Discrimination of patients with and without vertebral fractures as measured by ultrasound and DXA osteodensitometry.

This study compares dual X-ray absorptiometry (DXA) measurements of the hip and spine with quantitative ultrasound (QUS) parameters measured simultaneously at the calcaneal and phalangeal bone in 174 patients with and without vertebral fractures. The aim of this study was to compare the ability of DXA and QUS measurements to discriminate patients with and without osteoporotic vertebral fractures and to evaluate whether QUS measurements in addition to the DXA measurements improve the clinical discrimination between patients with and without osteoporotic vertebral fractures. T-scores determined by DXA measurements at the spine and hip and QUS measurements at the calcaneus provide similar information regarding the discrimination of women with and without vertebral fractures. Phalangeal QUS measurements did not discriminate between patients with and without vertebral fractures. The discriminative power of the combined use of DXA and calcaneal QUS measurements to discern between patients with and without vertebral fractures increases in women. In contrast, the combined use of DXA and phalangeal QUS measurements resulted in decreased discriminative power as compared to DXA measurements alone. The number of fractures was higher in the quartiles with lower T-scores of the DXA and calcaneal QUS measurements whereas no difference was seen in the T-score quartiles of the phalangeal QUS device. These findings suggest that DXA and QUS measurements at weight-bearing skeletal sites provide useful information for assessing women with an anamnestic risk of osteoporotic bone loss. For DXA and calcaneal QUS measurements in men as well as for phalangeal QUS, however, a clinical algorithm remains to be established to understand the diagnostic implications and related therapeutic consequences of the obtained measurements.

[The "needle man": more than 40,000 injections in 40 years]. / Der "Nadel-Mann": mehr als 40000 Injektionen in 40 Jahren.

HISTORY AND ADMISSION FINDINGS: A now 65-year-old man had undergone a subtotal thyroidectomy over 40 years ago, which postoperatively resulted in hypoparathyroidism. His doctor began daily intravenous injections of a calcium preparation (1880 mg to 3760 mg calcium per day, over 40000 injections during this period), a regimen continued subsequently by a total of more than 15 other doctors for over 40 years. On admission the patient complained of oral paresthesias and paresthesias of the limbs. INVESTIGATIONS: Low calcium and parathormone levels confirmed the diagnosis of hypoparathyroidism. TREATMENT AND COURSE: Normal levels of calcium were achieved after a short course of 1.25-dihydroxycalciferol. This was followed by the administration of cholecalciferol and calcium. The patient soon became symptom-free and calcium levels returned to normal. Late sequelae have been calcification of the basal ganglia, first signs of nephrocalcinosis and bilateral cataract. CONCLUSION: This case demonstrates that appropriate treatment of hypoparathyroidism [corrected] might not be given in every case.

[Fibrous dysplasia: differential diagnosis from Paget's disease]. / Fibröse Dysplasie - Morbus Paget: Möglichkeiten der Differenzierung.

HISTORY AND CLINICAL FINDINGS: A 27-year-old woman presented with chronic diffuse bone pain and skeletal deformities. Since the age of 3 years she had occipital hyperostosis. Since aged 13 years she had symptoms indicating spinal root involvement due to hyperkyphosis. For the last 6 years there was evidence of destructive and hyperplastic changes in the region of the middle ribs. Alkaline phosphatase (APL) had been elevated (> 250 U/l) for several years. Three years before the present admission the patient had been hospitalized elsewhere because of bone pain and had received intermittent infusions of pamindronate to a total of 600 mg. INVESTIGATIONS: Laboratory tests showed moderate rise in bone-specific APL and osteocalcin. Conventional x-ray examinations and computed tomography showed lesions in the occipital bone, sella turcica and ethmoid air cells. Several thoracic vertebral fractures were demonstrated. Skeletal scintigraphy indicated enrichment in the occipital and supraorbital regions, as well as in vertebrae and ribs. Dual energy x-ray absorptiometry (DEXA) showed osteopenia. Bone biopsy from the occipital lesion revealed fibrous dysplasia. TREATMENT AND COURSE: The diagnosis of fibrous dysplasia having been confirmed, cyclical treatment with i.v. pamidronate was given for 6 months. It was well tolerated and lessened the pain without changing the objective findings. CONCLUSION: In case of uncertain radiological and scintigraphic findings in the differential diagnosis of fibrous dysplasia, Paget's disease or bone tumor, it is essential to obtain a biopsy and, if available, perform gene analysis.

Alteration of the activity of the 11beta-hydroxysteroid dehydrogenase in pregnancy: relevance for the development of pregnancy-induced hypertension?

