-
[show abstract]
[hide abstract]
ABSTRACT: CONTEXT: Preliminary evidence points to aldosterone being not only prominently involved in the systemic regulation of the blood pressure but also to play a role in the pathophysiology of depression. OBJECTIVE: We evaluated whether the combination of hypertension and depressed symptomatology is useful to screen for individuals suffering an activation of the renin-angiotensin-aldosterone system (RAAS). DESIGN: We conducted a cross-sectional analysis in participants from the Cooperative Health Research in the Region of Augsburg (KORA) F4 Study conducted between 2006 and 2008 in Southern Germany. A total of 1805 participants of the F4 study were included in the study. METHODS: The association between aldosterone and renin levels and the different combinations of hypertension and depressed symptomatology was examined in four different models of multiple linear regression adjusted for age, sex, creatinine levels, potassium levels, body mass index (BMI) and behavioural risk factors. RESULTS: Individuals suffering both, depressed symptomatology and hypertension exhibited highly significantly increased aldosterone levels (p<0.001) and slightly, not significantly increased renin levels (p=0.08) compared to individuals with no depressed symptomatology and no hypertension. No significant activation of the RAAS was seen in only depressed or only hypertensive individuals. CONCLUSIONS: The finding of highly significantly increased aldosterone levels and increased renin levels in individuals suffering both, depressed symptomatology and hypertension provides further evidence for the involvement of the RAAS in the pathogenesis of depressed symptomatology. These findings have important implications for future research concerning the pathophysiological pathways that link depression and cardiovascular disease.
Psychoneuroendocrinology 04/2013; · 5.81 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: With adequate dose titration, pegvisomant normalizes IGF-I in up to 97% of patients with acromegaly. Pegvisomant is indicated for treatment-resistant disease but is expensive, particularly at a high dose. It has been used successfully in combination with somatostatin analogs. However, there are no therapeutic reports of pegvisomant in combination with dopamine agonists. Cabergoline is orally active, well-tolerated, and relatively inexpensive, and as monotherapy for acromegaly it is reported to normalize IGF-I in up to 30% of patients.
The aim of the study was to investigate the efficacy of cabergoline monotherapy and pegvisomant in combination with cabergoline to control serum IGF-I in patients with active acromegaly. Twenty-four patients were recruited into a United Kingdom, multicenter, open-label, prospective clinical trial.
We measured the change in serum IGF-I.
After 18 wk of dose titration to a maximum dose of 0.5 mg once daily, cabergoline monotherapy did not significantly reduce IGF-I (454 ± 219 baseline vs. 389 ± 192 ng/ml cabergoline), although two patients did normalize IGF-I. The addition of 10 mg pegvisomant daily for 12 wk significantly reduced IGF-I (389 ± 192 ng/ml cabergoline vs. 229 ± 101 ng/ml combination), and 68% achieved a normal IGF-I. Twelve weeks after cabergoline withdrawal, while continuing to receive pegvisomant 10 mg, only 26% of patients maintained an IGF-I within the reference range (229 ± 101 ng/ml combination vs. 305 ± 177 ng/ml pegvisomant). There were no significant changes in liver transaminases or glucose metabolism throughout the study.
These data suggest that combination treatment with cabergoline and pegvisomant is more effective at reducing IGF-I levels than either cabergoline or pegvisomant monotherapy.
The Journal of clinical endocrinology and metabolism 01/2012; 97(4):1187-93. · 6.50 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: PURPOSE: An elevated prevalence of sleep apnoea (SA) in patients with acromegaly has been suggested. METHODS: We performed polysomnographies in 52 patients with acromegaly (25 m, 27 f, age 51 years, range 19-82 years). Patients were defined having SA if they had more than five apnoeas or hypopnoeas per hour (respiratory disturbance index = RDI). The type of SA was divided into obstructive (OSA), central (CSA) or mixed (OSA+CSA). Seventeen patients had newly diagnosed disease, and 18 patients were treated with somatostatin analogues. RESULTS: Twenty-three patients had controlled disease activity (mean GH levels <1 μg/l during a 3-h profile and normalised IGF-1 levels). Twelve had active acromegaly despite medical treatment. Thirty patients (58%) had SA. Twenty-five of those had OSA, three had CSA, and two had mixed. Of the patients with active disease, 66% had SA, compared to 48% in the cured group. Significantly more patients with hypertension (n = 18) than without hypertension (n = 12, p = 0.041) had SA. Basal glucose was not significantly different between patients with (100 mg/dl, range 75-207 mg/dl) and without SA (92 mg/dl, range 74-120 mg/dl), but HbA1c was significantly higher in patients with SA (5.9% (4.9-9.0%) vs. 5.4% (4.3-6.1%), p = 0.001). A positive correlation between RDI and BMI (p = 0.04), RDI and age (p = 0.013) and RDI and disease activity (p = 0.014) was seen. No major correlation could be found between RDI and the duration of disease activity nor between RDI and GH levels. CONCLUSION: RDI correlates positively with disease activity but not with the duration of the disease. The parameters of the metabolic syndrome are positively associated to the degree of SA in acromegalic patients.
