Effects of Low-Level Laser Therapy on Oxidative Stress Levels...

Effects of Low-Level Laser Therapy on Oxidative Stress Levels, Fatigue and Quality of Life in Patients With Hashimoto Thyroiditis

Hashimoto's thyroiditis (HT) is the most commonly observed inflammatory and autoimmune disease of the thyroid gland. Many genetic and environmental factors play a role in the pathogenesis of the disease, including iodine exposure, drugs, chemicals, toxins, infections and smoking. In recent years, the relationship between oxidative stress level and thyroid autoantibodies in HT has attracted increasing attention of researchers. In the studies, it has been reported that oxidative stress levels may increase due to chronic inflammation, insufficient thyroid hormone levels, excessive autoimmune response and excessive iodine intake. Data from clinical studies clearly show that the balance between oxidants and antioxidants shifts towards the oxidative side in patients with autoimmune thyroiditis, suggesting that oxidative stress may be a key event in the pathophysiology of the disease, independent of thyroid function. Recent evidence has suggested that low-level laser therapy (LLLT) can improve thyroid function and reduce levels of thyroid peroxidase antibodies (TPOAb) in patients with hypothyroidism caused by chronic autoimmune thyroiditis. In the literature, data examining the effects of LLLT on oxidative stress level and quality of life in patients with HT is limited. As far as we know, it will be the first study examining the effect of LLLT on oxidative stress, fatigue and quality of life in cases diagnosed with HT. The aim of the study is to examine the effects of LT4 treatment combined with LLLT on thyroid autoimmunity, oxidative stress, fatigue and quality of life in patients with Hashimoto's diagnosis.

Hashimoto's thyroiditis (HT) is the most commonly observed inflammatory and autoimmune disease of the thyroid gland. HT is the main cause of spontaneous hypothyroidism in adults. Symptoms of hypothyroidism may develop within a few years in patients with initial euthyroidism. Many genetic and environmental factors play a role in the pathogenesis of the disease, including iodine exposure, drugs, chemicals, toxins, infections and smoking. In recent years, the relationship between oxidative stress level and thyroid autoantibodies in HT has attracted increasing attention of researchers. In the studies, it has been reported that oxidative stress levels may increase due to chronic inflammation, insufficient thyroid hormone levels, excessive autoimmune response and excessive iodine intake. OS occurs as a result of an imbalance between free radical production and antioxidant defense mechanisms. Data from clinical studies clearly show that the balance between oxidants and antioxidants shifts towards the oxidative side in patients with autoimmune thyroiditis, suggesting that oxidative stress may be a key event in the pathophysiology of the disease, independent of thyroid function. Gerenova et al. divided patients with a diagnosis of HT into three subgroups according to thyroid function (group 1-euthyroid, group 2-hypothyroid, and group 3-Levothyroxin treated patients) and pointed out cellular antioxidative deficiency in all stages of the disease. Standard treatment in patients with HT is lifelong levothyroxine (LT4) treatment, which adjusts the dose to reach normal circulating thyrotropin (TSH) levels. Studies have found persistent fatigue, psychological and general well-being, and impairments in cognitive function in patients with HT despite LT4 replacement therapy. Gomez et al. compared 152 hypothyroid women treated with levothyroxine and 238 women without hypothyroidism disorder. Female patients with hypothyroidism, despite being euthyroid, showed worse quality of life than the control group. It was emphasized that the quality of life of women with hypothyroidism should be evaluated and further research should be conducted. Recent evidence has suggested that low-level laser therapy (LLLT) can improve thyroid function and reduce levels of thyroid peroxidase antibodies (TPOAb) in patients with hypothyroidism caused by chronic autoimmune thyroiditis. LLLT is a non-invasive, painless, low-risk and low-cost method that uses the interaction of light with molecular structures to support anti-inflammatory effects and regeneration of biological tissues. In the literature, data examining the effects of LLLT on oxidative stress level and quality of life in patients with HT is limited. As far as we know, it will be the first study examining the effect of LLLT on oxidative stress, fatigue and quality of life in cases diagnosed with HT. The planned research is trying to improve and expand the existing literature on LLLT in cases with HT and to contribute to the treatment protocol in order to reduce the negative consequences that may be experienced in this group of patients now and in the future. These statements show the originality of the study. Purpose: The aim of the study is to examine the effects of LT4 treatment combined with LLLT on thyroid autoimmunity, oxidative stress, fatigue and quality of life in patients with Hashimoto's diagnosis.

Hashimoto Thyroiditis, Oxidative Stress, Low-Level Laser Therapy, Fatigue, Quality of Life, Autoimmune Thyroiditis, Depression, Sleep, Anxiety, Thyroid Hormones, Photobiomodulation Therapy

Low Level Laser Therapy (LLLT): Low-level laser therapy will be applied to the cases in addition to LT4 hormone replacement therapy. LLLT group will be treated using a continuous wave GaAIAs type diode laser (Intelect® Mobile Laser, Model No: 2779, Production Year: 2016; Chattanooga Group) device in the treatment area of 0.07 cm2. Continuous mode at 850 nm wavelength, 100 mW output power,1.43 W/cm2 power density and 28.57 J / cm2 energy density will be used.

Probes were placed in the sham laser group in a similar way as in the treatment group. The screen of the laser device was active; however, the energy was set as 0 J and the power as 0 mW , respectively,and the same operations were also performed.

