The thyroid gland and its hormones play a major role in human metabolism and growth. The thyroid can become diseased and produce too little or too much thyroid hormones. Thyroid disorders are prevalent all over the world, however epidemiological studies have been conducted mainly in western countries. It is estimated that 11% of Europeans have dysfunctional thyroids, but only half are aware of their condition.1 In the United States (US), around 13 million people are living with an undiagnosed thyroid illness.1 There are various thyroid disorders, but hypothyroidism is the most prevalent.2 Hypothyroidism is a medical condition in which the thyroid gland does not produce adequate amounts of thyroid hormones, so patients may present with complaints of weight gain, hair loss, muscle aches, fatigue, impaired memory, constipation, dry skin, cold intolerance and depressed mood.1,2 A less prevalent but not uncommon thyroid condition is hyperthyroidism. In this condition, there is an over production of thyroid hormones, so patients may present with irritability, fatigue, nervousness and heat intolerance.2,3 In the US, the main cause of hypothyroidism is autoimmune Hashimoto's thyroiditis (AIT), and hyperthyroidism is caused by Graves’ disease (GD).1,3 Both AIT and GD are autoimmune diseases, so it is likely that these patients will have anti-thyroid antibodies (aTA) against the gland.2 It is estimated that the occurrence of autoimmune thyroid disorders (ATD) in the US is around 5–7% of the population.1,3 However, the incidence of aTA may be much higher because it is not recommended to assess aTA in patients with normal thyroid function.4,5
If hypothyroidism is suspected, thyroid stimulating hormone (TSH) is the first serum lab test used to assess thyroid function.2,6 If TSH is within normal limits (WNL), current guidelines do not advice further assessment, regardless of symptoms. However, if TSH is abnormal, the level of the unbound thyroid hormone, thyroxine (free T4), should be obtained. If both lab values are abnormal, the provider may assess for the presence of either or both aTA: anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg).2,6,7 However, primary care providers may not draw aTA levels because treatment guidelines do not change if aTA are present. Ideally, the diagnosis of AIT is based on high TSH, low free T4, and the presence of aTA with lymphocytic infiltrates.2 Hyperthyroidism is diagnosed when serum TSH levels are subnormal or undetectable with elevated levels of free T4 and/or triiodothyronine (T3).3 Patients with hyperthyroidism and a symmetrically enlarged thyroid gland with a recent onset of orbitopathy do not require further evaluation for the cause of the overactive thyroid because the diagnosis of GD is likely.3 Levothyroxine, the synthetic form of T4, is first-line treatment for hypothyroidism and AIT, and the treatment goal is to achieve a clinically euthyroid state.5,7 A clinically euthyroid state is defined as reaching normal thyroid levels (TSH, freeT4 and T3) by means of supplementation.1,2 Eventual treatment for hyperthyroidism caused by GD is radioactive iodine which halts the production of thyroid hormone.3 Once thyroid levels are WNL, patients are considered clinically euthyroid despite the presence of lingering symptoms.2,5 Interestingly, at least 10% of patients with diseased thyroids continue to experience persistent symptoms even after supplementation and normalization of thyroid hormone levels.8
Providers have noticed a correlation between thyroid disorders and poor symptom control. Poor symptom control, or symptom distress (SD), is the degree of physical or mental upset, sorrow or misery experienced from a certain disease.9-11 Symptom distress is a phenomenon that affects every aspect of one's life such as the course of healing, one's mood and thought process, and ultimately survival.11 This phenomenon is experienced by patients with thyroid disease even with proper treatment and normal TSH and T4 levels.12 Researchers have found that any form of SD directly affects one's quality of life (QoL).13 Impaired cognitive function and depression are examples of SD. Patients with treated thyroid disorders have impaired psychological wellbeing and poor cognitive function which have a direct effect on their QoL.9 The etiology of SD in thyroid disease is poorly understood. Even in euthyroidism, it appears that patients with AIT and GD experience poor symptom control more often than those with the non-autoimmune forms of the disease.4,14-16 It has been hypothesized that patients with AIT and GD experience SD more often than those with other thyroid conditions. Therefore, ATD have worse QoL scores compared to those without the presence of aTA.9 It has been speculated that aTA may be the cause of SD in patients with ATD.5,15 Hence, the pathogenesis of ATD may be more complex and aTA could be pathogenic in nature, thus negatively affecting morbidity in this patient population.17-19
