bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential diagnosis of polyuric/polydipsic syndromes with the aid of urinary vasopressin measurement in adults
Authors: Diederich S. , Eckmanns T. , Exner P. , Al‐Saadi N. , Bähr V. , Oelkers W. 
Published: March 2003

OBJECTIVE A water deprivation test or a hypertonic saline infusion test with the measurement of plasma osmolality and plasma vasopressin are the gold standard tests in the differential diagnosis of polyuric syndromes. Because commercially available vasopressin kits are too insensitive for this approach, and the concentration of vasopressin in urine is much higher than in plasma, urinary vasopressin measurements may be an alternative to the more difficult plasma vasopressin measurement.DESIGN The diagnostic value of the measurement of urinary vasopressin with a rather insensitive commercially available vasopressin kit was compared with plasma vasopressin measurement by a highly sensitive radioimmunoassay (RIA).PATIENTS AND METHODS Thirteen normal subjects and 27 patients with polyuria/polydipsia were examined by an 8‐h fluid deprivation test. In all blood samples (0800 h, 1200 h, 1400 h and 1600 h) and in all urine collections (2‐hourly fractions), osmolality as well as vasopressin were measured.RESULTS Using plasma vasopressin measurement with a highly sensitive RIA as gold standard test, nine patients were classified as having primary polydipsia, whereas 18 had partial or complete cranial diabetes insipidus. Whereas the substitution of plasma vasopressin measurement by urinary vasopressin measurement alone did not provide 100% separation between both groups, the product of urinary vasopressin and urinary osmolality related to plasma osmolality completely separated the patients with primary polydipsia from those with diabetes insipidus. Urinary measurement of vasopressin and osmolality alone, which was recommended as a noninvasive diagnostic procedure in children, was too insensitive for exact differential diagnosis in our adult patients.CONCLUSIONS The simultaneous measurement of plasma vasopressin and plasma osmolality in a dehydration test is the most powerful diagnostic tool in the differential diagnosis of polyuria/polydipsia. However, if highly sensitive assays for plasma vasopressin measurements are not available, the measurement of urinary vasopressin with commercially available, less sensitive RIAs may be a diagnostic alternative, which showed nearly the same sensitivity as plasma vasopressin measurement in our study population.
Isolated growth hormone (GH) deficiency due to compound heterozygosity for two new mutations in the GH‐releasing hormone receptor gene
Authors: Salvatori Roberto , Fan Xiaoguang , Phillips John A. , Prince Melissa , Levine Michael A. 
Published: March 2003

OBJECTIVE Mutations in the GH releasing hormone receptor (GHRH‐R) have recently been shown to cause autosomal recessive isolated GH deficiency (IGHD). Patients who are homozygous for GHRH‐R mutations have a subnormal GH response to pharmacological agents that stimulate GH secretion and an appropriate response to exogenous GH therapy. We searched for mutations in the GHRH‐R gene in a family in which two of three siblings were affected by IGHD.DESIGN We sequenced the 13 coding exons, the intron‐exon boundaries and 327 bases of the promoter of the GHRH‐R gene from peripheral blood cell genomic DNA of an index patient.RESULTS Both affected individuals were compound heterozygotes for two previously undescribed GHRH‐R mutations: a change in codon 137 that replaces histidine with leucine (H137L), and a 5 bp deletion in exon 11 (Del 1140–1144). The patients' father was heterozygous for the H137L mutation, and the mother was heterozygous for the exon 11 deletion. We used site‐directed mutagenesis to create the mutants in wild‐type GHRH‐R cDNA. Transient transfection of GHRH‐R cDNAs in Chinese hamster ovary cells showed that cells transfected with both mutant receptors failed to increase cyclic AMP after treatment with GHRH.CONCLUSIONS We describe a family in which two siblings with IGHD were compound heterozygotes for two new mutations in the GHRH‐R gene. These results suggest that mutant alleles for GHRH‐R gene may be more common than previously suspected.
Occurrence of ventricular late potentials in patients with active acromegaly
Authors: Herrmann B. L. , Bruch C. , Saller B. , Ferdin S. , Dagres N. , Ose C. , Erbel R. , Mann K. 
Published: March 2003