In this study we evaluated the activity of renal 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) in patients with pregnancy-induced hypertension (PIH). A reduction of the activity of 11beta-HSD2 leads to pseudohyperaldosteronism due to insufficient interconversion of cortisol to its inactive 11-oxo-metabolite cortisone in the renal tubulus cell. We measured urinary free cortisol and cortisone in patients with and without PIH and calculated the urinary free cortisol to free cortisone ratio, which is well accepted as a correlate of the activity of renal 11beta-HSD2. One hundred twenty-six pregnant women were included. Fifty-nine patients had PIH (mean age 31.5 +/- 4.4 yr, blood pressure 158.7 +/- 16.0/100.8 +/- 9.5 mm Hg), and 67 were normotensive (mean age 29.4 +/- 4.6, blood pressure 112.6 +/- 8.9/68.8 +/- 8.6 mm Hg). The excretion rate of cortisol was increased in the PIH group (138.8 +/- 93.0 vs. 106.5 +/- 65.4 nmol/d, P = 0.027), whereas excretion rate of cortisone was similar (362.9 +/- 254.1 vs. 366.5 +/- 221.7 nmol/d, P = 0.933). The free cortisol to free cortisone ratio was significantly higher in the PIH group (0.47 +/- 0.25 vs. 0.31 +/- 0.12, P < 0.00002). Within this group, the patients with blood pressure in the uppermost quartile had a significantly higher free cortisol to free cortisone ratio than those in the lowest quartile [0.61 +/- 0.31 vs. 0.38 +/- 0.15 (P = 0.019) for diastolic, 0.60 +/- 0.29 vs. 0.35 +/- 0.13 (P = 0.012) for systolic, and 0.62 +/- 0.32 vs. 0.39 +/- 0.16 (P = 0.023) for mean blood pressure, respectively]. We conclude that a reduction of the activity of the 11beta-HSD2 is a relevant factor for the development of PIH. Whether the ratio of urinary free cortisol to free cortisone is a useful risk factor for the development of PIH must be investigated in further prospective studies.

[Therapy of the adrenocortical carcinoma with Lysodren (o,p'-DDD). Therapeutic management by monitoring o,p'-DDD blood levels]. / Therapie des Nebennierenrindenkarzinoms mit Lysodren (o,p'-DDD). Erfahrungen mit der Therapiesteuerung durch Monitoring der Serumspiegel von o,p'-DDD.

BACKGROUND: o,p'-DDD (1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)-ethane), which leads to a cytotoxic necrosis of the adrenal glands, currently is therapy of choice for metastasized adrenocortical carcinomas. Clinical experience is still poor, but most studies demonstrate an increment of survival time in patients treated with o,p'-DDD after incomplete surgery. The therapeutic range is close and therefore dosage is difficult, mainly based on clinical signs. Methods for routine determination of o,p'-DDD are not yet broadly available. PATIENTS AND METHOD: We developed a method for the determination of o,p'-DDD and report our experience with the monitoring of serum levels of o,p'-DDD in our patients. Nine patients have been included, eight patients with metastasized adrenocortical carcinoma were treated with o,p'-DDD. RESULTS: At time of evaluation six of eight patients had deceased, 27.9 +/- 25.1 months after recurrence of the disease. Time of survival for all patients was 28.2 +/- 22.0 months since diagnosis of recurrence. In three patients the target dose of 9-10 g/d could not be reached due to the clinical situation. The serum levels of these patients were low (6.3 +/- 4.2 micrograms/ml). Mean survival time was significantly longer for those patients who reached serum levels above 14 micrograms/ml in comparison to those who failed to reach such high levels (41.3 +/- 16.2 vs 6.3 +/- 3.6 months, p < 0.01). The dose which was necessary to reach high levels was individually different. All patients developed adrenocortical insufficiency. Other side effects were fatigue (seven patients), gastrointestinal problems and elevated liver enzymes (six patients each), changes in blood count (five patients) and central nervous disorder (four patients). All patients developing intolerable side effects had very high serum levels of o,p'-DDD (> 20 micrograms/ml). CONCLUSIONS: Our data confirm that the efficacy of a therapy with o,p'-DDD as well as the risk to develop intolerable side effects depend on the serum levels of o,p'-DDD. Monitoring of o,p'-DDD therapy by measuring serum levels of o,p'-DDD helps to adapt this therapy individually, avoiding serious side effects as well as to realize antitherapeutical resistance. Determination of o,p'-DDD serum levels helps to decide over intensification or cessation of therapy.

[Female pseudohermaphroditism in congenital adrenogenital syndrome as an incidental intraoperative finding in a 68 year old patient]. / Pseudohermaphroditismus femininus bei kongenitalem adrenogenitalem Syndrom als intraoperativer Zufallsbefund bei einem 68jährigen Patienten.

