical adenoma n= 10), plasma 18oxoF level early in the morning following an overnight fast was evaluated as well as plasma cortisol and aldosterone levels.RESULTS The plasma 18oxoF levels were significantly higher in the patients with adrenocortical disorders than in control subjects. The ratios of 18oxoF/cortisol and 18oxoF/ aldosterone were high in APA and in Cushing's disease and syndrome patients, respectively. In the control subjects and combined group of patients with Cushing's disease and syndrome, plasma 18oxoF level significantly correlated with plasma cortisol level but not with aldosterone level. However, in APA patients plasma 18oxoF level correlated significantly with both cortisol and aldosterone levels.CONCLUSION The production of 18oxoF was elevated as a result of the hyperactivity of 18‐hydroxylase and excess cortisol production in APA patients and in patients with Cushing's disease and syndrome, respectively. An excess 18oxoF production could be playing a role in the pathogenesis of hypertension in these patients. The correlation of plasma 18oxoF levels with plasma cortisol and aldosterone levels suggests that the production of 18oxoF is more dependent on the supply of cortisol than on 18‐hydroxylase activity in normal subjects and patients with Cushing's disease and syndrome.
Effect of atrial natriuretic factor infusion on basal and CRH‐stimulated ACTH, cortisol and aldosterone levels in patients with Cushing's or Addison's disease
Authors: Ambrosi B. , Sala C. , Bochicchio D. , Colombo P. , Gazzano G. , Fadin C. , Morganti A. , Faglia G. 
Published: March 2008

OBJECTIVES While it has been shown that atrial natriuretic factor (ANF) is able to inhibit CRH‐stimulated ACTH secretion in vitro, in normal men conflicting results on its effect on ACTH/cortisol responses to insulin and CRH have been reported. Since no data are available concerning the possible influence of ANF on the hypothalamic‐pituitary‐adrenal axis in states of ACTH hypersecretion, the effect of ANF on pituitary‐adrenal function in basal conditions and after CRH stimulation has been investigated in patients with Cushing's (n= 4) and Addison's disease (n= 4).DESIGN On two different days all patients underwent the following procedures: (a) α‐human ANF was infused, after a priming dose of 100 ng i.v., at a rate of 0·01 μg/kg/min over 5 hours. After 120 minutes of ANF infusion, oCRH (1 μg/kg) was i.v. injected as a bolus; (b) vehicle infusion was given over 5 hours and at 120 minutes oCRH was injected. Plasma ANF, ACTH, cortisol, aldosterone, renin activity and K+ were measured; heart rate and blood pressure were monitored.RESULTS In Cushing's disease plasma ANF rapidly increased within 30 minutes of the exogenous peptide infusion (from 27 ± 5 to 73 ± 14 pmol/l; mean ± SE), whereas in the vehicle study its concentration was unchanged. During the first 2 hours of both tests no significant modifications in ACTH levels were observed. After CRH the plasma ACTH peak was unchanged. Serum cortisol levels progressively declined during the first 2 hours of ANF infusion (from 778 ± 150 to 461 ± 48 nmol/l; P < 0·05), whereas no changes were observed during vehicle. After CRH serum cortisol rose to similar peaks. Plasma aldosterone levels were significantly reduced during the first 2 hours of ANF infusion (from 81 ± 20 to 35 ± 7 pmol/l P < 0·05), whereas no changes were found during vehicle. A similar aldosterone rise was induced by CRH during either vehicle or ANF. Mean plasma renin activity slightly declined and the changes were similar on both occasions. In Addison's disease ANF levels rose within 30 minutes of the peptide infusion (from 12·1 to 49·8 pmol/l), while they were unchanged during vehicle. A slight decline in ACTH levels in the first 2 hours was observed during either vehicle or ANF infusion. After CRH the plasma ACTH peaks were similar. Mean plasma renin activity was unaffected by vehicle, while ANF caused a decline during the first 2 hours (from 13·4 ± 0·8 to 7·7 ± 0·3 ng/ml/h). In all patients, heart rate, blood pressure and K+ were only slightly affected on both occasions.CONCLUSIONS (1) In patients with corticotrophin hypersecretion ANF does not influence basal and CRH‐stimulated ACTH secretion; (2) in Cushing's disease ANF inhibits cortisol and aldosterone basal secretion; this effect is not mediated by ACTH and is over‐ridden by CRH stimulation.
Seasonal variation in the diagnosis of Graves' disease
Authors: Westphai Sydney A. 
Published: March 2008