Eight target points (superior, mediolateral, inferior border of the right and left thyroid lobes, right and left sides of the isthmus) will be marked with a surgical pen by determining the thyroid borders on the skin by thyroid ultrasonography by the specialist physician. Low-level laser (28.57 J / cm2) fixed applications will be made on the thyroid gland, approximately 1 cm from each other. In practice, the patient's neck will be maintained in the extension position. Each application will last 20 seconds and the radiant energy will be 2 J, the tip of the laser will be kept in contact with the skin and upright. Duration of treatment is 6 sessions 2 days a week. The cumulative dose will be 96 J.

Biochemical parameters will be taken from the patient file routinely requested by the physician. For routine or whole blood analysis, leftover serum samples will be collected from the blood taken after fasting for 10-12 hours and the separated serum samples will be kept in a -80 °C refrigerator until the analysis day. The analysis of the collected samples will be examined in the Biochemistry Laboratory of Istanbul Medipol University. Oxidative Stress Index (OSI) will be calculated by measuring Total Oxidant Level (TOS) and Total Antioxidant Levels (TAS).

For routine or whole blood analysis, leftover serum samples will be collected from the blood taken after fasting for 10-12 hours and the separated serum samples will be kept in a -80 °C refrigerator until the analysis day. The analysis of the collected samples will be examined in the Biochemistry Laboratory of Istanbul Medipol University. Oxidative stress biomarkers will be examined.

For routine or whole blood analysis, leftover serum samples will be collected from the blood taken after fasting for 10-12 hours and the separated serum samples will be kept in a -80 °C refrigerator until the analysis day. The analysis of the collected samples will be examined in the Biochemistry Laboratory of Istanbul Medipol University. Oxidative stress biomarkers will be examined.

For routine or whole blood analysis, leftover serum samples will be collected from the blood taken after fasting for 10-12 hours and the separated serum samples will be kept in a -80 °C refrigerator until the analysis day. The analysis of the collected samples will be examined in the Biochemistry Laboratory of Istanbul Medipol University. Oxidative stress biomarkers will be examined.

For routine or whole blood analysis, leftover serum samples will be collected from the blood taken after fasting for 10-12 hours and the separated serum samples will be kept in a -80 °C refrigerator until the analysis day. The analysis of the collected samples will be examined in the Biochemistry Laboratory of Istanbul Medipol University. Oxidative stress biomarkers will be examined.

For routine or whole blood analysis, leftover serum samples will be collected from the blood taken after fasting for 10-12 hours and the separated serum samples will be kept in a -80 °C refrigerator until the analysis day. The analysis of the collected samples will be examined in the Biochemistry Laboratory of Istanbul Medipol University. Oxidative stress biomarkers will be examined.

Fatigue Severity Scale: The Fatigue Severity Scale (FSS) is a 9-item self-report questionnaire scale developed in 1989. The items are scored on a 7 point scale with 1 = strongly disagree and 7= strongly agree. The minimum score = 9 and maximum score possible = 63. Higher the score = greater fatigue severity. Another way of scoring: mean of all the scores with minimum score being 1 and maximum score being 7.

Fatigue Impact Scale: There are 40 items, each of which is scored 0 (no problem) to 4 (extreme problem), providing a continuous scale of 0-160. It is composed of three subscales that describe how fatigue impacts upon cognitive (10 items), physical (10 items) and psychosocial functioning (10 items).

Short Form-36 questionnaire: The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability.

Beck Anxiety Scale: A total score of 0 - 7 is interpreted as a "Minimal" level of anxiety; 8 - 15 as "Mild"; 16 - 25 as "Moderate", and; 26 - 63 as "Severe".

Beck Depression Scale: Scores of 0-13 indicate minimal depression, 14-19 (mild depression), 20-28 (moderate depression) and 29-63 (severe depression).

Pittsburgh Sleep Quality Index: In scoring the PSQI, seven component scores are derived, each scored 0 (no difficulty) to 3 (severe difficulty). The component scores are summed to produce a global score (range 0 to 21). Higher scores indicate worse sleep quality.

Epworth Sleepiness Scale: Score: Scores can be interpreted as follows: 0-5 lower normal daytime sleepiness. 6-10 normal daytime sleepiness. 11-12 mild excessive daytime symptoms. 13-15 moderate excessive daytime symptoms. 16-24 severe excessive daytime symptoms.

International Physical Activity Questionnaire Short Form: IPAQ-SF records the last 7 day recall for four intensity levels of physical activity which is vigorous-intensity activity, moderate-intensity activity, walking, and sitting. From IPAQ-SF, data were converted to Metabolic Equivalent minutes per week (MET-min/week) using. Compendium average MET score (Walking = 3.3 METs, Moderate Physical Activity = 4.0 METs and Vigorous Physical Activity = 8.0 METs).

Grip strength is a measure of muscular strength or the maximum force/tension generated by one's forearm muscles. It can be used as a screening tool for the measurement of upper body strength and overall strength. It is most useful when multiple measurements are taken over time to track performance. Jamar hand dynamometer was used to assess wrist grip strength.

Inclusion Criteria: Cases between the ages of 18-65 who applied to the Kosuyolu Istanbul Medipol Hospital Endocrinology and Metabolic Diseases Clinic between 2020-2021 and diagnosed as "Hashimoto Thyroiditis" by a specialist physician will be included in the study. Exclusion Criteria: Acute infection Use of immunosuppressants, immunostimulants and drugs that interfere with the production, transport, and metabolism of thyroid hormones Thyroid nodules Tracheal stenosis Serious illness History of exposure to ionizing radiation and/or neoplasia in the cervical region Malignancy and a history of thyroid surgery Hypothyrodism caused by postpartum thyroiditis Pregnancy and breastfeeding period Identification and diagnosis of the cases with neurological and psychiatric disorders.