bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subtle changes in serum thyrotrophin (TSH) and sex‐hormone‐binding globulin (SHBG) levels during long‐term follow‐up after radioactive iodine in multinodular non‐toxic goitre.
Authors: Jarlev A. E. , Faber J. , Hegedüs L. , Hansen J. Mølholm 
Published: March 2008

OBJECTIVE We investigated possible changes in the pituitary‐thyroid axis after radioactive iodine (RAI) treatment of multinodular non‐toxic goitre.DESIGN Consecutive patients with multinodular non‐toxic goitre, who remained euthyroid after radioactive iodine (RAI) treatment.PATIENTS Twenty‐three women with multinodular nontoxic goitre were followed after treatment with RAI.MEASUREMENTS Free T4 index (FT4I), FT3I, free T4, SHBG (Immunoradiometric assay), and a third‐generation TSH assay (chemiluminetric assay) TSH were measured. RESULTS Three weeks after RAI treatment TSH had decreased and SHBG Increased (P <0.05). Only 2/18 patients actually had suppressed TSH values, while 12/18 had values in between euthyroid and toxic levels. Trend analysis from 1.5 to 24 months after RAI treatment demonstrated a progressive increase in TSH (P <0.01) and gradual decrease in SHBG (P <0.02). No changes in FT4I, FT3I, or free T4 were found.CONCLUSION A third‐generation TSH assay gave detailed information about changes in thyroid status when TSH was below normal values. FT4I, FT3I, and free T4 seem to be less sensitive parameters than TSH and SHBG for recording subtle changes in thyroid status after RAI treatment of nodular non‐toxic goitre. We demonstrated that changes in the pituitary‐thyroid axis continue for a long time after RAI treatment of multinodular non‐toxic goitre. These patients should be followed up in order to detect possible late hypothyroidism.
Genetic linkage studies of X‐linked hypophosphataemic rickets in a Saudi Arabian family
Authors: Thakker R. V. , Farmery M. R. , Sakatl N. A. , Mllner R. D. G. 
Published: March 2008

OBJECTIVE, PATIENTS AND DESIGN X‐linked hypophos‐phataemic rickets (HYP) is the most common inherited form of rickets and the gene causing this disorder has been localized to Xp22.3‐p21.3 by linkage studies of affected families of Northern European origin. In addition, the locus order Xpter‐(DXS207‐DXS43, DXS197)‐HYP‐DXS41‐Xcen has been established and the flanking markers are useful for the presymptomatic diagnosis of HYP. However, a recent study indicates locus heterogeneity and this may hinder the use of the flanking markers for presymptomatic diagnosis in additional families and in particular those from different populations. We have therefore investigated one Saudi‐Arabian family (13 affected and six unaffected members) with hypophosphataemic rickets for linkage to these and other X‐linked markers. A total of 17 cloned human X chromosome sequences identifying restriction fragment length polymorphisms were used to localize the mutant gene causing this disorder in the Saudi Arabian family.RESULTS Nine (four from Xp and five from Xq) of the 17 X‐linked DNA probes proved informative and linkage was established between HYP and the DSX41 locus, peak LOD score = 4.22 (recombination fraction, ±= 0.00). A positive peak LOD score of 2.32 (. = 0.05) was also obtained between HYP and the DXS207 locus. Thus, the HYP gene in this Saudl Arabian family is linked to two of the four flanking markers which demonstrated linkage in families of Northern European origin.CONCLUSION We conclude that the X‐linked hypophosphataemic rickets gene in a Saudl Arabian family is located in the Xp22.3–p21.3, a region where this gene has previously been mapped by linkage studies of families of Northern European origin. Our studies have not demonstrated locus heterogeneity, so the flanking markers for HYP previously established in the families of Northern‐European origin will be useful in the genetic counselling and presymptomatic diagnosis of this disorder in the Saudi Arabian family.
Normal pattern of parathyroid response to blood calcium lowering in primary hyperparathyroidism: a citrate clamp study
Authors: Schwarz P. , Serensen H. A. , Momsen G. , McNair P. , Transbel I. 
Published: March 2008

