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E P M Corssmit

Publications and source records attributed to E P M Corssmit.

15 recordsLinked to original sources
PubMed2007

Malignant paragangliomas associated with mutations in the succinate dehydrogenase D gene.

INTRODUCTION: Malignant paragangliomas have been well described in carriers of mutations of the succinate dehydrogenase B (SDHB) gene, but have rarely been associated with mutations in the succinate dehydrogenase D (SDHD) gene. AIM: The aim of the study was to report the different clinical expression patterns of malignant paragangliomas in five patients with SDHD (D92Y) mutations observed in approximately 200 SDHD (D92Y) mutation carriers followed in our institution. RESULTS: Metastasis and/or local tumor invasion was documented 0 (n=2), 1, 18, and 30 yr after the initial diagnosis of paraganglioma. Malignancy was proven by paraganglioma bone metastases (n=2), intrathoracic paraganglioma with lymph node metastases, locally invasive head-and-neck paraganglioma with destruction of the petrosal bone, and locally invasive paraganglioma of the bladder with lymph node metastases. Four of the five patients developed catecholamine excess during follow-up due to intraadrenal paraganglioma (pheochromocytoma) (n=1), extra adrenal paraganglioma (n=2), and presumed subclinical disease (n=1). CONCLUSION: SDHD mutations (D92Y) are associated with malignant paragangliomas and catecholamine excess with remarkable interindividual variations despite the same mutation. We estimate that the prevalence of malignancy in carriers of D92Y mutations is at least 2.5%.

Adrenal Gland Neoplasms↗
PubMed2006

Uncontrolled acromegaly is associated with progressive mitral valvular regurgitation.

INTRODUCTION: Recent cross-sectional studies have documented an association between acromegaly and regurgitant valvular heart disease. The aim of this study was to evaluate the change in prevalence of valvular heart disease in relation to the clinical activity, because the natural history of valvular changes in acromegaly is unknown. PATIENTS AND METHODS: Valvular regurgitation was assessed in 37 acromegalic patients (18 patients with active disease, and 19 with controlled disease) by conventional two-dimensional and Doppler echocardiography before and after an interval of 1.9 years (range 1.5-3.0 years). RESULTS: At baseline, valvular regurgitation (mitral and aortic sites combined) was present in 46% of the patients and increased to 67% at follow-up (P=0.008). Mitral regurgitation increased significantly from 32% to 60% (P=0.002), but no change was noted for the aortic valve (27% vs. 31%, NS). In patients with active disease, valvular regurgitation increased significantly from 56% at baseline to 88% at follow-up (P=0.031) due to a significant increase of mitral regurgitation from 39% to 78% at follow-up (P=0.016). In contrast, no increase in valvular regurgitation was found in patients with controlled disease. CONCLUSION: The prevalence of mitral, but not aortic, valvular regurgitation increased in patients with active acromegaly during follow-up. Patients with acromegaly require adequate cardiac evaluation and follow-up to establish the extent and progression of valvular involvement.

Acromegaly↗
PubMed2006

Ghrelin differentially affects hepatic and peripheral insulin sensitivity in mice.

