bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of mild Leydig cell dysfunction following cytotoxic chemotherapy on bone mineral density (BMD) and body composition
Authors: Howell S. J. , Radford J. A. , Adams J. E. , Shalet S. M. 
Published: March 2003

BACKGROUNDOvert testosterone deficiency is associated with a reduction in BMD and alteration in body composition. However, there are few data concerning the impact of mild hypogonadism on these parameters.PATIENTS AND METHODWe have identified a cohort of 36 men aged < 55 years with mild Leydig cell impairment, defined by a raised LH level (LH ≥ 8 IU/l) in the presence of a testosterone level in the lower half of the normal range or frankly subnormal (< 20 nmol/l), following treatment with procarbazine‐containing chemotherapy regimens or high‐dose chemotherapy for haematological malignancy. These men underwent measurements of BMD (measured by dual‐energy X‐ray absorptiometry (DXA), single energy X‐ray absorptiometry (SXA) and quantitative CT (QCT)), body composition (DXA), markers of bone turnover, serum lipids and serum IGF‐1. To allow for changes that may be directly attributable to the underlying disease or its treatment, results were compared with those obtained in 14 men who had received the same chemotherapy for the same diseases but had normal LH and testosterone levels (controls).RESULTSWhen data from all 50 men were considered together there were significant reductions in BMD of the lumbar spine both by DXA (Z = − 0.34, P = 0.01) and QCT (Z = − 1.5, P < 0.0001), at the femoral neck (Z = − 0.52, P < 0.0001) and distal forearm (Z = − 0.21, P = 0.05). Mean femoral neck BMD was significantly lower in patients compared with controls (Z = − 0.68 vs. Z = − 0.11, P = 0.05) and there was a nonsignificant trend towards lower lumbar spine BMD measured by QCT (Z = − 1.64 vs. Z = − 1.10; P = 0.09). In addition, serum testosterone level and testosterone:LH ratio significantly correlated with femoral neck BMD (r = 0.28, P = 0.05 and r = 0.37, P = 0.008, respectively). There were no significant differences in lean body mass, fat mass and percentage fat between the patients and controls. There was, however, a difference in the distribution of body fat with a propensity for the patients to accrue truncal fat, and the serum testosterone level significantly inversely correlated with percentage of truncal fat (r = − 0.29, P = 0.04). There were no significant differences in lipid levels, IGF‐1 levels or markers of bone turnover between the patients and controls.CONCLUSIONSThese data suggest that mild Leydig cell impairment may have significant effects on bone mineral density and may result in subtle body composition changes, although in men who have received cytotoxic chemotherapy, other factors also contribute to the observed osteopenia. Testosterone replacement may be beneficial in some of these men and this requires further evaluation.
Increased prevalence of thyroid autoimmunity in patients successfully treated for Cushing's disease
Authors: Colao Annamaria , Pivonello Rosario , Faggiano Antongiulio , Filippella Mariagiovanna , Ferone Diego , Di Somma Carolina , Cerbone Gaetana , Marzullo Paolo , Fenzi Gianfranco , Lombardi Gaetano 
Published: March 2003

