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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 3  |  Issue : 1  |  Page : 28-31

Life events and quality of life in patients of Cushing's disease


1 Department of Psychiatry, Seth GSMC and KEM Hospital, Mumbai, Maharashtra, India
2 Department of Endocrinology, Seth GSMC and KEM Hospital, Mumbai, Maharashtra, India
3 Department of Psychiatry, LTMMC and LTMGH, Mumbai, Maharashtra, India

Date of Web Publication24-May-2019

Correspondence Address:
Dr. Neena Sawant
Department of Psychiatry, Seth GSMC and KEM Hospital, Parel, Mumbai - 400 012, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/aip.aip_49_18

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  Abstract 


Background: Cushing's disease (CD) is a rare endocrine disorder associated with increased serum levels of cortisol secreted due to an underlying tumour in pituitary. Stressful life events are known to aggravate CD and affect coping with the illness. Quality of life (QoL) may also be impaired due to physical changes, limitations in activity and emotional problems despite treatment of CD. Hence, we undertook this research to study the life events and QoL in patients of CD. Methods: Thirty-five patients of CD were enrolled from the endocrine outpatient department after written informed consent and institutional ethics approval. A pro forma for demographic variables and details of CD was administered with the Holmes and Rahe stressful life events scale Social Readjustment Rating Scale (SRRS) and short-form 36 (SF-36) health survey for general QoL and well-being. Results: Twenty-nine (82.5%) patients had low scores (<150) on SRRS 5 (14.28%) patients had scores in the medium range, whereas only 1 (2.86%) patient had a higher score. Thus, life events were not significant to aggravate the disease in our sample. A poor QoL was reflected in all 35 (100%) patients indicating severely impaired QoL on both mental and physical components. All the subdomains of SF-36, namely physical functioning, role limitation due to physical health and emotional health, energy/fatigue, emotional well-being, social functioning, pain and general health were affected. Conclusions: Life events experienced were not significant to worsen the underlying illness, but an impaired QoL in all spheres of functioning was evident. Liaison with the endocrinologist would also work towards improving the issues of body image disturbances and self-esteem for better prognosis for the patient.

Keywords: Cushing's disease, life events, quality of life


How to cite this article:
Sawant N, Sharma A, Shah N. Life events and quality of life in patients of Cushing's disease. Ann Indian Psychiatry 2019;3:28-31

How to cite this URL:
Sawant N, Sharma A, Shah N. Life events and quality of life in patients of Cushing's disease. Ann Indian Psychiatry [serial online] 2019 [cited 2019 Dec 13];3:28-31. Available from: http://www.anip.co.in/text.asp?2019/3/1/28/251360




  Introduction Top


Cushing's disease (CD) is a rare endocrine disorder associated with increased serum levels of cortisol secreted due to an underlying tumour in pituitary with an annual incidence of 2–3 cases per million.[1] The classic features of CD include central obesity, moon-face, hirsutism, insulin resistance, facial plethora, striae, proximal myopathy, scalp hair loss, acanthosis and menstrual irregularity.[2]

Life event is defined as a major event in person's life which changes a person's status or circumstances such as marriage, death of spouse and birth of a child. These life events require changes and adjustments in our day-to-day routine and might permanently impact life. Stress occurring from these changes in short term is good as it helps us to manage the required changes expected from us; however, long-term stress can be harmful. Researchers have found that life events can also aggravate the underlying CD and affect coping. Sonino et al.[3],[4] found that patients with CD reported significantly more stressful life events and the events had an objective negative impact. These findings indicate a causal role for stressful life events exclusively in pituitary-dependent CD and suggest a limbic-hypothalamic involvement in the pathogenesis of this condition.

CD has a considerable negative impact on patient health-related quality of life (QoL). Due to the disease burden, the QoL of patients gets impaired significantly resulting from physical pain, emotional turmoil of unacceptable changes in their general external appearances, limitation of activities of daily living and also immense lassitude and fatigue.[5],[6],[7] The data available from Indian studies are very limited in various aspects of CD, especially the health-related QoL. This study was a part of a larger research which looked into psychopathology, body dysmorphic disorder and self-esteem in patients of CD. This research looks into the impact of life events on CD and also studies the QoL of these patients. We hypothesised that the impact of life events over the last 1 year would be greater in these patients who have been recently diagnosed as CD. We also expected the QoL to be affected in the various psychosocial domains.


