bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of thyroid hormone autoantibodies in healthy subjects
Authors: Sakata Shigeki , Matsuda Masafumi , Ogawa Toru , Takuno Hiroshi , Matsul Ikuo , Sarui Hiroshi , Yasuda Keigo 
Published: March 2008

SummaryOBJECTIVE The prevalence of thyroid hormone autoantibodies in patients with thyroid disorders has been well described, although the results have been variable. However, the prevalence of thyroid hormone autoantibodies in apparently healthy subjects remains unknown and its determination was the main objective of this study. SUBJECTS AND METHODS Sera obtained from 880 healthy subjects (365 men and 515 women) were examined for thyroid hormone autoantibodies by immune precipitation using radiolabelled thyroid hormones or thyroid hormone analogues.RESULTS Anti‐triiodothyronine (T3) and anti‐thyroxine (T4) antibodies were detected in none (0%) and in 3 (0·34%), respectively, of the 880 individuals studied using radiolabelied thyroid hormones. Similar tests in 385 healthy subjects using radiolabelled thyroid hormone analogues (polyaminocarboxy T3 and T4) showed the presence of anti‐T3 and anti‐T4 antibodies in 3 (0·78%) and in 4 (1·04%), respectively. None of the subjects had both anti‐T3 and anti‐T4 antibodies. Thus, the prevalence of anti‐T3 or anti‐T4 antibodies among healthy population was concluded to be as high as 1·8%. Radiolabelled thyroid hormone analogue binding to purified immuno‐globulin G (IgG), with or without the addition of an excess of uniabelled thyroid hormones, confirmed specific binding of thyroid hormones to the thyroid hormone autoanti‐body‐positive IgGs. The presence and class speciflclty of thyroid hormone autoantibodies was confirmed by the Ouchteriony immunodiffusionlautoradiography method, which showed biphenotypic heavy chain (IgG and IgA) and kappa (κ) light chain specificities. Serum concentrations of free thyroid hormones and TSH in thyroid hormone autoantibody‐positive sera were within the normal range.CONCLUSIONS These results indicate that the Occurrence of thyroid hormone autoantibodies among the healthy Japanese population is fairly common. However, interference of thyroid hormone autoantibodies in the radio‐Immunnoassay of free thyroid hormones is exceptional.
Thyroid function and thyroid size in normal pregnant women living in an iodine replete area
Authors: Berghout Arie , Endert Erik , Ross Alec , Hogerzeil Hendrlkus V. , Smits Nico J. , Wlerslnga Wilmar M. 
Published: March 2008

SummaryOBJECTIVE The interpretation of the changes in thyroid hormone concentrations during normal pregnancy is a matter of debate involving, in some geographical regions, enhanced thyrold activity in early pregnancy and a hypothyroid state In the third trimester.A clinically detectable increase in thyroid size has been found in areas of mild iodine deficiency ('goitre of pregnancy'), but not in iodine replete areas.DESIGN A prospective study. We have studied thyroid size and function In normal pregnant women living In an iodine replete area.PATIENTS Healthy women before and during a normal pregnancy resulting from artificial Insemination (n= 10) and other women during the normal menstrual cycle (n= 11), in the iodine replete area of Amsterdam. MEASUREMENTS Thyroid volume was measured by ultrasonography. Plasma T4, free T3, free reverse T3, TSH, thyroxine binding globulln, hCG, progesterone and thyroid autoantibodies were measured.RESULTS Thyroid volume did not change during prep nancy (data given before pregnancy and during lst, 2nd and 3rd trimesters, respectively: 10·3 ± 5·1, 10·6 ±4·4, 9·6 ± 3·8 and 9·4 ±3·0 ml, NS). Free T4 and free T3 levels declined during pregnancy (13·7±2·0, 13·5 ±4·1, 11·2 ±2·8, 10·2 ±1·6pmol/l, P= 0·005; 4·55 ±0·63, 4·64 ± 0·88, 3·72 ± 0·67 and 4·01 ± 0·75pmol/l, P= 0·003), whereas free reverse T3 levels increased during pregnancy (0·16 ± 0·04, 0·19 ± 0·07, 0·14 ±0·03 and 0·20 ± 0·07pmol/l, P= 0·001). Thyroglobulin levels remained unchanged. Thyroid hormones and thyroid volume did not differ between folllcular and luteal phases of the menstrual cycle.CONCLUSION Thyrold volume does not increase during pregnancy in iodlne‐replete areas. The decrease in free T4 and free T3 and the Increase in free reverse T3 concentrations during pregnancy resemble the changes in thyroid hormones seen in non‐thyroidal illness. This could be a physiologlcal adaptation enabling energy conservation durlng the high metabolic demands of pregnancy.
Susceptibility to autoimmune thyroiditis in Down's syndrome is associated with the major histocompatibility class II DQA 0301 allele
Authors: Nicholson L. B. , Wong F. S. , Ewins D. L. , Butler J. , Holiand A. , Demaine A. G. , McGregor A. M. 
Published: March 2008

