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Self-perceived health status of patients with adrenal insufficiency receiving glucocorticoid replacement therapy – French data from a worldwide patient survey
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ScienceDirect www.sciencedirect.com Annales d’Endocrinologie 76 (2015) 9–12
Original article
Self-perceived health status of patients with adrenal insufficiency receiving glucocorticoid replacement therapy – French data from a worldwide patient survey Comment les patients présentant une insuffisance surrénale traitée par glucocorticoïdes per¸coivent-ils leur état de santé ? Données fran¸caises d’une enquête internationale Philippe Touraine a,∗ , Gaëlle Chenuc b , Claudine Colin c a
Department of endocrinology and reproductive medicine, IE3M, hôpital universitaire Pitié-Salpêtrière, UPMC, 47-83, boulevard de l’Hôpital, 75651 Paris cedex 13, France b Capionis, 183/189, avenue de Choisy, 75013 Paris, France c Association Surrénales, 14, avenue Anatole France, 76330 Notre Dame de Gravenchon, France
Abstract An international survey was undertaken to investigate current practices in glucocorticoid replacement therapy and self-perceived health status of patients with adrenal insufficiency, using a 39-item questionnaire. Results were published in 2012. We analyzed data from French patients, extracted from the database. Participants were recruited via a patient advocacy group to respond anonymously to a questionnaire developed by clinical experts. Ninety-four patients participated (primary adrenal insufficiency 79% and secondary adrenal insufficiency 16%). They were treated mainly with hydrocortisone (97.5%). Dosing regimens were once daily (8%), twice daily (38%), thrice daily (30%) or other (24%). Nearly 80% of the participants considered their affection to have an impact on their physical activity, work, family or social life and 38% reported absence from work/school in the last 3 months. Fatigue in the morning or during the day was a problem for 57% and 69% of respondents respectively. Eighty percent were concerned about long-term side effects of therapy, mainly osteoporosis (79%), fatigue (57%) and obesity (43%). Despite obvious biases in the survey, we should be alerted by the high number of patients’ complaints and the clear signs of quality of life impairment in this population, and think about strategies to improve their management. © 2014 Elsevier Masson SAS. All rights reserved. Keywords: Adrenal insufficiency; Glucocorticoid replacement therapy; Quality of life; Self-perceived health status
Résumé Une enquête internationale dont les résultats ont été publiés en 2012 a été réalisée pour décrire le traitement substitutif par glucocorticoïdes de l’insuffisance surrénale en pratique courante et l’auto-évaluation de leur état de santé par les patients en utilisant un questionnaire comportant 39 items. Nous avons analysé les données des patients franc¸ais, extraites de la base de données. Les participants ont été recrutés par l’intermédiaire d’une association de patients pour répondre anonymement à un questionnaire développé par des experts. Les données portent sur quatre-vingtquatorze patients (insuffisance surrénale primaire 79 % et secondaire 16 %). Ils étaient traités par hydrocortisone dans 97,5 % des cas. Les schémas posologiques étaient les suivants : une prise par jour (8 %), deux prises par jour (38 %), trois prises par jour (30 %) ou autre (24 %). Environ 80 % des participants considéraient que leur maladie avait un impact sur leur activité physique, professionnelle, familiale ou sociale et 38 % ont déclaré une absence au travail ou à l’école au cours des 3 derniers mois. La fatigue matinale ou au cours de la journée était considérée comme posant des
∗
Corresponding author. E-mail address: [email protected] (P. Touraine).
http://dx.doi.org/10.1016/j.ando.2014.09.003 0003-4266/© 2014 Elsevier Masson SAS. All rights reserved.
