Patients who have suffered Cushing’s syndrome may experience problems which negatively affect their quality of life (QoL), both physically and psychologically. These include central obesity, muscle weakness, body hair excess, delayed wound healing and easy bruising, skin erosions with minimal trauma, hypertension, hyperglycaemia, osteoporosis, menstrual irregularities, lack of libido and depression. Health care professionals devote their efforts to attain a biochemical cure, but often are less concerned with other features that may impair patients’ well-being and with the possibility that not all symptoms are completely reversible. Once hypercortisolemia is controlled, patients are considered “cured” and are supposed to be able to recover completely in the course of time. However, this does not always appear to be so and some of the physical and psychological problems may not revert completely, even after a long time.
Health related quality of life (HRQL) is the subjective perception of wellbeing from the patients’ point of view and can not be inferred from usual endocrine parameters; therefore, it needs to be taken into account separately. It is not yet clear how cortisol exerts its multiple effects on the body and mind, although it is known to affect glucose metabolism, protein wasting, coagulation, inflammatory processes and different parts of the brain.
HRQL is evaluated with different questionnaires that measure dimensions known to be affected to a greater or lesser extent. They are useful instruments to understand how a patient feels at a determined time point, how he/she evolves over time and how the patient compares to the normal population. Classically, among the generic questionnaires the SF-36 is a widely validated and used survey, with 8 domains: physical functioning, role limitations due to physical health, bodily pain, general health, vitality, social functioning, role limitations due to emotional health and mental health. Another is the Nottingham Health Profile, which evaluates 6 dimensions (mobility, pain, energy, sleep, emotional reaction and social isolation), or the EuroQoL, which apart from the dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression), includes a visual analog score, like a thermometer, to assess the subjective health status at the time-point when the patient is completing the questionnaire.
In recent years, several studies have addressed the HRQL in Cushing’s patients. Typically, HRQL is impaired at diagnosis when the patient is hypercortisolemic and improves after control of the disease. This has been observed using generic QoL questionnaires which allow comparison of different patient groups to a normal reference population. The generic questionnaires may be less sensitive in detecting changes over time, since they do not approach areas always involved in Cushing’s syndrome. However, when HRQL has been compared to that of healthy controls or even patients with other kinds of pituitary tumors, a clearly impaired QoL has been shown in patients diagnosed with Cushing’s syndrome.
During active Cushing’s, 85% complain of fatigue/weakness, 63% complain of changes in physical appearance, 63% report emotional instability, 49% report cognitive problems, 32% report depression, and 12% sleeping difficulties. 80% of patients report that Cushing’s interferes with family life and relations with their partner and 56% report that Cushing’s interferes with school/work performance. (1)
Lindsay et al (2) studied Cushing’s patients pre and post treatment and found improvements in all portions of the SF-36 in patients studied before surgery and an average of 3.2 years after curative surgery (range .7-5.4 years). Bodily pain, vitality, social functioning, role limitations due to emotional health, general health, and mental health improved to levels similar to the US population, while physical functioning, role limitations due to physical health and the physical summary scores remained well below the norm. This study included a symptom check list and found that the most common symptoms that remained after curative surgery were fatigue (41%), forgetfulness (35.7%), trouble sleeping (33.3%), depression (31.2 %), weight gain (30.4%) and decreased muscle strength or weakness (30.4%). The average time of time taken off work due to Cushing’s was 3.8 months and 81% were able to return to work.
Van Aken (3) also studied Cushing’s patients using the SF-36 in patients biochemically cured from Cushing’s (average 13.4 years ± 6.7). These results showed decreased physical and social functioning, limitations in role functions due to both physical and emotional problems, increased pain and decreased general well-being compared to age matched controls. In addition, this study used the Nottingham Health Profile questionnaire and found substantially lower QoL values in the areas of energy, pain, emotional reaction, sleep, physical ability and social isolation. In addition, this study did not identify radiotherapy as predictor of a lower QoL, while hypopituitarism was associated with lower QoL.
