2 183

S Burger-Stritt, A Eff and Patient education in adrenal 183:2 119–127 Clinical Study others insufficiency

Standardised patient education in adrenal insufficiency: a prospective multi-centre evaluation

Stephanie Burger-Stritt1,*, Annemarie Eff1,*, Marcus Quinkler2, Tina Kienitz3, Bettina Stamm4, Holger S Willenberg5, Gesine Meyer6, Johannes Klein7, Nicole Reisch8, Michael Droste9 and Stefanie Hahner1

1Endocrinology and Diabetes Unit, Department of Medicine I, University Hospital Wuerzburg, Wuerzburg, Germany, 2Endocrinology in Charlottenburg, Berlin, Germany, 3Department of Endocrinology, Diabetes and Nutrition, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany, 4Medical practice for Endocrinology, Saarbrücken, Germany, 5Division of Endocrinology and Metabolism, Rostock University Medical Center, Rostock, Germany, 6Endocrinology & Diabetes Unit, Department of Internal Medicine 1, Goethe- University Hospital Frankfurt, Frankfurt/Main, Germany, 7Medical Practice for Endocrinology, Lübeck, Germany, Correspondence 8Medizinische Klinik IV, Klinikum der Universität München, Munich, Germany, and 9Medical Practice for should be addressed Endocrinology & Diabetes, Oldenburg, Germany to S Hahner *(S Burger-Stritt and A Eff contributed equally to this work) Email [email protected]

Abstract

Objective: Patients with adrenal insufficiency (AI) suffer from impaired quality of life and are at risk of adrenal crisis (AC) despite established replacement therapy. Patient education is regarded an important measure for prevention of AC and improvement of AI management. A standardized education programme was elaborated for patients with chronic AI in Germany. Design: Longitudinal, prospective, questionnaire-based, multi-centre study. Methods: During 2-h sessions, patients (n = 526) were provided with basic knowledge on AI, equipped with emergency cards and sets and trained in self-injection of hydrocortisone. To evaluate the education programme, patients from European Journal of Endocrinology eight certified centres completed questionnaires before, immediately after and 6–9 months after training. Results: 399 completed data sets were available for analysis. Questionnaire score-values were significantly higher after patient education, indicating successful knowledge transfer (baseline: 17 ± 7.1 of a maximum score of 29; after training: 23 ± 4.2; P < 0.001), and remained stable over 6–9 months. Female sex, younger age and primary cause of AI were associated with higher baseline scores; after education, age, cause of AI and previous adrenal crisis had a significant main effect on scores. 91% of patients would dare performing self-injection after training, compared to 68% at baseline. An improvement of subjective well-being through participation in the education programme was indicated by 95% of the patients 6–9 months after participation. Conclusion: Patient group education in chronic AI represents a helpful tool for the guidance of patients, their self- assurance and their knowledge on prevention of adrenal crises. Repeated training and adaptation to specific needs, for example, of older patients is needed.

European Journal of Endocrinology (2020) 183, 119–127

https://eje.bioscientifica.com © 2020 European Society of Endocrinology Published by Bioscientifica Ltd. https://doi.org/10.1530/EJE-20-0181 Printed in Great Britain Downloaded from Bioscientifica.com at 09/28/2021 02:32:36AM via free access

