Search Results

You are looking at 1 - 10 of 11 items for

  • Author: Christoph Schmid x
Clear All Modify Search
Restricted access

Christoph Schmid

Rosén and Bengtsson have previously estimated—in a retrospective manner—long-term prognosis in patients with hypopituitarism living in the Göteborg region of Sweden (1). Life expectancy was found to be shortened; mortality was increased, not due to the primary disease (mainly pituitary tumours) but more to an increased risk of premature death from cardiovascular diseases; the risk of death from malignant tumours tended to be decreased. Bengtsson and colleagues, too, have reported epidemiologic data according to which excess mortality in patients with acromegaly is not due primarily to manifestations caused by tumour mass but rather to manifestations of growth hormone (GH) excess. The overall premature mortality was increased about three-fold due to cardiovascular and malignant disease (2). Excess death rate in patients with acromegaly is partially attenuated with therapy.

Rosén et al., in this issue, report on cardiovascular risk factors in patients with adult onset GH deficiency, i.e. patients with pituitary insufficiency

Restricted access

Susanne Keller, Christoph Schmid, Jürgen Zapf and E. Rudolf Froesch

Abstract.

IGF-I infused at pharmacological doses in healthy men markedly decreases C-peptide levels, whereas insulin levels remain within the normal range. One possible explanation is decreased insulin removal. As the liver is the major site of insulin degradation, we studied insulin degradation by HepG2 cells in the presence of IGF. We found that IGF-I at a concentration of 130 nmol/l inhibits insulin degradation by HepG2 cells when the initial insulin concentration is 0.34 nmol/l. The effect of IGF-I on insulin degradation is dose-dependent and the rate of insulin degradation is dependent on the insulin concentration. IGF-II is 6 to 10 times more potent than IGF-I in inhibiting 125I-insulin binding to HepG2 cells and in protecting insulin from being degraded. Thus, IGF-I and IGF-II inhibit insulin degradation most likely by competing for binding at insulin binding sites of liver cells.

Restricted access

Hans-Peter Guler, Jürgen Zapf, Christoph Schmid and E. Rudolf Froesch

Abstract.

IGF-I and -II share specific serum carrier proteins which elute on neutral Sephadex G-200 gel permeation chromatography at apparent molecular masses of 50 and 200 kD. The half-lives of free and carrier protein-bound 125I-IGF-I and -II were determined after bolus injections of the tracers into two normal adults. Labelled IGF-I and -II migrated first with the 50-kD and later with the 200-kD complex. In these complexes their apparent half-lives were 20–30 min and 12–15 h, respectively. The apparent half-life of free 125I-IGF-I and -II was 10–12 min. In a second set of experiments, recombinant human insulin-like growth factor I was infused during 6 days in two healthy adults at a dose of 20 μg · kg−1 · h−1 (corresponding to around 30 mg/day). Serum obtained before and during the infusion was subjected to neutral Sephadex G-200 gel permeation chromatography and fractions were pooled according to the apparent molecular masses at which the carrier protein complexes elute. IGF-I and -II in these pools were determined by RIA. Before the IGF-I infusion, 92 and 272 μg/l of IGF-I and -II were found in the 200-kD complex, 45 and 91 μg/l in the 50-kD complex, and 15 and 5 μg/l were present in the free form. Corresponding figures during the IGF-I infusion were 389 and 18 μg/l for the 200-Kd complex, 201 and 54 μg/l for the 50-kD complex, and 80 and < 1 μg/l for free IGF-I and -II. Using the half-lives of the tracer studies and the levels of the different molecular weight forms of IGF in serum, the production rates for IGF-I and -II were calculated to be 10 mg and 13 mg per day.

Free access

Peter Wiesli, Beat Schwegler, Beat Schmid, Giatgen A Spinas and Christoph Schmid

Objective: To determine whether systematic evaluation of cognitive function by the Mini-Mental State Examination (MMSE) allows the objective detection and documentation of cognitive deterioration in patients referred for evaluation of suspected hypoglycaemic disorders by the 72-h fast.

Design: Prospective case series.

