PMID- 24944332
OWN - NLM
STAT- MEDLINE
DCOM- 20140922
LR  - 20220410
IS  - 1479-683X (Electronic)
IS  - 0804-4643 (Print)
IS  - 0804-4643 (Linking)
VI  - 171
IP  - 3
DP  - 2014 Sep
TI  - Prospective evaluation of long-term safety of dual-release hydrocortisone 
      replacement administered once daily in patients with adrenal insufficiency.
PG  - 369-77
LID - 10.1530/EJE-14-0327 [doi]
AB  - OBJECTIVE: The objective was to assess the long-term safety profile of 
      dual-release hydrocortisone (DR-HC) in patients with adrenal insufficiency (AI). 
      DESIGN: Randomised, open-label, crossover trial of DR-HC or thrice-daily 
      hydrocortisone for 3 months each (stage 1) followed by two consecutive, 
      prospective, open-label studies of DR-HC for 6 months (stage 2) and 18 months 
      (stage 3) at five university clinics in Sweden. METHODS: Sixty-four adults with 
      primary AI started stage 1, and an additional 16 entered stage 3. Patients 
      received DR-HC 20-40 mg once daily and hydrocortisone 20-40 mg divided into three 
      daily doses (stage 1 only). Main outcome measures were adverse events (AEs) and 
      intercurrent illness (self-reported hydrocortisone use during illness). RESULTS: 
      In stage 1, patients had a median 1.5 (range, 1-9) intercurrent illness events 
      with DR-HC and 1.0 (1-8) with thrice-daily hydrocortisone. AEs during stage 1 
      were not related to the cortisol exposure-time profile. The percentage of 
      patients with one or more AEs during stage 1 (73.4% with DR-HC; 65.6% with 
      thrice-daily hydrocortisone) decreased during stage 2, when all patients received 
      DR-HC (51% in the first 3 months; 54% in the second 3 months). In stages 1-3 
      combined, 19 patients experienced 27 serious AEs, equating to 18.6 serious 
      AEs/100 patient-years of DR-HC exposure. CONCLUSIONS: This long-term prospective 
      trial is the first to document the safety of DR-HC in patients with primary AI 
      and demonstrates that such treatment is well tolerated during 24 consecutive 
      months of therapy.
CI  - (c) 2014 The authors.
FAU - Nilsson, A G
AU  - Nilsson AG
AD  - Department of EndocrinologySahlgrenska Academy, University of Gothenburg, 
      Sahlgrenska University Hospital, Grona Straket 8, SE-413 45 Gothenburg, 
      SwedenMedical AffairsViroPharma SPRL, Maidenhead, UKBiostatisticsViroPharma 
      IncorporatedDepartment of EndocrinologySkanes University Hospital, SE-205 02 
      Malmo, SwedenDepartment of Public Health and Clinical MedicineUmea University, 
      SE-901 87 Umea, SwedenSection of EndocrinologyDepartment of Medical and Health 
      Sciences, Faculty of Health Sciences, Linkoping University, SE-581 83 Linkoping, 
      SwedenDepartment of EndocrinologyDiabetes, and Metabolism, University 
      HospitalDepartment of PharmacyUppsala University, SE-751 85 Uppsala, 
      SwedenDepartment of Clinical PharmacologySahlgrenska Academy, University of 
      Gothenburg, SE-413 45 Gothenburg, SwedenAstraZeneca R&DMolndal, Sweden.
FAU - Marelli, C
AU  - Marelli C
AD  - Department of EndocrinologySahlgrenska Academy, University of Gothenburg, 
      Sahlgrenska University Hospital, Grona Straket 8, SE-413 45 Gothenburg, 
      SwedenMedical AffairsViroPharma SPRL, Maidenhead, UKBiostatisticsViroPharma 
      IncorporatedDepartment of EndocrinologySkanes University Hospital, SE-205 02 
      Malmo, SwedenDepartment of Public Health and Clinical MedicineUmea University, 
      SE-901 87 Umea, SwedenSection of EndocrinologyDepartment of Medical and Health 
      Sciences, Faculty of Health Sciences, Linkoping University, SE-581 83 Linkoping, 
      SwedenDepartment of EndocrinologyDiabetes, and Metabolism, University 
      HospitalDepartment of PharmacyUppsala University, SE-751 85 Uppsala, 
      SwedenDepartment of Clinical PharmacologySahlgrenska Academy, University of 
      Gothenburg, SE-413 45 Gothenburg, SwedenAstraZeneca R&DMolndal, Sweden.