AIMS/HYPOTHESIS: This study was conducted to evaluate the effects of ghrelin on insulin's capacity to suppress endogenous glucose production and promote glucose disposal in mice. To establish whether the growth hormone secretagogue (GHS) receptor can mediate the putative effect of ghrelin on the action of insulin, we also determined the metabolic effects of growth hormone releasing peptide 6 (GHRP-6), a specific GHS receptor agonist. In addition, we explored the biological significance of des-ghrelin (unacylated ghrelin) in this experimental context. MATERIALS AND METHODS: Vehicle (n=8), ghrelin (n=9), GHRP-6 (n=9), des-ghrelin (n=8) or a combination of des-ghrelin and ghrelin (n=7) were infused i.v. for 3 h. Simultaneously, endogenous glucose production and glucose disposal were measured by (14)C-glucose dilution during a hyperinsulinaemic-euglycaemic clamp. Tissue-specific glucose uptake in muscle and adipose tissue was measured using (3)H-2-deoxyglucose. RESULTS: During hyperinsulinaemia, glucose disposal was 31% higher in mice treated with ghrelin than in those treated with vehicle (77+/-16 and 59+/-8 micromol kg(-1) h(-1), respectively, p<0.05). This was in accordance with enhanced 2-deoxyglucose uptake in muscle in ghrelin-treated animals. In contrast, endogenous glucose production was less effectively suppressed by insulin during ghrelin infusion (46+/-22 vs 71+/-11% in controls, p<0.05). GHRP-6 did not affect insulin action. Des-ghrelin hampered insulin's capacity to inhibit endogenous glucose production, whereas it did not affect glucose disposal. The restraining effects of des-ghrelin and ghrelin on hepatic insulin action were abolished by simultaneous administration of both peptides. CONCLUSIONS/INTERPRETATION: Ghrelin hampers insulin's capacity to suppress endogenous glucose production, whereas it reinforces the action of insulin on glucose disposal, independently of food intake and body weight. These metabolic effects are unlikely to be mediated by the GHS receptor. Furthermore, simultaneous administration of des-ghrelin abolishes the inhibitory effect of ghrelin on hepatic insulin action.

Animals↗
PubMed2006

Quality of life in longterm exogenous subclinical hyperthyroidism and the effects of restoration of euthyroidism, a randomized controlled trial.

OBJECTIVE: The impact of prolonged subclinical hyperthyroidism on quality of life is unclear. Therefore, we evaluated quality of life in patients with differentiated thyroid carcinoma (DTC) on TSH-suppressive thyroxine therapy as a model for subclinical hyperthyroidism and we investigated whether restoration to euthyroidism affects quality of life. DESIGN: We performed a prospective, single-blinded, placebo-controlled, randomized trial of 6 months' duration with two parallel groups. PATIENTS AND METHODS: Twenty-four subjects with a history of differentiated thyroid carcinoma with > 10 years TSH-suppressive therapy with L-thyroxine completed the study. L-thyroxine dose was replaced by study medication containing L-thyroxine or L-thyroxine plus placebo. Medication was titrated to establish continuation of TSH suppression (low-TSH group) and euthyroidism (euthyroid group). Both groups consisted of 12 patients. We evaluated quality of life using five validated questionnaires. RESULTS: At baseline, the somatic disorder questionnaire (SDQ) indicated more somatic dysfunction in patients as compared with reference values, whereas the depression score (HADS) revealed a better score than the reference group. All other quality of life parameters were normal. At baseline, no significant differences between the low-TSH and the euthyroidism groups were observed. After 6 months, none of the quality of life parameters in the low-TSH group was different from baseline values. In the euthyroid group, motivation was significantly improved (Multidimensional Fatigue Index-20, P = 0.003), although this parameter did not differ from the reference group at baseline. A probable worsening in role limitations as a result of physical problems (Short Form-36; P = 0.050) was observed. No improvement in the SDQ score was observed. CONCLUSION: In summary, quality of life in patients with DTC and long-term subclinical hyperthyroidism in general is preserved. Restoration of euthyroidism in general does not affect quality of life.

Fatigue↗
PubMed2006

Glucose tolerance and lipid profile in longterm exogenous subclinical hyperthyroidism and the effects of restoration of euthyroidism, a randomised controlled trial.

OBJECTIVE: The impact of prolonged subclinical hyperthyroidism on glucose and lipid metabolism is unclear. Therefore, we evaluated glucose and lipid metabolism in patients with differentiated thyroid carcinoma (DTC) on TSH suppressive thyroxine therapy as a model for subclinical hyperthyroidism and investigated whether restoration to euthyroidism affects metabolism. DESIGN: We performed a prospective, single-blinded, placebo-controlled, randomised trial of 6 months duration with 2 parallel groups. PATIENTS: Twenty-five subjects with a history of differentiated thyroid carcinoma with > 10 years TSH-suppressive therapy with l-thyroxine completed the study. l-thyroxine dose was replaced by study medication containing l-thyroxine or l-thyroxine plus placebo. Medication was titrated to establish continuation of TSH suppression (low-TSH group, 13 patients) and euthyroidism (euthyroidism group, 12 patients). MEASUREMENTS: We evaluated glucose metabolism by glucose tolerance test and HOMA (IR) and lipid metabolism by lipid profile. In addition, we measured plasma concentrations of glucoregulatory hormones. RESULTS: At baseline, glucose tolerance, HOMA (IR), lipid profile and plasma concentrations of glucoregulatory hormones were within the normal range. No significant differences between the low TSH and euthyroidism group were observed. After 6 months, neither glucose nor lipid metabolism in the low TSH group were different from baseline values. CONCLUSION: In summary, glucose and lipid metabolism in patients with DTC and long-term subclinical hyperthyroidism in general are not affected. Restoration of euthyroidism in general does not affect glucose and lipid metabolism.