One study found that physical and psychological well-being was poorer in patients with aTA compared to those without aTA despite a euthyroid state in both groups.9 Multiple studies have discovered that there is a higher prevalence of depression in women with euthyroid AIT.20,21 The presence of aTA may be a vulnerability marker for depression because aTA have been positively associated with depression.22 Furthermore, it has been hypothesized that higher aTA levels are directly related to the degree one experiences SD. Increased SD and decreased QoL have been observed in clinically euthyroid ATD.9,13,15,16 A group of researchers noted health to be worse in patients with aTA levels double the reference range compared to patients with aTA levels below the defined cutoff level.13 Moreover, elevated concentrations of aTA was independently related to depression not related to thyroid dysfunction.23 A recent study found that over half of patients with abnormally high levels of aTA showed a significant decrease in attention span and cognitive function.19 Patients with higher aTA levels have scored worse in physical and psychological wellbeing categories compared to those with lower aTA levels.9 However, an older study suggested a correlation between thyroid disease and decreased cognitive function, independent of aTA.12 Nonetheless, the phenomenon of poor symptom control in patients with thyroid disorders has been studied and documented, so the relationship between QoL and SD, like cognitive dysfunction and depression, may be a constant battle for those living with a thyroid disorder, especially if aTA are present.9
Various instruments can quantify wellbeing and assess QoL in patients with chronic diseases. It is beneficial to measure QoL and SD in this patient population because chronic disorders are rarely life threatening. Therefore, the plan of care in patients with chronic diseases is to optimize QoL since there is more concern about disability rather than longevity. Quality of life has been studied extensively in patients with chronic health conditions. However, it was not until recently that QoL has been studied in patients with chronic benign thyroid disorders. Studies using health-related quality of life (HRQoL) questionnaires have found that treated thyroid patients have impaired well-being independent of thyroid function.12,14 The subjective assessment of how a medical situation affects one's physical, emotional and social function is measured using HRQoL evaluations.15 The generic short-form 36 (SF- 36) questionnaire measures eight aspects of health and is popular because it is dependable when assessing HRQoL in chronically ill patients.9 The first validated thyroid-specific HRQoL questionnaire, ThyPRO, was developed to track improvement of symptoms and QoL.16,24 A recent systematic review on HRQoL questionnaires used in thyroid patients found some surveys superior depending on the type of thyroid dysfunction.25 The pediatric population is also affected by ATD, so questionnaires that assess HRQoL have been validated for this age group. The PedsQL 4.0 is a generic HRQoL instrument which contains 23 items and encompasses four dimensions: physical, emotional, social and school functioning.26 Lingering symptoms such as impaired cognitive function, depression and other forms of SD can affect QoL, so the effect of these have been evaluated in patients with thyroid disease. Cognitive function can be assessed using the Memory Comparison Task (MCT) which is a validated questionnaire that assesses memory, executive function and attention.12 The Rand-36 subscale has been used to evaluate depression in patients with thyroid disorders.12 Symptom distress can be measured with the Symptom-Checklist-90-Revised (SCL-90-R), which is a five-point multidimensional symptom rating scale.9 These instruments have all been developed to assist researchers and providers in evaluating the effects that symptoms have on patients and their QoL.
