Article

Psychosocial Factors in Subjects with Thyroid-Associated Ophthalmopathy

Authors:
  • Psychiatrische Klinik Sanatorium Kilchberg, Zürich
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Abstract

General agreement has emerged that the perceptions of patients of how they are feeling and how they are able to function in daily life should be included in the evaluation and monitoring of the effects of disease and treatment. Thyroid-associated orbitopathy (TAO), an inflammatory autoimmune eye disease, affects 50%-60% of patients with Graves' hyperthyroidism. Having blurred vision and/or diplopia has a detectable and significant impact on functional status and well-being, especially in role limitations caused by physical health problems. Therefore, to assess the impact of TAO on quality of life, we performed a descriptive study on consecutive ophthalmopathy patients with varying degrees of severity of TAO. General quality of life was assessed using a brief, internationally accepted, and standardized general questionnaire: the Medical Outcomes Study (MOS-36). In comparison to a large German reference group, low scores on the MOS-36 were found. Marked and significant differences from the control group were especially observed for the following items: vitality, social functioning, mental health, health perceptions, and body pain. MOS-36 did not correlate with the duration or severity of the ophthalmopathy. These results demonstrate the impact of a common visual symptom on health status and well-being, as measured by the MOS-36. In addition, comparison of the impact of various symptoms and conditions provides important and potentially clinically relevant information. In conclusion, we have shown that TAO has a large influence on the quality of life of these patients. The negative impact on well-being seems not to be related to the usual clinical assessment. These findings underscore the need for quality of-life measurements in prospective and controlled clinical trials.

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... 7 Blurred vision and/or diplopia has a significant impact on functional status and well-being, especially in role limitations caused by physical health problems. 8 Health related quality of life (HRQL) can be defined as the physical, psychological, and social domains of health, as perceived by the patient. These parameters are influenced by experiences, beliefs, expectations and perceptions by patients of their disease and treatment. ...
... 18 The psychological burden of the progressive disfigurement resulting from TED is well recognized. 1,5,8,9 In fact TED may be a severely disabling condition because of its effects on vision and appearance. 2,8 The most common complaint regarding impaired visual function in our patients before treatment was "feeling hindered from doing something" (27.9%) which is comparable with the reports by Park et al 2 (34%) and Terwee et al 15 (35%). ...
... 1,5,8,9 In fact TED may be a severely disabling condition because of its effects on vision and appearance. 2,8 The most common complaint regarding impaired visual function in our patients before treatment was "feeling hindered from doing something" (27.9%) which is comparable with the reports by Park et al 2 (34%) and Terwee et al 15 (35%). In psychosocial function, most of our patients complained of altered appearance (55.7%) which was also the most prevalent psychosocial complaint in other studies (37-67%). ...
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To evaluate quality of life (QOL) before and after corticosteroid therapy for thyroid eye disease (TED) and to determine the impact of the disease on QOL. A modified TED-QOL questionnaire was completed by consecutive patients before and at least 6 months after steroid therapy. All patients were clinically and biochemically euthyroid during the course of the study. QOL was assessed in subscales of visual function, psychosocial, and educational/counseling; TED was classified by severity score (NOSPECS) and Mourits' clinical activity score. Overall, 61 patients including 18 (29.5%) male and 43 (70.5%) female subjects with mean age of 37.3±13.7 (range, 18-33) years were enrolled. Mean duration of thyroid dysfunction and TED were 40.1±44.8 and 26.5±38.2 months, respectively. Mean disease severity and activity significantly decreased, and visual and psychosocial function scores significantly improved following corticosteroid therapy for TED. Psychosocial score was significantly worse than visual function score before but not after steroid treatment. Linear regression analysis and Spearman correlation test showed no significant correlation between duration of thyroid dysfunction, duration of TED, disease severity and activity on one hand, and QOL scores on the other hand, before or after treatment. TED seems to adversely affect psychosocial activity more than visual function. Corticosteroid therapy significantly improves QOL. No significant correlation seems to exist between QOL scores and the severity or activity of TED.
... However, only a few studies have evaluated the impact of TED on patients' QOL in the USA. Similar to results of European studies [10,11], Bradley et al. [12] found impaired QOL in patients with TED, with diplopia being an influencing factor. Schotthoefer and Wallace [13] demonstrated QOL improvement following surgical correction of TED-related strabismus. ...
... To the best of our knowledge, this is the first study of its kind to include information from patients in the USA. Other QOL studies performed in Europe [9][10][11][17][18][19], Asia [20][21][22], Australia [23], and South America [24,25] have also shown a high impact of TED on patients' QOL. ...
... Therefore, ocular pain is likely a significant driver of QOL decrement in patients with TED. These findings are in agreement with prior studies which demonstrated that increasing disease activity [11,21,22,24,25] and ocular pain [10,11] significantly impair patient QOL. It should be noted that smaller, earlier published studies did not find a significant correlation between patient-perceived QOL and disease activity [20,29]. ...
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IntroductionThyroid eye disease (TED) is an autoimmune disease that causes retro-orbital inflammation and subsequent proptosis, corneal exposure, strabismus, and variable vision changes. European studies have shown that TED can severely impact quality of life (QOL), but little is known about the QOL of patients with TED in the USA. Given that patient QOL influences TED severity classifications and subsequent treatment, understanding physician-perceived patient QOL is extremely important.Methods This retrospective chart review (conducted in 2018) examined QOL in US patients with moderate-to-severe TED, as reported by treating physicians who regularly manage patients with TED (≥ 5 patients in prior 12 months). The physicians graded patients’ overall QOL (7-point Likert scale; 1 = “not at all impaired”, 7 = “extremely impaired”), assessing mental health, vision changes, and ocular structural signs/symptoms. Patient demographics and clinical findings were examined to understand the impact of disease presentation on physician-perceived QOL.ResultsMedical record data of 714 US patients with moderate-to-severe TED were provided by 181 physicians (73 endocrinologists, 108 ophthalmologists). Patients had a mean age of 49.4 (standard deviation [SD] 13.6) years, and 102 cases (14%) were severe. Anxiety and/or depression was reported in 36% of patients (an increase from the 18.9% prevalence reported for the USA in 2017 by the US National Institute of Mental Health; P < 0.001). The mean physician-reported QOL impact score was 4.1 (SD 1.5). Furthermore, 62 and 89% of patients with moderate and severe TED, respectively, had a high physician-perceived QOL impact (≥ 4). The higher QOL impact group had significantly higher rates of pain symptoms, visual disturbances (including diplopia), and orbito-facial structural changes. Higher disease activity and severity were associated with lower physician-perceived QOL.Conclusion Patients’ QOL, as evaluated by US physicians, is highly impacted by the activity and severity of TED. Additionally, mental health issues were more frequently reported by patients with TED than in the general US population. Ocular pain, strabismus, and diplopia appear to be main drivers of physician-perceived QOL impairment in this sample of US patients with TED.
... More specifically, pain behind the eyes, blurry vision, light sensitivity, and diplopia were all significantly more prevalent in patients with the lowest QOL. These findings are in agreement with prior studies, which have shown relationships between QOL and TED-related pain [11,24,25], vision loss [11], and diplopia [11,[25][26][27][28][29]. The current study also showed that patients who had undergone a surgical procedure for TED had a significantly lower QOL than patients who had not. ...
... The heavy psychosocial health burden of TED has been previously documented in populations around the globe [8,11,20,21,25,26,[31][32][33]. In agreement, mental health issues were highly prevalent (42%) in this cohort of chronic TED patients. ...
... It is likely that the low QOL group had the highest number of severe TED cases. Prior studies have shown that QOL decreases as TED severity increases [11,22,26,27,34,35], and it would be expected that patients with more severe TED would either seek out care more often or be followed more closely by their healthcare provider. However, because our data were patientreported, the clinical severity of TED could not be assessed. ...
Article
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Introduction: Thyroid eye disease (TED) is an autoimmune condition producing ocular pain, dysmotility, and ocular structure and function changes. As disease activity changes, redness, swelling, and pain can improve, but eye comfort, appearance, and motility alterations often persist. There are limited data on chronic TED patient-reported outcomes. This study examined chronic US TED patient-reported symptoms and quality of life (QOL). Methods: Existing data from an online survey regarding chronic TED signs/symptoms and patient QOL were retrospectively examined. The Graves' Ophthalmopathy QOL instrument (GO-QOL; 0-100, 100 = highest QOL) evaluated overall, appearance, and vision-related QOL. Influencing factors were examined by stratifying patients into low (overall QOL ≤ 50), moderate (> 50 and < 75), and high (≥ 75) QOL categories. Results: One hundred patients (47 women, 81 Caucasian, 45.2 ± 7.6 years) were included. The duration of inactive TED was 3.0 ± 4.6 years and total duration of TED was 5.8 ± 5.9 years. Patients reported an average of 20 doctor visits/year and high prevalence of anxiety (34%) and depression (28%). Prior TED treatments for the polled population included systemic corticosteroids during active TED (25%), orbital radiation (5%), and surgery (25%). The overall GO-QOL score was 60.5 ± 21.8 (vision-related: 58.6 ± 24.0, appearance-related: 62.3 ± 25.1). Patients with low QOL more frequently reported hypothyroidism, anxiety, and a larger number of chronic TED signs/symptoms (average: 4.2). Compared to high QOL patients, low QOL patients had more pain (39% vs. 13%), blurry vision (30% vs. 17%), and diplopia (27% vs. 3%, all p ≤ 0.025). Additionally, the low QOL group more often had TED-specific surgical history (45% vs. 10%, p = 0.002), more often reported disability/unemployment (21% vs. 3%, p = 0.055), and had a higher number of doctor visits (40 vs. 5 visits/person/year, p < 0.001). Conclusion: TED severely impacts patient QOL, despite becoming stable and chronic. Patients reported vision and appearance impairment and psychosocial impact long after acute TED had subsided.