While these generic questionnaires are useful, they do not take into account some specific problems of Cushing’s syndrome that may be crucial for QoL. This led to the development of the CushingQoL questionnaire, a specific questionnaire for the evaluation of the HRQL in Cushing’s Syndrome (4). To develop the questionnaire, ten patients were interviewed and asked to describe how Cushing’s affected their life. From these interviews, questions were formulated. The CushingQoL questionnaire is comprised of 12 questions with 5 possible answers, which can be completed in less than 5 minutes by the patient himself. The CushingQoL questionnaire addresses known problem areas in Cushing’s such as trouble sleeping, wound healing/bruising, irritability/mood swings/anger, self-confidence, physical changes, ability to participate in activities, interactions with friends and family, memory issues and future health concerns. This questionnaire was studied in 125 patients in Spain, France, Germany, Italy, and the Netherlands by 14 different investigators over a 2 month time period. The CushingQoL questionnaire results clearly indicated improvement following biochemical cure, especially since dimensions most frequently affected by hypercortisolemia were evaluated. Nevertheless, it has been observed that this improvement may not be complete.
Using the CushingQoL questionnaire, a lower value means a lower HRQL. Several items of interest include:
- Patients with a recent diagnosis (<24months) scored lower, 44 ± 22, versus those with an older diagnosis (>24 months) who scored 59 ± 20.
- Those without clinically active Cushing’s scored better, 56 ± 21 than those who had clinically active Cushing’s, 44 ± 22
- Those having no hospital admissions during the previous 2 years scored better, 59 ± 21 versus those who had had a recent hospital admission, 47 ± 22.
This initial experience has shown good acceptance among patients who became aware that some of the problems they experience can be related to Cushing’s syndrome. For health providers it identifies problems often not approached in clinical follow-up; in summary it may contribute to help to better understand impaired HRQL in Cushing’s Syndrome, and to find a way to improve it in the long term, for the benefit of the patients.
The CushingQoL questionnaire was developed in parallel with the ERCUSYN project. The aim of this project is to establish a European register on Cushing’s syndrome, in order to improve the available knowledge on this disease in different European countries and consequently to improve the care of the patients. Quality of life measures will be collected at baseline and at follow-up, in order to gain further insight into how Cushing’s Syndrome affects QoL. For more information about the ERCUSYN project you can visit www.ercusyn.eu.
Authors: Alicia Santos and Susan M Webb, MD (Winter, 2008)
Editor’s Note: Both Alicia Santos and Susan Webb are associated with the Endocrinology Department and Centro de Investigación Biomédica en Enfermedades Raras (CIBER-ER Unidad 747), Hospital Sant Pau, Autonomus University of Barcelona; Spain. Alicia Santos is a psychologist working in Hospital Sant Pau as the project manager of the ERCUSYN project. Susan Webb, MD is Professor of the Autonomous University of Barcelona, and an endocrinologist of the Hospital Sant Pau, with a special interest in pituitary diseases in general and Cushing’s syndrome and quality of life in particular. She leads the unit on Pituitary Diseases of the network of excellence funded by the Spanish Health Ministry (Centro de Investigación Biomédica en Red-Enfermedades Raras -CIBERER unit 747-) and is the ERCUSYN Coordinator, a project funded by the European Union, among other research interests.
1) Gotch PM. Cushing’s Syndrome From the Patient’s Perspective. Endocrinology and Metabolism Clinics of North America 1994 23 607-617.
2) Lindsey JR, et al. Long-Term Impaired Quality of Life in Cushing’s Syndrome despite Initial Improvement after Surgical Remission. Journal of Clinical Endocrinology and Metabolism 2006 91 447-453.
3) van Aken MO, et al. Quality of Life in Patients After Long-term Biochemical Cure of Cushing’s Disease. Journal of Clinical Endocrinology and Metabolism 2005 90 3279-3286.
4) Webb SM, et al. Evaluation of Health-Related Quality of Life in Patients with Cushing’s syndrome with a new questionnaire (CushingQoL). European Journal of Endocrinology 2008 158: 623-30