bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frequency of appearance of myeloperoxidase‐antineutrophil cytoplasmic antibody (MPO‐ANCA) in Graves' disease patients treated with propylthiouracil and the relationship between MPO‐ANCA and clinical manifestations
Authors: Noh Jaeduk Yoshimura , Asari Tomoki , Hamada Noboru , Makino Fuminori , Ishikawa Naofumi , Abe Yoshifumi , Ito Koichi , Ito Kunihiko 
Published: March 2003

OBJECTIVE Myeloperoxidase antineutrophil cytoplasmic antibody (MPO‐ANCA)‐positive vasculitis has been reported in patients with Graves' disease who were treated with propylthiouracil (PTU). The appearance of MPO‐ANCA in these cases was suspected of being related to PTU because the titres of MPO‐ANCA decreased when PTU was stopped. Nevertheless, there have been no studies on the temporal relationship between the appearance of MPO‐ANCA and vasculitis during PTU therapy, or on the incidence of MPO‐ANCA in untreated Graves' disease patients. Therefore, we sought to address these parameters in patients with Graves' disease.PATIENTS We investigated 102 untreated patients with hyperthyroidism due to Graves' disease for the presence of MPO‐ANCA, and for the development vasculitis after starting PTU therapy. Twenty‐nine of them were later excluded because of adverse effects of PTU or because the observation period was less than 3 months. The remaining 73 patients (55 women and 18 men), all of whom were examined for more than 3 months, were adopted as the subjects of the investigation. The median observation period was 23·6 months (range: 3–37 months).MEASUREMENTS MPO‐ANCA was measured at intervals of 2–6 months.RESULTS Before treatment, the MPO‐ANCA titres of all 102 untreated Graves' disease patients were within the reference range (below 10 U/ml). Three (4·1%) of the 73 patients were positive for MPO‐ANCA at 13, 16 and 17 months, respectively, after the start of PTU therapy. In two of them, the MPO‐ANCA titres transiently increased to 12·8 and 15·0 U/ml, respectively, despite continued PTU therapy, but no vasculitic disorders developed. In the third patient, the MPO‐ANCA titre increased to 204 U/ml and she developed a higher fever, oral ulcers and polyarthralgia, but the symptoms resolved 2 weeks after stopping PTU therapy, and the MPO‐ANCA titre decreased to 20·7 U/ml by 4 months after discontinuing PTU.CONCLUSIONS PTU therapy may be related to the appearance of MPO‐ANCA, but MPO‐ANCA does not appear to be closely related to vasculitis.
An audit of management of differentiated thyroid cancer in specialist and non‐specialist clinic settings
Authors: Kumar H. , Daykin J. , Holder R. , Watkinson J.C. , Sheppard M.C. , Franklyn J.A. 
Published: March 2003

OBJECTIVE Thyroid cancer is the most common endocrine malignancy but is none the less rare. Some aspects of its management remain controversial. Previous audits of patient management in the United Kingdom have revealed deficiencies, especially in communication between specialists. We have audited patient management in a large university‐associated teaching hospital, assessing points of good practice identified from published guidelines and reviews, and have compared findings in groups of patients managed jointly by specialists with an interest in thyroid cancer (including surgeon, endocrinologist and oncologist) with a group managed by other clinicians outside that setting.DESIGN AND PATIENTS Retrospective case‐note review of 205 patients with differentiated (papillary or follicular) cancer including group A (n = 134; managed in a specialist multi‐disciplinary clinic setting) and group B (n = 71; managed in other clinic settings). Points of good practice investigated were adequacy of surgery, surgical complications, prescription and adequacy of T4 treatment, adequacy of monitoring by measurement of serum thyroglobulin and action taken and appropriate administration of ablative radioiodine.RESULTS Deficiencies in management of the cohort as a whole were identified, including inadequate surgery and inadequate TSH suppression in approximately one‐fifth of the cases. Monitoring with thyroglobulin measurements and action when serum thyroglobulin was high were also inadequate in some cases and ablative radioiodine was not given, despite being indicated in 11·7% of the cohort. Inadequate surgery and failure to administer radioiodine were less common in those managed in a specialist clinic setting than in those managed in other clinic settings.CONCLUSIONS The findings highlight the need for locally agreed protocols in managing relatively rare endocrine disorders such as thyroid cancer and argue in favour of centralization of expertise and patient management in multi‐disciplinary specialist clinic settings.
Characterization of two novel mutations in the glucocorticoid receptor gene in patients with primary cortisol resistance
Authors: Ruiz Mini , Lind Ulrika , Gåfvels Mats , Eggertsen Gösta , Carlstedt‐Duke Jan , Nilsson Lennart , Holtmann Martin , Stierna Pontus , Wikström Ann‐Charlotte , Werner Sigbritt 
Published: March 2003