Sleep And Breathing 01/2012; · 1.84 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The renin-angiotensin-aldosterone-system (RAAS) is one of the most important systems involved in the pathogenesis of cardiovascular diseases. Its role in stress response has been generally neglected, although the progression of cardiovascular disease is considerably increased in the presence of stress and especially in the presence of depression risk. With the present analysis we aimed to evaluate whether the activity of the RAAS correlates with depressive symptomatology and with chronic stress. Moreover, we aimed to analyse whether stress response is altered in the presence of depressed symptomatology. We chose "living alone" to be our paradigm of chronic stress.
Aldosterone and renin levels were assessed in 1743 (829 men, 914 women) from the population-based KORA study (Cooperative Health Research in the Region of Augsburg). The relationship between aldosterone, renin levels and the different combinations of living alone and depressive symptomatology was examined in three different multiple linear regression models adjusted for age, sex, creatinine levels, potassium levels, body mass index (BMI) and bio-behavioural factors. Neither "living alone" nor depressive symptomatology alone were associated with an activation of the RAAS, but the combination of living alone and depressive symptomatology yielded a highly significant increase in the aldosterone (p<0.01) and renin level (p=0.03).
Our findings show that depressive symptomatology is associated with a hyper-responsiveness to chronic stress. Under the condition of chronic stress depressed individuals have an activated RAAS. Activation of the RAAS might explain the known increased risk of negative cardiovascular disease outcomes in this group.
Psychoneuroendocrinology 07/2011; 37(2):230-7. · 5.81 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: GH substitution in GH deficiency (GHD) must be subcutaneously administered daily. A new sustained-release formulation of GH (LB03002) has been developed, which has to be injected once a week. As a substudy to the phase III study, we performed this prospective study to evaluate the influence of LB03002 on metabolic variables and hormones.
Eleven patients with GHD [four women/seven men, 58 years (29-69 years)] without GH therapy were included in the study. Eight patients were treated with LB03002 for 12 months and three patients received placebo for 6 months followed by LB03002 for 6 months. A 3-h oral glucose tolerance test (OGTT) was performed at study entry and at study end. Additionally, IGF-I, cholesterol, LDL, HDL, triglycerides, leptin, ghrelin, HbA1c and C-peptide were measured. Body composition was evaluated by dual-energy X-ray absorptiometry (DXA), and waist/hip ratio (WHR) and waist/height (WHtR) ratio were measured by tape and scale.
Multiple of upper limit of normal (xULN) of IGF-I (0·23 (0·09-0·4) vs 0·71 (0·4-1·04), P < 0·01), WHR (0·98 (0·86-1·04) vs 1·01 (0·86-1·05), P < 0·05) and ghrelin levels [119·8 ng/l (67·7-266·6) vs 137 ng/l (67-289·5), P < 0·05] were significantly higher, whereas fat mass (FM) [34·7% (20·4-49·2) vs 32·4% (16·7-48·5), P < 0·05] and leptin [11·2 μg/l (3·3-55·7) vs 7·05 μg/l (2·4-54·3), P < 0·05] were significantly lower at study end. Glucose, insulin, HOMA-IR, ISI, HOMA-β, C-peptide and HbA1c during OGTT were not significantly different before and after GH substitution, neither were BMI, WHtR, bone mineral density and lipid variables.
Substitution with LB03002 showed statistically significant reduction in FM, which reduces leptin levels and increases ghrelin levels but does not seem to influence glucose and lipid metabolism.
