bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of post‐partum Graves' thyrotoxicosis by measurement of thyroid stimulating antibody in early pregnancy
Authors: Hidaka Yoh , Tamaki Haruo , Iwatani Yoshinorl , Tada Hisato , Mitsuda Nobuaki , Amino Nobuyuki 
Published: March 2008

SummaryOBJECTIVE Autoimmune thyroid diseases often occur after delivery. However, it has been difficult to predict who will develop Graves' thyrotoxicosis after delivery. We tried to establish a systematic method for predicting postpartum onset of Graves' thyrotoxicosis. DESIGN We followed up the pregnant women with antithyroid microsomal antibody (MCAb) from early pregnancy to the post‐partum period and analysed the relation between the activities of thyroid stimulating antibodies (TSAb) in early pregnancy and post‐partum occurrence of Graves' disease.PATIENTS Seventy‐one women with positive MCAb in early pregnancy were studied. They were randomly selected from 262 MCAb‐positive subjects found in 3405 consecutive early pregnant women who attended our maternity clinic during the last ten years.MEASUREMENTS MCAb was measured with a commercially available agglutination kit. For 71 MCAb‐positive subjects, TSH‐binding inhibitory immunoglobulin (TBII) and TSAb were measured in early pregnancy, and serially until 6 months after delivery for the subjects with either positive TBII or TSAb. Thyroid function and goitre size were recorded at every observation.RESULTS Among the 71 subjects, 7 showed positive TSAb in early pregnancy without any thyroid dysfunction; all 7 developed thyroid dysfunction in the post‐partum period. Five of them (70% of TSAb‐positive subjects) developed Graves' disease, two showing persistence and three transiently. None of 64 TSAb‐negative subjects developed Graves' thyrotoxicosis, though 44 developed various types of thyroid dysfunction as a result of postpartum autoimmune thyroiditis.CONCLUSION The Individuals at high risk of post‐partum onset of Graves' thyrotoxicosis can be found early in their pregnancy by the detection of TSAb. Overall occurrence of post‐partum Graves' disease in the general population is estimated above 0–54%, that is, one in 200 post‐partum women may develop Graves' thyrotoxicosis, although thyrotoxicosis may be transient in half of the patients.
Effect of FK‐506 on xenografted human Graves' thyroid tissue in severe combined immunodeficient mice
Authors: Yoshikawa Norio , Arreaza Guillermo , Mukuta Toshio , Resetkova Erika , Miller Naomi , Jamieson Christopher , Nishikawa Mitsushige , Lnada Mitsuo , Volpé Robert 
Published: March 2008

SummaryOBJECTIVE We studied the macrolide antibiotic FK‐506, an immunosuppressive agent, in an attempt to ameliorate the lesion of autoimmune thyroid disease in human thyroid tissue xenografted into severe combined immunodeficient (SCID) mice. It was not felt appropriate to employ this agent directly in patients with autoimmune thyroid disease because adequate therapeutic modalities are available and the introduction of new, experimental agents could not be justified. Moreover, the study of the tissue before and after treatment could not have been undertaken directly in patients.DESIGN Human thyroid xenografts from four patients with Graves' disease and two normal persons were xenografted into SCID mice. Two weeks after xenograft‐ing, human immunoglobulin G (IgG) was detectable in all SCID mice xenografted with Graves' thyroid tissue. Mice were divided into two groups with human IgG levels similar to each other. Mice in the first group were treated with FK‐506 daily for 6 weeks; mice in the second (similar) group were given phosphate‐buffered saline (PBS) only (control group).MEASUREMENTS Blood samples were taken every 2 weeks from the tail veins for human IgG, thyroid stimulating antibody, thyroperoxidase antibodies, thyroglobulin antibodies, and interferon‐gamma (IFN‐7). After 8 weeks treatment, animals were sacrificed; thyroid tissue was examined histologically and for thyrocyte HLA‐DR expression. FK‐506 was also added to thyrocytes in in‐vitro tissue culture conditions. RESULTS After 4–6 weeks of FK‐506 therapy, human IgG, all thyroid antibodies and IFN‐7 were suppressed, while the levels remained elevated in the control group. Lymphocytic infiltration virtually disappeared in the human thyroid tissue of the FK‐506‐treated mice and thyrocyte HLA‐DR expression markedly declined; in the control mice, lymphocytic infiltration remained heavy and HLA‐DR expression remained high. On the other hand, FK‐506 added directly to thyrocytes in vitro (without lymphocytes) did not reduce thyrocyte HLA‐DR expression.CONCLUSIONS FK‐506 appears to suppress the activation of intrathyroidal lymphocytes, but not thyrocytes. From these observations, it is concluded that this agent, by its action on intrathyroidal lymphocytes, is able to ameliorate the immunologically mediated histological and serological disturbance in human autoimmune thyroid disease, at least under these circumstances.
Renal leak of calcium in post‐menopausal osteoporosis
Authors: Nordin B. E. Christopher , Horowitz Michael , Need Allan , Morris Howard A. 
Published: March 2008

