Abstract
Purpose
This review aims to discuss the psychological aspects of Graves’ ophthalmopathy (GO), estimate the prevalence of depression and anxiety disorders in GO, examine whether these psychiatric disorders are more prevalent in GO than in Graves’ disease (GD) without eye disease, and evaluate the main contributors for depression and anxiety in GO.
Methods
A review of the literature.
Results
Both depression and anxiety are associated with GO. The prevalence of depression and anxiety disorders specifically in GO patients was estimated at 18–33% and 26–41%, respectively. The reported prevalence in GD patients ranged from 9% to 70% for depression and from 18% to 88% for anxiety disorders. Significantly higher levels of depression and anxiety were found in GD patients compared with patients with non-autoimmune hyperthyroidism. Conflicting results have been reported regarding the association of antithyroid autoantibodies with depression and anxiety disorders. Serum thyroid hormone levels do not correlate with the severity of depression and anxiety. An improvement of psychiatric symptoms is observed in hyperthyroid patients after treatment of thyrotoxicosis. Moreover, depression and anxiety are significantly related to impaired quality of life (QoL) in GO. Exophthalmos and diplopia were not associated with depression nor anxiety, but orbital decompression and strabismus surgery do seem to improve QoL in GO patients.
Conclusions
The results of this review suggest that altered thyroid hormone levels and autoimmunity are prognostic factors for depression and anxiety in GO. With regard to the visual and disfiguring aspects of GO as contributing factors for depression and anxiety, no decisive conclusions can be made.
Introduction
Graves’ ophthalmopathy (GO) is an autoimmune disease characterized by the inflammation of the periorbital tissues. Inflammation in GO may result in dry eyes, erythema, periorbital swelling, exophthalmos, conjunctivitis, upper eyelid retraction, diplopia, and even corneal ulceration and optic neuropathy (1). All these clinical manifestations make GO a vision-threatening and disfiguring illness, heavily affecting the quality of life (QoL) and mental well-being of patients. GO is six times more prevalent among women than men, with an annual incidence rate of 18 women and three men per 100,000 (1). Due to its pathogenesis, GO is closely related to autoimmunity of the thyroid gland. Eighty-five percent of GO patients have hyperthyroidism, most frequently caused by Graves’ disease (GD), 10% of GO patients are hypothyroid, and 5% are euthyroid (2). Among GD patients, 20–50% develop ophthalmopathy, making GO the most prominent extrathyroidal manifestation of GD (3). Besides increased levels of free thyroid hormones and reduced levels of thyroid-stimulating hormone (TSH), GD is characterized by elevated serum thyrotropin receptor antibodies (TRAb) and anti-thyroid peroxidase antibodies (TPOAb).
In the 1990s, multiple studies demonstrated a large negative impact of GO on the QoL of patients (4, 5). These studies, however, utilized general health-related quality of life (HRQL) questionnaires, which contained items of little relevance for GO specifically. To solve this problem, Terwee et al. developed a disease-specific QoL questionnaire for GO patients (GO-QoL), consisting of 16 questions pertaining to two aspects: visual functioning and appearance (6). Since then, the GO-QoL questionnaire has turned out to be a valid and reliable assessment tool for patients, even to evaluate the effects of different treatments (7, 8, 9).
Furthermore, many studies have reported the association of thyroid dysfunction and GD with psychiatric disorders, mainly depression and anxiety (10, 11). Although GD and GO are two highly associated diseases, most of these studies do not differentiate between GO and GD without eye disease. Pertaining to GO specifically, numerous studies have been performed on the quality of life of patients (12, 13, 14, 15, 16, 17, 18, 19, 20). Nevertheless, to date, few reports have discussed the prevalence of anxiety and depression in GO patients explicitly (13, 21). Consequently, it is not clear whether the altered thyroid hormone levels, the thyroid autoimmunity, or the visual and disfiguring aspects of GO are the main contributors for psychiatric disorders among GO patients. Previously, Bruscolini et al. published a review about neuropsychiatric disorders in GO; however, in this review, no clear distinction was made between studies on GD without eye disease versus GO specifically (22).
The present review aims to discuss the psychological aspects of GO, assess the prevalence of depression and anxiety in GO, and assess whether these psychiatric disorders are more prevalent among GO patients compared with GD patients without eye disease. In this review, we focus on depression and anxiety, because these two psychiatric disorders are the most prevalent among dysthyroid, GD, and GO patients. Additionally, the present review aims to assess the main contributors to depression and anxiety among GO patients.
Materials and methods
A literature search was conducted using the Medline, Embase, and Psycinfo databases. Specific keywords and their synonyms were used, including ‘Graves’ disease’, ‘Graves’ ophthalmopathy’, ‘hyperthyroidism’, ‘thyroid disorder’, ‘mood disorders’, ‘anxiety disorders’, and ‘depression’. The search was conducted without any limitations to the publication date. The publication date of the records found from the search ranged from 1922 to November 2022, when the search was conducted. One author filtered the records first based on the title, then based on the abstract, and finally based on the full text. Every English article with a relation to depression or anxiety disorders among dysthyroid, GD, or GO patients was included. On top of that, references from the retrieved studies that were relevant to the topic were also reviewed. For assessing the prevalence of depression and anxiety in GO, only studies that clearly mentioned that the population only consists of GO patients were used. The prevalence of depression and anxiety in GD without eye disease was assessed from studies that mention using a GD population without specifically mentioning eye disease.
Results
The literature search initially resulted in 776 records. Eventually, 44 articles from the literature search were included and analyzed for this review.
Relation of thyroid disorders and GD with depression and anxiety
The association of thyroid disorders with psychiatric disorders, especially mood disorders, has been described for a long time within the literature. Parry in 1825 and Graves in 1835 reported psychiatric manifestations in patients with thyroid dysfunction (23, 24). Both depression and anxiety are more prevalent in hyperthyroidism compared with hypothyroidism (approximately 50–65% vs 35–45%, respectively) (25, 26) (Table 1). Even though hyper- and hypothyroid patients have significantly higher prevalences of depression and anxiety compared with the healthy population, most psychiatric patients do not have thyroid dysfunction (27, 28). These results indicate a one-directional relation between thyroid dysfunction and psychiatric disorders. Likewise, numerous studies reported a correlation between Graves’ hyperthyroidism and depression and anxiety (29, 30, 31, 32, 33) (Table 1). Hamed et al. revealed that even GD in children is associated with higher frequencies and severities of depression, anxiety, and inattention (34). The association between thyroid dysfunction and GD with depression and anxiety could be explained through the altered levels of thyroid hormones that impact the nervous system. In fact, Naicker et al. found significant expression of TSH receptors in the limbic regions of healthy adults (35). Comparably, Schreckenberger et al. found regional metabolic changes within the limbic and paralimbic structures of hyperthyroid GD patients (36). Multiple recent studies have also reported that GO patients have altered brain connectivity (37, 38, 39, 40, 41).