FAU - Fitts, D
AU  - Fitts D
AD  - Department of EndocrinologySahlgrenska Academy, University of Gothenburg, 
      Sahlgrenska University Hospital, Grona Straket 8, SE-413 45 Gothenburg, 
      SwedenMedical AffairsViroPharma SPRL, Maidenhead, UKBiostatisticsViroPharma 
      IncorporatedDepartment of EndocrinologySkanes University Hospital, SE-205 02 
      Malmo, SwedenDepartment of Public Health and Clinical MedicineUmea University, 
      SE-901 87 Umea, SwedenSection of EndocrinologyDepartment of Medical and Health 
      Sciences, Faculty of Health Sciences, Linkoping University, SE-581 83 Linkoping, 
      SwedenDepartment of EndocrinologyDiabetes, and Metabolism, University 
      HospitalDepartment of PharmacyUppsala University, SE-751 85 Uppsala, 
      SwedenDepartment of Clinical PharmacologySahlgrenska Academy, University of 
      Gothenburg, SE-413 45 Gothenburg, SwedenAstraZeneca R&DMolndal, Sweden.
FAU - Bergthorsdottir, R
AU  - Bergthorsdottir R
AD  - Department of EndocrinologySahlgrenska Academy, University of Gothenburg, 
      Sahlgrenska University Hospital, Grona Straket 8, SE-413 45 Gothenburg, 
      SwedenMedical AffairsViroPharma SPRL, Maidenhead, UKBiostatisticsViroPharma 
      IncorporatedDepartment of EndocrinologySkanes University Hospital, SE-205 02 
      Malmo, SwedenDepartment of Public Health and Clinical MedicineUmea University, 
      SE-901 87 Umea, SwedenSection of EndocrinologyDepartment of Medical and Health 
      Sciences, Faculty of Health Sciences, Linkoping University, SE-581 83 Linkoping, 
      SwedenDepartment of EndocrinologyDiabetes, and Metabolism, University 
      HospitalDepartment of PharmacyUppsala University, SE-751 85 Uppsala, 
      SwedenDepartment of Clinical PharmacologySahlgrenska Academy, University of 
      Gothenburg, SE-413 45 Gothenburg, SwedenAstraZeneca R&DMolndal, Sweden.
FAU - Burman, P
AU  - Burman P
AD  - Department of EndocrinologySahlgrenska Academy, University of Gothenburg, 
      Sahlgrenska University Hospital, Grona Straket 8, SE-413 45 Gothenburg, 
      SwedenMedical AffairsViroPharma SPRL, Maidenhead, UKBiostatisticsViroPharma 
      IncorporatedDepartment of EndocrinologySkanes University Hospital, SE-205 02 
      Malmo, SwedenDepartment of Public Health and Clinical MedicineUmea University, 
      SE-901 87 Umea, SwedenSection of EndocrinologyDepartment of Medical and Health 
      Sciences, Faculty of Health Sciences, Linkoping University, SE-581 83 Linkoping, 
      SwedenDepartment of EndocrinologyDiabetes, and Metabolism, University 
      HospitalDepartment of PharmacyUppsala University, SE-751 85 Uppsala, 
      SwedenDepartment of Clinical PharmacologySahlgrenska Academy, University of 
      Gothenburg, SE-413 45 Gothenburg, SwedenAstraZeneca R&DMolndal, Sweden.
FAU - Dahlqvist, P
AU  - Dahlqvist P
AD  - Department of EndocrinologySahlgrenska Academy, University of Gothenburg, 
      Sahlgrenska University Hospital, Grona Straket 8, SE-413 45 Gothenburg, 
      SwedenMedical AffairsViroPharma SPRL, Maidenhead, UKBiostatisticsViroPharma 
      IncorporatedDepartment of EndocrinologySkanes University Hospital, SE-205 02 
      Malmo, SwedenDepartment of Public Health and Clinical MedicineUmea University, 
      SE-901 87 Umea, SwedenSection of EndocrinologyDepartment of Medical and Health 
      Sciences, Faculty of Health Sciences, Linkoping University, SE-581 83 Linkoping, 
      SwedenDepartment of EndocrinologyDiabetes, and Metabolism, University 
      HospitalDepartment of PharmacyUppsala University, SE-751 85 Uppsala, 
      SwedenDepartment of Clinical PharmacologySahlgrenska Academy, University of 
      Gothenburg, SE-413 45 Gothenburg, SwedenAstraZeneca R&DMolndal, Sweden.
