Cardiovascular risk and glucocorticoids:a Dutch National Registry of growth hormone treatment in adults with growth hormone deficiency analysis

Purpose: Patients with hypopituitarism are at increased cardiovascular risk, in part because of growth hormone deficiency (GHD), but probably also because of the overuse of glucocorticosteroids in concomitant adrenal insufficiency (AI). We hypothesized that patients with hypopituitarism that were on glucocorticosteroid replacement therapy for concomitant AI would have worse cardiovascular outcomes than those without. Methods: Retrospective nationwide cohort study. GHD patients from the Dutch National Registry of Growth Hormone Treatment in adults were grouped by the presence (AI; N = 1836) or absence (non-AI; N = 750) of concomitant AI, and differences between groups were analyzed for baseline characteristics and cardiovascular risk, at baseline and during GHRT. Results: At baseline, AI patients had higher levels of total and LDL cholesterol (both p &lt; 0.01). During GHRT, AI patients were more likely to use cardiovascular drugs (p ≤ 0.01), but we did not find worse outcomes for blood pressure, body composition, lipid and glucose metabolism. The risk of developing peripheral arterial disease (HR 2.22 [1.06–4.65]) and non-fatal cerebrovascular events (HR 3.47 [1.60–7.52]) was higher in AI patients, but these differences disappeared in the models adjusted for baseline differences. Conclusion: We found no clear evidence to support our hypothesis that patients with hypopituitarism and concomitant AI have worse cardiovascular outcomes than non-AI patients. This suggests that glucocorticoid replacement therapy in AI may be safer than previously thought. However, cardiovascular burden, events and medication use at baseline and during GHRT (in unadjusted models) were higher in AI; so the lack of power, the important role of (adjusting for) other risk factors, and the inability to distinguish between glucocorticoid treatment regimens may have influenced the outcomes.</p

Innovation Across Cultures: Connecting Leadership, Identification, and Creative Behavior in Organizations

Innovation is considered essential for today's organizations to survive and thrive. Researchers have also stressed the importance of leadership as a driver of followers' innovative work behavior (FIB). Yet, despite a large amount of research, three areas remain understudied: (a) The relative importance of different forms of leadership for FIB; (b) the mechanisms through which leadership impacts FIB; and (c) the degree to which relationships between leadership and FIB are generalizable across cultures. To address these lacunae, we propose an integrated model connecting four types of positive leadership behaviors, two types of identification (as mediating variables), and FIB. We tested our model in a global data set comprising responses of N = 7,225 participants from 23 countries, grouped into nine cultural clusters. Our results indicate that perceived LMX quality was the strongest relative predictor of FIB. Furthermore, the relationships between both perceived LMX quality and identity leadership with FIB were mediated by social identification. The indirect effect of LMX on FIB via social identification was stable across clusters, whereas the indirect effects of the other forms of leadership on FIB via social identification were stronger in countries high versus low on collectivism. Power distance did not influence the relations

Identity Leadership, Employee Burnout and the Mediating Role of Team Identification: Evidence from the Global Identity Leadership Development Project

Do leaders who build a sense of shared social identity in their teams thereby protect them from the adverse effects of workplace stress? This is a question that the present paper explores by testing the hypothesis that identity leadership contributes to stronger team identification among employees and, through this, is associated with reduced burnout. We tested this model with unique datasets from the Global Identity Leadership Development (GILD) project with participants from all inhabited continents. We compared two datasets from 2016/2017 (n = 5290; 20 countries) and 2020/2021 (n = 7294; 28 countries) and found very similar levels of identity leadership, team identification and burnout across the five years. An inspection of the 2020/2021 data at the onset of and later in the COVID-19 pandemic showed stable identity leadership levels and slightly higher levels of both burnout and team identification. Supporting our hypotheses, we found almost identical indirect effects (2016/2017, b = −0.132; 2020/2021, b = −0.133) across the five-year span in both datasets. Using a subset of n = 111 German participants surveyed over two waves, we found the indirect effect confirmed over time with identity leadership (at T1) predicting team identification and, in turn, burnout, three months later. Finally, we explored whether there could be a “too-much-of-a-good-thing” effect for identity leadership. Speaking against this, we found a u-shaped quadratic effect whereby ratings of identity leadership at the upper end of the distribution were related to even stronger team identification and a stronger indirect effect on reduced burnout

