Stefanie Neidert, Philipp Schuetz, Beat Mueller and Mirjam Christ-Crain
Suppression of the adrenal function after glucocorticoid treatment is common, potentially dangerous, and unpredictable. Identification of patients at risk is of clinical importance. We hypothesized that the dexamethasone suppression test predicts the development of corticosteroid-induced impaired adrenal function.
We included 39 healthy male volunteers. After a 1-μg ACTH test, all participants underwent an overnight 0.5-mg dexamethasone suppression test. Participants then took prednisone, 0.5 mg/kg body weight, for 14-day. After the withdrawal of prednisone, a 1-μg ACTH test was performed and a clinical score was assessed on days 1, 3, 7, and 21.
On days 1, 3, 7, and 21, 100, 50, 26.5 and 32.4% of the participants had a suppressed adrenal function. The risk of developing suppressed adrenal function decreased from 44 to 0% in patients with cortisol levels after the administration of dexamethasone in the lowest and highest quartiles respectively. Receiver operating curve (ROC) analysis performed to predict a suppressed adrenal function on day 7 after the withdrawal of prednisone showed an area under the curve (AUC) of 0.76 (95% confidence interval (CI) 0.58–0.89) for cortisol after the administration of dexamethasone, which was in the range of the AUC of 0.78 (95% CI 0.6–0.9) for pre-intervention cortisol after the administration of ACTH. Basal cortisol before intake of prednisone (AUC 0.62 (95% CI 0.44–0.78)) and the clinical score (AUC 0.64 (95% CI 0.45–0.79)) had significantly lower AUCs.
Circulating cortisol levels after a dexamethasone suppression test and a pre-intervention-stimulated cortisol level are predictive of later development of a suppressed adrenal function after a 14-day course of prednisone, and are superior to a clinical score or basal cortisol levels. This may allow a more targeted concept for the need of stress prophylaxis after cessation of steroid therapy.
Tristan Struja, Hannah Fehlberg, Alexander Kutz, Larissa Guebelin, Christian Degen, Beat Mueller and Philipp Schuetz
Identification of pretreatment risk factors predicting relapse in patients with hyperthyroidism of Graves’ disease after stopping anti-thyroid drugs (ATD) is decisive to guide therapeutic options.
We performed a systematic search and meta-analysis to study predictors for relapse after stopping ATD in patients with Graves’ disease.
Based on a pre-specified protocol, we searched PubMed, EMBASE and Cochrane in July 2015 for case–control, controlled and randomized-controlled trials reporting risk factors for relapse after stopping ATD. The primary endpoint was relapse of disease until follow-up. PRISMA and SIGN statements were used for reviewing the data and assessing the quality of included trials.
We included 54 trials with a total of 7595 participants. Most trials were small with moderate-to-high risk for bias. Ten trials were assessed only qualitatively (2227 patients), genomic data were reported in 13 trials (2178 patients) and 31 trials (4346 patients) were assessed quantitatively. In total, there were 3696 relapses in 7595 patients (48.7%). By using random-effects meta-analysis, orbitopathy, smoking, thyroid volume measured by sonography, goiter size, fT4, tT3, TRAb and TBII were significantly associated with relapse, whereas male vs female sex, age and initial tT4 level did not show significant associations.
This analysis found several risk factors to predict relapse in Graves’ disease, which can be combined in a risk score. Prospective studies should evaluate the prognostic accuracy of such a score to guide treatment decisions.
Bettina Winzeler, Nica Jeanloz, Nicole Nigro, Isabelle Suter-Widmer, Philipp Schuetz, Birsen Arici, Martina Bally, Claudine Blum, Andreas Bock, Andreas Huber, Beat Mueller and Mirjam Christ-Crain
Hyponatremia is the most common electrolyte abnormality in hospitalized patients and given its impact on mortality and morbidity, a relevant medical condition. Nevertheless, little is known about factors influencing long-term outcome.
This is a prospective observational 12-month follow-up study of patients with profound hyponatremia (≤125 mmol/L) admitted to the emergency department of two tertiary care centers between 2011 and 2013. We analyzed the predictive value of clinical and laboratory parameters regarding the following outcomes: 1-year mortality, rehospitalization and recurrent profound hyponatremia.
Median (IQR) initial serum sodium (s-sodium) level of 281 included patients was 120 mmol/L (116–123). During the follow-up period, 58 (20.6%) patients died. The majority (56.2%) were rehospitalized at least once. Recurrent hyponatremia was observed in 42.7%, being profound in 16%. Underlying comorbidities, assessed by the Charlson Comorbidity Index, predicted 1-year mortality (odds ratio (OR) 1.43, 95% confidence interval (CI) 1.25–1.64, P < 0.001). Furthermore, ‘s-sodium level at admission’ (OR 1.14, 95% CI 1.01–1.29, P = 0.036) and ‘correction of hyponatremia’ defined as s-sodium ≥135 mmol/L at discharge were associated with mortality (OR 0.47, 95% CI 0.23–0.94, P = 0.034). Mortality rate fell with decreasing baseline s-sodium levels and was lower in the hyponatremia category ≤120 mmol/L vs >120 mmol/L (14.8% and 27.8%, P < 0.01). Patients with s-sodium level ≤120 mmol/L were more likely to have drug-induced hyponatremia, whereas hypervolemic hyponatremia was more common in patients with s-sodium >120 mmol/L.
Hyponatremia is associated with a substantial 1-year mortality, recurrence and rehospitalization rate. The positive correlation of s-sodium and mortality emphasizes the importance of the underlying disease, which determines the outcome besides hyponatremia itself.
