bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of 6 years of growth hormone (GH) treatment on bone mineral density in GH‐deficient adults
Authors: Clanget C. , Seck T. , Hinke V. , Wüster C. , Ziegler R. , Pfeilschifter J. 
Published: March 2003

OBJECTIVE Adults with growth hormone (GH) deficiency are often osteopenic. Short‐term GH replacement therapy has been shown to improve bone mineral density (BMD). However, whether the increases in BMD are progressive with time is still unclear. We therefore examined long‐term changes in BMD with GH treatment in GH‐deficient adults over a period of 6 years.DESIGN  Open prospective GH therapeutic study.PATIENTS  Twelve GH‐deficient patients (four women, eight men) with a mean age of 42·5 years (range 24–61 years) at the beginning of GH replacement. Eleven patients suffered in addition from LH/FSH insufficiency, eight from TSH insufficiency and eight from ACTH insufficiency. Before the start of GH substitution, the insufficient anterior pituitary axes were fully substituted for an average of 9·8 years (range 2–22 years). Average daily GH dose was 2·4 IU (SD 0·86).MEASUREMENTS BMD and bone area were measured at annual intervals at the lumbar spine and at the proximal femur using dual‐X‐ray absorptiometry.RESULTS  Under GH substitution, serum insulin‐like growth factor I concentrations increased by 140 μg/l compared to pretherapeutic values (P = 0·0003). BMD at the lumbar spine increased by 0·16 g/cm2 (P = 0·0005), corresponding to a mean increase of 15·9% or an increase of the BMD Z‐score by 1·53 SD. Increases in BMD were independently observed from years 3 to 6 by a mean of 5·8% (P = 0·0087). This increase was paralleled by an increase in the area of the lumbar vertebrae. Bone area also increased at selected sites of the proximal femur, but there was no consistent increase in BMD at the proximal femur.CONCLUSION  GH therapy in GH‐deficient adults is able to progressively increase BMD and bone area at the lumbar spine over a period of at least 6 years. However, our study has several limitations, making it necessary to confirm these findings in further long‐term studies.
Alcohol consumption is associated with reduced prevalence of goitre and solitary thyroid nodules
Authors: Knudsen Nils , Bülow Inge , Laurberg Peter , Perrild Hans , Ovesen Lars , Jørgensen Torben 
Published: March 2003

OBJECTIVE Goitre prevalence is dependent on iodine intake and smoking habits, but further risk factors have only been examined briefly. We examined the association between alcohol consumption and the prevalence of thyroid enlargement and nodularity.DESIGN Cross‐sectional population study with ultrasonography of the thyroid gland and assessment of alcohol intake and smoking habits from questionnaires.SUBJECTS Four thousand six‐hundred and forty‐nine men and women aged 18–65 years, randomly selected from the Danish Civil Registration System.MEASUREMENTS Thyroid volume and prevalence of thyroid enlargement, multiple nodules or a solitary nodule in the thyroid.RESULTS Abstainers and participants with a low alcohol consumption (< 7 drinks/week) had the same prevalence of thyroid enlargement and nodularity, but participants with moderate (8–28 drinks/week for women, 8–42 for men) or high (> 28/42 drinks/week) alcohol consumption had much lower prevalence of thyroid abnormalities. Possible confounding by sex, age, iodine status and smoking was considered in all models. Odds ratios compared to abstainers for thyroid enlargement were 0·74 [95% confidence interval (CI) 0·57–0·96] for moderate‐ and 0·44 (95% CI 0·22–0·88) for high alcohol consumption. Odds ratios compared to abstainers for a solitary nodule were 0·64 (95% CI 0·42–0·96) for moderate‐ and 0·41 (95% CI 0·12–1·37) for high alcohol consumption. Mean thyroid volume was 13·5 ml among abstainers compared to 10·9 ml among participants with high alcohol consumption (P < 0·001). Both wine‐ and beer consumption were associated to lower prevalence of thyroid abnormalities.CONCLUSIONS Increasing levels of alcohol consumption were associated to lower prevalence of thyroid enlargement and to lower prevalence of a solitary nodule in the thyroid, and indications of a causal relationship were found.
Assessment of selective arterial calcium stimulation and hepatic venous sampling to localize insulin‐secreting tumours
Authors: Brändle Michael , Pfammatter Thomas , Spinas Giatgen A. , Lehmann Roger , Schmid Christoph 
Published: March 2003