10
P. Touraine et al. / Annales d’Endocrinologie 76 (2015) 9–12
difficultés à 57 % et 69 % des répondeurs respectivement. Quatre-vingts pourcent des participants étaient préoccupés par les effets secondaires à long terme du traitement, principalement l’ostéoporose (79 %), la fatigue (57 %) et l’obésité (43 %). En dépit des biais existants dans cette étude, nous devons être alertés par l’importance des plaintes des patients et les signes reflétant une altération de leur qualité de vie pour réfléchir à des stratégies d’amélioration de la prise en charge. © 2014 Elsevier Masson SAS. Tous droits réservés. Mots clés : Insuffisance surrénale ; Traitement glucocorticoïde substitutif ; Qualité de vie ; Perception de l’état de santé
1. Introduction
2. Methods
Adrenal insufficiency (AI) is a rare but serious condition comprising two different entities, namely primary AI (PAI: mostly due to autoimmune adrenalitis) with a prevalence of 93–140 per million and secondary AI (SAI: mostly due to pituitary diseases) with an estimated prevalence of 150–280 per million [1]. Standard treatment mainly consists of lifelong glucocorticoid replacement, alone or associated with mineralocorticoids in case of PAI. This therapy dramatically improved survival primarily because it prevents efficiently adrenal crises [1]. However, the disease remains associated with increased mortality rates compared with the general population, either in patients with PAI [2,3] or in those with SAI [4,5]. Cardiovascular diseases remain a leading cause of death in patients with AI [3,4] and this might be in relation with inappropriate replacement therapy, since it is well-known that supraphysiological levels of glucocorticoids increase cardiovascular morbidity and mortality. Yet, many studies have shown that AI patients have an unfavorable metabolic profile [6], and a reduced bone mineral density [7,8], which are also features of exposure to high cortisol levels over long-term periods. In addition, patients suffering from AI have significantly impaired quality of life [9]. Thus, one can assume that the current treatment of AI patients is not optimal. Guidelines have been issued in the US by the Endocrine Society for the management of congenital adrenal hyperplasia [10] and more recently, a consensus statement was published for primary AI [11]. However, management strategies may vary widely between clinicians and between patients; for instance, a study showed a huge variability in dosing regimens with 13 different schedules among 50 patients in a single center [12]. In this study, the percentages of patients with overor underdosing were 79%, 55% and 45% at 8 AM, 4 PM and midnight respectively. Actually, the modalities of treatment in daily practice remain largely unknown. Patients’ satisfaction with treatment and their self-perception of health status have not been very much investigated, while patients’ perception is increasingly recognized as a major issue in many therapeutic areas. Forss et al. recently published the results of an international survey conducted exclusively among AI patients in 34 countries [13]. They described current practices in glucocorticoid replacement therapy and the participants’ self-perceived health status, as reported by 1245 respondents [13]. In this article, we present the data obtained from the subgroup of French patients who participated in this international survey.
This open cross-sectional survey started on September 12th and ended on December 19th 2008. In France as in other countries, participants were recruited via a patient advocacy group, namely the “Association Surrénales” that informed its members about the survey and its objectives. A link to access the web-based questionnaire was sent upon request to those interested by the survey. Patients responded anonymously in order to protect the individual identity (no data on age or gender collected). No payment was associated with their participation in the survey. The questionnaire, developed by clinical experts, consisted of thirty-nine questions, including a mix of single select, multiple select and open questions. Most questions were subjective, relating to various aspects of health status and quality of life. The questionnaire has not been published nor validated in AI, it has been elaborated specifically for the purpose of the survey, then translated into national languages. The following information was collected: type of disease, type of glucocorticoid replacement therapy and satisfaction with this medication, impact of the disease on self-perceived subjective health, prevalence and impact of fatigue, opinion on long-term side effects of the treatment, hospitalizations and absenteeism from work or school (Appendix A). Patients answered the questionnaire directly on a website. Only descriptive statistics were used. The survey did not require any ethics committee approval. 3. Results Ninety-four patients participated in the survey in France (1245 worldwide). Sixty-four (79%) defined their disease as primary (Addison disease, adrenal disease causing dysfunction of adrenal glands or removed glands, congenital adrenal hyperplasia) and 13 (16%) as secondary (pituitary or hypothalamic diseases), while 4 (5%) were unsure on their type of adrenal insufficiency they had. Hormone replacement therapy was almost exclusively hydrocortisone (97.5% of patients). According to patients, the total daily dose had not been adjusted on body weight or body surface area in 56% of cases. Most patients were on a twice daily (38%) or thrice daily regimen (30%), while only 9% were on a once daily regimen and 24% of patients used other dosing schedules. Among those on a twice-daily regimen, 60% took their medication in the morning and in the afternoon and 40% in the morning and in the evening. Thirty percent of the participants were dissatisfied or very dissatisfied with their current treatment, whereas 62% were satisfied or very satisfied and 8% were
P. Touraine et al. / Annales d’Endocrinologie 76 (2015) 9–12
11
Table 1 Most important features of an optimal replacement medication according to AI patients (n = 66).
