Decreased physical activity, reduced QoL and presence of debilitating fatigue in patients with Addison's disease

Valk, Eline S van der; Smans, Lisanne C C J; Hofstetter, Hedwig; Stubbe, Janine; Vries, Marieke de; Backx, Frank; Hermus, A.R.M.M.; Zelissen, Pierre

doi:10.1111/cen.13059

Cited by 16 publications

(9 citation statements)

References 37 publications

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“…Numerous studies suggest that, in patients with AD, clinically relevant fatigue persists despite replacement therapy. For instance, Løvaŝ, Logeŧ, and Husebye (236) found that patients with AD selfreported reduced general health perception and vitality despite receiving replacement therapy with cortisone acetate and fludrocortisone. Similarly, van der Valk and colleagues (237) found that 48% of their patient sample (N = 328) self-reported abnormal fatigue; 61% reported severe fatigue.…”

Section: Sleep Disruptions In Admentioning

confidence: 99%

“…Similarly, van der Valk and colleagues (237) found that 48% of their patient sample (N = 328) self-reported abnormal fatigue; 61% reported severe fatigue. Researchers postulate that reports of increased daytime fatigue may be due to reduced quality of sleep in patients with AD and that relatively increased doses of HC may contribute to these sleep disruptions (3,236,238).…”

Section: Sleep Disruptions In Admentioning

confidence: 99%

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Sleep, Cognition and Cortisol in Addison’s Disease: A Mechanistic Relationship

2021

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Sleep is a critical biological process, essential for cognitive well-being. Neuroscientific literature suggests there are mechanistic relations between sleep disruption and memory deficits, and that varying concentrations of cortisol may play an important role in mediating those relations. Patients with Addison’s disease (AD) experience consistent and predictable periods of sub- and supra-physiological cortisol concentrations due to lifelong glucocorticoid replacement therapy, and they frequently report disrupted sleep and impaired memory. These disruptions and impairments may be related to the failure of replacement regimens to restore a normal circadian rhythm of cortisol secretion. Available data provides support for existing theoretical frameworks which postulate that in AD and other neuroendocrine, neurological, or psychiatric disorders, disrupted sleep is an important biological mechanism that underlies, at least partially, the memory impairments that patients frequently report experiencing. Given the literature linking sleep disruption and cognitive impairment in AD, future initiatives should aim to improve patients’ cognitive performance (and, indeed, their overall quality of life) by prioritizing and optimizing sleep. This review summarizes the literature on sleep and cognition in AD, and the role that cortisol concentrations play in the relationship between the two.

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Section: Sleep Disruptions In Admentioning

confidence: 99%

Section: Sleep Disruptions In Admentioning

confidence: 99%

Sleep, Cognition and Cortisol in Addison’s Disease: A Mechanistic Relationship

2021

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“…Current regimens of cortisol replacement therapy for patients lacking adrenal function do not replace ultradian rhythmicity and result in considerable morbidity. Several centers have confirmed that these treatment regimens result in impaired health-related quality of life (42)(43)(44)(45)(46)(47), adverse metabolic and cardiovascular risk profiles (48), increased levels of proinflammatory cytokines (49), and reduced activity, low motivation, and mental fatigue, with associated high levels of unemployment and disability benefits (43,(50)(51)(52). It was initially assumed that this was a direct consequence of the inability of oral medication to provide the normal circadian variation of cortisol, and that this could be improved by continuous s.c. infusions of the hormone.…”

mentioning

confidence: 99%

Ultradian rhythmicity of plasma cortisol is necessary for normal emotional and cognitive responses in man

Kalafatakis

Russell

Harmer

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

101

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Glucocorticoids (GCs) are secreted in an ultradian, pulsatile pattern that emerges from delays in the feedforward-feedback interaction between the anterior pituitary and adrenal glands. Dynamic oscillations of GCs are critical for normal cognitive and metabolic function in the rat and have been shown to modulate the pattern of GC-sensitive gene expression, modify synaptic activity, and maintain stress responsiveness. In man, current cortisol replacement therapy does not reproduce physiological hormone pulses and is associated with psychopathological symptoms, especially apathy and attenuated motivation in engaging with daily activities. In this work, we tested the hypothesis that the pattern of GC dynamics in the brain is of crucial importance for regulating cognitive and behavioral processes. We provide evidence that exactly the same dose of cortisol administered in different patterns alters the neural processing underlying the response to emotional stimulation, the accuracy in recognition and attentional bias toward/away from emotional faces, the quality of sleep, and the working memory performance of healthy male volunteers. These data indicate that the pattern of the GC rhythm differentially impacts human cognition and behavior under physiological, nonstressful conditions and has major implications for the improvement of cortisol replacement therapy.

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“…Due to the gradual onset and nonspecificity of initial symptoms, AI is a typical condition with a delayed diagnosis and a high rate of initial misdiagnosis (2,3). Although hormone replacement therapy results in improvement of symptoms in most patients, chronically treated patients report persistent morbidity and impairments in health-related quality of life (HR-QoL) (4)(5)(6)(7)(8). It is plausible that the impairments in HR-QoL are, at least partly, caused by intrinsic imperfections in hydrocortisone replacement strategies (5,9).…”

Section: Introductionmentioning

confidence: 99%

Clinical Unmet Needs in the Treatment of Adrenal Crisis: Importance of the Patient’s Perspective

et al. 2021

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Adrenal crisis is the most severe manifestation of adrenal insufficiency (AI), but AI can present with variable signs and symptoms of gradual severity. Despite current hormone replacement strategies, adrenal crisis is still one of the leading causes of mortality in AI patients. Although underlying factors explaining differences in interindividual susceptibility are not completely understood, several subgroups are particularly vulnerable to adrenal crises, such as patients with primary AI, and patients treated for Cushing’s syndrome. Currently, the health care professional faces several challenges in the care for AI patients, including the lack of reliable biomarkers measuring tissue cortisol concentrations, absence of a universally used definition for adrenal crisis, and lack of clinical tools to identify individual patients at increased risk. Also from the patient’s perspective, there are a number of steps to be taken in order to increase and evaluate self-management skills and, finally, improve health-related quality of life (HR-QoL). In this respect, the fact that inadequate handling of AI patients during stressful situations is a direct consequence of not remembering how to act due to severe weakness and cognitive dysfunction in the context of the adrenal crisis is quite underexposed. In this narrative review, we give an overview of different clinical aspects of adrenal crisis, and discuss challenges and unmet needs in the management of AI and the adrenal crisis from both the doctor’s and patient’s perspective. For the latter, we use original focus group data. Integration of doctor’s and patient’s perspectives is key for successful improvement of HR-QoL in patients with AI.

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Decreased physical activity, reduced QoL and presence of debilitating fatigue in patients with Addison's disease

Abstract: Physical activity is decreased in patients with Addison's disease, combined with a reduced subjective health-related QoL and increased fatigue.

Cited by 16 publications

References 37 publications

Sleep, Cognition and Cortisol in Addison’s Disease: A Mechanistic Relationship

Sleep, Cognition and Cortisol in Addison’s Disease: A Mechanistic Relationship

Ultradian rhythmicity of plasma cortisol is necessary for normal emotional and cognitive responses in man

Clinical Unmet Needs in the Treatment of Adrenal Crisis: Importance of the Patient’s Perspective

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