bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of vasopressin cell antibodies in some patients with autoimmune endocrine diseases without overt diabetes insipidus
Authors: De Bellis A. , Bizzarro A. , Paglionico V. Amoresano , Di Martino S. , Criscuolo T. , Sinisi A. A. , Lombardi G. , Bellastella A. 
Published: March 2008

SummaryOBJECTIVE Cytoplasmic autoantibodies to vasopressin cells (AVP) have been detected in patients with idiopathic central diabetes insipidus and only in one patient with endocrine autoimmune diseases without clinical diabetes insipidus. The aim of this study was to look for AVP cell antibodies (AVP‐cell‐Ab) in human sera of a large population of autoimmune endocrine disease patients without diabetes insipidus and to test whether an occurrence of these antibodies in some patients can be associated with partial impairment of posterior pituitary function.MEASUREMENT Sera from 410 patients (310 females, 100 males, age range 10–46 years) with autoimmune endocrine disorders (260 with thyroid autoimmune disease, and 150 with insulin dependent diabetes mellitus) without clinical diabetes insipidus, and from 100 normal subjects, were investigated for hypothalamic autoantibodies by an indirect immunofluorescence method. Positive sera were subsequently tested with specific rabbit anti AVP serum. RESULTS None of controls, but five out of 410 patients (1–2%) were AVP‐cell‐Ab positive. All positive and nine negative from the 410 screened patients were tested for posterior pituitary function. Two out of five AVP‐cell‐Ab positive patients showed partial diabetes Insipidus.CONCLUSION AVP cell antibodies can be shown in some patients with endocrine autoimmune disease without diabetes insipidus and can sometimes be associated with findings of partial posterior pituitary dysfunction. This suggests that clinical diabetes insipidus could be preceded by a long subclinical period characterized only by the occurrence of AVP‐cell‐Ab in the sera associated or followed by alterations in functional tests. Longitudinal studies are needed to confirm this hypothesis.
Double blind randomized study using oral or injectable bromocriptine in patients with hyperprolactinaemia
Authors: Ciccarelli E. , Grottoli S. , Miola C. , Avataneo T. , Lancranjan I. , Camanni F. 
Published: March 2008

SummaryOBJECTIVE A new long‐acting injectable form of bromocriptine has become available for long‐term treatment of hyperprolactinaemic patients. The objective of this study was to compare efficacy and tolerability of injectable and oral forms of bromocriptine.DESIGN A double‐blind randomized study. All patients received either one injection of bromocriptine 50 mg intramuscularly and placebo tablets for 28 days (Group A) or one placebo injection and oral bromocriptine 7 5 mg daily for 28 days (Group B).PATIENTS Twenty‐three (12 patients for Group A and 11 patients for Group B) hyperprolactinaemia patients with (19 patients) or without (4 patients) CT/MRI evidence of tumour were studied.MEASUREMENTS Plasma PRL levels and serum bromocriptine levels were assessed during a follow‐up of 42 days. MRI and/or CT were evaluated before and 28 days after the beginning of the study.RESULTS All patients had significant reductions of PRL levels from 1000 h and 1100 h of day 1 to 2000 h of day 35. Normoprolactinaemia was shown in eight patients of Group A and six of Group B on days 1‐28. Normal PRL levels were still present in five patients of Group A and in one patient of Group B on day 35; only three patients of Group A had normoprolactinaemia on day 42. A significantly greater decrease in Group A in comparison with Group B was shown at 1200 h on day 1 and at all times as a percentage decrease from basal levels. Significantly higher levels of bromocriptine were shown in Group A at all timepoints studied. No difference was shown in tolerability and incidence of side‐effects.CONCLUSION Our data show that injectable bromocriptine more frequently induced a prolonged normoprolactinaemia than did the oral drug. Moreover, bromocriptine levels released during injectable bromocriptine were significantly higher than during oral bromocriptine. On the other hand no difference was shown in the tolerability of bromocriptine according to the route of administration.
ACTH precursors characterize the ectopic ACTH syndrome
Authors: Stewar P. M. , Gibson S. , Crosby S. R. , Pennt R. , Holder R. , Ferry D. , Thatcher N. , Phillips P. , London D. R. , White A. 
Published: March 2008