SummaryOBJECTIVE Abnormalities of immune function, including thyroid autoimmunity, are common features of Down's syndrome, and the genetic associations of autoimmune thyroiditis have been extensively studied In otherwise normal patients with thyroid disease. In this study we have examined the HLA associations of autoimmune thyroid diseases in a cohort of adult subjects with Down's syndrome, to see whether they differed from those found in other populations.DESIGN AND MEASUREMENTS Restrlction fragment length polymorphism analysis was carried out in 41 subjects whose thyroid status was assessed by measuring thyroid function and autoantibody titres. The genotypes of subjects with and without hypothyroid autoimmune diseases were compared.SUBJECTS Forty‐one older subjects with Down's syndrome and an average age of 466 years under review by the Maudsley Hospital.RESULTS Hypothyrold autoimmune disease in thls study group was clearly associated with a 5·5‐kb Taql DQA restriction fragment length polymorphism (Pc= 0·013) corresponding to the major histocompatibility (MHC) class II DQA 0301 allele.CONCLUSIONS In contrast to Hashlmoto's thyroiditis and atrophic thyroiditis, there is a strong association between class II genotypes and hypothyroid autoimmune disease in Down's syndrome. This implies a role for a gene or genes on chromosome 21 in the development of autoimmune thyroid disease.
Imaging in endocrinology: use of a potential methodology for audit consensus development
Authors: Davies Melanie J. , Howlett Trevor A. 
Published: March 2008

SummaryOBJECTIVE To explore areas of consensus in the use of imaging techniques in the investigation of endocrine disorders.DESIGN A postal questionnaire sent to members of the Endocrine Section of the Royal Society of Medicine following a meeting of the Section In January 1993 on Imaging in Endocrinology.SUBJECTS Fifty‐two specialists completed the questionnaire which was sent in the first mailing after the meeting.MEASUREMENTS Consensus statements were defined as those In which greater than 75% of respondents either agreed or opposed the statement. Majority support or rejection was defined as greater than 50% In favour with less than 25% opposed or vice versa.RESULTS Many areas of consensus were defined particularly in the field of the use of Imaging in the investigation of pituitary disease. The questionnaire highlighted difficulties in obtaining a consensus view on the imaging techniques which should be employed in the investigation of thyroid, parathyroid and pancreatic disorders.CONCLUSION The results are a useful guide to areas in which further discussion and/or research is required. This methodology could, and we believe should, be applied to other areas of endocrine practice. Such results provide an initial data base to develop national audit guide‐lines on the use of imaging techniques in endocrine disorders.
Familial isolated primary hyperparathyroidism
Authors: Kassem M. , Zhang X. , Brask S. , Erlksen E. F. , Mosekilde L. , Kruse T. A. 
Published: March 2008

SummaryFamilial primary hyperparathyroidism (PHPT) Is usually encountered in the context of multiple endocrine neoplasia (MEN) syndromes. Few families have been reported in the literature where PHPT was the only abnormality. However, in these families no long‐term follow‐up data were reported and no genetic linkage studies were performed.OBJECTIVE We investigated a large family with a familial primary hyperparathyroidism for biochemical and genetic markers of multiple endocrine neoplasia syndromes. DESIGN A family screening study.PATIENTS Thirty‐seven family members participated in this study including 7 patients who had been previously operated upon for PHPT.MEASUREMENTS Serum calcium (albumin adjusted), was measured in all family members. Hypercalcaemic subjects and patients who had been operated upon for PHPT were assessed for biochemical markers of MEN syndromes (serum gastrin, prolactin, calcitonin, fasting plasma glucose and 24‐hours urinary excretion of adrenaline, noradrenaline and vanillylmandelic acid (VMA). Genetic linkage analysis was performed using DNA markers linked to chromosome 11q13, the presumed MEN type 1 (MEN‐1) locus.RESULTS Four new patients with PHPT and two with probable PHPT were discovered. No clinical or biochemical evidence of MEN syndromes could be detected. DNA marker pMS5l(D11S97) was Informative, maximum two‐point lodscore of 2·12 at a recombination fraction of 0·05 confirming linkage to chromosome 11q13.CONCLUSIONS Familial PHPT can exist as a separate clinical entity. Isolated familial PHPT is caused by mutation in a gene located in the MEN‐1 region on chromosome 11q13, possibly the MEN‐1 locus.
Effects of insulin‐like growth factor‐I on growth hormone and prolactin secretion and cell proliferation of human somatotrophinomas and prolactinomas in vitro
Authors: Atkin S. L. , Landolt A. M. , Fay P. , Jeffreys R. V. , Hipkin L. , White M. C. 
Published: March 2008