Prevalence of depression and anxiety in GD
Previous studies have reported various prevalences for depression and anxiety in GD patients, ranging from 9% to 70% for depression and from 18% to 88% for anxiety (11, 32, 33, 42, 43, 44). Placidi et al. found no significant difference in depression and anxiety frequencies between GD patients and patients with non-autoimmune hyperthyroidism (11). On the contrary, three larger and more recent studies found significantly higher levels of depression and anxiety in GD patients compared with patients with nodular goiter (42, 45, 46).
Relation of serum thyroid hormone levels and antithyroid antibodies with depression and anxiety
In general, authors reported that serum thyroid hormone levels (TSH, triiodine (T3) and thyroxine (T4)) do not correlate with levels of depression and anxiety, meaning that the severity of hyperthyroidism is not linked to the severity of depression and anxiety in hyperthyroid patients (33, 42, 44, 47, 48) (Table 1). Nonetheless, Krysiak et al. studied a population consisting only of females and noted that the severity of depression positively correlated with serum-free thyroid hormone levels and inversely correlated with serum TSH levels (46). In addition, Hamed et al. found lower serum TSH levels and higher serum T3 and T4 levels to be significant predictors of emotional and behavioral problems in pediatric GD patients (34). With regards to the association of antithyroid autoantibodies with depression and anxiety, conflicting results exist. Some studies mentioned that there is no relation between serum TRAb and depression and anxiety (42, 49), while others reported that higher concentrations of TRAb are associated with higher prevalences of depression and anxiety (34, 44, 46). Another study even reported that hyperthyroid GD patients at onset had significantly smaller volumes of amygdalae and hippocampi than healthy controls and that, within these patients, serum TRAb levels negatively correlated with the volumes of these regions (50). Pertaining to TPOAb, Bové et al. reported no connection with depression or anxiety. Other authors found that TPOAb-positivity is linked to depression in GD patients (46, 49, 51).
The effect of treatment of hyperthyroidism on depression and anxiety in dysthyroid and GD patients
Previous prospective studies have generally illustrated an improvement in psychiatric symptoms in hyperthyroid patients after treatment of thyrotoxicosis (52, 53, 54, 55). The same thing applies to the treatment of Graves’ hyperthyroidism (33, 54, 56, 57) (Table 1). Chattopadhyay et al. even reported that there was no significant improvement in psychiatric symptoms in GD patients between only anti-thyroid drug treatment (ATD) and ATD combined with anti-psychotropic medication (43). Yu et al. found that patients who became subclinically hypothyroid after treatment had significantly more depression compared to those who were euthyroid (49). This finding is consistent with the literature, as subclinical hypothyroidism has been linked to depression (58). In addition, some studies demonstrated that GD patients with depression were less likely to be cured and more likely to relapse into hyperthyroidism after treatment compared to GD patients without depression (57, 59). On the other hand, a few studies revealed residual psychiatric symptoms after patients achieved euthyroidism with treatment, indicating that the development of psychiatric manifestations in dysthyroid patients is not necessarily caused by altered thyroid hormone levels alone (60, 61).
Association of clinical features with depression and anxiety in GD patients.
| Clinical feature | Correlation with depression | Correlation with anxiety | Key findings |
|---|---|---|---|
| GD (without eye disease) | Correlation with depression | Correlation with anxiety | Significantly higher levels of depression and anxiety in GD patients compared with patients with nodular goiter (non-autoimmune hyperthyroidism) (29, 30, 31, 32, 33) |
| Thyroid dysfunction | Correlation with depression | Correlation with anxiety | Depression and anxiety more prevalent in hyperthyroidism than hypothyroidism (25, 26) |
| Serum thyroid hormone levels | No correlation with the severity of depression | No correlation with the severity of anxiety | The severity of hyperthyroidism is not linked to the severity of depression and anxiety (33, 42, 44, 47, 48) |
| Antithyroid antibodies | Conflicting results | Conflicting results | Some studies show association, others don’t (34, 42, 44, 46, 49, 50) |
| Treatment response | Improvement after treatment | Improvement after treatment | Improvement in psychiatric symptoms in hyperthyroid and GD patients after treatment of thyrotoxicosis (33, 54, 56, 57) |
The role of stress in the onset of GD
Many studies have been conducted on the influence of psychological stress on the onset of GD. Retrospective studies found that GD patients reported more negative life events and psychological stress within 12 months prior to GD onset compared to healthy controls (62, 63, 64, 65, 66, 67). Despite this, when it comes to prospective studies among euthyroid subjects, experiencing more psychological stress does not precipitate the onset of thyroid autoimmunity (68, 69). Some additional studies illustrated that the incidence of GD and hyperthyroidism did not increase during times of war when the population was exposed to acute and chronic stress (70, 71).
Psychiatric aspects of Graves’ ophthalmopathy
Prevalence of depression and anxiety in GO
From the few studies we found, the prevalence of depression and anxiety in GO patients was assessed between 18–33% and 26–41%, respectively (Table 2), compared to 8.2% and 1.1% in the general population (13, 21, 72, 73, 74, 75). One study reported exceptionally high depression and anxiety prevalences in GO patients (60% and 70%, respectively) (76).