-20-0181 European Journal of Endocrinology https://eje.bioscientifica.com emergency managementin a single-centrestudy( group meeting improved thepatients’ knowledge about showed thattheparticipation ina3-hGCeducation ( in childrenwasobserved of injection techniques on the management of AC positive effectofwritteninstructionsanddemonstration more structurededucationisneeded( skilled incopingwithstress,supportingtheviewthat patientswithchronicAIwere notsufficiently interviewed associated withmorenegativeillnessperceptions ( as stronger concerns about adverse effects of GCs were GCs ( had concernsregardingtheirreplacementtherapywith hormone replacementtherapyandthatmorethan50% were dissatisfiedwiththereceivedinformationontheir study documentedthatmorethan60%ofAIpatients crisis preventionandGCdoseadaptation( well’or‘well’informedabout of thepatientsfelt‘very suppositories orGCampules( were equippedwithemergencymedicationsuchasGC revealed thatonly30%oftheinvestigatedAIpatients not standardized and varies between centres. Two studies professional helpisprovided.However, educationissofar rapidly andindependentlyinemergencysituationsuntil education opensupthepossibilityforAIpatientstoact from homeorhealthcarefacilitiesin importance ( for example,incaseofgastroenteritisorfeverishigh mild andmoderatestress,parenteralGCadministration stressful events( dose-adjustment to cover the increased need in case of should furthermorebeeducatedinglucocorticoid(GC) to beequippedwithanemergencycardandset.They ( emphasize theimportantroleofawell-educatedpatient in theirmanagementbyhealthprofessionals,further disease, suchasreducedawarenessandlimitedexperience The specificdifficultiesusuallyassociatedwitharare as wellprotectionfromadrenalemergencies( maintenance ofgeneralwell-beinganddailylifeactivities of AI by the individual patient is thus essential for 4 attributed toinadequatehormonereplacement( mortality is well documented and has largely been reduced qualityoflifeandincreasedmorbidity In patientswithchronic adrenal insufficiency (AI), Introduction 17 , Clinical Study 5 , , Flemming According tocurrentguidelines,patientswithAIneed 18 6 22 , , 7 ). Thisisofrelevanceforthepatients’well-being 19 , 8 , , 20 9 15 , ). 10 ). Inalargesurvey, ACoccurredaway t al et 16 , 11 ). Besidesoraldoseadjustmentduring , . demonstratedthat46%of97 12 , 13 , 14 9 25 , ). Adequatemanagement 13 others S Burger-Stritt,AEffand ). Repping-Wuts ). Moreover, only64% 24 > 20% ( ). Furthermore,a 13 21 ). Another ). Patient 15 26 1 23 , t al et , ). 2 ). 16 , 3 ). , .