HISTORY AND CLINICAL FINDINGS: A 68-year-old man of small stature, previously always healthy and with a grown-up daughter, was suspected of having carcinoma of the colon with metastasis to the right kidney. At laparotomy internal female genitalia with cancerous changes were unexpectedly discovered in the left adnexae. The colon carcinoma, the right adrenocortical tumour and left adnexae were resected. INVESTIGATIONS: Histological examination revealed adenocarcinoma of the colon, right adrenocortical adenoma and a Brenner tumour of the left female adnexae. Postoperative tests showed increased levels of 17-OH-progesterone (3192 ng/dl), 21-desoxycortisol (1856 ng/dl) and of adrostenedione (745 ng/dl), while the concentrations of 17-OH pregnenolone, testosterone and mineralocorticoids were within normal limits. Chromosome analysis demonstrated karyotype 46 XX. DIAGNOSIS, TREATMENT AND COURSE: As far as could be ascertained, this is the first documented case in the German-speaking region of female pseudohermaphroditism diagnosed in an elderly person with uncomplicated virilizing congenital adrenogrenital syndrome due to 21-hydroxylase deficiency (deletion of CYP21 gene). To avoid a cortisone deficiency crisis the patient was regularly given hydrocortisone and he quickly recovered. But he died 6 months later of sequelae of the carcinoma of the colon. CONCLUSION: An adrenogenital syndrome should be excluded in a case of bilateral adrenocortical tumour. As this is usually benign, conservative treatment should be attempted. This case demonstrates the necessity of thorough examination which could have given an early indication of the underlying condition.

No advantage of the new combined octreotide-GHRH test over established GH-stimulation tests in the diagnosis of growth hormone deficiency (GHD) in adults.

OBJECTIVE: To evaluate the sensitivity and specificity of a combined octreotide (SMS)-GHRH test we compared it with established GH stimulation tests in the diagnosis of growth hormone deficiency (GHD) in adults. DESIGN: Because there is no universally agreed gold standard for the diagnosis of GHD in adults it is difficult to define the relative merits of different tests in patients with structural pituitary disease. We have addressed this by grouping patients according to the degree of concordance between three established tests (insulin (IHT), arginine (ARG) and GHRH stimulation test (GHRH)) and serum IGF-I levels and have subsequently analysed the frequency destribution of test results across defined groups: group 1, with complete GHD in all tests, group 2, with differences between tests with regard to the diagnosis of GHD and group 3, with normal GH response in all tests. The patients also underwent a new combined SMS-GHRH test, the results of which were compared with IHT, ARG and GHRH. MEASUREMENTS: Five hours after an octreotide injection GHRH was given intravenously and GH measured. RESULTS: ARG had the highest sensitivity (Se = 100%) and specificity (Sp = 100%) of the tests used. The IHT also diagnosed GHD with precision but showed false positive as well as false negative results (Se = 90%, Sp = 100%). Se and Sp of GHRH were lower than those of IHT and ARG (Se = 100%, Sp = 89%). The SMS-GHRH worked well and was superior to GHRH but had less precision than IHT and ARG (Se = 88%, Sp = 100%). CONCLUSION: We conclude that there is discordance between the three established tests and that the octreotide-GHRH test does not have any advantages for diagnosing GHD in adults. IGF-I levels can be used as a screening test only. The arginine test was the best conventional test in our study.

Administration of glycyrrhetinic acid: significant correlation between serum levels and the cortisol/cortisone-ratio in serum and urine.

In vitro, cortisol and aldosterone have a similar affinity to the mineralocorticoid receptor. The 11beta-hydroxysteroid dehydrogenase catalyzes the interconversion of cortisol to its inactive 11-oxo-metabolite cortisone. This interconversion is responsible for the in vivo specificity of the mineralocorticoid receptor. A defect of this enzyme leads to a pseudohyperaldosteronism with hypertension and hypokalemia, the so-called apparent mineralocorticoid excess syndrome. Glycyrrhetinic acid, a compound of licorice, also leads to pseudohyperaldosteronism by an inhibition of the 11beta-hydroxysteroid dehydrogenase. We studied the pharmacokinetics of glycyrrhetinic acid and its effect on the 11beta-hydroxysteroid dehydrogenase. Ten healthy students, aged 24 to 38 years, were included in the study. On the first day 500 mg glycyrrhetinic acid were given orally at 08.00 h. Blood and urine samples were taken prior to and 2, 4, 7, 10 and 24 hours after ingestion of glycyrrhetinic acid. We measured the serum level of cortisol, cortisone and glycyrrhetinic acid and the urinary excretion rates of cortisol, cortisone and their 20-dihydrometabolites. For determination of glycyrrhetinic acid and steroid levels we used a fully automated liquid chromatographic analyzer which allows the highly specific and simultaneous determination of steroid profiles even in the matrix of urine. Ratios of the 11-hydroxy- and 11-oxo-metabolites were calculated and correlated to the serum level of glycyrrhetinic acid. We found a significant correlation of the steroid-ratios to the serum levels of glycyrrhetinic acid. Coefficients of correlation were 0.9873, 0.7812, 0.7396 and 0.5844 between the serum level of glycyrrhetinic acid and the cortisol/cortisone-ratio in serum (p < 0.0001), the cortisol/cortisone-ratio in urine (p = 0.0279), the 20alpha-dihydrocortisol/20alpha-dihydrocortisone-ratio in urine (p = 0.0119) and the 20beta-dihydrocortisol/20beta-dihydrocortisone-ratio in urine (p = 0.0419), respectively. We conclude that the ratios of cortisol to cortisone and of the 20-dihydrometabolites of cortisol to the 20-dihydrometabolites of cortisone provide a simple noninvasive tool for monitoring the in-vivo activity of the 11beta-hydroxysteroid dehydrogenase.

