bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cushing’s Syndrome Due to Medullary Thyroid Carcinoma: Diagnosis by Proopiomelanocortin Messenger Ribonucleic Acid in Situ Hybridization
Authors: Smallridge R. C. , Bourne K. , Pearson B. W. , van Heerden J. A. , Carpenter P. C. , Young W. F. 
Published: October 2003

Abstract
Medullary thyroid carcinoma (MTC) rarely causes ectopic ACTH syndrome. We describe a 38-yr-old man with renal stones who had a 5-cm MTC removed in 1992. He was RET-protooncogene positive (codon 618). Serum calcitonin was 1597 pg/ml postoperatively. In 1996 he had rib fractures, bruising, weakness, and three to four stools per day. Laboratory studies revealed an elevated 24-h urine-free cortisol (780 μg/d), epinephrine (66 μg/d), and calcium (558 mg/d). Baseline serum cortisol was 23.9 μg/dl and decreased to 12.9 and 4.5 μg/dl after 2 mg and 8 mg dexamethasone suppression, respectively. Plasma ACTH was 170 pg/ml and decreased to 75 and 24 pg/ml after dexamethasone. Bone density t-score was −4.3 (trochanter). Computed tomography scans showed multiple cervical nodes and 2-cm right adrenal nodule. Magnetic resonance imaging (MRI) scan showed a prominent, homogeneous pituitary; the adrenal MRI scan was not typical for a pheochromocytoma. Serum CRH was less than 6.6 pg/ml. Bilateral adrenalectomy revealed two adjacent right adrenal pheochromocytomas and corrected the elevated urine cortisol (30 μg/d), epinephrine (0 μg/d), and calcium (281 mg/d) but not plasma ACTH (125 pg/ml). Neck dissection reduced calcitonin by 96% (5300 to 120 pg/ml) and ACTH by 91% (125 to 11 pg/ml). Carcinoembryonic antigen was reduced from 32.0 to 2.3 ng/ml. Immunohistochemical stain was negative for ACTH in the MTC-positive lymph nodes and the pheochromocytoma. Proopiomelanocortin mRNA by in situ hybridization was positive in the MTC but not in the pheochromocytoma. A repeat pituitary MRI scan was normal. The differential diagnosis of ACTH-dependent Cushing’s syndrome in this case included pituitary disease or ectopic ACTH, either from medullary thyroid carcinoma or pheochromocytoma. ACTH stains were unrevealing, but proopiomelanocortin mRNA in situ hybridization in MTC tissue and plasma ACTH response to neck dissection confirmed MTC as the source of ectopic ACTH.
Association of Morphological Characteristics with Precocious Puberty and/or Gelastic Seizures in Hypothalamic Hamartoma
Authors: Jung H. , Probst E. Neumaier , Hauffa B. P. , Partsch C.-J. , Dammann O. 
Published: October 2003

Abstract
The pathogenesis of central precocious puberty (PP) and/or gelastic seizures due to a hypothalamic hamartoma (HH) is still under debate. We evaluated the association of clinical symptoms with morphology and localization of the HH in 34 patients.
The majority (86.4%) of HHs in patients with isolated PP (n = 22; 68.2% females) revealed a parahypothalamic position without affecting the third ventricle (91%). Half of them were pedunculated, and 40.9% showed a diameter less than 10 mm. In contrast, 11 of 12 patients with seizures, eight of whom were male, presented with a sessile intrahypothalamic hamartoma, 10 of which distorted the third ventricle. Logistic regression analysis revealed an increased relative risk (RR) for epilepsy in males (RR, 4.3; 95% confidence interval, 0.96–19). However, combination of the risk factor gender with intrahypothalamic position (RR, 19; 1.3–285) and distortion of the third ventricle (RR, 10; 0.6–164) reduced the risk associated with male gender to 1.1.
The position of a HH and involvement of the third ventricle are likely to be more predictive for clinical characteristics than size and shape. Male gender was associated with an intrahypothalamic HH and epilepsy, suggesting a sexually dimorphic developmental pattern of this heterotopic mass.
Effect of Pamidronate Treatment in Children with Polyostotic Fibrous Dysplasia of Bone
Authors: Plotkin Horacio , Rauch Frank , Zeitlin Leonid , Munns Craig , Travers Rose , Glorieux Francis H. 
Published: October 2003