SummaryOBJECTIVE Heat intolerance is a well known symptom of Graves' disease. Therefore, it is possible that increased ambient temperature could influence the recognition of Graves' disease by unmasking or enhancing the symptom of heat intolerance. Our aim was to determine if there is a seasonal variation in the diagnosis of Graves' disease.DESIGN A retrospective study. SETTING A county hospital and clinic.PATIENTS Two hundred and seven patients with Graves' disease diagnosed from 1985 to 1992.RESULTS A high correlation was found between the temperature and the number of cases of Graves' disease diagnosed. A larger proportion of patients (68%) was diagnosed during the warmer half of the year, May‐October, than during the cooler half. The peak incidence of the diagnosis occurred in May, when 17–4% of the patients were diagnosed. Although the peak average monthly temperature occurs in July, the month of May corresponds to the time of the year when the temperature is making its largest positive change In the month‐to‐month variation. CONCLUSIONS Seasonal variations in the temperature can affect the incidence of the diagnosis of Graves' disease. The diagnosis is more common during the months of higher temperature.
Short‐term fasting in obesity fails to restore the blunted GH responsiveness to GH‐releasing hormone alone or combined with arginine
Authors: Procopio M. , Maccario M. , Grottoli S. , Oleandri S. E. , Boffano G. M. , Camanni F. , Ghigo E. 
Published: March 2008

SummaryOBJECTIVE Fasting is known to clearly increase both spontaneous and GHRH‐stimulated GH secretion in normal subjects and this effect is likely to be due to hypothalamic mechanism(s). Our aim was to clarify the effect of a 3 or 4‐day fast, on the GH response to GHRH alone or combined with arginine, an amino acid probably acting via inhibition of hypothalamic somatostatin release.DESIGN Two tests with GHRH (1 μg/kg i.v.), administered either alone or in combination with arginine (ARG, 0.5 g/kg i.v.) were performed, in a randomized order at least 3 days apart. In obese women the two tests were repeated after a 3 or 4‐day fast.PATIENTS Seven obese women (06, aged 17–54 years, BMI 42.4 ± 3.6 kg/m2, waist‐hip ratio (WHR) 0.85 ± 0.01) and ten healthy women, as control subjects (CS, aged 20–44 years, BMI 23.1 ± 1.1 kg/m2, WHR 0.79 ± 0.01) were studied.MEASUREMENTS Serum GH and IGF‐I levels were measured by radioimmunoassay. The GH secretory responses were expressed either as absolute values (mU/l) or as areas under the curve (AUC, mU/l/h) calculated by trapezoidal integration. IGF‐I concentrations were expressed as absolute values (μg/l) with reference to a pure recombinant IGF‐I preparation. Results are expressed as mean ± SEM.RESULTS Basal GH and IGF‐l levels in OB were lower than in CS (0.8 ± 0.2 vs 4.8 ± 1.0 mU/I, P< 0.0001 and 120.1 ± 21.4 vs 188.7 ± 13.1 μg/l, P <0.02, respectively). The GHRH‐induced GH rise in OB was lower (P <0.00001) than in CS (AUC 340.2 ± 81.0 vs 2125.0 ± 199.6 mU/l/h). ARG increased the GHRH‐induced GH rise in both groups, but in OB the GH response to ARG + GHRH (1458.4 ± 439.0 mU/l/h, P < 0.03 vs GHRH alone) remained lower (P <0.0001) than in CS (6396.2 ± 772.2 mU/l/h, P < 0.01 vs GHRH alone). In spite of a reduction in body weight and IGF‐I, Insulin and glucose levels, in OB fasting failed to modify both the basal GH levels and the somatotroph responsiveness to GHRH when administered either alone or combined with ARG. An increase in free fatty acids (FFA) was also found after fasting.CONCLUSIONS The results of this study demonstrate that in obesity the somatotroph hyporesponsiveness to GHRH, either alone or combined with arginine, is not improved by short‐term fasting. As fasting is considered a CNS mediated stimulus to GH secretion, its ineffectiveness in obesity does not support a hypothalamic pathogenesis and suggests that long standing metabolic alterations, such as hyperinsulinaemia and/or elevated free fatty acids, could play a major role in causing GH insufficiency in obese patients.
Thyroid cancer and thyroiditis in the goitrous region of Salta, Argentina, before and after iodine prophylaxis
Authors: Ruben Harach H. , Williams E. Dillwyn 
Published: March 2008