SummaryOBJECTIVE ACTH is secreted by the pituitary following processing of larger molecular weight precursors, proopiomelanocortin and pro‐ACTH. Ectopic ACTH syndrome refers to the secretion of ACTH by non‐pituitary tumours, but the predominant circulating form of proopiomelano‐cortin‐related peptides remains unclear.PATIENTS Fifteen patients with ectopic ACTH syndrome were compared to 20 patients with pituitary‐dependent Cushing's syndrome, 22 patients with small cell lung carcinoma but no evidence of Cushing's syndrome, and 25 controls.DESIGN AND MEASUREMENTS Measurement of plasma ACTH and ACTH precursors using specific monoclonal‐based immunoradiometric assays at 0900 h and, in five patients with ectopic ACTH syndrome, at 15‐minute intervals for 6‐24 hours.RESULTS ACTH precursors were grossly elevated in patients with ectopic ACTH syndrome (median 2194, range 139‐18000 pmoI/I) compared to patients with Cushing's disease (median 33, 8‐73 pmoI/I, P<0 001), patients with small cell lung carcinomas (38, 8‐117 pmoI/I, P<0 001) and controls (26, 10‐39 pmoI/I, P<0 001). ACTH levels were also elevated in ectopic ACTH syndrome (0900 h median 34, 11‐152 pmol/l) compared to patients with Cushing's disease (0900 h median 8, 3‐19 pmol/l), but not to the same degree as ACTH precursors. In contrast with Cushing's disease, ACTH was secreted in a non‐pulsatile fashion. ACTH precursors but not ACTH itself correlated wtih plasma Cortisol in patients with ectopic ACTH syndrome (r= 0‐65, P<005). Chromatographic analysis of plasma from a patient with ectopic ACTH syndrome confirmed ACTH precursors and not ACTH to be the predominant circulating form. With the cross‐reactivity of proopiomelanocortin and pro‐ACTH in the ACTH IRMA of <1 and <10% respectively, ACTH precursors could represent all the ACTH immunoreactivity in patients with ectopic ACTH syndrome.CONCLUSIONS Ectopic ‘ACTH’ is characterized by aberrant processing of proopiomelanocortin and should be more accurately referred to as ‘ectopic ACTH precursor syndrome’.
Gene screening in Japanese families with complete deficiency of thyroxine‐binding globulin demonstrates that a nucleotide deletion at codon 352 may be a race specific mutation
Authors: Takeda K. , Iyota K. , Mori Y. , Tamura Y. , Suehlro T. , Kubo Y. , Refetoff S. , Hashimoto K. 
Published: March 2008

SummaryOBJECTIVE Thyroxine‐binding globulin (TBG) is a serum protein that transports 75% of circulating thyroxine. Eleven naturally occurring mutations in the human TBG gene have been identified, ten of which alter the properties of the molecule. Three of these mutations produce complete deficiency of TBG (TBG‐CD) and four are associated with a second mutation in codon 283 (TBG‐poly) which is polymorphic in some ethnic groups but, when present alone, does not alter the properties of the TBG molecule. In this communication we investigate whether two unrelated Japanese families with TBG‐CD harboured the TBG‐CD J mutation in codon 352 associated with TBG‐CD in families residing in more distant locations of the Japanese Islands. In addition we examined the possible association with TBG‐poly and its incidence in the Japanese population.DESIGN Mutant alleles were identified by amplification of genomic DNAs by the polymerase chain reaction, using altele‐specific oligonucleotide primers.PATIENTS Eight family members and 25 normal subjects.MEASUREMENTS Serum free thyroxine and TBG concentration were measured by a conventional radioimmunoassay and a more sensitive enzyme immunoassay. Genomic DNAs were extracted from white blood cells and specific mutations at codons 352 and 283 were identified by allele‐specific amplification.RESULTS Three males and three females, whose serum TBG levels were decreased, had mutations at codon 352 as hemizygous and heterozygous, respectively. This mutation was not present in the DNA of any of the related or unrelated subjects with normal TBG concentration. The presence of TBG‐poly was demonstrated in only one heterozygous family member and in six out of 30 alleles (20%) in normal unrelated subjects. The frequency of this TBG polymorphism in the Japanese is similar to that of 16% reported in French Canadians.CONCLUSIONS We conclude that TBG‐CDJ might be a prevalent cause of complete deficiency of thyroxine‐binding globulin in the Japanese and that TBG‐poly probably appeared before the divergence of human races.
Morbidity and mortality in Cushing's disease: an epidemiological approach
Authors: Etxabe J. , Vazquez J. A. 
Published: March 2008