In May 2017, the reviewers searched the JBI Database of Systematic Reviews and Implementation Reports, the Cochrane Library, PROSPERO, and the Campbell Library, and were unable to locate a systematic review on this topic. Despite what is known about thyroid disease, poor symptom control is still experienced by multiple patients troubled by thyroid disorders.15 Poor symptom control increases the risk of developing co-morbidities, thus periodic assessment of lingering symptoms such as impaired cognitive function or depression in the clinical setting may drastically improve overall wellbeing and longevity. Increased SD and decreased QoL have been observed in patients with clinically euthyroid ATD.9,13,15,16 This phenomenon may be due to lack of knowledge regarding the autoimmune components of the diseases.13 If there is a connection between aTA, QoL and SD, current guidelines may be outdated. The recommended methods for diagnosing and treating thyroid disorders may not be appropriate for those with aTA. Therefore, the focus of this review is to evaluate the relationship between aTA and QoL in those with thyroid disorders. The intention is to bring to light the problems surrounding a well-known disorder, encourage further investigation to uncover the etiology of symptoms distress despite adequate treatment, and ultimately improve QoL in patients with thyroid disorders.
This review will consider studies that include patients of all ages and ethnicities from all countries who have been diagnosed with thyroid disorders. Thyroid disorders may include but are not limited to, autoimmune Hashimoto's thyroiditis, hypothyroidism, and/or Graves’ disease. Both female and males will be considered. This review will exclude studies that evaluate patients who are not considered to be in a euthyroid state or who are not clinically controlled via medication or other forms of treatment.
The phenomena of interest in this review is the presence or absence of anti-thyroid antibodies in patients with thyroid disorders. The presence or absence of anti-thyroid antibodies are detected through physical testing such as blood samples. Specific anti-thyroid antibodies are likely to include thyroid peroxidase antibodies and or thyroglobulin antibodies.
The outcome of interest is quality of life. Secondary outcomes include: symptom distress, cognitive function and depression, which may impact quality of life. The alteration in health-related quality of life can be determined by the use of a range of techniques, including questionnaires and interviews that allow symptoms to be assessed and quantified. The outcomes will be measured by questionnaires or surveys including, but not limited to: Study Short Form-36, ThyPRO, Rand-36 subscale, PedsQL 4.0, The Memory Comparison Task, and/or Symptom Checklist-90-Revised scale.
This review will consider analytical observational studies including prospective and retrospective cohort studies, case-control studies and analytical cross-sectional studies. Randomized controlled trials may also be included if they report an association between anti-thyroid antibodies and quality of life. Studies published in English will be included. Studies published since 1956 will be included since that is when the first anti-thyroid antibody was discovered.27
The search strategy will aim to find both published and unpublished studies. An initial limited search of PubMed and Embase has been undertaken to identify articles on this topic, followed by analysis of the text words contained in the titles and abstracts, and of the index terms used to describe these articles. This informed the development of a search strategy including keywords and index terms which will be tailored for each information source. A proposed search strategy for each database is detailed in Appendix I. The reference list of all studies selected for critical appraisal will be screened for additional studies.
The databases to be searched include:
- Academic Search Premier
The trial registers to be searched include:
- National Institutes of Health (NIH) Clinical Trials Databases
- Cochrane Central Register of Controlled Trials
The search for gray literature and unpublished studies will include:
- Google Scholar
- ProQuest Dissertations and Theses
Initial keywords to be used are:
- thyroid disorders, hypothyroidism, hyperthyroidism, Hashimoto's thyroiditis, autoimmune thyroid disease, Graves’ disease, euthyroid
- anti-thyroid antibodies, thyroid peroxidase antibodies, thyroglobulin antibodies, thyroid autoantibodies
- quality of life, health-related quality of life, thyroid-related quality of life, symptom distress, psychological well-being, cognitive function, depression
Following the search, all identified citations will be collated and uploaded into EndNote (Clarivate Analytics, PA, USA) and duplicates removed. Titles and abstracts will then be screened by two independent reviewers for assessment against the inclusion criteria for the review. Studies that may meet the inclusion criteria will be retrieved in full and their details imported into Joanna Briggs Institute System for the Unified Management, Assessment and Review of Information (JBI SUMARI). The full text of selected studies will be retrieved and assessed in detail against the inclusion criteria by two independent reviewers. Full text studies that do not meet the inclusion criteria will be excluded and reasons for exclusion will be provided in an appendix in the final systematic review report. Included studies will undergo a process of critical appraisal. The results of the search will be reported in full in the final report and presented in a PRISMA flow diagram. Any disagreements that arise between the reviewers will be resolved through discussion, or with a third reviewer.