SummaryOBJECTIVE The importance of iodine intake and thyroiditis in the pathogenesis of thyroid cancer remains controversial. We have investigated the natural history of thyroid cancer and thyroiditis in a goitrous region before and after iodine prophylaxis over a 31‐year period.DESIGN For the analysis of thyroid cancer the material was divided in two periods. The first 15 years (59 cases), including 5 years before prophylaxis, was compared with the second 16 years (85 cases), a period well after iodine supplementation of salt. Histological diagnosis of the tumours was based on the WHO system. Moderate to severe thyroiditis in the non‐tumoral surrounding thyroid from female patients was recorded. For this, the material was analysed in the two periods In relation to the introduction of iodine prophylaxis in 1963, taking account of the age of the patients.RESULTS Papillary carcinomas formed the largest group of tumours in both periods, with nearly twice as many in the second period as the first, while the numbers of follicular and medullary carcinomas remained about the same. The ratio of papillary to follicular carcinoma rose from 1.7:1 in the first period to 3.1:1 in the second. All three thyroid lymphomas were of the non‐Hodgkin's type, and all occurred in the second period in females aged over 50. A severe lymphoid thyroiditis was present in the two cases with assessable background thyroid tissue.The frequency of lymphoid infiltrate in females rose from 8% 11/12) before 1963 to 25% (18172) after prophylaxis in the whole series. After salt prophylaxis, thyroiditis was more frequent in patients with papillary carcinoma in general (31%), and clinically significant papillary carcinomas in particular (35%), than in those with non‐papillary tumours (6%) (X2, P < 0.05 and P < 0.025, respectively).CONCLUSIONS Our observations indicate that a high dietary intake of iodine may be associated with a high frequency of papillary carcinoma and thyroiditis, and that thyroiditis is more commonly associated with papillary carcinoma than with other thyroid tumours. The occurrence of non‐Hodgkin's lymphomas only in the post‐prophylaxis period may be linked to an increase in thyroiditis.
Melatonin and the pituitary‐thyroid axis status in blind adults: a possible resetting after puberty
Authors: Bellastella A. , Sinisi A. A. , Criscuolo T. , De Bellls A. , Carella C. , Lorio S. , Sinisi A. M. , Parlato F. , Venditto T. , Pisano G. 
Published: March 2008

SummaryOBJECTIVE Increased levels of free thyroid hormones have been previously described in prepubertal blind subjects and have been thought to be a consequence of a partial target organ refractoriness due to the early and prolonged lack of light perception. The aim of this study was to clarify whether this abnormality is permanent or transient and the interrelationships between melatonin and thyroid hormone secretion.MEASUREMENTS Total and free thyroid hormones, TSH, thyroxine‐binding globulin (TBG), reverse trilodothyronine (rT3) and melatonin were measured In plasma samples obtained at 0800 h (two hours after lights‐on) In a group of 11 totally (group 1) and 16 partially (group 2) blind adult patients and in 10 age‐matched healthy subjects.RESULTS Both totally and partially blind patients showed melatonin levels higher than in controls (330 ± 106 pmol/l, group 1 and 361 ± 159 pmol/l, group 2, respectively; controls: 53 ± 12 pmol/l, P < 0.001 vs both groups), but fT4, fT3, T4, T3 TSH, rT3 and TBG concentrations showed no significant differences from controls.CONCLUSIONS A possible resetting of pltuitary‐thyroid axis regulation can occur in blindness after puberty; variations of melatonin secretion could play a role in this. The inhibitory effect of melatonin on thyroid gland function found in animals does not seem to occur in humans. Elevated melatonin levels, both in patients with total blindness and in those with light perception only, suggest that more complex mechanisms other than light signalling are involved in the changes of melatonin secretion in blindness.
Spontaneous follicular and luteal function in infertile women with oligomenorrhoea: role of luteinizing hormone
Authors: Fleming R. , McQueen D. , Yates R. W. S. , Coutts J. R. T. 
Published: March 2008