AbstractIntravenous infusions with the bisphosphonate compound pamidronate decrease bone pain and reportedly can lead to refilling of dysplastic lesions in adults with fibrous dysplasia (FD) of bone. Here we describe the effects of this treatment approach in 18 children and adolescents (age at start of therapy, 6.2–17.5 yr; eight girls) with polyostotic FD, who received pamidronate for 1.2–9.1 yr (median, 3.8 yr). Treatment cycles with pamidronate (1–1.5 mg/kg·d on 3 consecutive days) were given every 4 months. Levels of serum alkaline phosphatase and urinary collagen type I N-telopeptide were elevated at baseline and decreased continuously during the first 3 yr of therapy. There was no radiographic evidence of filling of lytic lesions or thickening of the bone cortex surrounding the lesions in any patient. Histomorphometric results in dysplastic bone tissue of patients receiving pamidronate (n = 7; time of therapy, 1.4–4.8 yr) were similar to those of patients without medical therapy (n = 9). No serious side effects were noted. In conclusion, pamidronate therapy appears to be safe in children and adolescents with polyostotic FD. However, we found no clear evidence that pamidronate has an effect on dysplastic lesions in such patients.
Reversible Metaphyseal Dysplasia, a Novel Bone Phenotype, in Two Unrelated Children with Autoimmunepolyendocrinopathy-Candidiasis-Ectodermal Dystrophy: Clinical and Molecular Studies
Authors: Harris Mark , Kecha Ouafae , Deal Cheri , Howlett C. Rolfe , Deiss Dorothee , Tobias Vivienne , Simoneau-Roy Judith , Walker Jan 
Published: October 2003

AbstractWe report the association of an undescribed, reversible metaphyseal dysplasia (RMD) with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in two patients, one homozygous and one heterozygous for a 13-bp deletion in exon 8 of the autoimmune regulator (AIRE) gene. One patient also had a novel deletion in exon 6, resulting in a frameshift mutation and introduction of a STOP codon in exon 10. Their APECED phenotypes differed, but both patients developed progressive skeletal deformities and growth failure from early childhood. Radiological examination suggested a generalized abnormality of endochondral ossification, with irregular, flared, radioopaque regions in the metaphyses, subjacent to the growth plates. Histopathology in patient 1 showed islands of calcified cartilage within bone, consistent with impaired coupling of cartilage resorption with vascular invasion and ossification. Despite discordance for puberty, both patients experienced radiological resolution of their bone disease in their mid-teens, with improvement in histopathology in patient 1. RMD may constitute a rare phenotypic variation of APECED, possibly resulting from autoimmunity directed against skeletal proteins. We also demonstrated AIRE expression in chondrocytes derived from human fetal growth plates, primary culture of human chondrocytes, and two chondrosarcoma cell lines, suggesting a potential role for abnormal AIRE expression in the development of RMD.
Auxology Is a Valuable Instrument for the Clinical Diagnosis of SHOX Haploinsufficiency in School-Age Children with Unexplained Short Stature
Authors: Binder Gerhard , Ranke Michael B. , Martin David D. 
Published: October 2003

Abstract
SHOX (short stature homeobox-containing gene) mutations causing haploinsufficiency have been reported in some individuals with idiopathic short stature and in many patients with Leri-Weill-dyschondrosteosis. Around 80% of SHOX mutations are complete gene deletions, whereas diverse point mutations account for the rest. The aim of this study was to estimate the prevalence of SHOX mutations in children with idiopathic short stature and to give an unbiased characterization of the haploinsufficiency phenotype of such children. We recruited 140 children (61 girls), in our clinic, with idiopathic short stature, which was defined by the presence of normal IGF-I and free T4; a normal karyotype in females; the absence of endomysium antibodies, of chronic organic, psychological, or syndromatic disease; and by the lack of clear signs of any osteodysplasia. Height, arm span, and sitting height were recorded, and subischial leg length was calculated. Two highly polymorphic microsatellite markers located around the SHOX coding region (CA-SHOX repeat and DXYS233) were PCR-amplified with fluorescent primers and separated in an automatic sequencing machine. Analysis of parental DNA was performed in the probands who had only one fragment size of each of both markers. SHOX haploinsufficiency caused by a SHOX deletion was confirmed in three probands (2%), all females, who carried a de novo deletion through loss of the paternal allele. Their auxological data revealed a significant shortening of arms and legs in the presence of a low-normal sitting height, when compared with the other 137 children tested. Therefore, the extremities-trunk ratio (sum of leg length and arm span, divided by sitting height) for total height was significantly lower in the three SHOX haploinsufficient probands, in comparison with the whole group. This observation was confirmed with the auxological data of five additional patients (four females) previously diagnosed with SHOX haploinsufficiency; all but the youngest girl had height-adjusted extremities-trunk ratios more than 1 sd below the mean. All children with SHOX haploinsufficiency exhibited at least one characteristic radiological sign of Leri-Weill-dyschondrosteosis in their left-hand radiography, namely triangularization of the distal radial epiphysis, pyramidalization of the distal carpal row, or lucency of the distal ulnar border of the radius. Our observations suggest that it is rational to limit SHOX mutation screening to children with an extremities-trunk ratio less than 1.95 + 1/2 height (m) and to add a critical judgment of the hand radiography.
Oxidative Stress Is Associated with Adiposity and Insulin Resistance in Men
Authors: Urakawa Hideki , Katsuki Akira , Sumida Yasuhiro , Gabazza Esteban C. , Murashima Shuichi , Morioka Kohei , Maruyama Noriko , Kitagawa Nagako , Tanaka Takashi , Hori Yasuko , Nakatani Kaname , Yano Yutaka , Adachi Yukihiko 
Published: October 2003