Assessment of methodological quality
Selected studies will be critically appraised by two independent reviewers at the study level for methodological quality in the review using the standardized critical appraisal instruments from the Joanna Briggs Institute for appraising quantitative studies.28 Any disagreements that arise between the reviewers will be resolved through discussion and if necessary, with a third reviewer.
Data will be extracted from papers included in the review using the standardized data extraction tools in JBI SUMARI by two independent reviewers.28 The data extracted will include specific details about the exposure of interest including different exposure categories if applicable, populations, study methods and outcomes or dependent variables of significance to the review question and specific objectives. Any disagreements that arise between the reviewers will be resolved through discussion, or with a third reviewer. Authors of papers will be contacted to request missing or additional data where required.
Quantitative data, where possible, will be pooled in statistical meta-analysis using JBI SUMARI. All results will be subject to double data entry. Effect sizes expressed as correlation coefficients or mean differences, along with 95% confidence intervals, will be calculated for analysis. Heterogeneity will be assessed statistically using the standard chi-squared and I2 tests. The choice of model (random or fixed effects) and method for meta-analysis will be based on the guidance by Tufunaru et al. 2015.29 Subgroup analyses will be conducted where there is sufficient data to investigate co-morbid conditions, age of participant at QoL assessment, level of anti-thyroid antibodies, the presence of particular antibodies, and length of disease. Sensitivity analyses will be conducted to test decisions made regarding the presence of anti-thyroid antibodies on QoL. Where statistical pooling is not possible the findings will be presented in narrative form including tables and figures to aid in data presentation where appropriate. A funnel plot will be generated to assess publication bias if there are 10 or more studies included in a meta-analysis. Statistical tests for funnel plot asymmetry (Egger test, Begg test, Harbord test) will be performed where appropriate.
The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach for assessing confidence in the quality of evidence will be used for this review, with the results presented in a summary of findings table created using GRADEPro.
This systematic literature review is being undertaken as part of the requirements for a Doctor of Nursing Practice (DNP) degree.
Appendix I: Search strategy
- “quality of life” OR QOL OR HRQOL OR “health related quality of life” OR “quality measure*” OR symptom* OR wellbeing OR ThyPRO OR Quality of Life OR Health-Related Quality of Life OR Thyroid-related quality of life OR “Symptom* Distress” OR “Symptom* Experience” OR “psychological well-being” OR “cognitive function” OR “depression”
- thyroid* OR hashimoto* OR euthyroid* OR hypothyroid* OR hyperthyroid* OR “hashimoto thyroiditis” OR grave* OR “autoimmune thyroid*” OR “thyroid autoimmunity” OR “Thyroid Disorders” OR Hypothyroidism OR Hyperthyroidism OR “Hashimoto's Thyroiditis” OR “thyroid function” OR “thyroid dysfunction” OR “Autoimmune Thyroid Disease” OR “Graves’ Disease” OR Euthyroid
- “Anti-thyroid Antibodies” OR “Thyroid Peroxidase Antibodies” OR “Thyroglobulin Antibodies” OR “Thyroid Autoantibodies” OR antibodies OR anti-thyroid OR autoantibod* OR TPO OR thyroperoxidase OR anti-tpo OR anti-tg OR thyroglobulin OR antibod*
- #1 AND #2 AND #3
- (MH thyroid* OR TI thyroid* OR AB thyroid* OR disease* OR thyroid disease* OR TI thyroid disease* OR dysfunction* OR disorder*)
