Exercise training improves quality of life in women with subclinical hypothyroidism: a randomized clinical trial

Francisco Zacaron Werneck Emerson Filipino Coelho Saulo Peters Almas Marília Mendes do Nascimento Garcia Heloina Lamha Machado Bonfante Jorge Roberto Perrout de Lima Patrícia dos Santos Vigário Míriam Raquel Meira Mainenti Patrícia de Fátima dos Santos Teixeira Mário Vaisman About the authors

ABSTRACT

Objective:

The aim was to evaluate the quality of life (HRQoL) in women with subclinical hypothyroidism (sHT) after 16 weeks of endurance training.

Subjects and methods:

In the first phase, a cross-sectional study was conducted in which 22 women with sHT (median age: 41.5 (interquartile range: 175) years, body mass index: 26.2 (8.7) kg/m2, thyroid stimulating hormone > 4.94 mIU/L and free thyroxine between 0.8 and 1.3 ng/dL were compared to a group of 33 euthyroid women concerned to HRQoL. In the second phase, a randomized clinical trial was conducted where only women with sHT were randomly divided into two groups: sHT-Tr (n = 10) - participants that performed an exercise program - and sHT-Sed (n = 10) - controls. Exercise training consisted of 60 minutes of aerobic activities (bike and treadmill), three times a week, for 16 weeks. The HRQoL was assessed by the SF-36 questionnaire in the early and at the end of four months.

Results:

Women with sHT had lower scores on functional capacity domain in relation to the euthyroid ones (770 ± 23.0 vs. 88.8 ± 14.6; p = 0.020). The sHT-Tr group improved functional capacity, general health, emotional aspects, mental and physical component of HRQoL after training period, while the sHT-Sed group showed no significant changes.

Conclusion:

After 16 weeks of aerobic exercise training, there were remarkable improvements in HRQoL in women with sHT.

Keywords
Hypothyroidism; quality of life; exercise training; functional capacity

INTRODUCTION

Thyroid hormones (T3 and T4) act on most body cells, and changes in serum concentrations of these hormones cause impact on health of people (11. Hoermann R, Midgley JEM, Larisch R, Dietrich JW. Recent advances in thyroid hormone regulation: toward a new paradigm for optimal diagnosis and treatment. Front Endocrinol (Lausanne). 2017;8:364.). When thyroid hormones are normal and thyroid stimulating hormone (TSH) is above the reference values, subclinical hypothyroidism (sHT) is characterized (22. Surks MI1, Ortiz E, Daniels GH, Sawin CT, Col NF, Cobin RH, et al. Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA. 2004;291(2):228-38.). It is estimated that the prevalence of sHT in the general population is around 4% to 10%, which is higher among women (33. Sgarbi JA, Teixeira PFS, Maciel LMZ, Mazeto GMFS, Vaisman M, Montenegro Junior RM, et al. Consenso brasileiro para a abordagem clínica e tratamento do hipotireoidismo subclínico em adultos: recomendações do Departamento de Tireoide da Sociedade Brasileira de Endocrinologia e Metabologia. Arq Bras Endocrinol Metabol. 2013;57(3):166-83.).

The sHT patients may present signs and characteristic symptoms of hypothyroidism such as: fatigue, weight gain, dyslipidemia, psychological disorders, cardiovascular disorders, and increased risk of coronary artery disease and mortality (33. Sgarbi JA, Teixeira PFS, Maciel LMZ, Mazeto GMFS, Vaisman M, Montenegro Junior RM, et al. Consenso brasileiro para a abordagem clínica e tratamento do hipotireoidismo subclínico em adultos: recomendações do Departamento de Tireoide da Sociedade Brasileira de Endocrinologia e Metabologia. Arq Bras Endocrinol Metabol. 2013;57(3):166-83.,44. Cooper DS, Biondi B. Subclinical thyroid disease. Lancet. 2012;379(9821):1142-54.). The effects of hypothyroidism on health related quality of life (HRQoL) are well established (55. Gulseren S, Gulseren L, Hekimsoy Z, Cetinay P Ozen C,Tokatlioglu B. Depression, anxiety, health-related quality of life, and disability in patients with overt and subclinical thyroid dysfunction. Arch Med Res. 2006;37(1):133-9.77. Vigário Pdos S, Vaisman F Coeli CM, Ward L, Graf H, Carvalho G, et al. Inadequate levothyroxine replacement for primary hypothyroidism is associated with poor health-related quality of life-a Brazilian multicentre study. Endocrine. 2013;44(2):434-40.), but the results are controversial in sHT (33. Sgarbi JA, Teixeira PFS, Maciel LMZ, Mazeto GMFS, Vaisman M, Montenegro Junior RM, et al. Consenso brasileiro para a abordagem clínica e tratamento do hipotireoidismo subclínico em adultos: recomendações do Departamento de Tireoide da Sociedade Brasileira de Endocrinologia e Metabologia. Arq Bras Endocrinol Metabol. 2013;57(3):166-83.,44. Cooper DS, Biondi B. Subclinical thyroid disease. Lancet. 2012;379(9821):1142-54.).

