How Common is Fibromyalgia in Patients with Hypothyroidism?

Background: Fibromyalgia (FM) is the most common cause of chronic generalized musculoskeletal pain and it is generally accompanied by the other nonspecic common symptoms. The etiology and the pathophysiology is still not clear but also there are some studies that show a relationship between FM and thyroid diseases. So, in this study we aimed to determine the frequency of FM in patients with hypothyroidism and the variables that may affect this frequency. Methods: This is a cross-sectional, single center and prospective study. A total of 180 patients -who were applied to internal medicine outpatient clinics- included in the study and the patients who described the generalized musculoskeletal pain were consulted to the physical medicine and rehabilitation outpatient clinics. We have evaluated demographic data, laboratory, presence of thyroid disease and FM, and Beck Depression Questionnaire (BDQ) and FM Impact Questionnaire (FIQ) for FM patients. Results: 39.4% (n = 71) of the patients had FM and 60.6% (n = 109) of them did not. There was a positive corelation between FIQ score and age at diagnosis and disease duration. As the age at diagnosis and duration of disease increased, the FIQ score increased by 37.3% and 25.7%, respectively. In addition, as BDQ increased, the FIQ score increased by 44.8%. Conclusion: Signs and symptoms of hypothyroidism is similar to signs and symptoms of FM, and approximately 40% of patients with hypothyroidism could have FM concomittantly. Therefore, all patients with hypothyroidism should also be examined for FM.


Introduction
Fibromyalgia (FM) is the most common cause of chronic generalized musculoskeletal pain and it is generally accompanied by the other symptoms such as cognitive disturbance, fatigue, multiple somatic and psychiatric symptoms. The etiology and the pathophysiology is still not clear (1,2). There is no evidence of in ammation in affected (muscles, tendons, ligaments) tissues. The prevelance is approximately 2 to 3 percent and increases with age. It can affect both gender and all ages but it is more common in female, especially between ages of 20-55 years (3)(4)(5)(6). Diagnostic criteria consist of detailed anamnesis, physical examination and laboratory tests to exclude other causes of pain and fatigue. Due to di culties in diagnosis, 2016 American College of Rheumatology (ACR) revised bromyalgia criteria is widely used as a standardized approach. (5) Thyroid autoimmunity and thyroid disorders may contribute to FM. It is not clear how thyroid disorders contribute to FM development because there are limited number of studies in this eld. But according to an article published in 2012, the FM prevalence in autoimmune thyroid diseases has been reported to be between 30% and 40% (7). Therefore, the view that there is an increase in FM prevalence of people with thyroid disease has pushed researchers to investigate the cause and some questions have arisen; Is there any relationship between increased in ammatory markers, thyroid antibodies, duration of thyroid disease or other variables of the patients and how does it affect the risk of developing FM? Therefore, in this study, we aimed to determine the frequency of bromyalgia in patients with hypothyroidism and the variables that may affect this frequency.

Materials And Methods
This is a a single center, prospective, cross-sectional clinical study conducted at Bakirkoy Dr. Sadi Konuk Training and Research Hospital in between 10/07/2019 and 30/03/2020. Patients equal to or older than 18 years of age who were admitted to our hospital's internal medicine outpatient clinic for hypothyroidism or subclinical hypothyroidism were included in the study. Patients having an underlying disease such as malignancy, diabetes mellitus, rheumatic diseases, hypertension, atherosclerotic heart disease, major depression and using pregabalin, selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs) and tricyclic antidepressant drugs were excluded from the study. Patients' age, gender, height, weight, body mass index (BMI), age at diagnosis, disease duration, laboratory ndings and FM status were recorded. A total of 180 patients included in the study and the patients who described the generalized musculoskeletal pain were consulted to the physical medicine and rehabilitation outpatient clinics. The study was approved by Ethical Committee of Bakirkoy

Statistical analysis:
Descriptive statistical methods (mean, standard deviation, median, frequency, ratio, minimum, maximum) were used when evaluating the study data. Frequency and percentage values of categorical variables, arithmetic mean and standard deviation values of quantitative variables are presented. Percentage distributions and frequency values are given for categorical data. In the relationship analysis, Kendall'stau-b relationship analysis, which is suitable for a continuous categorical data was used.
Independent sample t test was used in group difference analysis. Signi cance was evaluated at the level of p <0.05.