SummaryOBJECTIVE Although Cushing's disease is a well documented clinical entity, there is no epidemiological information about it. The present study tries to obtain this information.DESIGN AND PATIENTS Forty‐nine patients affected by Cushing's disease living in Vizcaya (Spain) between 1975 and 1992 were considered for an epidemiological study.RESULTS The prevalence of known cases at the end of 1992 was 39.1 per million inhabitants. The average incidence of newly diagnosed cases was 2 4 cases per million people per year. Cushing's disease was more frequent in women (n= 46) than in men (n= 3), with a ratio of 15:1. Diabetes mellitus and hypertension were observed in 38.7 and 55.1% of patients, respectively. Remission of Cushing's disease was achieved in 36 out of 41 patients (87.5%). In general, the mortality was higher than that expected for the control population (standardized mortality ratio, SMR 3.8, 95% confidence interval, CI 2.5–17.9, P<0.03). Concerning the cause of death, the SMR of vascular disease was 5 (95% CI 3.4–48.6, P< 0.05). Higher age, persistence of hypertension and abnormalities of glucose metabolism after treatment, were independent predictors of mortality (multivariate analyses, P<0.01).CONCLUSIONS Prevalence of Cushing's disease was 39.1 cases/million inhabitants and average incidence was 2.4 cases/million per year. Mortality was elevated, due to vascular disease, associated with higher age, persistence of hypertension and impaired glucose metabolism.
Steroid receptor binding and messenger RNA expression in fibroids from untreated and gonadotrophin‐releasing hormone agonist pretreated women
Authors: Vollenhoven B. J. , Pearce P. , Herington A. C. , Healy D. L. 
Published: March 2008

SummaryOBJECTIVE The hypothesis of this study was that oestrogen may play a role in fibroid growth and that a lack of oestrogen may be the reason for gonadotrophin‐releasing hormone agonist (GnRHa) induced fibroid shrinkage. Therefore our aims were (1) to investigate oestrogen receptor (ER) and progesterone receptor (PR) binding in fibroids and myometrium from untreated women and in fibroids from GnRHa pretreated women, (2) to evaluate the mRNA expression of ER and PR in these tissues, and (3) to examine whether a correlation existed between receptor binding and mRNA expression for ER and PR.DESIGN Cytosolic ER and PR binding was assessed by the dextran‐coated charcoal technique and ER and PR mRNA expression was assessed using Northern blots of total RNA.PATIENTS Fibroid and corresponding myometrial specimens were obtained from 20 women undergoing hysterectomy while fibroid specimens only were obtained from 10 women undergoing myomectomy after at least 3 months pretreatment with GnRHa.RESULTS We found that (1) ER binding was twice and PR binding was three times as great in fibroid as in myometrium and that there was no difference in binding for either receptor between fibroids from untreated and GnRHa pretreated women, (2) ER and PR mRNA abundances were similar in fibroids and myometrium from untreated women and in fibroids from untreated and GnRHa pretreated women, and (3) ER binding and ER mRNA abundance in both groups of fibroids and myometrium were independent of each other, but there was a positive correlation between PR binding and PR mRNA abundance in untreated fibroids and myometrium but not in GnRHa pretreated tumours.CONCLUSIONS We conclude that (1) both oestrogen and progesterone may contribute to fibroid growth because of increased receptor binding in fibroids compared with myometrium and (2) in GnRHa treated women, fibroids may shrink because of a lowered circulating oestradiol level rather than because of a change in steroid receptor binding.
Familial dysalbuminaemic hyperthyroxinaemia and inherited partial TBG deficiency: first report
Authors: Langsteger Werner , Stockigt Jan R. , Docter Roel , Költringer Peter , Lorenz Oskar , Eber Otto 
Published: March 2008