There is evidence that sHT is associated to worse scores in HRQoL domains such as: functional capacity, health perception, vitality and emotional aspects (66. Vigário P Teixeira P Reuters V, Almeida C, Maia M, Silva M, et al. Perceived health status of women with overt and subclinical hypothyroidism. Med Princ Pract. 2009;18(4):317-22.88. Razvi S, McMillan CV, Weaver JU. Instruments used in measuring symptoms, health status and quality of life in hypothyroidism: a systematic qualitative review. Clin Endocrinol (Oxf). 2005;63(6):617-24.). In contrast, some studies do not support these findings (99. Bianchi GP Zaccheroni V, Solaroli E, Vescini F Cerutti R, Zoli M, et al. Health-related quality of life in patients with thyroid disorders. Qual Life Res. 2004;13(1):45-54.1111. Klaver EI, van Loon HC, Stienstra R, Links TP, Keers JC, Kema IP, et al. Thyroid hormone status and health-related quality of life in the LifeLines Cohort Study. Thyroid. 2013;23(9):1066-73.). In part, the divergence of results can be explained by the degree of change in TSH levels. It seems that worse HRQoL are observed in patients with TSH higher than 10 mIU/L (22. Surks MI1, Ortiz E, Daniels GH, Sawin CT, Col NF, Cobin RH, et al. Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA. 2004;291(2):228-38.,66. Vigário P Teixeira P Reuters V, Almeida C, Maia M, Silva M, et al. Perceived health status of women with overt and subclinical hypothyroidism. Med Princ Pract. 2009;18(4):317-22.), although recent cross-sectional study has not confirmed this hypothesis (1111. Klaver EI, van Loon HC, Stienstra R, Links TP, Keers JC, Kema IP, et al. Thyroid hormone status and health-related quality of life in the LifeLines Cohort Study. Thyroid. 2013;23(9):1066-73.).

Conventional treatment of sHT is done through hormone replacement with levothyroxine (L-T4) that is associated with decreased clinical manifestations in various organs and systems (44. Cooper DS, Biondi B. Subclinical thyroid disease. Lancet. 2012;379(9821):1142-54.,1212. Razvi S, Shakoor A, Vanderpump M, Weaver JU, Pearce SH. The influence of age on the relationship between subclinical hypothyroidism and ischemic heart disease: a metaanalysis. J Clin Endocrinol Metab. 2008;93(8):2998-3007.). It is emphasized, however, that it has produced conflicting results in the improvement of HRQoL and at the symptoms of patients in different studies (88. Razvi S, McMillan CV, Weaver JU. Instruments used in measuring symptoms, health status and quality of life in hypothyroidism: a systematic qualitative review. Clin Endocrinol (Oxf). 2005;63(6):617-24.,1313. Reuters VS, Almeida Cde P Teixeira Pde F Vigário Pdos S, Ferreira MM, Castro CL, et al. Effects of subclinical hypothyroidism treatment on psychiatric symptoms, muscular complaints, and quality of life. Arq Bras Endocrinol Metabol. 2012;56(2):128-36.).

