Pituitary (2022) 25:768–771 https://doi.org/10.1007/s11102-022-01245-9 REVIEW Quality of life impairment after a diagnosis of Cushing’s syndrome Susan M Webb1 · Elena Valassi2 Accepted: 16 June 2022 / Published online: 29 June 2022 © The Author(s) 2022 Abstract This brief review is devoted mainly to publications in the last 5 years dealing with health-related quality of life (QoL) after a diagnosis of endogenous hypercortisolism, due to pituitary-dependent Cushing’s disease (CD) or any other cause of Cushing syndrome (CS). Despite improvement after treatment, persistent physical morbidity, neurocognitive problems like worse executive capacity and memory as well as stress intolerance, depressive symptoms and more anxiety, lead to long-term impairment of QoL. Keywords Quality of life · Cushing syndrome · Memory impairment · Anxiety · Depression · Emotional distress Introduction Hypercortisolism impairs QoL Ninety years ago, psychiatric and neurocognitive conse- Impaired QoL and cognitive functions (including atten- quences of hypercortisolism were already described by tion and processing speed, visuospatial perception and con- Cushing in his original description of this syndrome [cited struction, executive function, verbal learning and memory, by 1]. In the last decades these most distressing neurocogni- visual learning and memory, verbal function and language tive complaints have been increasingly described, like loss skills, intelligence domain) are present at diagnosis in CS of memory, difficulties in concentration, coping with emo- compared to healthy controls [1, 3]. QoL is equally affected tions and with executive functions, intolerance to stress, by pituitary and adrenal causes of CS, on both the generic emotional incontinence, irritability, anxiety and depres- EuroQoL and specific CushingQoL questionnaire (more sion, that negatively impact on health-related quality of life sensitive to Cushing-related dimensions). Postoperatively, (QoL), which despite improving after adequate therapy to cognitive function improves in most domains, as well as control hypercortisolism, may not normalize [1–6]. Fur- QoL, but patients often still complain of having less mem- thermore, other persisting problems like sleep disturbances, ory than before [8]. After treatment, CushingQoL scores fatigue, muscle weakness and permanent weight gain con- are worse in pituitary than in adrenal patients, depending tribute to explain why patients with “cured” Cushing dis- on the remission status, which more frequently occurs in ease (CD) or any kind of endogenous Cushing syndrome the latter [8]. Additionally, older age and depression at diag- (CS) still do not feel well [2–7]. nosis predict worse long-term outcome for QoL, regardless of aetiology. In fact, depressive symptoms, which nega- tively impact QoL, are present in most CS patients, either at baseline or during follow-up [3, 5]. The high prevalence of depression is also evidenced by the 2- to 4-fold higher Susan M Webb use of antidepressants, anxiolytics and sleeping pills in CD webbsusan4@gmail.com than in controls, prior to and at diagnosis, and remains high 1 for antidepressants and sleeping pills 5 years after diagnosis Endocrinology Dept, Hospital Sant Pau, IIB-Sant Pau, Research Center for Pituitary Diseases; Dept Medicine, [9]. This is not surprising since after surgery patients expect Universitat Autònoma de Barcelona (UAB), CIBERER, Unit hypercortisolism and all its symptoms and consequences to 747, ISCIII, 08041 Barcelona, Spain be resolved; they are told their hormones have normalized 2 Endocrinology Dept, Germans Trias i Pujol Hospital & and yet they may feel worse than before, both physically Research Institute, Universitat Internacional de Catalunya and psychologically. Feeling helpless, bewildered, anxious (UIC), CIBERER, Unit 747, ISCIII, 08916 Badalona, Spain 13 Pituitary (2022) 25:768–771 769 and/or depressed is common, especially if in parallel they impact daily life and physical activity. Abnormal skeletal experience flare-ups of prior autoimmune conditions, car- muscle structure and function persist after long-term remis- pal tunnel syndrome or generalized pain related to postop- sion of hypercortisolism, with more intramuscular fat mass, erative adrenal insufficiency and glucocorticoid deprivation worse muscle performance and strength on physical testing [5] Fig. 1. Being unaware of what to expect by prior infor- and a greater prevalence of sarcopenia [4, 11]. Worse QoL mation and educational programs, may lead them to crash is seen in “cured” CS patients compared to controls, espe- down and be unable to cope, especially in stressful situa- cially if sarcopenia is present. They also experience more tions [5]. Experiencing less memory and executive capacity pain, easy bruising and worries on physical appearance in compared to their prior condition, is also very distressing, as the CushingQoL questionnaire, and poorer physical func- well as difficulty in coping with emotion; thus, being aware tioning on the generic SF-36 questionnaire. that this may occur and an empathetic attitude of their health Neuroimaging in CS evidences persistent reduction of providers is reassuring and helps to adapt to and cope with right hippocampal volume, grey matter volumes, cortical this new situation, benefiting health perception and QoL. thickness, white matter integrity especially in structures Five years after diagnosis and treatment for CS the use important for cognitive function and emotional processing, of anxiolytics decreases [9], probably reflecting improve- and altered resting state functional responses during cogni- ment in perceived co-morbidities and/or an acceptance and tive tasks [1]; a direct effect of chronic glucotoxicity on the adaptation to the “post-Cushing” situation. Nevertheless, central nervous system is thought to be involved in these CS patients still are prescribed three times more opioids as structural and functional impairments, which often do not pain-killers compared to general population after 