OBJECTIVE Primary glucocorticoid resistance is characterized by decreased sensitivity to cortisol signalling. We have performed genetic analysis of the glucocorticoid receptor (GR) gene in 12 unrelated patients with primary cortisol resistance as defined by a pathological dexamethasone suppression test.METHODS Exon specific polymerase chain reaction amplification of the GR gene and sequencing of each exon was carried out. The two mutations were characterized in vitro in terms of glucocorticoid driven reporter gene activity in a transient transfection assay and in a ligand binding assay. Molecular modelling of the R477H mutant was performed based on the X‐ray structure of the GR‐DNA binding domain.RESULTS Two novel mutations in the GR gene were found: R477H in the DNA‐binding domain which is the first reported mutation in that region of the human GR gene and G679S in the ligand binding domain. The R477H mutation showed no transactivating capacity, whereas the G679S mutation had reduced transactivation capacity compared to the wild‐type (wt) GR. When tested for ligand binding capacity, the G679S mutation had 50% binding affinity compared to the wt GR. The effect of the point mutation R477H was deduced by a comparison between the wt structure and the model of the mutant. The wt GR has direct and water mediated contact with the phosphate groups of the glucocorticoid responsive element (GRE) whereas, in the model, the mutation R477H has no contact with the GRE. The G679S mutation is located on the surface of the ligand binding domain, at a distance from the steroid‐binding site. A previously reported polymorphism, AAT to AAC at amino acid position 766, was found in four of the patients.CONCLUSIONS In two of 12 patients with clinical glucocorticoid resistance, mutant forms of GR could be found. The glucocorticoid resistance in vivo in these two patients corresponds to impaired function of the two mutated GR forms in two in vitro assays. The relevance of the conservative polymorphism for the glucocorticoid insensitivity noted in these patients remains to be clarified.
Complete surgical lymph node resection does not prevent authentic recurrences of medullary thyroid carcinoma
Authors: Franc S. , Niccoli‐Sire P. , Cohen R. , Bardet S. , Maes B. , Murat A. , Krivitzky A. , Modigliani E. , Medullary Study Group (getc) The French 
Published: March 2003

BACKGROUND Medullary thyroid carcinoma is a rare tumour derived from the thyroid parafollicular calcitonin‐secreting cells. Calcitonin is a very specific marker of this cancer that allows preoperative diagnosis. Serum calcitonin assay is particularly useful to define the postoperative state of patients (cured, apparently cured, not cured) and, because of its great sensitivity, it has a major place in the postoperative follow‐up.OBJECTIVE To identify, among patients thyroidectomized for medullary thyroid carcinoma (MTC), the characteristics of authentic recurrent MTC [re‐elevation of stimulated serum calcitonin (CT) level measured by a sensitive immunoradiometric assay, after postoperative normalization].PATIENTS AND METHODS We first collected, through the national registry of the French Calcitonin Tumour Study Group (GETC), patients who had undergone a total thyroidectomy with or without lymph node surgery and who were not cured at the last follow‐up visit. Among 453 such patients included in the database, 15 patients met the criteria for authentic recurrence as defined in previous studies: they had been first considered as cured during the 6 months following the initial surgical procedure (basal and pentagastrin‐stimulated serum calcitonin level ≤ 10 ng/l) but had a secondary rerise of their pentagastrin‐stimulated calcitonin level, over 10 ng/l. Eight of them even had an undetectable (< 2 ng/l) immediate postoperative CT, confirming the initial postoperative cure. The characteristics (age, nature of disease, stage at surgery and type of node dissection) of these 15 patients were studied.RESULTS According to the Tumour Node Metastasis classification, nine patients were T1 and, among them, five patients had had complete lymph node surgery without any evidence of nodal metastases (N0). The recurrence was 3·2 ± 2·2 years (range: 0·7–7·5) after the initial surgery.CONCLUSIONS 3·3% of patients not cured at the last visit had a recurrent MTC. This recurrence occurred whatever the stage, and even if the primary surgery for MTC was a priori complete. These results emphasize the need for a regular biochemical follow‐up because recurrence may appear many years after the initial surgery.
Effect of Sandostatin® LAR® on sleep apnoea in acromegaly: correlation with computerized tomographic cephalometry and hormonal activity
Authors: Ip M. S. M. , Tan K. C. B. , Peh W. C. G. , Lam K. S. L. 
Published: March 2003

