Assessment of Lung Dysfunction with Spirometry in Patients with Thyroid Disorders

Abstract

Thyroid hormones might lead to significant decrease in pulmonary ventilation in patients with dysfunctional thyroid disorders. The aim of the study was to assess the pulmonary ventilation in patients with thyroid dysfunctional states. This observational, cross-sectional study included 20 patients with hyperthyroidism, 20 patients with hypothyroidism and 20 euthyroid subjects. Serum FT3, FT4 and TSH levels were determined with the ElectroChemiLuminiscent immunoassay. Spirometry analysis was performed on portable spirometer SpiroUSB using the software Spida 5 for the analysis. We determined VC%, FVC%, FEV1% and FVC/ FEV1% Mean VC% was significantly lower in hyperthyroid (94,18±1,24%) and hypothyroid (96,13±1,09%) compared to euthyroid group of subjects (98,54±0,93%)(p<0,05). Mean FVC% value was also significantly lower in hyperthyroid (92,5±1,47 %) and hypothyroid (94,1±1,42%) compared to euthyroid group of subjects (99,2±1,15%) (p<0,05). Mean FEV1% values in hyperthyroid and hypothyroid groups (90,97±2,07% and 87,6±1,4% respectively) were significantly lower compared to control, euthyroid group of subjects (93,48±1,1 %)(p<0,05). In patients with hyperthyroidism significant positive correlation was observed between serum TSH level and FVC% (r=0,51; p<0,05), while in patients with hypothyroidism a significant, negative correlation was observed between serum TSH level and VC% (r = -0,627; p<0,01) and between serum TSH level and FVC% values (r = -0,514; p<0,01). Our study confirmed significantly lower VC% and FVC% in patients with dysfunctional thyroid states compared to healthy subjects. In our study a significant association between VC%, FVC% and serum TSH levels suggest that duration and a degree of thyroid disorders lead to reduced ventilator lung function in patients with thyroid dysfunction.

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Assessment of Lung Dysfunction with Spirometry in Patients with Thyroid Disorders

Assessment of Lung Dysfunction with Spirometry in Patients with Thyroid Disorders

Salih Valjevac1, Almira Hadzovic-Dzuvo2, Amina Valjevac2, Elma Kucukalic-Selimovic3, Orhan Lepara2 Novo Nordisk Pharma d.o.o., Sarajevo, Bosnia and Herzegovina1Physiology Department, Medical Faculty, University of Sarajevo, Bosnia and Herzegovina2 Institute for Nuclear Medicine, Clinical Centre University of Sarajevo, Bosnia and Herzegovina3

Original paper

SUMMARYThyroid hormones might lead to significant decrease in pulmonary ventilation in patients with dysfunctional thyroid disorders. The aim of the study was to assess the pulmonary ventilation in patients with thyroid dysfunctional states. This observational, cross-sectional study included 20 patients with hyperthyroidism, 20 patients with hypothyroidism and 20 euthyroid subjects. Serum FT3, FT4 and TSH levels were determined with the ElectroChemiLuminiscent immuno-assay. Spirometry analysis was performed on portable spirometer SpiroUSB using the software Spida 5 for the analysis. We

determined VC%, FVC%, FEV1% and FVC/ FEV1% Mean VC% was significantly lower in hyperthyroid (94,181,24%) and hypothyroid (96,131,09%) compared to euthyroid group of subjects (98,540,93%)(p<0,05). Mean FVC% value was also significantly lower in hyperthyroid (92,51,47 %) and hypothyroid (94,11,42%) compared to euthyroid group of subjects (99,21,15%) (p<0,05). Mean FEV1% values in hyperthyroid and hypothyroid groups (90,972,07% and 87,61,4% respectively) were significantly lower compared to control, euthyroid group of subjects (93,481,1 %)(p<0,05). In patients with hyperthyroidism significant positive correlation was observed between serum TSH

level and FVC% (r=0,51; p<0,05), whilein patients with hypothyroidism a significant, negative correlation was observed between serum TSH level and VC% (r = -0,627; p<0,01) and between serum TSH level and FVC% values (r = -0,514; p<0,01). Our study confirmed significantly lower VC% and FVC% in patients with dysfunctional thyroid states compared to healthy subjects. In our study a significant association between VC%, FVC% and serum TSH levels suggest that duration and a degree of thyroid disorders lead to reduced ventilator lung function in patients with thyroid dysfunction.