... The concept of quality of life (QOL) is relatively recent. It was first introduced into medicine during the mid-1960s (17,18), and since then, subjective wellbeing as well as the physical and mental ability to function in everyday life became the focus of attention in several studies (1,17,19,20). ...
... The concept of quality of life (QOL) is relatively recent. It was first introduced into medicine during the mid-1960s (17,18), and since then, subjective wellbeing as well as the physical and mental ability to function in everyday life became the focus of attention in several studies (1,17,19,20). ...
... However, rehabilitative and extraocular muscle final results frequently are poor and a considerable number of patients remain unhappy with their ultimate appearance. Also, the goal of medical care for most patients today is to obtain a more effective life and to preserve functioning and well being (17). ...
Article
To investigate the effect of pentoxifylline (PTX) in subjects with inactive Graves' ophthalmopathy (GO) through a specific quality of life (QOL) questionnaire and exophthalmometry readings. Eighteen females were randomly divided in two groups. Group A (n=9) was treated with PTX 1200 mg orally/day for 6 months. Group B (n=9) received placebo during the initial 6 months and then PTX for another 6 months. Proptosis measurements were carried out every 3 months and a questionnaire graded from 0 to 10 according to the severity of the symptoms was performed at baseline and after placebo and PTX administration. At baseline, Group A questionnaire score values were 5.5 (median; range 3.5 to 8.0), and 5.0 after 6 months (3.0 to 6.0; p=0.01). In Group B, baseline values were not significantly different after 6 months of placebo: 6.0 (4.5 to 7.0) and 5.5 (4.5 to 7.0), respectively. However, a significant change was observed 6 months after PTX: 4.0 (2.0 to 5.0; p<0.001). Patients in Group A had a progressive improvement of proptosis during PTX: at baseline, 23 mm (median; range 20 to 32); after 3 months, 23 mm (18 to 30; p=0.02); and after 6 months, 23 mm (18 to 30; p=0.005). In Group B, proptosis remained stable during placebo: at baseline, 23 mm (21 to 25); after 3 months, 23 mm (20 to 25); and after 6 months, 23.5 mm (20 to 25). A significant change was observed after 3 and 6 months of PTX: 22 mm (19 to 24; p=0.0006) and 20.8 mm (17 to 25; p=0.0003), respectively. Pentoxifylline seems to improve the QOL of patients in the inactive phase of GO. The objective findings of the proptosis readings corroborate to suggest that PTX may be an effective and promising drug in the inactive phase of GO.
... Previously, medicine was "doing the tuning" of the harp "with unprecedented skill", but was "having trouble with the harmony" (Elkinton, 1966). Thenceforth, medical care outcomes started to take into account also the patient's point of view (Kahaly et al., 2002;Testa & Simonson, 1996). ...
... There is also evidence that patients with GO are at higher risk of anxiety, depression and mood disturbance in general, especially those with active or severe disease (Farid et al., 2005; Gerding et al., 1997; Kahaly et al., 2005; Lee et al., 2010; Weng et al., 2019). Clinical activity and severity of GO are measured by the Clinical Activity Scores (a 7-item scale assessing two symptoms and 5 signs of inflammation of the anterior eye soft tissue), and the NOSPECS (a mnemonic composed of the describing classes of the ocular changes in GO: no physical signs or symptoms, only signs, soft tissue involvement, proptosis, extraocular muscle signs, corneal involvement, sight loss), respectively, both being associated with lower GO-QOL scores (Delfino et al., 2017; Kahaly et al., 2005; Park et al., 2004; Terwee et al., 2002).Two studies showed that patients with GO had lower SF-24 and SIP or SF-36 and HADS scores compared with two large reference groups(Gerding et al., 1997;Kahaly et al., 2002).Interestingly, in both studies duration and severity of GO did not correlate with SF scores(Gerding et al., 1997; Kahaly et al., 2002). However, 9 years later, one of these two groups demonstrated that both the visual functioning and the appearance scales of the GO-specific GO-QOL questionnaire correlate negatively with the severity and the activity of GO (Ponto et al., 2011). ...
Article
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Introduction. Increasing interest exists concerning the physical and mental wellbeing of patients with hyperthyroidism. Aim. This review aims at gathering the most updated literature on the quality of life (QoL) in patients with hyperthyroidism. Method: We searched PubMed from inception to May 20, 2020 for English language studies using the following entries: "hyperthyroidism AND quality of life", "Graves' disease AND quality of life", "diffuse toxic goiter AND quality of life", "toxic nodular goiter AND quality of life", "subclinical hyperthyroidism AND quality of life". Thirty-nine papers were finally reviewed. Results: Patients with hyperthyroidism have worse QoL than euthyroid subjects, especially if they have Graves' disease and Graves' orbitopathy. Treatment of hyperthyroidism with restoration of euthyroidism may not fully restore QoL even after many years, indicating that such patients have difficulties adapting to and coping with their illness, thus experiencing marked and longstanding limitations in physical, mental and psychosocial functioning. Conclusion. As differences exist on long-term outcomes between therapeutic options for hyperthyroidism, it is logical to hypothesize related differences in long-term changes in QoL. Future clinical and psychological studies could monitor QoL and its related domains across different stages of disease and deepen patients' trajectories of illness experience and the use of coping strategies to face their condition.
... Several studies have shown that TAO is the main reason for discomfort and decreased quality of life (QoL) (5)(6)(7)(8). ...
... When no consideration of the mode of treatment was taken into account, it was clear that patients with TAO had a significantly decreased QoL for a considerable amount of time after treatment ( Fig. 2a and b). This observation corroborated earlier finding by others when an eye-specific questionnaire had been used (6)(7)(8). ...
Article
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The objective of this study was to investigate quality of life (QoL) in patients with Graves' disease treated with radioiodine or antithyroid drugs. The design of the study consists of an open, prospective, randomized multicenter trial between radioiodine and medical treatment. A total of 308 patients were included in the study group: 145 patients in the medical group and 163 patients in the radioiodine group. QoL was measured with a 36-item Short Form Health Status Survey questionnaire (SF-36) at six time points during the 48-month study period. Patient who developed or got worse of thyroid-associated ophthalmopathy (TAO) at any time point during the 4-year study period (TAO group) had lower QoL when no respect was paid to the mode of treatment. TAO occurred in 75 patients who had radioiodine treatment at some time point during the study period as compared with TAO in 40 medically treated patients (P<0.0009). Comparisons between the group of patients who have had TAO versus the group without TAO, in relation to treatments and time, showed significantly decreased QoL scores for the TAO groups at several time points during the study. In patients without TAO, there were no differences in QoL related to mode of treatment. The QoL in patients with Graves' ophthalmopathy was similar in radioiodine and medically treated patients, but patients who developed or had worsening of TAO had decreased QoL independent of mode of treatment. Furthermore, patients with TAO recovered physically within 1 year but it took twice as long for them to recover mentally.
... More than 30% of patients with hyperthyroidism have been reported to be completely or partially work disabled (14), although the extent of sickness absence seem most pronounced in the time after treatment initiation (15,16). For Graves' orbitopathy, patients in remission reported a higher degree of work role limitations (SF-36) compared with the general population and patients with diabetes mellitus (17), and patients with active disease had a higher prevalence of work limitations and longer duration of sickness absence compared with the general population, healthy subjects, and patients with other thyroid or autoimmune diseases (18). However, these self-report studies are small and may suffer from selection bias due to patient nonresponse, in-formation bias if patients under-or overassess their work ability, or confounding because of the lack of proper control of comorbidity. ...
... These results are in line with reports from previous studies that Graves' orbitopathy impacts quality of life (9, 28), including work role functioning (17) and sickness absence (18). The present study suggests that in addition to the higher risk of sickness absence, socioeconomic costs of Graves' orbitopathy also entail difficulties getting back to work from sickness absence or unemployment and increased risk of disability pension. ...
Article
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Context: Little is known about how thyroid diseases affect work ability. Objective: The objective of this study was to evaluate the risk of work disability for patients with thyroid disease compared with the general population. Design, setting, and participants: In a longitudinal register study, outpatients (n = 862) with nontoxic goiter, hyperthyroidism, Graves' orbitopathy (GO), autoimmune hypothyroidism, or other thyroid diseases and their matched controls (n = 7043) were observed in the years 1994-2011 in Danish national registers of social benefits, health, and work characteristics. Cox regression analyses estimated adjusted hazard ratios (HRs) for the first year after diagnosis and subsequent years. Main outcome measures: Transitions between work, long-term sickness absence, unemployment, and disability pension were measured. Results: Patients differed significantly from the general population with regard to sickness absence, disability pension, return from sickness absence, and unemployment. In the first year after diagnosis, higher risks of sickness absence was seen for GO (HR 6.94) and other hyperthyroid patients (HR 2.08), who also had lower probability of returning from sickness absence (HR 0.62) and higher risk of disability pension (HR 4.15). Patients with autoimmune hypothyroidism showed a lower probability of returning from sickness absence (HR 0.62). In subsequent years, GO patients had significantly higher risk of sickness absence (HR 2.08), lower probability of return from sickness absence (HR 0.51), and unemployment (HR 0.52) and a higher risk of disability pension (HR 4.40). Hyperthyroid patients also had difficulties returning from sickness absence (HR 0.71). Conclusions: Thyroid patients' risk of work disability is most pronounced in the first year after diagnosis and attenuates in subsequent years. GO patients have the highest risk of work disability.