SummaryBACKGROUND Urine calcium after an overnight fast is higher in osteoporotic than in normal post‐menopausal women. The question is whether this is the cause or effect of the bone‐losing state.OBJECTIVE To establish whether the elevated obligatory calcium loss In osteoporotic women is due to a raised filtered load of calcium or to reduced renal tubular reabsorption of calcium.DESIGN Covariance analysis using total plasma calcium and its fractions as the covariates.PATIENTS Eighty‐two untreated post‐menopausal women without vertebral compression and 137 untreated postmenopausal with vertebral compression all between the ages of 61 and 75 years.MEASUREMENTS After an overnight fast, calcium, albumin, globulins, anion gap and bicarbonate were measured in the plasma, and calcium, sodium and creatinine In the urine. The calcium fractions in plasma and the calcium/creatinine and sodium/creatinine ratios in urine were calculated. Bone density was measured in the distal forearm.RESULTS The ultrafiltrable and Ionized calcium in the plasma and the calcium/creatinine ratio in the urine were significantly higher in the women with vertebral compression than in those without. On covariance analysis, neither total plasma calcium nor any of the plasma calcium fractions made a significant contribution to the difference in fasting urine calcium between normal and osteoporotic women, whether bone status was defined by vertebral compression or by bone density.CONCLUSIONS The increased obligatory calcium loss in osteoporotic women is not due to an increase in the filtered load of calcium and must therefore reflect reduced renal tubular reabsorption. This implies that the calcium loss in the urine Is not the result of increased bone resorption but is more likely to be causal.
A hormonal and radiological evaluation of adrenal gland in patients with acute or chronic pulmonary tuberculosis
Authors: Keleştimur Fahrettin , Ünlü Yalçin , Özesmi Mustafa , Tolu Ismet 
Published: March 2008

SummaryOBJECTIVE The adrenal glands may be involved in tuberculosis. The exact frequency and extent of adrenal involvement in tuberculosis are not well known. Although there are some studies regarding adrenal gland involvement, they are not sufficient because of inadequate endocrinological tests and radiological procedures. The aim of this study was to assess the adrenal gland in acute and chronic pulmonary tuberculosis and to compare it with the findings obtained in healthy subjects.DESIGN AND PATIENTS We studied 20 patients with acute pulmonary tuberculosis, 41 patients with chronic pulmonary tuberculosis and 20 healthy subjects. Involvement of the adrenal gland was assessed by basal Cortisol level, Cortisol response to Synacthen and adrenal computed tomography.MEASUREMENTS Cortisol levels were measured before, 30 and 60 minutes after Synacthen (250 μg i.v.) injection. Computerized tomography of the adrenals was carried out in 61 patients with tuberculosis and 20 healthy subjects.RESULTS Mean basal Cortisol level and 60‐minute Cortisol response to Synacthen were significantly higher in acute pulmonary tuberculosis than in chronic pulmonary tuberculosis and healthy subjects. Two patients with Addison's disease were diagnosed among the chronic tuberculous patients. Both length and thickness of the right and left adrenal gland were greater in patients with acute tuberculosis.CONCLUSION Adrenal enlargement demonstrated by computerized tomography is common in patients with acute pulmonary tuberculosis, but our findings show that Cortisol reserve is normal, in contrast to previous suggestions.
Characterization of 24‐hour growth hormone secretion in acromegaly: implications for diagnosis and therapy
Authors: Ho Ken K. Y. , Welssberger Andrew J. 
Published: March 2008

