scholarly journals Disease activity in acromegaly may be assessed 6 weeks after discontinuation of pegvisomant

2005 ◽  
Vol 152 (1) ◽  
pp. 47-51 ◽  
Author(s):  
W M Drake ◽  
R A Loureiro ◽  
C Parkinson ◽  
J P Monson ◽  
G M Besser ◽  
...  

Objective: Pegvisomant, a modified growth hormone (GH) molecule, is a novel medical therapy for acromegaly that functions as a GH receptor antagonist. Serum GH cannot be used as a marker of disease activity in patients taking this form of therapy, partly because GH levels rise on pegvisomant and partly because the drug cross-reacts with many routine GH assays. The purpose of this study was to assess the time for which it is necessary to discontinue pegvisomant prior to biochemical reassessment of acromegaly. Design and methods: This was a retrospective study of 13 patients (seven male, median age 61 years, range 43–77) enrolled in two separate, open-label studies of the efficacy and tolerability of pegvisomant in the treatment of acromegaly. All had been taking a stable dose of pegvisomant (median dose 15 mg daily, range 10–30) as monotherapy for at least 3 months before discontinuing the drug. After discontinuation of pegvisomant, serum IGF-I was measured at 0, 2, 4, 6 and 8 weeks in all patients. Serum GH (single sample) was measured in nine patients at 2, 4, 6 and 8 weeks, but not at baseline on account of the cross-reactivity of pegvisomant with the GH assay. Results: Mean serum IGF-I rose from 210±105 ng/ml (s.d.) at baseline to 392±175 ng/ml at 2 weeks after discontinuation of pegvisomant (P < 0.0001). Although there was no statistically significant change in mean serum IGF-I beyond 2 weeks (412±181, 392±152 and 399±150 ng/ml at 4, 6 and 8 weeks respectively; P = 0.13 (2 vs 4 weeks), 0.31 (4 vs 6 weeks) and 0.46 (6 vs 8 weeks), serum IGF-I rose by more than twice the interassay coefficient of variation (CV) in two of the 13 patients between weeks 2 and 4. The standard deviation of the difference in serum IGF-I between time points was calculated. The values declined from 118% (weeks 0–2) 17%, 19.7% and 10% (weeks 2–4, 4–6 and 6–8 respectively). The expected measure if there was no systematic change in base would be 15% (1.4 ×interassay CV). Mean serum GH was virtually unchanged at 2–8 weeks after cessation of pegvisomant therapy. Conclusions: These results suggest that the activity of acromegaly may be assessed by serum IGF-I levels 6 weeks after the discontinuation of pegvisomant.

1993 ◽  
Vol 129 (5) ◽  
pp. 409-413 ◽  
Author(s):  
Katharina M Main ◽  
Jörgen Lindholm ◽  
Mark Vandeweghe ◽  
Niels E Skakkebaek

The biochemical assessment of disease activity in acromegaly still presents a problem, especially in treated patients with mild clinical symptoms. We therefore examined the diagnostic value of the measurement of urinary growth hormone (GH) excretion in seventy unselected patients with acromegaly of different activity by comparing it to serum GH, serum insulin-like growth factor I (IGF-I) and clinical activity. There were highly significant, positive correlations between urinary GH and serum GH, serum IGF-I as well as clinical activity score (p<0.00005), although some overlap between the groups was observed. In seven patients with low serum GH values (<2.0 μg/l) discordant results were found. Two of the seven patients were clinically mildly active, but only IGF-I was either elevated or within the upper normal range; in three other patients who appeared clinically cured either IGF-I (N = 1) or urinary GH (n = 2) alone were increased. In the remaining two patients elevated serum IGF-I and urinary GH as well as activity score suggested disease activity. Thus, in the majority of cases, urinary GH was significantly correlated to the other three parameters, but added little information to that obtained by serum IGF-I. In conclusion, urinary GH measurements in difficult cases may provide a more direct information on the GH status than IGF-I.


2003 ◽  
pp. S15-S20 ◽  
Author(s):  
G Brabant

Acromegaly is caused by chronic excess secretion of growth hormone (GH) and resultant persistent elevation in concentrations of insulin-like growth factor-I (IGF-I), also called somatomedin-C. A number of diagnostic tests are available to support the diagnosis of acromegaly, but those that rely on measurement of serum GH concentrations have important limitations. Concentrations of serum IGF-I, which is produced principally in the liver and mediates the actions of GH, have been shown to correlate with clinical and metabolic markers of disease activity. Additionally, normalisation of IGF-I levels in acromegaly is associated with the resolution of symptoms and normal life expectancy. Thus, serum IGF-I is an important marker of disease activity and a sensitive, practical, and reliable measure of integrated GH concentrations in patients with acromegaly.