Oldenburg, amedicalpracticeforendocrinologyinBerlin, Wuerzburg, a medical practice for endocrinology in from eightcentres were included: University Hospital multicentre andquestionnaire-basedstudy. Patients The studywasconductedasaprospective,longitudinal, Study design Subjects andmethods safety regarding the managementofadrenalemergencies. and maintenanceofpatientknowledgethefeeling at theinitiatingcentreswithafocusonimprovement evaluate thisstandardizedpatienteducationprogramme of educationtotheirpatients. The aimof our studywasto German EndocrineSocietyandregularlyofferthisform Meanwhile, morethan70centreswerecertifiedbythe a standardizededucationprogrammeforpatientswithAI. including apracticaltraining wasprovidedbyanendocrine management andself-injection ofhydrocortisone during physical or psychological stress, AC,emergency Furthermore, knowledge ondoseadjustment of GCs information onadrenalphysiology andAIingeneral. per session).Theparticipantsreceivedbackground training forpatientsandtheirrelatives(4–10participants centres. Thepatienteducationconsistedofa2-hgroup that hadbeenelaboratedandconsentedbyallparticipating training materialincludingapower-pointpresentation a 1-daycertificationcourse.Thecentresusedthesame Endocrine Societyfortheeducationprogrammewithin All studycentreshadbeencertifiedbytheGerman Standardized patienteducation participation. informed consentwasobtainedfromallpatientsprior Clinicaltrials.gov identifier: NCT02694926. Written no. A2016-0088)andFrankfurt(permit283/15). following approvalofWuerzburg), Rostock(permit of Wuerzburg (permitno.278/14),CharitéBerlin(permit, approved bytheEthicsCommitteesofUniversities invited toparticipateintheevaluation.Thestudywas participated inthestandardizedpatienteducationwere under establishedcorticosteroidreplacementtherapywho in Luebeck.Patientsaged medical practiceinSaarbrueckenanda Hospital Frankfurt,theUniversityRostock,a the UniversityHospitalBerlin(Charité), insufficiency Patient educationinadrenal Recently, nineGermanendocrinecentresestablished Downloaded fromBioscientifica.com at09/28/202102:32:36AM ≥ 18 yearswithdocumentedAI 183 :2 120 via freeaccess European Journal of Endocrinology unpaired used as was used.Bonferroniand Dunnet-T3 procedurewere repeated-measures ANOVA withBonferronicorrection 24 (IBMSPSS,IBMCorp.). For comparisonofscores,a Statistical analysiswasperformed by PASW Statistics Statistical analysis higher levelofknowledge. sub-score: 10).Higherquestionnairescoresindicate a sub-score: 19)andemergencymanagement(maximum AI ingeneralaswellondoseadaptation(maximum (maximum achievablescore29)includingquestionson The secondpartofthequestionnairewasaknowledgetest scores, therefore, imply a higher degree of self-assurance. AC andself-assurancetodealwithincidentAC.Lower self-injection, self-assessmentoftheabilitytorecognize of thepatients’informationstatusonAI,doseadaptation, unsure’ (Scale1–5)forthefollowingitems:Self-assessment had toratefrom‘1 AC andtodealwith(onlyQ2Q3).Thepatients a self-injection,self-assessmentoftheabilitytoestimate dose adaptationandself-injection,confidencetoperform adjustment, feelingofsafety(educationstatus)inGC on quality of life, information status on AI and dose situation, perceived influence ofastandardizededucation injection, previousself-injectionduringanemergency an emergency card and set, previous education in self- The first part included questions on the availability of perception of AI, (ii) test of knowledge on AI and AC. of twoparts:(i)Questionsontheindividualcourseand for a follow-up appointment. The questionnaire consisted oratpresentation Q3 wasprovidedeitherbypostalservice immediately (Q2) and 6–9 months after education (Q3). received aquestionnaireatbaselinebefore(Q1), To evaluatetheeducationprogramme,allparticipants Questionnaire dose adjustmentandi.m.self-injection. administration together with written information on AI, card andmaterialrequiredforparenteralhydrocortisone In theend,allpatientswereequipped with an emergency s.c. self-injectionbythemselvesundermedicalsupervision. disease. Theywereinvitedtoperformani.m.oroff-label questions andexchangepersonalexperiencewiththeir end ofthisarticle).Patientshadtheopportunitytoask data, seesectionon nurse togetherwithanendocrinologist(Supplementary Clinical Study post hoc t -test (two groups, e.g. sex) or one-way ANOVA tests. For group comparison of scores an tests.Forgroupcomparison ofscoresan = supplementary materials supplementary very good/assured’to‘5 very others S Burger-Stritt,AEffand givenatthe = very bad/ very Study cohort Results below the median age of 55 years) and patients with longer withthedurationof disease. r the totalscoreagaincorrelated negativelywithage(Q2 duration ofdisease( with age( Q2: 8.7 1B Patient characteristicsaredisplayedin questionnaires andwereincludedinthefinalanalysis. after education);399patientscompletedallthree completed onlytwoquestionnaires(beforeanddirectly 526 patients with AI agreedtoparticipate. 127 patients were consideredasstatisticallysignificantwhen standard deviation( Gaussian distribution.Dataarepresentedasmeanand was performedtocorrelatemetricvariableswitha categorical variables.Furthermore,Pearsoncorrelation estimating equation(GEE)wasusedforcomparisonof metric variables. between twopointsintime,apaired ANOVA wasperformed.Forcomparisonofquestions of thesevariablesonthescores,a(multivariate)factorial ofapreviousACaswelltheinteractioneffects history main effectsofsex,age,causeAI,durationdiseaseand ( with BonferroniandDunnet-T3procedureas adaptation: Q1:11 Q2: 23 successful knowledge transfer. 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= 0.004; Q2 versus Q3 n 183 = 334) and assurance :2 123 via freeaccess European Journal of Endocrinology https://eje.bioscientifica.com treatment inaprospectiveanalysis ofAIpatients.Ofthese and ahigherrateofout-patientemergency intervals UK ( availability ofinformationon managementofACinthe whichwasattributedtoabroader over the5-yearinterval treatment inatimelymannerpre-hospitalsetting increased useofself-injectionandmorefrequentAC from UK, performed in 2013 and 2017/18, showed an inpatientsupport groups AC. Datafromalargesurvey provides animportantbasisforimprovedprevention of standardized groupeducationprogramme.Thiscertainly self-confidence tomanageACafterparticipationinour knowledge onmanagementofAIandACtheincreased An importantfindingofourstudyisthelastinggain in Discussion iatrogenic AIatanytime-point. female andmalepatientsorprimary, and secondary P an ACinQ2comparedtoQ3(2.2 Furthermore, patientsfeltbetterpreparedtomanage Q2 comparedtoQ3(2.2 and symptomsofincipientACwassignificantlybetterin The self-assessmentregardingtherecognitionofsigns Patients’ self-assessment–adrenalcrisis ** estimating equation(A)or (C) andage(D).Analyseswereperformedbygeneralised (Q3) patienteducation(A);dependentonsex(B),causeofAI injection before(Q1),directlyafter(Q2)and6–9months Percentage ofpatientswhowoulddaretoperformaself- Figure 3