Key words: thyroid dysfunction, spirometry, lung function

1. INTRODUCTION

Hyperthyroidism and hypothyroidism can cause disorders of respiratory function and disturbances of ventilation. Hypothyroidism is characterized by hypoventilation, while dyspnoea and hyperventilation are typical symptoms of hyperthyroidism. Ventilation responses to hypoxia and hypercapnia are reduced in hypothyroidism and increased in hyperthyroidism (1, 2).

Hyperthyroidism is associated with respiratory dysfunction, leading to an increase in respiratory rate, respiratory muscle weakness and pulmonary hypertension. The mechanism responsible for reduced pulmonary compliance in patients with hyperthyroidism is not clear, but there are several proposed theories: changes in functional residual capacity, pulmonary congestion and oedema, increased intrathoracic blood volume and chang-

es in the recoil of alveolar septa. Also, in patients with hyperthyroidism a signicant reduction in respiratory muscle strength particularly involving the diaphragm is common, which leads to reduced ventilation, especially during exercise (3). The prevalence of pulmonary arterial hypertension in patients with hyperthyroidism are 35%65% (4, 5). Studies that evaluated the static and dynamic parameters of pulmonary function with spirometry are inconsistent whether there is thyroid disease disorders lead to lung dysfunction. In patients with hyperthyroidism and hypothyroidism decreased values of vital capacity have been observed, while the values of forced vital capacity, forced expiratory volume were inconsistently decreased compared to healthy subjects (6, 7, 8). Assessment of pulmonary function with spirometry in patients with thyroid disorders are particu-

larly important, considering the fact that low levels of thyroid hormones can trigger bronchial hyperreactivity and obstructive pulmonary disorders. Although studies have shown that patients with hyperthyroidism are more prone to asthma exacerbation, it is not clear whether and to what extent the obstructive pulmonary disorder is present in patients with hyperthyroidism. Obstructive disease in patients with dysfunctional thyroid diseases may be due to direct eect of hormones on the lung function, but might also be due to the present cardiac diseases that oen accompany thyroid disorders. The aim of this study was to evaluate the lung ventilation in patients with thyroid disorders.

2. SUBjECTS AND METHODS

All participants of our study were selected from the subjects who performed control of thyroid hormon-

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Assessment of Lung Dysfunction with Spirometry in Patients with Thyroid Disorders

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Hyperthyroid group Hypothyroid group Euthyroid group VC% 94.18 1.24 96.13 1.09 98.54 0,93* FVC% 92.5 1.47 94.08 1.42 99.16 1.15* FEV1% 90.97 2.07 87.59 1.4 93.48 1.1* FEV1/FVC % 94,9 2,14 92,0 1,5 93,9 1,25 *significant difference between euthyroid and hyperthyroid and hypothyroid group

Table 1. Spirometry parameters in patients with thyroid dysfunction

FT3 FT4 TSH Hyperthyroidgroup

Hypothyroid group

Hyperthyroid group

Hypothyroid group

Hyperthyroid group

al status at the Institute of Nuclear Medicine, Clinical Centre of Sarajevo University, and had never been treated for thyroid dysfunction state. According to the serum FT3, FT4 and TSH values we included in total 60 subjects. Aer an overnight fast, all the subjects underwent full medical assessment, laboratory examinations. The exclusion criteria were: presence of clinically evident cardiovascular diseases, renal diseases, pituitary/hypothalamic disorders, diabetes mellitus and pregnancy. The study sample was divided into three, aged matched, groups: hyperthyroid group consisted of 20 subjects. Hyperthyroidism was dened by serum TSH level <0,1 mIU/L and increased serum FT4 level (>23 pmol/L). Hypothyroid group consisted of 20 subjects. Hypothyroidism was dened by serum TSH level >10 mIU/L and decreased serum FT4 level (<10 pmol/L). Euthyroid (control) group consisted of 20 subjects, with serum FT3, FT4 and TSH levels within the normal reference range. Approval for the study was obtained by the local Ethics Committee. All procedures on human subjects were performed in accordance with the latest version of Helsinki Declaration. All subjects included in the study signed an informed consent with careful explanation of the study procedures.

