Respiratory Manifestations of Hypothyroidism: A Systematic Review

Background: Hypothyroidism has been associated with increased pulmonary morbidity and overall mortality. A systematic review was conducted to identify the prevalence and underlying mechanisms of respiratory problems among patients with thyroid insufficiency. Methods: PubMed and EMBASE databases were searched for relevant literature from January 1950 through January 2015 with the following study eligibility criteria: English-language publications; adult subclinical or overt hypothyroid patients; intervention, observational, or retrospective studies; and respiratory manifestations. The Preferred Reporting Items for Systematic reviews and Meta-Analyses statement was followed, and Cochrane's risk of bias tool was used. Results: A total of 1699 papers were screened by two independent authors for relevant titles. Of 109 relevant abstracts, 28 papers underwent full-Text analyses, of which 22 were included in the review. Possible mechanisms explaining respiratory problems at multiple physiological levels were identified, such as the ventilator control system, diaphragmatic muscle function, pulmonary gas exchange, goiter caused upper airway obstruction, decreased capacity for energy transduction, and reduced glycolytic activity. Obstructive sleep apnea syndrome was found among 30% of newly diagnosed patients with overt hypothyroidism, and demonstrated reversibility following treatment. The evidence for or against a direct effect on pulmonary function was ambiguous. However, each of the above-mentioned areas was only dealt with in a limited number of studies. Therefore, it is not possible to draw any strong conclusions on any of these themes. Moreover, most studies were hampered by considerable risk of bias due for example to small numbers of patients, lack of control groups, randomization and blinding, and differences in body mass index, sex, and age between subjects and controls. Conclusion: Mechanistic data linking hypothyroidism and respiratory function are at best limited. This area of research is therefore open for retesting hypotheses, using appropriate study designs and methods.