  Methods Top


This study was conducted in the departments of psychiatry and endocrinology of a general hospital after institutional ethics committee approval and valid informed consent. All patients newly diagnosed as CD by the endocrinologist as per the following standard criteria were included in the study:[8],[9],[10],[11]

  1. Endogenous hypercortisolism diagnosed based on low-dose dexamethasone suppressed serum cortisol of >1.8 mcg/dl
  2. Adrenocorticotrophic hormone (ACTH) dependency defined as plasma ACTH >10 pg/ml
  3. The presence of pituitary adenoma on magnetic resonance imaging and/or proven central to peripheral ACTH gradient on cortisol-releasing hormone-stimulated inferior petrosal sinus sampling.


Forty-one patients were screened and 35 patients who were adults, willing to participate and without any prior history of mental illness were included in the study. Patients under treatment for psychiatric disorders were excluded from the study. All the patients were explained about the nature of the study and its implications and were assessed with the help of the following scales.

Tools

Holmes and Rahe life events stress scale

The Holmes and Rahe stressful life events scale has been used as the gold standard scale for measurement of life events and the stress associated to them. It was created by Thomas Holmes and Richard Rahe in 1967. There are a total of 41 items, each a specific life event associated with a score. Each score is multiplied to the number of times; such stressful situation has been experienced by the patient in the last 1 year. A score of 150+ gives a 50% chance of developing an illness, and a score of 300+ gives a 90% chance of developing an illness. SRRS scores were categorised as low (<150), medium (150–299) or high (≥300). The scale has a sensitivity of 75% and specificity of 68%.[12]

Quality of life scale – short form 36

The short-form 36 (SF-36) health survey is a modified version of the RAND scale for general QoL and well-being. It was developed by Ware et al. in 1992. It is a reported survey of patient health. The SF-36 is a measure of health status, which consists of eight related scaled scores, each scored on a 0–100 scale with all questions equally scored. Higher scores correspond to greater QoL and lower scores to lesser QoL. The reliability of scale is >90% with validity ranging from 80% to 90%.[13],[14],[15]

All the scales administered to the patients were translated to vernacular language and validated before use.

Statistics

Frequency distribution was used for studying the demographic variables, life events and QoL with mean and standard deviation.


  Results Top


Demographic variables

The mean age of the patient group was 32.9 ± 10.5 years with the ages ranging from 18 to 55 years. Twenty-three (65.71%) patients were between 20 and 40 years of age. Twenty-two patients (63%) of the study patients were married, 12 (34%) were unmarried and 1 of the patients was widowed. Our study sample was literate with 9 patients (23%) completing high school education, 11 patients graduation/post-graduation and only 4 patients being primary educated. Nearly two-thirds (62.6%) of the sample was unemployed with 8 patients doing skilled/clerical work and 5 patients being professionals. The socioeconomic class reflected in our sample included 60% (n = 21) from the lower socioeconomic class with 40% (n = 14) from middle socioeconomic strata.

Life events

On assessing patients for life events on the Holmes and Rahe Social Readjustment Rating Scale (SRRS), we found that 29 (82.5%) patients had low scores (<150), 5 (14.28%) patients had scores in the medium range, whereas only 1 (2.86%) patient had a higher score of more than 300. The total mean score was 124 ± 93 [Table 1].
Table 1: Life events as per Holmes and Rahe Social Readjustment Rating Scale

Click here to view


Quality of life

We applied the SF-36 to study the QoL in our patients. When judging the overall QoL, the scores were found to be on the lower range where every patient in our sample scored <50% of the scores, hence reflecting an overall poor QoL. The total mean score was 349 ± 209 [Table 2]a.


Click here to view


In our findings, a poor QoL was reflected as all the 35 (100%) patients scored <50% of the total score, thus indicating severely impaired QoL on both mental and physical components. The total mean score was 349 ± 209, whereas on physical component scale (PCS), the mean score was 180.37 ± 107.13 and, on mental component scale (MCS), the mean scores were 169.51 ± 107.71 [Table 2]b.

