bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suppression of serum thyrotropin with thyroxine in patients with Graves' disease: effects on recurrence of hyperthyroidism and thyroid volume
Authors: Pfeilschifter Johannes , Ziegler Reinhard 
Published: December 2008

Abstract
Based on findings that thyroxine may have a beneficial effect on the recurrence of Graves' hyperthyroidism, we prospectively studied the effects of a TSH suppressive treatment with thyroxine on the course of Graves' disease in fifty patients with recent onset of hyperthyroidism. After the normalization of serum tri-iodothyronine (T3) and thyroxine (T4) concentrations, one group of patients was randomly assigned to a combined treatment with carbimazole and a TSH suppressive dose of T4 for 12 months, followed by another 12 months of TSH suppressive therapy alone. The other group of patients also received carbimazole for one year, but T4 was only added as indicated to normalize elevated TSH serum concentrations, and patients received no therapy during the second year. By the end of the second year, a relapse of hyperthyroidism had occurred in 43% of the patients with and in 45% of the patients without suppressive T4 treatment. In those patients without a relapse of hyperthyroidism, initial thyroid size significantly (P = 0·01) decreased with time in both treatment groups. However, patients on suppressive T4 treatment tended to have a greater reduction in thyroid volume than patients with normal TSH serum concentrations (P = 005). In conclusion, we were unable to detect a preventive effect of exogenous TSH suppression on the recurrence of hyperthyroidism. However, our data suggest that TSH suppressive treatment may have a beneficial effect on thyroid enlargement in Graves' disease.
European Journal of Endocrinology 136 81–86
Neuropsychological development in a child with early-treated congenital hypothyroidism as compared with her unaffected identical twin
Authors: Bargagna Stefania , Chiovato Luca , Dinetti Daniela , Montanelli Lucia , Giachetti Cristina , Romolini Elisabetta , Marcheschi Mara , Pinchera Aldo 
Published: December 2008

Abstract
Objective: Neonatal screening for congenital hypothyroidism (CH) prevents the serious neuropsychological features of CH, but the question remains whether intelligence and motor skills of CH children treated early are completely normal.
Design: In this report we describe the rare case of two genetically identical twins, only one of whom was affected by CH due to thyroid agenesis. L-Thyroxine (9 μg/kg body weight/day) therapy was initiated at 27 days of age and was adequate throughout the follow-up.
Methods: Neuropsychological evaluation was performed on the twins in parallel from 3 months to 8 years of age.
Results: The CH twin (NB) did not show major neuromotor impairments but, compared with the unaffected twin (EB), she had a slight delay in postural/motor achievements and in language development that completely disappeared at 8 years of age. On standardised tests of intelligence, NB was indistinguishable from control children but, compared with her twin, she had lower IQ scores in most testing occasions up to 7 years of age (NB = 108 vs EB = 115). School achievements of NB did not significantly differ from those of her classmates but, compared with her twin, she scored worse in writing, mechanical reading, verbal memory, and possibly in arithmetic.
Conclusions: Because the twins were genetically and phenotypically identical, were raised in the same environment, and received a similar education, it is concluded that hypothyroidism in utero and in the first neonatal month was responsible for the lower neuropsychological achievements of the CH twin. While foetal hypothyroidism is at present unavoidable, earlier diagnosis and initiation of treatment in neonates with CH are important and highly recommended.
European Journal of Endocrinology 136 100–104
Simultaneous xenotransplantation of human Graves' thyroid tissue and autologous bone marrow cells in severe combined immunodeficient mice: successful reconstitution of human Graves' hyperthyroidism
Authors: Yoshikawa Norio , Nishikawa Mitsushige , Mori Shigeki , Tokoro Toshiko , Yamamoto Yoshihisa , Ikehara Susumu , Kumazawa Hirofumi , Yamashita Toshio , Inada Mitsuo 
Published: December 2008