Prevalences of depression and anxiety in GO patients.
| Author (year) | Population size (n) | Female (%) | Mean age +/− s.d. (years) | Prevalence depression (%) | Prevalence anxiety (%) | Questionnaire used to assess depression and anxiety (cut-off score) |
|---|---|---|---|---|---|---|
| Kahaly (2005) (73) | 102 | 78 | 41, 18–72 (median, range) | 23.5 | 40.2 | Hospital Anxiety and Depression Scale (HADS) (≥11) |
| Bunevicius (2005) (76) | 30 | 100 | 45 ± 14 | 60.0 | 73.0 | Standard Mini-International Neuropsychiatric Interview (MINI) |
| Lee (2010) (13) | 49 | 78 | 41.4 ± 13.4 | 32.7 | – | Beck Depression Inventory (BDI) (≥16) |
| Wickwar (2015) (21) | 121 | 72 | 47.1 ± 12.3 | 26.0 | 37.0 | Hospital Anxiety and Depression Scale (HADS) (≥11) |
| Cockerham (2021) (74) | 100 | 47 | 45.2 ± 7.6 | 28.0 | 34.0 | Self reported through an online survey |
| Wang (2021) (72) | 714 | 65 | 49.4 ± 13.6 | 18.3 | 26.3 | Diagnosis from clinical records |
Relation of depression and anxiety with QoL in GO patients
Multiple studies have reported a significant relationship between depression and anxiety with impaired quality of life (QoL) in GO patients (13, 73, 74). Some studies also conducted multivariable regression analyses to determine the unique predictors for QoL in GO patients. Kahaly et al. and colleagues found depression and anxiety to be the foremost predictors of HRQL in GO patients (73). Another study used the GO-QoL questionnaire, consisting of two subscales: an appearance-related QoL subscale and a vision-related QoL subscale (77). Two separate multiple regression models were made, one for each GO-QoL subscale. They found that depression, in addition to older age and GO asymmetry, made a significant independent contribution to vision-related QoL (21). Similarly, Wiersinga et al. noted that older patients reported significantly lower scores on the vision-related GO-QoL subscale (12). Furthermore, depression,appearance-related social anxiety, and social avoidance (assessed by the Derriford Appearance Scale) were reported as significant unique contributors to appearance-related QoL (21, 78). Another study reported that female GO patients reported more appearance-related problems compared to male patients (12). On the contrary, anxiety (HADS-Anxiety) was not found to be a unique contributor to either of the two GO-QoL subscales (21). The aforementioned tools gauge psychological symptoms from a patient perspective. In contrast, Wang and colleagues investigated QoL impact in GO patients as perceived by physicians. Physicians scored their perceptions on how GO impacted patients' QoL based on a 7-point Likert scale, with 1 being ‘not impaired at all’ and 7 being ‘extremely impaired’. In this study, the proportion of GO patients with depression progressively increased with higher physician-perceived QoL impact scores. The prevalence of anxiety, however, was stable across the spectrum of the physician-perceived QoL impact score (72).
Relation of patient/clinical characteristics with depression and anxiety in GO patients
No significant association was found between depression in GO patients and age or sex (13, 21, 72) (Table 3). One author noted no relation between depression in GO patients and GO or GD duration (13). Also, in multiple studies, GO duration was not associated with QoL, except for one study that noted an association between longer GO duration and lower QoL (12, 21, 72, 73). In addition, GO patients with lower QoL had significantly more doctor visits per year compared with patients with high QoL (21).
Association of demographic/clinical features with depression and anxiety in GO patients.
| Clinical feature | Correlation with depression | Correlation with anxiety | Key findings |
|---|---|---|---|
| Age | No correlation | – | Depression not significantly associated with age in GO patients (13, 21, 72) |
| Sex | No relation | – | Depression not significantly associated with sex in GO patients (13, 21, 72) |
| GO/GD duration | No relation | – | No significant association between depression and GO/GD duration (13) |
| Reported stressful life events 6 months prior to GO onset | Positive correlation | Positive correlation | Reported stressful life events correlate with higher depression and anxiety levels in GO patients (73) |
| GO Severity (EUGOGO) | Conflicting results | Conflicting results | Some studies show association, others do not (13, 72, 73, 80) |
| GO Activity (CAS score) | Conflicting results | Conflicting results | Some studies show association, others do not (13, 73, 81) |
| Exophthalmos | Conflicting results | Conflicting results | Mixed findings on the association between exophthalmos and depression/anxiety (13, 73, 80) |
| Diplopia | No relation | No relation | No significant association between diplopia and depression/anxiety (13, 80) |
| Orbital decompression surgery | Significantly improved depression | Significantly improved anxiety | Significantly improved depression and anxiety (86) |
The role of stress in the onset of GO
Kahaly and colleagues studied 102 GO patients, of whom 86 (84%) reported stressful life events within 6 months prior to GO onset. A positive correlation was described between reported stressful life events and levels of depression and anxiety in GO patients (73) (Table 3). Stressful life events were present significantly more often in optic neuropathy patients compared to GO patients without neuropathy. The main stressful life events reported by GO patients were extreme sleeping problems, changed professional situations, and financial difficulties (73). No association was noted between the occurrence of stressful life events and T3 concentrations, TRAb concentrations, and the presence of exophthalmos.
Relation of GO severity and GO activity with depression and anxiety
Conflicting results have been reported on the association of depression and anxiety with GO severity and GO activity (Table 3). Pertaining to GO severity (European Group on Graves’ Orbitopathy (EUGOGO) classification) two authors reported no significant link with depression in GO patients (13, 72, 79). In spite of that, in the study by Farid and colleagues, moderate to severe GO patients scored significantly higher on the depression subscale of the Profile of Mood States (POMS) as opposed to negligible to mild GO patients (80). However, no significant difference in GO severity was noted regarding the anxiety subscale of the POMS (80). Moreover, Kahaly et al. found significantly higher levels of depression and anxiety in severe GO patients versus mild GO patients (73). On the other hand, another study noted the opposite results: a significantly higher anxiety prevalence in patients with moderate GO than in those with severe GO (72). Concerning GO activity (clinical activity score (CAS score)), no significant relation was found with depression in GO patients in two studies (73, 81). In another study, however, depression in the GO patients was associated with a higher CAS score (13). Kahaly et al. did find significantly higher levels of anxiety in active GO patients compared with inactive GO patients, but Wang et al. reported no significant relation (73, 81).
Relation of GO signs and symptoms with depression and anxiety
Exophthalmos (assessed by Hertel exophthalmometer), one of the most prominent signs of GO, was not associated with depression or anxiety in two studies (13, 73). However, another author linked exophthalmos to higher levels of depression and anxiety (80) (Table 3). Moreover, no relation was found between diplopia (assessed by the Gorman score) and depression or anxiety (13, 80) (Table 3). Other studies found a significant relation between certain GO signs and symptoms on one hand, and QoL on the other hand. Cockerham et al. reported a significant relation between diplopia, photophobia, blurred vision, or preorbital pain, and QoL (74). Correspondingly, Wang and colleagues demonstrated that vision-related symptoms (diplopia, decreased vision, and color vision changes) and structural GO symptoms (strabismus, soft tissue swelling, conjunctival swelling, eyelid swelling, eyelid redness, conjunctival redness, corneal involvement, eyelid retraction, and eye muscle involvement) are significantly more prevalent in GO patients with lower QoL versus higher QoL (72). Nevertheless, exophthalmos, ocular dryness, and excessive tearing were equally prevalent in GO patients with high and low QoL (72).
