bluuebunny/crossref_metadata_2025_split huggingface dataset:
An audit of the management of thyroid cancer in a district general hospital
Authors: Vanderpump  , Alexander  , Scarpello  , Clayton  
Published: March 2003

OBJECTIVEThyroid cancer is the commonest endocrine malignancy yet it appeared to present infrequently to the endocrinologists at this large District General Hospital. The management of well‐differentiated thyroid cancer remains controversial with a wide variation in clinical practice. The aim of this survey was to determine the characteristics of the patients diagnosed with thyroid cancer and whether any deficiencies existed in the management of subjects diagnosed with thyroid cancer over a five‐year period using standards of care based upon long‐term outcome data and recently published USA guidelines.DESIGN AND PATIENTSRetrospective case‐note survey of all patients newly registered with thyroid cancer from 1990 to 1994 in North Staffordshire (estimated total population 450 000).RESULTSThe annual incidence of all thyroid cancer was two per 100 000 of which well‐differentiated tumours comprised 70%. Medical records were obtained in 48 new cases (91% of total) identified. Fifteen subjects who presented as surgical emergencies received only palliative treatment and had a poor outcome. Two patients presented with metastatic medullary thyroid carcinoma (3% of total). Thirty‐one patients (97% of whom presented with a thyroid nodule) were referred electively to either surgical (n = 22), ENT (n = 2) or endocrinology (n = 7) outpatients with well‐differentiated papillary (n = 17) and follicular (n = 14) tumours. Thirteen patients (42%) had fine‐needle aspiration cytology performed preoperatively. Of the 22 tumours (71%) greater than 1.5 cm, five (27%) had a total thyroidectomy and two (9%) also had radioiodine ablation. There was inadequate serum thyrotrophin suppression postoperatively in 12 patients (39%) and only five (16%) were being monitored for recurrence with serum thyroglobulin measurements.CONCLUSIONSDeficiencies in the optimum management of small, well‐differentiated thyroid cancers were identified. Improved communication between specialties has led to the development of an agreed management protocol to increase the quality of care offered to patients with thyroid cancer and for auditing the coordinated service in the future.
Current management of thyroid‐associated ophthalmopathy in Europe. Results of an international survey
Authors: Weetman A. P. , Wiersinga W. M. 
Published: March 2003

OBJECTIVETo determine how expert thyroidologists assess and treat thyroid‐associated ophthalmopathy (TAO), and if TAO affects treatment of coexistent Graves' hyperthyroidism.DESIGNMembers of the European Thyroid Association (ETA) were invited to answer a questionnaire which gave details of an index patient and nine variants differing in age, severity of TAO, thyroid state and the presence of diabetes. Eighty‐four responses were received from 19 European countries, representing approximately 60% of the clinically active ETA members.RESULTSDisease‐modifying treatment was not considered necessary by 18% for the index case with diplopia and proptosis but 77% used steroids alone or with another treatment; 5% used radiotherapy alone and 18% used it in combination with steroids. Worsening of eye signs after 8 weeks induced a significant shift away from steroids to radiotherapy, surgery, or other immunosuppression. For treatment of associated hyperthyroidism, antithyroid drugs were chosen by 84%, thyroidectomy by 10% and radioiodine by 6%. In recurrent hyperthyroidism, thyroidectomy was preferred by 43%, antithyroid drugs by 32%, and radioiodine by 25%. Major alterations in management of TAO were noted for only 2 of the 9 variants. Optic nerve involvement produced a more thorough evaluation of TAO as an in‐patient, and a preference for surgical decompression (42%). The presence of diabetes induced a greater use of surgery at the expense of steroids, but there was disagreement over the role of radiotherapy in diabetes.CONCLUSIONMarked geographical variation was noted, particularly in the treatment of thyroid‐associated ophthalmopathy. Observed consensus was nation‐wide rather than Europe‐wide. The appropriate treatment of the patient with thyroid‐associated ophthalmopathy, especially with diabetes or deteriorating eye signs, is controversial even amongst thyroid specialists.
Gestational transient hyperthyroxinaemia (GTH): screening for thyroid function in 23 163 pregnant women using dried blood spots
Authors: Tanaka Shinichi , Yamada Hideto , Kato Emi H. , Furuta Itsuko , Fukushi Masaru , Takasugi Nobuo , Fujimoto Seiichiro 
Published: March 2003