Abstract
Human thyroid xenografts and the autologous bone marrow (BM) cells from five patients with Graves' disease (GD) were simultaneously xenografted into severe combined immunodeficient (SCID) mice to study the role of BM cells for the perpetuation of human GD autoimmunity and hyperthyroidism. All SCID mice engrafted with thyroid tissue (TH) alone, TH+autologous peripheral blood mononuclear cells, and TH+autologous BM cells produced similar amounts of human IgG; however, the production in TH+BM-engrafted mice peaked later than that of mice without BM. Production of thyroperoxidase antibody and thyroglobulin antibody in TH+BM-bearing SCID mice peaked in later weeks after xenografting than in those without BM. Moreover, human Graves' hyperthyroidism was actually reconstituted in TH+BM-transplanted mice; this was confirmed by (A) significantly higher levels and longer periods of secreting thyroid-stimulating antibody than those in mice without BM engraftment, (B) persistent hyperthyroxinemia up to the end of the experiment, (C) extremely high radioiodine uptake of the xenografted thyroid tissue, and (D) histological findings of the maintenance of hyperplastic change of the xenografted thyroid epithelial cells. Human BM stem cells (CD34) were identified only in mice with TH+BM xenografts when analyzed by immunohistochemistry. In conclusion, (A) we have developed an animal model for human hyperthyroid GD by simultaneous xenotransplantation of GD thyroid tissue plus autologous BM cells into SCID mice, and (B) BM cells have a crucial role for perpetuating human GD autoimmunity and hyperthyroidism in this system.
European Journal of Endocrinology 136 213–222
Thyroid hormone and gene expression in the regulation of mitochondrial respiratory function
Authors: Pillar Timothy M , Seitz Hans Joachim 
Published: December 2008

Abstract
Thyroid hormone has a profound effect on cellular respiration. Abnormally high levels of this hormone accelerate respiration in conjunction with a general increase in metabolism while pathologically low amounts cause low levels of respiration with a general slowing of metabolic activity. The affect on respiration is primarily the result of changes in the expression of respiratory genes and modulation of inner membrane structure. This review focuses on the regulation of respiratory gene expression by thyroid hormone. Respiratory genes are encoded in both the nucleus and the mitochondrion, the products of which are required in stoichiometric amounts for proper assembly of the respiratory chain. Thyroid hormone influences the expression of a number of nuclear encoded respiratory genes at the level of mRNA and enhances expression of mitochondrially encoded respiratory genes. Therefore, thyroid hormone appears to affect gene regulation in two different cell compartments. The current evidence for a direct thyroid hormone/thyroid receptor regulation of these respiratory genes and possible indirect pathway(s) mediating the thyroid effect is discussed.
European Journal of Endocrinology 136 231–239
Regulation of the uncoupling protein gene expression
Authors: Silva J Enrique , Rabelo Rogerio 
Published: December 2008

Abstract
Uncoupling protein (UCP) is essential to the thermogenic function of brown adipose tissue (BAT). The thermogenic role of this protein is due to its capacity to uncouple oxidative phosphorylation in a regulated manner. The thermogenic potential of BAT is determined by its content of UCP. The gene encoding this protein is under complex regulation. Catecholamines, via cAMP, thyroid hormone and retinoic acid, directly stimulate the gene acting upon an upstream (−2·28/−2·49 kb) enhancer sequence, but cAMP may act upon other sequences of the gene as well. CCAAT enhancer binding proteins and peroxisome proliferation activator receptor (PPAR)γ2 have also been implicated in the regulation of the gene acting on discrete sequences. While the thyroid hormone response and retinoic acid response elements (TRE and RARE) have been well defined, the cAMP response elements (CRE) remain elusive. The two TREs are 27 bp apart between −2·33 kb and −2·39 kb. The synergism between cAMP and thyroid hormone seems to reside in a 39 bp sequence downstream (−2·28/−2·32 kb). The most important CRE, the RARE, a cell-specific enhancer and a putative PPAR element are all concentrated in a 90 bp regulatory element of great complexity (−2·40/−22·49 kb). Other hormones, such as insulin and glucocorticoids, and IGF-I also modulate the expression of the gene but their effects seem to be largely indirect. Understanding the regulation of the UCP gene expression may facilitate the development of interventions in obesity and related disorders.
European Journal of Endocrinology 136 251–264
Plasma dehydroepiandrosterone sulfate levels in patients with hyperfunctioning and non-hyperfunctioning adrenal tumors before and after adrenal surgery
Authors: Tóth Miklós , Rácz Károly , Varga Ibolya , Adleff Vilmos , Jakab Csilla , Fütõ László , Kiss Róbert , Gláz Edit 
Published: December 2008