Once daily Quick onset Few side effects Enduring efficacy over 24 hours Physiological therapy Low risk of adrenal crisis Price Other
Most important (%)
2nd most important (%)
3rd most important (%)
11.8 8.8 23.5 25 11.8 16.2 0 2.9
7.6 12.1 27.3 13.6 15.2 19.7 3.0 1.5
7.6 10.6 18.2 21.2 10.6 25.8 4.5 1.5
indifferent. Multiple daily dosing was reported as a problem by 46% of the respondents, mostly due to the risk of forgetting an intake. When asked which was the most important feature of an optimal replacement medication, 25% of participants responded “enduring efficacy over 24 hours”, 23.5% selected “few side effects” and 16.2% chose “low risk for adrenal crisis” (Table 1). A majority of participants (80%) was concerned about possible long-term side effects of glucocorticoid replacement therapy. Their major concern was osteoporosis (79%), followed by fatigue (57%), obesity (43%), cardiovascular problems (29%) and infectious diseases (27%). Three out of 4 respondents reported that AI impaired their quality of life (QoL) with varying degrees of severity (53% graded the impact on QoL as “quite a lot” or “very much”). Altered activities were mainly physical activity (62%) and work life (47%) (Fig. 1). A majority of respondents mentioned fatigue as a problem, whether it occurred in the morning or during the day (57% and 69% respectively) (Table 2). A more rapid onset of medication in the morning would be perceived as a benefit for 69% of respondents. Sixty-three percent of respondents declared that they sometimes modify their treatment due to fatigue: 31% change the dose, 12% change the time of intake and 20% change both time and dose. On average, the increase of glucocorticoid dose is decided at least once per week due to physical activity in 43% of patients and at least once per month due to intercurrent illness in 80%. Only fifty-seven percent of respondents considered themselves fit to work whereas 21% did not (unable to work or on sick leave), 11% were retired and 11% were unemployed. Among those able to work, 76% considered they could work full time while 9% could work 75% of time, 9% could work half time and 6% could work less than half time. Overall, 38% of respondents were absent from work or school for AI-related
Fig. 1. Changes in activities due to adrenal insufficiency (n = 68).
Table 2 Fatigue experienced as a problem by AI patients. n (%) Fatigue experienced as a problem in the morning (n = 67) Yes If yes, how much of a problem? (n = 34) Small Intermediate Big Very big Fatigue experienced as a problem during the day (n = 65) Yes If yes, how much of a problem? (n = 43) Small Intermediate Big Very big
38 (57) 2 (6) 17 (50) 10 (29) 5 (15) 45 (69) 5 (12) 17 (39) 18 (42) 3 (7)
reasons during the last 3 months (Fig. 2). Nearly one-half (48%) reported hospitalization within the last 12 months. This article presents the data of French patients who participated in a worldwide survey published by Forss et al. [13]. France was the third country after the US and Australia by the number of respondents. We are aware of obvious biases in patients’ selection. First, only the members of a single patient organization were invited to participate; second, only those with Internet access could respond; so, this subgroup of French patients may not represent the whole French AI population. Respondents’ profiles were heterogeneous and included pediatric patients with congenital adrenal hyperplasia. Moreover, numerous missing data make some answers difficult to interpret. We have no data on age, sex, and characteristics of the
Fig. 2. Number of days of absenteeism from work or school during the last 3 months (n = 22).
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P. Touraine et al. / Annales d’Endocrinologie 76 (2015) 9–12
disease. Finally, the questionnaire was not validated in AI and most questions were subjective and inaccurate. Yet, responses were consistent with those provided by patients from other countries [13], suggesting that difficulties encountered by AI patients (problems with multiple dosing regimens, fatigue, absenteeism from work or school and concerns about long-term side effects) are constant among various categories of patients and types of management. They result in a perception of poor health status and impaired quality of life. These signals should invite physicians to think about strategies to improve their patients’ management, including optimization of glucocorticoid replacement therapy, since current therapies do not reproduce adequately physiological cortisol circadian rhythm [14] and patient education that might be inspired from recommendations issued for other adrenal diseases [15]. 4. Conclusion This is the first report of a French patient survey in the field of AI and data show potential room for improvement in their management. Despite numerous biases, impaired self-perceived health status is striking in at least some AI patients. In the future, we should probably more focus on patients’ perception and make every effort to optimize treatment, with regard to individual patient profiles and living conditions. Moreover, we believe that implementation of patients’ education programs and publication of guidelines would be highly useful for patients and physicians. In addition, new formulations with better reproduction of cortisol physiological profile may probably help solving some side effects and practicability issues. 5. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. Acknowledgements We would like to thank the patients who participated in the survey, the “Association Surrénales” that allowed the participation of France and Viropharma that supported the study. Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.ando. 2014.09.003.
