bluuebunny/crossref_metadata_2025_split huggingface dataset:
Urinary excretion of pyridinoline and deoxypyridinoline measured by immunoassay in hypothyroidism
Authors: Nakamura Hirotoshi , Mori Tomoko , Genma Rieko , Suzuki Yoshikazu , Natsume Hiroko , Andoh Shinichiro , Kitahara Ryo , Nagasawa Shinsuke , Nishiyama Kozo , Yoshimi Teruya 
Published: November 2003

OBJECTIVE We measured pyridinium cross‐links, markers of bone resorption, by an enzyme‐linked immunosorbent assay (ELISA) in hypothyroid patients to see whether bone resorption was reduced in hypothyroidism and whether it increased with T4 treatment.DESIGN AND PATIENTS Eight hypothyroid patients, whose initial TSH levels were 268.1 ± 87.7 mU/l (mean ± SE), were treated with T4 (100μg/day). Urinary excretion of pyridinium cross‐links was assayed before and after T4 treatment.MEASUREMENTS Pyrilinks and Pyrilinks‐D kits were used. The Pyrilinks assay measures free forms of pyridinoline and deoxypyridinoline together (PYD), while the Pyrilinks‐D assay measures deoxypyridinoline (DPD) alone. The Pyrilinks reference ranges for normal subjects are 8–24nmol/mmol creatinine in males and 10–28nmol/mmol creatinine in normal premenopausal females. The DPD reference ranges obtained from normal men and women aged 40–50 years were 3.20 ± 0.75 (mean ± SD) nmol/mmol creatinine and 4.55 ± 1.22 nmol/mmol creatinine, respectively.RESULTS The sensitivity of the assay was enhanced by simply using less diluted urine samples. Concentrations of both compounds of the urinary pyridinium cross‐links were low in untreated hypothyroid patients and increased gradually as thyroid hormone status improved from hypothyroidism to euthyroidism. One month after treatment when the TSH levels in the patients were still as high as 74.4 ± 44.5 mU/l, urinary PYD excretion has increased to 2.6 times the pretreatment level. When the TSH levels of the patients decreased below 10 mU/l, both PYD and DPD increased significantly to 3.8 and 3.3 times pretreatment values, respectively.CONCLUSIONS Although hyperthyroidism or excess treatment with thyroid hormone has been known to induce bone resorption, this is the first report that urinary excretion of pyridinium cross‐links is reduced in hypothyroidism and is normalized by physiological thyroid hormone replacement.
Glucose turnover, fuel oxidation and forearm substrate exchange in patients with thyrotoxicosis before and after medical treatment
Authors: Møller Niels , Nielsen Søren , Nyholm Birgit , Pørksen Niels , George K. , Alberti M. M. , Weeke Jørgen 
Published: November 2003

OBJECTIVE Accelerated metabolism is a hallmark of thyrotoxicosis, but the underlying bioche mical mechanisms are incompletely understood and the majority of studies have investigated normal subjects rendered only modestly hyperthyroid for a brief period of time. We have therefore studied a group of thyrotoxic patients using several different techniques.DESIGN Twelve patients with newly diagnosed diffuse (10 patients) or nodular (2 patients) toxic goitre (10 women, 2 men; age 42.8 ± 3.2 years; BMI 21.6 ±0.7 kg/m2) before (‘pretreatment’) and after (‘treated’) 11.2 ± 1.0 weeks treatment with methimazole and compared these patients to a control group (‘control’) of 11 subjects (9 women, 2 men; age 40.5 ± 3.9 years; BMI 22.5 ± 1.0 kg/m2). All were studied for 3 hours in the basal state, using indirect calorimetry, isotope dilution for the measurement of glucose turnover and the forearm technique for assessment of muscle metabolism.RESULTS Prior to treatment patients with thyrotoxicosis were characterized by increased (P < 0.05) levels of T3 (3.75 ± 0.23 nmol/l (pretreatment), 1.89 ± 0.08 (treated) and 1.75 ± 0.11 (control)), resting energy expenditure (130.5 ± 3.5 (pretreatment), 107.7 ± 2.7 (treated) and 106.3 ± 3.1 (control), % of predicted), protein oxidation (0.67 ± 0.03 (pretreatment), 0.54 ± 0.06 (treated) and 0.46 ± 0.05 (control), mg/kg/min), lipid oxidation (1.34 ± 0.08 (pretreatment), 1.00 ± 0.06 (treated) and 1.02 ± 0.04 (control), mg/kg/min), endogenous glucose production (2.51 ± 0.13 (pretreatment), 1.86 ± 0.12 (treated) and 1.85 ± 0.12 (control), mg/kg/min), non‐oxidative glucose turnover (1.28 ± 0.16 (pretreatment), 0.75 ± 0.18 (treated) and 0.71 ± 0.11 (control), mg/kg/min) and a 50% increase in total forearm blood flow. Glucose oxidation (1.23 ± 0.09 (pretreatment), 1.13 ± 0.10 (treated) and 1.21 ± 0.11 (control) mg/kg/min), exchange of substrates in the muscles of the forearm and circulating levels of insulin, C‐peptide, growth hormone or glucagon were not influenced by hyperthyroidism. Propranolol (20 mg thrice daily) given to 7 of the patients for 2 days did not affect circulating levels of thyroid hormones, energy expenditure or glucose turnover rates.CONCLUSIONS These results suggest that all major fuel sources contribute to the hypermetabolism of thyrotoxicosis and that augmented non‐oxidative glucose metabolism may further aggravate the condition. All abnormalities diminish with medical treatment of the disease.
Expression of the transferrin receptor in human anterior pituitary adenomas is confined to gonadotrophinomas
Authors: Atkin S. L. , Burnett H. E. , Green V. L. , White M. C. , Lombard M. 
Published: November 2003