... 2 Patients with GO report feeling stared at by others and socially isolated as a consequence of their changed appearance 3 and this has a significant impact on mood. 4 There is also growing evidence that GO has a detrimental impact on vision-related daily functioning including reading, watching TV, and driving. [5][6][7] People with GO have been found to have a poorer quality of life than patients with other chronic conditions including diabetes, emphysema, and heart failure. ...
... [5][6][7] People with GO have been found to have a poorer quality of life than patients with other chronic conditions including diabetes, emphysema, and heart failure. 4,8 Although it is important to establish the impact GO may have on a patient's well-being, it is equally important to understand what factors explain how some people live within normal levels of mood and experience a better quality of life than others. ...
Article
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Aims: Graves’ orbitopathy (GO) is associated with changes in the appearance of the eyes and visual dysfunction. Patients report feeling socially isolated and unable to continue with day-to-day activities. This study aimed to investigate the demographic, clinical and psychosocial factors associated with quality of life in patients presenting for orbital decompression surgery. Methods: One hundred and twenty-three adults with GO due for orbital decompression at Moorfields Eye Hospital London were recruited prospectively. Clinical measures including treatment history, exophthalmos, optic neuropathy and diplopia were taken by an ophthalmologist. Participants completed psychosocial questionnaires, including the Graves’ Ophthalmopathy Quality of Life Scale (GO-QOL), the Hospital Anxiety and Depression Scale (HADS) and the Derriford Appearance Scale (DAS24). Hierarchical multiple regression analyses were used to identify predictors of quality of life. Results: Higher levels of potential cases of clinical anxiety (37%) and depression (26%) were found in this study sample than in patients with other chronic diseases or facial disfigurements. A total of 55% of the variance in GO-QOL visual function scores was explained by the regression model and age, asymmetrical GO and depressed mood were significant unique contributors. 75% of the variance in GO-QOL appearance scores was explained by the regression model and gender, appearance-related cognitions and depressed mood were significant unique contributors. Conclusions: Appearance-related quality of life and mood were particularly affected in this sample. Predominantly psychosocial characteristics were associated with quality of life. It is important when planning surgery for patients that clinicians are aware of factors that could potentially influence outcomes.
... Since there is no known previous report on the prevalence of giant hydrocele, we are constrained to compare the prevalence in this study with other forms of visibly disfiguring diseases such as Graves's ophthalmopathy. The prevalence of depression among patients with giant hydrocele in this study is considerably higher than the 45% prevalence recorded among patients with Graves's ophthalmopathy (Kahaly, Hardt, Petrak, & Egle, 2002;Paik & Yang, 2009). A higher prevalence among the hydrocele patients could have emanated from the involvement of sex organ with associated sexual problems (Babu, Mishra, & Nayak, 2009). ...
Article
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One of the dreaded disfiguring disease conditions among the Andoni tribesmen in the Nigerian Niger delta region is hydrocele, especially when its size is large (giant hydrocele) and it cannot be concealed. This case-control study was designed to evaluate the prevalence of depression among patients with giant hydrocele presenting to Bethesda Clinic Ngo, Andoni, Nigeria. A total of 52 patients were recruited into this study: 26 in the giant hydrocele group and 26 in the control group. Their age range was 23 to 78 years, with a mean age of 53.4 ± 15.5 years for the giant hydrocele group and 53.6 ± 14.2 years for the control group. The difference between the prevalence of depression among patients that presented with giant hydrocele (61.54%) and the controls (15.38%) was statistically significant (p = .0015). The authors conclude that depression is common among patients with giant hydrocele when compared with patients with other disease conditions.
... MOS SF-24, SIP Lower QOL scores as compared to a healthy reference population, and patients with diabetes, emphysema and heart failure. Egle, 1999 (6); Kahaly, 2002 (4) Germany TED (n=102), Healthy reference population (n=2914) MOS SF-36, LES, HADS, WCCL ...
Article
Thyroid eye disease (TED) is a chronic debilitating condition causing physical discomfort, facial disfigurement and impaired visual function. The physical consequences of TED could have a negative and lasting impact on patients' employment, hobbies and psychosocial function. In this review, we assess the evidence of the impact of TED on patients' quality of life (QOL) and also explore the effects of suboptimal quality of care on QOL of patients with this disease. It is hoped that recent initiatives, including the Amsterdam declaration, to raise the quality of care for patients with TED will help to improve their QOL.
... [1][2][3][4][5][6] The perceptions of patients of how they feel and how they are able to function in daily life should be included in the evaluation and monitoring of the effects of disease and treatment, which are influenced by a patient's experience, beliefs and expectations. [7][8][9][10] The outcomes of GO and its treatments are mostly assessed by biological measures such as activity and severity scores, which do not correlate well with the patient's subjective impression. 11 GO leads to a worse quality of life (QOL) score than many chronic disorders such as diabetes mellitus. ...
Article
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Purpose: To assess the changes in quality of life (QOL) of patients after treatment of their Graves’ ophthalmopathy (GO). Materials and Methods: In this prospective, cross-sectional study, the GO-QOL questionnaire was completed by 67 subjects before and at least 6 months after steroid treatment (61 subjects, group 1) or optic neuropathy orbital decompression (6 subjects, group 2). Visual, psychosocial, education and counseling scores (higher score = better health), GO severity and clinical activity scores and minimal clinically important difference (MCID) were recorded and analyzed for correlation and statistical significance. A P-value <0.05 was considered statistically significant. Results: The mean age of patient enrolled in the study was 38.3 years, with 43 females (64.2%). The mean duration of thyroid dysfunction and GO were 40.1 and 26.5 months, respectively. Two treatment groups were similar for all the variables (0.06 < P < 0.9), except for higher mean age in the orbital decompression group (45.2 versus 37.7 years) (P = 0.03). Mean severity, activity, visual function and psychosocial function scores significantly improved in group 1 (steroid group) (P < 0.05, all cases). A significant improvement in clinical activity score and psychosocial scores occurred in group 2 (decompression group) (P < 0.05). MCID was achieved in two-thirds of the patients, with no significant difference between groups (P > 0.05). There was no significant effect of duration of thyroid disease and GO and severity and activity of GO on QOL scores either before or after treatment (P > 0.05, all cases). Conclusion: Steroid treatment and orbital decompression significantly improve the QOL in GO. Duration, severity and activity of GO did not have a significant impact on the QOL.
... This is higher than the prevalence of depression found in patients with retinitis pigmentosa [20] and similar to patients with diabetes [25], cancer [26] , or myocardial in- farction [27]. Studies by Kahaly et al. [28] showed that 45% of patients with Graves' ophthalmopathy have anxiety or depression , and patients with Graves' ophthalmopathy score significantly lower than controls on measures of emotional role limitation and mental health. We assumed that both cosmetic disfigurement and functional impairment play key roles in causing emotional distress (including depression) in patients with Graves' ophthalmopathy. ...
Article
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To assess quality of life and depressive status in Korean patients with Graves' ophthalmopathy. A cross-sectional study of 49 patients (mean age, 41 years; sex ratio, M:F=11:38) with Graves' ophthalmopathy (referred to as the Graves' group) and 48 age-matched and sex-matched controls (mean age, 40.2 years; sex ratio, M:F=11:37) was performed using the Korean version of the 36-item Short-Form General Health Survey (SF-36) questionnaire and the Beck Depression Inventory (BDI). Survey data was compared among patients with mild, moderately severe, and sight-threatening Graves' ophthalmopathy and between patients with low (0 or 1) or high (2 or 3) Gorman scores. Those in the Graves' group scored significantly lower on all categories of the SF-36, as compared to the control group (p<0.05). The 4 patients with sight-threatening Graves' had significantly lower scores for physical functioning, role limitations due to physical health, and the physical component summary of the SF-36, when compared with the 28 patients with mild Graves' and the 17 patients with moderately severe Graves' (p<0.05). The 17 patients in the high Gorman score group had lower physical component summary scores than the 32 patients in the low Gorman score group (p=0.03). The 16 patients with BDI scores > or = 16 had significantly lower scores on the SF-36 and higher clinical activity scores, as compared to the 33 patients with BDI scores <16 (p<0.05). Patients with Graves' ophthalmopathy had reduced health-related quality of life and were more likely to be depressed, especially those with a sight threatening condition or significant diplopia. It is important to identify these patients to provide the necessary psychological support.
... The vast majority of these patients had thyroid hormone levels within the normal laboratory range. In addition, several studies have identified daily role limitations (Fahrenfort, Wilterdink, & van der Veen, 2000;Kahaly, Hardt, Petrak, & Egle, 2002;Saravanan et al., 2002) and difficulty maintaining employment (Nexø et al., 2014;. Although HRQOL studies have documented the frequency and type of subjective symptoms experienced by individuals with hypoor hyperthyroidism, it remains unknown why some people with thyroid diseases experience persistent subjective symptoms that are not always reflected in medical outcomes. ...
Article
Thyroid diseases evoke a complex range of psychological and physical symptoms. The psychosocial aspects of living with diseases causing hypo- or hyperthyroidism are poorly understood. In this article, we report the findings of a qualitative interview study in which we explored the lived experiences of 16 people with hypo- or hyperthyroidism. We purposefully selected participants from Danish outpatient clinics according to their diagnosis (Hashimoto's thyroiditis or Graves' disease with or without orbitopathy), age (18 to 65 years), and duration of treatment (more than 6 months). We used interpretative phenomenological analysis (IPA) as a theoretical frame and analytical approach and identified three superordinate themes: losing control over mental and physical states, ambiguous signs of disease, and negotiating sickness. We discuss the findings in the context of the recent literature on chronic illness and argue that these themes play an important role in the conceptualization and management of thyroid diseases.