SummaryOBJECTIVE Early studies of acromegaly undertaken before the general availability of insulin‐like growth factor I (IGF‐I) assays have used arbitrary and varying growth hormone (GH) threshold levels for diagnosing and assessing outcome of treatment for this disease. We have undertaken a detailed study of GH secretion and its relationship to IGF‐I levels to assess the usefulness of GH and IGF‐I measurements in the assessment of acromegaly.PATIENTS Thirty acromegalic subjects (12 untreated and 16 previously treated) and 30 age and sex‐matched normal subjects were studied.MEASUREMENTS Twenty‐four‐hour GH secretion was obtained from 20‐minute sampling and serum IGF‐I was measured. Comparisons were made of IGF‐I, mean 24‐hour GH concentration, and of the pulsatile and diurnal characteristics of GH secretion between the two groups.RESULTS IGF‐I levels In untreated acromegaly were elevated and clearly separated from the normal range. Mean 24‐hour GH concentrations in untreated and treated acromegalic subjects with elevated IGF‐I (>40 nmol/l) were greater than (P < 0.01), and showed good separation from, those of normal subjects only after age‐matching. From the 24‐hour prollfes, nadir GH levels In normal subjects fell below the level of detectability while those in untreated acromegalic subjects did not. Pulse amplitude (P<0.01), ratio of pulsatile to non‐pulsatile GH release and the night to daytime GH ratio (P<0 05) were significantly reduced in acromegaly. In the six patients who attained normal IGF‐I levels after surgery, pulsatile characteristics remained abnormal in four. Mean 24‐hour GH was significant related (r = 0.57) to IGF‐I. A random GH concentration >2.5 μg/l (5 mlU/l) has a sensitivity of 77% and specificity of 95% In identifying acromegalic patients who have biochemically active disease (elevated IGF‐I) after treatment.CONCLUSIONS Patients with active acromegaly secrete more GH than age‐matched normal controls. GH secretion in acromegaly is characterized by marked blunting of pulsatile secretion and, in contrast to normal subjects, the failure of GH to fall to undetectable levels at any time during the 24‐hour day. IGF‐I measurement is a more practical alternative in the diagnosis of acromegaly and in the assessment of therapeutic outcome. Since abnormalities of GH regulation may persist despite normalization of IGF‐I, a distinction between remission and cure should be made. Detailed post‐treatment evaluation of GH secretion is necessary to define the nature of underlying GH regulation and to evaluate the risk of disease recurrence.
Determinants of clinical outcome and survival in acromegaly
Authors: Rajasoorya C. , Holdaway I. M. , Wrightson P. , Scott D. J. , Ibbertson H. K. 
Published: March 2008

SummaryOBJECTIVE The extent to which treatment modifies the excess in morbidity and mortality in acromegaly remains uncertain. This study investigates the determinants of final outcome following therapy for acromegaly. DESIGN A retrospective analysis of patients treated at the Departments of Endocrinology and Neurosurgery, Auckland Hospital, New Zealand.PATIENTS One hundred and fifty‐one patients (63 females and 88 males) with acromegaly or gigantism treated between the years 1964 and 1989. The mean duration of follow‐up was 12 years (median 11 years).MEASUREMENTS Patients had their age, estimated duration of symptoms preceding diagnosis, serum GH at diagnosis, presence of diabetes mellitus, cardiovascular disease, hypertension and/or osteoarthritis at diagnosis and the last known serum GH documented. The final outcome at the time of study was graded under three classes: dead (n = 32), those with major complications (n =47) and those with minor/no complications (n = 67).RESULTS The mean age at diagnosis of acromegaly was 41 years and the average estimated duration of symptoms prior to diagnosis was 7 years, with older patients showing longer duration of symptoms preceding diagnosis (P= 0.0002). Final outcome (dead, alive with major complications, alive and well) was significantly worse in those with older age at diagnosis (P= 0.008), longer duration of symptoms before diagnosis (P= 0.03) and higher GH at last follow‐up (P=0.0001). In multivariate analysis, survival was significantly Influenced by the last known GH (P = 0.0001), presence of hypertension (P = 0.02) or cardiac disease (P = 0.03) at diagnosis, and duration of symptoms prior to diagnosis (P = 0.04). Survival In the acromegalic group, irrespective of treatment, was reduced by an average of 10 years compared with the non‐acromegalic population.CONCLUSIONS Acromegaly has a significant adverse effect on well‐being and survival. The predominant determinant of outcome is the final serum GH level following treatment.
Congenital euthyroid goitre with impaired thyroglobulin transport
Authors: Ohyama Yoshlhido , Hosoya Toichiro , Kameya Toru , Suzukl Noriaki , Nakamura Shinya , Kazaharl Kojl , Shlbayama Keiko , Yokota Yukifuml , Matsuura Nobuo 
Published: March 2008