Health effects of sulfur-related environmental air pollution. III. Nonspecific respiratory defense capacities.

Recently concern has been raised about health effects related to environmental sulfur and/or acidic aerosols. To assess long-term effects on respiratory lung function, 8 beagle dogs were exposed over a period of 13 mo for 16.5 h/day to 1.0 microm neutral sulfite aerosol with a particle associated sulfur(IV) concentration of 0.32 mg m(-3) and for 6 h/day to 1.1 microm acidic sulfate aerosol providing an hydrogen ion concentration of 15.2 micromol m(-3) for inhalation. Prior to exposure the dogs were kept under clean air conditions for 16 mo to establish physiological baseline values for each dog. A second group of eight dogs (control) was kept for the entire study under clean air conditions. Nonspecific defense mechanisms in the airways and in the peripheral lung were studied during chronic exposure of the combination of neutral sulfur(IV) and acidic sulfur(VI) aerosols. No functional changes of tracheal mucus velocity were found, in agreement with unchanged morphometry of the airways. However, the exposure resulted in changes of several alveolar macrophage (AM) mediated particle clearance mechanisms: (1) Based on in vivo clearance analysis and cultured AM studies using moderately soluble cobalt oxide particles, intracellular particle dissolution was significantly reduced since phagolysosomal proton concentration was decreased. We deduce exposure-related malfunction of proton pumps bound to the phagolysosomal membrane as a result of an increase of cytosolic proton concentration. (2) Based on in vivo clearance analysis using insoluble polystyrene particles, AM-mediated particle transport from the lung periphery toward ciliated terminal bronchioli and further to the larynx was significantly reduced. Activation of epithelial type II cells at the entrance of alveoli was inferred from observed type II cell proliferation at those alveolar ridges and enhanced secretion of alkaline phosphatase in the fluid of bronchoalveolar lavages. As a result, hypersecretion of chemotactic mediators by activated type II cells at these loci led to the observed decrease of particle transport toward ciliated bronchioli. (3) Based on in vivo clearance analysis using insoluble polystyrene particles, particle transport from the alveolar epithelium into interstitial tissues was increased and (4) particle transport to the tracheobronchial lymph nodes was significantly enhanced. Particle transport into interstitial tissues is the most prominent clearance pathway from the canine alveolar epithelium. We conclude that the deteriorated particle transport toward ciliated terminal bronchioli resulted in an enhanced particle transport across the epithelial membrane into interstitial tissues and the lymphatic drainage. The observed alterations in alveolar macrophage-mediated clearance mechanisms during chronic exposure of these air pollutants indicate an increased risk of health.

Health effects of sulfur-related environmental air pollution. II. Cellular and molecular parameters of injury.

Recently, concern has been raised about effects related to environmental sulfur and/or acidic aerosols. To assess long-term effects on nonrespiratory lung function, 8 beagle dogs were exposed over a period of 13 mo for 16.5 h/day to a neutral sulfite aerosol at a sulfur(IV) concentration of 0.32 mg m(-3) and for 6 h/day to an acidic sulfate aerosol providing a hydrogen concentration of 15.2 micromol m(-3) for inhalation. Prior to exposure the dogs were kept under clean air conditions for 16 mo to establish physiological baseline values for each animal. A second group of eight dogs (control) was kept for the entire study under clean air conditions. No clinical symptoms were identified that could be related to the combined exposure. Biochemical and cellular parameters were analyzed in sequential bronchoalveolar lavage (BAL) fluids. The permeability of the alveolo-capillary membrane and diethylenetriaminepentaacetic acid (DTPA) clearance was not affected. Similarly, oxidant burden of the epithelial lining fluid evaluated by levels of oxidation products in the BAL fluid protein fraction remained unchanged. Both the lysosomal enzyme beta-N-acetylglucosaminidase and the alpha-1-AT were increased (p <.05). In contrast, the cytoplasmic marker lactate dehydrogenase remained unchanged, indicating the absence of severe damages to epithelial cells or phagocytes. Various surfactant functions were not altered during exposure. Three animals showed elevated levels of the type II cell-associated alkaline phosphatase (AP), indicating a nonuniform response of type II cells. Significant correlations were found between AP and total BAL protein, but not between AP and lactate dehydrogenase, suggesting proliferation of alveolar type II cells. Absolute and relative cell counts in the BAL fluid were not influenced by exposure. Alveolar macrophages showed no alterations with regard to their respiratory burst upon stimulation with opsonized zymosan. The percentage of alveolar macrophages capable of phagocytozing latex particles was significantly decreased (p<.05), while the phagocytosis index was not altered. In view of the results of this and previous studies, we conclude that there is no synergism of effects of these two air pollutants on nonrespiratory lung functions. It is hypothesized that antagonistic effects of these air pollutants on phospholipase A2-dependent pathways account for compensatory physiological mechanisms. The results emphasize the complexity of health effects on lung functions in response to the complex mixture of air pollutants and disclose the precariousness in the risk assessment of air pollutants for humans.