... The initial, active phase can be dominated by inflammation of orbital soft tissues and expansion of fat that can accompany or be followed by progressive fibrosis and its attendant motility abnormalities. Thyroid eye disease (TED) also named thyroid-associated ophthalmopathy and Graves' orbitopathy, encompasses the orbital and periorbital manifestations of GD and causes substantial morbidity and reduced quality of life [1][2][3][4] . ...
Article
To identify components of a provisional clinical response index for thyroid eye disease using a modified Delphi technique. The International Thyroid Eye Disease Society conducted a structured, 3-round Delphi exercise establishing consensus for a core set of measures for clinical trials in thyroid eye disease. The steering committee discussed the results in a face-to-face meeting (nominal group technique) and evaluated each criterion with respect to its feasibility, reliability, redundancy, and validity. Redundant measures were consolidated or excluded. Criteria were parsed into 11 domains for the Delphi surveys. Eighty-four respondents participated in the Delphi 1 survey, providing 220 unique items. Ninety-two members (100% of the respondents from Delphi 1 plus 8 new participants) responded in Delphi 2 and rated the same 220 items. Sixty-four members (76% of participants) rated 153 criteria in Delphi 3 (67 criteria were excluded because of redundancy). Criteria with a mean greater than 6 (1 = least appropriate to 9 = most appropriate) were further evaluated by the nominal group technique and provisional core measures were chosen. Using a Delphi exercise, we developed provisional core measures for assessing disease activity and severity in clinical trials of therapies for thyroid eye disease. These measures will be iteratively refined for use in multicenter clinical trials.
... TAO is described as an alarming and crippling disease, which often develops into a chronic condition (12)(13)(14). A systematic international literature search has shown that it is well documented that thyroid diseases influence the patients' quality of life negatively and that TAO aggravates the situation (7,(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). Research by Bartley et al. (12) indicates that 10 years after the treatment ended, 32% of the respondents believed that their eyes were still abnormal and 28% were unsatisfied with the appearance of their eyes. ...
Article
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Thyroid-associated ophthalmopathy (TAO) is characterized by the altered appearance of face and eyes and changed visual function. TAO has been described as alarming and crippling. It is well documented that TAO influences the patient's quality of life negatively. However, little is known about how the bodily change complicates the patient's social behaviour in everyday situations. The aim of this study was to explore how social behaviour is influenced by the bodily change and what it means to patients with TAO. An ethnographic study was conducted using in-depth interviews and participant observation. A total of 13 patients, nine women and four men, diagnosed with moderate to severe TAO were included. Data analysis was performed concurrently using grounded theory technique. The local ethics committee approved the study, and all participants gave written informed consent. The study reveals that the experience of bodily change had considerable consequences for patients' involvement with people and maintenance of social relations. Uncontrollable eyes were the dominating experience. It contained four sub-themes; the experience of changed facial communication, the experience of being somebody else, the experience of being clumsy among others and the experience of being cut off from the outside world. The bodily change affected people's attitude and behaviour towards them and their own ways of being with people. They struggled to change social behaviour and avoid withdrawal. In their struggle, they used seven different coping strategies. The study contributes to clarification of essential aspects of living with TAO. The condition of uncontrollable eyes may have serious consequences for patients' social behaviour and relationships with others. Early identification of the impact of bodily change and planned support may help prevent serious quality of life change. © 2010 The Authors. Scandinavian Journal of Caring Sciences
... Some studies have demonstrated that patients with hyperthyroidism have impaired QoL, which persists many years after treatment (9). The treatment modality per se can influence the final outcome, and there are possible confounders such as GO (31)(32)(33), autoimmunity (9), and current thyroid function, even in subclinical forms, that can interfere with the final QoL result (34,35). The QoL of relapsed GD patients has rarely been studied, especially when comparing two different treatment regimens. ...
Article
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Background: Low doses of anti-thyroid drugs (ATD) for extended periods may be an alternative for Graves' disease (GD) patients who relapse after a course of ATD. Methods: Patients with GD relapse (n=238) after discontinuation of ATD therapy for 12-24 months were retrospectively analyzed in a non-randomized study. Radioiodine (RAI) treatment and L-thyroxine replacement was used in 114 patients, and a low-dose of methimazole (MMI) (2.5-7 mg/daily) was used in 124 patients. Thyroid dysfunction, Graves' Ophthalmopathy (GO) evolution, quality of life (QoL), and body weight were evaluated during the follow up. Results: The mean follow up was 80.8±35.3 months for the RAI group and 71.3 ± 40.3 months for the low-dose MMI group. No notable side effects were observed in either group. Thyroid dysfunction was predominant in the RAI group (p<0.001), and euthyroidism was more common in the MMI group (p<0.001). GO deterioration was mainly evaluated by clinical activity score (CAS)-it was higher in the RAI group (p< 0.0005) over all periods of follow up. Multivariate logistic analysis showed that RAI treatment was associated with no improvement in CAS during follow up (24 months: OR=3.51; CI=1.02-12.03, p<0.05. 36 months: OR=8.46; CI=1.47-48.58, p<0.05. 48 months: OR=19.52; CI=1.70-223.10, p<0.05. 60 months: OR=21.1; CI=1.5-298, p<0.05). Kaplan-Meier survival analysis confirmed this finding (p<0.0003 log-rank test). Assessment of QoL using Short Form Health Survey 36 parameters in stable euthyroid patients (at least six months) was similar in both groups. The RAI group patients gained more weight (p<0.005) particularly after 24 months of follow up. Conclusions: The use of low-doses of MMI is efficient and safe and offers better outcomes for GO than RAI treatment. Prolonged low-doses of MMI may be an alternative choice for relapsed GD patients particularly for GO patients or for patients who refuse a definitive treatment.
... There have been few studies investigating quality of life in this population of patients. Theref o re, it is imperative to clarify the psychosocial effects caused by this disease by means of studies on quality of life and on economic consequences (13)(14)(15)(16)(17)(18). It was the objective of this study to evaluate the impact of decompression on quality of life, accounting for both objective clinical benefit and subjective patient satisfaction. ...
Article
Graves' ophthalmopathy (GO) is an organ-specific autoimmune disease. Hydrophily of accumulated acidic mucopolysaccharides into bulbar adipose tissue leads to swelling of the eye muscles. Orbital surgical decompression is performed in severe cases of compressive optic neuropathy and severe corneal exposure or failure of steroid therapy. The study was designed to evaluate decompression surgery with respect to the clinical benefit and the patient's satisfaction by means of a disease-specific questionnaire. The 90-item study questionnaire was distributed to 105 patients with GO who underwent orbital decompression surgery at the authors' institution. A total of 88% of patients stated that decompression had helped them, 80% of the interviewees would undergo decompression again, 78% were content with their eye symptoms, and 71% were satisfied with the cosmetic result of decompression. Furthermore, analysis showed a clinically relevant increase in quality of life after surgery. The correlation between the clinical endpoint proptosis at last examination and the quality of life score proved to be significant (p=0.05). The large majority of interviewees were satisfied with the result of the orbital decompression. These results confirmed that disfiguring proptosis is an important indication for decompression surgery.
... Ophthalmopathy could contribute to the psychiatric morbidity shown by our patients. Recent studies have shown that ophthalmopathy impacts quality of life and psychological functioning [43][44][45], likely through psychosocial consequences of changed appearance. ...
Article
To evaluate the prevalence of mood and anxiety disorders in women with treated hyperthyroidism caused by Graves' disease and to compare them with the prevalence of such findings in women without past or present thyroid disease. Thirty inpatient women with treated hyperthyroidism and ophthalmopathy caused by Graves' disease and 45 women hospitalized for treatment of gynecologic disorders such as abnormal vaginal bleeding, benign tumors or infertility were evaluated for the prevalence of mood and anxiety diagnoses using a standard Mini-International Neuropsychiatric Interview and for mood and anxiety ratings using the Profile of Mood States (POMS). At the time of assessment, it was discovered that 14 of 30 women with treated hyperthyroidism caused by Graves' disease were still hyperthyroid, while 16 women were euthyroid. Significantly greater prevalence of social anxiety disorder, generalized anxiety disorder, major depression and total mood and anxiety disorders, as well as higher symptom scores on the POMS, was found in hyperthyroid women with Graves' disease in comparison with the control group. A prevalence of total anxiety disorder, as well as history of mania or hypomania and lifetime bipolar disorder, but not lifetime unipolar depression, was more frequent in both the euthyroid and the hyperthyroid subgroups of study women in comparison with the control group. These results confirm a high prevalence of mood and anxiety disorders in women with treated hyperthyroidism and ophthalmopathy caused by Graves' disease. Hyperthyroidism plays a major role in psychiatric morbidity in Graves' disease.
... In a separate analysis, we also investigated the risk of affective disorder for hospitalised patients with hyperthyroidism that did not have diagnoses indicating Graves' disease as the cause of hyperthyroidism. This was undertaken as Graves' hyperthyroidism, including Graves' ophthalmopathy, has in particular been associated with affective disorder (22,23). We used patients who had passed the thresholds for hospitalisation as control patients in order to reduce the effect of Berkson's bias (24). ...