Exercise is associated to a better HRQoL in different populations (1414. Imayama I, Alfano CM, Mason CE, Wang C, Xiao L, Duggan C, et al. Exercise adherence, cardiopulmonary fitness and anthropometric changes improve exercise self-efficacy and health-related quality of life. J Phys Act Health. 2013;10(5):676-89.,1515. Staniute M, Bunevicius A, Brozaitiene J, Bunevicius R. Relationship of health-related quality of life with fatigue and exercise capacity in patients with coronary artery disease. Eur J Cardiovasc Nurs. 2014;13(4):338-44.). However, few studies have investigated the effects of exercise on HRQoL of patients with sHT (1616. Garces-Arteaga A, Nieto-Garcia N, Suarez-Sanchez F,Triana-Reina HR, Ramírez-Vélez R. Influence of a medium-impact exercise program on health-related quality of life and cardiorespiratory fitness in females with subclinical hypothyroidism: an open-label pilot study. J Thyroid Res. 2013;2013:592801.). Thus, this study aimed at evaluating if exercise improves HRQoL in women with sHT. According to previous studies with subclinical disorders (1616. Garces-Arteaga A, Nieto-Garcia N, Suarez-Sanchez F,Triana-Reina HR, Ramírez-Vélez R. Influence of a medium-impact exercise program on health-related quality of life and cardiorespiratory fitness in females with subclinical hypothyroidism: an open-label pilot study. J Thyroid Res. 2013;2013:592801.,1717. Vigário Pdos S, Chachamovitz DS, Cordeiro MF, Teixeira Pde F, de Castro CL, de Oliveira FP, et al. Effects of physical activity on body composition and fatigue perception in patients on thyrotropin- suppressive therapy for differentiated thyroid carcinoma. Thyroid. 2011;21(7):695-700.), exercise is taken as hypothesis that also improve HRQoL in sHT.

SUBJECTS AND METHODS

Subjects

A total of 55 female participants were included, aged 20-60 years old, which composed two study groups: sHT group is consisted of 22 women recruited in the Endocrinology Service of Hospital and Maternity Terezinha de Jesus of Faculdade de Ciências Médicas e da Saúde de Juiz de Fora, Brazil. The inclusion criteria for the sHT group were: show two doses, with a minimum interval of four weeks of serum TSH above the adopted reference upper limit (4.94 mIU/L) and level of T4L within the reference range (0.70 to 1.48 ng/dL). The control group consisted of 33 euthyroid women with normal values of serum TSH, anti-TPO (antithyroid peroxidase antibody) and free T4 within the reference ranges for the used kits and absence of thyroid disease history. Others criteria adopted for both groups were: absence of comorbidities and no physical exercise program for at least three months. Patients with sHT or euthyroid participants with any chronic and/or cardiovascular disease, smokers, those who were using drugs or substances that could interfere in thyroid function, in heart rate or blood pressure, as well as those with musculoskeletal inability toperform physical exercises were excluded from the study. The study was approved by the local ethics committee (no. 0164/10), and all participating groups signed free informed term of consent prior to participation in the study.

Study design

Initially a cross sectional study comparing patients with sHT and euthyroid women concerned to signs and symptoms of hypothyroidism and HRQoL was performed. Subsequently, only sHT patients were randomized to participate or not in the exercise program. The patients were followed in both prospective study groups without masking. A resting echocardiography and exercise cardiopulmonary test were performed for clinical assessment of cardiac structure and cardiorespiratory function before the prospective phase. Two patients with severe changes in blood pressure and heart rate during the exercise test were excluded from randomization. Patients who participated in exercise training (n = 10) were denominated sHT-Tr, while those who did not participate in exercise training (n = 10) were denominated sHT-Sed. Exercise training consisted of aerobic activities, three times a week, for 16 weeks, supervised by the authors. The sHT-Sed patients were instructed for maintaining their usual daily life activities. After four months of intervention or observation, the tests conducted at the beginning of the study were repeated.

Hormonal measures, level of physical activity and anthropometric measures

The TSH, T4L and anti-TPO levels were measured by third generation chemiluminescenceimmunometric assay (BeckmanCoulter®, Access2®). The reference values for TSH and free T4 were 0.35 to 4.94 mUI/mL and 0.70 to 1.48 ng/dL, respectively. The anti- TPO levels > 35 UI/mL were considered positive. The level of physical activity was assessed using the Baecke's Habitual Physical Activity Questionnaire, in its translated version and validated for Portuguese (1818. Florindo A, Latorre M. Validação do questionário de Baecke de avaliação da atividade física habitual em homens adultos. Rev Bras Med Esporte. 2003;9:121-8.). In anthropometric assessment, body mass and height (Filizola scale with 0.1 kg and 10 mm precision, respectively), in order to calculate the Body Mass Index (BMI; kg/m2) were measured.