OBJECTIVE Non‐invasive localization modalities such as ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) often fail to localize insulinomas smaller than 2 cm in diameter. Recent studies have shown that the selective arterial stimulation and hepatic venous sampling (ASVS) technique using intra‐arterial calcium as the insulin secretagogue facilitates the regionalization of such occult insulinomas. This study assesses the sensitivity of ASVS in localizing insulin‐secreting tumours.SUBJECTS AND METHODS Eleven consecutive patients (8 women), aged 29–82 years, were studied over the past 4 years at our hospital. Hyperinsulinaemic hypoglycaemia due to an insulin‐secreting tumour was proven in all patients. Calcium gluconate (0·025 mEq/kg body weight) was injected directly into the arteries supplying the pancreas and the liver. Insulin levels were measured in samples taken from the right hepatic vein before and 30, 60 and 120 s after each injection. The ASVS technique was performed in all 11 patients; the results were compared with the surgical findings in 10 patients and the autopsy findings in 1 case. The ASVS results were also compared with the findings of other, previously performed imaging modalities.RESULTS ASVS correctly localized 4 insulin‐secreting tumours to the head, 3 to the body, 1 to the tail, 2 to the tail or body of the pancreas and 1 to the liver. Thus, the sensitivity was 100% (11/11) whereas other localization techniques were less sensitive: 7/11 tumours were detected by angiography, 4/8 by endosonography, 3/8 by CT and 1/6 by MRI. Insulinomas (confirmed by histological examination), sized 4–25 mm, were found in 10 patients. All were cured by selective surgery and remained free of hypoglycaemia over the next 1–4 years of follow‐up. An insulin‐secreting neuroendocrine tumour in the liver was documented in 1 case at autopsy.CONCLUSIONS Arterial stimulation and hepatic venous sampling is a very sensitive technique for preoperative localization of insulin‐producing tumours. It can help to plan minimally invasive surgery and to select an appropriate strategy for patients suffering from malignant tumours in others.
TSH‐receptor antibody measurement for differentiation of hyperthyroidism into Graves' disease and multinodular toxic goitre: a comparison of two competitive binding assays
Authors: Pedersen Inge Bülow , Knudsen Nils , Perrild Hans , Ovesen Lars , Laurberg Peter 
Published: March 2003

OBJECTIVES Graves' disease is characterized by stimulating autoantibodies to the TSH‐receptor (TRAb). The aim of this study was to compare the performance of a new TRAb assay based on competitive binding to recombinant human TSH‐receptors (H‐TRAb) with an assay employing purified porcine TSH‐receptors (P‐TRAb). Furthermore, to evaluate the applicability of the H‐TRAb assay to discriminate between patients with hyperthyroidism due to Graves' disease (GD) and multinodular toxic goitre (MNTG).DESIGN AND MEASUREMENTS H‐TRAb and P‐TRAb were measured in patients with newly diagnosed hyperthyroidism due to GD (n = 106) and MNTG (n = 94). For comparison, TRAb was measured in patients with primary autoimmune hypothyroidism, euthyroid subjects with an enlarged thyroid gland by ultrasound, and healthy controls (n = 100 for each group). Patients were consecutively included from a population survey.RESULTS If the cut‐off values recommended by the manufacturer for TSH‐receptor antibody positivity were used for evaluation, the sensitivity of the H‐TRAb assay vs. the P‐TRAb assay in diagnosing GD was: 95·3/67·9% (P < 0·001). Specificity was (H/P‐TRAb): 99/99%. The sensitivity of P‐TRAb was increased if the upper 97·5% limit of measurements in controls was used as cut‐off (H‐TRAb vs. P‐TRAb: 95·3/80·2%, P < 0·001). Specificity (H/P‐TRAb): 98/98%. The difference between assay performance may partly be due to a better technical performance of the H‐TRAb assay with more reliable results in the low range of measurements. However, even in GD patients with clearly measurable TRAb, 25% had a P‐TRAb < 50% of the value expected from the H‐TRAb measurement. This suggests that a subgroup of patients produce TRAb with a higher affinity for the human than the porcine TSH receptor. A relatively high proportion of patients with MNTG were TRAb positive (H‐TRAb/P‐TRAb: 17/9%). Characteristics of H‐TRAb positive and negative MNTG patients were compared. There was no difference between size of thyroid gland and number of nodules by ultrasonography. H‐TRAb positive patients had significantly higher serum T4 and T3 and a greater number were TPO‐Ab positive.CONCLUSIONS H‐TRAb diagnosed Graves' disease with a high sensitivity and specificity than P‐TRAb. The high occurrence of TRAb in multinodular toxic goitre might in part reflect an overlap between Graves' disease and multinodular toxic goitre in some patients.
Plasma leptin concentrations are associated with bone mineral density and the presence of vertebral fractures in postmenopausal women
Authors: Yamauchi Mika , Sugimoto Toshitsugu , Yamaguchi Toru , Nakaoka Daiki , Kanzawa Michiko , Yano Shozo , Ozuru Rieko , Sugishita Takeshi , Chihara Kazuo 
Published: March 2003