Adult↗
PubMed2006

Gut-brain axis: regulation of glucose metabolism.

Obesity and type II diabetes mellitus have reached epidemic proportions. From this perspective, knowledge about the regulation of satiety and food intake is more important than ever. The gut releases several peptides upon feeding, which affect hypothalamic pathways involved in the regulation of satiety and metabolism. Within the hypothalamus, there are complex interactions between many nuclei of which the arcuate nucleus is considered as one of the most important hypothalamic centres that regulates food intake. The neuropeptides, which are present in the hypothalamus and are involved in regulating food intake, also play a key role in regulating glucose metabolism and energy expenditure. In synchrony with the effects of those neuropeptides, gastrointestinal hormones also affect glucose metabolism and energy expenditure. In this review, the effects of the gastrointestinal hormones ghrelin, cholecystokinin, peptide YY, glucagon-like peptide, oxyntomodulin and gastric inhibitory polypeptide on glucose and energy metabolism are reviewed. These gut hormones affect glucose metabolism at different levels: by altering food intake and body weight, and thereby insulin sensitivity; by affecting gastric delay and gut motility, and thereby meal-related fluctuations in glucose levels; by affecting insulin secretion, and thereby plasma glucose levels, and by affecting tissue specific insulin sensitivity of glucose metabolism. These observations point to the notion of a major role of the gut-brain axis in the integrative physiology of whole body fuel metabolism.

Appetite Regulation↗
PubMed2006

GH deficiency in patients irradiated for acromegaly: significance of GH stimulatory tests in relation to the 24 h GH secretion.

BACKGROUND: Radiotherapy for pituitary adenomas frequently leads to GH deficiency (GHD). The characteristics of GH secretion in GHD induced by postoperative radiotherapy for acromegaly are not known. HYPOTHESIS: In the long term, stimulated and spontaneous GH release is not different between patients with GHD treated by postoperative radiotherapy for acromegaly or for other pituitary adenomas. DESIGN/SUBJECTS: We compared the characteristics of basal and stimulated GH secretion in patients with GHD, who had previously received adjunct radiotherapy after surgery for GH-producing adenomas (n=10) vs for other pituitary adenomas (n=10). All patients had a maximal GH concentration by insulin tolerance test (ITT) of 3 microg/l or less, compatible with severe GHD. Mean time after radiation was 17 and 18.7 years, respectively. Stimulated GH release was also evaluated by infusion of growth hormone-releasing hormone (GHRH), GHRH-arginine and arginine, and spontaneous GH by 10 min blood sampling for 24 h. Pulse analyses were performed by Cluster and approximate entropy. OUTCOMES: There were no differences between both patient groups in stimulated GH concentrations in any test. Spontaneous GH secretion was not different between both patient groups, including basal GH release, pulsatility and regularity. Pulsatile secretion was lost in two acromegalic and three non-acromegalic patients. Insulin-like growth factor-I (IGF-I) was below -2 s.d. score in nine patients in each group. CONCLUSION: Acromegalic patients treated by surgery and postoperative radiotherapy with an impaired response to the ITT do not differ, in the long term, in GH secretory characteristics from patients treated similarly for other pituitary tumors with an impaired response to the ITT. The ITT (or the GHRH-arginine test) is therefore reliable in establishing the diagnosis of GHD in patients treated for acromegaly by surgery and radiotherapy.