Abstract
To investigate the clinical significance of plasma dehydroepiandrosterone sulfate (DHEAS) measurements, 175 patients with histologically confirmed adrenal tumors, 10 cortisol-producing adenomas, 59 aldosterone-producing adenomas, 56 non-hyperfunctioning adenomas, 13 adrenocortical carcinomas, 13 adrenal cysts, and 24 adrenomedullary tumors were studied. Plasma DHEAS levels were expressed as percentage of the mean of sex- and age-matched groups of healthy, normal subjects (DHEAS %). We found that before adrenal surgery, DHEAS % values were significantly reduced in patients with cortisol-producing (mean, 15·2% of control; 95% confidence interval (CI), 9·4–24·7%), non-hyperfunctioning (28·4%; 22·4–36·0% as well as aldosterone-producing adrenocortical adenomas (55·4%; 47·1–65·1%) compared with controls, while values were normal in patients with adrenal cysts and in those with adrenomedullary tumors. Plasma DHEAS % values exhibited a great variability in adrenocortical carcinomas (mean, 84·0%; 95% CI, 33·2–212·5%). Death from adrenocortical carcinoma was more frequent in patients with high plasma DHEAS % values compared with those with low DHEAS %. During long-term postoperative monitoring, we found that plasma DHEAS levels of patients with aldosterone-producing and non-hyperfunctioning adenomas returned to normal in the second and fourth postoperative year respectively. In patients with cortisol-producing adenomas, plasma DHEAS remained suppressed for as long as 8 years after the operation. These findings show that except in adrenocortical carcinomas and cysts, plasma DHEAS levels are significantly decreased in all groups of adrenocortical tumors, including non-hyperfunctioning and aldosteroneproducing tumors. The extent of this decrease and the postoperative persistence of suppressed plasma DHEAS levels may be related to the glucocorticoid production of adrenocortical tumors.
European Journal of Endocrinology 136 290–295
Insulin-like growth factor receptors in normal and tumorous adult human adrenocortical glands
Authors: Weber Matthias M , Auernhammer Christoph J , Kiess Wieland , Engelhardt Dieter 
Published: December 2008

Abstract
We have identified and characterized insulin-like growth factor (IGF)-I and IGF-II/mannose-6phosphate (IGF-II/M6P) receptors in normal adult human adrenocortical tissue. Furthermore, we investigated the IGF-I receptor concentration and binding characteristics in benign and carcinomatous adrenocortical tumors. Membrane preparations of 14 normal adrenocortical glands showed a mean specific 125I-IGF-I binding (SB) of 5·0±0·5% and a competition by unlabeled ligands which is characteristic of the IGF-I receptor. The Scatchard analysis revealed a single class of high affinity binding sites with a dissociation constant (Kd) of 0·16±0·03 nmol/l, and a receptor concentration (RC) of 19·2±2·5 nmol/kg protein. Affinity cross-linking experiments with normal and tumorous adrenocortical tissue displayed a band at an apparent molecular mass of 135 kDa, corresponding to the size of the normal α-subunit of the IGF-I receptor. In agreement, 125I-IGF-II binding to normal adult human adrenocortical membranes was characteristic for the IGF-II/M6P receptor, and the Scatchard analysis revealed the presence of a single class of high affinity binding sites (SB 7·5±0·5, RC 1137±265 nmol/kg protein, Kd 2·20±0·46 nmol/l, n=6). The identity of the IGF-II/M6P receptor in adrenocortical tissue was further confirmed by Western blotting showing a specific band at 220 kDa. When 125I-IGF-I binding in adrenocortical hyperplasias (SB 4·1±0·4% RC 19·6± 2·0 nmol/kg protein, Kd 0·19±0·04 nmol/l, n=4) and adenomas (SB 4·0±1·1% RC 17·5± 3·1 nmol/kg protein, Kd 0·21±0·nmol/l,04 n=4) was compared with the 125I-IGF-I binding in normal adrenocortical tissue, similar IGF-I receptor concentration and binding kinetics were found. In contrast, three out of four hormonally active adrenocortical carcinomas showed a strongly elevated specific 125I-IGF-I binding with a 3- to 4-fold increase in IGF-I receptor concentration, as compared with normal adrenocortical tissue. This resulted in a significantly higher mean specific binding and receptor concentration in adrenocortical carcinomas, while the binding kinetics and the size of the α-subunit of the IGF-I receptor remained unaltered (n =4, SB 13·8±4·2%, RC 72·2 ± 21·3 nmol/kg protein, Kd 0·17±0·02 nmol/l). In summary, we show that intact IGF-I and IGF-II receptors are present in normal adult human adrenocortical tissue. While the abundance of the IGF-I receptor in adrenocortical hyperplasias and adenomas was similar to normal tissue, a strong overexpression of the intact IGF-I receptor was found in three out of four adrenocortical carcinomas.
European Journal of Endocrinology 136 296–303
Effect of ovariectomy and steroid hormone replacement on the recovery of arterial blood pressure following haemorrhage in anaesthetized Brattleboro rats
Authors: Morrissey Sinead E , Edwards Tom J , Wilson Karen J , Whitehead Saffron A , Laycock John F 
Published: December 2008