Signs and symptoms of hypothyroidism - Clinical score

The specific signals and symptoms of hypothyroidism were evaluated by Billewicz scale modified (1919. Zulewski H, Müller B, Exer P, Miserez AR, Staub JJ. Estimation of tissue hypothyroidism by a new clinical score: evaluation of patients with various grades of hypothyroidism and controls. J Clin Endocrinol Metab. 1997;82(3):771-6.). The scale consists of 12 clinical signals and symptoms of hypothyroidism: dry skin, rough skin, decreased sweating, weight gain, paresthesia, hoarseness, decreased hearing, constipation, periorbital edema, slow movements, cold skin, and slow Achilles reflex. A point (11. Hoermann R, Midgley JEM, Larisch R, Dietrich JW. Recent advances in thyroid hormone regulation: toward a new paradigm for optimal diagnosis and treatment. Front Endocrinol (Lausanne). 2017;8:364.) was assigned when the presence of signal or symptoms or zero (0) in his absence was found.

The maximum scale score is 12 points; scores lower than 3 are expected in euthyroid women; among 3 and 5, in sHT; and higher than 5 in hypothyroidism.

Measure of health related quality of life

The SF-36 (Medical Outcomes Study 36 - Item Short-Form Health Survey) was used to assess the HRQoL of participants in their translated version and validated for Portuguese (2020. Ciconelli RM, Ferraz MB, Santos W, Meinão I, Quaresma MR. Tradução para a língua portuguesa e validação do questionário genérico de avaliação de qualidade de vida SF-36 (Brasil SF-36). Rev Bras Reumatol. 1999;39(3):143-50.). The SF-36 is consisted of 36 items distributed in eight dimensions: functional capacity, physical aspects, pain, general health, vitality, social aspects, emotional aspects and mental health. The answers are presented in likert scale. The score of each domain ranges from 0 to 100 points and higher the score, higher HRQoL. The physical component was calculated by the average of the following scales: functional capacity, physical aspects, pain and general health; and the mental component: vitality, social aspects, emotional aspects and mental health.

Exercise program

The exercise program consisted of aerobic activities with supervision of a physical education professional, involved in the study. The frequency of training was three times a week for 16 weeks. Each aerobic exercise session consisted of 60 minutes, divided into four phases: heating (5 minutes), ergometric bicycle (25 minutes), treadmill (25 minutes) and resting (5 minutes). The training was individually prescribed based on exercise cardiopulmonary test and maximum heart rate estimated by age (HRmax = 220 - age). The training intensity was controlled by HR between 65 and 75% of HR. The training was continuous and participants could walk, walk with inclination or run in treadmill. The HR was monitored during training sessions by HR monitor (Polar®). Blood pressure and rate of perceived exertion were measured every 10 minutes. After exercise session, stretching exercises were performed by participants and also stimulated to drink fluids.

Statistical analysis

Descriptive analysis was presented as mean ± standard deviation or median (1st quartile, 3rd quartile). In the cross sectional study, comparisons between patients and euthyroid women were measured using Student's t tests or Mann-Whitney test. A two way repeated measures analysis of variance (ANOVA) (2X2) was performed to determine if significance differences between groups and time. If significant main effects or interactions were present a Bonferroni post hoc analysis was conducted. For the analysis of qualitative variables, Fisher's Exact Test was used. Relationship among quantitative variables was performed using Pearson's correlation test. As clinically relevant differences was considered the differences of at least 10 points on the scale of 0 to 100 (2121. Osoba D, Rodrigues G, Myles J, Zee B, Pater J. Interpreting the significance of changes in health-related quality-of-life scores. J Clin Oncol. 1998;16(1):139-44.). To assess the internal consistency of SF-36, the alpha Cronbach was used. All analyzes were carried out by using the statistical package SPSS 24.0 (IBM Corp., Armonk, NY). The significance level was set at P < 0.05.