OBJECTIVE Although total fat body mass (FM) is considered to be one of the major determinants of bone mass, the mechanism by which FM and bone mass are positively correlated remains unclear. Leptin, the product of the obese (ob) gene, is secreted from adipocytes and its plasma levels are known to be positively correlated with %fat (FM divided by total body weight). There is recent evidence suggesting that leptin directly stimulates osteoblastic differentiation. Thus it is possible that the anabolic action of this hormone on bone may participate in the positive correlation between FM and bone mass. In this study, we analysed the relationships between either plasma leptin levels or %fat vs. bone mineral density (BMD) values as well as the presence of vertebral compression fractures, and evaluated whether or not plasma leptin levels were associated with BMD or bone fragility in a manner independent of FM.PATIENTS One hundred and thirty‐nine postmenopausal women (age 48–78 years, mean 62·5), who visited our outpatient clinic for the evaluation of osteoporosis.DESIGN and MEASUREMENTS Plasma concentrations of leptin after an overnight fast were measured by radioimmunoassay. BMD values were measured by dual‐energy X‐ray absorptiometry (DXA) at the lumbar spine, femoral neck and whole body. Distal one‐third of radius BMD was measured by single photon absorptiometry (SPA). Vertebral fractures were assessed by lateral thoracic and lumbar spine radiographs.RESULTS Although neither plasma leptin levels nor %fat correlated with age, there was a significant positive correlation between plasma leptin levels and %fat (r = 0·563, P < 0·001). Plasma leptin levels were significantly and positively correlated with BMD values at all skeleton sites measured, and multiple regression analysis revealed that this positive relationship was still observed with BMD values of the femoral neck and of the whole body, even after %fat and age were taken into account. Moreover, plasma leptin levels but not %fat were significantly lower in women with vertebral fractures than in those without fractures. When multiple logistic regression analysis was performed with either plasma leptin value or %fat employed as independent variables, plasma leptin values but not %fat were selected as an index affecting the presence of vertebral fractures.CONCLUSION Our study showed that plasma leptin levels but not %fat are associated with BMD and the presence of vertebral fractures in postmenopausal women, suggesting that circulating leptin might play a physiological role in maintaining bone mass as well as better bone quality.
The role of 123I‐diagnostic imaging in the follow‐up of patients with differentiated thyroid carcinoma as compared to 131I‐scanning: avoidance of negative therapeutic uptake due to stunning
Authors: Siddiqi A. , Foley R. R. , Britton K. E. , Sibtain A. , Plowman P. N. , Grossman A. B. , Monson J. P. , Besser G. M. 
Published: March 2003

