| 1. |
- Abrahamsson, Niclas, et al.
(författare)
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Hypoglycemia in everyday life after gastric bypass and duodenal switch
- 2015
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 173:1, s. 91-100
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Tidskriftsartikel (refereegranskat)abstract
- Design: Gastric bypass (GBP) and duodenal switch (DS) in morbid obesity are accompanied by marked metabolic improvements, particularly in glucose control. In recent years, episodes of severe late postprandial hypoglycemia have been increasingly described in GBP patients; data in DS patients are scarce. We recruited three groups of subjects; 15 GBP, 15 DS, and 15 non-operated overweight controls to examine to what extent hypoglycemia occurs in daily life. Methods: Continuous glucose monitoring (CGM) was used during 3 days of normal activity. The glycemic variability was measured by mean amplitude of glycemic excursion and continuous overall net glycemic action. Fasting blood samples were drawn, and the patients kept a food and symptom log throughout the study. Results: The GBP group displayed highly variable CGM curves, and 2.9% of their time was spent in hypoglycemia (< 3.3 mmol/l, or 60 mg/dl). The DS group had twice as much time in hypoglycemia (5.9%) and displayed CGM curves with little variation as well as lower HbA1c levels (29.3 vs 35.9 mmol/mol, P < 0.05). Out of a total of 72 hypoglycemic episodes registered over the 3-day period, 70 (97%) occurred in the postprandial state and only about one-fifth of the hypoglycemic episodes in the GBP and DS groups were accompanied by symptoms. No hypoglycemias were seen in controls during the 3-day period. Conclusion: Both types of bariatric surgery induce marked, but different, changes in glucose balance accompanied by frequent, but mainly unnoticed, hypoglycemic episodes. The impact and mechanism of hypoglycemic unawareness after weight-reduction surgery deserves to be clarified.
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| 2. |
- Allen, D. B., et al.
(författare)
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GH safety workshop position paper: a critical appraisal of recombinant human GH therapy in children and adults
- 2016
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 174:2
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Tidskriftsartikel (refereegranskat)abstract
- Recombinant human GH (rhGH) has been in use for 30 years, and over that time its safety and efficacy in children and adults has been subject to considerable scrutiny. In 2001, a statement from the GH Research Society (GRS) concluded that 'for approved indications, GH is safe'; however, the statement highlighted a number of areas for on-going surveillance of long-term safety, including cancer risk, impact on glucose homeostasis, and use of high dose pharmacological rhGH treatment. Over the intervening years, there have been a number of publications addressing the safety of rhGH with regard to mortality, cancer and cardiovascular risk, and the need for long-term surveillance of the increasing number of adults who were treated with rhGH in childhood. Against this backdrop of interest in safety, the European Society of Paediatric Endocrinology (ESPE), the GRS, and the Pediatric Endocrine Society (PES) convened a meeting to reappraise the safety of rhGH. The ouput of the meeting is a concise position statement.
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| 3. |
- Almby, Kristina E., et al.
(författare)
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Effects of GLP-1 on counter-regulatory responses during hypoglycemia after GBP surgery
- 2019
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Ingår i: European Journal of Endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 181:2, s. 161-171
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim of the study was to explore the role of GLP-1 receptor activation on the counter-regulation and symptoms of hypoglycemia in subjects who have undergone gastric bypass surgery (GBP).Design: Experimental hyperinsulinemic–hypoglycemic clamp study.Methods: Twelve post-GBP subjects participated in a randomized cross-over study with two hyperinsulinemic, hypoglycemic clamps (glucose nadir 2.7 mmol/L) performed on separate days with concomitant infusions of the GLP-1 analog exenatide or with saline, respectively. Continuous measurements of metabolites and counter-regulatory hormones as well as assessments of heart rate variability and symptoms of hypoglycemia were performed throughout the clamps.Results: No effect of GLP-1 receptor activation on counter-regulatory hormones (glucagon, catecholamines, cortisol, GH) or glucose infusion rate was seen, but we found indications of a downregulation of the sympathetic relative to the parasympathetic nerve activity, as reflected in heart rate variability. No significant differences in symptom of hypoglycemia were observed.Conclusions/interpretation: Short-term exposure to a GLP-1 receptor agonist does not seem to impact the counter-regulatory hormonal and metabolic responses in post-GBP subjects during hypoglycemic conditions, suggesting that the improvement in symptomatic hypoglycemia post-GBP seen following treatment with GLP-1 receptor agonists may be mediated by mechanism not directly involved in counter-regulation.
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| 4. |
- Andela, C. D., et al.