Acromegaly↗
PubMed2005

Reversible diastolic dysfunction after long-term exogenous subclinical hyperthyroidism: a randomized, placebo-controlled study.

BACKGROUND: Subclinical hyperthyroidism has been reported to affect systolic and diastolic cardiac function. However, the reversibility of these effects is not well established. OBJECTIVE: Our objective was to investigate the presence and reversibility of cardiac abnormalities in patients with long-term exogenous subclinical hyperthyroidism. DESIGN: We conducted a prospective, single-blinded, placebo-controlled randomized trial of 6 months duration with two parallel groups. SETTING: The study occurred at the Leiden University Medical Center, a tertiary referral center for thyroid carcinoma. PATIENTS: As a model for subclinical hyperthyroidism, 25 patients with a history of differentiated thyroid carcinoma with more than 10 yr of TSH suppressive therapy with L-T4 were studied. INTERVENTIONS: L-T4 dose was replaced by study medication containing L-T4 or placebo. Medication was titrated in a single-blinded fashion to establish continuation of TSH suppression (low-TSH group) or euthyroidism (euthyroid group). MEASUREMENTS: We assessed serum levels of free T4 and TSH and used echo Doppler cardiography including tissue Doppler to establish left ventricular (LV) dimensions and function as well as diastolic function. Baseline echocardiography data were compared with 24 controls. RESULTS: There were no differences in baseline cardiac parameters and TSH levels between the two groups. Although mean LV mass index was increased as compared with 24 controls, only four patients had LV hypertrophy at baseline. This was not improved by restoration of euthyroidism. At baseline, diastolic function was impaired in all patients as indicated by abnormal values for the peak flow of the early filling phase (E, 55.3 +/- 9.5 mm/sec), the ratio of E and the peak flow of the atrial filling phase (E/A ratio, 0.87 +/- 0.13), the early diastolic velocity obtained by tissue Doppler (E', 5.7 +/- 1.3 cm/sec), and the peak atrial filling velocity obtained by tissue Doppler (A', 6.8 +/- 1.4 cm/sec), prolonged E deceleration time (234 +/- 34 msec), and isovolumetric relaxation time (121 +/- 15 msec). After 6 months, significant improvements were observed in the euthyroid group in the E/A ratio (+41%; P < 0.001), E deceleration time (-18%; P = 0.006), isovolumetric relaxation time (-25%; P < 0.001), E' (+31%; P < 0.001), and the E'/A' ratio (+40%; P < 0.001). CONCLUSIONS: We conclude that prolonged subclinical hyperthyroidism is accompanied by diastolic dysfunction that is at least partly reversible after restoration of euthyroidism. Because isolated diastolic dysfunction may be associated with increased mortality, this finding is of clinical significance.

Adult↗
PubMed2005

High fat diet induced hepatic insulin resistance is not related to changes in hypothalamic mRNA expression of NPY, AgRP, POMC and CART in mice.

The hypothalamic circuitry, apart from its impact on food intake, modulates insulin sensitivity to adapt metabolic conditions in the face of environmental fluctuations in nutrient availability. The purpose of the present study was to investigate the effects of 2 weeks high fat feeding in wildtype mice on (1) insulin sensitivity and triglyceride accumulation in liver and muscle in relation to (2) mRNA expression levels of Neuropeptide Y (NPY), Agouti-related protein (AgRP), pro-opiomelanocortin (POMC), and cocaine- and amphetamine-regulated transcript (CART) in the hypothalamus. Two weeks of high fat feeding induced hepatic insulin resistance in the presence of increased hepatic triglyceride accumulation. In muscle, however, 2 weeks of high fat feeding did not result in changes in insulin sensitivity or in triglyceride content. mRNA expression levels of NPY, AgRP, POMC, and CART in the hypothalamus were not different between the groups. This study shows that 2 weeks of high fat feeding in mice does not affect mRNA expression levels of NPY, AgRP, POMC or CART, in the whole hypothalamus, despite induction of hepatic, but not peripheral, insulin resistance. Therefore, a major physiological role of these neuroendocrine factors in the induction of hepatic insulin resistance during a high fat diet seems less likely.