OBJECTIVETransient elevation of serum free T4 (gestational transient hyperthyroxinaemia; GTH) occurs occasionally during normal pregnancy, especially in early gestation. However, the frequency of GTH and its clinical features remain unclear to date. The aim of this study was to determine the occurrence rate of GTH and the relation between serum levels of hCG, free T4 (fT4), and TSH in a large number of pregnant women.DESIGNThe four criteria of GTH were as follows: (1) no past history of thyroid disease, (2) negative tests for MCHA and TGHA, (3) no multiple pregnancies or trophoblastic disease and (4) transient hyperthyroxinaemia at less than 16 weeks of gestation. Thyroid function and hCG levels in 23 163 pregnant women were evaluated by mass sreening. If individual fT4 levels were more than the upper limit, blood re‐sampling and the clinical and laboratory analysis of thyroid function were performed to exclude women with thyroid disease. The concentrations of hCG, fT4, and TSH in women with GTH and normal pregnant controls (n = 218) were compared. Regression analysis was performed for the comparison between hCG, fT4, and TSH levels in women with GTH.MEASUREMENTSBlood samples were obtained using dried blood spots. Blood levels of fT4 was measured by radioimmunoassay, TSH and hCG were measured by fluoroimmunoassay. Anti‐microsome antibody (MCHA) and anti‐thyroglobulin antibody (TGHA) were measured by indirect agglutination reaction.RESULTSGTH was observed in 66 of 23 163 women. The overall occurrence rate of GTH was 0.285%. In 22 of the 66 GTH women, serum TSH was undetectable. Using regression analyses, the concentration of fT4 was correlated with hCG levels in women with GTH (P < 0.05, r = 0.269), whereas the concentration of TSH was not correlated with hCG or fT4 level. The concentrations (M ± SD) of fT4, TSH, and hCG in women with GTH were 42.5 ± 12.3 pmol/l, 0.20 ± 0.31 mU/l and 190.2 ± 98.8 × 103 IU/l, whereas those of controls were 14.6 ± 3.8 pmol/l, 1.43 ± 1.25 mU/l and 60.1 ± 45.1 × 103 IU/l. The concentrations of fT4 and hCG were significantly (P < 0.0001) higher than those of normal controls, and TSH was significantly (P < 0.0001) lower than those of normal controls.CONCLUSIONThe occurrence rate of gestational transient hyperthyroxinaemia was 0.285%, and could possibly be attributed to increased levels of circulating hCG. Based on the data obtained from a large number of pregnant women, we propose gestational transient hyperthyroxinaemia as a definite clinical entity.
No evidence for allelic association of a human CTLA‐4 promoter polymorphism with autoimmune thyroid disease in either population‐based case–control or family‐based studies
Authors: Heward  , Allahabadia  , Carr‐Smith  , Daykin  , Cockram  , Gordon  , Barnett  , Franklyn  , Gough  
Published: March 2003

OBJECTIVEThe cytotoxic T lymphocyte associated‐4 (CTLA‐4) gene is a candidate for T‐cell mediated autoimmune disease and polymorphism has been reported to be associated with both type 1 diabetes and autoimmune thyroid disease. A previously unreported polymorphism of the promoter region of the human CTLA‐4 gene has recently been described in a sample of a normal control population. We investigated the distribution of this polymorphism, situated at position ‐318 to the ATG start codon and resulting in a C–T change leading to an Mse I restriction site, in both population based case control studies and family studies in patients with Graves' disease (Caucasian and Hong Kong Chinese), autoimmune hypothyroidism and systemic lupus erythematosus (SLE).DESIGNTarget DNA was amplified using the polymerase chain reaction and the resulting product was digested using the Mse I restriction enzyme.PATIENTSOne hundred and ninety‐one white UK Caucasian and 98 Hong Kong Chinese patients with Graves' disease, 78 white UK Caucasian patients with Graves' disease plus family members, 92 white UK Caucasian patients with autoimmune hypothyroidism, 13 white UK Caucasian patients with autoimmune hypothyroidism plus family members, 132 white UK Caucasian patients with systemic lupus erythematosus, 355 white UK Caucasian control subjects and 82 Hong Kong Chinese control subjects.MEASUREMENTSFrequencies of the C and T alleles were compared between patients and control subjects using the χ2‐test and Fisher's exact test for small numbers.RESULTSNo association with the T allele was observed in any of the patient groups studied.CONCLUSIONThese data suggest that the C–T change in exon 1 of the promoter region of the CTLA‐4 gene does not play a role, nor is in linkage disequilibrium with a disease causing mutation, in the development of autoimmune disease.
Cytoplasmic staining of erbB‐2 but not mRNA levels correlates with differentiation in human thyroid neoplasia
Authors: Sugg Sonia L. , Ezzat Shereen , Zheng Lei , Rosen Irving B. , Freeman Jeremy L. , Asa Sylvia L. 
Published: March 2003