OBJECTIVE Patients with acromegaly have an increased risk of ventricular dysrhythmias and sudden death. Late potentials in a signal‐averaged electrocardiogram (SAECG), a predictor of ventricular dysrhythmias, are frequently seen in patients after previous myocardial infarction, but little is known about the prevalence of late potentials in acromegaly. The aim of our study was to investigate the prevalence of late potentials in patients with acromegaly and their relation to the activity of the disease and to myocardial hypertrophy.PATIENTS The study included 48 patients with acromegaly [27 males, 21 females, mean age 52·3 ± 14·2 years, 16 active disease, 32 cured or ‘well controlled’, under treatment with sandostatin analogues (12/32)] and 38 healthy volunteers as a control group.RESULTS Late potentials were detected in 9/16 (56%) patients with active acromegaly vs. 2/32 (6%) with cured/well controlled acromegaly (P = 0·001), defined as normal age‐related IGF‐1 levels and GH levels suppressible below 1 µg/l after an oral glucose load (75 g). Late potentials were not related to muscle mass index (127 ± 35 active vs. 123 ± 34 g/m2 cured/well controlled). The association of disease activity with the detection of late potentials was independent of age, gender, duration of the disease and body mass index. In comparison to the control group, the prevalence of late potentials was significantly higher in patients with acromegaly (23%) than in the control group (0%; P < 0·001).CONCLUSIONS Late potentials in the SAECG are frequently seen in active acromegaly and may represent an early and sensitive parameter to detect myocardial injury in acromegaly.
Urinary excretion of the aquaporin‐2 water channel exaggerated in pathological states of impaired water excretion
Authors: Saito Takako , Higashiyama Minori , Nakamura Tomoatsu , Kusaka Ikuyo , Nagasaka Shoichiro , Saito Toshikazu , Ishikawa San‐e 
Published: March 2003

OBJECTIVE The present study was undertaken to determine whether the hydro‐osmotic action of arginine vasopressin (AVP) is exaggerated in pathological states of impaired water excretion by measuring urinary excretion of the aquaporin‐2 (AQP‐2) water channel.PATIENTS AND MEASUREMENTS Eighteen hyponatraemic patients with impaired water excretion and 12 control subjects were studied during an acute oral water load (20 ml/kg body weight).RESULTS In the patient group plasma AVP levels were 1·6 pmol/l, relatively high compared to plasma osmolality of 279·8 mmol/kg. Urinary excretion of AQP‐2 under ad libitum water drinking was 41·1 fmol/umol creatinine in the patient group, a value significantly greater than that of 21·7 fmol/μmol creatinine in the control subjects. The acute water load verified the impairment in water excretion in the patient group, as the excretion of the water load was only 28·2% (control, 77·3%, P < 0·001) and the minimum urinary osmolality was as high as 437·3 mmol/kg (control, 122·9 mmol/kg, P < 0·001). Also, the minimum urinary excretion of AQP‐2 was significantly greater in the patient group than that in the control. There was a positive correlation between plasma AVP levels and urinary excretion of AQP‐2 in the control subjects (r = 0·56, P < 0·01). In contrast, the urinary excretion of AQP‐2 was exaggerated compared to the respective plasma AVP levels in the patient group, and thus the positive correlation disappeared.CONCLUSION These results indicate that hydroosmotic action of AVP is exaggerated more than that expected from plasma AVP levels in pathological states of impaired water excretion, with non‐suppressible, but normal, arginine vasopressin levels in spite of the hypo‐osmotic condition.
Elevated plasma non‐esterified fatty acid levels and insulin secretion in non‐diabetic relatives of type 2 diabetic patients
Authors: Butler T. J. , Barriocanal L. A. , Walker M. 
Published: March 2003

OBJECTIVE High non‐esterified fatty acid (NEFA) levels impair glucose‐stimulated insulin secretion from islets derived from non‐diabetic Zucker rats that are genetically predisposed to diabetes. We therefore examined the effect of elevated plasma NEFA levels on insulin secretion in non‐diabetic first‐degree relatives of type 2 diabetic patients who are at increased risk of developing diabetes.SUBJECTS AND STUDY DESIGN Normal glucose tolerant relatives (n = 9) and control subjects with no family history of diabetes were pair‐matched for age, sex, body mass index (BMI), insulin sensitivity and early insulin response during an oral glucose tolerance test (OGTT). Plasma NEFA levels were raised from 0 to 340 minutes by the infusion of 20% Intralipid and heparin. From 180 minutes, insulin secretion rates (IRSs) were assessed by stepped low‐dose glucose infusion.RESULTS The mean (geometric mean ± 95% CI) NEFA levels were comparable between relatives and control subjects (2·7 [2·1–3·6] and 2·1 [1·7–2·7] mmol/l, paired analysis, NS). Similarly, plasma glucose levels achieved at each glucose infusion step were comparable between the groups. However, there were no significant differences between the groups for ISR throughout the study.CONCLUSIONS Sustained elevation of plasma non‐esterified fatty acid levels does not decrease insulin secretion in non‐diabetic relatives of type 2 diabetic patients, and is therefore unlikely to be important in the development of the impaired pancreatic beta‐cell function in type 2 diabetes mellitus.
Plasma homocysteine is not a major risk factor for vascular disease in growth hormone deficient adults
Authors: Abdu T. A. M. , Elhadd T. A. , Akber M. , Hartland A. , Neary R. , Clayton R. N. 
Published: March 2003