RESULTS

Cross sectional study

The general characteristics and LQRH scores of women with sHT and euthyroid are shown in Table 1. In the sHT group, a total of 41% showed positive anti-TPO, while all euthyroid presented anti-TPO negative. There were no significant differences among groups regarding the variable potentials of confounding age (p = 0.85), body mass (p = 0.91), BMI (p = 0.94) and menopause status (p = 0.28). The sHT patients showed lower levels of physical activity (p < 0.001) and higher number of signals and symptoms (p = 0.02). Regarding LQRH, sHT patients showed lower scores on “functional capacity” domain (p = 0.02) compared to euthyroid. In other domains there were no significant differences observed between groups, however women with sHT showed consistently lower scores, except in “social aspects”. No relationship was found between TSH, signals and symptoms and life quality (p > 0.05). The internal consistency of 36 questions of SF-36 was satisfactory (Cronbach's alpha = 0.92). All domains also showed satisfactory coefficients (0.70 to 0.90). This means that the investigated sample reported high level of consistency in the answers to the survey questions.

Table 1
General characteristics and quality life scores of women with subclinical hypothyroidism (sHT) and euthyroid

Randomized clinical trial

After randomization, there were no significant differences between the sHT-Tr and sHT-Sed groups related to age (p = 0.25), TSH (p = 0.85), T4 (p = 0.74), body mass (p = 0.35), BMI (p = 0.35), level of physical activity (p = 0.11), signals and symptoms (p = 0.53), menopause and all domains of life quality life (p > 0.05).

Analyses revealed a significant (group x time) interaction effect concerned functional capacity, general health, emotional aspects, psychological component, and physical component (Table 2). The sHT-Tr group showed improvement in these domains. On the other hand, the sHT-Sed group after four months of observation, showed no significant changes in all domains assessed by SF-36. Both groups showed no significant changes in signals and symptoms number (p > 0.05).

Table 2
General characteristics and quality life scores of patients with subclinical hypothyroidism before and after 4 months of exercise training (sHT-Tr) or observation (sHT-Sed)

DISCUSSION

This study compared the HRQoL of women with sHT and the euthyroid and assessed the impact of physical exercise on this outcome. The main findings were: 1) sHT is associated to a worse perception of HRQoL; 2) Women with sHT showed improvements in multiple assessed domains of HRQoL after aerobic exercise training during four months.

In the cross sectional study, it was found that patients with sHT showed more signals and symptoms and lower functional capacity compared to control euthyroid group, what has been mentioned previously in other studies (66. Vigário P Teixeira P Reuters V, Almeida C, Maia M, Silva M, et al. Perceived health status of women with overt and subclinical hypothyroidism. Med Princ Pract. 2009;18(4):317-22.88. Razvi S, McMillan CV, Weaver JU. Instruments used in measuring symptoms, health status and quality of life in hypothyroidism: a systematic qualitative review. Clin Endocrinol (Oxf). 2005;63(6):617-24.). Besides that, in our study, there was a greater presence of signs and symptoms in sHT patients compared to the control group. Similar results were beforehand observed (1313. Reuters VS, Almeida Cde P Teixeira Pde F Vigário Pdos S, Ferreira MM, Castro CL, et al. Effects of subclinical hypothyroidism treatment on psychiatric symptoms, muscular complaints, and quality of life. Arq Bras Endocrinol Metabol. 2012;56(2):128-36.). Previously, a study reported that the presence of signals and symptoms of thyroid dysfunction may be related to decreased quality of life (1111. Klaver EI, van Loon HC, Stienstra R, Links TP, Keers JC, Kema IP, et al. Thyroid hormone status and health-related quality of life in the LifeLines Cohort Study. Thyroid. 2013;23(9):1066-73.). But it is difficult to distinguish sHT from the euthyroid only by signals and symptoms (2222. Biondi B, Cooper DS. The clinical significance of subclinical thyroid dysfunction. Endocr Rev. 2008;29(1):76-131.). This could explain the lack of difference in quality of life comparing these two groups in some studies (1111. Klaver EI, van Loon HC, Stienstra R, Links TP, Keers JC, Kema IP, et al. Thyroid hormone status and health-related quality of life in the LifeLines Cohort Study. Thyroid. 2013;23(9):1066-73.).