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< 0.001). ± 0.9, fever in a previous study ( proactive withregardtoGCdoseadjustmentsincaseof Patients whohadalreadyexperiencedanACweremore of complications of AI and aimed at a higher information be assumedthatthesepatientsalreadyweremoreaware baseline andafterstandardizedgroupeducation.Itmay higher totalscoresinthetestofknowledgebothat ofACinthepastalsoachieved that patientswithahistory AC weremorepronetodevelopan( of endocrine disease,femalesexandthosewithahistory AI,diabetesinsipidus,concomitantnon- that primary previous AC.InvestigationsonriskfactorsforACrevealed of AIandpatientswithouthistory patients withsecondary knowledge scoreswerelowerinmales,olderpatients, concepts. Bothatbaselineandafter6–9months,mean thatmayberelevantforadaptationofteaching observed education programme( patients, 71%hadalreadyparticipatedinourstandardized would dare to perform a self-injection and patients felt would daretoperformaself-injection andpatientsfelt after education. Moreover, significantly fewer patients slightly worsenedat6–9months comparedtofirsttesting adaptation as well as their assurance in self-management assessment regardingtheinformation statusonAI,dose would, therefore,bedesirable. confidence. Tools facilitatingemergency management patients, whichmayhavefurthercontributedtoreduced syringes wasfrequently overcharging particularly forolder education programme,preparationofthehydrocortisone fromour older patients.Basedonempiricalobservations specific oratleastmorefrequentlyrepeatedtraining for to self-inject. This leads to the consideration of more participants. Theywerefurthermorelessconfident and aftergroupeducationcompared to youngerstudy achieved significantlylowertotalscoresbothbefore Australian analysis( inan incidence ofinfectiousdisease,wasobserved advancing age, mainlyassociated with anincreased therapy ( be relatedtoinadequate management of replacement ( presented withalowerlevelofknowledgeontheirdisease the group representing those patients in our study who AIandcomorbidity,older malepatientswithsecondary revealeda higher mortality risk in Insufficiency Registry an AC.Remarkably, datafromtheEuropeanAdrenal invested moretimeinindividualpatienteducationafter status. Attendingphysiciansmayfurthermorehave insufficiency Patient educationinadrenal 28 ). Theincreasedmortalityinthisgroupwaspart Several differences between patient sub-groups were Another findingofourstudyisthatpatients’self- An increaseofhospitaladmissionsduetoACwith 28 ). 29 20 ). Inourstudy, olderpatients Downloaded fromBioscientifica.com at09/28/202102:32:36AM ). 9 ). This fits to our observation ). This fits to our observation 183 :2 9 , 12 , 13 , 124 27 via freeaccess ). European Journal of Endocrinology patient education. needed inthelong-termcourse toapprovethebenefit of frequency of AC, hospitalization rate and mortality are cannot beruledout. centres dependentontheeducatingmedicalprofessionals centres, atleastminorvariationsbetweenthestudy documented gainofknowledgeinpatientsfromall of groupeducationasabasistheprogrammeand less specializedcentres.Moreover, despitestandardisation in the training programme compared to patients from have receivedmoreinformationalreadybeforeinclusion specialized forthemanagementofAIandmaytherefore emergencies. Patientsweretreatedincentresthatare have thepossibilitytousethemincaseofrealadrenal however, notnecessarilyaweaknesssincepatientsalso resulting in higher scores. Using the available resources is, other persons(relatives)toanswerthequestionsoftest the helpofavailablewritteninformationonAIandACor education athome,itcannotbeexcludedthattheyused completed the follow-up questionnaire 6–9 months after the studyhassomelimitations:Sincemostpatients evaluated withinthisprospectivemulticentreanalysis, general medicine. endocrinologist, emergencyphysicianoraprofessionalin an emergencymustbefollowedbycontactingatreating inform thepatientsthatself-injectionofGCsincase courses areledbytrainedmedicalprofessionals, who in caseofAC.Thus,itisimportantthateducation the riskofdelayedcontactingmedicalprofessionals need ofimprovedpatientinformation. subjective