Author(s):  
Yoon Ju Bae ◽  
Alexander Gaudl ◽  
Sonia Jaeger ◽  
Stephanie Stadelmann ◽  
Andreas Hiemisch ◽  
...  

AbstractBackground:Dysregulation of the adrenal cortex has been assessed with measurement of salivary cortisol. So far salivary cortisol is routinely measured with immunoassay (IA). However, liquid chromatography-tandem mass spectrometry (MS) is known to offer better specificity. We compared the concentrations of salivary cortisol measured by MS and IA at basal and stress induced conditions and evaluated reasons for the difference in method-dependent cortisol results.Methods:Saliva samples (n=2703) were collected from 169 children (age range: 8–14 years; 81 healthy children; 55 with internalizing and 33 with externalizing disorders) under circadian conditions and during the Trier Social Stress Test for Children (TSST-C). Biochemical analyses were performed with MS for cortisol and cortisone, IA (IBL, RE62011) for cortisol, and enzyme kinetic assay for α-amylase.Results:MS and IA showed mostly comparable results for circadian activity and TSST-C response with similar statistical power. However, IA measured cortisol concentrations about 2.39-fold higher than MS. We found that this difference in measured values between MS and IA was mainly due to different standardization of IA compared to MS. In addition, at cortisol IA concentration below 5 nmol/L, cross-reactivity with cortisone was found to contribute to the lower concordance between MS and IA.Conclusions:Immunoassay and LC-MS/MS were largely comparable in the interpretation of salivary cortisol dynamics in stress research. But the IA method revealed a restricted accuracy in the measuring range below 5 nmol/L.


2020 ◽  
Vol 8 (1) ◽  
pp. e000773
Author(s):  
Carol H Wysham ◽  
Julio Rosenstock ◽  
Marion L Vetter ◽  
Hui Wang ◽  
Elise Hardy ◽  
...  

IntroductionInvestigate the effects of switching from two times per day exenatide to once-weekly exenatide administered by autoinjector (exenatide once-weekly suspension by autoinjector (QWS-AI)) or treatment with exenatide QWS-AI for 1 year.Research design and methodsIn this phase III open-label study, adults with type 2 diabetes were randomized to receive exenatide QWS-AI (2 mg) or exenatide two times per day (5 mcg for 4 weeks, followed by 10 mcg) for 28 weeks. During a subsequent non-randomized 24-week extension, patients who received exenatide two times per day were switched to exenatide QWS-AI and those randomized to exenatide QWS-AI continued this treatment. Efficacy measures included changes from baseline in glycated hemoglobin (A1C), fasting plasma glucose (FPG), and body weight.ResultsIn total, 315 patients (mean baseline A1C of 8.5%) completed the initial 28 weeks of randomized treatment with exenatide QWS-AI (n=197) or exenatide two times per day (n=118) and were included in the 24-week extension (mean A1C of 7.0% and 7.3%, respectively, at week 28). From weeks 28–52, patients who switched from exenatide two times per day to exenatide QWS-AI had additional A1C reductions of approximately 0.5% (mean A1C change from baseline of –1.4% at week 52) and further reductions from baseline in FPG. Patients who continued exenatide QWS-AI treatment for 52 weeks showed clinically relevant A1C reductions (mean A1C change from baseline of –1.3% at week 52). Body-weight reductions achieved through week 28 were sustained at week 52 in both groups. There were no unexpected safety concerns or changes in the safety profile among patients who switched from exenatide two times per day to exenatide QWS-AI or those who continued exenatide QWS-AI treatment for 52 weeks.ConclusionsSwitching from exenatide two times per day to exenatide QWS-AI resulted in further A1C reductions and maintenance of earlier decreases in body weight, while continued therapy with exenatide QWS-AI for 52 weeks maintained A1C and body-weight reductions, without additional safety or tolerability concerns.Trial registration numberNCT01652716.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 320.1-321
Author(s):  
E. Loibner ◽  
V. Ritschl ◽  
B. Leeb ◽  
P. Spellitz ◽  
G. Eichbauer-Sturm ◽  
...  