Health effects of sulfur-related environmental air pollution. I. Executive summary.

The motivation of simulating real-world environmental exposure in a number of long-term studies with dogs was to address the question of whether or not perpetual inhalation of air pollutants can initiate diseases in healthy lungs and can thus contribute to the increasing prevalence of respiratory diseases in industrialized countries. The major conclusion of this article is that this question has to be answered in the negative for the simultaneous inhalation of the major constituents of combustion-related air pollution, particle-associated sulfur(IV), and particle-associated hydrogen ions. Over 13 mo, 8 healthy beagle dogs were exposed in 2 whole-body chambers daily for 16.5 h to 1 microm neutral sulfite [sulfur(IV)] particles at a mass concentration of 1.5 mg m-3 and for 6 h to 1.1 microm acidic sulfate particles carrying 15 micromol m-3 hydrogen ions into the canine lungs. This longitudinal study was characterized by repeated observations of individual respiratory response patterns. To establish baseline data the dogs were repeatedly examined preexposure while the chambers were ventilated over 16 mo with clean air. Each individual served thus as its own control. Another eight dogs served as additional controls. They were housed in 2 chambers ventilated with clean air over the entire study period of 29 mo. To assess response patterns, respiratory lung function tests were performed pre- and postexposure, segmental lung lavages were repeatedly performed to obtain epithelial lining fluid from the lungs for analysis of cell content, cell function, and biochemical indicators of lung injury, and radiolabeled test particles were used to study pathways of intrapulmonary particle elimination. At the end of the study, the lungs of all animals were morphologically and morphometrically examined. Functional and structural responses were finally compared to those observed previously as a result of a sole exposure of canine lungs to neutral sulfite particles over 10 mo (Heyder et al., 1992). Interactions between responses induced by neutral sulfite and acidic sulfate particles occurred, but antagonism rather than synergism was observed. The responses induced by sulfur(IV) were less pronounced, not detectable, or even reversed when hydrogen ions were also delivered to the lungs. On the other hand, responses not induced by the sole exposure to sulfur(IV) were observed: The activity of alkaline phosphatase was elevated and type II pneumocytes proliferated. It can, however, be concluded that long-term exposure of healthy lungs to particle-associated neutral sulfur(IV) and hydrogen ions at concentration close to ambient levels causes subtle respiratory responses but does not initiate pathological processes in the lungs. In other words, the perpetual inhalation of sulfur(IV) and hydrogen ions from the atmospheric environment presents no health risk to the healthy lungs. It is thus also very unlikely that respiratory diseases can be initiated by the inhalation of these pollutants.

Health effects of sulfur-related environmental air pollution. IV. Respiratory lung function.

Recently concern has been raised about health effects related to environmental sulfur and/or acidic aerosols. To assess long-term effects on respiratory lung function, 8 beagle dogs were exposed over a period of 13 mo for 16.5 h/day to 1-microm neutral sulfite aerosol with a particle-associated sulfur(IV) concentration of 0.32 mg m(-3) and for 6 h/day to 1.1-microm acidic sulfate aerosol providing an hydrogen ion concentration of 15.2 micromol m(-3) for inhalation. Prior to exposure the dogs were kept under clean air conditions for 16 mo to establish physiological baseline values for each dog. A second group of eight dogs (control) was kept for the entire study under clean air conditions. Before and at the end of exposure, respiratory lung function was evaluated in both groups in anesthetized and mechanically ventilated animals. Lung volumes as well as static and dynamic lung compliances were measured. Series dead-space volumes and slopes of the alveolar plateau for respiratory (O2, CO2) and inert test gases (He, SF6) were determined from single-breath washout tracings. Monodisperse 0.9-microm DEHS droplets were used to assess convective mixing in the lungs and to evaluate airway dimensions in vivo. Gas exchange across the alveolar-capillary layer was characterized by membrane diffusing capacity for carbon monoxide and alveolar-arterial pressure differences for respiratory gases. A bronchial challenge with carbachol was used to assess airway responsiveness. In comparison to the control group, dogs exposed to sulfur(IV) and acidic aerosol exhibited no significant changes in any respiratory lung function parameter. Also the responsiveness of the bronchial airways to carbachol was not affected. In view of the results obtained in this and previous studies, we conclude that anticipated synergistic effects of the two air pollutants on pulmonary lung function were not observed. It is hypothesized that antagonistic effects of the air pollutants on the activity of phospholipase A2 play an important role and account for counteracting physiological compensatory mechanisms. The results emphasize the complexity of health effects on lung function in response to the complex mixtures of ambient air pollutants and witness the precariousness in the risk assessment of air pollutants for humans.