Methods: In 50 patients referred for evaluation of suspected hypoglycaemic disorders, the MMSE score (maximum 30 points) was assessed at the start and at the end of the fast.

Results: The fast was terminated before 72 h in 14 patients because they developed neuroglycopenic symptoms due to hypoglycaemic disorders. Their MMSE score fell from a median of 29 points (range 20–30) at the beginning to 17 points (range 0–24) at the termination of the fast. The score dropped by ≥6 points in all patients with hypoglycaemic disorders. Median (range) plasma glucose concentration at the end of the fast was 2.1 (1.1–2.5) mmol/l. Thirty-six individuals developed no neuroglycopenic symptoms throughout the 72-h fast, their MMSE score remained between 27 and 30 throughout the fast and their median plasma glucose concentration dropped to 2.9 (2–3.6) mmol/l.

Conclusions: Systematic evaluation of cognitive function by the MMSE at the beginning and at the termination of the fast allows objective determination and documentation of the deterioration of the cognitive state in patients with hypoglycaemic disorders. A decline in the cognitive performance by ≥6 points in the MMSE score rather than a distinct plasma glucose concentration should be used as the criterion to terminate the prolonged fast before 72 h.

Free access

Thomas Münzer, Andrea Hegglin, Tobias Stannek, Otto D Schoch, Wolfgang Korte, Daniel Büche, Christoph Schmid and Christoph Hürny

Objective

To investigate the long-term effects of nasal continuous positive airway pressure (CPAP) ventilation in patients with obstructive sleep apnea syndrome (OSAS) on body composition (BC) and IGF1.

Design

Observational study.

Subjects

Seventy-eight (11 females and 67 males) OSAS patients who were compliant with CPAP (age 51±1.1 years) participated in the study. We assessed body mass index (BMI), total body mass (TBM), total body fat (TBF; kg) and lean body mass (LBM; kg), abdominal subcutaneous (SC) and visceral (V) fat (cm2), and waist circumference (WC; cm) by magnetic resonance imaging, and IGF1 (ng/ml) before and after 7.8±1.3 months of CPAP use of an average of 5.9±1.2 h.

Results

Women had a higher BMI, WC; TBM, TBF, and more SC fat. Men had a higher LBM and more V fat. CPAP increased WC (+2.8±9.6 cm, P=0.02) and LBM (2.2±0.5 kg, P=0.006), but not IGF1. In men, CPAP increased BMI (0.5±0.2 kg/m2, P=0.02), WC (1.7±6.9 cm, P=0.002), TBM (1.7±0.4 kg, P=0.0001), LBM (1.5±0.4 kg, P=0.0003), SC fat (12.9±5.1 cm2, P=0.02), and IGF1 (13.6±4.2 ng/ml, P=0.002).

Compliance with CPAP increased LBM in men aged <60 years, but not in those aged >60 years, and IGF1 increased in men aged 40–60 years only.

Conclusions

Long-term CPAP increased LBM in both sexes and IGF1 in men, while fat mass remained unchanged, suggesting a sexually dimorphic response of IGF1 to CPAP. The role of the GH axis activity and age to this response is unclear. The metabolic consequences of changes in LBM are still to be determined. Future studies on the effects of CPAP on BC should include LBM as an outcome.

Restricted access

Katharina Binz, Christoph Schmid, Roger Bouillon, E Rudolf Froesch, Kay Jürgensen and Ernst B Hunziker

Binz K, Schmid C, Bouillon R, Froesch ER, Jürgensen K, Hunziker EB. Interactions of insulin-like growth factor I with dexamethasone on trabecular bone density and mineral metabolism in rats. Eur J Endocrinol 1994;130:387–93. ISSN 0804–4643