Animals↗
PubMed2005

Intracerebroventricular administration of melanotan II increases insulin sensitivity of glucose disposal in mice.

AIMS/HYPOTHESIS: The present study was conducted to evaluate the effects of central administration of melanotan II (MTII), a melanocortin-3/4 receptor agonist, on hepatic and whole-body insulin sensitivity, independent of food intake and body weight. METHODS: Over a period of 24 h, 225 ng of MTII was injected in three aliquots into the left lateral ventricle of male C57Bl/6 mice. The animals had no access to food. The control group received three injections of distilled water. Whole-body and hepatic insulin sensitivity were measured by hyperinsulinaemic-euglycaemic clamp in combination with [(3)H]glucose infusion. Glut4 mRNA expression was measured in skeletal muscle. RESULTS: Plasma glucose and insulin concentrations under basal and hyperinsulinaemic conditions were similar in MTII- and placebo-treated mice. Endogenous glucose production (EGP) and glucose disposal in the basal state were significantly higher in MTII-treated mice than in the control group (71+/-22 vs 43+/-12 micromol.min(-1).kg(-1), p<0.01). During hyperinsulinaemia, glucose disposal was significantly higher in MTII-treated mice (151+/-20 vs 108+/-20 micromol.min(-1).kg(-1), p<0.01). In contrast, the inhibitory effect of insulin on EGP was not affected by MTII (relative decrease in EGP: 45+/-27 vs 50+/-20%). Glut4 mRNA expression in skeletal muscle was significantly increased in MTII-treated mice (307+/-94 vs 100+/-56%, p<0.01). CONCLUSIONS/INTERPRETATION: Intracerebroventricular administration of MTII acutely increases insulin-mediated glucose disposal but does not affect the capacity of insulin to suppress EGP in C57Bl/6 mice. These data indicate that central stimulation of melanocortin-3/4 receptors modulates insulin sensitivity in a tissue-specific manner, independent of its well-known impact on feeding and body weight.

Animals↗
PubMed2005

Increased prevalence of catecholamine excess and phaeochromocytomas in a well-defined Dutch population with SDHD-linked head and neck paragangliomas.

OBJECTIVE: The aim of this study was to identify the prevalence of catecholamine excess and phaeochromocytomas in a well-defined population of people with hereditary head and neck paragangliomas. METHODS: We studied in a prospective follow-up protocol all consecutive patients referred to the Department of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands with documented head and neck paragangliomas and either a positive family history for paragangliomas or a proven SDHD gene mutation. Initial analysis included medical history, physical examination and the measurement of excretion of catecholamines in two 24-h urine collections. In the case of documented catecholamine excess iodinated meta-iodobenzylguanidine (123I-MIBG) scintigraphy and magnetic resonance imaging were done. RESULTS: Between 1988 and 2003, 40 consecutive patients (20 male and 20 female) with documented head and neck paragangliomas were screened. Biochemical screening revealed urinary catecholamine excess in 15 patients (37.5%). In nine of these 15 patients a lesion was found by 123I-MIBG scintigraphy. Exact localization by magnetic resonance imaging revealed phaeochromocytomas in seven of the 15 patients. One of the nine patients had an extra-adrenal paraganglioma. Histopathological examination in a subset of tumors displayed loss of heterozygosity of the wild-type SDHD allele in all cases. CONCLUSIONS: The prevalence of catecholamine excess (37.5%) and phaeochromocytomas (20.0%) is high in patients with familial head and neck paragangliomas. Therefore, patients with hereditary head and neck paragangliomas require lifelong follow up by biochemical testing for catecholamine excess.

Adrenal Gland Neoplasms↗
PubMed2004

Pituitary magnetic resonance imaging is not required in the postoperative follow-up of acromegalic patients with long-term biochemical cure after transsphenoidal surgery.