well-being in general, indicating a so far unmet participation inasystematictrainingalsoimprovedtheir videos mayhelptosustainthepatient’s knowledge. Furthermore, theuseofadditionaltoolslikeappsoronline case ofhospitaladmissionduetoadrenalinsufficiency. messages duringendocrineoutpatientconsultationsorin should becomplementedbyrepetitionofmaineducational advanced patienteducationcoursemaybehelpful.This the patients. In thiscontext, an allocationin a basicand appears tobeessentialandshouldrecommended ( competence inself-managementofstressfuleventsAI educational consultsarenotsufficienttoachievelasting to this,vanderMeij compared todirectlyaftereducation.Corresponding less assuredinthehandlingofanAC6–9monthsafter 30 Clinical Study ). Repetition of education in at least yearly intervals ). Repetitionofeducationinatleastyearlyintervals Although alargenumberofAIpatientshasbeen Self-management ofadrenalemergenciesmaybear Remarkably, mostpatientsofourstudyindicatedthat Further analysesfocusingon outcomemeasureslike t al et . observed that one or two thatoneortwo . observed others S Burger-Stritt,AEffand Disease’) to S Hahner as well as a research grant to S Burger-Stritt from the (within the CRC/Transregio 205/1 ‘The Adrenal: Central Relay in Health and (DFG) Forschungsgemeinschaft Deutsche the by supported was work This Funding be could that interest of conflict perceived asprejudicingtheimpartialityofthisstudy. no is there that declare authors The Declaration ofinterest EJE-20-0181 at paper the of version online the to linked is This Supplementary materials and subjectivewell-beinginAIpatients. improving patient care, managementofAC,self-assurance and repeatedpatienteducationbearsthepotentialof education inAIbyalargemulticentrestudy. Structured significant positiveeffectsofastandardizedgroup- (Lübeck) for their highly valuable support. they thank the department of department the thank they support. valuable highly their Britt for (Lübeck) Grube, Sandra and Doreen (Frankfurt), Sandler Maria Otte, (Rostock), Verbeek Christine Clemens Novikova, Elena Knauerhase, Zopf, Andreas Kathrin Elbelt, Ulf (Saarbrücken), Zeller Marion (Berlin), Kirchner Bauer, Janina Friedrich, Christiane Britta (Oldenburg), Pahl, Smadar Norkeweit (Würzburg), Pulzer Jessica Alina Rüger, Walter Horn, Silke thank their for excellent cooperation as well as all participating patients. They particularly study-centres participating all thank to like would authors The Acknowledgements approved the manuscript. and reviewed authors All manuscript. the of preparation and of study protocol and applications for authorities, conduct of the study preparation study, the of design the in involved was Hahner S study. the the of conduct and in design the in involved was involved Droste M study. the of conduct were Reisch N Klein, J Meyer, G Willenberg, H Stamm, B Kienitz, T study. the of conduct and design the in involved was Quinkler M analysis. data and collection data study, the of conduct authorities, for was Eff A applications of preparation manuscript. protocol, study of preparation the the in involved of preparation and analysis data study, the of preparation study, the of study protocol, preparationofapplications for authorities,conduct of design the in involved was Burger-Stritt S Author contributionstatement Nicole Reisch. S. Holger Munich: Britt. Sandra Klein, Johannes Rostock: Luebeck: Verbeek. Clemens Grube, Sandler. Maria Meyer, Doreen Otte, Christiane Novikova, Elena Knauerhase, Andreas Willenberg, Gesine Marion Stamm, Frankfurt: Bettina Zeller. Saarbruecken: Bauer. Charlottenburg: Britta Berlin Quinkler, Droste, Kirchner. Markus Janina Michael Elbelt, Ulf Oldenburg: Friedrich, Christiane Hahner. Zopf, Stefanie Kathrin Kienitz, Tina Berlin-Charité: Norkeweit. Jessica Pahl, Smadar Pulzer, Walter Alina Horn, Silke Rüger, Eff, Annemarie Burger-Stritt, Stephanie Wuerzburg: Study group IZKF Wuerzburg(Project-No.:Z-2/62). insufficiency Patient educationinadrenal In conclusion,thisprospectivestudydemonstrates . Downloaded fromBioscientifica.com at09/28/202102:32:36AM https://eje.bioscientifica.com 183 https://doi.org/10.1530/ :2 125 via freeaccess