OBJECTIVE Some patients with relapsed differentiated thyroid cancer may show rising thyroglobulin (Tg) levels despite a lack of 131I uptake on routine whole body imaging. A significant proportion of these patients, after therapy doses of 131I, may demonstrate positive 131I uptake with a subsequent fall in serum Tg, implying a therapeutic effect. Attempts to identify such patients by increasing the dose of the diagnostic 131I tracer may lead to inhibition of subsequent uptake after the therapy dose, an effect referred to as ‘stunning’ and associated with a reduction in therapeutic effect. 123I is a short half‐life γ‐emitter, thought to be unlikely to cause stunning, which may thus be more suitable than 131I for diagnostic imaging of thyroid cancer.DESIGN AND PATIENTS The efficacy of the 123I radionuclide was determined in a longitudinal study of 12 patients who were selected only because they showed elevated serum Tg and a negative diagnostic 131I whole body study prior to therapy with 131I.RESULTS There was almost complete concordance in uptake between 123I diagnostic imaging and the final scans carried out after 131I therapy (hereafter known as therapy studies) in 11 out of 12 patients at their first evaluation, in each of four patients receiving 123I at their second evaluation and in a single patient receiving 123I at a third evaluation. One patient had a positive 123I study but a negative 131I therapy study: following therapy Tg declined from 5·5 pg/l to undetectable levels, implying a therapeutic effect, and suggesting that the negative uptake was not the result of stunning. Two negative diagnostic 123I studies were followed by negative therapy studies, and thus there were no false negatives. 123I correctly identified disease in the nine patients with metastases in the lungs, mediastinum and bone at the first evaluation, in all four patients at the second evaluation and in the single patient at the third evaluation. At the end of the study, patients had received up to three 131I therapy doses, Tg had risen in four patients, fallen in eight and become undetectable in one patient.CONCLUSIONS 123I is highly sensitive in diagnosing local recurrence and metastatic disease, and produces scintigraphic images which concord well with uptake following 131I therapy. It is proposed that 123I imaging, in combination with serum Tg measurements, should replace 131I tracer imaging as an indicator of the potential efficacy of 131I therapy. Stunning, with its detrimental effects on 131I therapy, may thus be avoided. The possibility of false negative images due to the stunning phenomenon must always be borne in mind if there is a discrepancy between positive 131I imaging studies and a surprisingly negative subsequent 131I therapy scan.
Adrenocorticotropin stimulation tests in patients with hypothalamic‐pituitary disease: low dose, standard high dose and 8‐h infusion tests
Authors: Nye Elisabeth J. , Grice Jeffrey E. , Hockings Gregory I. , Strakosch Christopher R. , Crosbie Georgina V. , Walters Margaret M. , Torpy David J. , Jackson Richard V. 
Published: March 2003

OBJECTIVES Low doses of ACTH [1‐24] (0·1, 0·5 and 1·0 µg per 1·73 m2) may provide a more physiological level of adrenal stimulation than the standard 250 µg test, but not all studies have concluded that the 1·0 µg is a more sensitive screening test for central hypoadrenalism. Eight‐hour infusions of high dose ACTH [1‐24] have also been suggested as a means of assessing the adrenals' capacity for sustained cortisol secretion. In this study, we compared the diagnostic accuracy of three low dose ACTH tests (LDTs) and the 8‐h infusion with the standard 250 µg test (HDT) and the insulin hypoglycaemia test (IHT) in patients with hypothalamic‐pituitary disease.SUBJECTS AND DESIGN Three groups of subjects were studied. A healthy control group (group 1, n = 9) and 33 patients with known hypothalamic or pituitary disease who were divided into group 2 (n = 12, underwent IHT) and group 3 (n = 21, IHT contraindicated). Six different tests were performed: a standard IHT (0·15 U/kg soluble insulin); a 60‐minute 250 µg HDT; three different LDTs using 0·1 µg, 0·5 µg and 1·0 µg (all per 1·73 m2); and an 8‐h infusion test (250 µg ACTH [1‐24] at a constant rate over 8 h).RESULTS Nine out of the 12 patients in group 2 failed the IHT. Three out of 12 patients from group 2 who clearly passed the IHT, also passed all the ACTH [1‐24] stimulation tests. Seven of the 9 patients who failed the IHT, failed by a clear margin (peak cortisol < 85% of the lowest normal). Two of the 7 also failed all the ACTH [1‐24] tests. Five of the 7 patients had discordant results, four passed the 0·1 LDT, one (out of four) passed the 0·5 LDT, none (out of three) passed the 1·0 LDT, two passed the HDT and three passed the 8‐h test. Two patients were regarded as borderline fails in the IHT. Both passed the ACTH [1‐24] tests, although one was a borderline pass in the 8‐h test. Only five out of the 21 patients in group 3 showed discordance between the HDT and the LDTs. One patient passed the HDT and failed the 0·1 LDT, four patients failed the HDT but passed some of the different LDTS.CONCLUSIONS We conclude that in the diagnosis of central hypoadrenalism, ACTH [1‐24] stimulation tests may give misleading results compared to the IHT. The use of low bolus doses of ACTH [1‐24] (1·0, 0·5 or 0·1 µg) or a high dose prolonged infusion does not greatly improve the sensitivity of ACTH [1‐24] testing. Dynamic tests that provide a central stimulus remain preferable in the assessment of patients with suspected ACTH deficiency.
Severe hypomagnesaemia‐induced hypocalcaemia in a patient with Gitelman’s syndrome
Authors: Pantanetti Paola , Arnaldi Giorgio , Balercia Giancarlo , Mantero Franco , Giacchetti Gilberta 
Published: March 2003

