bluuebunny/crossref_metadata_2025_split huggingface dataset:
A 64 kDa membrane antigen is a recurrent epitope for natural autoantibodies in patients with Graves' thyroid and ophthalmic diseases*
Authors: Kendler David L. , Rootman Jack , Huber Gerold K. , Davies Terry F. 
Published: March 2008

SUMMARY objective We have explored the recently described 64 kDa extraocular muscle antigen that is associated with autoantibodies in the serum of patients with severe Grave's ophthalmopathy. The localization of the antigen and the specificity of autoantibodies for both eye muscle antigens and ophthalmopathy patients were investigated design Western blotting and immunoprecfpftatlon of metabolically labelled antigen from eye muscle and control tissues with sera from ophthalmopathy, Graves' without ophthalmopathy, and normals were used patients Sera from normals (n= 9), patients with recent onset Graves' ophthalmopathy (n= 23), and patients with Graves' disease without ophthalmopathy (n= 8) were utilized. measurements Immunoblots using detergent phase separated (amphiphilic) antigen preparations from fetal eye muscle, skeletal muscle and control tissues were quantitated. Metabolically labelled eye muscle and skeletal muscle antigens were immunoprecipitated using patient and control IgG results In the eye muscle detergent phase, immuno‐reactivity around 64 kDa was detected in 30% of the patients with ophthalmopathy (n= 23) as well as 38% of patients with Graves' disease and no ophthalmopathy (n= 8) and in 30% of normal sera (n= 9). There was significantly more of this antl‐64 kDa reactivity in sera from the ophthalmopathy patients compared with the normals (P > 0·01). 64 kDa reactivity to detergent phase antigens prepared from human thyroid, skeletal muscle, brain, and liver was also observed with these positive sera indicating the polyreactlvfty of the IgG interactions to conserved antigens in this region. conclusions We conclude that IgG antibodies binding to a recurrent 64 kDa antigen are present in many normal human sera, with increased concentrations detectable in sera from Graves' ophthalmopathy patients. Such ‘specificity‐crossover’ with similar molecular weight trans‐membrane antigens is likely to be caused by natural autoantibodies reacting with recurrent autoepitopes rather than a factor aetiological in the disease process
The pituitary gland is capable of responding to two successive doses of growth hormone releasing hormone (GHRH)
Authors: Suri D. , Hindmarsh P. C. , Matthews D. R. , Brain C. E. , Brook C. G. D. 
Published: March 2008

SUMMARYWe have studied the serum growth hormone (GH) response to two consecutive doses of growth hormone releasing hormone (GHRH) (50, 100, 200 μg) given 1, 2 or 3 h apart in seven adult males. The serum GH profile was analysed by deconvolution incorporating a variable half‐life for OH. All three doses of GHRH stimulated maximal GH secretion: 50 μg, 146.0 mU/min (SEM 24.0); 100 μg, 128.1 mU/min (SEM 14.3); 200 μg, 134.1 mU/min (SEM 20.5) (one‐way ANOVA, P = NS). The magnitude of the second secretory burst after the second dose of GHRH was less than that Induced by the first injection of GHRH, particularly when doses of 200 μg were used. Factors influencing the response to the second dose were the GH secretory status at the point that the stimulus was applied and the time interval between administration of the first and second doses. These studies demonstrate that the pituitary gland is capable of responding to two consecutive doses of GHRH although the second response is always less than the first. The data demonstrate the importance of using methods of assessing GH secretion and not relying simply on measured serum GH concentration values.
Testosterone‐secreting virilizing adrenal adenoma with human chorionic gonadotrophin receptors and 21‐hydroxylase deficiency
Authors: Leinonen Pekka , Ranta Tapio , Slegberg Rita , Pelkonen Risto , Heikkilä Päivi , Kahri Arvi 
Published: March 2008

SUMMARYA 60‐year‐old woman was evaluated for persistently elevated serum testosterone concentrations after bilateral ovariectomy. Her serum cortisol, androstenedione, dehydroepiandrosterone sulphate and 17‐hydroxyprogesterone levels were normal, and decreased after dexamethasone administration. Those of testosterone (17.8–18.4 nmol/l) were remarkably high (normal range 0.7–2.8 nmol/l), were not suppressed by dexamethasone, but clearly increased after hCG administration (up to 128 nmol/l). Computed tomography revealed an adenoma in the right adrenal gland and adrenal scintigraphy under dexamethasone suppression visualized this adenoma. A right adrenalectomy was performed. (1) The tumour was histologically and ultrastructurally adrenocortical adenoma of zona reticularis cell type. (2) The adenoma tissue contained hCG receptors (198 fmol/g). (3) During tissue culture both ACTH and hCG were capable of maintaining its testosterone production, which was attenuated with time without stimulation. (4) The adenoma tissue did not elaborate 21‐hydroxylated steroids In contrast to normal adrenal tissue. Thus the aberrant endocrine behaviour of this gonadotrophin‐responsive testosterone‐secreting adenoma of adrenal zona reticularis cell origin can be explained by ectopic functional hCG receptors and the lack of 21‐hydroxylase activity
Disturbance of osmoregulated thirst and vasopressin secretion in thyrotoxicosis
Authors: Harvey J. N. , Nagl D. K. , Baylis P. H. , Wllkinsont R. , Belchetz P. E. 
Published: March 2008