OBJECTIVE Several cardiovascular risk factors have been investigated in patients with adult growth hormone deficiency (GHD) to explain the observed increase in vascular mortality. Plasma homocysteine concentration has been identified recently as an independent risk factor for atherosclerosis. We wished to determine whether plasma homocysteine contributes to cardiovascular risk in adult GHD.METHOD Plasma homocysteine was measured by fluorescence polarization immunoassay in 45 GH‐deficient adults on stable conventional hormone replacement (25M, 20F), age range 23–76 years, and compared with 55 matched controls (30M, 25F), age range 21–77 years. All subjects were free from clinical hypertension, diabetes, ischaemic heart disease and peripheral vascular disease. Blood pressure, body mass index and waist hip ratio were recorded. Serum creatinine and fasting lipids were measured. Serum vitamin B12 and folate levels, important cofactors in the homocysteine metabolic pathways, were also measured.RESULTS Homocysteine levels were not different in patients and controls (9·75 [7·8–11·6]μmol/l vs. 9·65 [8·3–11·5]μmol/l, respectively, P = 0·88). Serum vitamin B12 was also not different (320·5 [262·0–427·5] pmol/l vs. 313·5 [277·0–460·5] pmol/l, respectively, P = 0·77). Serum folate levels were significantly lower in the patient group (7·05 [5·12–8·27] ng/ml vs. 7·80 [6·52–10·60] ng/ml, respectively, P = 0·03). When separated by gender, in males folate was not significantly different between patients and controls 7·05 [5·17–9·19]vs. 7·65 [6·15–10·22], P = 0·264, whereas in females, folate was significantly lower in patients at 7·05 [4·57–7·75] compared to controls at 8·4 [6·60–12·20], P = 0·01.CONCLUSION Plasma homocysteine levels are not significantly elevated in GH‐deficient adults and are unlikely to be a major risk factor for vascular disease in these individuals.
Serum lipoprotein changes following IGF‐I normalization using a growth hormone receptor antagonist in acromegaly
Authors: Parkinson C. , Drake W. M. , Wieringa G. , Yates A. P. , Besser G. M. , Trainer P. J. 
Published: March 2003

SummaryobjectiveActive acromegaly is associated with altered lipid metabolism. The purpose of this study was to investigate the effect of serum IGF‐I normalization on serum lipoproteins and insulin, in patients with acromegaly receiving the GH receptor antagonist pegvisomant.patientsTwenty patients (9 male, mean age 58·7 years, range 28–79) with active acromegaly (baseline serum IGF‐I > 130% the age‐related upper limit of normal) received pegvisomant and achieved a normal serum IGF‐I [585·2 ± 54·3 (mean ± SEM) to 169·2 ± 13·9 ng/ml,P < 0·0001].measurementsTotal cholesterol (TC), high‐density lipoprotein (HDL) cholesterol, triglyceride (TG), apolipoprotein B (apo B), apolipoprotein A1 (apo A1), lipoprotein a [Lp(a)] and insulin were measured in a single batch analysis on samples obtained at baseline and the first occasion of serum IGF‐I normalization. Low‐density lipoprotein (LDL) was calculated using the Friedewald formula. Paired analysis was performed using Student’s pairedt‐test and the Wilcoxon signed rank test.resultsNormalization of serum IGF‐I resulted in an increase in TC (5·0 ± 0·3 to 5·7 ± 0·4 mmol/l,P = 0·0068), an increase in LDL (3·0 ± 0·25 to 3·7 ± 0·31 mmol/l,P = 0·0093) and an increase in apo B (110·6 ± 7·76 to 127·1 ± 8·86 mg/l,P = 0·0014). TC and LDL increased in all but four patients. Despite a significant fall in fasting insulin levels (9·9 to 8·3 mU/l, range 8·85–19·8 to 6·33–11·6,P < 0·001) and insulin resistance (2·7 to 1·9, range 1·2–10·4 to 1–6·2,P < 0·001), mean serum TG and HDL levels were unaffected by IGF‐I normalization. The protein component of HDL, apo A1, increased (153 ± 4 to 166·4 ± 5·43 mg/l,P = 0·026) and Lp(a) declined (median 342 to 235 mg/l, range 60–1013 to 74–671),P = 0·0035). Baseline serum TC and LDL were below the age‐ and sex‐matched mean population value but after normalization of serum IGF‐I the distribution of serum TC and LDL values was similar to that of the general population.conclusionsActive acromegaly is associated with lowered mean serum TC and LDL. Successful management using pegvisomant increases lowered baseline serum TC and LDL levels, restoring the distribution of values to that of the general population, and improves insulin resistance. These findings are consistent with the reported lipoprotein changes following GH administration to normal and GH‐deficient individuals.
Relationships of urinary phyto‐oestrogen excretion to BMD in postmenopausal women
Authors: Kim M. K. , Chung B. C. , Yu V. Y. , Nam J. H. , Lee H. C. , Huh K. B. , Lim S. K. 
Published: March 2003

