Publications by authors named "T L C Wolters"

47 Publications

The association between treatment and systemic inflammation in acromegaly.

Growth Horm IGF Res 2021 Apr-Jun;57-58:101391. Epub 2021 Apr 30.

Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.

Objective: Acromegaly is characterized by an excess of growth hormone (GH) and insulin like growth-factor 1 (IGF1), and it is strongly associated with cardiovascular diseases (CVD). Both acute and long-lasting pro-inflammatory effects have been attributed to IGF1. Previous results suggest the presence of systemic inflammation in treated patients. Here we assessed the association between treatment of acromegaly, systemic inflammation and vascular function.

Design: Ex vivo cytokine production and circulating inflammatory markers were assessed in peripheral blood from treated and untreated acromegaly patients (N = 120), and compared them with healthy controls. A more comprehensive prospective inflammatory and vascular assessment was conducted in a subgroup of six treatment-naive patients with follow-up during treatment.

Results: Circulating concentrations of VCAM1, E-selectin and MMP2 were higher in patients with uncontrolled disease, whereas the concentrations of IL18 were lower. In stimulated whole blood, cytokine production was skewed towards a more pro-inflammatory profile in patients, especially those with untreated disease. Prospective vascular measurements in untreated patients showed improvement of endothelial function during treatment.

Conclusions: Acromegaly patients are characterized by a pro-inflammatory phenotype, most pronounced in those with uncontrolled disease. Treatment only partially reverses this pro-inflammatory bias. These findings suggest that systemic inflammation could contribute to the increased risk of CVD in acromegaly patients.
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April 2021

Predictors for Remission after Transsphenoidal Surgery in Acromegaly: A Dutch Multicenter Study.

J Clin Endocrinol Metab 2021 May;106(6):1783-1792

Department of Medicine, Endocrinology section, Pituitary Center Rotterdam, Erasmus University Medical Center, Rotterdam, The Netherlands.

Context: Transsphenoidal surgery (TSS) is the primary treatment of choice in acromegaly. It is important to identify patients in whom surgical cure is not attainable at an early stage, both to inform patients on expected treatment outcome and to select those who are more likely to need additional therapy.

Objective: To identify predictors for remission after TSS in acromegaly.

Methods: Large multicenter study with retrospective data collection from 3 tertiary neurosurgical referral centers in The Netherlands. We analyzed clinical data since 2000 from 3 cohorts (Groningen, Nijmegen, and Rotterdam, total n = 282). Multivariate regression models were used to identify predictors of early biochemical remission (12 weeks to 1 year postoperatively) according to the 2010 consensus criteria, long-term remission (age- and sex-normalized insulin-like growth factor 1 [IGF-1] and the absence of postoperative treatment until last follow-up), and relative IGF-1 and growth hormone [GH] reduction.

Results: A larger maximum tumor diameter (odds ratio [OR] 0.91, 95% CI 0.87-0.96, P ≤ .0001) was associated with a lower chance of early biochemical remission. A larger maximum tumor diameter (OR 0.93, 95% CI 0.89-0.97, P = .0022) and a higher random GH concentration at diagnosis (OR 0.98, 95% CI 0.96-0.99, P = .0053) were associated with a lower chance of long-term remission.

Conclusion: Maximum tumor diameter and random GH concentration at diagnosis are the best predictors for remission after TSS in acromegaly.
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May 2021

Generation of Fine Grained Demographic Information for Epidemiological Analysis.

Stud Health Technol Inform 2020 Jun;270:233-237

Department of Health Services Research, Carl von Ossietzky University Oldenburg, Oldenburg, Germany.

Cancer risks may be influenced by local exposures such as working conditions or nuclear waste repositories. To find influences, local accumulations of cancer rates are used, for which finely granulated data should be utilized. In particular, high-resolution demographic data for a reference population are important, but often not available for data protection reasons. Therefore, estimation methods are necessary to approximate small-scale demographic data as accurately as possible. This paper presents an approach to project existing epidemiological and public data to a common granularity with respect to attribute characteristics such as place of residence, age or smoking status to allow for analyses such as local accumulations and consistently falls below an average relative error of 5%.
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June 2020

Acromegaly, inflammation and cardiovascular disease: a review.

Rev Endocr Metab Disord 2020 12;21(4):547-568

Department of Internal Medicine, Radboud University Medical Center Nijmegen, Geert Grooteplein Zuid 10, 6525, GA, Nijmegen, The Netherlands.

Acromegaly is characterized by Growth Hormone (GH) and Insulin-like Growth Factor 1 (IGF-1) excess. Uncontrolled acromegaly is associated with a strongly increased risk of cardiovascular disease (CVD), and numerous cardiovascular risk factors remain present after remission. GH and IGF-1 have numerous effects on the immune and cardiovascular system. Since endothelial damage and systemic inflammation are strongly linked to the development of CVD, and have been suggested to be present in both controlled as uncontrolled acromegaly, they may explain the presence of both micro- and macrovascular dysfunction in these patients. In addition, these changes seem to be only partially reversible after remission, as illustrated by the often reported presence of endothelial dysfunction and microvascular damage in controlled acromegaly. Previous studies suggest that insulin resistance, oxidative stress, and endothelial dysfunction are involved in the development of CVD in acromegaly. Not surprisingly, these processes are associated with systemic inflammation and respond to GH/IGF-1 normalizing treatment.
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December 2020

Voice Characteristics in Patients with Acromegaly during Treatment.

J Voice 2020 Jan 28. Epub 2020 Jan 28.

Department of Internal Medicine, Division of Endocrinology, Radboud University Medical Center, Nijmegen, The Netherlands.

Background: Active acromegaly is characterized by Growth Hormone and Insulin-like Growth Factor (IGF)-1 excess. Voice complaints are common in active acromegaly and are suggested to be caused by effects of Growth Hormone or IGF-1 on vocal cords and the surrounding soft tissues. Prospective studies on the course of voice characteristics in acromegaly patients are scarce and results are conflicting. This study investigates objective changes in voice parameters, self-reported perception of voice and laryngostroboscopic features during the first 2.5 years of acromegaly treatment.

Material And Method: In this prospective study, acoustic voice analysis (and videolaryngostroboscopic examination were performed in 27 consecutive treatment-naive acromegaly patients at diagnosis (T), after 1 year (T) and after 2.5 years (T) of treatment. The voice handicap index (VHI-30) questionnaire was taken.

Results: During acromegaly treatment, VHI scores decreased, and mucosal edema & hypertrophy diminished. No significant changes in objective voice parameters were detected. The within-subject change in serum IGF-1 levels (97.3 (40.6-208) to 22.4 (10.2-34.1) nmol/L (P < 0.001)) during follow-up correlated positively with the changes in VHI questionnaire scores (R 0.32-0.45; P = 0.002-0.03).

Conclusions: At diagnosis and during acromegaly treatment, mean VHI scores were in the normal range, although they decreased during follow-up. Mucosal edema and hypertrophy largely resolved during treatment. No significant changes in objective voice parameters were observed. Voice characteristics are in the normal range in patients with acromegaly, but may change during treatment. However, voice complaints are important to discuss, since they may influence quality of life.
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January 2020