5 years normalize despite remission of hypercortisolism. of follow-up, but not anymore after 10 years. Interestingly, drug consumption 5 years after diagnosis did not differ Impact of Cushing’s syndrome on QoL as evaluated among CD patients in remission or with persistent hyper- by physicians cortisolism, as far as antidepressants, anxiolytics, sleep- ing pills, opioids, renin angiotensin system blockers and Perspectives on the recovery after treatment for CS are diver- antidiabetics, pointing out that morbidity is still increased gent between patients and physicians. While the desire of despite endocrine cure. Thus, residual physical and neuro- patients is to lead a normal life, without limitations or pain, psychiatric morbidity in CS also entails a high socio-eco- for the physician a normalization of biochemical data is the nomic impact and leads to reduced employment status and main item to consider a “cure”. Physicians tend to underes- increased requests for disability pensions [10]. timate the time to complete postoperative recovery, while Persistent muscle weakness, easy fatigability and tired- patients with adrenal etiologies experience longer dura- ness are common complaints in treated CS, which greatly tion of adrenal insufficiency requiring cortisol replacement Fig. 1 Impaired Quality of Life (QoL) in Cushing’s syndrome is determined by impaired health perception (due to persistent symptoms and morbidity), depressive symptoms and neurocognitive difficulties (including memory, executive functioning, intelligence and attention), leading to difficulties to cope with stress and emotions 13 770 Pituitary (2022) 25:768–771 [12]. Physicians overestimate the benefits of work, exercise symptoms, declared a reduced performance, and psycho- and activities, while patients find family/friends and rest to logical problems. Good medical care and competent doc- be helpful to cope with the complex postoperative period. tors helped most in coping with the illness. The majority, Although when asked, both providers and patients consider especially in the US, were interested in support groups and that education on recovery is important, only one third con- in courses on illness coping, or availability of information sidered to have received sufficient information from their brochures. Most declared to be willing to attend internet- physician for the postsurgical experience. Being empathetic based programs. All needed skilled physicians and long- and understanding the patients’ narrative of the experience term medical care in dealing with the effects of CD/CS. of recovery is important, if QoL is to be improved. In this respect, nurses tend to be better than doctors, and are highly appreciated by the patients [13, 14]. Conclusions Patients’ perception on the impact on QoL after Patient education and awareness of the physical and psy- Cushing’s syndrome chological aftermath in treated CS helps to overcome the postoperative period. Psychological interventions may be It is highly frustrating for patients who may find no under- required to treat depression and to improve long-term prog- standing in their managing health professionals, who con- nosis, subjective wellbeing and QoL. Apart from benefiting sider them cured, and yet they certainly do not feel healthy. the patients, their families, working and social capacity, it Awareness of these persistent physical and neuropsychiatric will reduce health costs. problems, as well as understanding, is essential, so that spe- cific treatment can be offered; providing information so they Author contribution SW wrote the initial text, which was read, edited and approved by both authors. are aware of these problems can be very therapeutic. Individ- ualized educational programs for pituitary patients aimed at Funding No funding was received to assist with the preparation of promoting autonomy and self-management improves QoL, this manuscript. satisfaction and health perception. New goals like reinforc- ing knowledge, sharing experiences, and improving self- Statements and Declarations confidence are observed [15]. Another self-management intervention program for pituitary patients and their partners Competing interests The authors have no competing interests to de- approached psychosocial issues, like self-efficacy, bother clare that are relevant to the content of this article. and needs for support, illness perceptions, coping and QoL; Open Access This article is licensed under a Creative Commons results were positive when compared with a control group Attribution 4.0 International License, which permits use, sharing, who did not follow the program. Improvements were seen adaptation, distribution and reproduction in any medium or format, in patient mood, self-efficacy, and vitality; partners reported as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate less anxiety and depressive symptoms [16]. Patients should if changes were made. The images or other third party material in this not blame themselves for not coping and be realistic for article are included in the article’s Creative Commons licence, unless work expectancies, socially or at home [5]. indicated otherwise in a credit line to the material. If material is not Objective information from physicians on postsurgical included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted recovery after CS, including duration, symptoms to expect, use, you will need to obtain permission directly from the copyright and helpful coping mechanisms are highly appreciated. holder. To view a copy of this licence, visit http://creativecommons. In contrast, failing to understand a patient’s conception of org/licenses/by/4.0/. recovery by health providers may lead the patient to feeling resentful. Fostering explicit education and discussions with the patients’ close environment, like partners and family, References mentioning the need for increased social support, tends to lead to deeper discussion and understanding between physi- 1. 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