Summaryobjective  Phyto‐oestrogens are plant compounds with both oestrogenic and anti‐oestrogenic properties. However, it is not known whether natural phyto‐oestrogens are beneficial or harmful in human osteoporosis. This study was performed to investigate the relationships between urinary phyto‐oestrogens and bone mineral density (BMD) in Korean postmenopausal women.design  The subjects were classified into osteoporotic, osteopenic and normal groups according to their BMD as defined by WHO criteria. We compared the urinary phyto‐oestrogens of each group and studied whether urinary phyto‐oestrogens correlate with BMD.patients  The subjects were 75 Korean postmenopausal women with ages ranging from 52 to 65 years (mean 58 ± 1·1 years). Mean number of years after menopause was 7·3 ± 1·3.measurements  Twenty‐four‐hour urinary phyto‐oestrogens were measured by gas chromatography–mass spectrometry (GCMS) and BMD by dual‐energy X‐ray absorptiometry (DXA, Lunar Expert‐XL, Lunar Co., WI, USA).results  In Korean postmenopausal women, urinary enterolactone (1·46 ± 1·11 µmol/day) was lower and daidzein (2·59 ± 3·25 µmol/day) was higher than in western women, and both levels were comparable to those in Japanese women. Daily urinary excretion of genistein and apigenin were 1·09 ± 0·912 and 0·48 ± 0·40 µmol/day, respectively. In subjects with osteoporosis, urinary enterolactone was lower (P < 0·05) but apigenin was significantly higher (P < 0·05) than in the controls. BMD of L2–L4 correlated positively with urinary enterolactone (r = 0·388, P < 0·01), and BMD of the femoral neck and Ward’s triangle correlated positively with urinary enterolactone (r = 0·271, P < 0·05 and r = 0·322, P < 0·05) but negatively with apigenin (r =−0·412, P < 0·01 and r = −0·395, P < 0·01). By multiple stepwise regression, the variables associated with spinal BMD were age, the amount of urinary apigenin and body mass index (BMI). The variables associated with femoral neck BMD were age and urinary apigenin.conclusions  From these results, we conclude that urinary phyto‐oestrogens, especially enterolactone and apigenin, are related to BMD in Korean postmenopausal women. Our results also suggest the pos‐sibility that phyto‐oestrogens have differential effects on bone density. Further studies are needed to clarify the exact biological roles of phyto‐oestrogenic components on bone metabolism.
Interpersonal testosterone transfer after topical application of a newly developed testosterone gel preparation
Authors: Rolf C. , Knie U. , Lemmnitz G. , Nieschlag E. 
Published: March 2003

