Germline mutations in succinate dehydrogenase (SDH) genes predispose carriers for developing paragangliomas, and studies on their quality of life (QoL) are scarce.
The objectives of this study were ...to assess QoL in patients with paragangliomas (PGL), to evaluate long-term QoL, and to explore potential differences in QoL between SDH mutation carriers and paraganglioma patients without an SDH mutation.
Cross-sectional, case-control study.
Tertiary referral center.
ONE HUNDRED AND SEVENTY FOUR PARAGANGLIOMA PATIENTS WERE INCLUDED: 25 SDHB, two SDHC, and 122 SDHD mutation carriers and 25 patients without an SDH mutation. They provided 100 peers as control persons. Furthermore, patients were compared with age-adjusted reference populations.
QOL WAS ASSESSED USING THREE VALIDATED HEALTH-RELATED QOL QUESTIONNAIRES: the Hospital Anxiety and Depression Scale, the Multidimensional Fatigue Index 20, and the Short Form 36.
Patients reported a significantly impaired QoL compared with their own controls, mainly on fatigue and physical condition subscales. Compared with age-adjusted literature values, patients had significantly impaired scores on physical, psychological, and social subscales. A decreased QoL was mainly related to paraganglioma-associated complaints. There was no difference in QoL between the various SDH mutation carriers or paraganglioma patients without an SDH mutation. QoL in asymptomatic mutation carriers, i.e. without manifest disease, did not differ from QoL of the general population. Long-term results in 41 patients showed no alteration in QoL besides a reduced level of activity.
QoL is decreased in paraganglioma patients but stable when measured over time.
The impact of childhood differentiated thyroid carcinoma (DTC) on psychosocial development has not yet been studied. The aim of this study was to evaluate the achievement of psychosocial ...developmental milestones in long-term survivors of childhood DTC.
Survivors of childhood DTC diagnosed between 1970 and 2013 were included. Reasons for exclusion were age <18 or >35 years at follow-up, a follow-up period <5 years or diagnosis with DTC as a second malignant neoplasm. Survivors gathered peer controls of similar age and sex (
= 30). A comparison group non-affected with cancer (
= 508) and other childhood cancer survivors (CCS) were also used to compare psychosocial development. To assess the achievement of psychosocial milestones (social, autonomy and psychosexual development), the course of life questionnaire (CoLQ) was used.
We included 39 survivors of childhood DTC (response rate 83.0%, mean age at diagnosis 15.6 years, and mean age at evaluation 26.1 years). CoLQ scores did not significantly differ between survivors of childhood DTC and the two non-affected groups. CoLQ scores of childhood DTC survivors were compared to scores of other CCS diagnosed at similar ages (
= 76). DTC survivors scored significantly higher on social development than other CCS, but scores were similar on autonomy and psychosexual developmental scales.
Survivors of childhood DTC showed similar development on social, autonomy, and psychosexual domains compared to non-affected individuals. Social development was slightly more favorable in DTC survivors than in other CCS, but was similar on autonomy and psychosexual domains.
Mutations in SDHD and SDHAF2 (both located on chromosome 11) give rise to hereditary paraganglioma almost exclusively after paternal transmission of the mutation, and tumours often show loss of the ...entire maternal copy of chromosome 11. The 'Hensen' model postulates that a tumour modifier gene located on chromosome 11p15, a region known to harbour a cluster of imprinted genes, is essential to tumour formation. We observed decreased protein expression of the 11p15 candidate genes CDKN1C, SLC22A18 and ZNF215 evaluated in 60 SDHD-mutated tumours compared to normal carotid body tissue and non-SDH mutant tumours.We then created stable knockdown in vitro models, reasoning that the simultaneous knockdown of SDHD and a maternally expressed 11p15 modifier gene would enhance paraganglioma-related cellular characteristics compared to SDHD knockdown alone. Knockdown of SDHD in SNB19 and SHSY5Y cells resulted in the accumulation of succinate, the stabilization of HIF1 protein and a reduction in cell proliferation.Compared to single knockdown of SDHD, knockdown of SDHD together with SLC22A18 or with CDKN1C led to small but significant increases in cell proliferation and resistance to apoptosis, and to a gene expression profile closely related to the known transcriptional profile of SDH-deficient tumours. Of the 60 SDHD tumours investigated, four tumours showing retention of chromosome 11 showed SLC22A18 and CDKN1C expression levels comparable to levels in tumours showing loss of chromosome 11, suggesting loss of protein expression despite chromosomal retention.Our data strongly suggest that SLC22A18 and/or CDKN1C are tumour modifier genes involved in the tumourigenesis of SDHD-linked paraganglioma.