- hypothyroidism OR hypothyro* OR myxedema OR subacute thyro* OR (primary hypothyro*) OR (overt hypothyro*) OR (non* autoimmune* thyroid*) OR [MH antibod* OR MH thyroid antibody* OR MH thyroiditis OR TPO OR thyroid peroxidase OR thyroglobulin OR antibody OR thyroglobulin antibody OR hashimoto* OR (autoimmune disease*) OR (autoimmune disorder*) OR (autoimmune thyroiditis) OR (autoimmune thyroid*) OR thyroiditis OR hashimoto OR hashimoto* OR hashimoto+ OR lymphocytic* OR (lympthocytic thyroid*) OR (Lymphomatous Thyroiditides) OR Lymphomat* OR TI antibod* OR AB antibod* OR autoantibod* OR anti- OR Hashimoto* struma OR hashimoto syndrome* OR grave*]
- quality of life OR MH quality of life OR TI quality of life OR health related quality of life OR TI health related quality of life OR health-related quality of life OR TI health-related quality of life OR QoL OR thyroid specific health related quality of life OR thyroid-specific health-related quality-of-life OR quality-of-life OR TI quality-of-life OR TI thyroid-specific health-related quality-of-life OR thyPRO OR thyroid-related quality of life OR AB thyPRO OR TI thyPRO OR symptomatic distress OR (symptomatic distress) OR (symptom* load) OR (Symptom* distress) OR (SF-36) OR (sf-36 questionnaire) OR cognitive function OR depression
- #1 AND #2 AND #3
- ‘thyroglobulin’ OR ‘thyroglobulin antibody’ OR ‘thyroid antibody’ OR ‘thyroglobulin blood level’ OR ‘thyroglobulin autoantibody’ OR ‘thyroid peroxidase’ OR ‘peroxidase antibody’ OR ‘thyroperoxidase antibody’
- ‘thyroid gland’/exp OR ‘thyroid gland’ OR ‘thyroid’/exp OR ‘thyroid’ OR ‘hypothyroidism’/exp OR ‘hypothyroidism’ OR ‘hyperthyroidism’/exp OR ‘hyperthyroidism’ OR ‘hypothyroidism diagnosis’/exp OR ‘hypothyroidism diagnosis’ OR ‘hypothyroidism complications’/exp OR ‘hypothyroidism complications’ OR ‘hashimoto disease’/exp OR ‘hashimoto disease’ OR ‘graves disease’/exp OR ‘graves disease’ OR ‘autoimmune thyroiditis’/exp OR ‘autoimmune thyroiditis’ OR ‘overt hypothyroidism’/exp OR ‘overt hypothyroidism’ OR ‘overt hyperthyroidism’/exp OR ‘overt hyperthyroidism’ OR ‘subclinical hypothyroidism’/exp OR ‘subclinical hypothyroidism’ OR ‘subclinical hyperthyroidism’/exp OR ‘subclinical hyperthyroidism’ OR ‘subclinical thyroid disease’/exp OR ‘subclinical thyroid disease’ OR ‘chronic thyroiditis’/exp OR ‘chronic thyroiditis’ OR ‘thyroiditis complications’/exp OR ‘thyroiditis complications’ OR ‘thyroiditis’/exp OR ‘thyroiditis’ OR ‘thyroiditis immunology’/exp OR ‘thyroiditis immunology’ OR ‘thyroiditis diagnosis’/exp OR ‘thyroiditis diagnosis’ OR ‘myxedema’/exp OR ‘myxedema’ OR ‘myxedema complications’/exp OR ‘myxedema complications’ OR ‘myxedema diagnosis’/exp OR ‘myxedema diagnosis’ OR ‘autoimmune hypothyroidism’/exp OR ‘autoimmune hypothyroidism’ OR ‘autoimmune hyperthyroidism’/exp OR ‘autoimmune hyperthyroidism’
- ‘quality of life’ OR ‘short form 36’ OR ‘cognition assessment’ OR ‘cognitive defect’ OR ‘symptom distress scale’ OR ‘health related quality of life questionnaire’ OR thypro OR ‘memory assessment’ OR ‘depression’ OR ‘symptom distress’
- #1 AND #2AND #3
- (((DE thyroid OR thyroid* OR “thyroid disease” OR “thyroid dysfunction*” OR “thyroid disorder*” OR hypothyroidism OR hypothyro* OR myxedema OR “subacute thyro*” OR “primary hypothyro*” OR “overt hypothyro*” OR “non* autoimmune* thyroid*” OR “Hashimoto* struma” OR “hashimoto syndrome*” OR “grave*” OR hashimoto* OR “autoimmune thyroiditis” OR “autoimmune thyroid” OR thyroiditis OR “lympthocytic thyroid” OR “Lymphomatous Thyroiditides” OR Thyroiditides OR “Hashimoto thyroiditis” OR “Hashimoto's thyroiditis” OR “Chronic autoimmune thyroiditis” OR “Autoimmune thyroiditis” OR “Autoimmune hypothyroidism” OR hyperthyroid* OR euthyroid*