Article
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The pattern of comorbidity between thyroid disorders and affective disorder is not fully known. We assessed whether hospitalisation with hyperthyroidism was a risk factor for hospitalisation with affective disorder and evaluated the temporal relationship between these events. A historical prospective cohort study comparing patients with hyperthyroidism with patients with non-toxic goitre or osteoarthritis, using existing data from Danish registers. The observational period was from 1 January 1977 to 31 December 1999. Three study cohorts were identified by their International Classification of Diseases (ICD) diagnoses at discharge from hospital and consisted of all patients with a first hospital admission with the index diagnoses of hyperthyroidism, osteoarthritis, or non-toxic goitre. Later admissions to psychiatric hospital wards with discharge ICD diagnoses of affective disorder were used as events of interest. Rates of re-admission were estimated using competing risks models in survival analyses. Age, sex, substance abuse, and calendar time were included as co-variables. A study sample of 183 647 patients discharged with an index diagnosis was identified. In total 1374 events occurred in the observational period. An index diagnosis of hyperthyroidism was associated with an increased risk of hospitalisation with affective disorder for both sexes and for all age-bands investigated, compared with the other index diagnoses. The risk was greatest in the first six months after index hospitalisation (rate ratio, 95% confidence interval: 3.60 (2.58-5.04)). Patients hospitalised with hyperthyroidism are at greater risk of re-admission with depressive disorder or bipolar disorder than control patients. This suggests that hyperthyroidism is associated with long-term mood disturbances.
... In addition, the mechanisms underlying TAO pathogenesis and developmental processes are also unknown (4). As there is currently no effective therapy for TAO, the purpose of early treatment is to control immune inflammation, and later treatment aims to improve facial features and protect visual function (5). Corticosteroids are the main drugs used to control immune responses in the eye (6). ...
Article
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The present study investigated the relationship between hyperthyroidism and thyroid-associated ophthalmopathy by examining saccade dynamics to identify defects in eye tracking in patients with hyperthyroidism with no pre-existing eye damage and sensitive indicators that discriminated eye tracking ability in hyperthyroidism. A total of 33 outpatients with hyperthyroidism and 26 healthy controls participated in visually guided saccade (VGS) analysis. Patients with hyperthyroidism were divided into groups based on their medication status (medicated vs. unmedicated). Main sequence analysis was performed to identify differences in peak velocity and duration, and a general linear model (GLM) was used to identify differences in latency, peak acceleration and peak deceleration among the groups. The present study compared differences in the Spearman's correlation coefficient of the duration of saccades and the acceleration asymmetric index (RAD) among the groups. Vmax values (Vmax was the asymptotic value of the PV of saccades of large amplitude) were significantly different between the healthy control and unmedicated-hyperthyroidism groups. The results of the GLM-based analysis indicated no significant differences in saccade latency among the three groups. Peak acceleration was significantly different between the healthy control and unmedicated-hyperthyroidism groups (P<0.01). Peak deceleration was significantly different between the healthy control, unmedicated- and medicated-hyperthyroidism groups (P<0.01). RAD was significantly different between the healthy control and medicated-hyperthyroidism groups (P=0.004). The results of the present study suggested that patients with hyperthyroidism with no pre-existing eye damage exhibited significantly altered saccade dynamics during VGS. Therefore, RAD may be used as an indicator to monitor the level of eye movement coordination.
... Health-related quality of life is defined as a subjective and multidimensional construct of health and wellbeing. The concepts of general health and physical, psychological, and social functioning are fundamental determinants of health-related quality of life 202 , which are markedly affected in patients with GD and GO [203][204][205][206][207][208] . Disfiguring proptosis and diplopia impair patients' quality of life both at home and at work. ...
Article
Graves’ disease (GD) is an autoimmune disease that primarily affects the thyroid gland. It is the most common cause of hyperthyroidism and occurs at all ages but especially in women of reproductive age. Graves’ hyperthyroidism is caused by autoantibodies to the thyroid-stimulating hormone receptor (TSHR) that act as agonists and induce excessive thyroid hormone secretion, releasing the thyroid gland from pituitary control. TSHR autoantibodies also underlie Graves’ orbitopathy (GO) and pretibial myxoedema. Additionally, the pathophysiology of GO (and likely pretibial myxoedema) involves the synergism of insulin-like growth factor 1 receptor (IGF1R) with TSHR autoantibodies, causing retro-orbital tissue expansion and inflammation. Although the aetiology of GD remains unknown, evidence indicates a strong genetic component combined with random potential environmental insults in an immunologically susceptible individual. The treatment of GD has not changed substantially for many years and remains a choice between antithyroid drugs, radioiodine or surgery. However, antithyroid drug use can cause drug-induced embryopathy in pregnancy, radioiodine therapy can exacerbate GO and surgery can result in hypoparathyroidism or laryngeal nerve damage. Therefore, future studies should focus on improved drug management, and a number of important advances are on the horizon. Graves’ disease is an autoimmune disease caused by autoantibodies to the thyroid-stimulating hormone receptor, causing hyperthyroidism. In this Primer, Davies and colleagues discuss the epidemiology, pathophysiology and diagnosis of Graves’ disease and highlight the need for better therapeutics for its management.
... [15] Previously, QOL was assessed by various multidomain health-related surveys (like MOS-SF24, HADS, POMS, and BDI), which had a disadvantage of being too general and unable to detect small, but clinically important changes. [16][17][18][19] Therefore, a disease-specific GO-QOL questionnaire was developed by Terwee et al. in the Dutch language which has two subscales (visual functioning and psychosocial consequences of changed appearance). [5] The patients with varying severity and clinical activity were included in this study. ...
Article
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Purpose: To validate the GO-specific quality of life (QOL) questionnaire in Hindi language and to determine the correlation of scores (visual functioning and appearance) with disease severity and activity. Methods: We recruited 114 consecutive patients with GO attending Endocrinology Clinic at tertiary care center. Eye examination was performed, and QOL was assessed by questionnaire. Results: The questionnaire was validated by 50 GO patients and test-retest reliability was performed in 15 patients. Hindi version GO-QOL was administered in 49 GO patients. GO was mild in 51.0% and sight-threatening in only 2.0% of cases. Orbitopathy was clinically active in only 10 (20.4%) cases. The GO-QOL scores (median) for visual function and appearance were 81.3 and 62.5, respectively. Patients with moderate-to-severe and sight-threatening GO had significantly lower median appearance scores (56.3 vs. 68.5, P= 0.01) compared to mild disease but no difference in visual scores. Patients with active disease had significant lower median visual function (53.1 vs. 85.7, P= 0.009) and psychosocial (appearance) scores (40.6 vs. 68.8, P= 0.03) compared to inactive disease. On multivariate regression analysis of GO-QOL scores, extraocular eye movement involvement (EOM), proptosis, and severity of eye disease were significantly associated with visual functioning while appearance was significantly associated only with the severity of eye disease. Conclusion: GO-QOL scores were significantly reduced in patients with GO.
... Patient quality of life [6][7][8][9][10] and mental health [11][12][13][14] are drastically affected by TED, with quality of care playing a large role [15]. Unfortunately, little is known about physician referral and treatment patterns in the United States, but patients with active, progressive TED may be treated with a wide range of therapies, with interventions widely varying from lubricating eye drops to systemic glucocorticoids to emergency orbital decompression surgery. ...
Article
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Introduction Limited data exist on US referral/management patterns for moderate-to-severe thyroid eye disease (TED), a disabling condition. Methods US ophthalmologists and endocrinologists experienced in treating TED provided medical record data of moderate-to-severe TED patients and information on referral/treatment practices. Data on signs/symptoms, medical/surgical treatments, treatment response, and referral history were collected. Moderate and severe cases were stratified to interrogate treatment/practice differences. Results A total of 181 physicians provided data on 714 patients (49.4 ± 13.6 years old, 65% women, 14% severe disease). Reporting physicians diagnosed 55% of patients themselves and solely managed 37% of cases, with similar referral/comanagement patterns between moderate and severe cases. Topical therapies included lubricating (79%) and glucocorticoid (39%) eye drops. Systemic therapies included oral glucocorticoids (36%), IV glucocorticoids (15%), and rituximab and/or tocilizumab (12%). Few patients underwent orbital radiation (4%) or surgical intervention (4%). IV glucocorticoids (33% vs. 12%), biologics (26% vs. 10%), orbital radiation (11% vs. 3%), and ocular surgery (12% vs. 3%) were used more often in severe versus moderate cases (all P < 0.001). However, severe disease was less responsive to therapy (very responsive to therapy: 28% vs. 49%, P < 0.001). Conclusions Participating physicians were primarily responsible for just over one-half of TED diagnoses, but solely treated <40% of patients. Severe TED was treated more often with surgery and systemic immunologic therapies than moderate disease, but was less likely to respond to treatment. These results reinforce that moderate-to-severe TED is difficult to treat with an unmet medical need in the United States.
... The reality for these patients is that their eyes are stared at by strangers (Roos and Murthy, 2019), their identities are changed (Estcourt et al., 2008), and their social functions are disabled (Coulter et al., 2007). Both social isolation and constant ocular disturbances impact the mental state of TAO patients (Kahaly et al., 2002). Evidence has shown that TAO patients underwent higher levels of anxiety and depression than people with other chronic diseases or facial disfigurements (Wickwar et al., 2015). ...