BACKGROUNDCushing's disease is characterized by abnormalities of immune function.OBJECTIVETo evaluate the prevalence of autoimmune thyroid diseases in patients with Cushing's disease (CD), after successful treatment and the possible association between previous nodular goitre or positive thyroid autoantibodies during the active phase of CD and the subsequent development of autoimmune thyroid diseases after cure.SUBJECTS AND METHODSTwenty patients with CD and 40 sex‐ and age‐matched healthy controls were considered for the study. In CD patients, thyroid ultrasonography and measurement of circulating free thyroxine (fT4), free triiodothyronine (fT3), thyroid stimulating hormone (TSH), antithyroglobulin (anti‐Tg) and antithyroperoxidase (anti‐TPO) antibodies were performed at diagnosis and 6 months after disease cure while in controls they were performed only at study entry.RESULTSSerum fT3, and fT4 levels were similar in patients, either during the active phase or after cure of the disease, and controls. Conversely, in the patients, serum TSH levels were significantly lower during active disease (0.4 ± 0.05 mU/l, P = 0.001) and significantly higher after disease cure (4.7 ± 0.1 mU/l, P < 0.001) than in controls (2.3 ± 0.4 mU/l). Four patients (20%) and 11 controls (27.5%) had positive anti‐Tg and/or anti‐TPO titre at study entry, while eight patients (40%) developed positive anti‐Tg and/or anti‐TPO titre after disease cure. The prevalence of positive antithyroid antibodies titre in cured CD patients was significantly higher than that observed in the same patients during the active disease (P = 0.008) and in controls (P = 0.031). A significantly higher prevalence of autoimmune thyroiditis was found in patients cured from CD (35%) than in patients with active CD (0%) (P = 0.016) and in controls (10%) (P = 0.031). A significant association was found between the presence of autoimmune thyroiditis after CD cure and the presence of a previous nodular goitre (P = 0.017) or positive thyroid autoantibodies titre (P = 0.007) during the active phase of the disease.CONCLUSIONPatients successfully treated for Cushing's disease have an increased prevalence of thyroid autoimmunity and autoimmune thyroiditis as compared to a control population. Therefore, patients with hypercortisolism need an accurate evaluation of thyroid function after remission of the disease in order to prevent the eventual onset of subclinical or overt post‐thyroiditis hypothyroidism.
Thyroperoxidase (TPO) immunostaining of the solitary cold thyroid nodule
Authors: Christensen Lise , Blichert‐Toft Mogens , Brandt Mathilde , Lange Martin , Bjerregaard Sneppen Simone , Ravnsbæk Joan , Mollerup Charlotte L. , Strange Lise , Jensen Flemming , Kirkegaard Jørgen , Sand Hansen Hanne , Sørensen Sven Sølvsten , Feldt‐Rasmussen Ulla 
Published: March 2003

OBJECTIVETo evaluate the value of immunostaining using the monoclonal antibody (MoAB47) against thyroperoxidase (TPO) in distinguishing between benign and malignant tumour cells in fine needle aspiration cytology (FNAC) samples obtained from a solitary cold nodule of the thyroid gland for the purpose of strengthening the indication for thyroid surgery.DESIGNA prospective, immunocytochemical study of FNACs taken from patients with solitary cold thyroid nodules who presented to Rigshospitalet, Copenhagen, Denmark, during the period April 1993 to May 1996. The first sample series was taken perioperatively in order to test the utility of the method. In the second part of the study samples were obtained preoperatively by ultrasonic guided aspiration. Tissue sections from the nodules obtained during a subsequent operation served as controls.PATIENTSOne hundred and eighty‐one patients, 150 women and 31 men, were studied. The age range was 14–89 years with a median age of 44 years. Fifty‐seven patients were excluded from the study for various reasons leaving us with a total of 124 nodules from 124 patients for final evaluation.METHODSFNAC cells and corresponding nodular tissue were stained by immunocyto– and immuno‐histochemistry using MoAb47 and by routine staining methods. Samples were considered benign if 80% or more of the epithelial‐looking cells of both the FNACs and the histological tissue sections of the nodule were stained by TPO. Consequently, samples were considered malignant if more than 20% of the epithelial‐looking cells failed to stain for TPO. Routinely stained tissue cells and sections served as diagnostic controls.RESULTSA pattern with negative TPO staining was found in all lesions which, by conventional histological staining, were subsequently proven to be malignant. A universal and reliable, positive TPO staining pattern was found in all subsequently proven benign lesions, with the exception of one out of 26 follicular adenomas. This gave the method a sensitivity of 1.0 (negative TPO staining = malignancy in 27 out of 27) and a specificity of 0.99 (positive TPO staining = benign lesion, in 96 out of 97). Positive and negative predictive values were 0.96 and 1.00 respectively.CONCLUSIONThyroperoxidase immunostaining of fine needle aspirates from solitary, scintigraphically cold nodules of the thyroid gland has proved to be an important and reliable diagnostic tool for distinguishing between benign and malignant nodules. Thus, patients might be spared further surgery if not otherwise indicated.
Low dose (1 μg) ACTH test in the evaluation of adrenal dysfunction in pre‐clinical Addison's disease
Authors: Laureti Stefano , Arvat Emanuela , Candeloro Paola , Di Vito Lidia , Ghigo Ezio , Santeusanio Fausto , Falorni Alberto 
Published: March 2003