- (((DE antibod* OR “thyroid antibody” OR TPO OR “thyroid peroxidase” OR thyroglobulin OR “thyroglobulin antibody” OR “TI antibody” OR autoantibod* OR “Anti-thyroglobulin” OR “Anti-thyroid peroxidase” OR “Anti–thyroid peroxidase antibodies” OR “Anti-TPO antibodies” OR “anti-TPO” OR “anti-Tg”
- (((DE quality of life” OR “health related quality of life” OR “health-related quality of life” OR QoL OR “thyroid specific health related quality of life” OR “thyroid-specific health-related quality-of-life” OR “quality-of-life” OR “thyroid-specific health related quality-of-life” OR thyPRO OR “thyroid-related quality of life” OR “mental well-being” OR “Physical well-being” OR “Physical wellbeing” OR “mental wellbeing” OR “mental well*” OR “Health perception” OR “Symptom Checklist-90-Revised” OR “SCL-90-R” OR “Patient-reported outcome measure” OR “Patient reported outcome measure” OR “Affective disorders” OR Cognition OR “Psychosocial well-being” OR “Mental Health” OR “Physical Health” OR “Clinical Variables” OR HRQOL OR “GO-QOL” OR ThyTSQ OR “cognitive function“ OR depression OR” symptom distress”
- #1 AND #2 AND #3
- ALL (thyroid OR hypothyroid OR *thyroid* OR euthyroid OR thyroiditis OR ”autoimmune thyroid“ OR hashimoto)
- ALL (”quality of life“ OR ”symptomatic distress“ OR ”cognitive function“ OR depression OR attention)
- ALL (”anti thyroid antibodies“ OR peroxidase OR ”anti-TPO“ ”thyroid autoantibodies“ OR ”thyroid antibodies“ OR *antibod*)
- #1 AND #2 AND #3
- Thyroid OR ”thyroid disease“ OR ”thyroid disorder“ OR ”Hashimoto's“ OR ”AutoImmune Thyroiditis“ OR Hyperthyroidism OR hypothyroidism OR Graves OR ”Graves Disease“
- “quality of life” OR “well being” OR “well-being” OR “health-related quality of life Or “cognitive function” OR “depression” OR “symptom distress”
- #1 AND #2
- #1 AND #2
ProQuest Dissertations and Theses
- thyroid OR “thyroid disease” OR “thyroid disorder*” OR hypothyroidism OR “autoimmune thyroiditis” OR “autoimmune thyroid” OR thyroiditis OR “Hashimoto thyroiditis” OR “Hashimoto's thyroiditis” OR “Chronic autoimmune thyroiditis” OR “Autoimmune thyroiditis” OR “Autoimmune hypothyroidism” OR “ Autoimmune hyperthyroidism” OR Grave's Disease
- “thyroid antibody” OR “thyroid peroxidase” OR “Anti-thyroid peroxidase” OR “Anti thyroid peroxidase antibodies”
- “sf-36 health-related quality of life” OR “quality of life” OR “health related quality of life” OR “thyroid specific health related quality of life” OR “thyroid-related quality of life” OR “Symptom Checklist-90-Revised” OR “Patient-reported outcome measure” OR “Patient reported outcome measure” OR “cognitive function” OR depression OR “symptom distress”
- #1 AND #2 #3
National Institutes of Health (NIH) Clinical Trials Databases
- quality of life
- #1 AND #2 AND #3
- #1 AND #2
Cochrane Central Register of Controlled Trials
- Quality of Life OR well-being OR health-related quality of life
- #1 AND #2 AND #3
Academic Search Premier
- thyroid* OR Hashimotos OR hypothyroidism OR hyperthyroidism OR Graves OR euthyroid*
- antibod* OR peroxidase OR thyroglobulin
- quality of life or well being or well-being or health-related quality of life OR cognitive function OR depression OR symptom distress
- #1 AND #2 AND #3
- Thyroid OR hashimoto OR Graves OR hypothyroidism OR thyroiditis OR hyperthyroidism
- “quality of life” OR QOL OR HRQOL OR ThyPRO OR “health related quality of life” OR “cognitive function” OR depression OR “symptom distress”
- antibody OR antithyroid peroxidase OR antithyroglobulin OR antithyroid antibodies
- #1 AND #2 AND #3
1. Garmendia MA, Santos PS, Guillen-Grima F, Galofre JC. The incidence and prevalence of thyroid dysfunction in Europe: a meta-analysis. J Clin Endocrinol Metab
2014; 99 3:923–931.