FAU - Ekman, B
AU  - Ekman B
AD  - Department of EndocrinologySahlgrenska Academy, University of Gothenburg, 
      Sahlgrenska University Hospital, Grona Straket 8, SE-413 45 Gothenburg, 
      SwedenMedical AffairsViroPharma SPRL, Maidenhead, UKBiostatisticsViroPharma 
      IncorporatedDepartment of EndocrinologySkanes University Hospital, SE-205 02 
      Malmo, SwedenDepartment of Public Health and Clinical MedicineUmea University, 
      SE-901 87 Umea, SwedenSection of EndocrinologyDepartment of Medical and Health 
      Sciences, Faculty of Health Sciences, Linkoping University, SE-581 83 Linkoping, 
      SwedenDepartment of EndocrinologyDiabetes, and Metabolism, University 
      HospitalDepartment of PharmacyUppsala University, SE-751 85 Uppsala, 
      SwedenDepartment of Clinical PharmacologySahlgrenska Academy, University of 
      Gothenburg, SE-413 45 Gothenburg, SwedenAstraZeneca R&DMolndal, Sweden.
FAU - Engstrom, B Eden
AU  - Engstrom BE
AD  - Department of EndocrinologySahlgrenska Academy, University of Gothenburg, 
      Sahlgrenska University Hospital, Grona Straket 8, SE-413 45 Gothenburg, 
      SwedenMedical AffairsViroPharma SPRL, Maidenhead, UKBiostatisticsViroPharma 
      IncorporatedDepartment of EndocrinologySkanes University Hospital, SE-205 02 
      Malmo, SwedenDepartment of Public Health and Clinical MedicineUmea University, 
      SE-901 87 Umea, SwedenSection of EndocrinologyDepartment of Medical and Health 
      Sciences, Faculty of Health Sciences, Linkoping University, SE-581 83 Linkoping, 
      SwedenDepartment of EndocrinologyDiabetes, and Metabolism, University 
      HospitalDepartment of PharmacyUppsala University, SE-751 85 Uppsala, 
      SwedenDepartment of Clinical PharmacologySahlgrenska Academy, University of 
      Gothenburg, SE-413 45 Gothenburg, SwedenAstraZeneca R&DMolndal, Sweden.
FAU - Olsson, T
AU  - Olsson T
AD  - Department of EndocrinologySahlgrenska Academy, University of Gothenburg, 
      Sahlgrenska University Hospital, Grona Straket 8, SE-413 45 Gothenburg, 
      SwedenMedical AffairsViroPharma SPRL, Maidenhead, UKBiostatisticsViroPharma 
      IncorporatedDepartment of EndocrinologySkanes University Hospital, SE-205 02 
      Malmo, SwedenDepartment of Public Health and Clinical MedicineUmea University, 
      SE-901 87 Umea, SwedenSection of EndocrinologyDepartment of Medical and Health 
      Sciences, Faculty of Health Sciences, Linkoping University, SE-581 83 Linkoping, 
      SwedenDepartment of EndocrinologyDiabetes, and Metabolism, University 
      HospitalDepartment of PharmacyUppsala University, SE-751 85 Uppsala, 
      SwedenDepartment of Clinical PharmacologySahlgrenska Academy, University of 
      Gothenburg, SE-413 45 Gothenburg, SwedenAstraZeneca R&DMolndal, Sweden.
FAU - Ragnarsson, O
AU  - Ragnarsson O
AD  - Department of EndocrinologySahlgrenska Academy, University of Gothenburg, 
      Sahlgrenska University Hospital, Grona Straket 8, SE-413 45 Gothenburg, 
      SwedenMedical AffairsViroPharma SPRL, Maidenhead, UKBiostatisticsViroPharma 
      IncorporatedDepartment of EndocrinologySkanes University Hospital, SE-205 02 
      Malmo, SwedenDepartment of Public Health and Clinical MedicineUmea University, 
      SE-901 87 Umea, SwedenSection of EndocrinologyDepartment of Medical and Health 
      Sciences, Faculty of Health Sciences, Linkoping University, SE-581 83 Linkoping, 
      SwedenDepartment of EndocrinologyDiabetes, and Metabolism, University 
      HospitalDepartment of PharmacyUppsala University, SE-751 85 Uppsala, 
      SwedenDepartment of Clinical PharmacologySahlgrenska Academy, University of 
      Gothenburg, SE-413 45 Gothenburg, SwedenAstraZeneca R&DMolndal, Sweden.