OBJECTIVE The human pituitary gland is affected selectively by conditions associated with iron deposition, but the mechanisms for this are unknown. In this study we have determined whether the transferrin receptor, which mediates iron uptake by cells, could be detected immunocytochemically in human pituitary adenomas in vitro.PATIENTS Data were derived from 35 patients undergoing transsphenoidal surgery and included 13 with clinically non‐functioning adenomas, 15 with acromegaly, 4 prolactinomas, 2 patients with Cushing’s disease and one patient with Nelson’s syndrome.MEASUREMENTS Transferrin receptor immunopositivity was determined for each adenoma in dispersed cell culture using a specific monoclonal antibody.RESULTS Eight of 13 clinically functionless adenomas showed immunopositive transferrin receptor expression, whilst adenomas from 15 patients with acromegaly, 4 prolactinomas, 2 Cushing’s syndrome and one patient with Nelson’s syndrome were negative. The eight transferrin receptor positive tumours were gonadotrophinomas and accounted for eight of the nine tumours which secreted and immunostained for FSH; all eight also secreted and immunostained for LH.CONCLUSIONS These findings may reflect a special requirement for iron by gonadotrophin secreting cells in comparison to other pituitary cell types and this could underlie the reasons why in the normal pituitary these cells are especially susceptible to malfunction in iron overload syndromes such as genetic haemochromatosis and β‐thalassaemia.
The impact of liver transplantation on endocrine status in men
Authors: Madersbacher Stephan , Ludvik Georg , Stulnig Thomas , Grünberger Thomas , Maier Ulrich 
Published: November 2003

OBJECTIVE There are few longitudinal data on the endocrine changes which occur after liver transplantation. We have therefore studied the impact of orthotopic liver transplantation (oLTX) on the hypothalamic–pituitary–gonadal hormone axis and sex steroid metabolism in men.PATIENTS AND STUDY DESIGN Ten male patients with end‐stage liver failure due to alcohol induced cirrhosis (n = 2), virus‐induced cirrhosis (n=5), primary biliary cirrhosis (n=1) and idiopathic cirrhosis (n=2) were included in a prospective study analysing the impact of oLTX on endocrine status. They were studied before and after oLTX with a mean follow‐up of 11.6 months (range 4–23) following transplantation.MEASUREMENTS Serum levels of LH, FSH, testosterone (TE), free TE, PRL, cortisol, oestradiol (E2) and sex hormone binding globulin (SHBG) were analysed with commercially available radioimmunoassays in all individuals before and after oLTX. Gonadotrophin releasing hormone stimulation tests were done in 5 patients before and after oLTX. Additionally, a complete urological assessment with a detailed questionnaire on sexual function was obtained from all individuals.RESULTS Prior to oLTX, endocrine status was invariably abnormal, the most prominent finding being a pathological decrease of TE in 90% and of free TE in all cases. After successful oLTX, all individuals had physiological levels of TE and of free TE which increased twofold (P<0.01) and tenfold (P<0.000 1), respectively. Additionally, serum gonadotrophin (LH/FSH) levels increased in the majority of patients, while E2 decreased following oLTX. Endocrine changes extended beyond the hypothalamic–pituitary–gonadal hormone axis, as shown by a decrease in PRL (P<0.02) and SHBG (P<0.01) after transplantation. GnRH tests revealed normal stimulation of LH and FSH before and after oLTX in all cases. Libido, potency and frequency of sexual intercourse improved significantly after oLTX in the majority of patients.CONCLUSIONS These findings demonstrate the ability of the hypothalamic–pituitary–gonadal hormone axis and sex steroid metabolism to resume physiological function following orthotopic liver transplantation in men. Correspondingly, sexual function returns to normal in the majority of patients, despite significant alterations prior to orthotopic liver transplantation.
Risk factors for secondary hyperparathyroidism in a nursing home population
Authors: Stein Mark S. , Scherer Samuel C. , Lynette Walton S. , Gilbert Richard E. , Ebeling Peter R. , Flicker Leon , Wark John D. 
Published: November 2003