Abstract
There is increasing evidence that ovarian steroids inhibit vascular responsiveness to the neurohypophysial hormone vasopressin. The present study examined the recovery of the arterial blood pressure following a single (2 ml/100 g body weight) haemorrhage in ovariectomized (OVX) Brattleboro rats with hereditary hypothalamic diabetes insipidus (BDI) and rats of the parent Long Evans (LE) strain. Some groups of OVX rats received subcutaneous implants of either 17β-oestradiol (E2) or progesterone 7 days prior to haemorrhage. The arterial blood pressure recovery immediately following haemorrhage was significantly impaired in both groups of steroid-treated OVX LE rats compared with the OVX controls (both comparisons P< 005). The impairment in blood pressure recovery seen in the steroidreplaced OVX LE rats was similar to that seen in pro-oestrous rats (when ovarian steroid levels are raised) compared with male rats of this strain (P<0·05). In contrast, ovariectomy with or without steroid replacement in BDI rats had no further effect on the already attenuated recovery of arterial blood pressure after haemorrhage in this strain. Heart rate responses to haemorrhage also showed strain differences, which were dependent on steroid treatment. Pro-oestrous female LE rats showed a small decrease in heart rate after haemorrhage, followed by a recovery process, and this initial bradycardia was markedly enhanced in the OVX steroid-treated animals. In contrast, untreated OVX LE rats showed an initial and sustained increase in heart rate which was significantly higher than in the steroid-treated OVX animals (P <0·05). All BDI rats, irrespective of treatment, consistently showed an increased heart rate after haemorrhage. In conclusion, ovarian steroid replacement in OVX LE, but not vasopressin-deficient BDI, rats was associated with an attenuated pressor recovery after haemorrhage. This provides further evidence for the existence of an important inhibitory interaction between ovarian steroids and vasopressin. The initial decrease in heart rate observed in pro-oestrous and steroid-treated OVX LE rats after haemorrhage also appears to be related to an ovarian steroid—vasopressin interaction.
European Journal of Endocrinology 136 330–337
Results of somatostatin receptor scintigraphy do not predict pituitary tumor volume- and hormone-response to octreotide therapy and do not correlate with tumor histology
Authors: Plöckinger Ursula , Bäder Michael , Hopfenmüller Werner , Saeger Wolfgang , Quabbe Hans-Jürgen 
Published: December 2008

Abstract
The value of somatostatin receptor scintigraphy (SRS) to predict the effect of somatostatin analog therapy on pituitary adenomas is not clear, due to the use of different radiopharmaceuticals (123I-Tyr3-octreotide and 111In-pentetreotide) and the small number of patients in previous studies. We used 111In-pentetreotide scintigraphy in 49 patients in order to (i) correlate SRS results with basal tumor volume as well as volume- and hormone-response to 3 months of octreotide therapy (Oct-Tx), (ii) identify tumor remnants after incomplete surgery and (iii) evaluate any correlation with immunohistology. Twenty-five patients had a GH-secreting adenoma (GH-A, 15 prior to intended surgery, 10 with persistent/recurrent disease after previous therapy). Twenty-four patients had a clinically nonfunctioning adenoma (NF-A). For SRS, planar and single photon emission computer tomographic images (SPECT) were recorded 4 h and 24 h post injection. SRS grading was as follows: GO, no uptake; Gl, uptake comparable to normal pituitary; G2, increased uptake; G3, very intense uptake. G2/3 was seen in 8/25 GH-A and in 12/24 NF-A. Pretreatment tumor volume (magnetic resonance imaging (MRI)) tended to be related to 111In-pentetreotide uptake in GH-A with a tumor visible on MRI (G0/1 (n=10) vs G2/3 (n=8): 3·6±1·9 vs 10·±6·5 cm3 (mean±s.e.), P=0·051), but not in NF-A (g0/1 (n=12) vs G2/3 (n=12): 17·0±10·1 vs 14·3±3·6 cm3). SRS did not identify a tumor remnant in the 7 MRI-negative patients with persistent post-operative acromegaly. Basal GH (6-h profile) and IGF-I in GH-A did not correlate with SRS results (G0/1 (n=17) vs G2/3 (n=8), GH: 32·3±18·2 vs 29·3±7·4 μg/l, IGF-I: 851±80 vs 1038±153 μg/l). During Oct-Tx of GH-A neither tumor shrinkage nor GH suppression was related to SRS results. In 6 NF-A classified as gonadotropinomas (by their plasma glycoprotein hormone or α-subunit concentrations, basally and/or in response to TRH) 111In-pentetreotide uptake was not different from that of the non-gonadotropin/non-secreting adenomas. SRS results were not related to the immunohistological subtype in 22 GH-A (monohormonal, mixed somatotrope/lactotrope, plurihormonal) or in 22 NF-A (null-cell adenomas, gonadotropinomas, silent hormonal adenomas). We conclude that 111In-pentetreotide SRS reflects tumor volume poorly in GH-A and not at all in NF-A. It does not predict the effect of Oct-Tx on the volume of both GH-A and NF-A, nor on the GH concentration in GH-A. 111In-pentetreotide SRS is unable to identify postoperative tumor remnants not visible on MRI.
European Journal of Endocrinology 136 369–376
C-type natriuretic peptide exerts stimulatory effects on the corticotropin-releasing hormone-induced secretion of hormones in normal man
Authors: Kellner Michael , Diehl Ines , Knaudt Kristina , Schüle Cornelius , Jahn Holger , Wiedemann Klaus 
Published: December 2008