FAU - Ryberg, M
AU  - Ryberg M
AD  - Department of EndocrinologySahlgrenska Academy, University of Gothenburg, 
      Sahlgrenska University Hospital, Grona Straket 8, SE-413 45 Gothenburg, 
      SwedenMedical AffairsViroPharma SPRL, Maidenhead, UKBiostatisticsViroPharma 
      IncorporatedDepartment of EndocrinologySkanes University Hospital, SE-205 02 
      Malmo, SwedenDepartment of Public Health and Clinical MedicineUmea University, 
      SE-901 87 Umea, SwedenSection of EndocrinologyDepartment of Medical and Health 
      Sciences, Faculty of Health Sciences, Linkoping University, SE-581 83 Linkoping, 
      SwedenDepartment of EndocrinologyDiabetes, and Metabolism, University 
      HospitalDepartment of PharmacyUppsala University, SE-751 85 Uppsala, 
      SwedenDepartment of Clinical PharmacologySahlgrenska Academy, University of 
      Gothenburg, SE-413 45 Gothenburg, SwedenAstraZeneca R&DMolndal, Sweden.
FAU - Wahlberg, J
AU  - Wahlberg J
AD  - Department of EndocrinologySahlgrenska Academy, University of Gothenburg, 
      Sahlgrenska University Hospital, Grona Straket 8, SE-413 45 Gothenburg, 
      SwedenMedical AffairsViroPharma SPRL, Maidenhead, UKBiostatisticsViroPharma 
      IncorporatedDepartment of EndocrinologySkanes University Hospital, SE-205 02 
      Malmo, SwedenDepartment of Public Health and Clinical MedicineUmea University, 
      SE-901 87 Umea, SwedenSection of EndocrinologyDepartment of Medical and Health 
      Sciences, Faculty of Health Sciences, Linkoping University, SE-581 83 Linkoping, 
      SwedenDepartment of EndocrinologyDiabetes, and Metabolism, University 
      HospitalDepartment of PharmacyUppsala University, SE-751 85 Uppsala, 
      SwedenDepartment of Clinical PharmacologySahlgrenska Academy, University of 
      Gothenburg, SE-413 45 Gothenburg, SwedenAstraZeneca R&DMolndal, Sweden.
FAU - Lennernas, H
AU  - Lennernas H
AD  - Department of EndocrinologySahlgrenska Academy, University of Gothenburg, 
      Sahlgrenska University Hospital, Grona Straket 8, SE-413 45 Gothenburg, 
      SwedenMedical AffairsViroPharma SPRL, Maidenhead, UKBiostatisticsViroPharma 
      IncorporatedDepartment of EndocrinologySkanes University Hospital, SE-205 02 
      Malmo, SwedenDepartment of Public Health and Clinical MedicineUmea University, 
      SE-901 87 Umea, SwedenSection of EndocrinologyDepartment of Medical and Health 
      Sciences, Faculty of Health Sciences, Linkoping University, SE-581 83 Linkoping, 
      SwedenDepartment of EndocrinologyDiabetes, and Metabolism, University 
      HospitalDepartment of PharmacyUppsala University, SE-751 85 Uppsala, 
      SwedenDepartment of Clinical PharmacologySahlgrenska Academy, University of 
      Gothenburg, SE-413 45 Gothenburg, SwedenAstraZeneca R&DMolndal, Sweden.
