Spirometry in Patients with Clinical and Subclinical Hypothyroidism

Hypothyroidism is defined as a clinical state resulting from insufficient secretion of thyroid hormone from thyroid gland due to some structural or/and functional impairments in thyroid hormone production (Kek PC et al., 2003, Dashe JS & Cunningham FG., 2001). Hypothyroidism effects all of the organ systems. Main clinical findings are fatigue, weakness, dryness and coarseness of the skin, cold intolerance, swelling of the extremities, hair loss, lack of concentration and memory, constipation, weight gain without loss of appetite, dyspnea, hoarseness of speech, menorrhagia, paraesthesia, hearing disorders, diffuse alopecia, bradycardia, delayed relaxation of tendon reflexes, carpal tunnel syndrome and serous cavitary effusions (Kek PC et al., 2003). All of these signs and symptoms recover after replacement of thyroid hormone (Larsen PR & Davies TF, 2003, Fatourechi V., 2001).). Subclinical hypothyroidism reflects the earliest stage of thyroid dysfunction with subjects having normal or decreased fT4, normal fT3 and decreased TSH levels. Since diagnosis depends on laboratory values, theoretically, no symptoms or signs are expected but yet patients may suffer from somnolence, weakness and fatigue (Kek PC et al., 2003).


Introduction
Hypothyroidism is defined as a clinical state resulting from insufficient secretion of thyroid hormone from thyroid gland due to some structural or/and functional impairments in thyroid hormone production (Kek PC et al., 2003, Dashe JS & Cunningham FG., 2001. Hypothyroidism effects all of the organ systems. Main clinical findings are fatigue, weakness, dryness and coarseness of the skin, cold intolerance, swelling of the extremities, hair loss, lack of concentration and memory, constipation, weight gain without loss of appetite, dyspnea, hoarseness of speech, menorrhagia, paraesthesia, hearing disorders, diffuse alopecia, bradycardia, delayed relaxation of tendon reflexes, carpal tunnel syndrome and serous cavitary effusions (Kek PC et al., 2003). All of these signs and symptoms recover after replacement of thyroid hormone (Larsen PR & Davies TF, 2003, Fatourechi V., 2001.).
Subclinical hypothyroidism reflects the earliest stage of thyroid dysfunction with subjects having normal or decreased fT 4 , normal fT 3 and decreased TSH levels. Since diagnosis depends on laboratory values, theoretically, no symptoms or signs are expected but yet patients may suffer from somnolence, weakness and fatigue (Kek PC et al., 2003).
In the English literature there exsists several studies revealing the effect of clinical hypothyroidism on respiratory and cardiovascular systems but we were not able to find any comparative effect of subclinical hypothyroidism on these systems. In this study we evaluated the respiratory function in subclinical hypothyroidism as well as comparing the results with clinical hypothyroidism and healthy control groups. Our aim was to determine if respiratory function was effected in subclinical hypothyroidism by using simple spirometry.

Materials and methods
Two hundred and sixty-seven subjects were enrolled in the study. None of the participants had a history of smoking, any respiratory illness or any other systemic pathology affecting the respiratory system. The patients did not suffer from goitre disturbing the respiratory function. The body mass indices (BMI) of all of the participants were under 30 kg/m 2 . Following the approval of the local ethics committee written informed consent was obtained from all of the participants.
Serum fT 3 , fT 4 levels were assessed by Chemiluminescent Competitive Enzyme Immunoassay method with Immulite 2000 of BIODPC. Serum TSH analysis was performed by Enzyme Chemiluminescent Immunometric Assay method with the same analyser. Normal range for TSH was <4.0 uIU/ml, 1.57-4.71 ng/ml for fT 3 , and 0.8-1.8 ng/ml for fT 4 . If the patients' serum fT 3 level was between 1.57-4.71 ng/ml, fT 4 was between 0.8-1.8 ng/ml and TSH level was >4.0 uIU/ml, they were included in the subclinical hypothyroidism group. On the other hand, if their serum levels of fT 3 was <1.57 ng/ml, fT 4 <0.8 ng/ml and TSH was >4.0 uIU/ml; they were included in the clinical hypothyroidism group. The control group consisted of subjects having normal fT 3 , fT 4 and TSH values.
The mean and standard deviation of parametric values were assessed with Students'-t test and ANOVA. Chi-square test was used when assessing the percentages of the groups and Pearson correlation was used to compare the groups. P<0.05 was considered as significant.