OBJECTIVE Secondary hyperparathyroidism may cause bone loss and structural deterioration of bone and may thus be a cause of fracture in the elderly. Vitamin D deficiency, renal impairment and medications are potential causes of hyperparathyroidism and may also directly predispose to fracture. We present the first findings of an ongoing study of hip fracture, vitamin D deficiency and hyperparathyroidism in a large Australian nursing home.DESIGN Descriptive prevalence study.PATIENTS Two hundred and fifty‐one nursing home residents were eligible for inclusion. Informed consent and successful venepuncture were obtained for 99. Residents were of median age 83 years with interquartile range (IR) 77–89 years.MEASUREMENTS 25‐Hydroxyvitamin D (25OHD), intact parathyroid hormone (PTH), creatinine and biochemistry, demographic data and current medications.RESULTS Fifty‐two per cent of 99 subjects had 25OHD below the reference range of 28–165 nmol/l and 96.5% were below the reference range mean. Those with low 25OHD had lower plasma calcium corrected for albumin than those with normal 25OHD (medians 2.34 vs 2.41mmol/l, 95% confidence interval for the difference between medians (CI) −0.10 to −0.04 mmol/l, P=0.0001) and higher PTH (medians 5.8 vs 3.9 pmol/l, CI 0.10–2.6pmol/l, P=0.0360). Twenty‐eight per cent of 97 residents had PTH above the upper reference range limit of 6.5 pmol/l. Residents receiving frusemide had higher PTH than other residents (medians 6.95 vs 3.45 pmol/l, CI 1.9–4.2pmol/l, P<0.0001). In linear modelling, the most important predictor of the natural logarithm of PTH was daily frusemide dose, adjusted R2 (Ra2)=31.8%, F=39.3, P<0.001. Creatinine and the reciprocal of 25OHD were other significant predictors with the final Ra2=39.4%, F=17.7, P<0.001.CONCLUSIONS Vitamin D deficiency is a common risk factor for secondary hyperparathyroidism in nursing home residents despite a climate in which vitamin D nutrition is thought to be ample. However, the daily frusemide dose is a more important predictor of PTH in this population.
Determination of renin, angiotensin converting enzyme and angiotensin II levels in human placenta, chorion and amnion from women with pregnancy induced hypertension
Authors: Kalenga M. K. , Thomas K. , De Gasparo M. , De Hertogh R. 
Published: November 2003

OBJECTIVE Pregnancy induced hypertension has been shown to be associated with a normal or low activity of the maternal circulating renin–angiotensin system (RAS) but little is known of the local RAS in placenta and fetal membranes. The present study attempts to determine, at full term of human preeclamptic pregnancies, the activity of the chorioplacental renin–angiotensin system.PATIENTS AND MEASUREMENTS We analysed the concentrations of active renin, prorenin, angiotensin converting enzyme (ACE) and angiotensin II in homogenates of human placenta and fetal membranes from preeclamptic patients at full term pregnancy. The values of renin, ACE and angiotensin II found in the patients with moderate preeclampsia (gestosis index 0–1) (n = 10) were compared with those of normal pregnant women (n = 8).RESULTS Our experiments showed that in preeclamptic pregnancies, the chorion membrane contained the highest concentrations of active renin (2905 ± 152 pg/g, mean ± SD), prorenin (21 315 ± 2849 pg/g) and ACE (1258 ± 302 U/g) whereas the placenta had more angiotensin II than the chorion and amnion (741 ± 45 vs 456 ± 40 and 428 ± 64 pg/g, respectively). In the placenta, as in the fetal membranes, no significant difference was found in the levels of active renin, ACE or angiotensin II between hypertensive patients and normal subjects but a slightly lower level of chorionic prorenin (P < 0.05) was observed in pregnancy induced hypertension.CONCLUSION These findings indicate that in moderate preeclampsia (gestosis index 0–1), the activity of the renin–angiotensin system in term human placenta and fetal membranes remains essentially normal.
The development, reliability and validity of a disease specific quality of life model for adults with growth hormone deficiency
Authors: Wallymahmed Maureen E. , Baker Gus A. , Humphris Gerry , Dewey Michael , MacFarlane Ian A. 
Published: November 2003