OBJECTIVEThe presence of 21‐hydroxylase autoantibodies (21OHAb) is a marker of adrenal autoimmunity and can be used to identify subjects with pre‐clinical Addison's disease. The low‐dose (1 μg) ACTH test (LDT) is more sensitive than the high‐dose (250 μg) test (HDT) for the diagnosis of pituitary adrenal insufficiency, but no information is available on the use of a LDT in subjects with autoimmune adrenalitis and primary adrenal insufficiency. The aim of our study was to evaluate the clinical use of the LDT in the diagnosis of early adrenocortical dysfunction in patients with adrenal autoantibodies.DESIGN AND METHODSFirstly, we evaluated the cortisol responses to both a LDT and a HDT in a group of 12 healthy volunteers. We then performed a LDT in 11 subjects positive for 21OHAb, but without clinical signs of Addison's disease identified by screening 920 patients with one or more organ‐specific autoimmune diseases. In all cases, the LDT was followed by a sequential HDT which was used as a control test of the sensitivity and specificity of the LDT.RESULTSIn healthy subjects, the peak cortisol levels after the LDT were similar to those after the classical HDT. In 21OHAb‐positive subjects, the LDT showed a pathological response in five out of 11 (45%) cases and the diagnostic concordance between the results of the LDT and those of the HDT was 100%. All the five cases with pathological LDT were also positive for adrenal cortex autoantibodies (ACA) and 4/5 had high levels of basal ACTH. One subject with pathological LDT developed clinical Addison's disease 4 months after the test had been performed.CONCLUSIONSOur study demonstrates that the low dose ACTH test has a high diagnostic sensitivity and specificity for primary adrenal insufficiency and suggests that it can accurately identify subjects with pre‐clinical adrenal dysfunction.
Expression of CYP27A, a gene encoding a vitamin D‐25 hydroxylase in human liver and kidney
Authors: Gascon‐Barré Marielle , Demers Christian , Ghrab Olfa , Theodoropoulos Catherine , Lapointe Réal , Jones Glenville , Valiquette Luc , Ménard Daniel 
Published: March 2003

Vitamin D3 (D3) is not active but must be hydroxylated at C‐25 in liver before acquiring its hormonal potential in the kidney. The sterol‐27 hydroxylase (gene symbol: CYP27A) catalyses the oxidation of sterol side chain in bile acid synthesis but the enzyme is also known as a D3−25 hydroxylase.The study examined the expression of the gene encoding CYP27A in adult and fetal human livers and kidneys.Thirty‐nine adults (18 men and 21 women; mean age 58 years in men and 57 years in women) and three normal fetuses gestational age 17–19 weeks were studied.Tissue CYP27A mRNA and serum 25OHD concentrations were measured.Normal specimens: CYP27A transcript was found to be higher in adult than in fetal livers but its expression was similar in adult and fetal kidneys. In fetuses, no difference was observed between CYP27A levels in livers and kidneys. In adult livers CYP27A levels were higher in women than in men. Hepatic CYP27A mRNA and serum 25OHD concentrations were both found to be higher in summer than in winter. Multiple linear regression analyses indicate that the season of the year and the serum 25OHD concentrations (but not 1,25(OH)2D concentrations) are the best predictors of CYP27A mRNA abundance in normal adult livers. In situ hybridization illustrates a clear label in hepatocytes which increases in intensity in the perivenous region of the hepatic acinus. Pathological specimens: In one man with an hepatic carcinoma there was a very large increase in CYP27A (> 1000 fold) compared to the level found in the normal liver. In that patient, serum 25OHD concentrations were found to be high considering the level of CYP27A mRNA in the normal hepatic area suggesting that the neoplastic tissue contributed to the C‐25 hydroxylation of vitamin D. Specimens obtained from two patients suffering from focal hepatic hyperplasia indicate that in one case the level of CYP27A mRNA was twice as high in the pathological than in the normal area while in the other its levels were similar in both areas. No difference in the CYP27A transcript was observed between specimens obtained from normal areas and those obtained form either an hepatic adenoma or from two intrahepatic colonic metastases. CYP27A is present not only in the human adult liver but also in the adult kidney, and in the fetal liver and kidney. Our findings illustrate that CYP27A can be significantly upregulated in certain pathological situations such as in hepatic carcinoma and that the neoplastic tissue could contribute to the circulating concentration of 25OHD.
A luminescent bioassay for thyroid blocking antibodies
Authors: Jordan N. J. , Rinderle C. , Ashfield J. , Morgenthaler N. G. , Lazarus J. , Ludgate M. , Evans C. 
Published: March 2003