Ultrasound transmission speed and ultrasound bone profile score (UBPS) of the phalanges in normal women and women with osteoporosis.

The distal metaphysis of the first phalanx of the fingers II-V is, like the vertebral body, a useful site for the measurement of mineralisation and structure of the bone because of the simultaneous presence of compact and trabecular bone. With an ultrasound device (DBM sonic 1200, IGEA, Italy), we measured the adSOS (the amplitude dependent speed of sound) and the UBPS (ultrasound bone profile score), a score which is calculated from the graphic traces of the receiving probe with an expert system which uses fuzzy-logic at phalanges II-IV, as well as bone mineral density (BMD) at lumbar spine using dual X-ray absorptiometry (DXA). Precision of the measurements was as follows: adSOS: short-time-CV% = 0.576, long-time-CV% = 1.1, SCV% = 5.9, RMSSD% = 1.825. UBPS: short-time CV% = 5.95. There was no correlation between adSOS or UBPS and lumbar BMD (DXA). There was a significant positive correlation between adSOS and UBPS, r = 0.804 (p<0.00001). The validity of adSOS and UBPS was examined in 25 young and healthy women (mean age: 33.4 year), 15 postmenopausal healthy women (mean age: 58.5 years), 17 women with osteopenia, (mean age: 52.4 years), as defined by a t-score between -1 to -2.5 SD as lumbar BMD (DXA), and 20 women with osteoporosis and vertebral fractures (mean age: 61.4 years). We compared the healthy postmenopausal women and the women with osteoporotic vertebral fractures, the z-score of the adSOS was below minus 1.5 SD and UBPS was below 40, sensitivity was 0.7 for adSOS, and 0.85 for UBPS, with a specificity 0.97 for adSOS, and of 0.93 for UBPS; positive predictive value: adSOS: 0.93, UBPS: 0.85. AdSOS declined with age (r= 0.694, p=0.021); the UBPS was not age dependent (r=-0.15, p = n.s.). The ROC-curve shows a value of 0.96 for adSOS and 0.94 for UBPS. AdSOS and UBPS could discriminate well between the healthy controls and the women with osteopenia or vertebral fractures (p<0.00001). These results show that adSOS and UBPS are precise parameters to be measured at the phalanges. The detection level of pathological changes in osteoporosis are similar between adSOS and lumbar BMD (DXA) and improved by using the UBPS. This might be explained by the influence of structural changes in bone on UBPS, rather than change in bone mineral alone. Prospective studies have to clarify the role of adSOS and UBPS in fracture prediction.

[Multiple endocrine neoplasia associated with multiple lipomas]. / Multiple endokrine Neoplasie assoziiert mit multiplen Lipomen.

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN-1) is characterized by tumors of the parathyroids, the neuroendocrine pancreas-duodenum and the anterior pituitary, but shows also a wide clinical variety of other symptoms. CASE REPORT: We present a case of a 68-year-old woman with a 18 year history of MEN-1 consisting of gastrinoma and primary hyperparathyroidism. Beside these typical symptoms, the patient suffered from thyroid adenoma, malignant kidney tumor and multiple subcutaneous lipomas. RESULT: While the number of autopsies declined from 113 in 1977 to 66 in 1984, the number of diagnostic techniques used increased continuously (94, 107, 118 and 140, amounting to 0.83, 1.34, 1.76 and 2.12 per patient). The premortal detection of abdominal abnormalities increased globally from 16.8 to 32.5%. This increase was largely due to better diagnosis of liver and gallbladder abnormalities which were in most cases of little relevance. CONCLUSION: Whether these non-endocrine tumors are associated to MEN-1 is unclear and has to be tested by examining the chromosomal regions 11q13 and 11q24/25 of the tumors sample, in which the possible MEN-1 involved tumor suppressor genes are located.

Quantitative ultrasonometry (QUS) for the evaluation of osteoporosis risk: reference data for various measurement sites, limitations and application possibilities.