OBJECTIVE The objective of the present study was to elucidate the parathyroid responsiveness by measurements of blood Ionized calcium and serum intact parathyrold hormone (PTH) concentrations, before and during trisodium citrate induced hypocalcaemia.PATIENTS AND CONTROLS Sixteen patients with primary hyperparathyroidism and 32 healthy volunteers.DESIGN Blood ionized calcium concentration was lowered by about 0.20 mmol/l and maintained at this level for 2 hours by blood ionized calcium controlled trisodium citrate infusion.MEASUREMENTS Serum PTH(1–84) was measured by an Immunoradiometric assay.RESULTS In patients and controls, baseline measurements of blood Ionized calcium were 1.39±0.07 vs 1.24±0.04 mmol/l (mean.SD) (P <0.001) and of serum PTH (1–84) 9.7.5.4 vs 3.2 1.1pmol/l (P<0.001). During a trisodium citrate clamp, serum PTH(1–84) rose to a maximal concentration after 5–10 minutes in both groups, the patients to 2–10 times baseline, whereas controls rose to 4–7 times baseline values. In both groups the peak of serum PTH(1–84) declined to a steady state concentration around 2–4 times baseline.CONCLUSIONS in conclusion, adenoma cells seem to react in almost the same way as normal parathyroid cells. They respond to initiation of hypocalcaemia by the release of preformed PTH(1–84), and continue to secrete increased amounts of PTH(1–84) during the maintenance of relative hypocalcaemia. The increased baseline concentrations of blood ionized calcium and serum PTH(1–84) and the serum PTH(1–84) response during blood ionized calcium lowering all suggest a shift upwards in the calcium set point.
A randomized double blind placebo controlled trial of the effects on bone metabolism of the combination of nafarelin acetate and norethisterone
Authors: Eldred J. M. , Haynes P. J. , Thomas E. J. 
Published: March 2008

OBJECTIVE We observed the effects on bone metabolism of the addition of different doses of oral norethisterone during treatment with the GnRH agonist nafarelin (Synarel, Syntex).PATIENTS Ninety‐four women with a subjective complaint of heavy menstrual blood loss or objective evidence of endometriosis received intra‐nasal nafarelin 400 μg daily for 6 months and also received, in a randomized, double blind manner, either 0.7 mg (n= 24), 1.4 mg (n= 23) or 2.45 mg (n= 23) of oral norethisterone or placebo (n= 24) daily. Follow‐up was continued for a further 6 months after treatment.RESULTS Thirty‐one patients (33%) left the study prematurely and three patients were non‐compliant with the study drug. By 6 months significant increases in urinary calcium/creatinine ratio were seen, compared to baseline, in the nafarelin and placebo (P=0.001, n= 14), 0.7 mg (P=0.04, n= 13) and 1.4 mg norethisterone groups (P=0.009, n= 17) but not in the nafarelin or 2.45 mg norethisterone groups (P= 0.72, n= 16). Densltometry of the spine, however, showed decreases at 6 months in all groups: 6.14% (P=0.0004, n= 11), 5.46%n= 0.0006, n= 13), 3.93% (P=0.008, n= 14) and 4.04% (P= 0.004, n= 16) for the groups receiving nafarelin and placebo, nafarelin and norethisterone 0.7, 1.4 and 2.45 mg respectively. Six months after stopping nafarelin, with or without norethisterone, bone mass was not different from baseline.CONCLUSION The concomitant daily use of up to 2.45 mg of norethisterone does not eliminate the bone deminerallzation seen during GnRH agonist therapy with nafarelin in premenopausal women.
The significance of a single serum LH measurement in women with cycle disturbances: discrepancies between immunoreactive and bioactive hormone estimates*
Authors: Fauser Bart C. J. M. , Pache Thierry D. , Hop Wim C. J. , de Jong Frank H. , Dahl Kristine D. 
Published: March 2008