Abstract
C-type natriuretic peptide and atrial natriuretic peptide have been reported to bind to distinct receptors and to exert opposing effects on different systems. Although it is known that atrial natriuretic peptide inhibits the corticotropin-releasing hormone-stimulated hormone release in man, the corresponding action of C-type natriuretic peptide has so far not been characterized. We investigated the effects of 30-min infusions of 150 and 300 μg C-type natriuretic peptide on adrenocorticotropin, cortisol, and prolactin release stimulated by 100 μg corticotropin-releasing hormone and on cardiovascular parameters in 8 healthy male volunteers. Compared with placebo, 300 μg C-type natriuretic peptide significantly (P<0·05) enhanced the stimulation of cortisol (area under curve (arbitrary units): 520 ± 35 vs 651 ± 55) and prolactin (area under curve: 29 ± 3 vs 37 ± 5). Adrenocorticotropin levels were increased, but the differences did not reach statistical significance (maximum increment: 27±4 vs 36± 2 pg/ml). C-type natriuretic peptide at a dose of 150 μg had no clear effect on these hormones and C-type natriuretic peptide also produced no cardiovascular or subjective effects. Our data suggest stimulatory effects of C-type natriuretic peptide on corticotropinreleasing hormone-induced hormone release and offer further evidence for a complex role of different natriuretic peptides in endocrine regulation.
European Journal of Endocrinology 136 388–393
Anti-obesity and anti-diabetic effects of CL316,243, a highly specific β3-adrenoceptor agonist, in Otsuka Long-Evans Tokushima Fatty rats: induction of uncoupling protein and activation of glucose transporter 4 in white fat
Authors: Umekawa Tsunekazu , Yoshida Toshihide , Sakane Naoki , Saito Masayuki , Kumamoto Kenzo , Kondo Motoharu 
Published: December 2008

Abstract
The anti-obesity and anti-diabetic effects of a highly specific β3-adrenoceptor agonist, CL316.243 (CL; β1:β2:β3=0:1:100 000), were investigated in Otsuka Long-Evans Tokushima Fatty (fatty) and LongEvans Tokushima Otsuka (control) rats. Daily injection of CL (0·1 mg/kg, s.c.) to these rats (10 weeks old) for 14 weeks caused a significant reduction in body weight (fatty, 27% control, 15%), associated with a marked decrease in fat pad weight (inguinal: fatty, 60%; control, 36%; retroperitoneal: fatty, 75%; control, 77%) without affecting food intake. The levels of uncoupling protein mRNA and protein levels of uncoupling protein (UCP), as well as guanosine 5′-diphosphate-binding (a reliable index of thermogenesis) in brown adipose tissue, were lower in the fatty than in the control rats. However, after CL treatment, these parameters in brown adipose tissue increased significantly 2- to 3-fold in both groups. Furthermore, uncoupling protein was induced in white adipose tissue as well as in brown adipose tissue. The fatty rats showed hyperglycemia and hyperinsulinemia during the glucose tolerance test, but CL ameliorated these parameters.
These findings suggest that decreased thermogenesis in brown adipose tissue may be one of the causes of obesity in the fatty rats and that administration of CL prevents obesity by decreasing white fat mass, by activating brown adipose tissue thermogenesis, and by inducing uncoupling protein in white adipose tissue. Furthermore, CL treatment may inhibit diabetes mellitus by ameliorating obesity and by activating glucose transporter 4 in white adipose tissue and brown adipose tissue.
European Journal of Endocrinology 136 429–437