Background:Gender differences in prevalence and disease course are known in various rheumatic diseases; however, investigations of gender difference concerning therapeutical response have yielded variable results.Objectives:The aim of this retrospective study was to investigate, whether a gender difference in response rate to biological disease-modifying antirheumatic drugs (bDMARDs) and apremilast in bDMARD-naïve patients could be observed across the three most prevalent inflammatory arthritis diseases: rheumatoid arthritis (RA), spondylarthritis (SpA) and psoriatic arthritis (PsA). Additionally, a response to individual TNF blockers was investigated in this respect.Methods:Data from bDMARD-naïve RA-, SpA- and PsA-patients from Bioreg, the Austrian registry for biological DMARDs in rheumatic diseases, were used. Patients with a baseline (Visit 1=V1) and follow-up visits at 6 months (Visit 2=V2) and 12 months (Visit 3=V3) were included and response to therapy with TNF-inhibitors (TNFi), furthermore to therapy with rituximab, tocilizumab and apremilast was analyzed according to gender. The remaining bDMARDs were not analyzed due to small numbers. Key response-parameter for RA was disease activity score (DAS28), whereas for PsoA the Stockerau Activity Score for Psoriatic Arthritis (SASPA) and for SpA the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) were employed; in addition, the Health assessment Questionnaire (HAQ) was used. Data were analyzed in R Statistic stratified by gender using Kruskal-Wallis and Wilcoxon tests.Results:354 women and 123 men with RA (n=477), 81 women and 69 men with PsA (n=150), 121 women and 191 men with SpA (n=312) were included. No significant differences in biometrics was seen between female and male patients at baseline in all diseases.In RA patients overall DAS28 decreased from baseline (V1) to V2 and V3 (DAS28: V1: male: 4.38 [3.66, 5.11], female: 4.30 [3.68, 5.03], p(m/f) = 0.905; V2: male: 2.66 [1.73, 3.63], female: 3.10 [2.17, 3.98], p(m/f) = 0.015; V3: male: 2.25 [1.39, 3.36], female: 3.01 [1.87, 3.87], p(m/f) = 0.002). For TNF inhibitors (n=311), there was a significant difference between genders at V2 (Fig.1a). Patients receiving Rituximab (n=41) displayed a significantly higher DAS28 at baseline in females, which diminished in the follow up: V1: (p(m/f) p=0.002; V2: p=0.019; V3: p=0.13); response to tocilizumab (n=63) did not show any gender differences.In PsA patients overall SASPA decreased from baseline (V1) to V2 and V3 (SASPA: V1: male: 4.00 [2.80, 5.20], female: 4.40 [2.80, 5.80], p(m/f) = 0.399; V2: male: 2.20 [1.20, 3.50], female: 3.40 [2.00, 5.00], p(m/f) = 0.071; V3: male: 1.80 [0.80, 2.70], female: 3.01 [2.35, 4.80], p(m/f) = 0.001). For TNF inhibitors (n=79), there was a significant difference between genders at V3 (Fig 1a). For Apremilast (n=39), there was a significant difference between genders at V2 (Fig.1c).In SpA patients overall BASDAI decreased from baseline (V1) to V2 and V3 (BASDAI: V1: male: 4.70 [2.88, 6.18], female: 4.80 [3.30, 6.20], p(m/f) = 0.463; V2: male: 3.05 [2.00, 4.60], female: 3.64 [2.62, 5.41], p(m/f) = 0.039; V3: male: 3.02 [1.67, 4.20], female: 3.65 [2.18, 5.47], p(m/f) = 0.016). In V3 a differential BASDAI in response to TNFi (n=299) was observed (Fig.1a).Possible differences of response to individual TNFi (etanercept, infliximab, other TNFi) measured by HAQ were investigated in all diseases together. The difference between male and females was significant at baseline for all 3 TNFi; whereas with the use of ETA the significant difference was carried through to V2 and V3, it was lost with the use of IFX and was variable with the other TNFi (Fig.1b)Figure 1.Conclusion:Female patients showed a statistically lower response to TNFi in all three disease entities (RA, SpA and PsoA) to a variable degree in our homogenous central european population. Interestingly, the difference was not uniform across individual TNFi when measured by HAQ. Gender differences were also seen in response to Apremilast.Disclosure of Interests:Elisabeth Loibner: None declared, Valentin Ritschl: None declared, Burkhard Leeb Speakers bureau: AbbVie, Roche, MSD, Pfizer, Actiopharm, Boehringer-Ingelheim, Kwizda, Celgene, Sandoz, Grünenthal, Eli-Lilly, Grant/research support from: TRB, Roche, Consultancies: AbbVie, Amgen, Roche, MSD, Pfizer, Celgene, Grünenthal, Kwizda, Eli-Lilly, Novartis, Sandoz;, Peter Spellitz: None declared, Gabriela Eichbauer-Sturm: None declared, Jochen Zwerina: None declared, Manfred Herold: None declared, Miriam Stetter: None declared, Rudolf Puchner Speakers bureau: AbbVie, BMS, Janssen, Kwizda, MSD, Pfizer, Celgene, Grünenthal, Eli-Lilly, Consultant of: AbbVie, Amgen, Pfizer, Celgene, Grünenthal, Eli-Lilly, Franz Singer: None declared, Ruth Fritsch-Stork: None declared