Purpose
Tumors in the carotid bodies may interfere with their function as peripheral chemoreceptors. An altered control of ventilation may predispose to sleep-disordered breathing. This study aimed ...to assess whether patients with unilateral or bilateral carotid body tumors (uCBT or bCBT, respectively) or bilateral CBT resection (bCBR) display sleep-disordered breathing and to evaluate the global contribution of the peripheral chemoreceptor to the hypercapnic ventilatory response.
Methods
Eight uCBT, eight bCBT, and nine bCBR patients and matched controls underwent polysomnography. The peripheral chemoreflex drive was assessed using euoxic and hyperoxic CO
2
rebreathing tests. Daytime sleepiness and fatigue were assessed with the Epworth Sleepiness Scale and the Multidimensional Fatigue Index.
Results
All patient groups reported significant fatigue-related complaints, but no differences in excessive daytime sleepiness (EDS) were found. The apnea/hypopnea index (AHI) did not differ significantly between patient groups and controls. Only in bCBT patients, a trend towards a higher AHI was observed, but this did not reach significance (
p
= 0.06). No differences in the peripheral chemoreflex drive were found between patients and controls.
Conclusions
Patients with (resection of) CBTs have more complaints of fatigue but are not at risk for EDS. The presence or resection of CBTs is neither associated with an altered peripheral chemoreflex drive nor with sleep-disordered breathing.
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.
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)Hglucose infusion. Glut4 mRNA expression was measured in skeletal muscle.
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).
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.
Context:
Paraganglioma (PGL) patients and succinate dehydrogenase (SDH) gene mutation carriers at risk for PGLs have a decreased quality of life (QoL). QoL may be affected by the strategy an ...individual uses when dealing with a stressful situation, ie, specific coping styles. Understanding the various approaches to coping may allow the development of targeted interventions to improve patient QoL.
Objective:
The objective of the study was to assess coping styles in PGL patients and SDH mutation carriers.
Design:
This was a cross-sectional study.
Setting:
The study was conducted at a tertiary referral center.
Patients and Methods:
Coping styles were assessed using the Utrecht Coping List. The results from the study cohort were compared with a control group and data derived from the literature. Potential differences in coping styles between the various SDH mutation carriers and PGL patients without an SDH mutation were explored.
Results:
Of the 174 patients who responded, 122 were SDHD, 25 SDHB, and 2 SDHC mutation carriers. An additional 25 patients lacked an SDH mutation. They recruited 100 peers as controls. Compared with the general population, the study cohort was more avoidant of problems (P < .001) and reported less expression of emotion (P < .01). Compared with patients with other conditions, they sought more social support (P < .001). There were no significant differences in coping styles between the various categories of mutation carriers or PGL patients lacking a mutation.
Conclusions:
Coping styles of PGL patients and SDH mutation carriers differ from those of control and reference groups and include an avoidant coping style and a lack of emotional expression.
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.
Sporadic pheochromocytomas are detected by clinical signs and symptoms, whereas pheochromocytomas in patients with a known hereditary predisposition for these tumors are detected by repetitive ...screening for catecholamine excess.
To document the clinical, biochemical, and pathological differences between patients with sporadic pheochromocytomas, detected by signs and symptoms and patients with pheochromocytomas, detected by biochemical screening in established hereditary syndromes.
Retrospective follow-up study.
We included 60 consecutive patients diagnosed with pheochromocytoma (pheochromocytomas detected by signs and symptoms: n=28 and pheochromocytomas detected by screening: n=32) in our center.
Patients with pheochromocytomas detected by screening presented with less complaints of diaphoresis (P<0.01), palpitations (P=0.01), paleness (P=0.01), nausea (P<0.01), and vomiting (P=0.01) compared with patients with symptomatic pheochromocytomas. Patients with pheochromocytomas detected by screening tended to be younger at the time of diagnosis (41+/-2 vs 47+/-3 years, P=0.07). In addition, patients with pheochromocytomas detected by screening had significantly lower rates of 24-h urinary catecholamine excretion, and considerably smaller tumors (3.7+/-0.5 vs 7.3+/-0.7 cm, P<0.01).
Pheochromocytomas detected by screening of patients with a hereditary predisposition have a much lower prevalence of signs and symptoms, lower catecholamine excess, and smaller tumors, compared with sporadic pheochromocytomas, detected by signs and symptoms. These data support the benefits of screening for pheochromocytomas in patients with hereditary syndromes predisposing for these tumors.
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.
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.
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.
The efficacy of lanreotide Autogel and octreotide LAR was equal, notwithstanding that these drugs are administered in a different way and have different pharmacokinetics.
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