Osteoporosis is a wide-spread disease characterized by low bone mass, deterioration of bone structure and typical fractures, which lead to pain, disability and high costs for health systems. Quantitative Ultrasonometry (QUS) is a new, non-invasive method to study bone density and structure in vivo. This technique has the following advantages: it is safe; it is easy to use, there is no radiation load on the patient, and instruments can be transported and are relatively cheap, as compared with the substantially more expensive methods of traditional osteodensitometry (dual X-ray absorptiometry = DXA, quantitative computed tomography = QCT). For measuring the osteoporosis risk, QUS has the same value as the conventional radiological osteodensitometry methods (QCT, DXA) The combination ofQUS, DXA and QCT improves the message. At present, there are three measurement sites for QUS measurement at the skeleton: the calcaneus, the tibia and the phalanges. The oldest method is the calcaneus measurement, and instruments with and without a water bath are available for this purpose. QUS might be a screening method for osteoporosis. Currently QUS can already be used in clinical practice. It can, for example, be an aid in decision-making for female patients who do not wish to have a postmenopausal hormone replacement therapy (HRT) or who can only barely tolerate doses with a bone-protective effect. In addition, patients can be examined before and after a glucocorticoid therapy with regard to a possible loss in bone mass. As a third possibility, QUS provides a further opportunity for subdividing into development stages patients with an established osteoporosis resulting in fractures, since there is an indication that by means of QUS it may be possible to account for more structural bone changes than with the traditional DXA or QCT methods. Treatment can also be monitored by means of QUS. As prospective studies have shown, increases in SOS by HRT and alendronate and precision error of QUS are lower than expected changes. Due to the greater practicability of QUS (no radiation load, portable instruments), this method ought to be further used in research and clinical settings, and more experience ought to be collected with this method so that wide-ranging experience can help the management of our patients.

Measurement of forearm bone mineral density: comparison of precision of five different instruments.

Measurement of bone mineral density (BMD) is used for clinical estimation of fracture risk in osteoporosis. The precision of the method is important for the evaluation of true and clinical relevant changes in BMD in patients with osteoporosis. We measured BMD of the forearm in 14 young, healthy probands (10 males, 4 females), aged 24. 6 +/- 1.5 years with five different instruments using dual-energy X-ray absorptiometry (DXA), single-photon absorptiometry (SPA), and peripheral quantitative computed tomography (pQCT). Precision was expressed as the percentage coefficient of variation (CV%). In addition, the standardized CV% (sCV%) and the root mean square standard deviation (rmsSD%) was calculated for long-term precision. CV% ranged from 1.04 (SPA, distal BMD) to 2.75% (pQCT, trabecular BMD) for short-term precision and from 1.49 (DXA, QDR 1000, 1/3-distal BMD) to 4.33% (SPA, ultradistal) for long-term precision, respectively. The results for the rmsSD% were higher but correlated well with the CV%. A change that exceeds 2 radical2 CV% has been considered as being significant. On this basis, 24.0 +/- 5.1% (mean +/- SEM) of the participants in our study would be expected to have a significant change in BMD without any correlation to the time-delay between the two measurements. Measurements of BMD were done at two locations with all five instruments: ultradistal and middistal BMD using DXA and SPA and total and trabecular BMD using pQCT, respectively. Coefficients of correlation for "between-instrumental" correlation were greater than 0.5 for almost all instruments. Distal and ultradistal BMD measured by SPA and trabecular and total BMD measured by pQCT correlated better with ultradistal BMD measured by DXA. Correspondingly, "within-instrumental" correlation was better for pQCT and SPA than for DXA. The coefficients of correlation between the different DXA methods were greater than 0.95 when corresponding locations were compared. We conclude that the clinical value of monitoring bone loss by measurement of forearm BMD is compromised by the low precision which was seen for DXA methods as well as for SPA and even pQCT in young healthy controls.

[Osteosonography of the phalanges of men]. / Osteosonographie der Phalangen bei Männern.

BACKGROUND: The distal metaphysis of the first phalanx of the fingers II to V is, like the vertebral body, a useful site for the measurement of mineralisation and structure of the bone, because of the simultaneous presence of compact and trabecular bone. METHOD: With an osteosonographic device (DBM sonic 1200, IGEA, Italy) we measured in 38 young and healthy men, 14 elderly and healthy men, 18 men with osteopenia, 8 men with osteoporosis and vertebral fractures and 10 men with long-standing cortisone medication, the adSOS (amplitude-dependent speed of sound) and the UBPS (ultrasound bone profile score) at the phalanges, as well as bone mineral density (BMD) at lumbar spine using dual-X-ray absorptiometry (DXA). RESULTS: There was no correlation between adSOS or UBPS and lumbar BMD (DXA). There was a significant positive correlation between adSOS and UBPS, r = 0.826 (p < 0.00001). AdSOS declined with age (r = 0.694, p = 0.021); the UBPS was not age-dependent (r = -0.15, p = n.s.), as expected. AdSOS and UBPS could discriminate significantly between the young and healthy controls and the men with osteopenia/vertebral fractures or oral steroids (p < 0.00001). The DXA could be significantly discriminate all healthy controls from the patients with osteopenia or vertebral fractures. It could not significantly discriminate the healthy controls from the patients taking oral glucoconticoids. Only the UBPS could significantly discriminate this group from the healthy controls. CONCLUSION: These results show, that adSOS and UBPS are precise parameters to be measured at the phalanges. The detection level of pathological changes in osteoporosis are similar between adSOS and lumbar BMD (DXA) and improved by using UBPS. This might be explained by the influence of structural changes in bone on UBPS, rather than changes in bone mineral alone. Prospective studies have to clarify the role of adSOS and UBPS in fracture prediction.

