End-tidal CO₂ levels lower in subclinical and overt hypothyroidism than healthy controls; no relationship to thyroid function tests

Background: Hypoventilation is a frequently suspected complication of hypothyroidism. Objective: In this study we examined the hypothesis that changes in alveolar ventilation, as measured by end-tidal carbon dioxide (Et-CO₂), differ between patients with mild (subclinical) and overt (clinical) thyroid hormone deficiency, and both differ from healthy control subjects. Methods: A total of 95 subjects, including 33 with subclinical hypothyroidism (an elevated thyroid-stimulating hormone (TSH) level and a normal thyroxin (fT₄) level), 31 with overt hypothyroidism (elevated TSH and decreased fT₄), and 31 healthy controls. All subjects were female and were evaluated clinically by an endocrinologist for evidence of thyroid disease and categorized on the basis of thyroid hormone levels. Et-CO₂ was measured using a capnograph. Et-CO₂ levels were measured three times and the mean value was considered as the mean level for the individual. Results: Mean Et-CO₂ values of the subclinical hypothyroidism group were significantly lower than those of the healthy controls (31.79 ± 2.75 vs 33.81 ± 2.38; P = 0.01). Moreover, mean Et-CO₂ values for the overt hypothyroidism group were significantly lower than those for healthy controls (32.13 ± 3.07 vs 33.81 ± 2.38; P = 0.04). There was a significant correlation between Et-CO₂ values and TSH levels (r = -0.24; P = 0.01). However, Et-CO₂ values were not correlated with fT₄ levels (r = 0.13; P = 0.20). Conclusions: Alveolar ventilation, as inferred from lower Et-CO₂ levels, is higher in subjects with subclinical hypothyroidism and overt hypothyroidism (lower Et-CO₂) than in healthy controls. Furthermore, Et-CO₂ levels have no relationship to the levels of TSH or fT₄. The lower Et-CO₂ in these patients with hypothyroidism, particularly at the subclinical stage, suggests presence of hyperventilation, which may be related to direct effect of TRH on respiratory center or to local changes within the lung.