2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
M Gegenava ◽  
SA Bergstra ◽  
H Maassen ◽  
CF Allaart

Abstract Funding Acknowledgements Type of funding sources: None. Background Rheumatoid arthritis (RA) is a chronic autoimmune disease with a high prevalence of cardiovascular morbidity and mortality. Purpose: purpose of our project was to investigate the association between disease activity and systolic and diastolic blood pressure (SBP, DBP) in patients with recent-onset rheumatoid arthritis (RA 2010 criteria) or undifferentiated arthritis (UA) who were treated to target disease activity score (DAS)&lt;1.6 in the IMPROVED study. Methods: The associations between disease activity and SBP/DBP were tested for 610 patients (364 RA, 246 UA), cross-sectionally and over time. GEE analyses were performed with both SBP and DBP as outcome measures and disease activity categories (DAS&lt;1.6;&gt;1.6 but ≤2.4; &gt;2.4), CRP level, treatment arms or the number of visits on a certain drug as potential predictors in separate analyses. Separate analyses tested potential contributions of gender, anti-cyclic citrullinated peptide antibodies (ACPA) status, and fulfilling the 2010 ACR/EULAR (American college of rheumatology/ European league against rheumatism) classification criteria. In addition association of BP with various levels of disease activity was tested with T-test. Results: At the baseline mean (SD) SBP was 133 (20) and DBP mean (SD) was 80 (10).  SBP &gt; 140mm Hg was observed in 40% of patients and DBP &gt; 90 mm Hg  in 21% of patients. SBP and DBP statistically significantly decreased during 5 years follow up (mainly during year 1), but the difference in mm Hg was small. Estimates from GEE analysis showed that patients with high DAS &gt;2.4 (HDAS) had a statistically significantly higher SBP (average 3 mm Hg higher, 95% CI 1.7; 4.2, p &lt; 0.01), than the patients in with DAS ≤2.4. ANOVA analyses showed a statistically significant association between SBP and DAS. In addition, post hoc analyses showed that patients with HDAS had a statistically significantly higher  SBP (mean (SD) 132 (19) than the patients with DAS &lt; 1.6 (remission) (mean (SD) 129 (20), p &lt; 0.01), and patients in LDAS but DAS≥1.6 had a statistically significantly higher SBP (mean (SD) 131 (19) than the patients in remission (mean (SD)  129 (20), p = 0.02) (Figure 1), whereas no association was found between DAS category and DBP. Gender, ACPA status or fulfilling the 2010 classification criteria did not influence the relation between DAS and blood pressure. Conclusions: In patients with RA or UA, a higher DAS is associated with higher blood pressure, but the clinical impact is unclear. Abstract Figure 1


2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Sang Youn Jung ◽  
Jung Hee Koh ◽  
Ki-Jo Kim ◽  
Yong-Wook Park ◽  
Hyung-In Yang ◽  
...  