SummaryBACKGROUND Abnormalities of the serum thyroid hormone binding proteins are not uncommon but, when properly asessed, they do not present diagnostic difficulties. In contrast, the presence of two inherited defects of thyroid hormone transport, of the type presented in the family described here, may cause a major problem in diagnosis and has not been described previously.METHODS All conventional thyroid function tests were carried out. In addition, thyroid hormone binding to serum proteins was assessed by agarose gel electrophoresis, and thyroxine binding globulin by immunoassays and by immunodiffusion. The affinity of TBG for thyroxine and its maximal binding capacity were assessed by Scatchard analysis.RESULTS Tests carried out on 22 members of the family revealed familial dysalbuminaemic hyperthyroxinaemia in 10 family subjects. All five living siblings of the propositus had familial dysalbuminaemic hyperthyroxinaemia and two tested transmitted this trait to their children and grandchildren. This was not the case with the propositus. Partial thyroxine binding globulin deficiency only, inherited presumably from the propositus' mother, was found in two family members. Both thyroxine binding globulin deficiency and familial dysalbuminaemic hyperthyroxinaemia were detected in the propositus and in his male nephew, masking the typical laboratory abnormalities associated with each of these defects.CONCLUSIONS Coexistence of two inherited defects of thyroid hormone transport proteins produce atypical thyroid function test abnormalities, which can be misinterpreted as thyroid hormone dysfunction.
Gene deletion causing adrenal hypoplasia congenita and hypogonadotrophic hypogonadism
Authors: Matfin G. , Sheaves R. , Muscatelli F. , Walker A. , Monaco A. , Grant D. , Nwose O. , Wass J. A. H. 
Published: March 2008

SummaryWe report a patient with X‐linked adrenal hypoplasia congenita and hypogonadotrophic hypogonadism in whom there were no clinical or biochemical features of either glycerol kinase deficiency or Duchenne muscular dystrophy. (The adrenal hypoplasia congenita and glycerol kinase loci map in Xp21 distal to Duchenne muscular dystrophy, and proximal to DXS727.) DNA isolated from our patient was analysed by PCR amplification with primers for appropriate loci in the Xp21 region. This analysis revealed the absence of DXS319, which lies near the adrenal hypoplasia congenita deletion critical region, and the presence of DXS727, which is distal to the gene. The absence of glycerol kinase deficiency biochemically and clinically was consistent with the presence of one glycerol kinase exon product from PCR primers P17/P18 which lies within the glycerol kinase gene. The hypogonadotrophic hypogonadism is universally found in X‐linked adrenal hypoplasia congenita and is thought to be pituitary in origin. These findings suggest that a gene locus resulting in hypogonadotrophic hypogonadism is present in the Xp21 region and is an integral part of the adrenal hypoplasia congenita gene or in close relationship to it.
Inhibin as a marker for hydatidiform mole: a comparative study with the determinations of intact human chorionic gonadotrophin and its free β‐subunit
Authors: Badonnel Y. , Barbé F. , Legagneur H. , Poncelet E. , Schweitzer M. 
Published: March 2008

SummaryOBJECTIVE The purpose of the study was to evaluate plasma inhibin as a marker of hydatidiform mole and to compare the results with intact human chorionic gonadotrophin (hCG) and its free β‐subunit.DESIGN Serial determinations of the plasma concentrations of inhibin, intact human chorionic gonadotrophin and its free β‐subunit in cases of hydatidiform mole over an average period of 140 days.PATIENTS Five cases of hydatidiform mole, including patients with spontaneous remission after evacuation or persistent trophoblastic disease.MEASUREMENTS Immunoreactive Inhibin, hCG and free hCG β‐subunit were measured using standard enzyme immunoassays.RESULTS inhibin and free hCG β‐subunit levels were greater than in normal pregnant women at the same gestational age. Only intact hCG could detect the persistence of trophoblastic tissue.CONCLUSIONS Our data suggest that inhibin, intact human chorionic gonadotrophin and free β‐subunit might be useful as diagnostic markers of molar pregnancies. However, the original method of intact hCG determination Is still superior for follow‐up.
Comparative effects of GH, IGF‐I and insulin on serum sex hormone binding globulin
Authors: Gafny M. , Silbergeld A. , Kilnger B. , Wasserman M. , Laron Z. 
Published: March 2008