Glucocorticoid treatment causes osteoporosis and growth retardation in humans. Insulin-like growth factor I (IGF-I) stimulates differentiation and replication of cultured osteoblast-like cells and induces longitudinal bone growth in IGF-I-deficient rats. We investigated the influence of subcutaneously infused IGF-I on bone and mineral metabolism of male rats treated with a high dose of dexamethasone. Dexamethasone was added to the drinking water in a concentration of 1 mg/l. After 30 days of dexamethasone treatment, recombinant human IGF-I (300 μg/day) or solvent was infused sc by osmotic minipumps for 21 days while dexamethasone was continued. Age-matched untreated male rats served as healthy controls. Dexamethasone-treated rats lost weight. Their IGF-I levels were decreased to 36% of healthy controls. Infusion of IGF-I resulted in an increase in IGF-I serum levels (582% compared to healthy controls) and allowed some weight gain. Osteocalcin and calcitriol levels were markedly decreased in dexamethasone-treated rats and were not influenced significantly by IGF-I infusion. In contrast, IGF-I treatment restored the free calcitriol concentration (molar ratio of calcitriol to vitamin D-binding protein) towards normal. Furthermore, infusion of IGF-I partially corrected the dexamethasone-induced hyperinsulinemia. Histomorphometric analysis revealed no difference in vertebral trabecular bone density (i.e. growth-independent bone remodeling) between the three groups. In contrast, mean trabecular bone density in tibial metaphyses was increased markedly by dexamethasone, presumably due to osteoclast inhibition. Insulin-like growth factor I infusion did not significantly influence these structural metaphyseal bone parameters. We conclude that IGF I-infusion in male rats treated with high doses of dexamethasone reduces insulin resistance and restores calcitriol production but not osteoblast function or responsiveness to calcitriol.

K Binz, Division de Diabétologie, Hôpital Cantonal Universitaire, 1211 Geneva, Switzerland

Free access

Lisa Sze, Christoph Schmid, Konrad E Bloch, René Bernays and Michael Brändle

Objective: Sleep apnoea syndrome (SAS) is common in acromegaly and both diseases are independently associated with hypertension and insulin resistance contributing to increased morbidity and mortality. Pituitary surgery remains the principal treatment modality in acromegaly. The aim of this study was to assess the prevalence and risk factors of SAS in acromegaly and to analyze the effect of transsphenoidal adenomectomy on SAS and cardiovascular risk factors.

Subjects and methods: Thirteen consecutive patients (seven women and six men, aged 25–77 years) with newly diagnosed acromegaly were prospectively studied. Biochemical assessment (IGF-I, GH, acid labile subunit, fasting blood glucose (FBG), insulin), overnight respiratory polygraphy, and an Epworth Sleepiness scale score (ESS) were obtained before and 12 weeks after surgery. SAS was defined by an ESS ≥ 10 and ≥ 5 apnoeas/hypopnoeas (central or obstructive) per hour.

Results: Six of the thirteen (46%) patients had SAS. Risk factors were male gender (83.3 vs 14.3% without SAS) and long disease duration until diagnosis of acromegaly (10.2 ± 3.2 vs 4.6 ± 3.6 years, mean ± s.d.). Ten patients had a homeostasis assessment model score ≥ 4 indicating insulin resistance and one had diabetes mellitus requiring insulin. Seven patients had hypertension (≥ 140/90 mmHg). Postoperatively, GH and IGF-I levels decreased, but only five patients were cured. However, SAS resolved in all patients irrespective of whether acromegaly was cured or not. FBG (5.5 ± 1.2 vs 4.8 ± 0.4 mmol/l) and systolic blood pressure (150.8 ± 18.5 vs 130.8 ± 17.5 mmHg) decreased in all SAS patients.

Conclusion: We found a high prevalence of SAS in acromegaly patients, in particular, in men and those with long duration of disease. Importantly, a marked reduction of GH excess by transsphenoidal adenomectomy may cure SAS and improve insulin resistance and hypertension.

Restricted access

Christoph Schmid, Irene Schläpfer, Eva Futo, Margaretha Waldvogel, Jürg Schwander, Jürgen Zapf and E Rudolf Froesch

Osteoblast-like cells prepared from neonatal rat calvariae and grown under serum-free conditions produce IGF-1 and IGFBPs. In contrast to growth hormone, T3 and PTH increased both IGF-1 mRNA expression and net IGF-1 release in calvaria cells. In addition, they stimulated net production of IGFBP-3 and of an IGFBP with an apparent molecular weight of 32 kDa which was recognized by an antiserum against rat IGFBP-2. Bone cells expressed remarkably high levels of mRNA for IGFBP-2, the predominant IGFBP in serum of newborn rats. T3 at low physiological concentrations but not growth hormone stimulated IGFBP-2 mRNA expression and IGFBP-2 production in bone cells in vitro. Thus, IGFBPs are differentially regulated by these hormones and may play an autocrine/paracrine regulatory role in bone.