When our patients were assessed on the various subdomains of SF-36 to gauge the impairment in functioning in the various spheres of life, then all our patients scored poorly on all the subdomains of physical functioning (46.57 ± 29.37), role limitation due to physical health (42.85 ± 28.16), role limitation due to emotional health (46.6 ± 34.58), energy/fatigue (27.55 ± 32.71), emotional well-being (44.48 ± 31.48), social functioning (45.71 ± 28.75), pain (51.65 ± 31.20) and general health (39.28 ± 31.67) [Table 2]c.


  Discussion Top


Life events

The various life events experienced by our patients were increased in the number of arguments with their spouse, personal illness, increase loans, change in financial state, trouble with in-laws, changes in social activities, sleeping habits and social activities. In events such as vacations, death of close friend, retirement and outstanding personal achievement, our patients had low scores. Hence, only 6 patients had scores ranging from 150 to 300 while the others did not score so high. Majority of the patients had not experienced life events of a higher rank such as death, divorce, separation and jail term, which is responsible for higher scores on the scale. Only 1 patient had death of spouse about 8 months before being diagnosed as CD which could be considered as a causative factor as reported by researchers[3],[4] though the statistical significance cannot be proved. The remaining 5 patients scored on financial loss, marital separation, economic burden, fired from work, etc. Thus, the life events experienced by our sample were not significant to cause worsening of their underlying illness despite the fact that they had been recently diagnosed as CD and had experienced these life events in the last 1 year.

Implications of the life events on chances of developing an illness are high i.e., around 90% if the scores are more than 300. Our findings are contrary to those of Sonino et al.[3] who in their study amongst 30 patients of CD showed that patients with CD reported significantly more stressful life events than a normal control group. The results were suggestive of a causal relationship between stressful life events and CD. Such relationship largely pertains to the hypothalamic–pituitary forms of the illness. This is in agreement with a multifactorial model of pathogenesis in CD and with current understanding of the complex interdependence of neurophysiological, biochemical and behavioural factors.[3],[4]

Fabre et al.[16] in their study of analysing relation of perceived stress of life events and onset of metabolic syndrome also reported that life events were significantly more prevalent in patients with the metabolic syndrome independent of the effects of age and body mass index, especially in patients with increased serum cortisol levels.

Quality of life

The SF-36 QoL looks into various domains of the life functioning and can be broadly categorised into the PCS and MCS. The physical component looks into factors such as pain, role limitation due to physical health, energy/fatigue and physical functioning. These factors reflect the amount of impairment of QoL in the physical domain. The MCS looks into factors such as role limitation due to emotional health, general health, social functioning and emotional well-being, thus giving an assessment of the mental health.

CD affects overall QoL in a negative way as there is bodily pain which makes it difficult for the patients to function normally giving rise to limitations in day-to-day activities of daily living. The hormonal disturbances also have a negative impact over the energy levels and most of the patients complain of bodily weakness or early/easy fatigability. Most patients are affected by the impact of the changes in their physical appearances which then result in impairment of social functioning, thus limiting the patients to indoors. Several studies have reported a poor QoL in patients of CD, and some of pre- and posttreatment outcomes found QoL to be significantly impaired before the treatment was initiated in patients of CD.[17] Nader et al. found a wide range of neuropsychiatric symptoms in former and active CD patients which led to serious impairments in QoL. They felt that the normalisation of pathologically increased laboratory values did not lead to an improvement of the patients subjectively felt well-being.[18]

The impaired QOL after long-term remission of CD may be explained by irreversible glucocorticoid-induced changes in the central nervous system. Alternatively, persisting physical impairments or psychological distress of living with a previous disease and treatment might also play a role. Finally, long-term endocrine withdrawal effects may have led to irreversible alterations in perceived QoL.[6],[7] In some studies after treatment residual impairment primarily of physical scores, especially physical functioning, role limitations due to physical health and PCS domains still persisted.[6]

Hawn et al.[19] reported an objective decrease in QoL in 11 patients, nine of whom reported that their health improved after surgical treatment. Factors which contribute to persistent long-term impairment in QoL are irreversible effects of hypercortisolism on neurological function or physical conditioning. Elevated cortisol levels in CD are associated with cognitive decrements and loss of brain volume.[20] Furthermore, the apparent decrease in hippocampal volume associated with functional impairments in cognition is only partially reversible upon correction of hypercortisolism.