Article
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Purpose The purpose of the study was to investigate the brain functional alteration in patients with thyroid-associated ophthalmopathy (TAO) by evaluating the spontaneous neural activity changes using resting-state functional magnetic resonance imaging (rs-fMRI) with the amplitude of low-frequency fluctuation (ALFF) method. Materials and Methods The rs-fMRI data of 30 TAO patients (15 active and 15 inactive) and 15 healthy controls (HCs) were included for analyses. The ALFF values were calculated and compared among groups. Correlations between ALFF values and clinical metrics were assessed. Results Compared with HCs, active TAOs showed significantly decreased ALFF values in the left middle occipital gyrus, superior occipital gyrus, and cuneus. Compared with inactive TAOs, active TAOs showed significantly increased ALFF values in the bilateral precuneus. Additionally, inactive TAOs showed significantly decreased ALFF values in the left middle occipital gyrus, superior occipital gyrus, cuneus, and bilateral precuneus than HCs. The ALFF value in the right precuneus of TAOs was positively correlated with clinical activity score ( r = 0.583, P < 0.001) and Mini-Mental State Examination (MMSE) score ( r = 0.377, P = 0.040), and negatively correlated with disease duration ( r = −0.382, P = 0.037). Moreover, the ALFF value in the left middle occipital gyrus of TAOs was positively correlated with visual acuity ( r = 0.441, P = 0.015). Conclusion TAO patients had altered spontaneous brain activities in the left occipital lobe and bilateral precuneus. The neuropsychological aspect of the disease should be noticed during clinical diagnosis and treatment.
Article
Purpose: Thyroid-associated ophthalmopathy (TAO) is an autoimmune disorder associated with Graves' disease and can seriously decrease quality of life. Current therapeutic regimens have considerable side-effects and are not always able to restore normal function and appearance. Timing and a proper choice of therapy are critical but require careful patient evaluation. The present paper aims to describe clinical symptoms and signs of TAO and their relevance for management. Results and Conclusions: Thyroid-associated ophthalmopathy has an initial active inflammatory phase which usually lasts for 6–24 months but which may not infrequently continue for several years. The severity of the subsequent clinical manifestations is determined by the degree of optic nerve involvement, corneal involvement, eye muscle dysfunction and exophthalmus, and also by the degree of subjective illness and disfigurement. Disease severity is the key determinant of indication for therapy, while inflammatory activity is the key determinant of therapeutic choice. Immunosuppressive therapy may be used in the inflammatory stage, while reconstructive surgery should be postponed to the inactive phase. Emergency surgery may be needed for vision-threatening situations during the active stage.
Article
Previous randomized trials have suggested an association between radioiodine treatment for Graves' hyperthyroidism and thyroid-associated ophthalmopathy (TAO). The aim of the study was to compare the occurrence of worsening or development of TAO in patients who were treated with radioiodine or antithyroid drugs. We conducted a randomized trial (TT 96) with a follow-up of 4 yr. PATIENTS, SETTING, AND INTERVENTION: Patients with a recent diagnosis of Graves' hyperthyroidism were randomized to treatment with iodine-131 (163 patients) or 18 months of medical treatment (150 patients). Early substitution with T(4) was given in both groups. Worsening or development of TAO was significantly more common in the iodine-131 treatment group (63 patients; 38.7%) compared with the medical treatment group (32 patients; 21.3%) (P < 0.001). The risk for de novo development of TAO was greater in patients treated with iodine-131 (53 patients) than with medical treatment (23 patients). However, worsening of TAO in the 41 patients who had ophthalmopathy already before the start of treatment was not more common in the radioiodine group (10 patients) than in the medical group (nine patients). Smoking was shown to influence the risk of worsening or development of TAO, and smokers treated with radioiodine had the overall highest risk for TAO. However, in the group of smokers, worsening or development of TAO was not significantly associated with the choice of treatment for hyperthyroidism. Radioiodine treatment is a significant risk factor for development of TAO in Graves' hyperthyroidism. Smokers run the highest risk for worsening or development of TAO irrespective of treatment modality.
Article
Thyroid-associated ophthalmopathy (TAO) is an autoimmune disorder that can be divided into three clinical subtypes: congestive, myopathic and mixed ophthalmopathy. It is probably caused by immune cross-reactivity between orbital and thyroid antigens. The best candidate antigens are the thyrotropin receptor and the novel protein, G2s, which is now identified as a fragment of the winged helix transcription factor, FOXP1. The relationship between radioiodine therapy and TAO is controversial, with two randomised controlled trials showing a transient worsening of the eye disease after treatment. The diagnosis of TAO is a clinical one, based on the presence of specific symptoms and signs. Orbital imaging, preferably magnetic resonance imaging, is useful when the diagnosis is in doubt and in patients with suspected optic neuropathy who may benefit from early intervention. Despite their lack of specificity, orbital antibodies may add weight to the diagnosis and may potentially be a useful tool in classifying the different subtypes of TAO and in monitoring disease activity. While antibodies against G2s and the thyrotropin receptor are seen in all subtypes, those against Fp and collagen XIII may be associated with the myopathic and congestive subtypes, respectively, where Fp is the flavoprotein subunit of the mitochondrial enzyme, succinate dehydrogenase. In most patients, TAO is self-limiting and no specific treatment is required. When treatment is indicated, glucocorticoids are the mainstay of therapy. Orbital radiotherapy improves the efficacy of glucocorticoids, but is probably less beneficial as monotherapy. Orbital surgery is best reserved for patients with 'burnt out' inactive disease, but urgent orbital decompression may be required for optic neuropathy. The severity and clinical activity of TAO are important in determining the need for specific treatment and the likelihood of success with medical therapy, respectively.
Article
Graves' disease is the most common cause of hyperthyroidism and is frequently complicated by ophthalmopathy, which can be a debilitating component of the disease, resulting in impaired quality of life. The management of Graves' disease aims to restore the patient to a euthyroid state and minimise the extent of extrathyroidal manifestations such as ophthalmopathy. Management options include medical therapy, radioactive iodine (RAI) and surgical intervention in the form of thyroid resection. Graves' ophthalmopathy (GO) is often resistant to or even aggravated by medical therapy and RAI, both of which have unpredictable relapse rates. The extent of thyroidectomy in the management of benign thyroid disease remains controversial. Total thyroidectomy is being increasingly favoured as the procedure of choice for treatment of benign thyroid disease. Recent study has indicated that it can be performed with minimal complications at a rate comparable to the less radical subtotal thyroidectomy. The predictable outcome and lack ofdisease recurrence make it an attractive option for benign conditions such as Graves' disease. In addition, there is increasing evidence that total thyroidectomy may have a beneficial effect, inducing an improvement in eye signs and symptoms in cases of GO. This review discusses the indications for surgical intervention in Graves' disease, with specific focus on the extent of resection and the relative merits of subtotal and total thyroidectomy in patients with GO.
Article
The goal of medical care for most patients today is to obtain a more effective life and to preserve functioning and well-being. Scoring standardized responses to standardized questions is an efficient way to measure health status and individual health-related quality of life. Compared to a general population, patients with thyroid orbitopathy (TO) show a poor quality of life both in physical as well as in psychosocial dimensions. A large section of TO patients is not only physically ill, they also exhibit psychic illness. Consequently, among the majority of the TO patients, psychic and social factors in addition to physical ones play a role in their experience of their illness and essentially characterize their quality of life. According to these results, accompanying psychosomatic treatment would be indicated among roughly half of all TO patients.
Article
Thyroid eye disease (TED) is the most common cause of proptosis in adults, and should always be a consideration in patients with unexplained diplopia, pain, or optic nerve dysfunction. At least 80% of TED is associated with Graves disease (GD), and at least 50% of patients with GD develop clinically evident symptomatic TED. The most confusing patients for doctors of all subspecialties are the patients with eye symptoms and signs that precede serum evidence of a thyroid imbalance. Management of TED may include immunosuppressive medications, radiation, or surgery. Although the prognosis for optic nerve function is excellent, the restrictive dysmotility can result in permanent disability. Orbit and eyelid reconstruction are reserved for stable, inactive patients and are the final steps in minimizing facial alterations and enhancing the patient's daily functioning.
Article
General health-related quality of life is markedly impaired in patients with Graves' ophthalmopathy (GO), and even worse than in patients with other chronic conditions like diabetes, emphysema or heart failure. A disease-specific quality-of-life questionnaire for GO has been developed, the so-called GO-QOL, consisting of two subscales: one for visual functioning (8 questions referring to limitations due to decreased visual acuity and/or diplopia) and one for appearance (8 questions referring to limitations in psychosocial functioning due to changes in appearance). The GO-QOL was found to be a valid and reliable instrument. A minimal clinically important difference (MCID) in the GO-QOL score was derived from data obtained before and after specific eye treatments. Based on the patient's opinions, changes of > or = 6 points (minor surgery) or > or = 10 points (surgical decompression, immunosuppression) are recommended as MCID. It is concluded that the GO-QOL is an useful instrument for measuring changes over time in visual functioning and appearance of GO patients. The GO-QOL is available in six languages, and can be used as a separate outcome measure in clinical studies.
Article
Health-related quality of life (HQOL) is a concept that aims to understand the totality of an individual’s experience of their disease state. This can include the physical, psychosocial, emotional, and psychological effects of a disease state. A complex and multifactorial concept, HQOL can be challenging to measure accurately and reliably. Thyroid eye disease (TED), as a multifaceted physically debilitating and facial disfiguring disorder, presents unique challenges and opportunities in the measurement of HQOL. Multiple distinct tools have been developed for this purpose, each has been constructed, assessed, and utilized. This discussion surveys the landscape of TED-related QOL measurement and presents challenges for the future. Clinicians and clinical researchers should implement TED-related QOL measurement as part of routine TED care and as a primary outcome in TED clinical trials. We recommend utilizing the Graves’ ophthalmopathy (GO)-QOL routinely in clinical practice and as a primary outcome in TED clinical trials. If the GO-QOL is too time-consuming or in mild TED, a faster alternative is the TED-QOL.