Effect of GO-specific treatment on depression, anxiety and GO-QoL
Orbital decompression and strabismus surgery were shown to significantly improve appearance-related GO-QoL and vision-related GO-QoL (17, 18, 20, 82, 83, 84, 85). Additionally, radiotherapy significantly improved the visual functioning aspect of GO-QoL, while eyelid lengthening and blepharoplasty significantly improved the appearance-related aspect of GO-QoL (17, 83). Steroid treatment was also shown to improve GO-QoL (20, 84). Regarding the effects of GO-specific treatment on depression and anxiety in patients, only one study mentions that the levels of depression and anxiety significantly reduced after orbital decompression surgery (86) (Table 3).
Discussion
Depression and anxiety are associated with and highly prevalent in GO (Table 4). Thyroid dysfunction is associated with depression and anxiety, with some studies even showing significant expression of TSH receptors in the limbic regions of healthy adults and regional metabolic changes in the limbic and paralimbic structures of GD patients (35, 36). The severity of hyperthyroidism, however, is not associated with the severities of depression and anxiety (33, 42, 44, 47, 48). Generally, an improvement in psychiatric symptoms is reported when reaching euthyroidism after treatment (52, 53, 54, 55, 56, 57). Nonetheless, a few studies noted long-term psychological complaints among patients after remission of hyperthyroidism (60, 61). The reported prevalence of depression and anxiety in both GD and GO are particularly discordant. This discordance could be explained due to the use of different psychometric assessment tools and the small population sizes used in these studies. Furthermore, the problem with many of these studies is the lack of distinction between GO and GD without eye disease. In this review, the prevalence of anxiety and depression in GO was assessed by using studies that clearly mentioned that the population only consists of GO patients. The prevalence of depression and anxiety in GD without eye disease, however, was assessed from studies that mention using a GD population without specifically mentioning eye disease. It is possible that these studies also included GD patients with eye disease (i.e. GO patients), without specifically mentioning the eye aspect of the disease. Consequently, it is difficult to decisively estimate, based on the current literature, whether depression and anxiety are more prevalent in GO than in GD without eye disease.
Key findings regarding quality of life in GO patients.
| Clinical feature | Key findings |
|---|---|
| Depression | Depression is a significant predictor of impaired QoL in GO patients (13, 21, 73, 74) |
| Anxiety | Anxiety is not a unique contributor to QoL in GO patients (21) |
| Age | Older age is associated with lower vision-related QoL (12, 21) |
| Appearance-related social anxiety and social avoidance | Appearance-related social anxiety and social avoidance contribute to appearance-related QoL (21, 78) |
| Female gender | Female GO patients report more appearance-related problems compared to male patients (12) |
| Exopthalmos | Exopthalmos is equally prevalent in patients with high and low QoL (72) |
| Diplopia | Significant relation between diplopia and QoL (72, 74) |
| Orbital decompression surgery | Improves appearance-related and vision-related QoL (17, 18, 20, 82, 83, 84, 85) |
| Strabismus surgery | Improves appearance-related and vision-related QoL (17, 18, 20, 82, 83, 84, 85) |
| Radiotherapy | Improves vision-related QoL (17, 83) |
| Eyelid lenghtening and blepharoplasty | Improves appearance-related QoL (17, 83) |
| Steroid treatment | Improves appearance-related and vision-related QoL (20, 84) |
Regardless, it is evident that depression and anxiety are more prevalent in GD than in non-autoimmune hyperthyroidism, indicating that autoimmunity also contributes to psychiatric disorders among GO patients (42, 45, 46). Multiple studies even noted an association between antithyroid antibodies and depression and anxiety (34, 44, 46, 49, 51). This is in agreement with the literature, as autoimmune disease has been linked to psychiatric disorders (87). On the other hand, some studies reported no significant relation between antithyroid antibodies and depression and anxiety (42, 49).
Both depression and anxiety are associated with lower GO-QoL (13, 73, 74). Depression is a significant contributor to impaired QoL in GO, while HADS-anxiety (which focuses primarily on general anxiety disorder symptoms) is not (21, 72). Moreover, older age is a significant contributor to impaired visual-related QoL, while female sex and social anxiety and avoidance (Derriford Appearance Scale) are significant contributors to impaired appearance-related QoL (12, 21).
On top of that, conflicting results exist on the relation between depression and anxiety with GO severity and activity, with some studies reporting an association, while others reporting none (13, 72, 73, 80, 81). These conflicting results could also be explained by the various assessment tools used to assess depression and anxiety and the small population sizes of these studies. Moreover, exophthalmos, the most notable sign of GO, was not associated with depression or anxiety (13, 72). Likewise, no relation was found between diplopia and depression or anxiety (13, 80). Despite that, both exophthalmos and diplopia are associated with impaired GO-QoL, and both orbital decompression and strabismus surgery significantly improve GO-QoL (82, 83). Additionally, orbital decompression has been shown to significantly reduce the levels of depression and anxiety among GO patients (83).
The results we have examined suggest that altered thyroid hormone levels and autoimmunity are prognostic factors for depression and anxiety in GO patients. Regarding the visual and disfiguring aspects of GO as contributors to depression and anxiety, no decisive conclusions can be made.
To conclude, due to a paucity of studies investigating the prevalence of depression and anxiety in GO, the lack of concordance of these results, and the small population sizes of these studies, it is difficult to make general conclusions in this area of research. To solve this problem, we propose that a single, validated assessment tool for psychiatric disorders should be designed specifically for GO patients and used to assess the prevalence and contributors of psychiatric disorders among GO in a large study population.
Declaration of interest
The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the study reported.
Funding
This work received funding from the Orbital center Amsterdam, Department of Ophthalmology, Amsterdam University Medical Center.