SummaryOBJECTIVE The serum level of sex hormone binding globulin (SHBG) changes inversely with that of both insulin and Insulin‐like growth factor (IGF‐I), during several nutritional conditions, as well as In response to GH treatment. However, with exogenous IGF‐I administration, endogenous IGF‐I increases, while insulin decreases. In order to study the separate roles of these hormones in controlling SHBG metaboilsm, we compared SHBG levels in patients treated with IGF‐I and GH.DESIGN AND PATIENTS Serum levels of IGF‐I, Insulin and SHBG were measured before and during the treatment of patients with IGF‐I or GH. Blood samples were drawn in the fasting state, prior to and during therapy, 24 hours after drug administration.Sixteen children and adults with Laron syndrome (LS) received daily s.c. injections of IGF‐I (120–150μg/kg) for up to 5 months. Three adults with isolated GH deficiency (IGHD) received daily s.c. Injections of GH (0·03–0·06 U/kg) for 16 months. Two groups of nine prepubertal children with constitutional short stature (CSS) received GH (0·1 U/kg/day) for 3 months.MEASUREMENTS Serum levels of insulin and acid extractable IGF‐I were determined by RIA, and that of SHBG by IRMA.RESULTS Basal insulin and SHBG levels were within normal range In the LS, IGHD and CSS patients. IGF‐I levels were low in LS and IGHD patients, and normal In the CSS children. The mean peak response to chronic therapy was as follows: In LS patients, IGF‐I administration decreased insulin levels to 62%, and increased SHBG levels by 64% above basal values. Chronic GH therapy in IGHD caused a marked rise in both IGF‐I levels (473%), and insulin levels (96%), and a gradual decline of SHBG to 75% of the basal concentration. In GH treated CSS patients, serum IGF‐I peaked at 80% and insulin levels at 102% above the respective basal levels, while SHBG decreased to 83% after 5 days of treatment.CONCLUSION The results obtained in Laron syndrome, isolated GH deficiency and constitutional short stature patients treated with IGF‐I or GH, indicate that serum insulin had consistently an inverse relation with the levels of circulating SHBG. No relation was found between IGF‐I and SHBG levels.
Expression patterns of messenger ribonucleic acids encoding prohormone convertases (PC2 and PC3) in human pituitary adenomas
Authors: Hashimoto Kunihiko , Koga Masafumi , Kouhara Haruhiko , Arita Norio , Hayakawa Toru , Kishimoto Tadamitsu , Sato Bunzo 
Published: March 2008

SummaryOBJECTIVE Prohormone convertases (PC2 and PC3) have been reported to play an important role for prohormone processing in rodent pituitaries. However, expression of mRNAs encoding these enzymes has not been characterized In human pituitaries. in addition, altered or Insufficient prohormone processing has been reported in some human pituitary adenomas. Thus, the expression patterns of these mRNAs in non‐tumorous and tumorous human pituitaries should be examined.DESIGN Total RNAs were extracted from non‐tumorous or tumorous human pituitaries to analyse PC2 and PC3 mRNA expression.SAMPLES Five ACTH producing adenomas, 11 GH producing adenomas, one PRL producing adenoma and five non‐functioning adenomas were obtained at surgery. Two non‐tumorous pituitaries were also included in this study.MEASUREMENTS The contents were quantitatively measured by Northern blot analysis using rat PC3 cDNA or human PC2 cDNA as a probe. The method was also developed for the detection of PC2 mRNA by Southern blot analysis of reverse transcriptase‐polymerase chain reaction (RT‐PCR) products.RESULTS PC2 and PC3 mRNAs in non‐tumorous samples were detected by Northern blot analysis whereas their contents in tumorous samples varied from high levels to undetectable. Marked variation of PC3 mRNA levels was observed among GH producing adenomas. ACTH producing adenomas were observed to express PC3 mRNA. Northern blot analysis also revealed that PC2 mRNA levels in ACTH producing adenomas were low except for one sample. PC2 mRNA expression in GH producing adenomas was confirmed by Southern blot analysis of RT‐PCR products. This procedure also confirmed the various levels of PC2 mRNA expression among ACTH producing adenomas.CONCLUSION The expression of PC2 and PC3 mRNA in human pituitaries has been confirmed. However, their expression has been observed to vary quantitatively and not to be restricted to certain types of pituitary cells.