Article
To evaluate the validity and responsiveness of a German-language version of the disease-specific Graves orbitopathy quality-of-life questionnaire (GO-QOL). Prospective cross-sectional study. At a multidisciplinary university orbital center, 310 consecutive unselected Graves orbitopathy outpatients answered the GO-QOL before undergoing complete ophthalmic and endocrine assessment. The main outcome measures were the GO-QOL and its 2 subscales, Visual Functioning and Appearance. The QOL scores for the subscales Visual Functioning and Appearance were (mean ± SE) 72.5 ± 1.4 and 71.3 ± 1.5, respectively. Visual Functioning and Appearance were higher in mild (82.2 ± 2.2 and 86.0 ± 17.6) than in moderate to severe (66.6 ± 1.8, p < .001, 95% CI 15.6-2.9 and 65.5 ± 25.5, P < .001, 95% CI 15.1-26.0) and in sight-threatening Graves orbitopathy (41.9 ± 9.9, P < .001, 95% CI 25.4-55.3 and 58.5 ± 9.0, P < .001, 95% CI 15.0-39.4). Visual Functioning and Appearance were also lower in active (63.3 ± 2.2 and 64.5 ± 2.2) than in inactive stages (77.0 ± 1.9; P < .001, 95% CI 7.9-19.3 and 78.3 ± 1.8, P < .001, 95% CI 8.2-19.2). Visual Functioning was 81.6 ± 1.8 in patients without and 62.4 ± 2.0 in patients with diplopia (P < .001, 95% CI 13.8-24.6). Appearance was lower in those receiving psychotherapy (64.7 ± 3.2) than in those without psychotherapy (74.6 ± 1.6, P = .005, 95% CI 3.0-16.7). Significant ceiling effects (≥15% at the highest value of the subscale) were observed for Appearance in 59 patients (19%) and for Visual Functioning in 85 patients (27%). The German-language version of the GO-QOL shows evidence of validity in Graves orbitopathy and it usefully complements ophthalmic assessment in these patients.
Article
Graves’ disease is an autoimmune disorder that is the most common cause of hyperthyroidism. Other symptoms associated with the disease are goitre, ophthalmopathy, and psychiatric manifestations such as mood and anxiety disorders and, sometimes, cognitive dysfunction. Graves’ hyperthyroidism may result in these latter manifestations via the induction of hyperactivity of the adrenergic nervous system. This review addresses the psychiatric presentations, and their pathophysiology and treatment, in patients with hyperthyroidism, based on literature identified by a PubMed/MEDLINE database search. Although the focus is on mental symptoms associated with Graves’ disease, it is not always clear from the literature whether patients had Graves’ disease: in some studies, the patients were thought to have Graves’ disease based on clinical findings such as diffuse goitre or ophthalmopathy or on measurements of thyroid antibodies in serum; however, in other studies, no distinction was made between Graves’ hyperthyroidism and hyperthyroidism from other causes. Antithyroid drugs combined with β-adrenoceptor antagonists are the treatments of choice for hyperthyroidism, as well as for the psychiatric disorders and mental symptoms caused by hyperthyroidism. A substantial proportion of patients have an altered mental state even after successful treatment of hyperthyroidism, suggesting that mechanisms other than hyperthyroidism, including the Graves’ autoimmune process per se and ophthalmopathy, may also be involved. When psychiatric disorders remain after restoration of euthyroidism and after treatment with β-adrenoceptor antagonists, specific treatment for the psychiatric symptoms, especially psychotropic drugs, may be needed.
Chapter
Patients with thyroid-associated eye disease (TED) are at increased risk of psychological disturbances such as anxiety and depression, resulting in impaired quality of life. Several standardized instruments, ranging from generic health-related questionnaires to those specific to TED, have been used to measure psychological changes and impact on quality of life. Altered appearance caused by TED seems to be most significant in decreasing quality of life by negatively influencing facial expression, communication, self-perception, and social interactions. However, deficits in visual functioning and the subsequent limitations in daily activities can also contribute. Diminished work productivity and healthcare costs may cause financial strain. Changes in quality of life scores do not always correlate with objective measures of clinical disease burden, supporting the argument for incorporating independent quality of life assessments into routine care. We propose that quality of life and psychological assessment be a routine component of multidisciplinary TED management.
Chapter
Eye disease related to dysregulation of thyroid signalling can vary from minimally symptomatic eye dryness to severe proptosis with vision-threatening optic nerve compression. The degree to which patients’ eye disease affects their health-related quality of life can vary to an equal degree. Objective measures of eye pathology do not correlate well with patients’ subjective symptoms, making patient-reported measures vital to the treatment and care of those with thyroid eye disease. Several instruments to assess quality of life are available in both clinical and research settings with focuses on general health, eye-specific health, and thyroid disease-related health. Studies carried out with these surveys have identified eye discomfort, diplopia, and change in appearance as factors which more greatly affect a patient’s social and emotional well-being. More severe symptoms can lead to disability and a significant negative economic impact, thus compounding the emotional distress. Improved ability to quantify how thyroid eye disease affects a person leads to more personally tailored treatments and an opportunity for holistic patient care.
Article
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The main goal of therapy for Graves' orbitopathy (GO) is to restore visual function and to improve quality of life (QOL); therefore, the idea of self-assessment of eye changes by the patient has been developed. We developed a validated Polish version of the GO-QOL questionnaire (GO-QOLpl). As an original version we used the English version of GO-QOL, which consists of 15 questions summarised in two subscales. GO-QOLpl was translated and validated in accordance with standard principles for translation of patient-reported outcomes (PRO). GO-QOLpl is a linguistically validated version of the original GO-QOL questionnaire, which is recommended by the European Group of Graves' Orbitopathy (EUGOGO). We strongly support the use of GO-QOLpl for the assessment of QOL among Polish patients with GO in clinical practice. (Endokrynol Pol 2015; 66 (4): 362-366).
GO is common in patients with Graves' disease and is associated with significant morbidity. The clinical presentation is varied and often the diagnosis is delayed. Careful clinical assessment usually leads to an accurate diagnosis, though in a minority of atypical presentations imaging and other diagnostic tests may be necessary. The natural history is well-documented, but work is still required in developing measures of grading of the disease to assist in clinical decision-making.
Article
In the acute, thyrotoxic phase, patients with Graves' disease often have both thyrotoxic and neuropsychiatric symptoms. The purpose of this prospective study was to examine health-related quality of life (HRQOL) in newly diagnosed and untreated Graves' patients and the effect of antithyroid medical treatment on HRQOL. In addition, we examined the potential influence of thyroid hormones and psychiatric symptoms on the impairment of HRQOL in the thyrotoxic phase. A total of 30 consecutively referred patients with newly diagnosed and untreated Graves' disease and 34 age-, sex- and education-matched healthy volunteers were included in the study. HRQOL was assessed with the Medical Outcome Study 36-item Short-Form Health Status Survey (SF-36) before treatment, after reaching euthyroidism and 1 year after initiation of treatment. In the thyrotoxic phase of Graves' disease, HRQOL was significantly impaired, in physical, mental and social dimensions. After reaching euthyroidism, the patients reported much fewer limitations on the subscales of SF-36. One year after initiation of treatment, all SF-36 scores had normalized. However, in some patients, HRQOL continues to be impaired even 1 year after initiation of treatment, as reviewed by the individual analysis. The reduced HRQOL in the acute phase of Graves' disease was correlated to depressive and anxiety symptoms, but thyroid-associated orbitopathy also influenced HLQOL. Impaired HRQOL is common in the acute phase of Graves' disease. A significant proportion of the patients demonstrated persistent HRQOL impairment 1 year after initiation of treatment. Improvement of HRQOL in these patients remains a challenge for the clinician.
Article
Objective. This study was conducted to assess the impact of Graves' orbitopathy on the quality of life in our population by using disease-specific questionnaire (GO-QOL) recommended by the European Group on Graves' Orbitopathy (EUGOGO). Methods. The study was conducted as a prospective cross-sectional and longitudinal trial that included adult patients of both sexes with GO. The quality of life assessment was performed with the standardized questionnaire of the European Group on Graves' orbitopathy. The study included 39 people (34 women, 5 men) who were, from September 2007 to January 2009, examined for the existence of GO. Results. Data obtained from the analysis of questionnaires showed that the quality of life of patients with Graves' orbitopathy was significantly diminished in our population, and that the higher the disease activity score was the lower the quality of life score was. The severity of the disease correlated with the deterioration of the quality of life. This correlation was present in both functional and especially in emotional aspects of the disease. Conclusion. The disease-specific questionnaire proved to be a useful instrument for the quality of life assessment in our population. Although some questions specific to our population become apparent through the interview with patients, we think that it is necessary to keep the original form of GO-QOL questionnaire, not only for the purpose of comparison of data, but also because of the need for Serbia to become suitable for EUGOGO membership.
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To investigate if there is any published evidence of impaired quality of life in conditions which are corrected by oculoplastic surgery and whether there is proven benefit in the quality of life such procedures. We searched a number of databases to determine the level of evidence available for common conditions amenable to oculoplastic surgery. Search terms concentrated on quality of life measures rather than anatomical correction of deformities. The level of evidence available for different conditions was very variable. Certain conditions had extensive research documenting reduction in quality of life, with some evidence for improvement after surgery. Some other common conditions had little or no evidence supporting of reduction in quality of life to support the need for surgery. The evidence is sparse for quality of life improvement after some of our most commonly performed procedures. Many of these procedures are now being identified by primary care trusts (PCTs) as of "low clinical value", and are no longer being routinely commissioned in certain parts of the UK. There is a need to address this lack of evidence to determine whether oculoplastic surgery should continue to be commissioned by PCTs.