Determination of 18 beta-glycyrrhetinic acid in human serum using the fully automated ALCA-system.

We report a method for the determination of 18 beta-glycyrrhetinic acid (glycyrrhetinic acid) in human serum using the ALCA-system. The technology of the ALCA-system is based on the principles of adsorptive and desorptive processes between liquid and solid phases. The assay is run fully automated and selective. Procedural losses throughout the analysis are negligible, thereby allowing for external calibration. The calibration curve is linear up to 10 mg/l and concentrations as low as 10 micrograms/l are detectable. CV is 2.5% for within- and 7.5% for between-assay precision at a level of 50 micrograms/l and 1.2% for within- and 8.5% for between-assay precision at a level of 500 micrograms/l. Specific and expensive reagents are not necessary and time-consuming manual operations are not involved. This assay can be selected from a wide spectrum of methods at any time. Thus, the present method is well-suited for drug monitoring purposes in the routine laboratory. In a pharmacokinetic study we measured serum levels of glycyrrhetinic acid in ten healthy young volunteers after ingestion of 500 mg glycyrrhetinic acid. Maximum levels of glycyrrhetinic acid were 6.3 mg/l 2 to 4 hours after ingestion. Twenty-four (24) hours after ingestion seven probands still had glycyrrhetinic acid levels above the detection limit with a mean level of 0.33 mg/l.

[The Wolfram syndrome: diabetes mellitus, hypacusis, optic atrophy and short stature in STH deficiency]. / Wolfram-Syndrom: Diabetes mellitus, Hypakusis, Optikusatrophie und Kleinwuchs bei STH-Mangel.

HISTORY AND CLINICAL FINDINGS: A 43-year-old man was known for 3 years to have diabetes mellitus. For 2 months before admission he had symptoms of hyperglycaemia with polyuria, polydipsia, weight loss, as well as impairment of vision and declining fitness. In addition to bilateral deafness he was clearly of normally proportioned short stature (150 cm). INVESTIGATIONS: The levels of blood sugar (221 mg/dl), HbA1c(10.2%), triglycerides (496 mg/dl) and cholesterol (323 mg/dl) were raised, while the concentration of somatotropic hormone was diminished, both before and after arginine administration. Fundoscopy revealed concentric diminution of the visual fields with left amblyopia. Visual evoked potentials and colour sense testing revealed bilateral optical atrophy, and the audiogram demonstrated deafness. These findings provided the diagnosis of Wolfram syndrome, namely insulin-dependent diabetes mellitus, deafness, optical atrophy and small stature with somatotropic hormone deficiency. TREATMENT AND COURSE: On insulin treatment the metabolic state became normal (HbA1c 7.5%, normal lipid profile). It was decided that the deficiency in somatotropic hormone regulation did not require treatment. CONCLUSION: Cardinal symptoms of the autosomally recessive Wolfram syndrome are insulin-dependent diabetes and optic nerve atrophy. Several types of hormonal abnormalities are associated with it, including a deficiency in the somatotropic axis. To obtain early and adequate hormonal substitution requires extensive endocrinological diagnosis of a disease which frequently becomes manifest in childhood or adolescence.

[Bisphosphonate therapy in osteoporosis. Inhibition of trabecular perforation by aminobisphosphonate]. / Bisphosphonat-Therapie der Osteoporose. Hemmung der Trabekelperforation durch Aminobisphosphonate.

After many years of experience with bisophosphonates in the treatment of "tumor osteopathy" and Paget's disease, these substances have now also been approved for use in the treatment of osteoporosis. Owing to their high affinity for calcium hydroxyapatite, the bisphosphonates are deposited in the bony surface, and the aminobisphosphonates exert their effect at the site of active resorption via direct inhibition of active osteoclasts. As a result of this inhibition of the osteoclastic bone resorption, trabecular perforation is reduced and during the course of bone remodelling by the activity of the osteoblasts, boneformation occurs. In addition to an increase in bone density, both etidronate and alendronate have been shown to inhibit vertebral fractures in patients with osteoporosis. In addition, in patients with preexisting fractures, alendronate is able, at the same time, to lower the incidence of fractures of the femoral neck. With proper administration, the associated occasional gastrointestinal side effects can be avoided. The introduction of bisphosphonates into the treatment of osteoporosis is definitely an enrichment of the therapeutic spectrum in conjunction with the basic treatment comprising calcium, vitamin D, diet and physical measures.