Results
Among 120 patients enrolled into the study with subclinical hypothroidism, 114 of them were women and 6 were men while there were 86 women and 3 male patients with clinical hypothyroidism. Control group consisted of 51 women and 9 men. The mean age of the patients was 43±13 years and 41±13 years with subclinical hypothyroidism and clinical hypothyroidism, respectively. The mean age was 41±12 years in the control group. There was not a significant difference between groups regarding age (

Conclusion
Hypothyroidism and subclinical hypothyroidism is a clinical disorder occuring frequently in community. Literature research reveals many studies regarding the effects of clinical hypothyroidism on respiratory and cardiovascular systems. But there exists no study concerning the effect of subclinical hypothyroidism on respiratory system nor there exists any study comparing healthy subjects to clinical hypothyroid patients in terms of respiratory function tests. Therefore we aimed to assess the respiratory function of patients with subclinical hypothyroidism in comparison with clinical hypothyroidism and healthy subjects.
The incidence of primary hypothyroidism is 2% in women and 0.2% in men.
Hypothyroidism effects all of the organ systems (Kek PC et al., 2003, Larsen PR & Davies TF, 2003. The clinical presentation of thyroid hormone deficiency alters from one person to another depending on the duration, cause and the degree of deficiency. The decrease in both expiratory and inspiratory muscle strength (Siafakas NM et al., 1992), alveolar hypoventilation due to depression of hypoxic and hypercapnoeic ventilatory drives (Kahaly GJ, 2000) and decrease in maximal breathing and diffusing capacity (Zwillich CW et al., 1975) are evident in patients with hypothyroidism. These impairments are reversible with hormone replacement therapy. Respiratory infections are more common than healthy people (Harrison RN & Tattersfield AE., 1984, Krishnan R et al., 1984. Obstructive sleep apnea syndrome is common in severe hypothyroidism but it is reversible with restoration of a euthyroid state (Larsen PR & Davies TF, 2003). The prominent features like somnolence, apathy and lethargy may also recover with replacement therapy (Krishnan R et al., 1984, Jameson JL & Weetman AP, 2001. Muscle strength measurement and sleep investigation is not routine analysis in these patients, so simple spirometric evaluation is preferred. Thus, we used only spirometric measurements in our study since this method is easier, more available and cheaper than other respiratory function tests. Siafakas et al. found a significant decrease in the strength of inspiratory and expiratory muscles in patients with clinical hypothyroidism. In the mentioned study, vital capacity (VC), forced vital capacity (FVC), forced vital capacity one second (FEV 1 ), FEV 1 /FVC were significantly lower in patients with clinical hypothyroidism compared to healtly controls. In our study, the patients with clinical hypothyroidism had significantly lower spirometric parameters such as vital capacity (VC), forced vital capacity (FVC), forced vital capacity in one second (FEV 1 ), FEV 1 /FVC, peak expiratory flow (PEF) and forced expiratory flow 25-75 (FEF 25-75) than control group.
Subclinical hypothyroidism reflects the earliest stage of thyroid dysfunction. Chronical autoimmune thyroiditis, subacute thyroiditis, thyroidectomy, radioactive iodine treatment, insufficient thyroid hormone replacement therapy may be the cause of subclinical hypothyroidism. The rate of progression to clinical hypothyroidism from subclinical hypothyroidism is about 7,8 %-17,8 %. Initiating therapy doesn't change the natural course of the illness, but it prevents the progression of clinical hypothyroidism , Surks MI & Ocampo E., 1996.
Subclinical hypothyroidism is a common phenomenon seen more often in women with increasing age. The prevalance in women is 6-8 % and 3 % in men (Kek PC et al., 2003, Surks MI & Ocampo E., 2004. In our study 114 female and 6 male patients had subclinical hypothyroidism. Theoretically no symptoms or findings are expected in subclinical hypothyroidism. On the contrary, almost all of our patients suffered from at least one or more of the symptoms like fatigue, weakness and somnolence. This situation revealed that clinical findings also associated to spirometric abnormalities. Fatigue is observed in subclinical hypothyroidism because of muscle dysfunction. Diagnosis depends on laboratory evaluation. (Kahaly GJ, 2000.
The effect of subclinical hypothyroidism on several organ systems are well known, whereas the effect on respiratory system is not fully understood (Col NF et al., 2004, Beyer IW et al., 1998. The study we designed led us to the conclusion that the measurements of spirometric variables are higher in subclinical hypothyroidism than in clinical hypothyroidism but lower than healthy subjects reaching statistical significance.
In conclusion it is possible to claim that respiratory system is effected in subclinical hypothyroidism. Since subclinical hypothyroidism is common in general population, the patients at high risk who had clinical signs and symptoms may be screened with simple spirometry.