Article
Objectives: To report photographic evidence of eyebrow tissue expansion in patients with thyroid-associated orbitopathy (TAO) and to demonstrate consistency in grading through the use of standardized photographs. Methods: A retrospective cohort study of patients referred for evaluation of TAO in an orbitofacial tertiary care center between January 1, 2000, and December 31, 2010. A grading key was produced with representative views of each of 4 grades (0 [no expansion] to 3 [severe expansion]), corresponding to increasing severity of eyebrow tissue expansion. Photographs of each study patient, including both premorbid and morbid photographs, were retrieved from an electronic medical record system and graded by 6 independent, masked observers using this 4-point system. Results: Seventy-five patients with TAO were identified for inclusion. The average grade was 0.3 for premorbid eyes and 1.1 for morbid eyes. Intraclass correlation coefficients for the premorbid photographs were 0.705 and 0.632 for the right and left eyes, respectively. Intraclass correlation coefficients for the morbid photographs were 0.921 and 0.916 for the right and left eyes, respectively. Conclusions: Eyebrow tissue expansion is a common manifestation in TAO. Comparison of premorbid and morbid photographs is a useful means to identify and characterize the extent of brow involvement. The use of a grading key improves the consistency of identifying and grading eyebrow tissue expansion. Recognition of the eyebrow tissue as distinct anatomically in TAO may be crucial to rehabilitation of these patients, which may entail multiple surgical procedures.
Article
General health-related quality-of-life (QoL) questionnaires (MOS SF-24 and SF-36) and the more sensitive disease-specific QoL questionnaire (GO-QoL) both indicate substantial impairment of quality of life in patients with Graves' ophthalmopathy (GO). The GO-QoL contains 8 questions on visual functioning and 8 questions on appearance; answers on each subscale are transformed to scores ranging from 0 (worst) to 100 (best). The minimal clinically important difference in scores is ≥10 points for invasive therapies, but a change of 6 points on one of both subscales is already perceived by patients as beneficial and associated with an important change in daily functioning. The GO-QoL is well validated, widely used, and available in eight languages. The GO-QoL is recommended as an independent primary outcome measure in randomized clinical trials. Incorporating the GO-QoL in the routine assessment of GO in daily clinical practice is also recommended: although unproven, it is likely to improve the quality of care by identifying patients who are in need for psychological support in order to address poor psychosocial functioning and low self-esteem.
Article
Postoperative quality of life (QoL) after surgery for Graves' disease is not well documented, and the effect of different surgical operations has not been compared. This study examines the impact on QoL of a shift in policy from operations intended to preserve thyroid function (PF) to those ablating thyroid function (AF). A cross-sectional assessment was performed on patients who underwent surgery for Graves' disease between 1986 and 2008 in a tertiary endocrine surgical unit. Patients completed the Short Form 36 (SF-36) questionnaire by post. SF-36 scores, including the physical and mental component summaries, were compared with the general population and by operative intent (AF vs. PF). Statistical analyses were performed using SPSS 16.0. Of 150 patients, 3 had died of unrelated causes and 14 were not contactable. In the remaining 133 patients, the median age at time of assessment was 46 years (interquartile range 42-50) and 43 years (interquartile range 33-47) in the PF and AF groups, respectively. From these patients, 87 questionnaires (65.4% response rate) were completed with an item completion rate of 99.3%. The median follow-up was 18.4 years for PF and 7.9 years for AF surgery. Of 87 respondents, 38 (43.7%) underwent PF and 49 (56.3%) AF surgery. Study participants reported lower scores across all SF-36 subscales than British norms (p<0.05). Comparisons on operative intent showed no significant difference in long-term QoL (p>0.05). The shift to ablative surgery simplifies postoperative management with no adverse effect on QoL, justifying this practice from a patient perspective.
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The importance of patient-reported outcomes such as health-related quality of life (HRQL) in clinical research is increasingly acknowledged. In order to yield valid results, the measurement properties of HRQL questionnaires must be thoroughly investigated. One aspect of such a validation process is the demonstration of content validity, i.e. that the questionnaire covers all relevant aspects. We review studies reporting on consequences of thyroid disorders and present the frequency of identified aspects, both overall HRQL issues and classical thyroid symptoms, in order to evaluate which issues are relevant for patients with thyroid diseases. Furthermore, existing questionnaires for thyroid patients are reviewed. A systematic search was performed in the Medline, Cinahl and Psycinfo databases and the reference lists of the relevant articles were hand-searched. Seventy-five relevant studies were identified. According to these studies, patients with untreated thyroid disease suffer from a wide range of symptoms and have major impairment in most areas of HRQL. Furthermore, the studies indicate that impairments in HRQL are also frequent in the long term. Six HRQL questionnaires for thyroid patients were identified. Generally, data supporting the validity of these questionnaires were sparse. According to the available literature, the quality of life of thyroid patients is substantially impaired over a wide range of aspects of HRQL in the untreated phase and continues to be so in many patients also in the long term. Studies systematically exploring the relative importance of these various aspects to thyroid patients are lacking, as is a comprehensive, validated thyroid-specific HRQL questionnaire.
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To study mood disturbance in Graves ophthalmopathy. Forty-eight patients (mean age, 55 years; 40 women and 8 men) with Graves ophthalmopathy from a university-based referral center were classified into two groups, 24 with moderate/severe disease (study group) and 24 with negligible/mild disease (control group). The groups were matched with regard to demographic and medical characteristics. All participants completed a mood survey to assess differences in degree of emotional distress. The Profile of Mood States survey, a 65-item self-reported inventory designed to assess emotional distress, was the primary outcome measure. A total mood disturbance score was assigned by summing the scores derived on the 6 subscales of the survey--tension, depression, vigor, confusion, fatigue, and anger. Analysis of variance revealed that patients with moderate/severe Graves ophthalmopathy showed significantly greater emotional distress than patients with mild/negligible Graves ophthalmopathy on the Profile of Mood States mean total score (P<.001). Additionally, patients who had disfigurement (proptosis) as the predominant clinical feature had significantly elevated emotional distress compared with the control group (P = .01), whereas no significant difference was detected between the control group and patients with diplopia as the predominant clinical feature (P = .20). Patients with moderate to severe Graves ophthalmopathy have significant mood disturbance, especially when disfiguring signs are predominant. We propose that evaluation of the psychological burden of the disease should be considered in routine follow-up and in decisions regarding treatment.
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We describe the functioning and well-being of patients with depression, relative to patients with chronic medical conditions or no chronic conditions. Data are from 11,242 outpatients in three health care provision systems in three US sites. Patients with either current depressive disorder or depressive symptoms in the absence of disorder tended to have worse physical, social, and role functioning, worse perceived current health, and greater bodily pain than did patients with no chronic conditions. The poor functioning uniquely associated with depressive symptoms, with or without depressive disorder, was comparable with or worse than that uniquely associated with eight major chronic medical conditions. For example, the unique association of days in bed with depressive symptoms was significantly greater than the comparable association with hypertension, diabetes, and arthritis. Depression and chronic medical conditions had unique and additive effects on patient functioning.
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Enhancing daily functioning and well-being is an increasingly advocated goal in the treatment of patients with chronic conditions. We evaluated the functioning and well-being of 9385 adults at the time of office visits to 362 physicians in three US cities, using brief surveys completed by both patients and physicians. For eight of nine common chronic medical conditions, patients with the condition showed markedly worse physical, role, and social functioning; mental health; health perceptions; and/or bodily pain compared with patients with no chronic conditions. Each condition had a unique profile among the various health components. Hypertension had the least overall impact; heart disease and patient-reported gastrointestinal disorders had the greatest impact. Patients with multiple conditions showed greater decrements in functioning and well-being than those with only one condition. Substantial variations in functioning and well-being within each chronic condition group remain to be explained.
Article
Describes the development of a new instrument, the Life Experiences Survey (LES), for the measurement of life changes. The LES is a 57-item self-report measure that is divided into 2 sections: Section 1 consists of 47 items that refer to life changes in a wide variety of situations; Section 2 consists of 10 items that are designed primarily for use with students. It was designed to eliminate certain shortcomings of previous life stress measures and allows for separate assessment of positive and negative life experiences as well as individualized ratings of the impact of events. The reliability and possible sex differences of the LES are discussed, and the LES is compared with the State-Trait Anxiety Inventory, the Marlowe-Crowne Social Desirability Scale, the Psychological Screening Inventory, the Beck Depression Inventory, Rotter's Internal–External Locus of Control Scale, and the Schedule of Recent Experiences using undergraduate samples. Several studies bearing on the usefulness of the Life Experiences Survey are presented and the implications of the findings are discussed.
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  • Muthny
  • Freiburger Fa
  • Fragebogen
  • Fkv Krankheitsver-Arbeitung
  • Beltz
  • Weinheim
Muthny FA 1989 Freiburger Fragebogen zur Krankheitsver-arbeitung, FKV. Beltz, Weinheim. Address reprint requests to: George J. Kahaly Department of Medicine and Endocrinology/Metabolism Gutenberg University Hospital Langenbeckstr. 1 Mainz 55101
Measuring Functioning and Well-Being. The Medical Outcomes Study Approach
  • A L Stewart
  • J E Ware
Stewart AL, Ware JE (eds) 1992 Measuring Functioning and Well-Being. The Medical Outcomes Study Approach. Duke University Press, Durham, London.
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  • U Buss
  • R P Snaith
Herrmann C, Buss U, Snaith RP 1995 HADS-D. Hospital Anxiety and Depression Scale. Toronto, Seattle.