Summary. objective To assess the effect of untreated thyrotoxicosis on osmoregulated thirst sensation and AVP secretion.design Measurements were made at 30‐minute Intervals while untreated thyrotoxic patients were given sodium chloride 855 mmol/l Intravenously for 2 hours followed by water drinking adlibitum for 2 hours. The protocol was repeated when the patients were euthyroid.patients Eight newly diagnosed thyrotoxic patients were studied.measurements Thirst sensation (visual analogue scale), plasma osmolality, AVP and plasma renin activity were measured.results Prior to osmotic stimulation and after plasma osmolality had been returned to normal by drinking water, thirst sensation was Increased in the thyrotoxic state. Plasma AVP showed an exaggerated response to hypertonic saline in the patients when they were thyrotoxic. Increasing plasma osmolality produced a linear Increase in thirst sensation and log linear increase in plasma AVP. However, in the thyrotoxic state both these relations were altered. The apparent osmolar thresholds for onset of thirst sensation and AVP release were similar (281 and 280 mosm/kg respectively) and were reduced similarly In the thyrotoxic state (269 and 274 mosm/kg respectively).conclusions The osmostat mechanisms which regulate thirst sensation and AVP release are reset In the thyrotoxic state. The responses of thirst sensation and of plasma AVP to increasing plasma osmolality are altered similarly, suggesting that thyrotoxicosls affects both homeostatic functions by a common mechanism.
Stimulation and suppression of intact parathyroid hormone (PTH1–84) in normal subjects and hyperparathyroid patients
Authors: Lips Paul , Netelenbos J. Coen , Doorn' Lena van , Hackeng Wll H. L. , Llps Cees J. M. 
Published: March 2008

Summary. objective Because of an overlap between serum PTH values In healthy controls and hyperparathyroid patients we sought to evaluate a short stimulation and suppression test for differentiating the two groups.subjects Subjects were 34 patients with primary hyperparathyroidlsm (PHPT) and 25 healthy controls.design After stimulation with Intravenous EDTA (10 mg/kg body weight In 5 minutes) blood samples were obtained for up to 15 minutes. After an oral calcium dose of 1 g, blood samples were obtained at 1 and 2 hours. After an Intravenous calcium dose (2.5 mg/kg body weight in 30 seconds), blood samples were obtained serially for 20 minutes.measurement Serum PTH(1–84) was measured by a double antibody technique.results The intravenous EDTA test resulted in an average 2‐6‐fold Increase of serum PTH(1–84) In hyperparathyroid patients, whereas it increased 10.5‐fold in controls. A response was absent in three of 23 patients. There was an overlap in results between patients with mild hyperparathyroldism and controls. The oral calcium dose decreased serum PTH(1–84) In patients to 0.73 and in controls to 0.55 of the basal value, but six of 15 patients and two of 12 controls did not respond. The intravenous calcium test resulted in a drop of serum PTH(1–84) In hyperparathyrold patients to 0.51 and in control subjects to 0.40 of the basal value, and non‐responders were not observed. There was a strong correlation between the responses to the EDTA and the calcium Infusion tests In the patients (r=0.97, P < 0.1). Fasting serum calcium and serum PTH(1–84) showed a positive correlation in PHPT patients (r= 0.75, P< 0.001) and a negative correlation in control subjects (r= ‐0.41, P<0.05). Based on these relationships, hyperparathyrold patients and controls could be completely separated.conclusion The wide range of responses to stimulation and suppression tests and the correlation between these responses in hyperparathyroid patients indicate various degrees of autonomy. As the response to these tests Is less marked In patients than in controls and both groups still overlap, these tests are not useful for the diagnosis of primary hyperparathyroldism.
Prevalence of thyroid deficiency in pregnant women
Authors: Klein R. Z. , Haddow J. E. , Falx J. D. , Brown R. S. , Hermos R. J. , Pulkkinen A. , Mitchell M. L. 
Published: March 2008