SummaryA case of congenital goitre with defective thyroglobulin (Tg) synthesis was studied from the clinical, biochemical and morphological perspectives. The patient, a 5.5‐year‐old boy, who was clinically euthyroid, showed a positive perchlorate discharge test (37.2%). However, the lodlna‐tion system seemed to be normal since radioiodine uptake into the thyroid was very high, and inspection of the H2O2‐generating system using thyroid slices and an assay for peroxidase activity In microsomes showed no abnormalities. On the other hand, virtually no Tg was detected In the serum, and the amount of Tg in thyroid tissue, estimated with gel electrophoresis, was below 10% of the normal value, the quality of Tg being unchanged. Morphological observations demonstrated the presence of Tg in the markedly distended rough endoplasmic reticulum of the cytoplasm of follicular cells and a lack of Tg in the colloid of the follicular lumen. These results suggest that the thyroid is defective in Tg synthesis, probably associated with Impaired transport of Tg from the cells to the lumen.
Short‐term fasting in obesity fails to restore the blunted GH responsiveness to GH‐releasing hormone alone or combined with arginine
Authors: Bouloux P‐M. G. , Fakeeh M. 
Published: March 2008

SummaryOBJECTIVE Fasting is known to clearly increase both spontaneous and GHRH‐stimulated GH secretion in normal subjects and this effect is likely to be due to hypothalamic mechanism(s). Our aim was to clarify the effect of a 3 or 4‐day fast, on the GH response to GHRH alone or combined with arginine, an amino acid probably acting via inhibition of hypothalamic somatostatin release.DESIGN Two tests with GHRH (1 μg/kg i.v.), administered either alone or in combination with arginine (ARG, 0.5 g/kg i.v.) were performed, in a randomized order at least 3 days apart. In obese women the two tests were repeated after a 3 or 4‐day fast.PATIENTS Seven obese women (06, aged 17–54 years, BMI 42.4 ± 3.6 kg/m2, waist‐hip ratio (WHR) 0.85±0.01) and ten healthy women, as control subjects (CS, aged 20–44 years, BMI 23.1 ±1.1 kg/m2, WHR 0.79 ± 0.01) were studied.MEASUREMENTS Serum GH and IGF‐I levels were measured by radioimmunoassay. The GH secretory responses were expressed either as absolute values (mU/l) or as areas under the curve (AUC, mU/l/h) calculated by trapezoidal integration. IGF‐I concentrations were expressed as absolute values (μg/l) with reference to a pure recombinant IGF‐I preparation. Results are expressed as mean ± SEM.RESULTS Basal GH and IGF‐l levels in OB were lower than in CS (0.8 ± 0.2 vs 4.8±1.0 mU/I, P<0.0001 and 120.1 ± 21.4 vs 188.7 ± 13.1 μg/l, P <0.02, respectively). The GHRH‐induced GH rise in OB was lower (P <0.00001) than in CS (AUC 340.2 ± 81.0 vs 2125.0 ± 199.6 mU/l/h). ARG increased the GHRH‐induced GH rise in both groups, but in OB the GH response to ARG + GHRH (1458.4 ± 439.0 mU/l/h, P < 0.03 vs GHRH alone) remained lower (P <0.0001) than in CS (6396.2 ± 772.2 mU/l/h, P < 0.01 vs GHRH alone). In spite of a reduction in body weight and IGF‐I, Insulin and glucose levels, in OB fasting failed to modify both the basal GH levels and the somatotroph responsiveness to GHRH when administered either alone or combined with ARG. An increase in free fatty acids (FFA) was also found after fasting.CONCLUSIONS The results of this study demonstrate that in obesity the somatotroph hyporesponsiveness to GHRH, either alone or combined with arginine, is not improved by short‐term fasting. As fasting is considered a CNS mediated stimulus to GH secretion, its ineffectiveness in obesity does not support a hypothalamic pathogenesis and suggests that long standing metabolic alterations, such as hyperinsulinaemia and/or elevated free fatty acids, could play a major role in causing GH insufficiency in obese patients.
Prevalence of Helicobacter pylori in acromegalic patients during treatment with octreotide
Authors: Jones S. L. , Patchett S. , Anderson J. V. , Farthing M. J. G. , Besser G. M. , Wass J. A. H. 
Published: March 2008