Blood samples were taken from all patients to determine their serum FT3, FT4 and TSH which were determined using electrochemiluminescence immunoassay ECLIA on Elecsys 2010 (Roche Diagnostic). All measurements were performed at the Institute of Nuclear Medicine, University of Sarajevo Clinics Centre. The analytic range extends from 535,00 pg/mL. Lung function parameters were analysed using portable SpiroUSB spirometer (Micro Medical, Auburn, Main, USA) connected to portable computer using the Spida 5 so-ware (Micro Medical, Auburn, Main, USA). We determined the parameters of the dynamic spirometry: VCvital capacity, FVCforced vital capacity, FEV 1Forced expiratory volume in the 1st second, the FVC/FEV1 ratio. Using Spida 5 soware, predicted values and the percentage of pre-

dicted values were calculated for VC VC%, FVCFVC%, FEV1FEV1% and FVC/FEV1FVC/FEV1% for each subject based on the subjects height, age and sex. For normal distributed variables, values are expressed as mean SEM. Dierences in mean between groups were tested using a t-test. Correlation between continuous variables was tested with Spearmans rank correlation analysis. Two-tailed p values < 0.05 were considered statistically signicant. Statistical analysis was performed using SPSS statistical soware system (version 16.0, SPSS Inc., Chicago, Illinois, USA).

3. RESULTS

Average VC%, FVC% and FEV1% values were signicantly lower in subjects with hyperthyroidism and in subjects with hypothyroidism compared to euthyroid subjects

In hyperthyroid group of subjects a signicant positive correlation between TSH and FVC% values (r = 0.51, p < 0.05) (Table 2). In the group of subjects with hypothyroidism a signicant positive correlation between serum FT3 levels and VC% (r = 0.54, p <0.05) was observed. There was also a negative correlation between serum TSH levels and VC% (r = -0.627, p <0.01) and between serum TSH levels and FVC% (r = -0.514, p < 0.01)

(Table 2) in subjects with hypothyroidism. In euthyroid group of subjects there was no signicant correlation between thyroid hormones, TSH and the ventilation parameters.

4. DISCUSSION

Examining the dynamic parameters of lung function we found a signicantly lower values of VC%, FVC% and FEV1% between the two groups with thyroid disorders and control euthyroid group. Our results in hyperthyroid group of subjects are consistent with the results of Kalahy et al. (9) who also found signicantly lower FVC% (90.3%) and FEV1% (88.6%) values in hyper-thyroid compared to euthyroid subjects. Goswami et al. (8) also found lower values of FVC% and FEV1% in hyperthyroid patients compared to healthy subjects. In the aforementioned study, aer adequate treatment aimed to lower levels of thyroid hormones, there was a significant increase in the value of VC, FEV1 and total lung capacity. The authors also found that conversion of hyperthyroid to euthyroid status signicantly enhances the strength of diaphragm contraction during deep inspiration. Respiratory muscle weakness or myopathy induced hyperthyroidism are possible explanations for the results observed in the study. In the above study, 88.8% of patients with hyperthyroidism had signs of dyspnoea, which may be caused by increased respiratory centre stimulation, increased airow resistance, decreased lung compliance and weakness of respiratory muscles (8).

Our results in hypothyroid subjects are consistent with the results of Martinez et al.(10) and Laden-son et al. (11) who also conrmed

Hypothyroid group

VC% r = -0,46 r = 0,54* r = -0,305 r = 0,414 r = 0,322 r = -0,627** FEV1% r = 0,245 r = 0,349 r = -0,213 r = 0,313 r = -0,01 r = -0,388 FVC% r = -0,218 r = -0,375 r = -0,38 r = -0,428 r = 0,51* r = -0,514* FEV1/FVC% r = 0,278 r = 0,122 r = -0,145 r = 0,057 r = -0,302 r = -0,011 rSpearman correlation coefitients; *p < 0,05

Table 2. Correlation coefficients between thyroid hormones and lung function parameters in hyperthyroid and hypothyroid group

| Original paper

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Assessment of Lung Dysfunction with Spirometry in Patients with Thyroid Disorders

that the hypothyroidism is associated with decreased vital capacity, FEV1, FVC and total lung capacity. The authors suggested that alveolar hypoventilation and decreased inspiratory muscle strength might be a possible explanation. Martinez et al. (10) have conrmed that patients with hypothyroidism develop diaphragmal dysfunction, which can vary from mild forms associated with reduced tolerance to physical eort, to very severe forms of diaphragmatic weakness which even might imitate diaphragmatic paralysis. The authors of the study showed that these changes are reversible with Levothyroxin therapy even aer only 8 weeks (10, 11).