Summary. objective The present study was designed to determine the current prevalence of gestational hypothyroidism, since maternal thyroxine deficiency is associated with poor obstetric outcomes and mental retardation in the surviving offspring.design TSH concentrations were measured In the sera of women at 15—18 weeks of gestation. Those sera with TSH concentrations above 6 mU/l and the two sera closest In order with TSH concentrations below 6 mU/l were further analysed for T4, FT4, TBG, and antithyrold antibodies. Study criteria for hypothyroidism were sera with elevated concentrations of TSH plus both a free T4 concentration and a total T4 concentration and /or T4/TBG ratio more than two standard deviations below the mean for the control pregnant women.patients The sera were from 2000 consecutive women In Maine being tested for alpha‐fetoprotein concentration at 15–18 weeks of gestation.results TSH concentrations above 6 mU/l ere found in the sera of 49 women, 2.5% of the pregnant women. Six women with elevated TSH concentrations (range 6.9–54 mU/l) had both a FT4 concentration and a T4/TBG ratio and/or a T4 concentration more than two standard deviations below the respective control means, meeting the study criteria for thyroid deficiency, and thus giving a prevalence of 0.3%. The remaining 43 women with elevated TSH concentrations were classified as having compensated thyroid disease although some may have been hypothyroid. Fifty‐eight per cent of women with TSH concentrations above 6 mU/l and 90% of the women with elevated TSH concentrations and at least one thyroxine index more than two standard deviations below the control means had positive titres of antithyroid antibodies as opposed to 11% of the controls.conclusions Although it is not known what severity of maternal thyroid deficiency is necessary to cause fetal brain damage, the present data Indicate a sufficiently high prevalence of thyroid dysfunction to demand Investigation of the mental development of the offspring of women with thyroid dysfunction and of the effect of replacement therapy.
Changes in circulating thyroid hormone levels and systolic time intervals in acute hypothyroidism
Authors: Price D. E. , O'Malley B. P. , Northover B. , Rosenthal F. D. 
Published: March 2008

Summary. objective We have previously reported that, In thyrotoxic patients treated with carbimazole, serum T4 and T3 levels are the first parameters to return to normal, followed by the systolic time Interval (STI, a marker of thyroid function at tissue level) and then the serum TSH. The aim of this study was to compare the rate of change of thyroid hormones, TSH and STI in treated hypothyroid patients after the sudden withdrawal of thyroxine.design and patientsSerum T4, T3 (free and total) and TSH were measured in 12 patients taking thyroxine for primary hypothyroidism; seven were biochemically euthyroid and five were over‐replaced, as defined by an elevated free T4 and a sub‐normal TSH. Thyroxine was withdrawn and the measurements repeated three times a week until the STI rose above the euthyroid range (0.26–0.32).results After stopping thyroxine, the serum TSH and STI left the normal range, in advance of the free T4 and T3, after 9.5 × 0.95 and 12.2 × 1.5 days respectively (mean‐. SEM). The TSH was the first parameter to leave the euthyroid range In all subjects except one in whom the serum TSH was fully suppressed (< 0.05 mU/l) Initially. In the euthyroid group the TSH and STI increased rapidly after stopping thyroxine (time to leave euthyroid range 7.4 × 0.8 and 9.4 × 0.7 days respectively). In contrast, In the over‐replaced group serum TSH and STI became elevated after 12.4 × 1.0 days (P < 0.005 vs euthyrold group) and 16.0 × 2.7 days (P < 0.05 vs euthyroid group) respectively. There was no delay In the fall in serum T4 or T3 in the over‐replaced group when compared with the euthyrold group. CONCLUSIONS in the evolution of primary hypothyroidism, markers of thyroid function at a tissue level (TSH and STI) become abnormal In advance of thyroid hormones. After stopping thyroxine therapy in treated hypothyroid patients, there is a delayed rise in STI and serum TSH levels in subjects with a subnormal TSH level, as compared with those with a normal TSH on treatment. This suggests mild tissue thyrotoxicosis in these Individuals.
Glucocorticoid receptors in lymphocytes in anorexia nervosa
Authors: Glrardln E. , Garoscio‐Cholet M. , Dechaud H. , Lejeune H. , Carrier E. , Tourniaire J. , Pugeat M. 
Published: March 2008