OBJECTIVES Sleep apnoea has been reported to occur in subjects with acromegaly. This study evaluates the relationship among biochemical activity, sleep apnoeic activity and upper airway anatomic profile in acromegaly, and the effect of Sandostatin® LAR®, a long‐acting somatostatin analogue, on these parameters.PATIENTS Fourteen subjects with acromegaly were recruited.MEASUREMENTS Subjects were assessed at baseline and those with apnoea‐hypopnoea index (AHI) ≥ 5 were reassessed after 6 months of treatment with Sandostatin® LAR® 20–30 mg IMI 4‐weekly. Biochemical activity was assessed with levels of GH and IGF‐1. Sleep disordered breathing was assessed with overnight polysomnography. Upper airway anatomic profile was defined with computerized tomographic cephalometry.RESULTS Of 14 subjects (age 42·0 ± 8·1 years, mean ± SD; 11 men) at baseline, there was a positive correlation between GH and tongue length (VT; P = 0·004), and between AHI and cephalometric indices: length of soft palate (PMU; P = 0·002); mandibular plane‐hyoid bone distance (MPH; P = 0·017), maximum thickness of soft palate (Max‐SP; P = 0·018) and VT (P = 0·027). Eight patients had sleep disordered breathing (AHI ≥ 5) which was predominantly obstructive in nature (AHI = 29·4 ± 22·6). After treatment, there were significant improvements in hormonal profile: GH, mU/l (before, 51·5 ± 27·8; after, 8·0 ± 7·4; P = 0·017) and IGF‐1, nmol/l (before, 95·5 ± 23·4; after, 35·0 ± 12·4; P = 0·012); sleep‐disordered breathing: AHI (before, 29·4 ± 22·6; after, 13·4 ± 11·12; P = 0·025), snoring episodes (before, 486 ± 240; after, 165 ± 170; P = 0·05); cephalometric indices, mm: MPH (before, 18·8 ± 12·1; after, 14·8 ± 8·4; P = 0·018), VT (before, 72·3 ± 4·4; after, 69·7 ± 4·3; P = 0·05). There was a positive correlation between the reduction in GH and AHI (r = 0·738, P = 0·037).CONCLUSIONS The findings demonstrated that there was correlation between sleep apnoea severity and soft tissue overgrowth at the upper airway region in acromegaly. They also suggest that Sandostatin® LAR® improved obstructive sleep apnoea in acromegaly, and the effect might be partly mediated via a reduction in upper airway soft tissue, in particular that of the tongue, concomitant with a reduction in GH levels.
Thyroid function in the newborn in relation to maternal thyroid status during labour in a mild iodine deficiency endemic area in Sudan
Authors: Eltom Aboud , Eltom Mohamed , Idris Mohamed , Gebre‐Medhin Mehari 
Published: March 2003