The most common respiratory symptoms in patients suering with hypothyroidism are cough, shortness of breath and increased production of sputum (12). In patients with hypothyroidism the respiratory rate is decreased with subsequent hypoventilation which leads to mild hypercapnia. Hypercapnia stimulates the respiratory centre, which cannot respond to an increased need for ventilation due to the decreased levels of thyroid hormones (12). In addition, decreased levels of thyroid hormones lead to decreased expression of -adrenergic receptors which oen causes bronchial tree hyper reactivity. Birring et al (12) noted that in patients with low levels of thyroid hormone there is an increased sensitivity of the cough reex, and increased airway hyper responsiveness, and an increased number of inammatory cells in sputum. Obstructive sleep apnoea is a common symptom in patients with hypothyroidism. In hypothyroidism, deposits of mucopolysaccharides and protein extravasations lead to oedema favouring the development of obstructive sleep apnoea (7). In our study, the average values of VC%, FVC% and FEV1% in both hyperthyroid and in hypothyroid group were within the reference value. A possible explanation for these results is the fact that the study had included patients with subclinical and clinical hyperthyroidism and hypothyroidism. Since we wanted to avoid the eects of therapy on the respiratory function, we chose

the newly diagnosed patients with thyroid disorders. Cakmak et al. (13) found that in patients with subclinical hypothyroidism there is a signi-cant reduction in lung function. The authors evaluated the parameters of lung function in patients with sub-clinical hypothyroidism and in the control, healthy group of subjects and found signicantly lower values of FVC, FVC%, FEV1 and FEF25-75 in patients with subclinical hypothyroidism. In our study, we observed signicant positive correlation between serum levels of TSH and FVC% in hyperthyroid subjects. Low TSH levels suggest longer duration of disease, and in these subjects FVC% were signicantly lower. In hypothyroid subjects we also found negative correlation between serum levels of TSH and FVC%, and between TSH and VC%. In our hypothyroid group of subjects serum TSH levels ranged from 5 mIU / L to 20mIU / L. These ndings suggest that the higher levels of TSH, the longer duration of illness, is associated with lower FVC% values. In patients with hypothyroidism we found statistically signicant positive correlation between FT3 and VC%. However, in euthyroid subjects we found no signicant correlation between thyroid hormones and parameters of lung function. Our results therefore support the thesis that the degree and the duration of thyroid disorder is associated with lower FVC% values and poor pulmonary function. Cakmak et al. (13) in group of patients with clinical hypothyroidism, found a signicant negative correlation between TSH and FVC%. Also, in their study a signicant positive correlation between FT3 and FEF25-75, FEF25-75%, PEF and% PEF values was observed. In patients with subclinical hypothyroidism the authors also found a signicant positive correlation between FT4 and FEF25-75, FVC and FVC% values. The causes for the above association between thyroid dysfunction and ventilation can be numerous. In patients with hypothyroidism the causes for reduced respiratory function are decreased inspiratory muscle strength, hypoventilation, hypercapnia, increased bronchial reactivity, pleural eusion and protein

extravasations into the tissue which can lead to oedema. In patients with hyperthyroidism, possible mechanisms responsible for reduction in respiratory function are increased respiratory rate, respiratory muscle weakness, reduced lung compliance, pulmonary congestion and oedema, increased intrathoracic blood volume, and pulmonary hypertension.

5. CONCLUSION

Our study showed that a thyroid disorders causing hyperthyroidism and hypothyroidism could cause disorders of respiratory function and ventilation.

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Corresponding author: Salih Valjevac, MD. Novonordisk, Sarajevo, Bosnia and Herzegovina. E-mail: [email protected]

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