SummaryOBJECTIVE There is a paucity of longitudinal endocrine studies of infertile patients with oligomenorrhoea. We have assessed the frequency and quality of spontaneous follicular development and Meal function in patients with ollgomenorrhoea and infertility (PCOS), and have related the observed criteria to circulating LH activity.DESIGN Prospective detailed investigations in a cohort of unselected patients.PATIENTS Infertile women with oligomenorrhoea (PCOS, n= 131) presenting to the Infertility clinic at the Royal Infirmary, Glasgow.MEASUREMENTS Patients were monitored with frequent plasma oestradiol (E2) concentration assessments over a minimum period of 3 weeks, starting more than 2 weeks after a menstrual bleed. When follicular maturation was identified the patient provided daily blood samples through to her ensuing menstrual bleed, and E2, progesterone, total testosterone, FSH and LH were assessed in these samples. Luteal phase progesterone profiles were assessed between the days LH surge +2 and LH surge +6 by means of a progesterone Index.RESULTS Forty‐eight per cent of the patients showed evidence of follicular development. The oestradiol profiles in the patients showing follicular growth were normal, but the progesterone curve was sub‐normal in the early luteal phase, due to a high proportion of deficient luteal phases. The mean LH concentrations were elevated in the whole group, but no difference was observed between the mean LH values for those patients showing spontaneous follicular development and those who did not, and the incidence of ovulation was similar In the normal LH and elevated LH groups. Similarly, no relation was established between LH and the quantitative assessment of luteal phase progesterone profiles (progesterone Index), and the distribution of progesterone Indices was similar in the normal LH and elevated LH groups.Testosterone concentrations were positively correlated with LH (p= 0.008) but not with the incidence of spontaneous follicular growth. There was no significant difference in the incidence of spontaneous ovulation between the patients with elevated or normal mean follicular phase testosterone concentrations.CONCLUSION The data indicate that both LH and testosterone secretion in PCOS were closely linked, but that neither was directly linked to the incidence or inhibition of spontaneous follicular development in PCOS, or to the disturbance in luteal phase progesterone profiles.
Osteoporosis in Turner's syndrome and other forms of primary amenorrhoea
Authors: Davies Melanie C. , Gulekli Bulent , Jacobs Howard S. 
Published: March 2008

SummaryOBJECTIVE Osteopenia in Turner's syndrome is well recognized. This study is aimed to elucidate whether this is an intrinsic feature of the disorder, or is a nonspecific feature resulting from oestrogen deficiency.DESIGN Comparison of bone mineral density and fracture rate in Turner's patients and in 46,XX women with equivalent oestrogen deprivation from other causes. SUBJECTS One hundred and twenty women In the reproductive age range (16‐45 years): 40 with Turner's syndrome, 40 with other forms of primary amenorrhoea, and 40 healthy controls matched to patients for duration of oestrogen usage.MEASUREMENTS Measurement of bone mineral density in the lumbar spine (and femoral neck in some subjects) by dual‐energy X‐ray absorptiometry, and reported history of fracture.RESULTS Vertebral bone mineral density was similar In women with Turner's syndrome (mean 0.84, SD 0.11 g/cm2) and those with other causes of primary amenorrhoea (mean 0.81, SD 011 glcm2; P= 026). Both groups had severe osteopenia compared with healthy controls (mean 1‐06, SD 0.09 g/cm2, P < 0.0005, confirmed after correction for height and weight). Fractures had been sustained by 45% (10/22) of Turner's patients for whom information was available, a high frequency compared with controls (P= 0.014); half of these were at ‘osteoporotic’ sites of fracture (wrist, vertebra, femoral neck).CONCLUSION Osteopenia in Turner's syndrome is not an intrinsic feature specific to this disorder, but results from extreme oestrogen deprivation. Early treatment with oestrogen is therefore recommended.
Effect of octreotide on circulating IGF‐I chromatographic profile: evidence for an inhibitory action on the formation of the 150‐kDa ternary complex
Authors: Barreca A. , Carlola G. , Ponzanl P. , Arvigo M. , Foppianl L. , Glordano G. , Minuto F. 
Published: March 2008