2. Fitzgerald PA. Papadaki MA, McPhee SJ. Endocrine disorders. Current Medical Diagnosis & Treatment
55th edNew York: McGraw-Hill Education; 2016. 1078–1189.
3. Ross DS, Burch HB, Cooper DS, Greenlee CM, Laurberg P, Maia AL, Rivkees SA, Samuels M, Sosa JA, Stan MN, Walter MA. Thyroid
2016; 26 10:1343–1421.
4. Bianchi GP, Zaccheroni V, Solaroli E, Vescini F, Cerutti R, Zoli M, Marchesini G. Health-related quality of life
in patients with thyroid disorders
. Qual Life Res
2004; 13 1:45–54.
5. Antonelli A, Ferrari SM, Corrado A, Di Domenicantonio A, Fallahi P. Autoimmune thyroid disorders
. Autoimmun Rev
2015; 14 2:174–180.
6. Jameson J, Mandel SJ, Weetman AP. Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J. Disorders of the thyroid gland. McGraw-Hill Education, Harrison's principles of internal Medicine [Internet]
. United States of America: 2015.
7. Nicoll D, Lu C, Pignone M, McPhee SJ. Nicoll D, Lu C, Pignone M, McPhee SJ. Diagnostic Algorithms. The McGraw-Hill Companies Inc, Pocket guide to diagnostic tests [Internet]
. United States of America: 2012.
8. Promberger R, Hermann M, Pallikunnel SJ, Seemann R, Meusel M, Ott J. Quality of life
after thyroid surgery in women with benign euthyroid goiter: influencing factors including Hashimoto's thyroiditis. Am J Surg
2014; 207 6:974–979.
9. Mussig K, Kunle A, Sauberlich AL, Weinert C, Ethofer T, Saur R, et al. Thyroid peroxidase antibody positivity is associated with symptomatic distress in patients with Hashimoto's thyroiditis. Brain Behav Immun
2012; 26 4:559–563.
10. Rotondi M, de Martinis L, Coperchini F, Pignatti P, Pirali B, Ghilotti S, et al. Serum negative autoimmune thyroiditis displays a milder clinical picture compared with classic Hashimoto's thyroiditis. Eur J Endocrinol
2014; 171 1:31–36.
11. Armstrong TS. Symptoms experience: A concept analysis. Oncol NursForum
2003; 30 4:601–606.
12. Wekking EM, Appelhof BC, Fliers E, Schene AH, Huyser J, Tijssen JG, et al. Cognitive functioning and well-being in euthyroid patients on thyroxine replacement therapy for primary hypothyroidism. Eur J Endocrinol
2005; 153 6:747–753.
13. Ott J, Promberger R, Kober F, Neuhold N, Tea M, Huber JC, et al. Hashimoto's thyroiditis affects symptom load and quality of life
unrelated to hypothyroidism: a prospective case-control study in women undergoing thyroidectomy for benign goiter. Thyroid
2011; 21 2:161–167.