OBJECTIVE Adults with GH deficiency frequently complain of lack of energy, fatigue, social isol ation and problems with sexual relationships resulting in a low perceived quality of life. Previous studies of quality of life (QOL) in GH deficient adults have involved small numbers of patients and used measures not specifically designed for this patient population. We have devised a health related QOL model specifically designed for use in adults with GH deficiency and to assess the impact of future GH replacement therapy.DESIGN Six measurements were chosen for inclusion in the model. Two were adapted for use after clinical interviews with 12 adult GH deficient patients: the Impact and the Life Fulfilment scales. The others were the Nottingham Health Profile, the Hospital Anxiety and Depression Scale, the Self‐Esteem Scale and the Mental Fatigue Questionnaire. The reliability of the 6 measures was assessed by 2 methods: test re‐test correlation and internal consistency (Cronbach's α). The validity of the Impact and Life Fulfilment scales was assessed by correlation with the other 4 scales.PATIENTS Questionnaires were completed by 32 adults with hypothalamic pituitary disorders and GH deficiency (11 male, mean age 35.1 years), with a stimulated maximum serum GH response less than 10 mU/l (mean 2.96).Two had previously received GH injections in childhood. The questionnaires were also completed by 32 age and sex matched control subjects.RESULTS The 6 scales had test re‐test correlations of 0.70–0.92 indicating reliability over time. The Impact and Life Fulfilment Scales and the Mental Fatigue Questionnaire had Cronbach's α scores of greater than 0.6 indicating their potential for use in clinical trials. The Impact and Life Fulfilment scales correlated significantly with many physical and psychological domains from the other 4 scales indicating these were valid in the assessment of health related QOL in GH deficient adults. Compared to the controls the patients with GH deficiency were significantly psychosocially disadvantaged in terms of depression, self‐esteem, mental fatigue and life fulfilment.CONCLUSION The results of the reliability and validity studies indicate that this health related quality of life model for use with adults with GH deficiency is a potentially valid and reliable tool that could be used to assess the effect of GH treatment.
Thyroid peroxidase: evidence for disease gene exclusion in Pendred's syndrome
Authors: Gausden Eleanor , Armour John A. L. , Coyle Beth , Coffey Rebecca , Hochberg Ze'ev , Pembrey Marcus , Britton Keith E. , Grossman Ashley , Reardon William , Trembath Richard 
Published: November 2003

OBJECTIVE Pendred's syndrome is an association between congenital neurosensory deafness and goitre with abnormal discharge of iodide following perchlorate challenge, indicating a defect of iodide organification. Although Pendred's syndrome may cause up to 7.5% of all cases of congenital deafness, the molecular basis of the association between the hearing loss and the thyroid organification defect remains unknown. We chose to investigate the role of the thyroid peroxidase (TPO) gene as the genetic defect in Pendred's syndrome.DESIGN A highly informative variable number tandem repeat (VNTR), located 1.5kb downstream of exon 10 of the TPO gene,was used to search for genetic linkage in multiple sibships affected by Pendred's syndrome.PATIENTS Seven kindreds were recruited from the UK, each with at least two affected members. We have also examined a large inbred Israeli family with two affected offspring and five unaffected children.MEASUREMENTS Individuals were assigned affected status based on the characteristic clinical features of Pendred's syndrome, namely the presence of congenital sensorineural hearing loss and the appearance in early life of a goitre. Additionally, at least one affected member from each sibship had a characteristic positive perchlorate discharge test (Morgans & Trotter, 1958). PCR amplification of genomic DNA at the TPO VNTR allowed assignment of genotypes to each individual and the calculation of a two‐point LOD scoreRESULTS In six of the nine sibships analysed we found obligatory recombination between TPO and Pendred's syndrome. Non‐complementation observed in affected parents with an affected offspring excluded TPO in an affected sibship with genotype sharing and supports a hypothesis of genetic homogeneity for Pendred's syndrome. In two sibships, mutation of the TPO gene as the cause of Pendred's syndrome could not be excluded.CONCLUSIONS These data suggest that defects at the thyroid peroxidase locus on chromosome 2 are not the major cause of Pendred's syndrome.
Homozygous nonsense mutation in the insulin receptor gene of a patient with severe congenital insulin resistance: leprechaunism and the role of the insulin‐like growth factor receptor
Authors: Kaplowitz Nicholas , Furlanetto Richard W. 
Published: November 2003

