Search Results
Search for other papers by Dirk Weismann in
Google Scholar
PubMed
Search for other papers by Andreas Schneider in
Google Scholar
PubMed
Department of Molecular Surgery and Medicine, Karolinska Institute, Stockholm, Sweden
Search for other papers by Charlotte Höybye in
Google Scholar
PubMed
Hyponatremia (HN) is a common condition, with a large number of etiologies and a complicated treatment. Although chronic HN has been shown to be a predictor of poor outcome, sodium-increasing treatments in chronic stable and asymptomatic HN have not proven to increase life expectancy. For symptomatic HN, in contrast, the necessity for urgent treatment has broadly been accepted to avoid the development of fatal cerebral edema. On the other hand, a too rapid increase of serum sodium in chronic HN may result in cerebral damage due to osmotic demyelinisation. Recently, administration of hypertonic saline bolus has been recommended as first-line treatment in patients with moderate-to-severe symptomatic HN. This approach is easy to memorize and holds the potential to greatly facilitate the initial treatment of symptomatic HN. First-line treatment of chronic HN is fluid restriction and if ineffective treatment with tolvaptan or in some patients other agents should be considered. A number of recommendations and guidelines have been published on HN. In the present review, the management of patients with HN in relation to everyday clinical practice is summarized with focus on the acute management.
Department of Endocrinology, Department of Molecular Medicine and Surgery, Metabolism and Diabetology, Karolinska University Hospital, 171 76 Stockholm, Sweden
Search for other papers by Charlotte Höybye in
Google Scholar
PubMed
Search for other papers by Erik Wahlström in
Google Scholar
PubMed
Search for other papers by Petra Tollet-Egnell in
Google Scholar
PubMed
Search for other papers by Gunnar Norstedt in
Google Scholar
PubMed
The diagnostic value of insulin-like growth factor 1 (IGF1) for GH deficiency (GHD) in adults is not optimal. Molecular profiling could be used for biomarker discovery. The aim of this pilot study was to compare the serum metabolome between GHD patients and healthy controls, and identification of potential markers for diagnosis and/or for individual GH dosing. A total of ten patients with GHD, median age of 55 years and BMI of 27 kg/m2, were compared with ten healthy age- and gender-matched controls. The serum metabolic profiles were generated using gas chromatography-coupled mass spectroscopy on fasting samples taken in the morning from the controls and at baseline and during 6 months of GH replacement in the patients with GHD. The difference in low-molecular weight compounds (LMC) distinguished the healthy controls from GHD patients. Among 285 measured metabolites, 13 were identified as being most important in differentiating GHD patients from controls. Of these, 11 could not be structurally annotated but many were classified as lipids. The difference in the LMC pattern persisted despite normalisation of IGF1 following GH replacement. GH replacement increased the levels of specific fatty acid compounds and decreased the levels of certain amino acids. No metabolite changed in response to GH treatment, to the same extent as IGF1. The measurement of 285 metabolites resulted in a unique pattern in GHD, but changes in the metabolite patterns during GH treatment were limited. The utility of metabolomics to find new markers in GHD and GH replacement remains to be further elucidated.