Summaryobjective Transdermal testosterone gel treatment is an effective androgen substitution therapy with several advantages over conventional substitution therapies. Whereas side‐effects due to overdosing of hypogonadal patients are unlikely, testosterone gel application without protection may cause severe side‐effects in other subjects (partners, family members) by contamination. Therefore, the risk of testosterone transfer of a newly developed 2·5% testosterone gel preparation was evaluated.design In two clinical randomized open single‐centre studies on healthy male volunteers the percentage of testosterone remaining on the skin after gel application over time (n = 12) and the possibility of a transfer of testosterone to another person (n = 28) was evaluated. In the second study the endogenous testosterone production in the receiving subjects was suppressed by injecting 400 mg norethisterone enanthate (NETE).results After 8 h approximately 60% of testosterone applied to the skin could be recovered. When the skin had been previously washed with water, only about 14% of applied testosterone could be recovered. After intense skin contact with a volunteer who had applied testosterone before on his forearm, no increase in testosterone serum levels could be found in NETE‐suppressed men.conclusion Although considerable amounts of testosterone remain on the intact skin for several hours after evaporation of the alcohol vehicle, contamination of a second, especially female or prepubertal, subject causing side‐effects seems very unlikely.
Ectopic growth hormone‐releasing hormone secretion by thymic carcinoid tumour
Authors: Boix E. , Picó A. , Pinedo R. , Aranda I. , Kovacs K. 
Published: March 2003

SummaryThe case of a 33‐year‐old‐woman with Multiple Endocrine Neoplasia Type 1 (MEN1) syndrome and acromegaly due to ectopic growth hormone‐releasing hormone (GHRH) secretion by a thymic carcinoid tumour is reported. Immunohistochemistry revealed positive immunoreactivity for GHRH, vasoactive intestinal polypeptide, somatostatin and alpha‐subunit in the tumour cells. A previously undescribed new germ line mutation of the MEN1 protein gene was revealed.
99mTechnetium pentavalent dimercaptosuccinic acid scintigraphy in the follow‐up of clinically nonfunctioning pituitary adenomas after radiotherapy
Authors: Colao Annamaria , Ferone Diego , Lombardi Gaetano , Lastoria Secondo 
Published: March 2003

SummaryBACKGROUND It is still difficult to differentiate pituitary adenoma remnants from postradiotherapy fibrosis by computed tomography (CT) or magnetic resonance imaging (MRI), especially in patients with clinically nonfunctioning pituitary adenomas (NFA), lacking circulating markers to follow disease progression or cure.OBJECTIVE We investigated the usefulness of scintigraphy with technetium‐99m pentavalent dimercaptosuccinic acid [99mTc(V)DMSA], shown previously to detect most pituitary GH‐ and PRL‐secreting adenomas and NFA, with tumour‐to‐background ratios (T/B) as high as 25‐fold.PATIENTS Eighteen patients with NFA (study group), 10 patients with GH‐ and three patients with PRL‐secreting adenomas (control group), all of whom had undergone previous surgery.DESIGN The study was an open longitudinal design. Pituitary CT/MRI and 99mTc(V)DMSA scintigraphy was performed before and 1, 3 and 5 years after conventional radiotherapy. Tumour size was measured as maximal diameter of the residual lesion, while uptake of 99mTc(V)DMSA was measured as a T/B ratio.RESULTS At study entry, pituitary 99mTc(V)DMSA uptake was found in 13 NFA (72·2%), seven GH‐secreting (70%) and all PRL‐secreting adenomas; remnant tumour was documented by CT/MRI in all 31 patients. Maximal remnant diameter was significantly higher in patients with positive (13·3 ± 0·9 mm) than in those with negative scintigraphy (7·0 ± 0·3 mm, P < 0·001). During the 5‐year follow‐up postradiotherapy, a significant decrease in 99mTc(V)DMSA uptake (9·7 ± 0·8 vs. 3·2 ± 0·5, P < 0·0001) occurred in all but three patients. Two NFA patients died of tumour invasion 19 and 36 months after radiotherapy and one acromegalic patient had no change in his hormone levels. In the eight negative patients (five NFA and three GH), scintigraphy remained negative throughout follow‐up. A remarkable shrinkage of the remnant tumour was observed in both the patients with negative (from 7·0 ± 0·3 to 1·9 ± 0·6 mm, P < 0·001) and in those with positive scintigraphy (from 13·3 ± 0·9 to 7·3 ± 0·6 mm, P < 0·001). At the end of the study, CT/MRI showed evident remnant tumour in 13 of 16 NFA (81·2%), nine GH‐secreting (90%) and all three prolactinomas (100%), while the scintigraphy was negative (T/B < 1) or faintly positive (T/B 1–2) in eight of 16 NFA (50%), five GH‐secreting (50%) and one prolactinoma (33·3%).CONCLUSIONS Functional imaging of pituitary remnant adenomas (> 10 mm in size) by 99mTc(V)DMSA depicts viable pituitary adenoma remnants. This approach may be of clinical value in patients with clinically nonfunctioning adenomas to monitor the effects of radiotherapy.