SummaryBACKGROUND Octreotide, a synthetic long‐acting analogue of somatostatin, now has an establlshed role in the treatment of acromegaly. In acromegalic patients treated with octreotide there is an increased incidence of gallstones and possibly gastritis.OBJECTIVES (1) To compare the seroprevalence of Helicobacter pylori (H. pylori) infection, in acromegalic patients treated with octreotide to that in patients given other treatment modalities. (2) To study retrospectively the temporal relatlon between H. pylori acquisition and octreotide treatment.PATIENTS Three groups of acromegalic patients were studied; 35 (20 M) had been treated wlth octreotide, 17 (10 M) with bromocriptine and 19 (12 M) had received no pharmacological intervention (untreated, surgically treated or treated with radiotherapy).DESlGNlMEASUREMENTS The presence of H. pylori infection was assessed serologically (Bio‐Rad GAP test for IgG), using stored serum, on the most recent sample from each patient and on serial samples from patients treated with octreotlde.RESULTS The prevalence of H. pylori seropositivity was similar in each treatment group, 34, 35 and 37%, respectively. Mean age and duration of acromegaly were similar in the first two groups. Patients who had never received medical treatment were slightly younger. GH levels were similar in all three groups. Patients on octreotide who were seropositive for H. pylori did not differ from those with negative serology with respect to age, duration of acromegaly, duration of octreotide treatment or serum GH level. Serial samples in octreotide treated patients showed a change in status in only one patient; 18 patients continued with negative serology during a mean period of 30 (range 4–62) months. In each of the 6 patients with persistently positive serology during octreotide treatment, stored samples predating octreotide therapy were shown to have already been positive.CONCLUSIONS The seroprevalence of H. pylori infection in acromegalic patients does not appear to be increased in a manner dependent on the type or duration of medical treatment. In particular, octreotide therapy, while causing the development of histological gastritis in some patients, does not appear to induce the development of H. pylori infection.
Whole body and regional soft tissue changes in growth hormone deficient adults after one year of growth hormone treatment: a double‐blind, randomized, placebo‐controlled study
Authors: Hansen T. B. , Vahl N. , Jergensen Jens O.L. , Christlansen Jens S. , Hagen C. 
Published: March 2008

SummaryOBJECTIVE Adults with GH deficiency (GHD) exhibit changes in body composition. Studies of the effects of GH substitution on body composition have been short‐term or not adequately controlled. The purpose of this study was to evaluate the long‐term effects of GH on soft tissue using dual‐energy X‐ray absorptlometry (DEXA). This technique enables assessment of whole body as well as regional soft tissue composition.DESIGN A double‐blind, randomized, placebo‐controlled study in patients with acquired GHD. The therapeutic regime consisted of biosynthetic human GH (2.0 lU/m2 per day) or placebo, given as a daily subcutaneous injection at 2000 h for 12 months.PATIENTS Twenty‐nine patients with acquired GHD (GH < 10 μg/l (< 20 mU/I) following standard provocative tests) in whom additional hormone replacement was maintained.MEASUREMENTS Soft tissue determinations by DEXA scan, height, weight, foot volume and finger clrcumference were recorded together with serum IGF‐I at baseline and after 12 months.RESULTS Twelve months of GH therapy induced a total fat mass (FM) reduction of (mean ± SEM) 4.88 ± 0.58 kg (P < 0–002) (n= 13) corresponding to 21.5% of the total FM. The reduction in fat was most marked in the trunk, i.e. 3.07 ± 0.29 kg (P < 0–002) corresponding to 61% of the total FM reduction. Total lean soft tissue mass (LSTM) increased by 3.31 ± 0.81 kg (P < 0.001). Regional changes for arm and leg in the GH group amounted to 0.32 ± 0.08 kg (P < 0002) and 0.71 ± 0.14 kg (P < 0.002), respectively, without accompanying significant changes in truncal LSTM between the groups.The foot volume was Increased by 55.8 ± 15.7 ml (P < 0007) and the finger circumference by 2.67 ± 0.5 mm (P < 0005) on active treatment with no significant changes in the placebo group.CONCLUSIONS Twelve months of GH therapy induced marked changes in soft tissue; fat mass was reduced, particularly in the trunk (61 % of total fat mass reduction) whereas lean soft tissue mass increased more in the extremities. The data imply that GH‐induced changes in body composition are maintained with long‐term therapy.