(författare)
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MECHANISMS IN ENDOCRINOLOGY Cushing's syndrome causes irreversible effects on the human brain: a systematic review of structural and functional magnetic resonance imaging studies
- 2015
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 173:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cushing's syndrome (CS) is characterized by excessive exposure to cortisol, and is associated with both metabolic and behavioral abnormalities. Symptoms improve substantially after biochemical cure, but may persist during long-term remission. The causes for persistent morbidity are probably multi-factorial, including a profound effect of cortisol excess on the brain, a major target area for glucocorticoids. Objective: To review publications evaluating brain characteristics in patients with CS using magnetic resonance imaging (MRI). Methods: Systematic review of literature published in PubMed, Embase, Web of Knowledge, and Cochrane databases. Results: Nineteen studies using MRI in patients with CS were selected, including studies in patients with active disease, patients in long-term remission, and longitudinal studies, covering a total of 339 unique patients. Patients with active disease showed smaller hippocampal volumes, enlarged ventricles, and cerebral atrophy as well as alterations in neurochemical concentrations and functional activity. After abrogation of cortisol excess, the reversibility of structural and neurochemical alterations was incomplete after long-term remission. MRI findings were related to clinical characteristics (i.e., cortisol levels, duration of exposure to hypercortisolism, current age, age at diagnosis, and triglyceride levels) and behavioral outcome (i.e., cognitive and emotional functioning, mood, and quality of life). Conclusion: Patients with active CS demonstrate brain abnormalities, which only partly recover after biochemical cure, because these still occur even after long-term remission. CS might be considered as a human model of nature that provides a keyhole perspective of the neurotoxic effects of exogenous glucocorticoids on the brain.
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| 5. |
- Beamish, Andrew J., et al.
(författare)
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Should bariatric surgery be performed in adolescents?
- 2017
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 176:4
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Tidskriftsartikel (refereegranskat)abstract
- Adolescent obesity has markedly increased worldwide in both its extent and prevalence in recent decades and obesity prevention strategies are failing. As a result, effective treatment strategies are urgently needed. As behavioral and pharmacological treatment approaches have only moderate effects in severe obesity, bariatric surgery has begun to emerge as a treatment option. In this debate article, we offer arguments opposing and supporting bariatric surgery in the treatment of severe obesity in adolescents. Bariatric surgery has superior therapeutic outcomes with respect to weight loss and resolution of comorbid diseases over other existing treatments. However, long-term outcomes after bariatric surgery in adolescents are only just beginning to emerge. Furthermore, the procedures are generally considered irreversible, apart from gastric banding. Most importantly, not all adolescents seem to benefit greatly from bariatric surgery and we are not yet able to reliably identify those who stand to gain the greatest benefit. The authors agree that adolescent bariatric surgery should be offered exclusively within formal adolescent obesity programs, delivered by specialist multidisciplinary child/adolescent obesity teams, and within specialist centers, in order to optimize outcomes and minimize potential detrimental effects. Patients and their family/carers must be educated regarding the benefits and risks, potential side effects, expected changes in eating behavior and the lifelong requirement for regular medical follow-up after surgery. Before embarking upon a surgical treatment pathway in adolescents with severe obesity, it may also be beneficial to ensure compliance to treatment is demonstrated, in order to minimize the risk of nutritional deficiencies and associated potential complications.
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| 6. |
- Burman, Pia, et al.
(författare)
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Limited value of cabergoline in Cushing's disease : a prospective study of a 6-week treatment in 20 patients
- 2016
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Ingår i: European Journal of Endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 174:1, s. 17-24
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT AND OBJECTIVE: The role of cabergoline in Cushing's disease (CD) remains controversial. The experience is limited to case reports and few open studies that report the effects determined after ≥1 month of treatment. In prolactinomas and dopamine-responsive GH-secreting tumours, effects of cabergoline are seen within days or weeks. Here, we searched for short-term effects of cabergoline in CD.DESIGN: Twenty patients (19 naïve and one recurrent) were included in a prospective study. Cabergoline was administered in increasing doses of 0.5-5 mg/week over 6 weeks.METHODS: Urinary free cortisol (UFC) 24 h, morning cortisol and ACTH, and salivary cortisol at 0800, 1600 and 2300 h were determined once weekly throughout. Diurnal curves (six samples) of serum cortisol were measured at start and end.RESULTS: At study end, the median cabergoline dose was 5 mg, range 2.5-5 mg/week. The prolactin levels, markers of compliance, were suppressed in all patients. During the treatment, hypercortisolism varied, gradual and dose-dependent reductions were not seen. Five patients had a >50% decrease of UFC, three had a >50% rise of UFC. Salivary cortisol at 2300 h showed a congruent >50% change with UFC in two of the five cases with decreased UFC, and in one of the three cases with increased UFC. One patient with decreases in both UFC and 2300 h salivary cortisol also had a reduction in diurnal serum cortisol during the course of the study.CONCLUSIONS: Cabergoline seems to be of little value in the management of CD. Only one patient had a response-like pattern. Given the known variability of disease activity in CD, this might represent a chance finding.
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| 7. |
- Castinetti, Frederic, et al.