OBJECTIVEAmplification and overexpression of the erbB‐2 proto‐oncogene in human carcinomas may have prognostic significance. Its role in thyroid carcinoma is controversial. We investigated human thyroid tumours for erbB‐2 gene amplification, activating mutations in the transmembrane domain, quantitative mRNA expression and protein expression.MATERIALS AND METHODSDNA and mRNA were extracted from 47 morphologically characterized, frozen thyroid tumours including 10 nodular hyperplasias, 3 follicular carcinomas and 34 papillary carcinomas (4 with tall‐cell features, 2 with insular and 2 with anaplastic de‐differentiation). DNA amplification was analysed by differential PCR. The transmembrane domain of erbB‐2 was sequenced in all tumours for activating mutations in position 659. Levels of mRNA expression were determined by competitive mRNA RT–PCR. Immunohistochemistry (IHC) for erbB‐2 protein expression in corresponding paraffin‐embedded samples was evaluated.RESULTSOur results showed no DNA amplification of erbB‐2. Sequencing of the transmembrane domain of erbB‐2 revealed no activating mutations. The level of mRNA expression was variable, 11 papillary carcinomas showing statistically significant elevated mRNA levels compared with corresponding normal thyroid tissue; however, this did not correlate with other indicators of poor prognosis. In contrast to elevated mRNA levels in tumours, the level of protein staining correlated with degree of differentiation, normal and hyperplastic tissue being strongly positive and poorly differentiated tumours negative.CONCLUSIONThere are no mutations or amplifications of the erbB‐2 gene in human thyroid tumours. Elevated erbB‐2 mRNA expression in some thyroid tumours is not associated with clinical features of poor prognosis; however, the significance of the elevated mRNA levels is unclear, as it did not result in protein overexpression. Instead, cytoplasmic erbB‐2 protein detection by IHC correlates with differentiation of human thyroid tumours and may be a feature of good prognosis.
A new chemiluminescent assay for the rapid detection of thyroid stimulating antibodies in Graves' disease
Authors: Watson  , Ajjan  , Phipps  , Metcalfe  , Weetman  
Published: March 2003

OBJECTIVEThyroid stimulating antibodies (TSAb) are the cause of Graves' disease (GD). At present, these antibodies can only be measured using bioassays, which are generally time consuming and difficult to apply to whole serum. Here we describe a new chemiluminescent assay for the detection of TSAb in serum samples.METHODSA Chinese hamster ovary (CHO) cell line, stably transformed with a reporter plasmid containing the firefly luciferase gene under the transcriptional control of multiple cAMP responsive elements (CRE), was transfected with the human thyroid stimulating hormone (TSH) receptor. A clonal cell line, (NA‐4), was obtained which showed a dose‐dependent increase in luciferase activity in response to bovine and human TSH stimulation. NA‐4 was subsequently used to study TSAb activity in 42 GD sera.RESULTSOf the GD sera 25 (60%) produced an increase in luciferase activity of 1.4–9 fold that obtained with control sera. Results were compared with an established bioassay for TSAb, based on the direct measurement of intracellular cAMP, and there was a significant correlation between the two assays (r = 0.8; P < 0.0001). IgG from GD patients, but not controls, also increased luciferase activity in NA‐4 cells using concentrations as low as 3mg/l in selected samples.CONCLUSIONThe present report describes a simple, sensitive and rapid assay for the detection of TSAb, with application both in the clinical analysis of GD patient sera and as a potential research tool for use in the isolation of TSAb monoclonal antibodies.
One‐year follow‐up of quality of life in adults with untreated growth hormone deficiency
Authors: Badia X. , Lucas A. , Sanmartí A. , Roset M. , Ulied A. 
Published: March 2003