The first Dutch SDHB founder deletion in paraganglioma – pheochromocytoma patients

Contains fulltext : 81280.pdf (publisher's version ) (Open Access)BACKGROUND: Germline mutations of the tumor suppressor genes SDHB, SDHC and SDHD play a major role in hereditary paraganglioma and pheochromocytoma. These three genes encode subunits of succinate dehydrogenase (SDH), the mitochondrial tricarboxylic acid cycle enzyme and complex II component of the electron transport chain. The majority of variants of the SDH genes are missense and nonsense mutations. To date few large deletions of the SDH genes have been described. METHODS: We carried out gene deletion scanning using MLPA in 126 patients negative for point mutations in the SDH genes. We then proceeded to the molecular characterization of deletions, mapping breakpoints in each patient and used haplotype analysis to determine whether the deletions are due to a mutation hotspot or if a common haplotype indicated a single founder mutation. RESULTS: A novel deletion of exon 3 of the SDHB gene was identified in nine apparently unrelated Dutch patients. An identical 7905 bp deletion, c.201-4429_287-933del, was found in all patients, resulting in a frameshift and a predicted truncated protein, p.Cys68HisfsX21. Haplotype analysis demonstrated a common haplotype at the SDHB locus. Index patients presented with pheochromocytoma, extra-adrenal PGL and HN-PGL. A lack of family history was seen in seven of the nine cases. CONCLUSION: The identical exon 3 deletions and common haplotype in nine patients indicates that this mutation is the first Dutch SDHB founder mutation. The predominantly non-familial presentation of these patients strongly suggests reduced penetrance. In this small series HN-PGL occurs as frequently as pheochromocytoma and extra-adrenal PGL

Clostridium perfringens septicaemia with massive intravascular haemolysis: A case report and review of the literature

We describe the case of a 74-year-old man with cholangitis, complicated by Clostridium perfringens septicaemia and massive intravascular haemolysis. Clostridium perfringens septicaemia is a rare but well-known cause of massive intravascular haemolysis. Here we review 40 similar cases published since 1990. Most cases involve immunocompromised patients with underlying haematological disorder (22.5%), pancreatic or gastric cancer (12.5%) and/or diabetes (30.0%). Focus of infection is mostly hepatobiliary (45.0%), intestinal or gynaecological after invasive procedure. Eighty percent of reviewed cases did not survive; the median time between admission and death was only eight hours. If an attempt was made to remove the focus of infection (i.e. by drainage of liver abscess, cholecystectomy, hysterectomy or ER CP), this proved to be a strong prognostic indicator of survival. However, in many of the cases the patient had already gone into shock or died before a diagnosis could be made. In severely ill patients with fever and haemolysis on the emergency department Clostridium perfringens septicaemia should always be considered, since early antibiotic treatment and if possible removal of the focus of infection can rescue patients from an otherwise fatal outcome

Effect of low-normal and high-normal IGF-1 levels on memory and wellbeing during growth hormone replacement therapy: A randomized clinical trial in adult growth hormone deficiency

