Measurements of general quality of life are significantly lower in patients with TED. Compared to a large published reference group using the Medical Outcomes Study (MOS-24) and three subscales of the Sickness Impact Profile (SIP), TED patients had lower scores in the categories of physical functioning, social functioning, mental health, health perceptions, and bodily pain [14]. Another study using a 105-item questionnaire combining items from the NEI-VFQ, the Short Form (SF-12), an adapted version of the Dermatology-Specific Quality of Life (DSQL) instrument, and questions specific to TED, found statistically significant lower scores for all measures of quality of life compared to a control group [15]. These included all subscores of the NEI-VFQ (except color vision), both physical and mental components of the SF-12, and the self-perception and social desirability scales. Overall lower quality of life was neither age specific nor gender specific [15].

The prevalence of psychiatric disturbance is greater among patients with TED compared to controls. TED patients have increased emotional distress, with almost half of patients suffering from symptoms of anxiety and/or depression [16]. Based on the Hospital Anxiety and Depression Scale (HADS), one study estimated the prevalence of psychiatric disorders to be 32 % among a population of TED patients, of which 19 % had depressive disorders and 19 % had current anxiety disorders [17]. Using the Mini-International Neuropsychiatric Interview, Graves’ patients were found to have significantly greater prevalence of anxiety disorders, major depression, and total mood disorders even compared to hospitalized patients with other diseases [18].

The increased prevalence of psychiatric disturbances among these patients can be attributed, in part, to the ocular symptoms, functional impairments and changes in appearance produced by TED. Looking at specific subgroups using the Profile of Mood States (POMS) instrument, TED patients for whom proptosis was the predominant feature experienced significantly greater emotional distress than patients for whom strabismus or muscle restriction was the predominant feature [19]. Similarly, on the Middlesex Hospital Questionnaire, patients with proptosis experienced significantly increased anxiety, depression, and phobia when compared to those with TED related muscle restriction [20]. Therefore, not only does proptosis cause functional impairment such as significant dry eye, but it is also associated with psychological distress.

Although this chapter focuses primarily on the effects of TED signs and symptoms, underlying thyroid dysfunction should also be considered when evaluating psychological disturbances in TED patients. Both hyperthyroidism and hypothyroidism have been associated with an increased risk of mood disorders that usually resolve when euthyroidism is achieved [21, 22]. Hypothyroidism results in depressive symptoms due to low production of triiodythyronine (T3, generally considered a “mood-enhancing” hormone), whereas hyperthyroidism causes an increase in free total thyroxine (T4) resulting in a relative decrease in T3 [21]. However, some patients can experience altered mood even after being rendered euthyroid [23–25]. One proposed explanation is that the presence of antithyroid antibodies alone, regardless of the clinical thyroid state, may be linked to a higher prevalence of psychiatric disorders, via a shared underlying immune-mediated neuroendocrine pathway [26, 27]. Other studies have challenged this proposition by showing that the prevalence of antithyroid antibodies does not differ between psychiatric inpatients and controls [28, 29]. Furthermore, some of the studies reporting a linkage between antithyroid antibodies and psychiatric disease failed to control for previous exposure to lithium, which has antithyroid activity and could promote the formation of antibodies, thereby confounding results [21, 30, 31]. Whether or not thyroid autoimmunity ultimately proves to share a common pathogenesis with psychiatric disease, a patient’s thyroid hormone state can produce mood changes in patients with TED independent of eye symptoms (Fig. 13.2).

Appearance-related concerns among TED patients have been reported to be as high as 90 %, with greater frequency in younger patients and females [7]. Because physical appearance is closely tied with self-perception, confidence, and identity, the disfiguring changes inflicted by TED can affect these personality traits. In a Dutch study using the GO-QoL, 71 % of patients felt that TED had negatively affected their self-confidence, and more than half felt that they were watched by other people [7]. Similarly, in an Australian cohort assessed using an English language version of the GO-QoL, 33 % of patients reported that their self-confidence had been impaired “a little,” while 44 % of patients reported that their self-confidence had been impaired “very much” [32]. Among a German group, 38 % reported impaired self-perception [33]. One of the themes that emerged from an open-ended qualitative analysis of TED patients was the development of an altered identity among TED patients as a result of changes in appearance and abilities [34]. Female gender has also been associated with a greater decline in self-perception [15].

The changes in appearance in TED also affect these patients’ social relationships and their interactions with others. The lid retraction, proptosis, and decreased blinking associated with TED can make a patient look hostile, angry, or startled when that is not their intent [3]. Due to a lack of control over facial expression and communication, TED patients may experience altered attitudes and behavior from others, leading to difficult social interactions and strained personal relationships. These patients endorse feeling like they are somebody else, feeling clumsy around others, and feeling cut off from the outside world; they struggle to avoid social withdrawal [12]. Both men and women also report a decline in social desirability [15]. Besides changes in facial appearance, the changes in patients’ mood, psychological disturbances, and impaired self-perception may also affect social relationships (Fig. 13.2).

Functional deficits encountered in TED patients include altered visual acuity, decreased lacrimation, diplopia, and orbital/ocular pain [35]. Pain in particular is a symptom more frequently experienced in TED than in other eye diseases. It may be secondary to exposure keratitis caused by eyelid malposition, or a feeling of elevated pressure associated with periorbital edema, extraocular muscle enlargement, increased orbital fat, and proptosis [15]. One criticism of the GO-QoL is that it does not have any items related to ocular pain and therefore fails to capture an important element of how TED affects quality of life [6].

These functional deficits can limit daily activities. Many patients report impairments in driving, leisure activities, reading, and television viewing [7, 32, 36]. The effects on daily activities may also contribute to mood issues. For example, deficits in visual functioning and the resulting impairment in participating in hobbies may lead to anhedonia and increase the likelihood of developing depression. Quality of life studies in allied conditions of visual impairment, such as dry eye syndrome and ocular surface disease, have also uncovered connections between reduced visual function, interference with activities of leisure and daily living, and a higher prevalence of depression [37–42]. The complex interactions appearance, function, mood, and quality of life in TED are summarized in Fig. 13.2.

TED incurs considerable direct healthcare expense as well as indirect costs to the individual and society due to impaired productivity. A significant correlation has been found between the costs of TED and the scores on the GO-QoL [43]. In a study of these economic effects in a cohort of TED patients, 36 % were on sick leave, 28 % were disabled, 5 % had retired early, and 3 % had lost their jobs as a result of their disease [33]. Patients with more severe disease were on sick leave for longer periods and more likely to be disabled [33]. A decreased ability to work may also contribute to mood disturbances (Fig. 13.2), incurring considerable emotional and psychological cost in addition to financial losses.