Thyroid blocking antibodies (TBAb) have a role in the development of hypothyroidism and in the neonate are responsible for transient hypothyroidism. Specific measurement of TBAb requires a bioassay, but current methods are lengthy and cumbersome. We describe a rapid luciferase‐based method for the detection of TBAb using the lulu* cell line which is suitable for the provision of a clinical serviceChinese hamster ovary (CHO) cells were transfected with human TSH‐R together with G418 resistance and a cAMP responsive luciferase construct. Stable pools of transfected cells were selected and clones identified by limiting dilution. Clone lulu* gave the best response to stimulation by TSH and was used to develop a bioassay for TBAb. The luminescent bioassay conditions have been optimized and validated using 12 serum samples from patients found to be TBAb positive in a bioassay using an established method quantifying cAMP by radioimmunoassay (RIA). The effect of thyroid stimulating antibodies (TSAb) on the calculation of Inhibition Index (InI) using two previously described formulae have been investigated and we have used serum containing both TSAb and TBAb to investigate detection of TBAb in samples containing more than one type of activity. Lulu* displays a dose dependent increase in luciferase expression in response to stimulation with bovine (b) TSH which is more effective in serum free medium than in salt free buffer. TSH stimulated luciferase expression can be inhibited by TBAb in either serum or an immunoglobulin preparation. Using optimized assay conditions, challenging 10% serum against 1 U/l bTSH in culture medium, we have tested 31 euthyroid sera to determine a reference range: InI values >23% were considered positive. Twelve samples previously shown to contain TBAb by an established method quantifying cAMP by RIA were positive by the luciferase‐based assay. Of control sera, 20/20 systemic lupus erythematosus, 13/14 rheumatoid arthritis, 12/12 multinodular goitre were negative.We demonstrated that if more complex formulae are used to calculate InI, false positive TBAb results can be obtained in samples containing only TSAb. Finally, when sera contain both TSAb and TBAb, the net activity of stimulating and blocking antibodies is detected in the bioassay. Where TSAb are also present, analysis of serum may be required at several dilutions to detect TBAb.We describe the production of a new cell line, lulu*, and its use to develop a luminescent bioassay for TBAb suitable for clinical use. Comparing two established methods of calculating TBAb, we found that they do not give identical results. In light of this, the high prevalence reported for TBAb in some studies has to be considered with caution.
Increasing incidence of childhood Graves' disease in Hong Kong: A follow‐up study
Authors: Wong Gary W. K. , Cheng P. S. 
Published: March 2003

OBJECTIVE Childhood Graves' disease has been reported to be rare but preliminary epidemiological data on its incidence appeared to be high in Hong Kong Chinese children. The aim of this study is to determine the incidence of childhood Graves' disease in Hong Kong and to analyse whether there is an increasing trend of the incidence.PATIENTS AND DESIGN We established a registry of childhood Graves' disease at our centre to collect cases from four districts in Hong Kong. The diagnosis of Graves' disease was based on clinical features, diffused enlargement of thyroid gland, raised free thyroxine or triiodothyronine levels, suppressed TSH levels, and the presence of thyroid receptor antibodies. Confirmed cases of Graves' disease who resided in any of the four districts were used to calculate the incidence for the study period between 1989 and 1998.RESULTS One hundred and eighteen Chinese children under 15 years of age had a confirmed diagnosis of Graves' disease during the study period from January 1989 to December 1998. There were 11 boys and 107 girls giving a male to female ratio of 1 : 9·7. The overall incidence rates were 3·2/100 000/year and 6·5/100 000/year for the two periods 1989–93 and 1994–98, respectively. The incidence rates for girls have increased significantly (P < 0·001) from 3·8/100 000/year in 1989 to 14·1/100 000/year in 1998. The current incidence of childhood Graves' disease in our population is about eight times that reported in Danish children.CONCLUSIONS This study confirms the high incidence of childhood Graves' disease in Hong Kong and documents an increasing trend for girls. Further studies are required to reveal possible genetic or environmental factors responsible for such epidemiology in Hong Kong Chinese children.
Double‐blind placebo‐controlled trial of oral dehydroepiandrosterone in patients with advanced HIV disease
Authors: Piketty C. , Jayle D. , Leplege A. , Castiel P. , Ecosse E. , Gonzalez‐Canali G. , Sabatier B. , Boulle N. , Debuire B. , Le Bouc Y. , Baulieu E.‐E. , Kazatchkine M. D. 
Published: March 2003