Department of Clinical Chemistry, Karolinska University Hospital, Stockholm, Sweden
Search for other papers by Anna Sjöström in
Google Scholar
PubMed
Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
Search for other papers by Susanne Rysz in
Google Scholar
PubMed
Center for Neurology, Academic Specialist Center, Stockholm, Sweden
Search for other papers by Henrik Sjöström in
Google Scholar
PubMed
Department of Endocrinology, Karolinska University Hospital, Stockholm, Sweden
Search for other papers by Charlotte Höybye in
Google Scholar
PubMed
Acute systemic diseases, such as severe infections, can lead to electrolyte and acid-base alterations. To study the presence of electrolyte imbalance in severe COVID-19, we investigated the frequency and consequences of changes in electrolyte and acid-base patterns over time. We performed a retrospective cohort study including 406 patients with severe COVID-19. Levels of electrolytes, base excess, pH, serum osmolality, and hematocrit, the first 2 weeks of hospitalization, were collected daily from the laboratory database and clinical data from patients’ medical records. We found that hyponatremia was present in 57% of the patients at admission and 2% in hypernatremia. However, within 2 weeks of hospitalization 42% of the patients developed hypernatremia, more frequently in critically ill patients. Lower levels of sodium and potassium during admission were associated with the need for mechanical ventilation. Decreased pH at admission was associated with both death and the need for mechanical ventilation. Hypernatremia in the ICU was combined with rising base excess and a higher pH. In the group without intensive care, potassium levels were significantly lower in the patients with severe hypernatremia. Presence of hypernatremia during the first 2 weeks of hospitalization was associated with 3.942 (95% CI 2.269–6.851) times higher odds of death. In summary, hypernatremia was common and associated with longer hospital stay and a higher risk of death, suggesting that the dynamics of sodium are an important indicator of severity in COVID-19.
Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden
Search for other papers by Charlotte Höybye in
Google Scholar
PubMed
Search for other papers by Laia Faseh in
Google Scholar
PubMed
Department of Medicine, Karlstad Hospital, Karlstad, Sweden
Search for other papers by Christos Himonakos in
Google Scholar
PubMed
Search for other papers by Tomasz Pielak in
Google Scholar
PubMed
Search for other papers by Jesper Eugen-Olsen in
Google Scholar
PubMed
Growth hormone deficiency (GHD) syndrome is associated with adverse levels of several risk factors for cardiovascular diseases (CVD), including metabolic inflammation. However, the impact of GHD and GH treatment on low-grade inflammation is unknown. The aim of the study was to establish the level of the low-grade inflammation biomarker soluble urokinase plasminogen activator receptor (suPAR) in adults with GHD and the response to long-term GH treatment. Measurements of suPAR and CRP were performed in bio-bank serum samples from 72 adults, 34 males and 38 females, with GHD before and during at least 5 years of GH treatment. Mean age was 52.5 ± 15.5 years, BMI 27.3 ± 5 kg/m2. Clinical evaluations and blood sampling were performed at routine visits. Data on demography, anthropometry, lab results and clinical events were retrieved from post-marketing surveillance study databases and medical records. suPAR and high-sensitive (hs) CRP were analysed using ELISA and immunochemistry, respectively. At baseline blood pressure, lipid profile and fasting glucose were within the normal reference range. Baseline geometric mean and 95% CI of suPAR was 2.9 (2.7–3.3) ng/mL and of CRP 2.3 (0.6–4.0) mg/L. Mean follow-up was 8 ± 2 years. The suPAR levels remained stable during follow-up, although individual increases were seen on occurrence or presence of co-morbidities. In contrast, levels of CRP decreased. In conclusion, the decrease in CRP and indirectly the absence of an expected increase in suPAR over time indicates a favourable effect of GH on low-grade inflammation.