OBJECTIVES Data on neonatal and maternal thyroid function during labour in a mild iodine deficiency endemic area are lacking. The current study focuses on elucidating the thyroid function during labour, in a group of pregnant women who live in an area of mild iodine deficiency in Sudan compared to that observed in their corresponding newborns.MEASUREMENTS Serum concentrations of TSH, thyroglobulin (Tg), triiodothyronine (T3) and free thyroxine (FT4) were investigated during labour in a group of mothers and their neonates residing in an area with mild iodine deficiency in Sudan (n = 76 mother–newborn pairs).DESIGN Maternal blood samples were taken on two occasions: first, during the third trimester of pregnancy (weeks 32–39); and, second, just before delivery. Cord blood samples were obtained by a doctor or a trained midwife during delivery.RESULTS The median concentrations (and interquartile ranges) of neonatal TSH, Tg, T3 and FT4 were 6·8 (4·7–12·4) mU/l, 61 (40·2–98·2) µg/l, 0·9 (0·8–1·2) nmol/l and 14·2 (13·4–15·9) pmol/l, respectively. The corresponding levels for the mothers during labour were 2·3 (1·9–3·2) mU/l, 33 (15·0–56·8) µg/l, 2·6 (2·0–2·9) nmol/l and 11·4 (10·3–13·3) pmol/l, respectively. The median neonatal serum concentrations of TSH, Tg and FT4 were significantly higher than the corresponding maternal levels (P < 0·0001, P < 0·0001, P < 0·0001, respectively). In contrast, the median maternal serum concentration of T3 was significantly higher than that of the neonates (P < 0·0001). When the different neonatal thyroid parameters were compared with each other, significant correlations were observed between TSH and FT4 (r = 0·4, P = 0·001); Tg and T3 (r = −0·3, P = 0·04) and Tg and FT4 (r = 0·5, P = 0·0001). Women with Tg concentrations above 20 µg/l showed a higher median TSH concentration and lower median FT4 concentration than those with Tg concentrations below 20 µg/l (P < 0·001, P < 0·001, respectively). Nevertheless, the thyroid function of neonates born of mothers with elevated Tg was similar to that of neonates born of mothers with low Tg levels. No significant changes had occurred in the thyroid function parameters between the third trimester of pregnancy and during the time of labour. The thyroid function indicators of the babies born by vaginal delivery did not differ significantly from those of the babies born by Caesarian section.CONCLUSIONS The study suggests that, in areas with mild iodine deficiency, neonates may be at the limit of decompensation as evidenced by their enhanced TSH and Tg levels as well as increased T4 compared to their mothers. This finding must not create a false sense of well‐being and points rather to the urgency of iodine supplementation of mothers even in areas with mild iodine deficiency, as in this part of Sudan. The mode of delivery, whether by spontaneous vaginal delivery or Caesarian section, did not seem to affect the thyroid function of the newborn.
Paradoxical elevations in serum IGF‐II and IGF binding protein‐2 in acromegaly: insights into the regulation of these peptides
Authors: Renehan Andrew G. , Toogood Andrew A. , Ryder W. David , Jones Jenny , Potten Christopher S. , O'Dwyer Sarah T. , Shalet Stephen M. 
Published: March 2003

OBJECTIVE Circulating insulin‐like growth factor (IGF)‐II and IGF binding protein‐2 (IGFBP‐2) are frequently altered, often in parallel, in numerous pathologies including neoplastic disease but little is known about their normal regulation. This study compared serum IGF‐II and IGFBP‐2 distributions between acromegalics and a large normal adult population to explore possible determinants.PATIENTS Sixty acromegalic patients undergoing screening colonoscopy (age range 25–81 years); normative data from 306 healthy adults (age range 20–89 years).MEASUREMENTS Serum IGF‐I, IGF‐II, IGFBP‐2 and IGFBP‐3 were measured in healthy adults and acromegalics. Mean growth hormone (GH) levels were obtained for acromegalic patients. Differences were compared using t‐tests (unadjusted) and multiple regression models (adjusted for age and gender). Correlations were expressed as Pearson's coefficient (r).RESULTS For acromegalic patients, GH was significantly correlated with IGF‐I (r = 0·50; P < 0·001) and IGFBP‐3 (r = 0·29; P = 0·03) but not IGF‐II or IGFBP‐2. Contrary to expectations, mean IGF‐II and IGFBP‐2 levels were significantly raised in the acromegalics compared with normals [adjusted mean difference (95% CI) = 226 (181, 271) µg/l and 305 (200, 410) µg/l, respectively]. Ten acromegalic patients had colorectal neoplasia but their presence did not contribute to the elevations in serum IGF‐II and IGFBP‐2. The (IGF‐I + IGF‐II)/IGFBP‐3 molar ratios were remarkably constant in both healthy adults and acromegalics, but the relationships of the ligands individually with IGFBP‐3 were not linear: as IGFBP‐3 increased, IGF‐I also increased whereas IGF‐II initially increased but then decreased. IGFBP‐2 did not correlate with IGF‐II, but molar concentration significantly correlated with the IGF‐II/IGFBP‐3 molar ratio (r = 0·40; P = 0·001).CONCLUSIONS Serum IGF‐II and IGFBP‐2 levels were paradoxically elevated in acromegalics, independent of the presence of colorectal neoplasia. The (IGF‐I + IGF‐II)/IGFBP‐3 molar ratio appears to be pivotal in determining IGF‐II values, which, in turn, expressed as a ratio of IGFBP‐3, is related to IGFBP‐2. These observations offer new insights into the regulation of these peptides.
Demonstration of anti‐TSH antibody in TSH binding inhibitory immunoglobulin‐positive sera of patients with Graves’ disease
Authors: Ochi Yukio , Hamazu Masanari , Kajita Yoshihiro , Nagata Atsuo 
Published: March 2003