SummaryOBJECTIVE IGF‐I inhibits GH secretion from normal and some tumorous pituitary tissue, and has been shown to be mitogenic for gonadotrophinoma cells in vitro. It is not known whether IGF‐l affects somatotrophinoma cellular proliferation or the secretion of other hormones, such as PRL and α‐subunit, which are often co‐secreted by these tumours. We have therefore examined the effects of IGF‐l on proliferation and hormonal secretion of human somatotrophinomas and prolactinomas in vitro.DESIGN Pituitary adenoma tissue was dispersed to single cells in monolayer culture. The effects of 100 nw IGF‐I on GH, PRL and α‐subunit secretion were determined over 4‐hour and over 4‐day periods, and a 4‐day dose‐response study using 1–100 nM IGF‐I was performed on two tumours. Adenoma cell S‐phase proliferation was determined after bromodeoxyuridine Incorporation for 1 hour after 4 days, using a double immunostaining method.RESULTS Over 4 hours, 100 nw IGF‐I had no effect on GH, PRL or α‐subunit secretion in 7 tumours. Over 4 days, 100 nw IGF‐I reduced GH secretion In 518 somatotrophinomas (range 17–84%, P < 0·05) compared to controls, with tumours responding to IGF‐I having lower basal serum and in‐vitro GH levels than tumours unaffected by IGF‐I (P < 0·05). There was no effect on α‐subunit secretion in any of the three tumours studied. PRL co‐secretion was increased In 315 somatotrophinomas compared to control (20, 30 and 37%, P < 0·05), with tumours responding to IGF‐I being associated with lower basal serum and in‐vitro PRL levels than those tumours unaffected by IGF‐I. IGF‐I also increased PRL secretion in 2/2 prolactinomas (27 and 32%, P < 0·05) compared with control. GH was inhibited and PRL secretion was stimulated by 1 and 10 nw IGF‐I in the two dose‐response studies. The proliferative labelling index did not exceed 1·9% in any tumour and no proliferative effect was found with 100 nw IGF‐I in any somatotrophinoma.CONCLUSION IGF‐I inhibited tumorous GH in 62% and stimulated PRL secretion in 71 % of tumours over 4 days, without affecting α‐subunit secretion or being mitogenic for somatotrophinoma cells in vitro. No hormonal effects were observed over short (4‐hour) incubations. IGF‐I may be a newly recognized factor directly stimulating tumorous PRL secretion.
The severity of growth hormone deficiency in adults with pituitary disease is related to the degree of hypopituitarism
Authors: Toogood Andrew A. , Beardwell Colin G. , Shalet Stephen M. 
Published: March 2008

SummaryOBJECTIVE A number of studies of the effect of GH replacement therapy in adult patients with GH deficlency have been published, but the definition of GH deficiency has varied considerably. In order to define severe GH deficiency more critically we have determined GH status in the context of gonadotrophin, ACTH and TSH secretion in adult patients with pituitary disease.DESIGN Analysis of peak GH response to an insulin tolerance test performed during comprehensive assessment of pituitary function.PATIENTS One hundred and ninety non‐acromegalic patients (96 male) with pituitary disease whose ages ranged from 16 to 72 (mean 39·4) years.MEASUREMENTS The patients were divided into four groups according to the number of anterior pituitary hormone deficiencies demonstrated; isolated GH deficiency (GHD0), or GH deficiency plus an additional one, two or three pituitary hormone deficits (GHD1, GHD2, GHD3).RESULTS The four groups were matched for age and blood glucose nadir during the ITT. The median (interquartile range) GH peaks were GHD0, 10·0 (5·4–16); GHD1, 4·0 (2·7–7·7); GHD2, 2·0 (1–2·9); GHDB, 1·8 (1–3·2) mU/l. There was a Significant downward trend in the medians (P < 0·0001). The differences between GHD0 and GHD1, and GHD1 and GHD2, were highly significant (P < 0·0001); however, there was no difference between GHD2 and GHD3. Ninety‐one per cent of patients in combined groups GHD2 and GHD3, 55% in GHD1 and 24% in GHD0 had a peak GH < 5 mU/l.CONCLUSIONS Our study has shown that GH deficiency is variable according to the degree of hypopltuitarism present and that the greater the number of pituituary hormone deficits the more severe the GH deficiency. These observations will help to clarify the diagnosis of GH deficiency In adult life.
Acute changes in thyroid volume and function following 131I therapy of multinodular goitre
Authors: Nygaard Birte , Faber Jens , Hegedüs Laszlo 
Published: March 2008