OBJECTIVE We evaluated the significance of single serum LH estimates (as assessed by radiometric assay (IRMA) and Leydig cell in‐vitro bioassay (BIO)) for the diagnosis of polycystic ovary syndrome (PCOS) in women with infertility and cycle abnormalities.DESIGN Hormonal and clinical comparisons between subgroups were made based on classification according to (a) rigid clinical and endocrine (excluding LH) characteristics of PCOS, (b) elevated IRMA‐LH concentrations, (c) BIO‐LH levels. In addition, androgen modulation of LH biopotency was studied in these patients.PATIENTS Ninety‐nine women presenting at our infertility Unit with oligo/amenorrhoea.MEASUREMENTS AND RESULTS Of the total study group, 35 women were diagnosed positive as PCOS and 42 showed elevated IRMA‐LH levels. Only 51% (n= 18) of PCOS patients showed elevated IRMA‐LH levels, and in PCOS significantly higher levels of BIO‐LH, androstenedione, oestrone, and BIO/IRMA‐LH ratios were found as compared to non‐PCOS patients. In the group with elevated IRMA‐LH only 43% (n= 18) of subjects were diagnosed as PCOS, and no difference in BIO/IRMA‐LH ratios was found. With increasing BIO‐LH levels the probability of PCOS rises sharply (P < 0.001), whereas this probability is of only marginal significance (P <0.06) for IRMA‐LH. In the total study group a correlation is observed between serum testosterone (T) levels and IRMA‐LH (r= 0.47), and BIO‐LH (r= 0.51) concentrations. This correlation is absent comparing serum T and BIO/IRMA‐LH ratios (r= 0.15).CONCLUSIONS Results presented in this study indicate that (1) women with infertility and oligo/amenorrhoea classified based on signs of PCOS or IRMA‐LH levels, exhibit different clinical and endocrine characteristics, (2) only 51% of PCOS women exhibit elevated IRMA‐LH concentrations, and only 43% of women with elevated IRMA‐LH were diagnosed as PCOS, (3) IRMA‐LH levels are a poor predictor of PCOS, whereas the predictive value of BIO‐LH is better, (4) elevated BIO/IRMA‐LH ratios in PCOS are dependent on alterations in BIO‐LH, rather than IRMA‐LH concentrations, and (5) no correlation was observed between serum T levels and BIO/IRMA‐LH ratios.
Comparison of measures of body composition in a trial of low dose growth hormone replacement therapy
Authors: Orme S. M. , Sebastian J. P. , Oldroyd B. , Stewart S. P. , Grant P. J. , Stickland M. H. , Smith M. A. , Belchetz P. E. 
Published: March 2008

OBJECTIVE We assessed the effects of the administration of low dose growth hormone in growth hormone deficient adults on body composition and physical performance. We compared the validity of different measures of body composition in GH treated adults.DESIGN An uncontrolled longitudinal study of eight patients with GH deficiency who were treated with 4 units of biosynthetic growth hormone (Norditropin), three times a week. Subjects were studied for 8 weeks.PATIENTS Eight patients with acquired growth hormone deficiency as defined by <5mU/1 GH following standard provocative investigations in whom other hormone replacement was optimized.MEASUREMENTS IGF‐I was measured on day 1 and after 4 and 8 weeks of treatment with recombinant human growth hormone. Body composition was estimated by dual energy X‐ray absorptiometry, bioelectrical impedance, skinfold anthropometry, total body potassium measurement and by computerized tomography of a representative cross‐sectional area of thigh on day 1 and following 8 weeks of treatment. Exercise capacity was measured on an electromechanical bicycle and palmar grip strength was measured using a Jamar dynamometer on day 1 and after 8 weeks.RESULTS IGF‐I increased significantly. Exercise capacity and maximum heart rate achieved on the electromechanical bicycle increased significantly. Grip strength did not change. There was a significant increase in fat‐free mass and a decline in fat mass as shown by dual energy X‐ray absorptiometry and bioelectrical impedance. However, this was not confirmed by other methods. No side‐effects were noted.CONCLUSIONS This study shows that a low dose of biosynthetic growth hormone can elevate IGF‐I levels and have a pronounced physical impact in the growth hormone deficient adult without the side‐effects seen at higher dosage schedules. Over a 2 month period the increase in fat‐free mass may be due to an increase in total body water; however, the decline in fat mass is a genuine effect.
Suppressive therapy with levothyroxinefor solitary thyroid nodules
Authors: Reverter J. L. , Lucas A. , Salinas I. , Audi L. , Foz M. , Sanmarti A. 
Published: March 2008