OBJECTIVEThe aim of the study was to evaluate the impact on health‐related quality of life (HRQoL) in untreated GHD patients using the disease‐specific Assessment of Growth Hormone Deficiency in Adults (AGHDA) questionnaire.DESIGN AND PATIENTSA cohort of 356 consecutive adult GHD patients, diagnosed after the age of 18 years, from the endocrinology units of 37 Spanish hospitals were included over a 6‐month period in a longitudinal observational quality‐of‐life study. In addition, patients' HRQoL scores were compared to those obtained from a random sample of 963 subjects from the general population recruited by trained interviewers in a 6‐month period and matched by age and sex to figures of the 1991 Spanish census.MEASUREMENTSPatients were evaluated at baseline and after 12‐months. Socio‐demographic and health variables such as age,sex, level of education, income level, number of chronic diseases and self‐reported health status were recorded at baseline and follow‐up visits. Patients underwent physical and analytical examination and completed the AGHDA questionnaire. A survey including socio‐demographic, self‐reported health status and the AGHDA questionnaire was administered at the individuals' homes.RESULTSMean score for patients at baseline was 9.4 (CI = 8.4–10.4) and at 12 months 10 (CI = 8.8–11). HRQoL was worse in the case of older patients with a low level of education, lower income levels, reporting having an associated chronic disease and poor self‐reported health status (P < 0.01). Untreated GHD patients maintain or slightly worsen their HRQoL after 12 months of follow‐up, with high individual variability. Although AGHDA scores worsened during the observation period, differences were not statistically significant. AGHDA mean score in controls was 5.49 (CI = 5.27–5.71). Comparison of the mean AGHDA scores between patients and controls previously standardized by level of education and age were statistically different (P < 0.01), indicating that patients declared a worse HRQoL than the general population except for those aged 60–69 years. GHD patients presented a deterioration in HRQoL almost double that of the general population.CONCLUSIONSThese results permit comparison of patients' scores against reference scores with regard to the desirable effect of treatment. Future use of the AGHDA questionnaire in clinical trials should try to establish a relationship between biological and HRQoL changes.
Recent primary transnasal surgical outcomes associated with intraoperative growth hormone measurement in acromegaly
Authors: Abe Takumi , Lüdecke Dieter K. 
Published: March 2003

OBJECTIVESince 1983, we have measured GH intraoperatively to improve the surgical outcome for acromegalic patients with GH secreting pituitary adenomas. Here, we present the recent results of primary surgery in patients with acromegaly to examine the effect of improved surgical techniques and experience.PATIENTS AND MEASUREMENTIntraoperative GH concentrations were measured in 78 consecutive acromegalic patients who had not previously undergone surgery between May 1992 and April 1994 (45 females and 33 males, age range, 21–70 years, mean, 47.1 ± 1.3). All patients were followed for at least 3 years. Direct transnasal tumour extirpation was performed. Intraoperative GH measurements were assayed 0, 20 and 60 min after tumour removal. A plasma GH level ≤ 4.5 μg/l at 60 min after initial tumour removal was used as a criterion of radical tumour removal. In cases with intraoperative plasma GH concentrations ≥ 40 μg/l prior to tumour resection, the half‐life of the GH concentration at 20 min was used to assess completeness of tumour removal. In these cases, it was defined as having acheived a 50% reduction in plasma GH at 20 min compared to 0 min after tumour resection. To obtain intraoperative GH measurements, mild anaesthesia was continued for an average of 82± 23 min.RESULTSRadical tumour removal was determined intraoperatively in 51 patients and subsequently confirmed in 50 patients (98.0%). In 18 of 27 patients with incomplete tumour removal, immediate reoperation was performed under continuous anaesthesia. In 11 of these 18 patients, endocrinological remission was achieved (14.1%; 11/78). None of the remaining nine patients who did not undergo secondary surgery achieved remission. Secondary surgery improved the remission rate from 85.7% (12/14) to 92.9% (13/14) in microadenomas and from 70.1% (38/54) to 88.9% (48/54) in non‐invasive macroadenomas. Remission was not observed in patients with image‐proven extrasellar extension.CONCLUSIONSSecondary surgery based on intraoperative GH measurement improves the outcome of tumour resection in patients with non‐invasive GH secreting macroadenomas.
A low individualized GH dose in young patients with childhood onset GH deficiency normalized serum IGF‐I without significant deterioration in glucose tolerance
Authors: Bülow Birgitta , Marie Erfurth Eva 
Published: March 2003