SummaryGitelman’s syndrome (GS) is characterized by hyperreninaemic hyperaldosteronism, hypokalaemia, metabolic alkalosis, hypomagnesaemia and hypocalciuria and is due to a defect of the Na–Cl cotransporter at the distal tubule, which may appear in a sporadic or in a familial form. It is an autosomal recessive disorder associated with normal or reduced blood pressure. We report a case of severe hypomagnesaemia‐induced hypocalcaemia in a 39‐year‐old Caucasian woman with GS. The patient had impaired parathormone (PTH) responsiveness to peripheral stimuli, as proved by the marked PTH increase and normalization of plasma calcium levels after acute and chronic administration of magnesium salts. Secondary normotensive hyperreninaemic hyperaldosteronism with hypokalaemia and metabolic alkalosis was also present. Normal plasma renin activity (PRA) and aldosterone levels were restored by administration of an inhibitor of prostaglandin synthesis. The electrolyte imbalance was successfully corrected with chronic treatment with magnesium and potassium salts. Genetic analysis identified a compound heterozygous mutation in the Na‐Cl cotransporter gene (NCCT), confirming the diagnosis of GS. The striking feature of this case of GS was impaired PTH responsiveness to peripheral stimuli determined by hypomagnesaemia and the resulting severe hypocalcaemia, which had not previously been described in this syndrome.
Long‐term follow‐up of patients with bone metastases from differentiated thyroid carcinoma – surgery or conventional therapy?
Authors: Zettinig Georg , Fueger Barbara J. , Passler Christian , Kaserer Klaus , Pirich Christian , Dudczak Robert , Niederle Bruno 
Published: March 2003

Summaryobjective Surgery of bone metastases from differentiated thyroid carcinoma seems indicated in individual patients. This study was performed (1) to analyse retrospectively patients with bone metastases from differentiated thyroid carcinoma and (2) to evaluate the impact of surgery of bone metastases on survival.patients and design We analysed 41 consecutive patients with bone metastases from differentiated thyroid carcinoma who had undergone thyroid surgery at Vienna University Hospital since 1966. The median follow‐up time was 12 years. There were 24 females and 17 males with a mean age of 60 ± 12 years. Primary tumour histology was follicular in 35 and papillary in six patients. Radioiodine treatment was performed in 32 with a mean administered activity of 27 ± 24 GBq 131I. Metastases restricted to the skeleton were found in 22 whereas in 19 individuals additional extraskeletal distant metastases were seen. Twenty‐seven patients had multiple bone metastases. In 21 individuals, up to five bone metastases were surgically removed with the intention of cure.results Univariate analysis identified total thyroidectomy (P = 0·003), lymph node surgery (P = 0·001), radioiodine therapy (P = 0·036), and the absence of extraskeletal distant metastases (P = 0·017) as significant predictors of survival. Multivariate analysis failed to identify significant prognostic factors. In the subgroup of patients with distant metastases limited to the bones, univariate analysis identified, in addition to thyroid and lymph node surgery, the surgical extirpation of the bone metastases as a significant prognostic factor associated with improved survival (P = 0·025).conclusions These findings indicate that in patients without additional extraskeletal distant metastases, the radical surgical extirpation of bone metastases from differentiated thyroid carcinoma might be associated with improved survival.