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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.

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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.