Webb et al.[21] in their review said that QoL in CD is worse in active disease and often improvement after successful therapy is often incomplete. This is due to persistent physical and psychological comorbidities which affect patients of CD even years after adequate endocrine treatment. They reported that physical symptoms such as extreme fatigability, central obesity with limb atrophy, hypertension, fractures, skin abnormalities, psychological and cognitive problems, difficulties to concentrate and emotional distress severely impair the patients' and often make it difficult for many patients to overcome the aftermath of treated Cushing's syndrome.

Lindsay et al. also reported that in active CD, all domains of SF-36 were affected in a higher magnitude as compared to mental health and bodily pain which was moderately impaired in their series of patients. They also reported that the presence of physical and mental symptoms was inversely related to PCS and MCS scores and detected significantly higher SF-36 PCS scores in patients in remission compared with those with a definite previous recurrence and in those who indicated possible recurrence.[6]


  Conclusions Top


The results of this study imply that life events did not play a role in propagating CD the illness, but all the patients had a severely impaired QoL on both mental and physical components and in all the spheres of functioning.

Clinical implications

It is important for the physician to be aware to enquire about this as it can lead to disturbances in physical, mental and emotional well-being of the patients of CD. Liaison with the endocrinologist would work towards improving the prognosis for the patient.

The limitations of our study include a small sample size and a selection bias of the patient group seen at a tertiary care hospital. We did not study the confounding variables which could have had an impact on the study objectives. A prospective study looking at life events, emotional and behavioural changes and improving the functioning of the patients would give more information on the psychiatric outcomes in patients of CD after treatment.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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2.
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3.
Sonino N, Fava GA, Grandi S, Mantero F, Boscaro M. Stressful life events in the pathogenesis of Cushing's syndrome. Clin Endocrinol (Oxf) 1988;29:617-23.  Back to cited text no. 3
    
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Sonino N, Fava GA, Boscaro M. A role for life events in the pathogenesis of Cushing's disease. Clin Endocrinol (Oxf) 1993;38:261-4.  Back to cited text no. 4
    
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Sonino N, Bonnini S, Fallo F, Boscaro M, Fava GA. Personality characteristics and quality of life in patients treated for Cushing's syndrome. Clin Endocrinol (Oxf) 2006;64:314-8.  Back to cited text no. 5
    
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Lindsay JR, Nansel T, Baid S, Gumowski J, Nieman LK. Long-term impaired quality of life in Cushing's syndrome despite initial improvement after surgical remission. J Clin Endocrinol Metab 2006;91:447-53.  Back to cited text no. 6
    
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Wagenmakers MA, Netea-Maier RT, Prins JB, Dekkers T, den Heijer M, Hermus AR, et al. Impaired quality of life in patients in long-term remission of Cushing's syndrome of both adrenal and pituitary origin: A remaining effect of long-standing hypercortisolism? Eur J Endocrinol 2012;167:687-95.  Back to cited text no. 7
    
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Newell-Price J, Trainer P, Perry L, Wass J, Grossman A, Besser M, et al. Asingle sleeping midnight cortisol has 100% sensitivity for the diagnosis of Cushing's syndrome. Clin Endocrinol (Oxf) 1995;43:545-50.  Back to cited text no. 8
    
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Elamin MB, Murad MH, Mullan R, Erickson D, Harris K, Nadeem S, et al. Accuracy of diagnostic tests for Cushing's syndrome: A systematic review and metaanalyses. J Clin Endocrinol Metab 2008;93:1553-62.  Back to cited text no. 9
    
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Reimondo G, Paccotti P, Minetto M, Termine A, Stura G, Bergui M, et al. The corticotrophin-releasing hormone test is the most reliable noninvasive method to differentiate pituitary from ectopic ACTH secretion in Cushing's syndrome. Clin Endocrinol (Oxf) 2003;58:718-24.  Back to cited text no. 11
    
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Holmes TH, Rahe RH. The social readjustment rating scale. J Psychosom Res 1967;11:213-8.  Back to cited text no. 12
    
13.
Ware JE Jr., Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 1992;30:473-83.  Back to cited text no. 13
    
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Nader S, Burkhardt T, Vettorazzi E, Milian M, Aberle J, Petersenn S, et al. Health-related quality of life in patients after treatment of Cushing's disease. Exp Clin Endocrinol Diabetes 2016;124:187-91.  Back to cited text no. 18
    
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21.
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    Tables

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