Abstract Background Tapering or stopping biological disease-modifying anti-rheumatic drugs has been proposed for patients with rheumatoid arthritis (RA) in remission, but it frequently results in high rates of recurrence. This study evaluates the efficacy and safety of tacrolimus (TAC) as maintenance therapy in patients with established RA in remission after receiving combination therapy with tumor necrosis factor inhibitor (TNFi) and methotrexate (MTX). Methods This 24-week, prospective, open-label trial included patients who received TNFi and MTX at stable doses for ≥24 weeks and had low disease activity (LDA), measured by Disease Activity Score-28 for ≥12 weeks. Patients selected one of two arms: maintenance (TNFi plus MTX) or switched (TAC plus MTX). The primary outcome was the difference in the proportion of patients maintaining LDA at week 24, which was assessed using a logistic regression model. Adverse events were monitored throughout the study period. Results In efficacy analysis, 80 and 34 patients were included in the maintenance and switched arms, respectively. At week 24, LDA was maintained in 99% and 91% of patients in the maintenance and switched arms, respectively (odds ratio, 0.14; 95% confidence interval, 0.01–1.59). Drug-related adverse effects tended to be more common in the switched arm than in the maintenance arm (20.9% versus 7.1%, respectively) but were well-tolerated. Conclusion This controlled study tested a novel treatment strategy of switching from TNFi to TAC in RA patients with sustained LDA, and the findings suggested that TNFi can be replaced with TAC in most patients without the patients experiencing flare-ups for at least 24 weeks. Trial registration Korea CDC CRIS, KCT0005868. Registered 4 February 2021—retrospectively registered


2002 ◽  
pp. 319-323 ◽  
Author(s):  
Y Rakover ◽  
A Silbergeld ◽  
I Lavi ◽  
R Masalha ◽  
IB Shlomo

OBJECTIVES: In the majority of children with short stature, the etiology is unknown. Mutations of the GH receptor (GHR) have been reported in a few children with apparent idiopathic short stature (ISS). These patients had low IGF-I, IGF-binding protein-3 (IGFBP-3) and GH-binding protein (GHBP), but a normal or exaggerated GH response to provocative stimuli, suggestive of partial GH insensitivity (GHI). We attempted to identify children with partial GHI syndrome, based on their response to GH provocative stimuli and other parameters of the GH-IGF-I axis. SUBJECTS AND METHODS: One hundred and sixty-four pre-pubertal children (97 boys, 67 girls) aged 7.2 (0.5-16.75) years were studied. All had short stature with height <3rd centile. The weight, bone age (BA) and body mass index (BMI) of the subjects, as well as the parents' heights and mid parental height (MPH) were assessed. Basal blood samples were taken for IGF-I, IGFBP-3 and GHBP. All subjects underwent a GH provocative test with either clonidine, arginine or insulin. The subjects were divided into three groups: (A) patients with peak GH concentration <18 mIU/l in two different provocative tests (GH deficiency - GHD, n=33); (B) patients with peak GH between 18.2 and 39.8 mIU/l (normal response, n=78); (C) patients with peak GH >40 mIU/l (exaggerated GH response, n=53). RESULTS: No significant differences were found in age, height (standard deviation score (SDS)), parental height (SDS) and the difference between chronological age and bone age (DeltaBA) between the groups. Patients with GHD were heavier (P=0.039) and had significantly higher BMI (SDS) (P=0.001) than the other groups. MPH (SDS) was lower in the group of exaggerated responders (P=0.04) compared with the other groups. No significant differences were found between the groups for the biochemical parameters when expressed nominally or in SDS, except for IGFBP-3 (SDS), which was lower in the GHD group (P=0.005). The GHBP levels were not lower in the group of exaggerated GH response to provocative stimuli. Height (SDS) correlated negatively with basal GH values in pooled data of all the subjects (r=-0.358, P<0.0001), in normal responders (r=-0.45, P<0.0001) and in the exaggerated responders (r=-0.341, P<0.0001), but not in the GHD group. CONCLUSION: Exaggerated GH response to provocative tests alone does not appear to be useful in identifying children with GHI.


1996 ◽  
Vol 271 (2) ◽  
pp. E223-E231 ◽  
Author(s):  
L. Goya ◽  
F. Rivero ◽  
M. A. Martin ◽  
R. Arahuetes ◽  
E. R. Hernandez ◽  
...  

The effect of refeeding and insulin treatment of undernourished and diabetic neonatal rats, respectively, on the regulation of insulin-like growth factor (IGF) and insulin-like growth factor binding protein (IGFBP) was investigated. The changes in body weight, insulinemia, glycemia, serum IGF-I, and growth hormone (GH) as well as the increase of the 30-kDa IGFBP in undernourished and diabetic neonatal rats previously shown elsewhere were reversed by refeeding and insulin treatment, respectively. Also, changes in liver mRNA expression of IGF-I and-II and IGFBP-1 and -2 were restored in refed undernourished and IGF-I and IGFBP-1 levels recovered in insulin-treated diabetic rats. However, serum GH was still below normal after rehabilitation in both situations. Thus the present results support the idea of a GH-independent IGF/ IGFBP regulation mediated by a balance of insulin and nutrients as has already been suggested in previous neonatal studies.


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