FAU - Skrtic, S
AU  - Skrtic S
AD  - Department of EndocrinologySahlgrenska Academy, University of Gothenburg, 
      Sahlgrenska University Hospital, Grona Straket 8, SE-413 45 Gothenburg, 
      SwedenMedical AffairsViroPharma SPRL, Maidenhead, UKBiostatisticsViroPharma 
      IncorporatedDepartment of EndocrinologySkanes University Hospital, SE-205 02 
      Malmo, SwedenDepartment of Public Health and Clinical MedicineUmea University, 
      SE-901 87 Umea, SwedenSection of EndocrinologyDepartment of Medical and Health 
      Sciences, Faculty of Health Sciences, Linkoping University, SE-581 83 Linkoping, 
      SwedenDepartment of EndocrinologyDiabetes, and Metabolism, University 
      HospitalDepartment of PharmacyUppsala University, SE-751 85 Uppsala, 
      SwedenDepartment of Clinical PharmacologySahlgrenska Academy, University of 
      Gothenburg, SE-413 45 Gothenburg, SwedenAstraZeneca R&DMolndal, SwedenDepartment 
      of EndocrinologySahlgrenska Academy, University of Gothenburg, Sahlgrenska 
      University Hospital, Grona Straket 8, SE-413 45 Gothenburg, SwedenMedical 
      AffairsViroPharma SPRL, Maidenhead, UKBiostatisticsViroPharma 
      IncorporatedDepartment of EndocrinologySkanes University Hospital, SE-205 02 
      Malmo, SwedenDepartment of Public Health and Clinical MedicineUmea University, 
      SE-901 87 Umea, SwedenSection of EndocrinologyDepartment of Medical and Health 
      Sciences, Faculty of Health Sciences, Linkoping University, SE-581 83 Linkoping, 
      SwedenDepartment of EndocrinologyDiabetes, and Metabolism, University 
      HospitalDepartment of PharmacyUppsala University, SE-751 85 Uppsala, 
      SwedenDepartment of Clinical PharmacologySahlgrenska Academy, University of 
      Gothenburg, SE-413 45 Gothenburg, SwedenAstraZeneca R&DMolndal, Sweden.
FAU - Johannsson, G
AU  - Johannsson G
AD  - Department of EndocrinologySahlgrenska Academy, University of Gothenburg, 
      Sahlgrenska University Hospital, Grona Straket 8, SE-413 45 Gothenburg, 
      SwedenMedical AffairsViroPharma SPRL, Maidenhead, UKBiostatisticsViroPharma 
      IncorporatedDepartment of EndocrinologySkanes University Hospital, SE-205 02 
      Malmo, SwedenDepartment of Public Health and Clinical MedicineUmea University, 
      SE-901 87 Umea, SwedenSection of EndocrinologyDepartment of Medical and Health 
      Sciences, Faculty of Health Sciences, Linkoping University, SE-581 83 Linkoping, 
      SwedenDepartment of EndocrinologyDiabetes, and Metabolism, University 
      HospitalDepartment of PharmacyUppsala University, SE-751 85 Uppsala, 
      SwedenDepartment of Clinical PharmacologySahlgrenska Academy, University of 
      Gothenburg, SE-413 45 Gothenburg, SwedenAstraZeneca R&DMolndal, Sweden 
      gudmundur.johannsson@gu.se.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20140618
PL  - England
TA  - Eur J Endocrinol
JT  - European journal of endocrinology
JID - 9423848
RN  - WI4X0X7BPJ (Hydrocortisone)
SB  - IM
MH  - Adrenal Insufficiency/blood/*diagnosis/*drug therapy
MH  - Adult
MH  - Cross-Over Studies
MH  - Drug Administration Schedule
MH  - Female
MH  - Follow-Up Studies
MH  - Headache/chemically induced/diagnosis
MH  - Humans
MH  - Hydrocortisone/*administration & dosage/*adverse effects
MH  - Male
MH  - Middle Aged
MH  - Nasopharyngitis/chemically induced/diagnosis
MH  - Prospective Studies
PMC - PMC4106399
EDAT- 2014/06/20 06:00
MHDA- 2014/09/23 06:00
PMCR- 2014/09/01
CRDT- 2014/06/20 06:00
PHST- 2014/06/20 06:00 [entrez]
PHST- 2014/06/20 06:00 [pubmed]
PHST- 2014/09/23 06:00 [medline]
PHST- 2014/09/01 00:00 [pmc-release]
AID - EJE-14-0327 [pii]
AID - EJE140327 [pii]
AID - 10.1530/EJE-14-0327 [doi]
PST - ppublish
SO  - Eur J Endocrinol. 2014 Sep;171(3):369-77. doi: 10.1530/EJE-14-0327. Epub 2014 Jun 
      18.