Results
In our study, 180 patients who admitted to our outpatients clinic and newly diagnosed or with a known diagnosis of hypothyroidism or subclinical hypothyroidism were evaluated for FM. The study population was consisted of 166 women (92.2%) and 14 men (7.8%). In all patients, 39.4% (n = 71) of them had FM and 60.6% (n = 109) did not have FM. Descriptive statistical information for some variables was given in Table 1.   and vitamin D; only there was a positive corelation between FIQ score and age at diagnosis and disease duration, but no signi cant corelation was found with other variables. As the age at diagnosis and duration of disease increased, the FIQ score increased by 37.3% and 25.7%, respectively. Analysis of BDQ and FIQ scores with the variables were shown in Table 5. In addition, the relationship between BDQ and FIQ score was examined and found that as BDQ increased, the FIQ score increased by 44.8%.   Also, studies recently reported that there was an association between thyroid autoimmunity and FM. (11,12,13) In a study conducted with 79 patients diagnosed with hashimato thyroiditis (HT) in 2017 (14), the presence of FM was evaluated, and the frequency of FM in these patients was 62%. In patients with HT and FM, anti-TPO levels and duration of the disease were signi cantly higher in patients with HT than those without FM. But in that study, researchers did not observe a signi cant difference between groups for age, weight, height and BMI. They also found a strong positive correlation between FIQ and disease duration, age, TSH, Anti-TPO. They performed multiple regression analysis and TPOAb was seen to be an independent risk factor in FM patients.
In our study, the frequency of FM in patients with hypothyroidism and /or subclinical hypothyroidism, was found to be %39,4 and female (F) / male (M) ratio was 68/3 with female dominance. But we could not nd any signi cant difference between presence of FM and thyroid antibodies, disease duration, body mass index, age at diagnosis.
In another cross-sectional study (15) with 500 hashimato thyroiditis patients and 310 age and sex matched control patients, patients were evaluated for non-speci c rheumatic manifestations. It was determined that there were minimal differences in regard to rheumatic manifestations between the groups and the most common manifestations were polyarthralgias and myalgias/ bromyalgia, and nonspeci c rheumatoid manifestations observed threefold more in HT patients. When comparing HT patients with and without rheumatological manifestations, the ratio of female/male was high (24:1 vs 5:1) and with higher age at the time of diagnosis. In our study, the absence of a control group was a limitation, but similarly in our study, the ratio of female/male was high (F:M = 68:3).
In the study conducted by Soy et al. (16), the presence of rheumatic diseases was investigated in 65 autoimmune thyroid patients. Hypothyroidism was detected in 50 patients (77%), hyperthyroidism was detected in 12 patients (18%) and 3 patients (5%) was euthyroid. In all patients, 56 of the them were female, 9 were male and 62% of the patients had various rheumatic disease with the most common was (20%) bromyalgia. In our study the frequency of bromyalgia in patients with thyroid disfunciton was common with a rate of %39.4 and consistent with this study female gender was higher.

Conclusion
It should be kept in mind that the signs and symptoms of hypothyroidism is similar to signs and symptoms of FM, and approximately 40% of patients with hypothyroidism could have FM concomittantly. So the presence of a diagnosis of hypothyroidism should not cause us to miss the diagnosis of FM in these patients. Therefore, all patients with hypothyroidism should also be examined for FM.

Declarations
Funding: None Con icts of interest/Competing interests: The author reports no con icts of interest in this work.
Ethics approval: The study was approved by Ethical Committee of Bakirkoy Dr. Sadi Konuk Training and Research Hospital with the number of 2019/13/10-8/07/2019.
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