Summary. objective The aim was to explore the down‐regulation of the glucocortlcoid receptors during hypercortlsolaemla in anorexia nervosa.design Urine and plasma samples were obtained for cortisol determination and blood lymphocytes were Isolated for receptor binding studies.patients Sixteen anorexic patients, aged 16–27 years, with a meanSEM body mass Index of 14.2.2.0 (ranging from 11.1 to 17.4), and 15 normal women were studied. Six patients were reinvestigated after a significant weight gain.measurements The binding capacity and affinity of the glucocorticold receptors were measured with dexamethasone as llgand on lymphocytes.results In patients, both total and free plasma cortisol concentrations were higher than in the normal women, as was their urinary free cortisol; the number of giucocorticold receptors per cell (Ro) and the binding affinity (Kd) for dexamethasone were, however, not significantly different (Ro: 7687.1750 vs 7347.1285 sites/cell; Kd: 7.7.2.4 vs 7.4.1.7 nM at 24.C). After weight gain (14.2 to 16.2 kg/ m2), receptor numbers were 8421 .2126 (pre) and 9011 . 500 (post) sites/cell, which are not significantly different (p>0.2); the Kd was unchanged (9.3.2.6 vs 9.2.2.4 nM).conclusions Hypercortlsolaemla does not down‐regulate the lymphocyte glucocorticoid receptors In anorexia nervosa and a post‐receptor defect might be Involved in peripheral tissue resistance to the effects of gtucocortlcold hormones in undernutrition.
Association between autoimmune thyroid disease and Familial Alzheimers disease
Authors: Ewins David L. , Rossor Martin N. , Butler Joan , Rogues Penelope K. , Mullen Michael J. , McGregor Alan M. 
Published: March 2008

Summary. objective To determine the prevalence of autoimmune thyroid disease in Familial Alzheimer's Disease kindreds and to ascertain whether there is any evidence for genetic linkage between the two conditions.design Retrospective study of Familial Alzheimer's Disease kindreds.patients Seventy affected and unaffected family members from 12 kindreds.measurements Antl‐thyroglobulin and anti‐microsomal autoantibody status was determined using an enzyme‐linked immunosorbent assay. Thyrotrophin levels were determined by an Immunoradiometric assay.results Of the family members, 41.4% had evidence of autoimmune thyroid disease, with significant co‐segregation between the presence of thyroid autoantibodles and the development of Alzheimer's disease (p<0.01).conclusions This study demonstrates a very high prevalence of autoimmune thyroid disease In Familial Alzhelmer's Disease kindreds and suggests that a genetic factor contributing towards the development of auto‐Immune thyroid disease may be located on chromosome 21 within close proximity to the Familial Alzheimer's Disease gene.
Clonidine pretreatment modifies the growth hormone secretory pattern induced by shortterm continuous GRF infusion in normal man
Authors: Lima L. , Arce V. , Diaz M. J. , Tresguerres J. A. F. , Devesa J. 
Published: March 2008

Summary. objective The aim of this study was to Investigate the effect of a single dose of clonidlne on the pattern of GH release in response to a 10‐hour continuous GRF infusion in normal man.design Plasma GH was analysed In samples withdrawn at 20‐mlnute Intervals, from 0900 to 1900 h, according to the following protocols: in a control study, a placebo was given at 1000 h; in other experiments, clonidlne (300 μg, oraily) was given at 1000 h, alone or together with a continuous intravenous Infusion of GRF 1–29 (0.3 μg/kg/h) starting at this time. In another experiment, the continuous Infusion of GRF 1–29 was preceded by placebo administration at 1000 h.patientsEight normal volunteers (four women and four men), aged 19–24 years were studied. MEASUREMENTS Plasma GH levels were measured by RIA. Analysis of the pattern of GH secretion was performed using cluster analysis.resultsClonidlne induced a slight but significant increase In plasma GH values, peaking 60 to 120 minutes later; however, no significant changes were observed in Indices of total and pulsatile GH release for the whole sampling period in this study. Continuous GRF administration led to increased episodic GH secretion, by augmentIng GH peak amplitude, although peak frequency was not modified. An increase in interpulse GH values was also observed during GRF infusion. Pretreatment with clonidine clearly changed the pattern of GH release during GRF infusion: the amount of GH secreted was significantly higher, the number of GH peaks significantly Increased, and almost all the GH was secreted within them.conclusionsThese data concord with our previous demonstration that clonidlne disrupts the hypothalam‐somatotroph rhythm by Inhibiting the hypothaiamic release of somatostatin. Given that clonidlne pretreatment induced a more physiological episodic pattern of GRF‐ induced GH release, the possibility of combining clonidipe and GRF therapy for short stature In children is envisaged.
Effect of pyridostigmine and pirenzepine on GH responses to GHRH in hyperthyroid patients
Authors: Valcavl R. , Dieguez C. , Zini M. , Page M. D. , Dottl C. , Portioli I. , Scanlon M. F. 
Published: March 2008