OBJECTIVEMany GH deficient (GHD) patients have impaired glucose tolerance and GH substitution in these patients has caused deleterious effects on glucose tolerance with hyperinsulinaemia. This further impairment of glucose tolerance might be due to an unphysiologically high dose of GH. Whether such a deterioration can be avoided by an optimal GH replacement dose is not known. In most previous studies, the GH dose was calculated according to body weight or body surface area and not adjusted according to the serum IGF‐I response.DESIGNThe study was of open design and investigations were performed before the start of GH substitution and after nine months of treatment. The GH dose was adjusted according to the response in serum IGF‐I, and in patients with sub‐normal serum IGF‐I levels (all but two) we aimed for a serum IGF‐I level in the middle of the normal range. The median GH dose at the end of the study was 0.14 IU/kg/week.PATIENTSTen patients, eight males and two females, with childhood onset GHD were examined. Their median age was 27 years (range 21–28).MEASUREMENTSOvernight and 24‐h fasting levels of glucose, insulin and IGFBP‐1 were measured. Directly after the 24‐h fast an oral glucose tolerance test (OGTT), with measurements of glucose, insulin and IGFBP‐1 was performed. An intravenous glucose tolerance test (IVGTT) was performed after overnight fasting. Body composition was measured with bioimpedance analysis (BIA) and quality of life was assessed using a self‐rating questionnaire, Qol‐AGHDA.RESULTSAfter GH treatment, there were no significant changes in glucose tolerance, measured by overnight and 24‐h fasting levels of glucose, insulin and IGFBP‐1, an oral glucose tolerance test (after 24‐h fasting) and an intravenous glucose tolerance test (after overnight fasting). Percentage fat mass and BMI correlated negatively with both the 24 h fasting IGFBP‐1 levels and the IGFBP‐1 responses after the OGTT. All patients decreased their percentage of fat mass measured by BIA [median −2.9%; range −1.0–(−6.6); P = 0.005]. The administered GH dose correlated negatively with the relative change in whole body resistance (r = −0.66; P = 0.04). All, but one of the patients improved their quality of life score after GH therapy.CONCLUSIONSIn a group of young patients with childhood onset GH deficiency, 9 months of treatment with a low GH dose (median 0.14 IU/kg/week) caused no significant deterioration of glucose tolerance. The strong negative associations between BMI or percentage fat mass and IGFBP‐1 suggest that serum IGFBP‐1 is more closely related than insulin to body composition in GH deficient patients. It is important to consider which critical endpoints should determine the GH dose. We would suggest that, apart for normalizing the serum IGF‐I level, another main endpoint should be normalization of, or at least avoidance of any deterioration in glucose tolerance.
Laparoscopic adrenalectomy for phaeochromocytoma: endocrinological and surgical aspects of a new therapeutic approach
Authors: Col V. , De Cannière L. , Collard E. , Michel L. , Donckier J. 
Published: March 2003

OBJECTIVESTo evaluate the results of laparoscopic resection of phaeochromocytoma with a focus on pre‐and intra‐operative endocrinological and pharmacological aspects.DESIGNRetrospective study based on review of case notes and intraoperative anaesthetic records.PATIENTSEight patients (four men, four women) aged 13 to 70 (median: 45) years with symptomatic phaeochromocytoma (two patients with MEN IIa syndrome) diagnosed 6–36 months before adrenalectomy in four patients and just before operation in the four remaining patients. All patients presented with hypertension.MEASUREMENTSPre‐ and postoperative blood pressure (BP) was assessed using a sphygmomanometer, intraoperative measurements being obtained by intra‐arterial line. Adrenaline (A), noradrenaline (NA), metadrenaline (metA), normetadrenaline (normetA) and vanillylmandelic acid (VMA) were measured in 24‐h urine samples. Adrenal imagery consisted in all patients of abdominal computed tomography and [131I] metaiodobenzylguanidine (MIBG) scintigraphy, and in 2 patients, adrenal magnetic resonance imaging and octreotide scintigraphy. Determination of plasma volume was performed by isotopic method.RESULTSMedian (range) preoperative systolic and diastolic BP was 140 (130–240) and 90 (80–150) mm Hg, respectively. Predominant catecholamine secretion consisted of A in four patients (A pattern) and of NA (NA pattern) in the other four. Tumours smaller than 30 mm usually secreted A while larger ones secreted NA. Pre‐ and intra‐operative BP control was straightforward in all but two patients with preferential NA secretion. The median number of systolic and diastolic BP peaks were higher in patients with NA pattern (n = 6, range: 3–9) than in those with A pattern (n = 1.5, range: 1–6). Total duration of pneumoperitoneum ranged from 120 to 240 (median: 195) min. Intra‐ and post‐operative complications included intra‐abdominal bleeding, laparoscopically controlled (in one case), and upper pole kidney ischaemia in another. Postoperative hospital stay ranged from 4 to 11 days. All patients were asymptomatic postoperatively and pharmacologically controlled hypertension persisted in two of themCONCLUSIONSLaparoscopic adrenalectomy is a safe and efficient technique to remove phaeochromocytoma in terms of intra‐ and postoperative morbidity, with a low complication rate. Pre‐ and intra‐operative pharmacological blood pressure control is as effective as in conventional adrenalectomy, with greater instability in noradrenaline secreting tumours.