European Journal of Endocrinology https://eje.bioscientifica.com References of theGermanEndocrineSociety(DGE). Hypertonus’ und Steroide ‘Nebenniere, Section the of project a was study The advice. statistical their for Augsburg UNIKA-T at Munich LMU the of epidemiology the as well as Wuerzburg of University the of epidemiology 11 10 9 8 7 6 5 4 3 2 1 Clinical Study Ritzel K, Beuschlein F, Mickisch A,Osswald A,Schneider HJ, Reisch N, Willige M, Kohn D,Schwarz HP, Allolio B,Reincke M, Hahner S, Spinnler C,Fassnacht M,Burger-Stritt S,Lang K, Burger-Stritt S, Pulzer A&Hahner S.Qualityoflifeand Kluger N, Matikainen N,Sintonen H,Ranki A,Roine RP&Schalin- Hahner S, Loeffler M,Fassnacht M, Weismann D, Koschker AC, Lovas K, Loge JH&Husebye ES.Subjectivehealthstatus Burman P, Mattsson AF, Johannsson G,Hoybye C,Holmer H, Erichsen MM, Lovas K,Fougner KJ,Svartberg J,Hauge ER, Bensing S, Brandt L,Tabaroj F, Sjoberg O,Nilsson B,Ekbom A, Bergthorsdottir R, Leonsson-Zachrisson M,Oden A&Johannsson G. doi.org/10.1210/jc.2013-1470) of ClinicalEndocrinologyandMetabolism adrenalectomy inCushing’s syndrome:asystematicreview. Schopohl J &Reincke M.Clinicalreview: Outcomeofbilateral doi.org/10.1530/EJE-12-0161) deficiency. of adrenalcrisesoverlifetimeinpatientswith21-hydroxylase Quinkler M, Hahner S&Beuschlein F. Frequencyandcauses org/10.1210/jc.2014-3191) Clinical EndocrinologyandMetabolism with chronicadrenalinsufficiency:aprospectivestudy. Allolio B. Highincidenceofadrenalcrisisineducatedpatients Milovanovic D, Beuschlein F, Willenberg HS, Quinkler M& (https://doi.org/10.1159/000443918) what isurbanmyth? expectancy inpatientswithadrenalinsufficiency:whatistrueand org/10.1111/cen.12484) factors. – impactofreplacementtherapy, comorbiditiesandsocio-economic Jantti C. Impairedhealth-relatedqualityoflifeinAddison’s disease 0685) Metabolism based oncross-sectionalanalysis. status in256patientswithadrenalinsufficiencyonstandardtherapy Quinkler M, Decker O,Arlt W&Allolio B.Impairedsubjectivehealth 2265.2002.01466.x) Endocrinology patientswithAddison’sin Norwegian disease. 4059) Metabolism to anincreasedmortality. during acutestress,anddenovomalignantbraintumorscontribute Deaths amongadultpatientswithhypopituitarism:hypocortisolism Dahlqvist P, Berinder K,Engstrom BE,Ekman B,Erfurth EM doi.org/10.1530/EJE-08-0550) death. rate inAddison’s disease,butyoungpatientsareatriskofpremature Bollerslev J, Berg JP, Mella B&Husebye ES.Normaloverallmortality 697–704. adrenocorticalinsufficiency.primary incidence patterninpatientswithisolatedorcombinedautoimmune Blomqvist P &Kampe O.Increaseddeathriskandalteredcancer 4849–4853. based study. Premature mortalityinpatientswithAddison’s disease:apopulation- European Journal ofEndocrinology European Journal Clinical Endocrinology (https://doi.org/10.1111/j.1365-2265.2008.03340.x) 2007 2013 European Journal ofEndocrinology European Journal (https://doi.org/10.1210/jc.2006-0076) Journal ofClinicalEndocrinologyand Metabolism Journal 2002 92 98 56 3912–3922. 1466–1475. Frontiers of Hormone ResearchFrontiers ofHormone 581–588. Journal ofClinicalEndocrinologyand Journal 2014 (https://doi.org/10.1046/j.1365- (https://doi.org/10.1210/jc.2007- (https://doi.org/10.1210/jc.2012- Journal ofClinicalEndocrinologyand Journal 81 2015 Clinical Endocrinology 511–518. others S Burger-Stritt,AEffand 2009 2013 100 2012 160 98 Clinical 407–416. 3939–3948. (https://doi. 233–237. 167 2016 35–42. 46 Journal of Journal (https://doi. 2008 171–183. 2006 (https:// et al Journal Journal (https:// (https:// . 69 91