Abstract
To investigate the direct relationship of oxidative stress with obesity and insulin resistance in men, we measured the plasma levels of 8-epi-prostaglandin F2α (PGF2α) in 14 obese and 17 nonobese men and evaluated their relationship with body mass index; body fat weight; visceral, sc, and total fat areas, measured by computed tomography; and glucose infusion rate during a euglycemic hyperinsulinemic clamp study.
Obese men had significantly higher plasma concentrations of 8-epi-PGF2α than nonobese men (P &lt; 0.05). The plasma levels of 8-epi-PGF2α were significantly correlated with body mass index (r = 0.408; P &lt; 0.05), body fat weight (r = 0.467; P &lt; 0.05), visceral (r = 0.387; P &lt; 0.05) and total fat area (r = 0.359; P &lt; 0.05) in all (obese and nonobese) men. There was also a significant correlation between the plasma levels of 8-epi-PGF2α and glucose infusion rate in obese men (r = −0.552; P &lt; 0.05) and all men (r = −0.668; P &lt; 0.01). In all subjects, the plasma levels of 8-epi-PGF2α were significantly correlated with fasting serum levels of insulin (r = 0.487; P &lt; 0.01).
In brief, these findings showed that the circulating levels of 8-epi-PGF2α are related to adiposity and insulin resistance in men. Although correlation does not prove causation, the results of this study suggest that obesity is an important factor for enhanced oxidative stress and that this oxidative stress triggers the development of insulin resistance in men.
Direct Measurements of the Permeability Surface Area for Insulin and Glucose in Human Skeletal Muscle
Authors: Gudbjörnsdóttir Soffia , Sjöstrand Mikaela , Strindberg Lena , Wahren John , Lönnroth Peter 
Published: October 2003

Abstract
To elucidate mechanisms regulating capillary transport of insulin and glucose, we directly calculated the permeability surface (PS) area product for glucose and insulin in muscle.
Intramuscular microdialysis in combination with the forearm model and blood flow measurements was performed in healthy males, studied during an oral glucose tolerance test or during a one-step or two-step euglycemic hyperinsulinemic clamp.
PS for glucose increased significantly from 0.29 ± 0.1 to 0.64 ± 0.2 ml/min·100 g after oral glucose tolerance test, and glucose uptake increased from 1.2 ± 0.4 to 2.6 ± 0.6 μmol/min·100 g (P &lt; 0.05). During one-step hyperinsulinemic clamp (plasma insulin, 1.962 pmol/liter), PS for glucose increased from 0.2 ± 0.1 to 2.3 ± 0.9 ml/min·100 g (P &lt; 0.05), and glucose uptake increased from 0.6 ± 0.2 to 5.0 ± 1.4 μmol/min·100 g (P &lt; 0.05). During the two-step clamp (plasma insulin, 1380 ± 408 and 3846 ± 348 pmol/liter), the arterial-interstitial difference and PS for insulin were constant. The PS for glucose tended to increase (P = not significant), whereas skeletal muscle blood flow increased from 4.4 ± 0.7 to 6.2 ± 0.8 ml/min·100 ml (P &lt; 0.05).
The present data show that PS for glucose is markedly increased by oral glucose, whereas a further vasodilation exerted by high insulin concentrations may not be physiologically relevant for capillary delivery of either glucose or insulin in resting muscle.
Correlation between the Loss of Thyroglobulin Iodination and the Expression of Thyroid-Specific Proteins Involved in Iodine Metabolism in Thyroid Carcinomas
Authors: Gérard A.-C. , Daumerie C. , Mestdagh C. , Gohy S. , de Burbure C. , Costagliola S. , Miot F. , Nollevaux M.-C. , Denef J.-F. , Rahier J. , Franc B. , De Vijlder J. J. M. , Colin I. M. , Many M.-C. 
Published: October 2003