Severe congenital insulin resistance in the syndrome of leprechaunism is caused by mutations in the insulin receptor gene. We report a patient with leprechaunism who was homozygous for a mutation resulting in the absence of cell surface insulin receptors. To determine whether the receptor for Insulin‐like growth factor‐I (IGF‐I) is involved in the phenotype of leprechaunism, we studied the effect of insulin and of IGF‐I on cells from this patient. The patient had a homozygous C → T substitution at base pair 8212 in exon 12 of the insulin receptor gene, creating a premature stop codon. This nonsense mutation is in the extracellular portion of the receptor and truncates the insulin receptor proximal to its transmembrane anchor, resulting in the absence of cell surface insulin receptors. This finding indicates that complete absence of the insulin receptor is compatible with life. Secondly, DNA synthesis was studied in skin derived fibroblasts in response to increasing concentrations of either insulin or Insulin‐like growth factor ‐I (IGF‐I), and was assessed by 3H‐thymidine incorporation. In this patient’s cells, both of these hormones increased 3H‐thymidine incorporation, and the effect was blocked by α‐IR3, a monoclonal antibody that blocks activation of the IGF‐I receptor. These findings confirmed the absence of the insulin receptor and indicated that insulin acts here through activation of the IGF‐I receptor. These data support the contention that the phenotypic and metabolic abnormalities of leprechaunism result from the combination of lack of insulin receptor action and over‐activation by insulin of the type 1 IGF receptor.
Vasopressin levels in Cushing's disease: inferior petrosal sinus assay, response to corticotrophin‐releasing hormone and comparison with patients without Cushing's disease
Authors: Colao Annamaria , Ferone Diego , Di Sarno Antonella , Tripodi Francesca S. , Cerbone Gaetana , Marzullo Paolo , Boudouresque Françoise , Oliver Charles , Merola Bartolomeo , Lombardi Gaetano 
Published: November 2003

BACKGROUND Higher vasopressin (AVP) levels have been found in the inferior petrosal sinus ipsilateral to the ACTH‐secreting adenoma than in the contralateral one, suggesting a potential pathogenetic role of AVP in Cushing's disease. DESIGN In order to investigate AVP release, plasma ACTH and AVP concentrations were assayed in the inferior petrosal sinuses and in the peripheral blood before and after CRH stimulation. PATIENTS Twenty patients with Cushing's disease and 12 with other pituitary diseases were subjected to simultaneous and bilateral inferior petrosal sinus sampling for diagnostic purposes. Ten healthy sex and age‐matched subjects served as control for peripheral AVP values. MEASUREMENTS Plasma ACTH concentrations were measured by RIA using commercial kits. Plasma AVP concentrations were assayed by RIA in acetone extracts of 1–2 ml plasma. RESULTS Plasma AVP levels in the inferior petrosal sinuses were significantly higher in Cushing's disease than in patients with other pituitary diseases (P<0.05) and in both groups AVP levels were higher in the inferior petrosal sinuses than in the peripheral blood (P<0.01). In Cushing's disease, ACTH, but not AVP levels, were higher in the inferior petrosal sinus ipsilateral to the adenoma than in the contralateral one (P<0.01). Seven patients showed a significant ACTH and AVP increase (greater than 50% of baseline) after CRH stimulation in the inferior petrosal sinus ipsilateral to the adenoma. Conversely, no change was found in AVP levels in the remaining 13 patients. When AVP values were analysed in relation to surgical cure, higher inferior petrosal sinus levels (P<0.05) were found in 6 patients with poor outcome: 4 of these patients had significantly decreased plasma AVP concentrations (by 32–43% of baseline) after CRH bolus. Peripheral AVP levels were similar in healthy subjects and patients with Cushing's disease whereas they were significantly reduced in patients with other pituitary diseases (P<0.002). CONCLUSIONS The results of this study show that patients with Cushing's disease and poor surgical outcome had the highest AVP levels in our series. CRH administration caused different effects on AVP levels: it increased them in 35% of patients whereas there was no response in the remaining patients. On the basis of these findings, it is hypothesized that AVP might be involved in the persistence of ACTH hypersecretion in a subset of patients poorly responsive to surgery.