References
- 1↑
Bahn RS. Graves’ ophthalmopathy. New England Journal of Medicine 2010 362 726–738. (https://doi.org/10.1056/NEJMra0905750)
- 2↑
McAlinden C. An overview of thyroid eye disease. Eye and Vision 2014 1 9. (https://doi.org/10.1186/s40662-014-0009-8)
- 3↑
Bartalena L, & Tanda ML. Clinical practice. Graves’ ophthalmopathy. New England Journal of Medicine 2009 360 994–1001. (https://doi.org/10.1056/NEJMcp0806317)
- 4↑
Gerding MN, Terwee CB, Dekker FW, Koornneef L, Prummel MF, & Wiersinga WM. Quality of life in patients with Graves’ ophthalmopathy is markedly decreased: measurement by the medical outcomes study instrument. Thyroid 1997 7 885–889. (https://doi.org/10.1089/thy.1997.7.885)
- 5↑
Kahaly GJ, Hardt J, Petrak F, & Egle UT. Psychosocial factors in subjects with thyroid-associated ophthalmopathy. Thyroid 2002 12 237–239. (https://doi.org/10.1089/105072502753600205)
- 6↑
Terwee CB, Gerding MN, Dekker FW, Prummel MF, & Wiersinga WM. Development of a disease specific quality of life questionnaire for patients with Graves’ ophthalmopathy: the GO-QOL. British Journal of Ophthalmology 1998 82 773–779. (https://doi.org/10.1136/bjo.82.7.773)
- 7↑
Choi YJ, Lim HT, Lee SJ, Lee SY, & Yoon JS. Assessing Graves’ ophthalmopathy-specific quality of life in Korean patients. Eye 2012 26 544–551. (https://doi.org/10.1038/eye.2011.359)
- 8↑
Ponto KA, Hommel G, Pitz S, Elflein H, Pfeiffer N, & Kahaly GJ. Quality of life in a German graves orbitopathy population. American Journal of Ophthalmology 2011 152 483–490.e1. (https://doi.org/10.1016/j.ajo.2011.02.018)
- 9↑
Terwee CB, Gerding MN, Dekker FW, Prummel MF, van der Pol JP, & Wiersinga WM. Test-retest reliability of the GO-QOL: a disease-specific quality of life questionnaire for patients with Graves’ ophthalmopathy. Journal of Clinical Epidemiology 1999 52 875–884. (https://doi.org/10.1016/s0895-4356(9900069-4)
- 10↑
Fischer S, & Ehlert U. Hypothalamic-pituitary-thyroid (HPT) axis functioning in anxiety disorders. A systematic review. Depression and Anxiety 2018 35 98–110. (https://doi.org/10.1002/da.22692)
- 11↑
Placidi GP, Boldrini M, Patronelli A, Fiore E, Chiovato L, Perugi G, & Marazziti D. Prevalence of psychiatric disorders in thyroid diseased patients. Neuropsychobiology 1998 38 222–225. (https://doi.org/10.1159/000026545)
- 12↑
Wiersinga WM, Prummel MF, & Terwee CB. Effects of Graves’ ophthalmopathy on quality of life. Journal of Endocrinological Investigation 2004 27 259–264. (https://doi.org/10.1007/BF03345275)
- 13↑
Lee H, Roh HS, Yoon JS, & Lee SY. Assessment of quality of life and depression in Korean patients with Graves’ ophthalmopathy. Korean Journal of Ophthalmology 2010 24 65–72. (https://doi.org/10.3341/kjo.2010.24.2.65)
- 14↑
Iacobæus L, & Sahlin S. Evaluation of quality of life in patients with Graves’ ophthalmopathy, before and after orbital decompression. Orbit 2016 35 121–125. (https://doi.org/10.1080/01676830.2016.1176049)
- 15↑
Zeng P, Fan SX, Li ZJ, Peng YY, Hu YX, Xu MT, & Wang M. Evaluation of the Graves’ orbitopathy-specific Quality of Life Questionnaire in the mainland Chinese population. Journal of Ophthalmology 2019 2019 7602419. (https://doi.org/10.1155/2019/7602419)
- 16↑
Delampady K, Reddy SVB, & Yadav SB. Assessing the quality of life in Indian Graves’ orbitopathy patients and validation of Hindi version of GO-QOL questionnaire. Indian Journal of Ophthalmology 2020 68 1617–1621. (https://doi.org/10.4103/ijo.IJO_2183_19)
- 17↑
Woo T, Li C, Ganesananthan S, Rajendram R, Uddin J, Lee RWJ, Dayan C, & Taylor P. The effect of ophthalmic surgery for Graves’ orbitopathy on quality of life: a systematic review and meta-analysis. Thyroid 2022 32 177–187. (https://doi.org/10.1089/thy.2021.0411)
- 18↑
Luisa V, Riccardo T, Stefano P, & Manlio G. Effectiveness of orbital decompression for endocrine orbitopathy and impact on quality of life: a retrospective study. Journal of Cranio-Maxillo-Facial Surgery 2021 49 867–874. (https://doi.org/10.1016/j.jcms.2021.03.001)
- 19↑
Sharma A, Stan MN, & Rootman DB. Measuring health-related quality of life in thyroid eye disease. Journal of Clinical Endocrinology and Metabolism 2022 107(Supplement 1) S27–S35. (https://doi.org/10.1210/clinem/dgac230)
- 20↑
Zloto O, Sagiv O, Priel A, Cukierman-Yaffe T, Tirosh A, Agmon-Levin N, Madgar S, Serlin T, & Simon GB. Quality of life of patients with thyroid eye disease: 3-year follow-up in a multidisciplinary clinic in Israel. Graefe’s Archive for Clinical and Experimental Ophthalmology 2021 259 2009–2015. (https://doi.org/10.1007/s00417-021-05103-5)
- 21↑
Wickwar S, McBain HB, Ezra DG, Hirani SP, Rose GE, & Newman SP. Which factors are associated with quality of life in patients with Graves’ orbitopathy presenting for orbital decompression surgery? Eye 2015 29 951–957. (https://doi.org/10.1038/eye.2015.76)
- 22↑
Bruscolini A, Sacchetti M, La Cava M, Nebbioso M, Iannitelli A, Quartini A, Lambiase A, Ralli M, de Virgilio A, & Greco A. Quality of life and neuropsychiatric disorders in patients with Graves’ orbitopathy: current concepts. Autoimmunity Reviews 2018 17 639–643. (https://doi.org/10.1016/j.autrev.2017.12.012)
- 23↑
Parry CH. Collections from the unpublished medical writings of the late Caleb Hillier Parry, vol 2, pp 112. London, UK: Underwoods, 1825.
- 24↑
Graves RJ. Newly observed affection of the thyroid gland in females. London Medical and Surgical Journal 1835 7 516–517.