insufficiency Patient educationinadrenal 25 24 23 22 18 17 16 15 14 12 26 21 20 19 13 Fleming LK, Rapp CG&Sloane R.Caregiverknowledgeandself- Flemming TG &Kristensen LO.Qualityofself-careinpatients Tiemensma J, Andela CD,Pereira AM,Romijn JA,Biermasz NR Chapman SC, Llahana S,Carroll P&Horne R.Glucocorticoid Kampmeyer D, Lehnert H,Moenig H,Haas CS&Harbeck B.Astrong Hahner S, Hemmelmann N,Quinkler M,Beuschlein F, Spinnler C& Bornstein SR, Allolio B,Arlt W, Barthel A,Don-Wauchope A, Allolio B. Extensiveexpertiseinendocrinology. Adrenalcrisis. Meyer G, Badenhoop K&Linder R.Addison’s diseasewith Smans LC, Van derValk ES, Hermus AR&Zelissen PM.Incidence Repping-Wuts HJ, Stikkelbroeck NM,Noordzij A,Kerstens M& White KG. Aretrospectiveanalysisofadrenalcrisisinsteroid- Burger-Stritt S, Kardonski P, Pulzer A,Meyer G,Quinkler M& Harbeck B, Brede S,Witt C, Sufke S,Lehnert H&Haas C. Hahner S, Loeffler M,Bleicken B,Drechsler C,Milovanovic D, congenital adrenalhyperplasia. confidence ofstressdosinghydrocortisoneinchildrenwith 2796.1999.00538.x) Medicine on replacementtherapywithhydrocortisone. 3668–3676. perceptions. hydrocortisone intakeareassociatedwithmorenegativeillness medication: concernsandstrongerbeliefsaboutthenecessityof & Kaptein AA.Patientswithadrenalinsufficiencyhatetheir 664–671. dissatisfaction withinformation. therapy foradrenalinsufficiency:nonadherence,concernsand doi.org/10.1111/cen.12609) limits andreality. Allolio B. Timelines inthemanagementofadrenal crisis–targets, org/10.1210/jc.2015-1710) Endocrinology andMetabolism an EndocrineSocietyclinicalpracticeguideline. et al Hammer GD, Husebye ES,Merke DP, Murad MH,Stratakis CA org/10.1530/EJE-14-0824) ofEndocrinology European Journal Endocrinology adrenal crises:GermanHealthInsuranceData2010–2013. polyglandular autoimmunitycarriesamorethan2.5-foldriskfor Endocrinology of adrenalcrisisinpatientswithinsufficiency. org/10.1530/EJE-12-1094) ofEndocrinology European Journal strategy forimprovingself-management topreventadrenalcrisis. Hermus AR. Aglucocorticoideducation groupmeeting:aneffective e55–e60. Disorders dependent patients:causes,frequencyandoutcomes. 2018 with adrenalinsufficiency–aprospectivestudy. Hahner S. Managementofadrenalemergenciesineducatedpatients doi.org/10.1507/endocrj.EJ14-0612) challenge tophysicians? Glucocorticoid replacementtherapyinadrenalinsufficiency–a 33 and multicentreevaluation. replacement treatmentinadrenalinsufficiency:aninterdisciplinary need forimprovingtheeducationofphysiciansonglucocorticoid 597–602. prevention strategies. adrenal crisisinchronicinsufficiency:theneedfornew Fassnacht M, Ventz M, Quinkler M&Allolio B.Epidemiologyof e13–e15. . Diagnosis and treatment of primary adrenalinsufficiency: . Diagnosisandtreatmentofprimary 89 22–29. 1999 2019 (https://doi.org/10.1016/j.pedn.2011.03.009) (https://doi.org/10.1111/cen.12991) (https://doi.org/10.1530/EJE-09-0884) (https://doi.org/10.1210/jc.2014-1527) (https://doi.org/10.1016/j.ejim.2016.04.006) Journal ofClinicalEndocrinologyandMetabolism Journal 2016 2016 246 19 (https://doi.org/10.1111/cen.13608) 129. Clinical Endocrinology 497–501. 85 84 347–353. 17–22. European Journal ofEndocrinology European Journal (https://doi.org/10.1186/s12902-019-0459-z) Endocrine Journal Downloaded fromBioscientifica.com at09/28/202102:32:36AM European Journal of Internal Medicine ofInternal European Journal 2016 (https://doi.org/10.1046/j.1365- (https://doi.org/10.1111/cen.12865) Journal ofPediatricNursing Journal 2013 2015 (https://doi.org/10.1111/cen.13043) Clinical Endocrinology 101 172 169 364–389. 2015 2015 R115–R124. 17–22. 183 82 Journal of Internal ofInternal Journal :2 62 497–502. Clinical Endocrinology Journal ofClinical Journal (https://doi. (https://doi. 463–468. BMC Endocrine 2010 2016 Clinical (https://doi. 2011 (https:// Clinical 2014 162 84 (https:// 126

