Review
Health-related quality of life in primary and secondary adrenal insufficiency Expert Review of Pharmacoeconomics & Outcomes Research 2014.14:873-888. Downloaded from informahealthcare.com by Emory University on 04/19/15. For personal use only.
Expert Rev. Pharmacoecon. Outcomes Res. 14(6), 873–888 (2014)
Anna Aulinas*1 and Susan M Webb1,2 1 Endocrinology/Medicine Departments, Sant Pau Biomedical Research Institute, Hospital de Sant Pau, Universitat Auto`noma de Barcelona, C/Sant Antoni Maria Claret, 167, 08025-Barcelona, Spain 2 Center for Biomedical Network Research on Rare Diseases (CIBERER Unit 747), ISCIII. *Author for correspondence: Tel.: +34 935 565 661 Fax: +34 935 565 602 [email protected]
Adrenal insufficiency (AI) is characterized by a deficient production of glucocorticoids with or without associated mineralcorticoid and/or adrenal androgen deficiencies. Despite the low prevalence of AI, its impact on the affected patient is very high, and can be life-threatening disease if not adequately treated. Several glucocorticoid treatment regimens are available, but none is capable of perfectly imitating the cortisol circadian rhythm. Cortisol rhythmicity and treatment of other possible concomitant conditions often associated (e.g., autoimmune disorders and panhypopituitarism) are essential to improve outcome of AI. Morbidity often present in treated AI include an unhealthy metabolic profile, bad quality of sleep, infertility, sexual dysfunction and worse health-related quality of life. This review focuses on psychological morbidity and impaired quality of life in patients with primary or secondary AI of any origin, including a special section devoted to congenital adrenal hyperplasia. KEYWORDS: Addison’s disease • congenital adrenal hyperplasia • health-related quality of life • primary adrenal insufficiency • quality of life • secondary adrenal insufficiency
Adrenal insufficiency (AI) is a rare disease in which adrenal cortisol production is reduced. AI is a life-threatening disorder that may be due to primary adrenal failure (mainly Addison’s disease [AD], due to impaired function of the adrenal gland), secondary adrenal insufficiency (SAI) (impairment of the hypothalamic–pituitary–axis [HPA], due to pituitary disease that interferes with corticotropin secretion) or tertiary AI (suppression of corticotropin-releasing hormone and corticotropin synthesis, the most common cause being long-term administration of high doses of exogenous glucocorticoids [GCs]) [1]. The incidence of primary adrenal insufficiency (PAI) has increased over the last years, with an estimated incidence now of 4.4– 6.0 new cases per million population per year [2]. SAI is more common, with an estimated prevalence of 150–280 per million population. On the other hand, congenital adrenal hyperplasia (CAH) is the commonest genetic endocrine disorder, which can cause AI and it is the most frequent cause of PAI in children (70%) [3]. AI in CAH is due to mutations of different enzymes, most frequently of the 21-hydroxylase gene, a key enzyme in cortisol
informahealthcare.com
10.1586/14737167.2014.963559
and aldosterone synthesis and resulting in androgen excess. Other variants of CAH involve mutations of different enzymes (e.g., 11-hydroxylase, aldosterone synthase, 17-ahydroxylase, 3-b-hydroxysteroid dehydrogenase or StAR protein deficiencies). In contrast to PAI, CAH is usually associated with excessive androgens if not treated; therefore, we have considered CAH as a separate clinical entity. A high prevalence of co-morbidities and more than twofold increased mortality ratio has been observed in AI patients, despite correct hydrocortisone (HC) and/or mineralocorticoid replacement therapy (TABLE 1) [4–10]. Unhealthy metabolic profile, impaired fertility and quality of life (QoL) have also been observed in patients with CAH [11]. This review focuses on the psychological morbidity and impaired QoL in patients with AI of any origin. Clinical features & morbidity in patients with AI
Clinical presentation of AI is non-specific. Because of this, diagnosis is often delayed, not recognized by physicians or misdiagnosed, most commonly as gastrointestinal disturbance.
2014 Informa UK Ltd
ISSN 1473-7167
873
Review
Aulinas & Webb
Table 1. Studies examining mortality in patients with adrenal insufficiency. Study (year)
Subjects
Findings/outcomes
Ref.
Bergthorsdottir et al. (2006)
675 (995F/680M)
SMR 2.19 (1.91–2.51) for men and 2.86 (2.54–3.2) for women compared with background population, mainly due to cardiovascular, malignant and infectious diseases
[4]
Bensing et al. (2008)
3299 (1940F/1359M)
SMR 2.5 (2.3–2.7) for men and 2.9 (2.7–3) for women. Highest risk diagnosed in childhood
[9]
Erichsen et al. (2009)
811
Elevated SMR 1.5 (1.09–2.01) patients diagnosed
Health-related quality of life in primary and secondary adrenal insufficiency Expert Review of Pharmacoeconomics & Outcomes Research 2014.14:873-888. Downloaded from informahealthcare.com by Emory University on 04/19/15. For personal use only.