- 25↑
Gorkhali B, Sharma S, Amatya M, Acharya D, & Sharma M. Anxiety and depression among patients with thyroid function disorders. Journal of Nepal Health Research Council 2020 18 373–378. (https://doi.org/10.33314/jnhrc.v18i3.2499)
- 26↑
Kathol RG, & Delahunt JW. The relationship of anxiety and depression to symptoms of hyperthyroidism using operational criteria. General Hospital Psychiatry 1986 8 23–28. (https://doi.org/10.1016/0163-8343(8690060-5)
- 27↑
Loosen PT. Hormones of the hypothalamic-pituitary-thyroid axis: a psychoneuroendocrine perspective. Pharmacopsychiatry 1986 19 401–415. (https://doi.org/10.1055/s-2007-1017278)
- 28↑
Vandoolaeghe E, Maes M, Vandevyvere J, & Neels H. Hypothalamic-pituitary-thyroid-axis function in treatment resistant depression. Journal of Affective Disorders 1997 43 143–150. (https://doi.org/10.1016/s0165-0327(9601426-7)
- 29↑
Bunevicius R, Peceliuniene J, Mickuviene N, Bunevicius A, Pop VJ, & Girdler SS. Mood and thyroid immunity assessed by ultrasonographic imaging in a primary health care. Journal of Affective Disorders 2007 97 85–90. (https://doi.org/10.1016/j.jad.2006.05.029)
- 30↑
Chen HH, Yeh SY, Lin CL, Chang SN, & Kao CH. Increased depression, diabetes and diabetic complications in Graves’ disease patients in Asia. QJM 2014 107 727–733. (https://doi.org/10.1093/qjmed/hcu069)
- 31↑
Dai F, Yuan L, Fang J, Zhang Q, & Wang K. Impaired decision making under risky conditions in the acute phase of Graves’ thyroitoxicosis. Neuroscience Letters 2017 661 1–4. (https://doi.org/10.1016/j.neulet.2017.08.058)
- 32↑
Trzepacz PT, McCue M, Klein I, Levey GS, & Greenhouse J. A psychiatric and neuropsychological study of patients with untreated Graves’ disease. General Hospital Psychiatry 1988 10 49–55. (https://doi.org/10.1016/0163-8343(8890084-9)
- 33↑
Vogel A, Elberling TV, Hørding M, Dock J, Rasmussen AK, Feldt-Rasmussen U, Perrild H, & Waldemar G. Affective symptoms and cognitive functions in the acute phase of Graves’ thyrotoxicosis. Psychoneuroendocrinology 2007 32 36–43. (https://doi.org/10.1016/j.psyneuen.2006.09.012)
- 34↑
Hamed SA, Attiah FA, Abdulhamid SK, & Fawzy M. Behavioral assessment of children and adolescents with Graves’ disease: a prospective study. PLoS One 2021 16 e0248937. (https://doi.org/10.1371/journal.pone.0248937)
- 35↑
Naicker M, & Naidoo S. Expression of thyroid-stimulating hormone receptors and thyroglobulin in limbic regions in the adult human brain. Metabolic Brain Disease 2018 33 481–489. (https://doi.org/10.1007/s11011-017-0076-3)
- 36↑
Schreckenberger MF, Egle UT, Drecker S, Buchholz HG, Weber MM, Bartenstein P, & Kahaly GJ. Positron emission tomography reveals correlations between brain metabolism and mood changes in hyperthyroidism. Journal of Clinical Endocrinology and Metabolism 2006 91 4786–4791. (https://doi.org/10.1210/jc.2006-0573)
- 37↑
Chen W, Hu H, Wu Q, Chen L, Zhou J, Chen H-H, Xu X-Q, & Wu F-Y. Altered static and dynamic interhemispheric resting-state functional connectivity in patients with thyroid-associated ophthalmopathy. Frontiers in Neuroscience 2021 15 799916. (https://doi.org/10.3389/fnins.2021.799916)
- 38↑
Jiang YP, Yang YC, Tang LY, Ge QM, Shi WQ, Su T, Shu HY, Pan YC, Liang RB, Li QY, et al.Altered spontaneous brain activity patterns in dysthyroid optic neuropathy: a resting-state fMRI study. Journal of Integrative Neuroscience 2021 20 375–383. (https://doi.org/10.31083/j.jin2002037)
- 39↑
Luo L, Wen H, Gao L, Li R, Wang S, Wang Z, & Li D. Morphological brain changes between active and inactive phases of thyroid-associated ophthalmopathy: a voxel-based morphometry study. Brain Research 2022 1790 147989. (https://doi.org/10.1016/j.brainres.2022.147989)
- 40↑
Wang Y, Shao Y, Zhang H, Wang J, Zhang P, Zhang W, & Chen H. Comprehensive analysis of key genes and pathways for biological and clinical implications in thyroid-associated ophthalmopathy. BMC Genomics 2022 23 630. (https://doi.org/10.1186/s12864-022-08854-5)
- 41↑
Wu Q, Hu H, Chen W, Chen H-H, Chen L, Zhou J, Liu H, Wu F-Y, & Xu X-Q. Disrupted topological organization of the brain structural network in patients with thyroid-associated ophthalmopathy. Investigative Ophthalmology and Visual Science 2021 62 5. (https://doi.org/10.1167/iovs.62.4.5)
- 42↑
Bové KB, Watt T, Vogel A, Hegedüs L, Bjoerner JB, Groenvold M, Bonnema SJ, Rasmussen ÅK, & Feldt-Rasmussen U. Anxiety and depression are more prevalent in patients with Graves’ disease than in patients with nodular goitre. European Thyroid Journal 2014 3 173–178. (https://doi.org/10.1159/000365211)
- 43↑
Chattopadhyay C, Chakrabarti N, & Ghosh S. An assessment of psychiatric disturbances in Graves disease in a medical college in eastern India. Nigerian Journal of Clinical Practice 2012 15 276–279. (https://doi.org/10.4103/1119-3077.100620)
- 44↑
Fukao A, Takamatsu J, Kubota S, Miyauchi A, & Hanafusa T. The thyroid function of Graves’ disease patients is aggravated by depressive personality during antithyroid drug treatment. BioPsychoSocial Medicine 2011 5 9. (https://doi.org/10.1186/1751-0759-5-9)
- 45↑
Brix T, Brandt F, Folkestad L, & Hegedus L. Mental health is negatively impacted by hyperthyroidism and differs between Graves’ disease and toxic nodular goiter. A nationwide registerbased study. European Thyroid Journal 2019 8(Supplement 1) 19–20. (https://doi.org/10.1159/000501012)