(författare)
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Radiotherapy as a tool for the treatment of Cushing's disease
- 2019
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 180:5
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Tidskriftsartikel (refereegranskat)abstract
- Treatment of Cushing's disease (CD) is one of the most challenging tasks in endocrinology. The first-line treatment, transsphenoidal pituitary surgery, is associated with a high failure rate and a high prevalence of recurrence. Re-operation is associated with an even higher rate of a failure and recurrence. There are three main second-line treatments for CD - pituitary radiation therapy (RT), bilateral adrenalectomy and chronic cortisol-lowering medical treatment. All these treatments have their limitations. While bilateral adrenalectomy provides permanent cure of the hypercortisolism in all patients, the unavoidable chronic adrenal insufficiency and the risk of development of Nelson syndrome are of concern. Chronic cortisol-lowering medical treatment is not efficient in all patients and side effects are often a limiting factor. RT is efficient for approximately two-thirds of all patients with CD. However, the high prevalence of pituitary insufficiency is of concern as well as potential optic nerve damage, development of cerebrovascular disease and secondary brain tumours. Thus, when it comes to decide appropriate treatment for patients with CD, who have either failed to achieve remission with pituitary surgery, or patients with recurrence, the pros and cons of all second-line treatment options must be considered.
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| 8. |
- Christiansen, J. S., et al.
(författare)
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Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations
- 2016
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 174:6
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH). Participants: A closed meeting of 55 international scientists with expertise in GH, including pediatric and adult endocrinologists, basic scientists, regulatory scientists, and participants from the pharmaceutical industry. Evidence: Current literature was reviewed for gaps in knowledge. Expert opinion was used to suggest studies required to address potential safety and efficacy issues. Consensus process: Following plenary presentations summarizing the literature, breakout groups discussed questions framed by the planning committee. Attendees reconvened after each breakout session to share group reports. A writing team compiled the breakout session reports into a draft document that was discussed and revised in an open forum on the concluding day. This was edited further and then circulated to attendees from academic institutions for review after the meeting. Participants from pharmaceutical companies did not participate in the planning, writing, or in the discussions and text revision on the final day of the workshop. Scientists from industry and regulatory agencies reviewed the manuscript to identify any factual errors. Conclusions: LAGH compounds may represent an advance over daily GH injections because of increased convenience and differing phamacodynamic properties, providing the potential for improved adherence and outcomes. Better methods to assess adherence must be developed and validated. Long-term surveillance registries that include assessment of efficacy, cost-benefit, disease burden, quality of life, and safety are essential for understanding the impact of sustained exposure to LAGH preparations.
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| 9. |
- Crawford, Andrew A., et al.
(författare)
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Morning plasma cortisol as a cardiovascular risk factor : findings from prospective cohort and Mendelian randomization studies
- 2019
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Ingår i: European Journal of Endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 181:4, s. 429-438
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The identification of new causal risk factors has the potential to improve cardiovascular disease (CVD) risk prediction and the development of new treatments to reduce CVD deaths. In the general population, we sought to determine whether cortisol is a causal risk factor for CVD and coronary heart disease (CHD).Design and methods: Three approaches were adopted to investigate the association between cortisol and CVD/CHD. First, we used multivariable regression in two prospective nested case-control studies (total 798 participants, 313 incident CVD/CHD with complete data). Second, a random-effects meta-analysis of these data and previously published prospective associations was performed (total 6680 controls, 696 incident CVD/CHD). Finally, one- and two-sample Mendelian randomization analyses were performed (122,737 CHD cases, 547,261 controls for two-sample analyses).Results: In the two prospective nested case-control studies, logistic regression adjusting for sex, age, BMI, smoking and time of sampling, demonstrated a positive association between morning plasma cortisol and incident CVD (OR: 1.28 per 1 SD higher cortisol, 95% CI: 1.06-1.54). In the meta-analysis of prospective studies, the equivalent result was OR: 1.18, 95% CI: 1.06-1.31. Results from the two-sample Mendelian randomization were consistent with these positive associations: OR: 1.06, 95% Cl: 0.98-1.15.Conclusions: All three approaches demonstrated a positive association between morning plasma cortisol and incident CVD. Together, these findings suggest that elevated morning cortisol is a causal risk factor for CVD. The current data suggest strategies targeted at lowering cortisol action should be evaluated for their effects on CVD.
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| 10. |
- Crona, Joakim, et al.
(författare)
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Genetics of neuroendocrine tumors
- 2016
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 174:6, s. R275-R290
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Forskningsöversikt (refereegranskat)abstract
- Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms, arising from neuroendocrine cells that are dispersed throughout the body. Around 20% of NETs occur in the context of a genetic syndrome. Today there are at least ten recognized NET syndromes. This includes the classical syndromes: multiple endocrine neoplasias types 1 and 2, and von Hippel-Lindau and neurofibromatosis type 1. Additional susceptibility genes associated with a smaller fraction of NETs have also been identified. Recognizing genetic susceptibility has proved essential both to provide genetic counseling and to give the best preventive care. In this review we will also discuss the knowledge of somatic genetic alterations in NETs. At least 24 genes have been implicated as drivers of neuroendocrine tumorigenesis, and the overall rates of genomic instability are relatively low. Genetic intra-tumoral, as well as inter-tumoral heterogeneity in the same patient, have also been identified. Together these data point towards the common pathways in NET evolution, separating early from late disease drivers. Although knowledge of specific mutations in NETs has limited impact on actual patient management, we predict that in the near future genomic profiling of tumors will be included in the clinical arsenal for diagnostics, prognostics and therapeutic decisions.
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