Clinical Endocrinology 06/2011; 76(1):88-95. · 3.17 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Pegvisomant (peg) is a GH receptor antagonist. In de novo acromegalic patients with high GH levels, ghrelin and leptin levels are reduced, suggesting a direct GH-mediated effect. The aim of our study was to evaluate whether peg treatment in acromegalic patients may abolish the GH impact on ghrelin and leptin levels.
Ghrelin, leptin and endogenous GH were measured in ten peg-treated acromegalic patients (three females/seven males, 47 years (28-57)), ten patients with active (act) and ten patients with inactive disease (inact) as well as in ten gender-, age- and body mass index (BMI)-matched healthy volunteers (controls). Endogenous GH was measured using a special in-house assay without interference by peg; total ghrelin and leptin were determined using a commercial RIA and an immunofluorometric in-house assay respectively.
Age and BMI did not differ significantly between groups. Endogenous GH was significantly higher in peg (6.3 μg/l (1.5-41)) and act (9.3 μg/l (1.7-70)) compared with controls (0.1 μg/l (0.1-3.1)) and inact (0.35 μg/l (0.1-2.0), P<0.001). Ghrelin was significantly higher in peg (232 ng/l (96-351)) compared with act (102 ng/l (33-232), P<0.01), whereas ghrelin was not significantly different between the other groups. Leptin was highest in controls (19 μg/l (4-57)) and lowest in act (6 μg/l (2-21)), but this difference did not reach significance.
Treatment with peg seems to disrupt the feedback loop of ghrelin and GH, leading to elevated ghrelin levels. Furthermore, peg therapy appears not to have a strong impact on leptin levels, as acromegalic patients with and without peg treatment showed similar leptin levels.
European Journal of Endocrinology 11/2010; 163(5):727-34. · 3.42 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Treatment with pegvisomant, an antagonist of growth hormone (GH) receptors, increases GH levels in a dose dependent manner. Cabergoline can suppress GH secretion in approximately 40% of acromegalic patients. However, the acute effects of cabergoline have not been studied in patients treated with pegvisomant. We performed this cross-sectional study to evaluate endogenous GH after an additional single cabergoline administration.
9 acromegalic patients on pegvisomant therapy were included. A 6h GH profile after pegvisomant alone (P) and a 9h profile in combination with oral cabergoline 0.5mg (PC) were performed. After 3 or 6h, all patients received a standardized light mixed meal. Endogenous serum GH and pegvisomant levels were measured by special in-house assays. The GH assay showed no interference with pegvisomant.
Endogenous GH levels at baseline did not differ significantly between the profiles (P: 16.5 μg/l (range 3.2-36.6 μg/l), PC: 8.0 μg/l (1.6-48 μg/l), p>0.05). In both profiles, GH fluctuated before meal. GH decreased more pronounced in PC but this decrease was not statistically significant. After meal, a significant decline in endogenous GH levels from 16.4 μg/l (0.4-27.1 μg/l, 100%) to 8.1 μg/l (0.2-24.7 μg/l, 66%) appeared in P at 300 min (p<0.01). Also in PC a decline from 7.8 μg/l (1.1-29.6 μg/l, 100%) to 5.2 μg/l (0.4-23.9 μg/l, 75%) at 300 min was observed but it was not significant.
Endogenous GH is not significantly decreased after a single oral cabergoline application during pegvisomant treatment in acromegaly.
Growth hormone & IGF research: official journal of the Growth Hormone Research Society and the International IGF Research Society 10/2010; 20(5):338-44. · 2.35 Impact Factor
-
Hormone and Metabolic Research 06/2010; 42(6):371-3. · 2.19 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Aldosterone excess in the context of primary aldosteronism (PA) has been associated with impaired glucose tolerance and diabetes mellitus. We retrospectively assessed the prevalence of diabetes mellitus in patients from the German Conn's Register and compared the data with those from hypertensive subjects of a population-based survey. In a case-control study, we have compared 638 patients with PA from the German Conn's registry who were treated in 6 German centers with 897 hypertensive control subjects from the population-based F3 survey of the Cooperative Health Research in the Region of Augsburg (KORA). The samples were matched for age, sex, and blood pressure in a 1:1 ratio. Risk factors associated with the presence of diabetes mellitus were calculated in 638 patients with PA and 897 hypertensive controls. In the case control study, the diabetes prevalence was calculated in 338 cases and controls. In patients with primary aldosteronism, age, BMI, and a higher number of antihypertensive drugs (lowest tertile vs. highest tertile) were variables associated with diabetes mellitus. In contrast, serum potassium and plasma aldosterone concentrations were not associated with higher diabetes prevalence, whereas diastolic blood pressure was inversely associated with diabetes mellitus. Diabetes mellitus was more prevalent in patients with PA than in 338 matched controls (23 vs. 10% in controls). Our data for the German population show that diabetes mellitus is more prevalent in patients with primary aldosteronism than in hypertensive controls.