- 46↑
Krysiak R, Kowalcze K, & Okopien B. Sexual function and depressive symptoms in young women with overt hyperthyroidism. European Journal of Obstetrics, Gynecology, and Reproductive Biology 2019 234 43–48. (https://doi.org/10.1016/j.ejogrb.2018.12.035)
- 47↑
Trzepacz PT, Klein I, Roberts M, Greenhouse J, & Levey GS. Graves’ disease: an analysis of thyroid hormone levels and hyperthyroid signs and symptoms. American Journal of Medicine 1989 87 558–561. (https://doi.org/10.1016/s0002-9343(8980614-x)
- 48↑
Saravanan P, Visser TJ, & Dayan CM. Psychological well-being correlates with free thyroxine but not free 3,5,3’-triiodothyronine levels in patients on thyroid hormone replacement. Journal of Clinical Endocrinology and Metabolism 2006 91 3389–3393. (https://doi.org/10.1210/jc.2006-0414)
- 49↑
Yu J, Tian AJ, Yuan X, & Cheng XX. Subclinical hypothyroidism after 131I-treatment of Graves’ disease: a risk factor for depression? PLoS One 2016 11 e0154846. (https://doi.org/10.1371/journal.pone.0154846)
- 50↑
Holmberg M, Malmgren H, Heckemann RA, Johansson B, Klasson N, Olsson E, Skau S, Starck G, & Filipsson Nyström H. A longitudinal study of medial temporal lobe volumes in Graves disease. Journal of Clinical Endocrinology and Metabolism 2022 107 1040–1052. (https://doi.org/10.1210/clinem/dgab808)
- 51↑
Oomen HA, Schipperijn AJ, & Drexhage HA. The prevalence of affective disorder and in particular of a rapid cycling of bipolar disorder in patients with abnormal thyroid function tests. Clinical Endocrinology 1996 45 215–223. (https://doi.org/10.1046/j.1365-2265.1996.d01-1558.x)
- 52↑
Zeitlhofer J, Saletu B, Stary J, & Ahmadi R. Cerebral function in hyperthyroid patients. Psychopathology, psychometric variables, central arousal and time perception before and after thyreostatic therapy. Neuropsychobiology 1984 11 89–93. (https://doi.org/10.1159/000118059)
- 53↑
Kathol RG, Turner R, & Delahunt J. Depression and anxiety associated with hyperthyroidism: response to antithyroid therapy. Psychosomatics 1986 27 501–505. (https://doi.org/10.1016/S0033-3182(8672656-X)
- 54↑
Paschke R, Harsch I, Schlote B, Vardarli I, Schaaf L, Kaumeier S, Teuber J, & Usadel KH. Sequential psychological testing during the course of autoimmune hyperthyroidism. Klinische Wochenschrift 1990 68 942–950. (https://doi.org/10.1007/BF01646652)
- 55↑
Harsch I, Paschke R, & Usadel KH. The possible etiological role of psychological disturbances in Graves’ disease. Acta Medica Austriaca 1992 19(Supplement 1) 62–65.
- 56↑
Calissendorff J, Mikulski E, Larsen EH, & Möller M. A prospective investigation of Graves’ disease and selenium: thyroid hormones, auto-antibodies and self-rated symptoms. European Thyroid Journal 2015 4 93–98. (https://doi.org/10.1159/000381768)
- 57↑
Chen DY, Schneider PF, Zhang XS, He ZM, Jing J, & Chen TH. Mental health status and factors that influence the course of Graves’ disease and antithyroid treatments. Experimental and Clinical Endocrinology and Diabetes 2012 120 524–528. (https://doi.org/10.1055/s-0032-1323807)
- 58↑
Davis JD, Stern RA, & Flashman LA. Cognitive and neuropsychiatric aspects of subclinical hypothyroidism: significance in the elderly. Current Psychiatry Reports 2003 5 384–390. (https://doi.org/10.1007/s11920-003-0073-6)
- 59↑
Fukao A, Takamatsu J, Murakami Y, Sakane S, Miyauchi A, Kuma K, Hayashi S, & Hanafusa T. The relationship of psychological factors to the prognosis of hyperthyroidism in antithyroid drug-treated patients with Graves’ disease. Clinical Endocrinology 2003 58 550–555. (https://doi.org/10.1046/j.1365-2265.2003.01625.x)
- 60↑
Bommer M, Eversmann T, Pickardt R, Leonhardt A, & Naber D. Psychopathological and neuropsychological symptoms in patients with subclinical and remitted hyperthyroidism. Klinische Wochenschrift 1990 68 552–558. (https://doi.org/10.1007/BF01667147)
- 61↑
Fahrenfort JJ, Wilterdink AM, & van der Veen EA. Long-term residual complaints and psychosocial sequelae after remission of hyperthyroidism. Psychoneuroendocrinology 2000 25 201–211. (https://doi.org/10.1016/s0306-4530(9900050-5)
- 62↑
Kung AW. Life events, daily stresses and coping in patients with Graves’ disease. Clinical Endocrinology 1995 42 303–308. (https://doi.org/10.1111/j.1365-2265.1995.tb01879.x)
- 63↑
Radosavljević VR, Janković SM, & Marinković JM. Stressful life events in the pathogenesis of Graves’ disease. European Journal of Endocrinology 1996 134 699–701. (https://doi.org/10.1530/eje.0.1340699)
- 64↑
Sonino N, Girelli ME, Boscaro M, Fallo F, Busnardo B, & Fava GA. Life events in the pathogenesis of Graves’ disease. A controlled study. Acta Endocrinologica 1993 128 293–296. (https://doi.org/10.1530/acta.0.1280293)
- 65↑
Topcu CB, Celik O, & Tasan E. Effect of stressful life events on the initiation of Graves’ disease. International Journal of Psychiatry in Clinical Practice 2012 16 307–311. (https://doi.org/10.3109/13651501.2011.631016)
- 66↑
Winsa B, Adami HO, Bergström R, Gamstedt A, Dahlberg PA, Adamson U, Jansson R, & Karlsson A. Stressful life events and Graves’ disease. Lancet 1991 338 1475–1479. (https://doi.org/10.1016/0140-6736(9192298-g)
- 67↑