Regarding the quality of life, there is controversy concerned to the results of studies involving patients with sHT (33. Sgarbi JA, Teixeira PFS, Maciel LMZ, Mazeto GMFS, Vaisman M, Montenegro Junior RM, et al. Consenso brasileiro para a abordagem clínica e tratamento do hipotireoidismo subclínico em adultos: recomendações do Departamento de Tireoide da Sociedade Brasileira de Endocrinologia e Metabologia. Arq Bras Endocrinol Metabol. 2013;57(3):166-83.). In our study, a worse quality of life in women with sHT was observed, mainly through the reduction of functional capacity compared to the euthyroid ones. Corroborating our results, there are studies that observed lower scores of functional capacity in women with sHT, associated with the worst perceptions of health, vitality and emotional aspects (66. Vigário P Teixeira P Reuters V, Almeida C, Maia M, Silva M, et al. Perceived health status of women with overt and subclinical hypothyroidism. Med Princ Pract. 2009;18(4):317-22.88. Razvi S, McMillan CV, Weaver JU. Instruments used in measuring symptoms, health status and quality of life in hypothyroidism: a systematic qualitative review. Clin Endocrinol (Oxf). 2005;63(6):617-24.).

An earlier research found that patients with sHT showed lower scores in physical and psychological aspects and greater complaints related to fatigue, which cause damage to their daily activities (55. Gulseren S, Gulseren L, Hekimsoy Z, Cetinay P Ozen C,Tokatlioglu B. Depression, anxiety, health-related quality of life, and disability in patients with overt and subclinical thyroid dysfunction. Arch Med Res. 2006;37(1):133-9.). According to these authors, the decreased quality of life negatively influences mood and enhance anxiety and depression rates in sHT. In addition, studies showed lower functional capacity, general health and physical aspect (66. Vigário P Teixeira P Reuters V, Almeida C, Maia M, Silva M, et al. Perceived health status of women with overt and subclinical hypothyroidism. Med Princ Pract. 2009;18(4):317-22.) and worst health perception by patients with sHT, especially in the vitality factor, related to the psychological aspect (88. Razvi S, McMillan CV, Weaver JU. Instruments used in measuring symptoms, health status and quality of life in hypothyroidism: a systematic qualitative review. Clin Endocrinol (Oxf). 2005;63(6):617-24.). However, studies on Italy (99. Bianchi GP Zaccheroni V, Solaroli E, Vescini F Cerutti R, Zoli M, et al. Health-related quality of life in patients with thyroid disorders. Qual Life Res. 2004;13(1):45-54.), Australia (1010. Bell RJ, Rivera-Woll L, Davison SL, Topliss DJ, Donath S, Davis SR. Well-being, health-related quality of life and cardiovascular disease risk profile in women with subclinical thyroid disease - a community-based study. Clin Endocrinol (Oxf). 2007;66(4):548-56.) and Netherlands (1111. Klaver EI, van Loon HC, Stienstra R, Links TP, Keers JC, Kema IP, et al. Thyroid hormone status and health-related quality of life in the LifeLines Cohort Study. Thyroid. 2013;23(9):1066-73.) populations prove no worsening in quality of life in patients with sHT.

Studies have earlier identified worst quality of life in sHT (99. Bianchi GP Zaccheroni V, Solaroli E, Vescini F Cerutti R, Zoli M, et al. Health-related quality of life in patients with thyroid disorders. Qual Life Res. 2004;13(1):45-54.,1111. Klaver EI, van Loon HC, Stienstra R, Links TP, Keers JC, Kema IP, et al. Thyroid hormone status and health-related quality of life in the LifeLines Cohort Study. Thyroid. 2013;23(9):1066-73.). The results could be related not for disease diagnosis itself, but by the fact that patients are labeled as “sick” or their conscience are sick. Quality of life is a multidimensional and subjective construct, difficult for defining and systematization, which makes complex its operationalization (2323. Pucci GCMF, Rech CR, Fermino RC, Reis RS. Associação entre atividade física e qualidade de vida em adultos. Rev Saude Publica. 2012;46(1):166-79.). This, in part, could explain the divergent results reported in previous studies. Furthermore, another explanation would be no standardization of the criteria for assessing quality of life (2424. Conn VS, Hafdahl AR, Brown LM. Meta-analysis of quality-of-life outcomes from physical activity interventions. Nurs Res. 2009;58(3):175-83.).