Hormone and Metabolic Research 06/2010; 42(6):435-9. · 2.19 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Recent evidence demonstrates an increased incidence of primary aldosteronism (PA) in approximately 10% of the hypertensive population, making noninvasive and simple screening methods necessary. The aim of the present study was to apply a time-resolved fluorescence immunoassay for the measurement of aldosterone in saliva and the establishment of a cut-off to identify patients with a high likelihood for PA requiring subsequent screening with the aldosterone to renin ratio. Saliva was collected (AM and PM) to ascertain an optimum time with best discriminating power between healthy and disease states. Plasma aldosterone, after overnight recumbency and 4 h later, was collected for posture testing. The participants included 53 PA patients (aged 14-78), 54 with essential hypertension (EH, aged 19-82), and 38 healthy volunteers (aged 19-56). Saliva aldosterone (SA) (median, 25-75(th)%) in PA was found at 90 pg/ml (61-139) compared to 53 pg/ml (40-85) in EH, with discrimination between PA versus EHs best in the morning (cutoff: 81 pg/ml, 77% sensitivity, 82% specificity). Saliva aldosterone decreases throughout the day in patients with adenomas [APA AM: 123 pg/ml (92-213) vs. PM: 79 pg/ml (41-116)], but not in those with bilateral hyperplasia [BAH AM: 85 pg/ml (59-115)] vs. pm 69 pg/ml (57-114). Morning SA alone allows discrimination between PA and controls, though with significant overlap against EHs, leading to a high number of false positives. More promising is the use of diurnal variation in SA in distinguishing between APA and BAH. The decline in SA seen in patients with APA presents a more constant finding compared to posture testing, which fails to correctly classify a large number of patients.
Hormone and Metabolic Research 03/2010; 42(6):400-5. · 2.19 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This cross-sectional study was performed to evaluate the effect of long-term GH substitution on leptin and ghrelin in GH deficiency (GHD).
Leptin and ghrelin were measured after glucose load for 3 h in 52 pat and 10 age- and BMI-matched healthy controls. 22 GHD pat were on GH substitution (GH-Sub) for a median of 10 yr (range 2-27 yr). 30 age- and BMI-matched GHD pat were not substituted for at least 2 yr (non-Sub).
Basal leptin (8 microg/l (1-130) vs. 16 microg/l (3-89), p<0.05) and AUC of leptin (p<0.05) was significantly lower in GH-Sub compared to non-Sub. In the control group, leptin was higher compared to GH-Sub and similar to non-Sub (19 microg/l (4-57)). Ghrelin (baseline: non-Sub 113 ng/l (61-270), GH-Sub 145 ng/l (83-280), controls 131 ng/l (83-274)) were slightly but not significantly lower for non-Sub. After glucose load, a significant decrease in leptin appeared in both GHD groups, but not in the control group. Ghrelin decreased significantly in all groups.
Lipolytic GH causes lower leptin in GH-Sub. The reason for similar ghrelin might be the compensating effect of acute GH suppression and stimulating low fat mass on ghrelin. Leptin regulation after glucose load is impaired in GHD, whereas ghrelin regulation seems to be not effected.
Regulatory Peptides 07/2009; 158(1-3):40-6. · 2.11 Impact Factor
-
J Manolopoulou,
P Mulatero,
C Maser-Gluth,
P Rossignol,
A Spyroglou,
Y Vakrilova,
S Petersenn,
O Zwermann,
P F Plouin,
M Reincke, M Bidlingmaier
[show abstract]
[hide abstract]
ABSTRACT: Saliva is a readily available biological fluid, making it convenient in diagnosis of diseases and in multi-sampling protocols. Several salivary steroids give a useful index of free plasma levels. Increased incidence of primary aldosteronism (PA) in approximately 10% of the hypertensive population has increased interest in the mineralocorticoid aldosterone.