After successful transsphenoidal surgery for acromegaly, life-long follow-up is required, because 10-15% of patients develop recurrence of disease. We assessed whether it is safe to perform postoperative follow-up with only biochemical evaluation in acromegalic patients initially cured by transsphenoidal surgery. We studied 32 patients cured after transsphenoidal surgery for acromegaly during a follow-up of 8.7 +/- 6.4 yr (mean +/- sd). Serial measurements of serum GH during glucose tolerance test and magnetic resonance imaging (MRI) scans were performed. Serial MRI scans were reevaluated by three independent neuroradiologists, who were blinded for the clinical and biochemical data, for growth of suspected tumor tissue. Twenty-three patients remained biochemically cured in the long term, whereas nine of the 32 patients developed recurrence of disease, indicated by elevated serum GH concentrations during glucose tolerance test and clinical symptoms/signs. None of the 23 patients with long-term biochemical cure showed growth of tumor tissue according to two neuroradiologists, whereas the third neuroradiologist assessed three of 23 patients as having tumor growth despite continuing biochemical cure. In the nine patients with biochemical recurrence, no tumor growth was found in the series of postoperative MRI scans, according to two of the three independent radiologists, whereas the third radiologist found tumor growth in four patients with recurrent disease. In conclusion, in patients with acromegaly, initially cured by transsphenoidal surgery, it appears safe to check for recurrent disease during long-term follow-up of these patients by biochemical markers only.

Acromegaly↗
PubMed2004

Octreotide long-acting repeatable and lanreotide Autogel are equally effective in controlling growth hormone secretion in acromegalic patients.

OBJECTIVE: Recently a new depot preparation of the long-acting somatostatin analogue, lanreotide Autogel was introduced for the treatment of acromegaly. Like octreotide long-acting repeatable (LAR), it has high binding affinity for the somatostatin receptor subtype SSTR 2 and less binding affinity for SSTR 5. We hypothesized that the ability to suppress growth hormone (GH) secretion in patients with acromegaly would be similar for these depot preparations. PATIENTS AND STUDY DESIGN: Seven patients (mean age+/-S.E.M. 48.4+/-7 years) on long-term octreotide LAR treatment at a monthly injection interval for a mean of 2.8 years were enrolled in the study. They underwent a GH secretory profile study with 10 min sampling for 24 h, 28 days after an injection. At 2, 4 and 6 weeks after the next injection fasting GH profiles (every 30 min for 3.5 h) and serum IGF-I measurements were measured. These investigations were repeated 12 months later, when the patients were on an individually titrated stable dose of lanreotide Autogel. RESULTS: Secretory characteristics and total 24 h GH secretion, estimated by deconvolution analysis of the 10 min 24 h plasma GH concentrations, did not show differences between these two long-acting somatostatin analogues. Both drugs were equally effective in GH and IGF-I suppression as measured at 2, 4 and also at 6 weeks following an injection. CONCLUSION: The efficacy of lanreotide Autogel and octreotide LAR was equal, notwithstanding that these drugs are administered in a different way and have different pharmacokinetics.

Acromegaly↗
PubMed2003

Outcome of palliative embolization of bone metastases in differentiated thyroid carcinoma.

We investigated the effects of selective embolization in patients with symptomatic bone metastases of differentiated thyroid carcinoma. A total of 41 embolizations was performed in 16 patients. We studied the follow-up (range, 2 months to 8.6 yr) after the first embolization by evaluation of clinical symptoms and tumor dimensions. Success was defined as an improvement in clinical symptoms without tumor progression. The procedure was successful in 24 of 41 occasions (59%). Twenty-six embolizations were preceded or followed up by additional therapies, consisting of surgery (laminectomy), external irradiation, or radioiodine. Subgroup analysis revealed that these additional therapies did not influence the success rate; however, a potential effect on success duration may be present: for embolizations without additional radioiodine or external irradiation therapy, the median success duration was 6.5 months; for embolizations combined with additional radioiodine or external irradiation, this was 15 months (P = 0.0146). The ultimate outcome of the patients was unfavorable: nine patients died and five patients have progressive disease. We concluded that selective embolization of bone metastases may be considered a palliative therapy that may induce rapid, but transient, relief of symptoms. Combination with radioiodine or external irradiation may prolong the duration of success.

Adenocarcinoma, Follicular↗