SummaryOBJECTIVE The increasing use In clinical practice of octreotide (a somatostatin analogue which inhibits the secretion of GH and other peptide hormones) led us to study the effects of this treatment on GH, Insulin‐like growth factors (IGF)‐I and II and IGF‐binding protein (IGFBP)‐3, as well as on circulating IGFBP complexes in acromegalic patients.DESIGN The circulating concentrations of GH, IGF‐I, IGF‐II and IGFBP‐3 were measured In acromegaiic patients before and after 3, 6, 9, and 12 months of treatment with octreotide (group I: n = 5), and compared with those found In a group of patients (group II) treated with bromocriptine (n= 3), cabergoline (n= 7) radiotherapy (n= 3) or surgical therapy (n= 2). In pools of serum obtained from patients treated with octreotide, dopaminergic drugs, surgery and radiation, before and after therapy, immunoreactive IGF‐I and IGFBP‐3 were also evaluated after Superdex 200 gel filtration in neutral conditions.RESULTS Before treatment, the concentration of IGF‐I and IGFBP‐3 were above the normal range in all patients, while IGF‐II levels were slightly reduced. After treatment with octreotide, IGF‐I (P= 0·004), IGF‐II (P= 0·02) and IGFBP‐3 (P<0·001) were significantly reduced as compared to basal levels. In subjects of group II, only IGF‐I concentration was significantly reduced by the treatment (P= 0.02), and a negative correlation between IGF‐I and IGF‐II concentrations was found (r=−0·58, P < 0·0001). After gel filtration immunoreactive IGF‐I and IGFBP‐3 were found in the 150‐kDa mol.wt. region in serum obtained from untreated patients and from treated patients of group II, while in the serum of octreotide‐treated patients the IGF‐I and IGFBP‐3 peaks were shifted to the 60‐kDa mol.wt. region, thus suggesting that the acid‐lablle subunit of the 150‐kDa complex was drastically reduced. Since the GH concentrations in groups I and II were similar (M ± SEM; 13·8 ± 7·4 and 21·2±10·6mu/l respectively), the marked reduction in acid‐labile submit in the octreotide treated patients can be explained by a direct Inhibitory effect of somatostatin on the subunit.CONCLUSIONS Octreotide exerts an Inhibitory effect not only on IGF‐I but also on IGF‐II. The reduced formation of the 150‐kDa complex probably causes an increased metabolic clearance rate of IGF peptides which can account for the reduced concentration of both IGFs after treatment with octreotide.
The IGF‐I receptor sub‐membrane domain is intact in GH‐secreting pituitary tumours
Authors: Greenman Yona , Prager Dlane , Melmed Shlomo 
Published: March 2008

SummaryBACKGROUND AND OBJECTIVE Clinical acromegaly is Characterized by dysregulation of somatotroph GH secretion In the presence of high circulating serum IGF‐I levels. Physiologically, IGF‐I exerts a negative feedback on GH secretion at both the hypothalamic and the pituitary levels. We have previously shown that the 943 and 950 tyrosine residues In the IGF‐I receptor β‐subunit are required for ligand signalling to the GH gene, as substitution of these residues abrogates IGF‐I signal transduction. To determine whether a mutation within the IGF‐I receptor sub‐membrane domain may be Involved In the pathogenesis of GH secreting tumours, we studied this region In these tumours.DESIGN Exon 15 of the IGF‐I receptor containing both the 943 and 950 tyrosines was analysed In 19 GH‐secreting tumours by single‐strand conformation polymorphism (SSCP) analysis of polymerase chain reaction (PCR) products. Tumour DNA and patients’lymphocyte DNA, which served as normal controls, were analysed.RESULTS All samples exhibited normal migration patterns In the SSCP analysis which was further confirmed by direct DNA sequencing.CONCLUSIONS We conclude that mutations In the IGF‐I receptor sub‐membrane domain which disrupt the negative feedback loop are not Involved In the pathogenesis of acromegaly.