A biotinylated-aldosterone tracer and a commercially available antibody are used in a time-resolved fluorescence immunoassay (TR-FIA) to measure salivary aldosterone (SA). Saliva was collected in various multi-sampling protocols: Investigation of diurnal rhythm in healthy and PA patients, ACTH stimulation test and posture test in healthy subjects.
Method validation showed a sensitivity of 19 ng/L and intra-/inter-assay precision between 7.2-10.1% and 8.7-15.7%, respectively. SA correlated significantly (y = 0.2995x +/- 0.01, r(2)=0.60) to plasma aldosterone measured by a commercial radioimmunoassay. SA (median; 95%CI) was at 111 (95-127)ng/L in PA (n=84) and 50 (44-56)ng/L in healthy subjects (n=60). After change in posture, aldosterone increased in both, saliva (57 (47-63)ng/L to 95 (84-117)ng/L) and plasma (26 (26-41)ng/L to 135 (110-181)ng/L). Peak levels were reached after 1h, and were higher in females than in males.
SA correlates well to plasma aldosterone and mirrors responses during conditions of stress. SA is significantly higher in PA, and the diurnal rhythm seen in the healthy is blunted in PA. We additionally found gender-dependent differential responses to posture, with higher increases in females. Measurement of aldosterone in saliva presents a useful and convenient method for application in multi-sampling studies.
Steroids 06/2009; 74(10-11):853-8. · 2.83 Impact Factor
-
E Born-Frontsberg,
M Reincke,
L C Rump,
S Hahner,
S Diederich,
R Lorenz,
B Allolio,
J Seufert,
C Schirpenbach,
F Beuschlein, M Bidlingmaier,
S Endres,
M Quinkler
[show abstract]
[hide abstract]
ABSTRACT: Primary aldosteronism (PA) is associated with vascular end-organ damage.
Our objective was to evaluate differences regarding comorbidities between the hypokalemic and normokalemic form of PA.
This was a retrospective cross-sectional study collected from six German centers (German Conn's registry) between 1990 and 2007.
Of 640 registered patients with PA, 553 patients were analyzed.
Comorbidities depending on hypokalemia or normokalemia were examined.
Of the 553 patients (61 +/- 13 yr, range 13-96), 56.1% had hypokalemic PA. The systolic (164 +/- 29 vs. 155 +/- 27 mm Hg; P < 0.01) and diastolic (96 +/- 18 vs. 93 +/- 15 mm Hg; P < 0.05) blood pressures were significantly higher in hypokalemic patients than in those with the normokalemic variant. The prevalence of cardiovascular events (angina pectoris, myocardial infarction, chronic cardiac insufficiency, coronary angioplasty) was 16.3%. Atrial fibrillation occurred in 7.1% and other atrial or ventricular arrhythmia in 5.2% of the patients. Angina pectoris and chronic cardiac insufficiency were significantly more prevalent in hypokalemic PA (9.0 vs. 2.1%, P < 0.001; 5.5 vs. 2.1%, P < 0.01). Overall, cerebrovascular comorbidities were not different between hypokalemic and normokalemic patients, however, stroke tended to be more prevalent in normokalemic patients.
Our data indicate a high prevalence of comorbidities in patients with PA. The hypokalemic variant is defined by a higher morbidity than the normokalemic variant regarding some cardiovascular but not cerebrovascular events. Thus, PA should be sought not only in hypokalemic but also in normokalemic hypertensives because high-excess morbidity occurs in both subgroups.
The Journal of clinical endocrinology and metabolism 02/2009; 94(4):1125-30. · 6.50 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: At diagnosis, approximately 50% of adults with severe GH deficiency (GHD) have an IGF-I within the reference range. It is unclear whether in such patients serum IGF-I levels are regulated by factors other than GH.
We performed a double-blind, randomized, placebo-controlled, cross-over study to investigate the effect of the GH receptor antagonist - pegvisomant (20 mg daily for 14 days) on GH and IGF-I levels in three cohorts: patients with GHD and a normal IGF-I (NORMS); patients with GHD and a low IGF-I (LOWS) and healthy volunteers (CONS).