References [1] Arlt W, Allolio B. Adrenal insufficiency. Lancet 2003;361:1881–93. [2] Bensing S, Brandt L, Tabaroj F, Sjoberg O, Nilsson B, Ekbom A, et al. Increased death risk and altered cancer incidence pattern in patients with isolated or combined autoimmune primary adrenocortical insufficiency. Clin Endocrinol (Oxf) 2008;69:697–704. [3] Bergthorsdottir R, Leonsson-Zachrisson M, Oden A, Johannsson G. Premature mortality in patients with Addison’s disease: a population-based study. J Clin Endocrinol Metab 2006;91:4849–53. [4] Sherlock M, Ayuk J, Tomlinson JW, Toogood AA, Aragon-Alonso A, Sheppard MC, et al. Mortality in patients with pituitary disease. Endocr Rev 2010;31:301–42. [5] Fernandez-Rodriguez E, Lopez-Raton M, Andujar P, Martinez-Silva IM, Cadarso-Suarez C, Casanueva FF, et al. Epidemiology, mortality rate and survival in a homogeneous population of hypopituitary patients. Clin Endocrinol (Oxf) 2013;78:278–84. [6] Filipsson H, Monson JP, Koltowska-Haggstrom M, Mattsson A, Johannsson G. The impact of glucocorticoid replacement regimens on metabolic outcome and comorbidity in hypopituitary patients. J Clin Endocrinol Metab 2006;91:3954–61. [7] Lovas K, Gjesdal CG, Christensen M, Wolff AB, Almas B, Svartberg J, et al. Glucocorticoid replacement therapy and pharmacogenetics in Addison’s disease: effects on bone. Eur J Endocrinol 2009;160: 993–1002. [8] Zelissen PM, Croughs RJ, van Rijk PP, Raymakers JA. Effect of glucocorticoid replacement therapy on bone mineral density in patients with Addison disease. Ann Intern Med 1994;120:207–10. [9] Hahner S, Loeffler M, Fassnacht M, Weismann D, Koschker AC, Quinkler M, et al. Impaired subjective health status in 256 patients with adrenal insufficiency on standard therapy based on cross-sectional analysis. J Clin Endocrinol Metab 2007;92:3912–22. [10] Speiser PW, Azziz R, Baskin LS, Ghizzoni L, Hensle TW, Merke DP, et al. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2010;95:4133–60. [11] Husebye ES, Allolio B, Arlt W, Badenhoop K, Bensing S, Betterle C, et al. Consensus statement on the diagnosis, treatment and follow-up of patients with primary adrenal insufficiency. J Intern Med 2014;275: 104–15. [12] Simon N, Castinetti F, Ouliac F, Lesavre N, Brue T, Oliver C. Pharmacokinetic evidence for suboptimal treatment of adrenal insufficiency with currently available hydrocortisone tablets. Clin Pharmacokinet 2010;49:455–63. [13] Forss M, Batcheller G, Skrtic S, Johannsson G. Current practice of glucocorticoid replacement therapy and patient-perceived health outcomes in adrenal insufficiency – a worldwide patient survey. BMC Endocr Disord 2012;12:8. [14] Nunes M-L, Tabarin A. Les actualités de l’insuffisance surrénalienne. Ann Endocrinol 2008;69:S44–52. [15] HAS. Syndrome de cushing. Protocole national de diagnostic et de soins; Septembre 2008.