Tristan Struja, Marina Kaeslin, Fabienne Boesiger, Rebecca Jutzi, Noemi Imahorn, Alexander Kutz, Luca Bernasconi, Esther Mundwiler, Beat Mueller, Mirjam Christ-Crain, Fabian Meienberg, Fahim Ebrahimi, Christoph Henzen, Stefan Fischli, Marius Kraenzlin, Christian Meier and Philipp Schuetz
First-line treatment in Graves’ disease is often done with antithyroid agents (ATD), but relapse rates remain high making definite treatment necessary. Predictors for relapse risk help guiding initial treatment decisions.
We aimed to externally validate the prognostic accuracy of the recently proposed Graves’ Recurrent Events After Therapy (GREAT) score to predict relapse risk in Graves’ disease.
Design, setting and participants
We retrospectively analyzed data (2004–2014) of patients with a first episode of Graves’ hyperthyroidism from four Swiss endocrine outpatient clinics.
Main outcome measures
Relapse of hyperthyroidism analyzed by multivariate Cox regression.
Of the 741 included patients, 371 experienced a relapse (50.1%) after a mean follow-up of 25.6 months after ATD start. In univariate regression analysis, higher serum free T4, higher thyrotropin-binding inhibitor immunoglobulin (TBII), younger age and larger goiter were associated with higher relapse risk. We found a strong increase in relapse risk with more points in the GREAT score from 33.8% in patients with GREAT class I (0–1 points), 59.4% in class II (2–3 points) with a hazard ratio of 1.79 (95% CI: 1.42–2.27, P < 0.001) and 73.6% in class III (4–6 points) with a hazard ratio of 2.24 (95% CI: 1.64–3.06, P < 0.001).
Based on this retrospective analysis within a large patient population from a multicenter study, the GREAT score shows good external validity and can be used for assessing the risk for relapse in Graves’ disease, which influence the initial treatment decisions.
Philipp Schuetz, Jörg D Leuppi, Roland Bingisser, Michael Bodmer, Matthias Briel, Tilman Drescher, Ursula Duerring, Christoph Henzen, Yolanda Leibbrandt, Sabrina Maier, David Miedinger, Beat Mueller, Andreas Scherr, Christian Schindler, Rolf Stoeckli, Sebastien Viatte, Christophe von Garnier, Michael Tamm and Jonas Rutishauser
To analyze prospectively the hypothalamic–pituitary–adrenal (HPA) axis and clinical outcome in patients treated with prednisone for exacerbated chronic obstructive pulmonary disease (COPD).
Prospective observational study.
Subjects and methods
Patients presenting to the emergency department were randomized to receive 40 mg prednisone daily for 5 or 14 days in a placebo-controlled manner. The HPA axis was longitudinally assessed with the 1 μg corticotropin test and a clinical hypocortisolism score at baseline, on day 6 before blinded treatment, at hospital discharge, and for up to 180 days of follow-up. Prednisone was stopped abruptly, irrespective of the test results. Patients discharged with pathological test results received instructions about emergency hydrocortisone treatment.
A total of 311 patients were included in the analysis. Mean basal and stimulated serum total cortisol levels were highest on admission (496±398 and 816±413 nmol/l respectively) and lowest on day 6 (235±174 and 453±178 nmol/l respectively). Pathological stimulation tests were found in 63, 38, 9, 3, and 2% of patients on day 6, at discharge, and on days 30, 90, and 180 respectively, without significant difference between treatment groups. Clinical indicators of hypocortisolism did not correlate with stimulation test results, but cortisol levels were inversely associated with re-exacerbation risk. There were no hospitalizations or deaths as a result of adrenal crisis.
Dynamic changes in the HPA axis occur during and after the treatment of acute exacerbations of COPD. In hypocortisolemic patients who were provided with instructions about stress prophylaxis, the abrupt termination of prednisone appeared safe.
Fahim Ebrahimi, Andrea Widmer, Ulrich Wagner, Beat Mueller, Philipp Schuetz, Mirjam Christ-Crain and Alexander Kutz
Adrenal insufficiency in the outpatient setting is associated with excess morbidity, mortality, and impaired quality of life. Evidence on its health-care burden in medical inpatients is scarce. The aim of this study was to assess the health-care burden of primary adrenal insufficiency (PAI) and secondary adrenal insufficiency (SAI) among hospitalized inpatients.
Design and methods
In this nationwide cohort study, adult medical patients with either PAI or SAI hospitalized between 2011 and 2015 were compared with propensity-matched (1:1) medical controls, respectively. The primary outcome was 30-day all-cause in-hospital mortality. Main secondary outcomes included ICU admission rate, length-of-hospital stay, 30-day and 1-year all-cause readmission rates.
In total, 594 hospitalized cases with PAI and 4880 cases with SAI were included. Compared with matched controls, in-hospital mortality was not increased among PAI or SAI patients, respectively. Patients with adrenal insufficiency were more likely to be admitted to ICU (PAI: OR 1.9 (95% CI, 1.27 to 2.72) and SAI: OR 1.5 (95% CI, 1.35 to 1.75)). Length of hospital stay was prolonged by 1.0 days in PAI patients (8.9 vs 7.9 days (95% CI, 0.06 to 1.93)), and by 3.3 days in SAI patients (12.1 vs 8.8 days (95% CI, 2.82 to 3.71)), when compared with matched controls. Patients with SAI were found to have higher 30-day and 1-year readmission rates (14.1 vs 12.1% and 50.0 vs 40.7%; P < 0.001) than matched controls.
While no difference in in-hospital mortality was found, adrenal insufficiency was associated with prolonged length of hospital stay, and substantially higher rates of ICU admission and hospital readmission.