SummaryOBJECTIVE Many textbooks claim that radioIodine (131I) treatment should be given with care to a goitre with substernal extension, for fear of acute swelling of the gland and thus respiratory problems. Since 131I Is used increasingly in the treatment of non‐toxic as well as toxic goitre we have evaluated the acute changes in thyroid volume following 131I therapy.DESIGN Evaluation of potential acute changes in thyroid volume and function after 131I treatment in patients with non‐toxic goitre treated because of compression symptoms or for cosmetic reasons, as well as In patients with toxic goitre.PATIENTS Out‐patients with multinodular goitre, either non‐toxic (n= 20) or toxic (n= 10). Excluded were patients with a substernal goitre.MEASUREMENTS Ultrasonically determined thyroid volume and standard thyroid function variables were Investigated before and 2, 7, 14, 21, 28 and 35 days after treatment.RESULTS In non‐toxic goitres the thyroid volume did not increase significantly, the maximum increase in the median volume being 4% on day 7. Serum levels of free T3 and free T4 Indices increased by 20% (day 7) and 13% (day 14) (P= 0·002), respectively.Likewise thyroid volume in toxic nodular goitre did not change significantly after 131I treatment (maximum median increase was 2%). None of the patients presented symptoms of tracheal compression.CONCLUSIONS 131I treatment of non‐toxic as well as toxic multinodular goitre does not seem to increase thyroid volume.
Variability of serum thyroglobulin levels is determined by a major gene
Authors: Premawardhana L. D. K. E. , Lo S. S. S. , Phillips D. I. W. , Prentice L. M. , Smith B. Rees 
Published: March 2008

SummaryOBJECTIVE There are large variations in the circulating concentrations of thyroglobulin. The purpose of this study was to explore the possibility of a genetic basis for the variability of serum concentration of thyroglobulin (Tg) in euthyroid individuals.DESIGN The serum concentration of thyroglobulin (Tg) varies several‐fold in euthyroid individuals. Other circulating proteins also show wide normal ranges of concentration and these variations have been shown to have a genetic as well as an environmental basis. To explore the possibility of a genetic bash for variability in serum Tg levels, an analysis was made of serum Tg levels in 44 pairs of identical twins and 66 nuclear families who were euthyroid and thyroid autoantibody negative (thereby eliminating subclinical autoimmune thyroid disease and Tg autoantibody Interference with the Tg assay).RESULTS Each pair of identical twins tended to have a similar Tg level and the overall correlation was highly significant (r= 0·734, P < 0·001). There was no relation between Tg and TSH levels In the twins (r= 0·119; P= 0·366). Segregation analysis of the 66 families showed that where both parents had Tg levels above the overall median for the subjects (males, 19 μg/l; females, 33 μg/l), 73% of the offspring also had concentrations above these levels, compared with 30% of the offspring when one parent had a high Tg level and only 16% in families where neither parent had a high Tg level.CONCLUSIONS Complex segregation analysis using the computer program Pointer suggested that variability in Tg levels was the result of a major dominant‐like gene effect (accounting for 80% of the variability) combined with a multifactorial component. Thyroglobulin, a template for thyroid hormone production, is also a major thyroid autoantigen and inherited variations in serum Tg levels may have implications for the pathogenesis of auto‐Immune thyroid disease.
Bone mineral density and metabolism in premenopausal women taking l‐thyroxine replacement therapy
Authors: Garton Mark , Reid Ivan , Loveridge Nigel , Robins Simon , Murchison Lilian , Beckett Geoffrey , Reid David 
Published: March 2008