Summary objective To evaluate the effect of treatment with TSH suppressive dose of levothyroxine In patients with benig nthyroid nodules. design Prospective randomized study. Group A (n= 20) patients received levothyroxine and group B (n= 20) patients did not. The dose of levothyroxine was adjusted to obtain an effective suppression of TSH. A clinical, analytical and morphological (with ultrasound) review was performed every 3 months. The mean ± SD follow‐upperiod was 6·10±2·2 months. patients Forty euthyrold women with solitary thyroid nodule on palpation, cold on sclntlgraphy and cytologically benign without contraindication participated. measurements At entry: biochemical and hormonal parameters, thyroid sclntigraphy and thyroid ultrasonography. Every 3 months additional determinations of thyroid hormones and TSH levels were carried out, if necessary, to verify effective TSH suppression. Every 6 months thyroid ultrasound imaging was performed. results Patients were euthyroid at entry into the study. The mean dose of levothyroxine necessary to obtain TSH suppression was 2·82±0·6 μg/kg/day. No significant modification in the thyroid nodule diameter (mean ± SD 2·6±1·2 vs 2·5±1·2 cm) or in the thyroid nodule volume(10·3±11·9 vs 10·1±12·2 ml) were observed in group A. In group B the results were similar (2·8±0·9 vs 2·7±1·8 cm and 9·2±6·4 vs 9·2±9·5 ml, respectively). No differences were found in either group in the number of nodules that reduced significantly their volume (four and three, respectively). conclusions The suppressive therapy with levothyroxine was not effective In reducing nodule sizes in patients withsolitary benign thyroid nodules.
Circadian rhythm of plasma testosterone in men with idiopathic hypogonadotrophic hypogonadism before and during pulsatile administration of gonadotrophin‐releasing hormone
Authors: Simonl Manuela , Montaninl Vanna , Fustini Marco Faustini , Rio Graziano Del , Cionl Katia , Marrama Paolo 
Published: March 2008

Summary objective The aim was to investigate whether a pulsatile discharge of LH from the pituitary Is necessary to achieve the circadian secretion of testosterone. design The daily rhythm of the androgen has been studied in patients with idiopathic hypogonadotrophic hypogonadism (IHH) both in the absence of therapy and during pulsatile administration of gonadotrophln releasing hormone (GnRH). patients Six patients with IHH and ten normal subjects were analysed. Blood sampling was performed at 2‐hourly intervals, for 24 hours. The IHH patients then received synthetic GnRH i.v. at the rate of one pulse every 2 hours (10 μg/pulse). On day 11 of treatment, blood samples were taken for the rhythm analysis every 2 hours, for 24 hours. measurements Plasma testosterone and LH were measured in the individual samples by radioimmunoassay. Evaluation of the rhythm was performed by cosinoranalysis. results A significant circadian rhythm of plasma testosterone was statistically validated In the normal subjects, whereas no rhythm was detected in the IHH patientsin the absence of therapy. On day 11 of GnRH pulsatile administration the IHH patients showed normal testosterone levels and a statistically indistinguishable from the corresponding values in the normal subjects. Plasma LH did not show statistically significant circadian variations, either In the control group or in the IHH patients before or during therapy. conclusions We conclude that a physiological circadian rhythm of plasma testosterone can be obtained, In IHH men, by treatment with GnRH. Since the pulsatile administration of exogenous GnRH at constant dosesinduced a circadian rhythm in testosterone and no dally variations in LH were evident, we suggest that, although a pulsatile secretion of LH is probably necessary for the synchronization of the circadian rhythm with acrophase inthe morning, the testosterone variations might be theresults of a local testicular modulation of LH action.
A novel variant of growth hormone (GH) insufficiencyfollowing low dose cranial irradiation
Authors: Crowne E. C. , Moore C. , Wallace W. H. B. , Ogllvy‐Stuart A. L. , Addison G. M. , Morris‐Jones P. H. , Shalet S. M. 
Published: March 2008

Summary objective We aimed to Investigate the effect of low dose (1800 cGy) prophylactic cranial Irradiation on physiological growth hormone secretion. design We performed an analysis of 24‐hour serum GH profiles using 20‐mlnute sampling. patients Forty‐four children were studied, of whom 21 were long‐term survivors of acute lymphoblastlc leukaemia and 23 were normal children. They were further subdivided into prepubertal, pubertal and post‐pubertal groups. measurements GH profiles were analysed by autocorrelation, Fourier transformation and spectral analysis of stationarlzed data, and peak detection using the Pulsar peak detection program. results In the normal children, there was a significant increase in the median (range) area under the curve (AUC) of the GH profile between the prepubertal and pubertal groups (62 (11–124) and 137 (142–158) IU/l/h respectively, (P < 0·01)). There was also a change In the spectral analysis through puberty. The dominant frequencies were spread widely in the prepubertal and post‐pubertal groups but sharply focused in the pubertal group. In the cranlally irradiated children there was no significant increase in AUC between the prepubertal (62(13–110) IU/l/h) and pubertal groups (92 (14–163) IU/l/h). The wide range of dominant frequencies persisted in the pubertal cranially irradiated group due to the presence of additional high frequency pulses. The impression of a disturbance of the periodicity of GH secretion in the cranlally irradiated pubertal group was further supported by the finding that the autocorrelation function in this group alone was not significantly different from that which would arise from random data. conclusions A novel form of GH Insufficiency has been observed after low dose Irradiation In childhood in which an abnormality of periodicity and a quantitative reduction In GH secretion appears restricted to puberty.
Correlation of HLA types and clinical findings in Japanese patients with hyperthyroid Graves' disease: evidence indicating the existence of four subpopulations
Authors: Inoue Daisuke , Sato Kaoru , Enomolo Tetsuya , Sugawa Hideo , Maeda Masahiro , Inoko Hidetoshi , Tsuji Kimiyoshi , Mori Toru , Imura Hlroo 
Published: March 2008