In the follow-up study, exercise training improves HRQoL after four months of intervention. There were increased domain scores for functional capacity, general aspects of health, emotional aspects and psychological and physical component. After 4 months of training, the patients had functional capacity values, general health, emotional aspects and higher mental and physical component of the normative values of Brazilian healthy women of the same age (2525. Laguardia J, Campos MR, Travassos C, Najar AL, Anjos LA, Vasconcelos MM. Dados normativos brasileiros do questionário Short Form-36 versão 2. Rev Bras Epidemiol. 2013;16(4):889-97). Similar benefits were observed by other researchers (1616. Garces-Arteaga A, Nieto-Garcia N, Suarez-Sanchez F,Triana-Reina HR, Ramírez-Vélez R. Influence of a medium-impact exercise program on health-related quality of life and cardiorespiratory fitness in females with subclinical hypothyroidism: an open-label pilot study. J Thyroid Res. 2013;2013:592801.), who conducted a study which evaluates the influence of a medium impact exercise program in relation to quality of life and cardiorespiratory fitness of women with sHT. Participants were subjected to a program that consisted of activity for 3 weekly sessions of 60 minutes during 12 weeks. After 12 weeks of intervention, women showed improvement in quality of life, through a higher score in most domains of SF-36, especially in relation to vitality, general health, social aspects of health and mental health. Furthermore, participants who were subjected to exercise program increased their cardiovascular fitness. In patients with subclinical hyperthyroidism it was found improvement in relation to the disease symptoms, especially in the perception of fatigue after 12 weeks of aerobic training (1717. Vigário Pdos S, Chachamovitz DS, Cordeiro MF, Teixeira Pde F, de Castro CL, de Oliveira FP, et al. Effects of physical activity on body composition and fatigue perception in patients on thyrotropin- suppressive therapy for differentiated thyroid carcinoma. Thyroid. 2011;21(7):695-700.).

It is unknown the actual mechanism responsible for the psychological effects of physical exercise, although it is recognized that it is an interaction of psychophysiological factors. In patients with coronary artery disease, for example, poor quality of life is associated to reduced exercise ability (1414. Imayama I, Alfano CM, Mason CE, Wang C, Xiao L, Duggan C, et al. Exercise adherence, cardiopulmonary fitness and anthropometric changes improve exercise self-efficacy and health-related quality of life. J Phys Act Health. 2013;10(5):676-89.,1515. Staniute M, Bunevicius A, Brozaitiene J, Bunevicius R. Relationship of health-related quality of life with fatigue and exercise capacity in patients with coronary artery disease. Eur J Cardiovasc Nurs. 2014;13(4):338-44.) and more tendency to fatigue (1515. Staniute M, Bunevicius A, Brozaitiene J, Bunevicius R. Relationship of health-related quality of life with fatigue and exercise capacity in patients with coronary artery disease. Eur J Cardiovasc Nurs. 2014;13(4):338-44.). It is known that physical exercise is the main intervention used for physical fitness improvement and that it is positively related to quality of life (1414. Imayama I, Alfano CM, Mason CE, Wang C, Xiao L, Duggan C, et al. Exercise adherence, cardiopulmonary fitness and anthropometric changes improve exercise self-efficacy and health-related quality of life. J Phys Act Health. 2013;10(5):676-89.,1515. Staniute M, Bunevicius A, Brozaitiene J, Bunevicius R. Relationship of health-related quality of life with fatigue and exercise capacity in patients with coronary artery disease. Eur J Cardiovasc Nurs. 2014;13(4):338-44.,2323. Pucci GCMF, Rech CR, Fermino RC, Reis RS. Associação entre atividade física e qualidade de vida em adultos. Rev Saude Publica. 2012;46(1):166-79.,2626. Gillison FB, Skevington SM, Sato A, Standage M, Evangelidou S. The effects of exercise interventions on quality of life in clinical and healthy populations; a meta-analysis. Soc Sci Med. 2009;68(9):1700-10.). A systematic review to assess the association between physical activity and quality of life found that, in cross-sectional and longitudinal studies, the highest level of physical activity was related to a better perception of quality of life in apparently healthy adults or in different conditions of disease, regardless of sex (2323. Pucci GCMF, Rech CR, Fermino RC, Reis RS. Associação entre atividade física e qualidade de vida em adultos. Rev Saude Publica. 2012;46(1):166-79.). Moreover, a meta-analysis concluded that individuals with chronic diseases who received intervention to increase the level of physical activity improved their quality of life and that those who received supervised interventions showed the best result (2424. Conn VS, Hafdahl AR, Brown LM. Meta-analysis of quality-of-life outcomes from physical activity interventions. Nurs Res. 2009;58(3):175-83.).