Free access

Diane L Möller-Goede, Michael Brändle, Klara Landau, Rene L Bernays and Christoph Schmid

Objective

To assess frequency, symptoms and outcome of pituitary apoplexy (PA) among pituitary adenoma patients, to gain better insight into risk factors for bleeding into pituitary adenoma and to estimate the sequelae of PA by means of a matched control group.

Method

By reviewing charts of 574 patients with pituitary adenoma, we analysed incidence, symptoms and outcome of PA and potential risk factors for developing PA by means of a control group (patients with pituitary adenoma without PA).

Results

In total, 42 suffered from PA, all had macroadenomas; 30/217 male (14%) and 12/179 female (7%) macroadenoma patients, 32/194 patients with clinically non-functioning (16.5%) and 10/202 with clinically active (5.0%) macroadenoma were affected. Antithrombotic therapy predisposed patients to PA (P=0.026), diabetes mellitus and hypertension did not (P=1.00). Patients with PA and pituitary adenoma patients without PA had similar frequencies of hypopituitarism (45 vs 48%, P>0.05) and visual field defects (38 vs 55%, P>0.05), but ophthalmoplegia was significantly more common (76 vs 5%, P<0.001) in patients with PA. Nearly all patients were treated by surgery; most recovered from ophthalmoplegia, whereas visual function improved only moderately. Endocrine outcome was worse in patients with PA than in patients without PA.

Conclusions

Male sex and characteristics of the adenoma itself (especially tumour size and tumour type) rather than patient's cardiovascular risk factors such as diabetes and hypertension seem to predispose to PA; antithrombotic therapy may also be important.

Free access

Marian Christoph Neidert, Lisa Sze, Cornelia Zwimpfer, Johannes Sarnthein, Burkhardt Seifert, Karl Frei, Henning Leske, Elisabeth Jane Rushing, Christoph Schmid and René-Ludwig Bernays

Objective

Klotho is a lifespan-influencing gene expressed mainly in the kidneys. Soluble α-Klotho (αKL) is released into the circulation. In this study, we present baseline αKL serum levels of patients with acromegaly compared with controls with other pituitary adenomas and assess changes following transsphenoidal surgery.

Design

Prospective controlled study.

Methods

We measured soluble αKL (sandwich ELISA) and IGF1 (RIA) in sera of 14 patients (eight females and six males) with active acromegaly and in 22 control patients (13 females and nine males) operated for non-GH-producing pituitary adenomas. Immunohistochemical staining for Klotho was performed in resected adenomas and in normal pituitary tissue samples.

Results

Soluble αKL was high in the acromegaly group preoperatively (median 4217 pg/ml, interquartile range (IQR) 1812–6623 pg/ml) and declined after surgery during early follow-up (2–6 days; median 645 pg/ml, IQR 550–1303 pg/ml) (P<0.001) and during late follow-up (2–3 months post-operatively; median 902 pg/ml, IQR 497–1340 pg/ml; P<0.001). In controls, preoperative soluble αKL was significantly lower than in acromegalics, 532 pg/ml (400–677 pg/ml; P<0.001). Following surgery, soluble αKL remained low during early and late follow-up – changes over time within the control group were not statistically significant. These results were independent of age, sex and kidney function. Klotho staining was equal or slightly decreased in GH-positive adenomas compared with controls.

Conclusion

High soluble αKL serum levels were specific to GH-producing adenomas and decreased rapidly following adenoma removal. Thus, soluble αKL appears to be a new specific and sensitive biomarker reflecting disease activity in acromegaly. Similar Klotho staining patterns in controls and acromegalics suggest that the rise in serum αKL is caused by systemic actions of pituitary GH rather than due to increased expression of Klotho by the pituitary (adenoma).