Search for other papers by Charlotte Höybye in
Google Scholar
PubMed
Search for other papers by Andreas F H Pfeiffer in
Google Scholar
PubMed
Search for other papers by Diego Ferone in
Google Scholar
PubMed
Search for other papers by Jens Sandahl Christiansen in
Google Scholar
PubMed
Search for other papers by David Gilfoyle in
Google Scholar
PubMed
Search for other papers by Eva Dam Christoffersen in
Google Scholar
PubMed
Search for other papers by Eva Mortensen in
Google Scholar
PubMed
Search for other papers by Jonathan A Leff in
Google Scholar
PubMed
Search for other papers by Michael Beckert in
Google Scholar
PubMed
TransCon growth hormone is a sustained-release human growth hormone prodrug under development in which unmodified growth hormone is transiently linked to a carrier molecule. It is intended as an alternative to daily growth hormone in the treatment of growth hormone deficiency. This was a multi-center, randomized, open-label, active-controlled trial designed to compare the safety (including tolerability and immunogenicity), pharmacokinetics and pharmacodynamics of three doses of weekly TransCon GH to daily growth hormone (Omnitrope). Thirty-seven adult males and females diagnosed with adult growth hormone deficiency and stable on growth hormone replacement therapy for at least 3 months were, following a wash-out period, randomized (regardless of their pre-study dose) to one of three TransCon GH doses (0.02, 0.04 and 0.08 mg GH/kg/week) or Omnitrope 0.04 mg GH/kg/week (divided into 7 equal daily doses) for 4 weeks. Main outcomes evaluated were adverse events, immunogenicity and growth hormone and insulin-like growth factor 1 levels. TransCon GH was well tolerated; fatigue and headache were the most frequent drug-related adverse events and reported in all groups. No lipoatrophy or nodule formation was reported. No anti-growth hormone-binding antibodies were detected. TransCon GH demonstrated a linear, dose-dependent increase in growth hormone exposure without accumulation. Growth hormone maximum serum concentration and insulin-like growth factor 1 exposure were similar after TransCon GH or Omnitrope administered at comparable doses. The results suggest that long-acting TransCon GH has a profile similar to daily growth hormone but with a more convenient dosing regimen. These findings support further TransCon GH development.
Search for other papers by Christine Poitou in
Google Scholar
PubMed
Search for other papers by Anthony Holland in
Google Scholar
PubMed
Search for other papers by Charlotte Höybye in
Google Scholar
PubMed
Search for other papers by Laura C G de Graaff in
Google Scholar
PubMed
Search for other papers by Sandrine Bottius in
Google Scholar
PubMed
Search for other papers by Berit Otterlei in
Google Scholar
PubMed
Search for other papers by Maithé Tauber in
Google Scholar
PubMed
Prader–Willi syndrome (PWS), the most common form of syndromic obesity, is a complex neurodevelopmental genetic disorder including obesity with hyperphagia, endocrine and metabolic disorders and also psychiatric disorders. The most frequent endocrine disturbances include hypogonadism and growth hormone (GH) deficiency. Hypothyroidism and central adrenal insufficiency can also be observed but are less frequent. The transition of individuals with PWS from adolescence to adult life is challenging because of multiple comorbidities and complex disabilities. Individuals and caregivers face psychological, medical and social issues. This period of profound changes is thus prone to disruptions, and the main risks being the worsening of the medical situation and loss to follow-up of the individuals. Medical care may be poorly adapted to the needs of individuals because of a lack of knowledge concerning the syndrome and also lack of the necessary specific skills. A multidisciplinary panel composed of several experts in PWS met in November 2021 during an European Reference Network on Rare Endocrine Conditions (Endo-ERN) webinar. They presented complementary aspects of PWS from the perspective of the transition including psychiatric, pediatric and adult endocrinological and parent’s and patient’s points of view and shed light on the best way to approach this pivotal period.
Search for other papers by Charlotte Höybye in
Google Scholar
PubMed
Search for other papers by Beverly M K Biller in
Google Scholar
PubMed
Search for other papers by Jean-Marc Ferran in
Google Scholar
PubMed
Search for other papers by Murray B Gordon in
Google Scholar
PubMed
Search for other papers by Nicky Kelepouris in
Google Scholar
PubMed
Search for other papers by Navid Nedjatian in
Google Scholar
PubMed
Search for other papers by Anne H Olsen in
Google Scholar
PubMed
Search for other papers by Matthias M Weber in
Google Scholar
PubMed
Adult growth hormone deficiency (AGHD) is associated with an increased risk of cardiovascular (CV) disease. Long-term growth hormone (GH) treatment could improve CV outcomes. The objective of this study was to evaluate CV disease risk in patients with AGHD who received GH replacement therapy for up to 10 years as part of NordiNet® IOS (NCT00960128) and the ANSWER Program (NCT01009905). The studies were observational, non-interventional and multicentre, monitoring long-term effectiveness and safety of GH treatment. NordiNet® IOS involved 23 countries (469 sites) across Europe and the Middle East. The ANSWER Program was conducted in the USA (207 sites). This analysis included patients aged 18–75 years who were GH naïve at study entry, who had ≤10 years of GH treatment data and who could be assessed for CV risk for at least 1 follow-up year. The main outcome measure was risk of CV disease by age 75 years, as calculated with the Multinational Cardiovascular Risk Consortium model (Brunner score) using non-high-density lipoprotein cholesterol adjusted for age, sex and CV risk factors. The results of this analysis showed that CV risk decreased gradually over the 10-year period for GH-treated patients. The risk was lower for patients treated for 2 and 7 years vs age- and sex-matched control groups (not yet started treatment) (14.51% vs 16.15%; P = 0.0105 and 13.53% vs 16.81%; P = 0.0001, respectively). This suggests that GH treatment in people with AGHD may reduce the risk of CV disease by age 75 years compared with matched controls.