2016 26

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European Journal of Endocrinology

28 27 Clinical Study Quinkler M, Ekman B,Zhang P, Isidori AM,Murray RD& White K &Arlt W. AdrenalcrisisintreatedAddison’s disease:a cen.13609) Clinical Endocrinology characterizationandassociations. Insufficiency Registry-patient EU-AIR Investigators.MortalitydatafromtheEuropeanAdrenal 2010 predictable butunder-managedevent. 162 115–120. (https://doi.org/10.1530/EJE-09-0559) 2018 89 30–35. (https://doi.org/10.1111/ others S Burger-Stritt,AEffand European Journal ofEndocrinology European Journal

Accepted 6May2020 Revised versionreceived22April2020 Received 1March2020

insufficiency Patient educationinadrenal 30 29 van derMeij NT, vanLeeuwaarde RS,Vervoort SC &Zelissen PM. Rushworth RL &Torpy DJ. Adescriptivestudyofadrenalcrisesin cen.13083) Clinical Endocrinology Self-management supportinpatientswithadrenalinsufficiency. (https://doi.org/10.1186/1472-6823-14-79) those withbacterialinfections. adults withadrenalinsufficiency:increasedriskageandin 2016 Downloaded fromBioscientifica.com at09/28/202102:32:36AM 85 652–659. BMC EndocrineDisorders https://eje.bioscientifica.com (https://doi.org/10.1111/ 183 :2 2014 14 127 79. via freeaccess