14. Winther KH, Cramon P, Watt T, Bjorner JB, Ekholm O, Feldt-Rasmussen U, et al. Disease-specific as well as generic quality of life
Is widely impacted in autoimmune hypothyroidism and improves during the first six months of levothyroxine therapy. PLoS One
2016; 11 6:e0156925.
15. Uysal HB, Ayhan M. Autoimmunity affects health-related quality of life
in patients with Hashimoto's thyroiditis. Kaohsiung J Med Sci
2016; 32 8:427–433.
16. Watt T, Hegedus L, Bjorner JB, Groenvold M, Bonnema SJ, Rasmussen AK, et al. Is Thyroid Autoimmunity per se a Determinant of Quality of Life
in Patients with Autoimmune Hypothyroidism? Eur Thyroid J
2012; 1 3:186–192.
17. Dardano A, Bazzzichi L, Bombardieri S, Monzani F. Symptoms in euthyroid Hashimoto's thyroiditis: is there a role for autoimmunity itself? Thyroid
2012; 22 3:334–335.
18. Bianchin S, Coffin C, Viader F, Ruf J, Carayon P, Potier F, et al. Anti-thyroperoxidase antibodies from patients with Hashimoto's encephalopathy bind to cerebellar astrocytes. Journal of neuroimmunology
2007; 192 (1–2):13–20.
19. Leyhe T, Mussig K, Weinert C, Laske C, Haring HU, Saur R, et al. Increased occurrence of weaknesses in attention testing in patients with Hashimoto's thyroiditis compared to patients with other thyroid illnesses. Psychoneuroendocrinology
2008; 33 10:1432–1436.
20. Giynas AM, Uguz F, Askin R, et al. The prevalence of depression and anxiety disorders in patients with euthyroid Hashimoto's thyroiditis: a comparative study. Gen Hosp Psychiatry
2014; 36 1:95–98.
21. Kirim S, Keskek SO, Ko€ksal F, et al. Depression in patients with euthyroid chronic autoimmune thyroiditis. Endocr J
2012; 59 8:705–708.
22. van de Ven AC, Muntjewerff JW, Netea-Maier RT, de Vegt F, Ross HA, Sweep FC, et al. Association between thyroid function, thyroid autoimmunity, and state and trait factors of depression. Acta Psychiatr Scand
2012; 126 5:377–384.
23. Pop VJ, Maartens LH, Leusink G, van Son MJ, Knottnerus AA, Ward AM, et al. Are autoimmune thyroid dysfunction and depression related? J Clin Endocrinol Metab
1998; 83 9:3194–3197.
24. Watt T, Cramon P, Hegedus L, Bjorner JB, Bonnema SJ, Rasmussen AK, et al. The thyroid-related quality of life
measure ThyPRO has good responsiveness and ability to detect relevant treatment effects. J Clin Endocrinol Metab
2014; 99 10:3708–3717.
25. Wong CK, Lang BH, Lam CL. A systematic review of quality of thyroid-specific health-related quality-of-life instruments recommends ThyPRO for patients with benign thyroid diseases. J Clin Epidemiol
26. Spirkova A, Dusatkova P, Peckova M, Kolouskova S, Snajderova M, Obermannova B, et al. Treated Autoimmune Thyroid Disease Is Associated with a Decreased Quality of Life
among Young Persons with Type 1 Diabetes. Int J Endocrinol
27. Roitt IM, Doniach D, Campbell PN, Vaughan Hudson R. Auto-Antibodies in Hashimoto's Disease: Lymphadenoid goitre. The Lancet
1956; 268 6947:820–821.
28. The Joanna Briggs Institute. Joanna Briggs Institute Reviewers’ Manual: 2014 edition. Australia: The Joanna Briggs Institute; 2014.
29. Tufanaru C, Munn Z, Stephenson M, Aromataris E. Fixed or random effects meta-analysis? Common methodological issues in systematic reviews of effectiveness. Int J Evid Based Healthc
2015; 13 3:196–207.