BACKGROUND: The aim of the present study was to investigate the effect of low-normal and high-normal levels of IGF-1 in growth hormone (GH) deficient adults on cognition and wellbeing during GH treatment. METHODS: A randomized, open-label, clinical trial including 32 subjects receiving GH therapy for at least 1 year. Subjects were randomized to receive either a decrease (IGF-1 target level of - 2 to - 1 SDS) or an increase of their daily GH dose (IGF-1 target level of 1 to 2 SDS) for a period of 24 weeks. Memory was measured by the Cambridge Neuropsychological Test Automated Battery, selecting the Pattern Recognition Memory task and the Spatial Working Memory. Wellbeing was measured as mood by the Profile of Moods States questionnaire, and quality of life by the Nottingham Health Profile and QoL Assessment in GH Deficiency in Adults questionnaires. RESULTS: Data from 30 subjects (65.6% male, mean age 46.6 (9.9 SD) years), who fulfilled the target levels, were analyzed. Females in the low dose treatment arm were found to have a better working memory and a better strategic memory control after 24 weeks as opposed to the females in the high treatment arm. With respect to mood, the decrease in IGF-1 levels in females within the low treatment arm was associated with more fatigue and less vigor. CONCLUSIONS: The adjustment of GH dose in female patients seems to have a narrow window. A dose too high may impair prefrontal cognitive functioning, while a dose too low may result in decreased vigor

Personalized approach to growth hormone replacement in adults

Growth hormone (GH) deficiency (GHD) in adults is well-characterized and includes abnormal body composition, reduced bone mass, an adverse cardiovascular risk profile, and impaired quality of life. In the early 1990s, it was also shown that patients with hypopituitarism without GH replacement therapy (GHRT) had excess mortality.Today, GHRT has been shown to decrease or reverse the negative effects of GHD. In addition, recent papers have shown that mortality and morbidity are approaching normal in hypopituitary patients with GHD who receive modern endocrine therapy including GHRT. Since the first dose-finding studies, it has been clear that efficacy and side effects differ substantially between patients. Many factors have been suggested as affecting responsiveness, such as sex, age, age at GHD onset, adherence, and GH receptor polymorphisms, with sex and sex steroid replacement having the greatest impact. Therefore, the individual tailoring of GH dose is of great importance to achieve sufficient efficacy without side effects. One group that stands out is women receiving oral estrogen replacement, who needs the highest dose. Serum insulin-like growth factor-1 (IGF-1) is still the most used biochemical biomarker for GH dose titration, although the best serum IGF-1 target is still debated. Patients with GHD due to acromegaly, Cushing’s disease, or craniopharyngioma experience similar effects from GHRT as others

Cardiovascular risk profile in growth hormone-treated adults with craniopharyngioma compared to non-functioning pituitary adenoma: a national cohort study

Context: Cardiovascular (CV) risk profile might differ between growth hormone-treated patients with craniopharyngioma and non-functioning pituitary adenoma (NFPA), since patients with craniopharyngioma more frequently suffer from hypothalamic metabolic disruption. Objective: The aim of this study is to investigate the CV risk profile in adult patients with craniopharyngioma compared to NFPA before and after treatment with growth hormone (GH) replacement therapy due to severe GH deficiency. Design: A sub-analysis of the Dutch National Registry of Growth Hormone Treatment in Adults was performed, in which we compared 291 patients with craniopharyngioma to 778 patients with NFPA. CV risk profile and morbidity were evaluated at baseline and during long-term follow-up within and between both groups. Results: At baseline, patients with craniopharyngioma demonstrated higher BMI than patients with NFPA, and men with craniopharyngioma showed greater waist circumference and lower HDL compared to men with NFPA. During follow-up, BMI, as well as diastolic blood pressure among patients using antihypertensive drugs, deteriorated in the craniopharyngioma group compared to the NFPA group. Lipid profile improved similarly in both groups over time. No differences were found between groups in the occurrence of diabetes mellitus, cerebrovascular accidents, CV disease, or overall mortality. Conclusion: This study suggests that overall CV risk profile is worse in craniopharyngioma patients with GH deficiency compared to patients with NFPA. During GH replacement therapy, patients with craniopharyngioma demonstrated an increase in BMI over time, where BMI remained stable in patients with NFPA. Also, diastolic blood pressure did not improve with antihypertensive drugs in craniopharyngioma patients as seen in patients with NFPA