ScienceDirect www.sciencedirect.com Annales d’Endocrinologie 76 (2015) 9–12
Original article
Self-perceived health status of patients with adrenal insufficiency receiving glucocorticoid replacement therapy – French data from a worldwide patient survey Comment les patients présentant une insuffisance surrénale traitée par glucocorticoïdes per¸coivent-ils leur état de santé ? Données fran¸caises d’une enquête internationale Philippe Touraine a,∗ , Gaëlle Chenuc b , Claudine Colin c a
Department of endocrinology and reproductive medicine, IE3M, hôpital universitaire Pitié-Salpêtrière, UPMC, 47-83, boulevard de l’Hôpital, 75651 Paris cedex 13, France b Capionis, 183/189, avenue de Choisy, 75013 Paris, France c Association Surrénales, 14, avenue Anatole France, 76330 Notre Dame de Gravenchon, France
Abstract An international survey was undertaken to investigate current practices in glucocorticoid replacement therapy and self-perceived health status of patients with adrenal insufficiency, using a 39-item questionnaire. Results were published in 2012. We analyzed data from French patients, extracted from the database. Participants were recruited via a patient advocacy group to respond anonymously to a questionnaire developed by clinical experts. Ninety-four patients participated (primary adrenal insufficiency 79% and secondary adrenal insufficiency 16%). They were treated mainly with hydrocortisone (97.5%). Dosing regimens were once daily (8%), twice daily (38%), thrice daily (30%) or other (24%). Nearly 80% of the participants considered their affection to have an impact on their physical activity, work, family or social life and 38% reported absence from work/school in the last 3 months. Fatigue in the morning or during the day was a problem for 57% and 69% of respondents respectively. Eighty percent were concerned about long-term side effects of therapy, mainly osteoporosis (79%), fatigue (57%) and obesity (43%). Despite obvious biases in the survey, we should be alerted by the high number of patients’ complaints and the clear signs of quality of life impairment in this population, and think about strategies to improve their management. © 2014 Elsevier Masson SAS. All rights reserved. Keywords: Adrenal insufficiency; Glucocorticoid replacement therapy; Quality of life; Self-perceived health status
Résumé Une enquête internationale dont les résultats ont été publiés en 2012 a été réalisée pour décrire le traitement substitutif par glucocorticoïdes de l’insuffisance surrénale en pratique courante et l’auto-évaluation de leur état de santé par les patients en utilisant un questionnaire comportant 39 items. Nous avons analysé les données des patients franc¸ais, extraites de la base de données. Les participants ont été recrutés par l’intermédiaire d’une association de patients pour répondre anonymement à un questionnaire développé par des experts. Les données portent sur quatre-vingtquatorze patients (insuffisance surrénale primaire 79 % et secondaire 16 %). Ils étaient traités par hydrocortisone dans 97,5 % des cas. Les schémas posologiques étaient les suivants : une prise par jour (8 %), deux prises par jour (38 %), trois prises par jour (30 %) ou autre (24 %). Environ 80 % des participants considéraient que leur maladie avait un impact sur leur activité physique, professionnelle, familiale ou sociale et 38 % ont déclaré une absence au travail ou à l’école au cours des 3 derniers mois. La fatigue matinale ou au cours de la journée était considérée comme posant des
∗
Corresponding author. E-mail address: [email protected] (P. Touraine).
http://dx.doi.org/10.1016/j.ando.2014.09.003 0003-4266/© 2014 Elsevier Masson SAS. All rights reserved.