Summary objectives To re‐evaluate the associations of HLA types with Japanese patients having hyperthyroid Graves' disease, HLA types and clinical findings were correlated. design Four independent clinical findings (ophthalmopathy, family history, age at onset and size of goitre) and two autoantibody titres, thyrotrophin binding inhibitor immunoglobulin (TBII) and anti‐thyroid microsmall antibody (anti‐M), were analysed. patients Eighty‐eight Japanese patients with hyperthyroid Graves' disease and 186 control subjects were assessed. measurement Serological HLA typing was performed on 73 antigens In HLA‐A, ‐B, ‐C, ‐DR and ‐DQ loci. HLA‐D and ‐DP (29 antigens) were determined by the restricted fragment length polymorphism (RFLP) methods. TBII and anti‐M were measured by commercially available kits. results Patients with potent antibody tltres had HLA antigens commonly seen among all the patients with Graves' disease. Interestingly, however, HLA‐B35 and ‐Cw11 were found to relate with negative and/or weak TBII, and HLA‐B7 and absence of HLA‐Aw19 with negative antl‐M. Significant associations were observed between HLA‐DRw8 and large goitre and absence of ophthalmopathy, and between HLA‐DQw4 and a negative family history of diffuse goitre (corrected P < 0·05). Several other antigens were also found to be significant. Among these antigens, four pairs of MHC classes I and II were found to relate to the clinical findings independently. HLA‐DQw4 and negative ‐A31 pair was closely related to ophthalmopathy, negative family history and late onset of disease. The HLA‐B5 and ‐Dw12 pair was associated with ophthalmopathy, positive family history and early onset of disease. The HLA‐A11 and negative ‐DPw2 pair was associated with ophthalmopathy, negative family history and early onset of disease. The HLA‐Bw46 and ‐DRw8 pair did not increase in frequency above that seen with HLA‐DRw8 alone. These four antigen groups (HLA‐DRw8, HLA‐DQw4 and negative‐A31, HLA‐B5 and ‐Dw12, and HLA‐A11 and negative ‐DPw2) were observed in the majority (68%) of patients with Graves' disease and at a significantly higher incidence than in the control group (P < 0·05). conclusion There are four subpopulations of Japanese patients with hyperthyroid Graves' disease. This is one of the reasons why the association of HLA types in Japanese patients is rather weak when they are studied as one group.
Thyrotoxicosis and hyperemesis gravidarum associated with a serum activity which stimulates human thyroid cells in vitro
Authors: Kennedy R. L. , Darne J. , Davies R. , Price A. 
Published: March 2008

Summary objective To investigate in‐vitro thyroid stimulatory activity In the serum of patients with hyperemesis gravidarum and thyrotoxicosis. design Serum from hyperthyroid patients was incubated with cultures of human thyroid cells. Attempts were made to neutralize stimulatory activity with antisera to hCG. patients Five patients presenting In early pregnancy with hyperemesis and thyrotoxicosis. measurements Serum concentrations of thyroid hormones (total and free), TSH and hCG. Accumulation of extracellular cAMP in response to serum. results All five patients had biochemical hyperthyroidism with no evidence of an underlying autoimmune disease. The mean cAMP accumulation over 4 hours with sera from 12 non‐pregnant controls was 130·6 (121·1–142·8), from 12 pregnant controls 132·4 (118·1–143·8), compared with values of 144·7, 159·1, 166·2, 178·9 and 320·5 for the thyrotoxic patients. The stimulatory activity could not be neutralized by addition of anti‐hCG or by depleting the sera of hCG. conclusions Thyrotoxicosis may present with hyperemesis in early pregnancy. Clinical and biochemical features may be masked by the pregnancy or by the intercurrent illness. The hypothesis that hCG is a thyroid stimulator in patients with hyperemesis gravidarum is not supported by the immuno‐neutrallzation data in this study.