Pegvisomant decreased IGF-I in CONS and NORMS [158.5 (101-206) vs. 103 (77-125) microg/l, P < 0.01; 124 (81-136) vs. 95 (51-113) microg/l, P < 0.01 respectively], but not in LOWS [31 (< 31-32) vs. 34.5 (< 31-38) microg/l], and this was associated with an increase in mean 24 h GH in CONS [0.49 (0.12-0.89) to 1.38 (0.22-2.45) microg/l (P = 0.03)] and in NORMS [69 (0-320)% from 0.1 (< 0.1-0.13) to 0.17 (0.11-0.42) microg/l (P = 0.03)], but not in the LOWS. The peak GH response to arginine was increased by pegvisomant in CONS and NORMS [6.1 (0.8-9) vs. 20.4 (13.1-28.8) microg/l, P = 0.03; 0.4 (0.1-0.5) vs. 0.5 (0.3-0.6) microg/l, respectively], but not in LOWS.
These data indicate that patients with severe GHD with a normal IGF-I are able to increase GH secretion in response to a pegvisomant-induced fall in IGF-I, whereas those with low IGF-I levels are unable to increase GH secretion. Therefore circulating IGF-I appears to be GH-independent in GHD patients with a low IGF-I, but remains partially GH-dependent in GHD patients with a normal IGF-I.
Clinical Endocrinology 01/2009; 70(3):439-45. · 3.17 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Co-treatment with somatostatin analogues and growth hormone receptor antagonists in acromegaly might be a new treatment option abolishing the negative effects of monotherapy. Nevertheless, little is known about the acute effect of the combined treatment on endogenous GH and pegvisomant levels.
Ten acromegalic patients on constant pegvisomant therapy were included. Two 6-h GH secretion profiles were performed once after pegvisomant alone (P), the other after an additional 100 microg octreotide sc injection (PO). After 180 min, all patients received a standardized light mixed meal. Endogenous serum GH and pegvisomant levels were measured by special in-house assays. In addition, insulin and glucose were measured.
In the combined profile PO, a significant decrease of median endogenous GH was seen (p<0.01, median percentage decline 75.2%, range 23.7-88.2), which was not seen in profile P. Seven of 10 patients had a decline >70% and might be seen as responders. After meal, endogenous GH significantly decreased only in profile P (p<0.01). Pegvisomant levels did not differ significantly between profiles and did not change significantly during the tests. After meal, glucose levels rose higher and later and insulin levels lower and later in profile PO than in profile P.
During pegvisomant treatment, endogenous GH can be reduced significantly by acute application of a somatostatin analogue. Therefore, in acromegalic patients on pegvisomant therapy GH regulation due to somatostatin analogues seems to be preserved.
Growth hormone & IGF research: official journal of the Growth Hormone Research Society and the International IGF Research Society 12/2008; 19(3):245-51. · 2.35 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Elevated BMI, fat mass and food intake increases leptin whereas ghrelin is reduced. Ghrelin stimulates growth hormone (GH) secretion. This prospective cross-sectional study was performed to investigate the influence of GH excess on leptin and ghrelin levels at baseline and after glucose load in a large group of acromegalic patients.
Leptin, ghrelin, GH, glucose and insulin concentrations were measured during a 3 h OGTT in 17 active, 25 inactive patients without medication (inact) and 8 inactive patients treated successfully with somatostatin analogues (inact-SA). Leptin concentration was measured using an in-house immunofluorometric assay, total serum ghrelin by a commercially available radioimmunoassay. Leptin was corrected for BMI.
During OGTT, no significant difference of baseline, nadir or AUC of leptin/BMI was seen between the groups (baseline leptin/BMI: act: 0.26 microgm(2)/lkg (0.06-0.87); inact: 0.34 microgm(2)/lkg (0.03-1.79); inact-SA: 0.29 microgm(2)/lkg (0.03-1.47). A slight but significant reduction of leptin/BMI occurred in all groups during OGTT (active p<0.001, inact p<0.001, inact-SA p<0.05). Inact had higher ghrelin levels (130 ng/L (69-292) compared to active (102 ng/L (27-232); p=n.s.). Inact-SA had significantly lower ghrelin levels (88 ng/L (72-113)) than inact (p<0.001). There was a significant decline of ghrelin during OGTT in all groups (active p<0.001, inact p<0.001, inact-SA p<0.05).