10
P. Touraine et al. / Annales d’Endocrinologie 76 (2015) 9–12
difficultés à 57 % et 69 % des répondeurs respectivement. Quatre-vingts pourcent des participants étaient préoccupés par les effets secondaires à long terme du traitement, principalement l’ostéoporose (79 %), la fatigue (57 %) et l’obésité (43 %). En dépit des biais existants dans cette étude, nous devons être alertés par l’importance des plaintes des patients et les signes reflétant une altération de leur qualité de vie pour réfléchir à des stratégies d’amélioration de la prise en charge. © 2014 Elsevier Masson SAS. Tous droits réservés. Mots clés : Insuffisance surrénale ; Traitement glucocorticoïde substitutif ; Qualité de vie ; Perception de l’état de santé
1. Introduction
2. Methods
Adrenal insufficiency (AI) is a rare but serious condition comprising two different entities, namely primary AI (PAI: mostly due to autoimmune adrenalitis) with a prevalence of 93–140 per million and secondary AI (SAI: mostly due to pituitary diseases) with an estimated prevalence of 150–280 per million [1]. Standard treatment mainly consists of lifelong glucocorticoid replacement, alone or associated with mineralocorticoids in case of PAI. This therapy dramatically improved survival primarily because it prevents efficiently adrenal crises [1]. However, the disease remains associated with increased mortality rates compared with the general population, either in patients with PAI [2,3] or in those with SAI [4,5]. Cardiovascular diseases remain a leading cause of death in patients with AI [3,4] and this might be in relation with inappropriate replacement therapy, since it is well-known that supraphysiological levels of glucocorticoids increase cardiovascular morbidity and mortality. Yet, many studies have shown that AI patients have an unfavorable metabolic profile [6], and a reduced bone mineral density [7,8], which are also features of exposure to high cortisol levels over long-term periods. In addition, patients suffering from AI have significantly impaired quality of life [9]. Thus, one can assume that the current treatment of AI patients is not optimal. Guidelines have been issued in the US by the Endocrine Society for the management of congenital adrenal hyperplasia [10] and more recently, a consensus statement was published for primary AI [11]. However, management strategies may vary widely between clinicians and between patients; for instance, a study showed a huge variability in dosing regimens with 13 different schedules among 50 patients in a single center [12]. In this study, the percentages of patients with overor underdosing were 79%, 55% and 45% at 8 AM, 4 PM and midnight respectively. Actually, the modalities of treatment in daily practice remain largely unknown. Patients’ satisfaction with treatment and their self-perception of health status have not been very much investigated, while patients’ perception is increasingly recognized as a major issue in many therapeutic areas. Forss et al. recently published the results of an international survey conducted exclusively among AI patients in 34 countries [13]. They described current practices in glucocorticoid replacement therapy and the participants’ self-perceived health status, as reported by 1245 respondents [13]. In this article, we present the data obtained from the subgroup of French patients who participated in this international survey.
This open cross-sectional survey started on September 12th and ended on December 19th 2008. In France as in other countries, participants were recruited via a patient advocacy group, namely the “Association Surrénales” that informed its members about the survey and its objectives. A link to access the web-based questionnaire was sent upon request to those interested by the survey. Patients responded anonymously in order to protect the individual identity (no data on age or gender collected). No payment was associated with their participation in the survey. The questionnaire, developed by clinical experts, consisted of thirty-nine questions, including a mix of single select, multiple select and open questions. Most questions were subjective, relating to various aspects of health status and quality of life. The questionnaire has not been published nor validated in AI, it has been elaborated specifically for the purpose of the survey, then translated into national languages. The following information was collected: type of disease, type of glucocorticoid replacement therapy and satisfaction with this medication, impact of the disease on self-perceived subjective health, prevalence and impact of fatigue, opinion on long-term side effects of the treatment, hospitalizations and absenteeism from work or school (Appendix A). Patients answered the questionnaire directly on a website. Only descriptive statistics were used. The survey did not require any ethics committee approval. 3. Results Ninety-four patients participated in the survey in France (1245 worldwide). Sixty-four (79%) defined their disease as primary (Addison disease, adrenal disease causing dysfunction of adrenal glands or removed glands, congenital adrenal hyperplasia) and 13 (16%) as secondary (pituitary or hypothalamic diseases), while 4 (5%) were unsure on their type of adrenal insufficiency they had. Hormone replacement therapy was almost exclusively hydrocortisone (97.5% of patients). According to patients, the total daily dose had not been adjusted on body weight or body surface area in 56% of cases. Most patients were on a twice daily (38%) or thrice daily regimen (30%), while only 9% were on a once daily regimen and 24% of patients used other dosing schedules. Among those on a twice-daily regimen, 60% took their medication in the morning and in the afternoon and 40% in the morning and in the evening. Thirty percent of the participants were dissatisfied or very dissatisfied with their current treatment, whereas 62% were satisfied or very satisfied and 8% were
P. Touraine et al. / Annales d’Endocrinologie 76 (2015) 9–12
11
Table 1 Most important features of an optimal replacement medication according to AI patients (n = 66).