Summaryobjectives The presence of anti‐TSH antibodies in Graves’ patients with unusually low TSH binding inhibitory immunoglobulin (TBII) has been reported. Recently, we found the first case of an anti‐TSH antibody in TBII‐positive sera of patients with Graves’ disease. The prevalence and immunological specificity of this anti‐TSH antibody were examined.design The presence of 125I‐bovine(b) TSH binding antibody in TBII positive serum was examined by prolonged incubation of more than 1 day because only weak binding occurred after 1 h incubation at 37°C. The clinical course of these patients and binding characteristics of anti‐bTSH antibody were examined.results The corrected method‐TBII activity (%)[1 – (a – b)/(c – d)] × 100 and the standard method‐TBII activity (%) [1 – (a – d)/(c – d)] × 100 [a, 125I‐bTSH binding with TSH receptor (R) in the presence of test serum; b, 125I‐bTSH binding with test serum; c, 125I‐bTSH binding with TSH R in the presence of normal serum; d, 125I‐bTSH binding with normal serum] were calculated. The corrected method‐TBII activity was always higher than the standard method‐TBII activity in anti‐bTSH antibody‐positive serum. Anti‐bTSH antibody‐positive cases in TBII‐positive Graves’ disease were found in approximately 1% of Graves’ patients. Anti‐bTSH antibodies were confirmed as IgG from the increase of precipitated radioactivity by adding rabbit antihuman IgG antibody after the incubation of 125I‐bTSH with test serum. These antibodies bind with not only bTSH, bTSH(α) and bLH, but also porcine (p)TSH, pTSH(α) and pFSH. However, these antibodies did not bind with human TSH. Binding of 125I‐bTSH with patient’s serum was neither inhibited by other Graves’ thyroid stimulating antibody (TSAb), nor thyroid blocking antibody (TBAb) in primary hypothyroidism.conclusions The presence of anti‐bTSH antibody in TBII‐positive serum of high titre means that TBII‐positive sera cannot rule out the absence of anti‐bTSH. Thus, determination of 125I‐bTSH binding with test serum in TSH receptor assays is necessary to determine the precise TBII activity and to detect anti‐bTSH antibody.
Skin fibroblasts of children with idiopathic short stature show an increased mitogenic response to IGF‐I and secrete more IGFBP‐3
Authors: Kamp G. A. , Ouwens D. M. , Hoogerbrugge C. M. , Zwinderman A. H. , Maassen J. A. , Wit J. M. 
Published: March 2003

Summaryobjective and patients To study differences in cellular parameters of GH and IGF‐I responsiveness in skin fibroblasts of 14 children with idiopathic short stature (ISS) treated with recombinant human GH and 13 children with normal height. Secondly, to investigate whether these cellular parameters can predict the growth response to GH treatment in children with ISS.design and measurements The mitogenic responsiveness to GH and IGF‐I was investigated by 3H‐Thymidine incorporation. Insulin‐like growth factor binding protein‐3 (IGFBP‐3) levels in the media were measured by radioimmunoassay (RIA).results No significant mitogenic responses were observed to various doses of GH (1000, 5000 or 50·000 ng/ml) in children with ISS or controls. ISS fibroblasts showed an increased mitogenic response to IGF‐I (10 ng/ml) compared to controls (mean ± SD 5·9 ± 2·4‐ vs. 4·2 ± 1·5‐fold stimulation, P < 0·05), and GH enhanced this effect in both groups. IGFBP‐3 secretion was increased in ISS fibroblasts when compared to controls under all conditions examined (basal, 200 and 5000 ng/ml GH, 10 ng/ml IGF‐I for 24 and 48 h). High IGFBP‐3 levels were related to low mitogenic responses to IGF‐I or to GH + IGF‐I in children with ISS (r = –0·7, P < 0·05), but not in controls. Within the ISS group, an enhanced mitogenic response to IGF‐I in vitro was related to more extreme short stature before GH treatment (r = –0·70, P < 0·05) and to a relatively impaired response to high dose GH treatment in vivo (r = –0·52, P < 0·05).conclusion The demonstration of high IGFBP‐3 levels and enhanced mitogenic response to IGF‐I shows that ISS fibroblasts have different cellular characteristics compared to controls of normal height. It is hypothesized that in ISS an alteration of the signal transduction pathway between the GH receptor and IGFBP‐3 synthesis results in a local imbalance with high IGFBP‐3 levels and lower IGF‐I availability for the IGF‐I receptor. This may be reflected by an increased IGF‐I responsiveness in vitro which is associated with an impaired capacity to grow in vivo.