GH only has a slight influence on leptin secretion. Ghrelin levels are lowered by GH and SA. Nevertheless, the physiological decreasing effect of glucose load on ghrelin secretion is preserved.
Experimental and Clinical Endocrinology & Diabetes 06/2008; 117(3):135-41. · 1.69 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We present the case of a 46-year-old woman with acromegaly currently being treated with the growth hormone (GH) receptor antagonist pegvisomant showing strongly fluctuating IGF-I levels. We prospectively measured estradiol, IGF-I, IGF-I binding protein, acid labile subunit, basal endogenous GH, binding protein and pegvisomant levels for 6 months every week. Estradiol levels showed a strongly negative correlation with IGF-I (r = -0.733, P < 0.001), and less so with ALS (r = -0.433, P < 0.05) and IGFBP3 (r = -0.590, P < 0.01). Estradiol was not significantly correlated with endogenous GH or pegvisomant levels. Likewise, IGF-I did not correlate with endogenous GH or pegvisomant levels. In our patient, endogenous estradiol levels have a significant influence on IGF-I levels. When female acromegalic patients on permanent pegvisomant treatment show fluctuating IGF-I levels, estradiol levels should be taken into consideration.
Pituitary 05/2008; 13(1):89-93. · 1.83 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Data on the involvement of aldosterone in the regulation of the renin-angiotensin-aldosterone system (RAAS) in rodents are still scarce, partly due to the high sample volumes needed by commercially available assays and to the very low aldosterone concentrations present. We have developed a highly sensitive and non-isotopic immunoassay, requiring a volume of only 50 microl serum for a duplicate measurement, employing a highly specific monoclonal antibody against aldosterone. The assay was validated in human and mouse samples and exhibited a linear working range from 10 to 1000 pg/ml. Values obtained after a chromatographic purification step correlated significantly to the dichloromethane extraction ordinarily used. Basal aldosterone values were measured in 75 mouse hybrids and found within the linear range (173+/-21 pg/ml), with no significant difference between males and females. Additionally, we show an increase in serum aldosterone in mice from 3 to 11 weeks of age. Mice of the same genetic background were treated with dexamethasone intraperitoneally (n=7), resulting in significantly decreased concentrations (35+/-3 vs 114+/-33 pg/ml in controls; P<0.001). In contrast, adrenocorticotropic hormone resulted in significantly increased serum aldosterone (603+/-119 pg/ml; n=7; P<0.001), as did the physiological stimulation of the RAAS by a high K(+)/low Na(+) diet (1369+/-703 vs 172+/-36 pg/ml). In conclusion, we have developed and validated an extremely sensitive assay for determination of aldosterone concentrations from very small serum samples, which could be especially useful in pharmacological intervention studies in rodent models.
Journal of Endocrinology 02/2008; 196(2):215-24. · 3.55 Impact Factor
-
Annales d Endocrinologie 10/2007; 68(4):306-7. · 0.74 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Gigantism is rare with the majority of cases caused by a growth hormone (GH)-secreting pituitary adenoma. Treatment options for GH-secreting pituitary adenomas have been widened with the availability of long-acting dopamine agonists, depot preparations of somatostatin analogues, and recently the GH receptor antagonist pegvisomant.
A 23-year-old male patient presented with continuous increase in height during the past 6 years due to a GH-secreting giant pituitary adenoma. Because of major intracranial extension and failure of octreotide treatment to shrink the tumour, the tumour was partially resected by a trans-frontal surgical approach. At immunohistochemistry, the tumour showed a marked expression of GH and a sparsely focal expression of prolactin. Somatostatin receptors (sst) 1-5 were not detected. Tumour tissue weakly expressed dopamine receptor type 2. The Gs alpha subunit was intact. Conversion from somatostatin analogue to pegvisomant normalized insulin-like-growth-factor-I (IGF-I) levels and markedly improved glucose tolerance.
Pegvisomant is a potent treatment option in patients with pituitary gigantism. In patients who do not respond to somatostatin analogues, knowledge of the SST receptor status may shorten the time to initiation of pegvisomant treatment.
Experimental and Clinical Endocrinology & Diabetes 03/2007; 115(3):198-202. · 1.69 Impact Factor