Once daily Quick onset Few side effects Enduring efficacy over 24 hours Physiological therapy Low risk of adrenal crisis Price Other
Most important (%)
2nd most important (%)
3rd most important (%)
11.8 8.8 23.5 25 11.8 16.2 0 2.9
7.6 12.1 27.3 13.6 15.2 19.7 3.0 1.5
7.6 10.6 18.2 21.2 10.6 25.8 4.5 1.5
indifferent. Multiple daily dosing was reported as a problem by 46% of the respondents, mostly due to the risk of forgetting an intake. When asked which was the most important feature of an optimal replacement medication, 25% of participants responded “enduring efficacy over 24 hours”, 23.5% selected “few side effects” and 16.2% chose “low risk for adrenal crisis” (Table 1). A majority of participants (80%) was concerned about possible long-term side effects of glucocorticoid replacement therapy. Their major concern was osteoporosis (79%), followed by fatigue (57%), obesity (43%), cardiovascular problems (29%) and infectious diseases (27%). Three out of 4 respondents reported that AI impaired their quality of life (QoL) with varying degrees of severity (53% graded the impact on QoL as “quite a lot” or “very much”). Altered activities were mainly physical activity (62%) and work life (47%) (Fig. 1). A majority of respondents mentioned fatigue as a problem, whether it occurred in the morning or during the day (57% and 69% respectively) (Table 2). A more rapid onset of medication in the morning would be perceived as a benefit for 69% of respondents. Sixty-three percent of respondents declared that they sometimes modify their treatment due to fatigue: 31% change the dose, 12% change the time of intake and 20% change both time and dose. On average, the increase of glucocorticoid dose is decided at least once per week due to physical activity in 43% of patients and at least once per month due to intercurrent illness in 80%. Only fifty-seven percent of respondents considered themselves fit to work whereas 21% did not (unable to work or on sick leave), 11% were retired and 11% were unemployed. Among those able to work, 76% considered they could work full time while 9% could work 75% of time, 9% could work half time and 6% could work less than half time. Overall, 38% of respondents were absent from work or school for AI-related
Fig. 1. Changes in activities due to adrenal insufficiency (n = 68).
Table 2 Fatigue experienced as a problem by AI patients. n (%) Fatigue experienced as a problem in the morning (n = 67) Yes If yes, how much of a problem? (n = 34) Small Intermediate Big Very big Fatigue experienced as a problem during the day (n = 65) Yes If yes, how much of a problem? (n = 43) Small Intermediate Big Very big
38 (57) 2 (6) 17 (50) 10 (29) 5 (15) 45 (69) 5 (12) 17 (39) 18 (42) 3 (7)
reasons during the last 3 months (Fig. 2). Nearly one-half (48%) reported hospitalization within the last 12 months. This article presents the data of French patients who participated in a worldwide survey published by Forss et al. [13]. France was the third country after the US and Australia by the number of respondents. We are aware of obvious biases in patients’ selection. First, only the members of a single patient organization were invited to participate; second, only those with Internet access could respond; so, this subgroup of French patients may not represent the whole French AI population. Respondents’ profiles were heterogeneous and included pediatric patients with congenital adrenal hyperplasia. Moreover, numerous missing data make some answers difficult to interpret. We have no data on age, sex, and characteristics of the
Fig. 2. Number of days of absenteeism from work or school during the last 3 months (n = 22).
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P. Touraine et al. / Annales d’Endocrinologie 76 (2015) 9–12
disease. Finally, the questionnaire was not validated in AI and most questions were subjective and inaccurate. Yet, responses were consistent with those provided by patients from other countries [13], suggesting that difficulties encountered by AI patients (problems with multiple dosing regimens, fatigue, absenteeism from work or school and concerns about long-term side effects) are constant among various categories of patients and types of management. They result in a perception of poor health status and impaired quality of life. These signals should invite physicians to think about strategies to improve their patients’ management, including optimization of glucocorticoid replacement therapy, since current therapies do not reproduce adequately physiological cortisol circadian rhythm [14] and patient education that might be inspired from recommendations issued for other adrenal diseases [15]. 4. Conclusion This is the first report of a French patient survey in the field of AI and data show potential room for improvement in their management. Despite numerous biases, impaired self-perceived health status is striking in at least some AI patients. In the future, we should probably more focus on patients’ perception and make every effort to optimize treatment, with regard to individual patient profiles and living conditions. Moreover, we believe that implementation of patients’ education programs and publication of guidelines would be highly useful for patients and physicians. In addition, new formulations with better reproduction of cortisol physiological profile may probably help solving some side effects and practicability issues. 5. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. Acknowledgements We would like to thank the patients who participated in the survey, the “Association Surrénales” that allowed the participation of France and Viropharma that supported the study. Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.ando. 2014.09.003.
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