SummaryBACKGROUND AND OBJECTIVE Excess endogenous thyroxine causes bone loss, but the effects of exogenous thyroxine are disputed. We report on bone mass and metabolism in women taking l‐thyroxine therapy.DESIGN Cross‐sectional and longitudinal studies.PATIENTS Cross‐sectional study: 40 healthy premenopausal women with autoimmune thyroiditis taking either physiological (serum TSH usually normal, 0·35–3·3 mU/l) or suppressive (serum TSH usually < 0·35 mu/l) doses of l‐thyroxine; patients were also compared with previously acquired age and weight matched premenopausal volunteers with no history of thyroid dysfunction. Longitudinal study: 28 patients were followed‐up ≥ 1 year later.MEASUREMENTS In all subjects bone mineral density (BMD) was measured at the anteroposterior lumbar spine and left hip (femoral neck, greater trochanter and Ward's area) using dual‐energy X‐ray absorptiometry, and physical activity assessed using the Framingham physical activity index. Serum osteocalcin (OC), PTH and vitamin D, and urinary pyridinoline and deoxypyridinoline excretion were measured in patients.RESULTS Cross‐sectional study: The patient groups were well matched for disease duration and physical activity although the suppressed group were slightly younger (mean 3·1 (SD 7·5) vs 43·3 (3·9) years, P < 0·05). BMD, serum OC, PTH and vitamin D, and urinary cross‐link excretion did not differ significantly between the two groups. Multivariate analysis of the whole group suggested that BMD at the femoral neck and greater trochanter was related positively to weight and physical activity and negatively to thyroxine dose (μg/kg/day) and patient age. At the lumbar spine BMD was reduced non‐specifically in the presence of thyroid disease and treatment, but this effect appeared to decline with increasing duration of therapy. A similar analysis of the patient group suggested that urinary cross‐link excretion correlated positively with thyroxine dose, and negatively with duration of treatment. Longitudinal study: Annualized changes in BMD were inversely related to thyroxine dose (μg/kg/day) at all sites but achieved statistical significance only at the femoral neck and Ward's area.CONCLUSION We did not find any effect of persistent historical TSH suppression on current bone mass, and this might relate to the relative insensitivity of older TSH assays. However, the cross‐sectional and longitudinal data suggest that high daily doses of thyroxine In relation to patient body weight might adversely affect bone mass, particularly at the hip. These findings support the contention that excess exogenous thyroxine might predominantly deplete skeletal sites, such as the femoral neck, rich in cortical bone.
Amplification of nocturnal melatonin secretion in women with functional secondary amenorrhoea: relation to endogenous oestrogen concentration
Authors: Okatani Yujl , Sagara Yusuke 
Published: March 2008

SummaryBACKGROUND AND OBJECTIVE Although there is extensive evidence that melatonin inhibits gonadotrophin secretion in animals, there is a parity of data on the relation between melatonin and ovarian function in humans. The purpose of this study was to evaluate the relation between endogenous oestrogen concentrations and nocturnal melatonin secretion occurring in patients with secondary amenorrhoea (SA).DESIGN AND PATIENTS Nocturnal serum melatonin concentrations were determined in 20 women with SA, 5 women with endometriosis showing normal menstrual cycles and 11 volunteers with normal menstrual cycles.MEASUREMENT Serum melatonin concentrations were determined by high performance liquid chromatography with electrochemical detection. Differences in melatonin concentrations were examined by analysis of variance.RESULTS Nocturnal melatonin concentrations in patients with SA were significantly higher than in normal women (P < 0·01 vs women with normal menstrual cycles). There were significant negative correlations between cummulative melatonin levels (between 2000 and 0800 h) and serum 17β‐oestradiol (r= ‐0·561, p < 0·01) and between peak serum melatonin values and the serum 17β‐oestradiol (r= ‐0·608, P < 0·01) in SA. Intravenous administration of a conjugated oestrogen (Premarin 20 mg) significantly suppressed nocturnal melatonin secretion (P < 0·05). A low oestrogen state, induced by long‐term (3·5 months) GnRH agonist treatment (900 μg/day of buserelin acetate) of the women with endometriosis produced an increase in nocturnal melatonin secretion comparable to that found in SA women.CONCLUSION Our findings suggest that elevated nocturnal melatonin secretion in women with secondary amenorrhoea may be related to their low oestrogen concentrations.