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Michael Roden, Peter Nowotny, Heinrich Vierhapper and Werner Waldhäusl

Abstract.

To evaluate the sensitivity of basal TSH concentrations as determined by an "ultrasensitive" IRMA-assay (RIA-gnost h-TSH-monoclonal, Behring) versus a "negative" TRH test (defined as an increment of TSH ≥0.2 mU/l 20 min after administration of 400 μg TRH iv) in the diagnosis of hyperthyroidism we examined 193 consecutive patients from our thyroid outpatient clinic: 34 patients displayed hyperthyroidism (total T4: 184.4±26.0 μmol/l, effective thyroxine index: 1.25±0.08), whereas 12 had isolated T3-hyperthyroidism (total T3: 3.47±0.48 nmol/l). Employing the producer's definition of subnormal ("suppressed") bTSH concentrations (≤0.1 mU/l), only 19 (41.3%) hyperthyroid patients would have been detected; on the other hand, one euthyroid patient would have been recognized false positively as hyperthyroid. Using the TRH test as criterion led to the correct diagnosis in 42 (sensitivity: 91.3%) hyperthyroid patients, whereas two had low bTSH concentrations (≤0.5 mU/l), but a normal TSH response to TRH (>2.0 mU/l). Raising the threshold concentration to 0.2 and, subsequently, to 0.4 mU TSH/l increased the number of correct results to 38 (sensitivity: 82.6%) and 43 (93.5%), respectively. This was associated with a concomitant decrease in specificity in the diagnosis of hyperthyroidism from 93.7 (0.1 mU/l) to 27.9% (0.4 mU/l). In conclusion, despite ultrasensitive methods for estimation of low TSH concentrations, the TRH test remains an irreplaceable tool for the correct diagnosis of hyperthyroidism.

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Clemens Fürnsinn, Peter Nowotny, Michael Roden, Madeleine Rohac, Thomas Pieber, Sabina Parzer and Werner Waldhäusl

To compare the effect of short- vs long-term amylin infusion on insulin sensitivity, glucose tolerance and serum calcemia, euglycemic-hyperinsulinemic clamp (26 pmol·kg−1·min−1) and glucose tolerance tests (2.4 mmol/kg over 30 min) were performed in lean Zucker rats. Three infusion protocols were employed: control group: 24 h of iv saline; short-term amylin exposure: 22 h of iv saline followed by 2 h of iv amylin (20 μg/h); long-term amylin exposure: 24 h of iv amylin (20 μg/h). Insulin resistance was induced by short-term amylin infusion during euglycemic clamping, as shown by a 41% decrease in space-corrected glucose infusion rates (μmol·kg−1·min−1; control group, 106.0±15.0; short-term iv amylin, 62.7±15.0; p<0.00 5). After long-term amylin exposure, insulin sensitivity was identical to control values (109.9±6.7). This fading action of amylin was confirmed by data from the glucose tolerance test, demonstrating glucose intolerance after short- but not after long-term amylin exposure. Serum calcium concentration decreased during short-term (2 h) amylin infusion (from 2.52±0.15 to 2.09±0.12 mmol/l; p<0.01) and hypocalcemia of a similar extent also was present after 22 h and 24 h of amylin exposure (2.10±0.09 and 2.04±0.14 mmol/l, respectively). The data demonstrate that short-term amylin infusion induces insulin resistance and glucose intolerance, both of which vanish during long-term (>22 h) amylin exposure, being apparently independent of induced hypocalcemia.

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Sabina Baumgartner-Parzer, Oswald Wagner, Peter Nowotny, Heinrich Vierhapper and Werner Waldhäusl

Baumgartner-Parzer S, Wagner 0, Nowotny P, Vierhapper H, Waldhäusl W. Stimulation of endothelin-1 production by thrombin, but lack of interference by high ambient glucose in vitro. Eur J Endocrinol 1994;130:271–5. ISSN 0804–4643

Diabetic vascular disease is associated with a state of hypercoagulability and altered endothelial properties, leading to elevated plasma levels of endothelium-derived peptides and proteins, e.g. endothelin-1. von Willebrand factor or fibronectin. This study determined dynamic immunoreactive endothelin-1 secretion by human umbilical vein endothelial cells exposed to thrombin (5 × 106 mU/l) in the presence (40 mmol/l) and absence (5.5 mmol/l) of excessive glucose in the cell culture medium. Exposure to high glucose and thrombin concentrations was initiated after cell confluency and applied for 24 h for measurements of endothelin-1 and for 2 and 5 h for the determination of preproendothelin-1, von Willebrand factor and fibronectin messenger ribonucleic acid. Comparisons were made versus cells incubated with normal glucose concentrations or with high mannose or NaCl concentrations as osmotic control. Neither preproendothelin-1, fibronectin and von Willebrand factor messenger ribonucleic acid expression nor endothelin-1 release was affected by high concentrations of glucose, mannose or sodium chloride.