In clinical practice, the decision for whether or not treating the patient with sHT is connected to observed signals and symptoms, including patient complaints (33. Sgarbi JA, Teixeira PFS, Maciel LMZ, Mazeto GMFS, Vaisman M, Montenegro Junior RM, et al. Consenso brasileiro para a abordagem clínica e tratamento do hipotireoidismo subclínico em adultos: recomendações do Departamento de Tireoide da Sociedade Brasileira de Endocrinologia e Metabologia. Arq Bras Endocrinol Metabol. 2013;57(3):166-83.). Treatment with levothyroxine is generally associated with reduced pain, improvements in overall health and physical aspects (1313. Reuters VS, Almeida Cde P Teixeira Pde F Vigário Pdos S, Ferreira MM, Castro CL, et al. Effects of subclinical hypothyroidism treatment on psychiatric symptoms, muscular complaints, and quality of life. Arq Bras Endocrinol Metabol. 2012;56(2):128-36.), but not necessarily with better quality of life (2727. Burns RB, Bates CK, Hartzband P, Smetana GW. Should We Treat for Subclinical Hypothyroidism?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center. Ann Intern Med. 2016;164(11):764-70.,2828. Rugge JB, Bougatsos C, Chou R. Screening and treatment of thyroid dysfunction: an evidence review for the U.S. Preventive Services Task Force. Ann Intern Med. 2015;162(1):35-45.). In the present study, from the clinical point of view, the improvement observed in the quality of life of patients after physical training was moderate to high magnitude (> 10 points in SF-36 scales) (2121. Osoba D, Rodrigues G, Myles J, Zee B, Pater J. Interpreting the significance of changes in health-related quality-of-life scores. J Clin Oncol. 1998;16(1):139-44.). Thus, it is plausible to speculate that the improvement in the quality life of patients with sHT may be due to increased level of physical activity, physical fitness improvement and reduced signals and symptoms. Therefore, physical activity can be used as a strategy to improve health perception of these patients and should be encouraged by doctors and stimulate as a key element for the adoption of a healthy lifestyle for patients with sHT. Furthermore, the assessment of quality of life should be used in the diagnostic of these patients.

It is known that most patients with sHT tend to normalize spontaneously the TSH, especially those with TSH < 10 mIU/l. This normalization has no a well - defined pattern, although most patients may normalize their TSH levels between 6 and 18 months (2929. Díez JJ, Iglesias P, Burman KD. Spontaneous normalization of thyrotropin concentrations in patients with subclinical hypothyroidism. J Clin Endocrinol Metab. 2005;90(7):4124-7). In this same study, more than half of the patients had negative anti-TPO, and the changes in TSH were not correlated to the presence of anti-TPO (2727. Burns RB, Bates CK, Hartzband P, Smetana GW. Should We Treat for Subclinical Hypothyroidism?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center. Ann Intern Med. 2016;164(11):764-70.). In this study, all patients practically showed TSH < 10 mIU/l. The effects of physical training on thyroid hormones are still a matter of debate in the literature and should be investigated in further studies. As limitations of the study, include the small sample size and the performed research only with women, not allowing, thus, expanding the results for male individuals.

In conclusion, the results suggest that women with subclinical hypothyroidism tend to have consistently lower scores on domains of quality of life compared to euthyroid women. However, physical exercise has been able to adjust these losses and therefore, should be encouraged in this group of patients. Further studies are necessary to better understand the optimal dose and the type of exercise would be more efficient to improve quality of life in women with sHT.

Acknowledgements

this study was funded by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Universidade Federal de Ouro Preto (UFOP).

  • Disclosure: no potential conflict of interest relevant to this article was reported.

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Publication Dates

  • Publication in this collection
    Oct 2018

History

  • Received
    12 Mar 2018
  • Accepted
    16 July 2018
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