Search for other papers by Anita Hokken-Koelega in
Google Scholar
PubMed
Search for other papers by Aart-Jan van der Lely in
Google Scholar
PubMed
Search for other papers by Berthold Hauffa in
Google Scholar
PubMed
Search for other papers by Gabriele Häusler in
Google Scholar
PubMed
Search for other papers by Gudmundur Johannsson in
Google Scholar
PubMed
Search for other papers by Mohamad Maghnie in
Google Scholar
PubMed
Search for other papers by Jesús Argente in
Google Scholar
PubMed
Search for other papers by Jean DeSchepper in
Google Scholar
PubMed
Search for other papers by Helena Gleeson in
Google Scholar
PubMed
Search for other papers by John W Gregory in
Google Scholar
PubMed
Search for other papers by Charlotte Höybye in
Google Scholar
PubMed
Search for other papers by Fahrettin Keleştimur in
Google Scholar
PubMed
Search for other papers by Anton Luger in
Google Scholar
PubMed
Search for other papers by Hermann L Müller in
Google Scholar
PubMed
Search for other papers by Sebastian Neggers in
Google Scholar
PubMed
Search for other papers by Vera Popovic-Brkic in
Google Scholar
PubMed
Search for other papers by Eleonora Porcu in
Google Scholar
PubMed
Search for other papers by Lars Sävendahl in
Google Scholar
PubMed
Search for other papers by Stephen Shalet in
Google Scholar
PubMed
Search for other papers by Bessie Spiliotis in
Google Scholar
PubMed
Search for other papers by Maithé Tauber in
Google Scholar
PubMed
Objective
Seamless transition of endocrine patients from the paediatric to adult setting is still suboptimal, especially in patients with complex disorders, i.e., small for gestational age, Turner or Prader–Willi syndromes; Childhood Cancer Survivors, and those with childhood-onset growth hormone deficiency.
Methods
An expert panel meeting comprised of European paediatric and adult endocrinologists was convened to explore the current gaps in managing the healthcare of patients with endocrine diseases during transition from paediatric to adult care settings.
Results
While a consensus was reached that a team approach is best, discussions revealed that a ‘one size fits all’ model for transition is largely unsuccessful in these patients. They need more tailored care during adolescence to prevent complications like failure to achieve target adult height, reduced bone mineral density, morbid obesity, metabolic perturbations (obesity and body composition), inappropriate/inadequate puberty, compromised fertility, diminished quality of life and failure to adapt to the demands of adult life. Sometimes it is difficult for young people to detach emotionally from their paediatric endocrinologist and/or the abrupt change from an environment of parental responsibility to one of autonomy. Discussions about impending transition and healthcare autonomy should begin in early adolescence and continue throughout young adulthood to ensure seamless continuum of care and optimal treatment outcomes.
Conclusions
Even amongst a group of healthcare professionals with a great interest in improving transition services for patients with endocrine diseases, there is still much work to be done to improve the quality of healthcare for transition patients.