AbstractProgress in biotechnology has provided useful tools for tracing proteins involved in thyroid hormone synthesis in vivo. Mono- or polyclonal antibodies are now available to detect on histological sections the Na+/I− symporter (NIS) at the basolateral pole of the cell, the putative iodide channel (pendrin) at the apical plasma membrane, thyroperoxidase (TPO), and members of the NADPH-oxidase family, thyroid oxidase 1 and 2 (ThOXs), part of the H2O2-generating system. The aim of this study was to correlate thyroglobulin (Tg) iodination with the presence of these proteins. Tg, T4-containing Tg, NIS, pendrin, TPO, ThOXs, and TSH receptor (TSHr) were detected by immunohistochemistry on tissue sections of normal thyroids and various benign and malignant thyroid disorders. Tg was present in all cases. T4-containing Tg was found in the adenomas, except in Hurthle cell adenomas. It was never detected in carcinomas. NIS was reduced in all types of carcinomas, whereas it was detected in noncancerous tissues. Pendrin was not expressed in carcinomas, except in follicular carcinomas, where weak staining persisted. TPO expression was present in insular, follicular carcinomas and in follicular variants of papillary carcinomas, but in a reduced percentage of cells. It was below the level of detection in papillary carcinomas. The H2O2-generating system, ThOXs, was found in all carcinomas and was even increased in papillary carcinomas. Its staining was apical in normal thyroids, whereas it was cytoplasmic in carcinomas. The TSHr was expressed in all cases, but the intensity of the staining was decreased in insular carcinomas. In conclusion, our work shows that all types of carcinomas lose the capacity to synthesize T4-rich, iodinated Tg. In follicular carcinomas, this might be due to a defect in iodide transport at the basolateral pole of the cell. In papillary carcinomas, this defect seems to be coupled to an altered apical transport of iodide and probably TPO activity. The TSHr persists in virtually all cases.
Adiposity Contributes to Differences in Left Ventricular Structure and Diastolic Function with Age in Healthy Men
Authors: Gates Phillip E. , Gentile Christopher L. , Seals Douglas R. , Christou Demetra D. 
Published: October 2003

Abstract
We sought to examine the influence of adiposity in age-associated changes in the left ventricle (LV) in a cohort of 113 healthy men, aged 20–79 yr, by measuring LV structure and diastolic function (echocardiography), whole body composition, and regional adiposity (dual energy x-ray absorptiometry). Aging was associated with increased levels of adiposity, greater wall thickness to chamber radius ratio, LV concentric remodeling, and reduced LV diastolic function (all P &lt; 0.05). Bivariate correlation analysis showed that mean LV wall thickness, a concentric LV morphology, and diastolic function were related to adiposity (r = −0.63 to 0.51; all P &lt; 0.05). The relation between age and both mean LV wall thickness and concentric remodeling was reduced after controlling for percentage total body fat (by 38% and 54%, respectively), percentage abdominal fat (by 42% and 62%), and the abdominal/thigh fat ratio (by 35% and 46%). The diastolic function-age relation was reduced after controlling for percentage total body fat (by 35%), percentage abdominal fat (by 39%), and the abdominal/thigh fat ratio (by 29%). There were no apparent differences in the contribution of percentage total body fat, percentage abdominal fat, or abdominal/thigh fat to the association between age and LV structure/diastolic function. We conclude that increasing adiposity contributes to the LV remodeling/reduced diastolic function that occurs with aging in healthy men.
The Hypoparathyroidism of Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy Protective Effect of Male Sex
Authors: Gylling Mikhail , Kääriäinen Essi , Väisänen Riitta , Kerosuo Laura , Solin Marja-Liisa , Halme Leena , Saari Seppo , Halonen Maria , Kämpe Olle , Perheentupa Jaakko , Miettinen Aaro 
Published: October 2003