Yoshiuchi K, Kumano H, Nomura S, Yoshimura H, Ito K, Kanaji Y, Ohashi Y, Kuboki T, & Suematsu H. Stressful life events and smoking were associated with Graves’ disease in women, but not in men. Psychosomatic Medicine 1998 60 182–185. (https://doi.org/10.1097/00006842-199803000-00013)
- 68↑
Chiovato L, & Pinchera A. Stressful life events and Graves’ disease. European Journal of Endocrinology 1996 134 680–682. (https://doi.org/10.1530/eje.0.1340680)
- 69↑
Effraimidis G, Tijssen JGP, Brosschot JF, & Wiersinga WM. Involvement of stress in the pathogenesis of autoimmune thyroid disease: a prospective study. Psychoneuroendocrinology 2012 37 1191–1198. (https://doi.org/10.1016/j.psyneuen.2011.12.009)
- 70↑
Bastenie PA. Diseases of the thyroid gland in occupied Belgium. Lancet 1947 1 789–791. (https://doi.org/10.1016/s0140-6736(4791542-0)
- 71↑
Hadden DR, & McDevitt DG. Environmental stress and thyrotoxicosis. Absence of association. Lancet 1974 2 577–578. (https://doi.org/10.1016/s0140-6736(7491892-3)
- 72↑
Wang Y, Sharma A, Padnick-Silver L, Francis-Sedlak M, Holt RJ, Foley C, Massry G, & Douglas RS. Physician-perceived impact of thyroid eye disease on patient quality of life in the United States. Ophthalmology and Therapy 2021 10 75–87. (https://doi.org/10.1007/s40123-020-00318-x)
- 73↑
Kahaly GJ, Petrak F, Hardt J, Pitz S, & Egle UT. Psychosocial morbidity of Graves’ orbitopathy. Clinical Endocrinology 2005 63 395–402. (https://doi.org/10.1111/j.1365-2265.2005.02352.x)
- 74↑
Cockerham KP, Padnick-Silver L, Stuertz N, Francis-Sedlak M, & Holt RJ. Quality of life in patients with chronic thyroid eye disease in the United States. Ophthalmology and Therapy 2021 10 975–987. (https://doi.org/10.1007/s40123-021-00385-8)
- 75↑
Kessler RC, Avenevoli S, Costello EJ, Georgiades K, Green JG, Gruber MJ, He JP, Koretz D, McLaughlin KA, Petukhova M, et al.Prevalence, persistence, and sociodemographic correlates of DSM-IV disorders in the National Comorbidity Survey Replication Adolescent Supplement. Archives of General Psychiatry 2012 69 372–380. (https://doi.org/10.1001/archgenpsychiatry.2011.160)
- 76↑
Bunevicius R, Velickiene D, & Prange AJ Jr. Mood and anxiety disorders in women with treated hyperthyroidism and ophthalmopathy caused by Graves’ disease. General Hospital Psychiatry 2005 27 133–139. (https://doi.org/10.1016/j.genhosppsych.2004.10.002)
- 77↑
Park JJ, Sullivan TJ, Mortimer RH, Wagenaar M, & Perry-Keene DA. Assessing quality of life in Australian patients with Graves’ ophthalmopathy. British Journal of Ophthalmology 2004 88 75–78. (https://doi.org/10.1136/bjo.88.1.75)
- 78↑
Carr T, Moss T, & Harris D. The DAS24: a short form of the Derriford Appearance Scale DAS59 to measure individual responses to living with problems of appearance. British Journal of Health Psychology 2005 10 285–298. (https://doi.org/10.1348/135910705X27613)
- 79↑
Bartalena L, Baldeschi L, Dickinson A, Eckstein A, Kendall-Taylor P, Marcocci C, Mourits M, Perros P, Boboridis K, Boschi A, et al.Consensus statement of the European Group on Graves’ orbitopathy (EUGOGO) on management of GO. European Journal of Endocrinology 2008 158 273–285. (https://doi.org/10.1530/EJE-07-0666)
- 80↑
Farid M, Roch-Levecq AC, Levi L, Brody BL, Granet DB, & Kikkawa DO. Psychological disturbance in graves ophthalmopathy. Archives of Ophthalmology 2005 123 491–496. (https://doi.org/10.1001/archopht.123.4.491)
- 81↑
Wang Y, Padnick-Silver L, Francis-Sedlak M, Holt RJ, Foley C, & Douglas RS. Inflammatory and noninflammatory thyroid eye disease: comparison of disease signs, symptoms, and quality of life in patients in the United States. Endocrine Practice 2022 28 842–846. (https://doi.org/10.1016/j.eprac.2022.06.003)
- 82↑
Jellema HM, Merckel-Timmer E, Kloos R, Saeed P, & Mourits MP. Quality of life improves after strabismus surgery in patients with Graves’ orbitopathy. European Journal of Endocrinology 2014 170 785–789. (https://doi.org/10.1530/EJE-13-0973)
- 83↑
Terwee CB, Dekker FW, Mourits MP, Gerding MN, Baldeschi L, Kalmann R, Prummel MF, & Wiersinga WM. Interpretation and validity of changes in scores on the Graves’ ophthalmopathy quality of life questionnaire (GO-QOL) after different treatments. Clinical Endocrinology 2001 54 391–398. (https://doi.org/10.1046/j.1365-2265.2001.01241.x)
- 84↑
Kashkouli MB, Heidari I, Pakdel F, Jam S, Honarbakhsh Y, & Mirarmandehi B. Change in quality of life after medical and surgical treatment of graves’ ophthalmopathy. Middle East African Journal of Ophthalmology 2011 18 42–47. (https://doi.org/10.4103/0974-9233.75884)
- 85↑
Jellema HM, Saeed P, Mombaerts I, Dolman PJ, Garrity J, Kazim M, Dhrami-Gavazi E, Lyons C, Nieuwkerk P, & Mourits MP. Objective and subjective outcomes of strabismus surgery in Graves’ orbitopathy: a prospective multicentre study. Acta Ophthalmologica 2017 95 386–391. (https://doi.org/10.1111/aos.13367)
- 86↑
Wickwar S, McBain H, Ezra DG, Hirani SP, Rose GE, & Newman SP. The psychosocial and clinical outcomes of orbital decompression surgery for thyroid eye disease and predictors of change in quality of life. Ophthalmology 2015 122 2568–76.e1. (https://doi.org/10.1016/j.ophtha.2015.08.030)
- 87↑
Davison K. Autoimmunity in psychiatry. British Journal of Psychiatry 2012 200 353–355. (https://doi.org/10.1192/bjp.bp.111.104471)