Expert Rev. Pharmacoecon. Outcomes Res. 14(6), 873–888 (2014)
Anna Aulinas*1 and Susan M Webb1,2 1 Endocrinology/Medicine Departments, Sant Pau Biomedical Research Institute, Hospital de Sant Pau, Universitat Auto`noma de Barcelona, C/Sant Antoni Maria Claret, 167, 08025-Barcelona, Spain 2 Center for Biomedical Network Research on Rare Diseases (CIBERER Unit 747), ISCIII. *Author for correspondence: Tel.: +34 935 565 661 Fax: +34 935 565 602 [email protected]
Adrenal insufficiency (AI) is characterized by a deficient production of glucocorticoids with or without associated mineralcorticoid and/or adrenal androgen deficiencies. Despite the low prevalence of AI, its impact on the affected patient is very high, and can be life-threatening disease if not adequately treated. Several glucocorticoid treatment regimens are available, but none is capable of perfectly imitating the cortisol circadian rhythm. Cortisol rhythmicity and treatment of other possible concomitant conditions often associated (e.g., autoimmune disorders and panhypopituitarism) are essential to improve outcome of AI. Morbidity often present in treated AI include an unhealthy metabolic profile, bad quality of sleep, infertility, sexual dysfunction and worse health-related quality of life. This review focuses on psychological morbidity and impaired quality of life in patients with primary or secondary AI of any origin, including a special section devoted to congenital adrenal hyperplasia. KEYWORDS: Addison’s disease • congenital adrenal hyperplasia • health-related quality of life • primary adrenal insufficiency • quality of life • secondary adrenal insufficiency
Adrenal insufficiency (AI) is a rare disease in which adrenal cortisol production is reduced. AI is a life-threatening disorder that may be due to primary adrenal failure (mainly Addison’s disease [AD], due to impaired function of the adrenal gland), secondary adrenal insufficiency (SAI) (impairment of the hypothalamic–pituitary–axis [HPA], due to pituitary disease that interferes with corticotropin secretion) or tertiary AI (suppression of corticotropin-releasing hormone and corticotropin synthesis, the most common cause being long-term administration of high doses of exogenous glucocorticoids [GCs]) [1]. The incidence of primary adrenal insufficiency (PAI) has increased over the last years, with an estimated incidence now of 4.4– 6.0 new cases per million population per year [2]. SAI is more common, with an estimated prevalence of 150–280 per million population. On the other hand, congenital adrenal hyperplasia (CAH) is the commonest genetic endocrine disorder, which can cause AI and it is the most frequent cause of PAI in children (70%) [3]. AI in CAH is due to mutations of different enzymes, most frequently of the 21-hydroxylase gene, a key enzyme in cortisol
informahealthcare.com
10.1586/14737167.2014.963559
and aldosterone synthesis and resulting in androgen excess. Other variants of CAH involve mutations of different enzymes (e.g., 11-hydroxylase, aldosterone synthase, 17-ahydroxylase, 3-b-hydroxysteroid dehydrogenase or StAR protein deficiencies). In contrast to PAI, CAH is usually associated with excessive androgens if not treated; therefore, we have considered CAH as a separate clinical entity. A high prevalence of co-morbidities and more than twofold increased mortality ratio has been observed in AI patients, despite correct hydrocortisone (HC) and/or mineralocorticoid replacement therapy (TABLE 1) [4–10]. Unhealthy metabolic profile, impaired fertility and quality of life (QoL) have also been observed in patients with CAH [11]. This review focuses on the psychological morbidity and impaired QoL in patients with AI of any origin. Clinical features & morbidity in patients with AI
Clinical presentation of AI is non-specific. Because of this, diagnosis is often delayed, not recognized by physicians or misdiagnosed, most commonly as gastrointestinal disturbance.
2014 Informa UK Ltd
ISSN 1473-7167
873
Review
Aulinas & Webb
Table 1. Studies examining mortality in patients with adrenal insufficiency. Study (year)
Subjects
Findings/outcomes
Ref.
Bergthorsdottir et al. (2006)
675 (995F/680M)
SMR 2.19 (1.91–2.51) for men and 2.86 (2.54–3.2) for women compared with background population, mainly due to cardiovascular, malignant and infectious diseases
[4]
Bensing et al. (2008)
3299 (1940F/1359M)
SMR 2.5 (2.3–2.7) for men and 2.9 (2.7–3) for women. Highest risk diagnosed in childhood
[9]
Erichsen et al. (2009)
811
Elevated SMR 1.5 (1.09–2.01) patients diagnosed