OBJECTIVE Plasma levels of dehydroepiandrosterone sulphate (DHEA‐S) decrease with the progression of HIV disease. Here, we report on the efficacy and safety of the oral administration of DHEA as replacement therapy, in patients with advanced HIV disease, in a trial that was primarily aimed at assessing quality of life.DESIGN The trial was randomized and double‐blind. Thirty‐two patients were allocated to either DHEA 50 mg per day for 4 months (n = 14) or a matching placebo (n = 18). Clinical data, virological and immunological surrogate markers of HIV infection, plasma levels of DHEA‐S and the Medical Outcomes Study HIV Health Survey (MOS‐HIV) quality of life scale were recorded every month.RESULTS The mean age of the patients was 40 ± 11 years. The mean CD4 cell count at baseline was 32·5 ± 32·4 × 106/l. The mean DHEA‐S plasma level at baseline was 5·23 ± 0·76 µmol/l. No side‐effects related to DHEA occurred during the study. A statistically significant increase in the levels of DHEA‐S was observed in the treated group throughout the study (P < 0·01). A significant improvement in the Mental Health and Health Distress dimension of MOS‐HIV was observed in the DHEA treated group; P = 0·001 and 0·004, respectively. No change in CD4 cell counts was seen during follow‐up.CONCLUSIONS The administration of DHEA in patients with advanced HIV infection results in improved mental function scores as assessed by the MOS‐HIV quality of life scale.
Relationship between the number and impact of stressful life events and the onset of Graves' disease and toxic nodular goitre★
Authors: Matos‐Santos A. , Nobre E. Lacerda , Costa J. Garcia E , Nogueira P. J. , Macedo A. , Galvão‐Teles A. , De Castro J. Jácome 
Published: March 2003

BACKGROUND In the last few decades, several studies have suggested a possible association between Stressful Life Events (SLEs) and the onset of Graves' Disease (GD). However, others have criticised this association and it has not yet been possible to prove it unequivocally. At present, we are not aware of studies correlating SLE and non autoimmune thyrotoxicosis.OBJECTIVE To assess possible associations between SLEs, the onset of GD and the onset of non autoimmune thyrotoxicosis (toxic nodular goitre, TNG).DESIGN A case–control retrospective study.PATIENTS This study included 93 subjects, divided into three groups of 31 each: GD, TNG and control (CG). The GD and TNG patients had thyroid disease diagnosed within the last 12 months, with clinical and biochemical confirmation. In the CG, psychopathological and endocrine disturbances had been ruled out. All three groups consisted of nine males (29%) and 22 females (71%). The mean age was 38·4 ± 10·9 years in the GD group, 48·3 ± 11·1 years in the TNG group and 41·1 ± 11·8 years in the CG group. SLEs were evaluated (number and impact) for the 12 months preceding the onset of symptoms of thyroid disease.MEASUREMENTS SLE occurrences and their impact on each group of cases were measured. To assess SLEs, we used the Life Experiences Survey (LES). Our statistical analysis included descriptive techniques and parametric and/or nonparametric comparative tests. P < 0·01 was considered statistically significant. Odds ratios were also calculated.RESULTS Patients with GD had a significantly greater number of SLEs compared to the TNG group and the CG (P < 0·001). The number and impact of negative SLEs were significantly higher in GD compared to TNG and CG (P < 0·001). The difference between TNG and CG was not significant (P > 0·01). GD had a higher impact of positive SLEs than TNG (P = 0·004), and no significant differences were found between the GD group and CG. Neutral SLEs were similar in the three groups.CONCLUSIONS These results suggest that SLEs are a precipitating factor of the onset of GD. We also demonstrated that SLEs do not seem to have any conclusive relationship with the onset of TNG.
Association between lithium use and thyrotoxicosis caused by silent thyroiditis
Authors: Miller Karen K. , Daniels Gilbert H. 
Published: March 2003

OBJECTIVE To determine the incidence of silent thyroiditis in lithium users and characterize lithium‐associated thyrotoxicosis.DESIGN Retrospective record review.PATIENTS 400 consecutive patients (300 with Graves' disease and 100 with silent thyroiditis) who underwent radioiodine scanning of the thyroid.MEASUREMENTS Odds of lithium exposure.RESULTS The odds of lithium exposure were increased 4·7‐fold in patients with silent thyroiditis compared with those with Graves' disease (95% CI: 1·3, 17). Lithium‐associated silent thyroiditis occurred with an incidence rate of approximately 1·3 cases per 1000 person‐years, and lithium‐associated thyrotoxicosis occurred with an incidence rate of approximately 2·7 cases per 1000 person‐years, higher than the reported incidence rates of silent thyroiditis (< 0·03–0·28 cases per 1000 person‐years) and of thyrotoxicosis (0·8–1·2 cases per 1000 person‐years) in the general population.CONCLUSION Thyrotoxicosis caused by silent thyroiditis might be associated with lithium use.