Sabina Baumgartner-Parzer, Department of Medicine III, Division of Endocrinology and Metabolism, Währinger Gürtel 18-20, 1090 Vienna, Austria

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Michaela Riedl, Christina Maier, Georg Zettinig, Peter Nowotny, Wolfgang Schima and Anton Luger

Objectives: To evaluate the efficacy of fluconazole as an alternative treatment for controlling hypercortisolism in Cushing’s syndrome and to determine its effect on glucocorticoid production in vitro.

Design: Case report and in vitro study in a University Clinic.

Case: An 83 year old patient presented with recurrence of Cushing’s syndrome due to pulmonary metastases three years after unilateral adrenalectomy. During a near fatal episode of sepsis she was started on fluconazole 200 mg/day intravenously which normalised cortisol excretion. The therapy was continued orally for 18 months. Upon temporary discontinuation and reintroduction of treatment, cortisol levels increased and normalized, respectively. At month 16, fluconazole had to be increased to a dose of 400 mg/day to keep cortisol excretion in the normal range. Disease progression was slow and no side effects occurred.

In vitro results: Fluconazole in a concentration of 500 μM nearly abolished corticosterone production over 24 h from the adrenal adenoma cell line Y-1 (8.6 ± 0.5% compared with control, P < 0.0001) and significantly reduced corticosterone production in concentrations of 50 μM (48.3 ± 1.9% vs. control, P < 0.0001) and 5 μM (80.5 ± 8.5% vs. control, P < 0.05).

Conclusion: These results demonstrate for the first time that fluconazole normalises cortisol concentrations in vivo in a patient with Cushing’s syndrome with adrenal carcinoma and inhibit glucocorticoid production in vitro in a cell line. Thus, fluconazole might be useful in controlling glucocorticoid excess in Cushing’s syndrome and because of its lower toxicity might be preferable to ketoconazole.

Free access

Imke Schamarek, Christian Herder, Bettina Nowotny, Maren Carstensen-Kirberg, Klaus Straßburger, Peter Nowotny, Alexander Strom, Sonja Püttgen, Karsten Müssig, Julia Szendroedi, Michael Roden, Dan Ziegler and on behalf of the German Diabetes Study Group

Objective

Subclinical inflammation has been implicated in the development of diabetic sensorimotor polyneuropathy (DSPN), but studies using electrophysiological assessment as outcomes are scarce. Therefore, we aimed to investigate associations of biomarkers reflecting different aspects of subclinical inflammation with motor and sensory nerve conduction velocity (NCV) in individuals with diabetes.

Design and methods

Motor and sensory NCV was assessed in individuals with recently diagnosed type 2 (n=352) or type 1 diabetes (n=161) from the baseline cohort of the observational German Diabetes Study. NCV sum scores were calculated for median, ulnar and peroneal motor as well as median, ulnar and sural sensory nerves. Associations between inflammation-related biomarkers, DSPN and NCV sum scores were estimated using multiple regression models.

Results

In type 2 diabetes, high serum interleukin (IL)-6 was associated with the presence of DSPN and reduced motor NCV. Moreover, higher levels of high-molecular weight (HMW) adiponectin, total adiponectin and their ratio were associated with prevalent DSPN and both diminished motor and sensory NCV, whereas no consistent associations were observed for C-reactive protein, IL18, soluble intercellular adhesion molecule-1 and E-selectin. In type 1 diabetes, only HMW and total adiponectin showed positive associations with motor NCV.

Conclusions

Our results point to a link between IL6 and both DSPN and slowed motor NCV in recently diagnosed type 2 diabetes. The reverse associations between adiponectin and NCV in type 1 and type 2 diabetes are intriguing, and further studies should explore whether they may reflect differences in the pathogenesis of DSPN in both diabetes types.