Summary. objective We wished to investigate whether thyrotoxicosis can influence the cholinergic modulation of GH secretion.design Pyridostigmine was given orally, then GHRH injected i.v., and levels were measured. In a separate study, pirenzepine was injected i.v., then GHRH, and growth hormone levels were measured. PATIENTS Thyrotoxic patients were compared with normal subjects.measurementsGH was measured from – 30 to + 120 minutes at intervals of 15 minutes.results Pyridostigmine markedly increased GH responses to GHRH in normal subjects, but not in thyrotoxic patients. Pirenzepine abolished the GH response to GHRH in thyrotoxic patients.conclusions GH responses to GHRH in hyperthyroid patients were suppressed by cholinergic muscarlnic receptor blockade with pirenzepine. Activation of cholinergic pathways with pyridostigmine did not increase GH responses to GHRH In these patients. This may be a consequence of increased hypothalamic cholinergic function or reduced hypothalamic GHRH activity in hyperthyroidism. Our findings demonstrate a further mechanism by means of which thyroid status may affect the secretory activity of the somatotroph.
Laron‐type dwarfism with apparently normal high affinity serum growth hormone‐binding protein
Authors: Buchanan C. R. , Maheshwari H. G. , Norman M. R. , Morrell D. J. , Preece M. A. 
Published: March 2008

Summary. objective Normal serum contains a high affinity GH‐binding protein, which appears to be Identical with the extracellular domain of the GH receptor. It Is normally absent from the serum of patients with Laron‐type dwarf‐ism. We wished in this study to define the serum GH‐binding protein status of a family with Laron‐type dwarf‐ism.design and patientsWe performed an open case study of an Asian family In which three sisters (aged 3 to 15 years) had the phenotype of Laron‐type dwarfism. Sera from a fourth, unrelated girl with Laron‐type dwarfism and subjects without endocrine disorders were used as control samples.measurements Laron‐type dwarfism was confirmed by demonstration of elevated serum GH levels and low serum IGF‐I levels on Immunoassay, with serum IGF‐I levels falling to rise during treatment with GH. Serum GH‐binding proteins were characterized using gel chromatography on Sephacryl S‐100HR following Incubation of serum with 125I‐GH, Scatchard analysis of ligand binding, and by polyacrylamide gel electrophoresis after covalent cross‐linking to 125I‐GH.resultsAll members of the family had high affinity serum GH‐binding protein activity similar in size, circulating levels and apparent affinity for GH to that of normal subjects. This contrasted with the very low serum GH‐binding protein activity in the unrelated child with Larontype dwarfism and previous reports of serum GH‐binding protein levels In this disorder.conclusionsThe affected patients may possess a novel biochemical defect which results in GH‐resistance and reduced production of IGF‐I in the presence of normal serum GH‐binding protein levels.
Influence of thyroxine treatment on thyroid size and anti‐thyroid peroxidase antibodies in Hashimoto's thyroiditis
Authors: Hegedüs Laszlo , Hansen Jens Melholm , Feldt‐Rasmussen Ulla , Hansen Bo Melholm , Høier‐Madsen Mimi 
Published: March 2008

Summary.objectiveit has been postulated that a decrease in thyroid size can be achieved by thyroxine treatment in patients with goitrous Hashimoto's thyroiditis but no objective data are available. We have therefore Investigated the Influence of thyroxine treatment on ultrasonically determined thyroid size. We also measured serum antithyroid peroxldase antibodies.designConsecutive patients with goitrous Hashimoto's thyroiditis was studied.patientsThirteen women participated; all had goitrous thyroiditis.treatmentTo render them euthyroid thyroxine was given for 24 months.measurementsThyroid size was measured ultra‐sonically and antithyroid peroxidase antibodies were measured using a commercial radloimmunological method.resultConcomitant with the gradual increase in serum free thyroxine and free triiodothyronlne Index values and a fall in serum thyrotrophin level, a gradual decrease in thyroid volume from 50.4 ± 6.8 ml (mean ± SEM) to 34.1 ± 5.7 ml (32%),P< 0.001 was demonstrated. Anti‐thyroid peroxidase antibodies were present In high concentrations in all subjects but the mean serum level was not significantly changed at 24 months after. Initiation of treatment.conclusionA clinically significant reduction in thyroid volume related to normalization of thyroid function but unrelated to changes in antithyroid peroxidase antibody can be achieved duringl‐thyroxine treatment of hypothyrold goitrous Hashimoto's thyroiditis.