AbstractIn autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, hypoparathyroidism (HP) is the most common endocrine component. It occurs in most (but not all) patients. Determinants of its occurrence are unknown, and there is no proof for its autoimmune nature. Recently, the Ca2+-sensing receptor (CaSR) was reported to be an autoantigen in HP. With our group of 90 patients, we aimed at identifying the determinants and pathomechanism of HP. For the determinants, we evaluated gender and the HLA class II. For the pathomechanism, we searched for parathyroid autoantibodies, including antibodies against CaSR and PTH. Also, we studied whether AIRE is expressed in the human parathyroid, because its absence could be a pathogenetic factor. We found a clear gender linkage with lower and later incidence in males. Of the 14 patients who had escaped HP, 13 were males. This was associated with adrenal failure, which was the first or only endocrinopathy in 47% of males vs. 7% of females. In contrast, we found no linkage to the HLA class II. By immunofluorescence, 19% of the patients had antibodies to parathyroid epithelia. By immunoblotting, these recognized several parathyroid proteins. No antibodies were observed against the CaSR or PTH. By RT-PCR, AIRE mRNA was not found in the parathyroid.
The Pathophysiology of Diabetes Involves a Defective Amplification of the Late-Phase Insulin Response to Glucose by Glucose-Dependent Insulinotropic Polypeptide—Regardless of Etiology and Phenotype
Authors: Vilsbøll T. , Knop F. K. , Krarup T. , Johansen A. , Madsbad S. , Larsen S. , Hansen T. , Pedersen O. , Holst J. J. 
Published: October 2003

Abstract
The effect of the insulinotropic incretin hormone, glucagon-like peptide-1 (GLP-1), is preserved in typical middle-aged, obese, insulin-resistant type 2 diabetic patients, whereas a defective amplification of the so-called late-phase plasma insulin response (20–120 min) to glucose by the other incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), is seen in these patients. The aim of the present investigation was to evaluate plasma insulin and C-peptide responses to GLP-1 and GIP in five groups of diabetic patients with etiology and phenotype distinct from the obese type 2 diabetic patients. We studied (six in each group): 1) patients with diabetes mellitus secondary to chronic pancreatitis; 2) lean type 2 diabetic patients (body mass index &lt; 25 kg/m2); 3) patients with latent autoimmune diabetes in adults; 4) diabetic patients with mutations in the HNF-1α gene [maturity-onset diabetes of the young (MODY)3]; and 5) newly diagnosed type 1 diabetic patients. All participants underwent three hyperglycemic clamps (2 h, 15 mm) with continuous infusion of saline, 1 pmol GLP-1 (7–36)amide/kg body weight·min or 4 pmol GIP pmol/kg body weight·min. The early-phase (0–20 min) plasma insulin response tended to be enhanced by both GIP and GLP-1, compared with glucose alone, in all five groups. In contrast, the late-phase (20–120 min) plasma insulin response to GIP was attenuated, compared with the plasma insulin response to GLP-1, in all five groups. Significantly higher glucose infusion rates were required during the late phase of the GLP-1 stimulation, compared with the GIP stimulation. In conclusion, lack of GIP amplification of the late-phase plasma insulin response to glucose seems to be a consequence of diabetes mellitus, characterizing most, if not all, forms of diabetes.
Final Height and Body Mass Index among Adult Survivors of Childhood Brain Cancer: Childhood Cancer Survivor Study
Authors: Gurney James G. , Ness Kirsten K. , Stovall Marilyn , Wolden Suzanne , Punyko Judy A. , Neglia Joseph P. , Mertens Ann C. , Packer Roger J. , Robison Leslie L. , Sklar Charles A. 
Published: October 2003

AbstractThe objectives of this study were 1) to compare final height and body mass index (BMI) between adult survivors of childhood brain cancer and age- and sex-matched population norms, 2) to quantify the effects of treatment- and cancer-related factors on the risk of final height below the 10th percentile (adult short stature) or having a BMI of 30 kg/m2 or more (obesity). Treatment records were abstracted and surveys completed by 921 adults aged 20–45 yr who were treated for brain cancer as children and were participants in the multicenter Childhood Cancer Survivor Study. Nearly 40% of childhood brain cancer survivors were below the 10th percentile for height. The strongest risk factors for adult short stature were young age at diagnosis and radiation treatment involving the hypothalamic-pituitary axis (HPA). The multivariate odds ratio for adult short stature among those 4 yr of age or younger at diagnosis, relative to ages 10–20 yr, was 5.67 (95% confidence interval, 3.6–8.9). HPA radiation exposure increased the risk of adult short stature in a dose-response fashion (trend test, P &lt; 0.0001). Adjuvant chemotherapy was not an independent risk factor for adult short stature. BMI distribution in survivors did not differ appreciably from that of population norms; however, in females, young age at diagnosis and HPA radiation dose (trend test, P &lt; 0.001) were associated with risk of obesity. Except for patients treated with surgery only, survivors of childhood brain cancer are at very high risk for adult short stature, and this risk increases with radiation dose involving the HPA. We did not find a corresponding elevated risk for obesity.