INTRODUCTION — Many thyroid diseases can lead to pulmonary problems, including hypothyroidism, hyperthyroidism, nodular goiter, and thyroid cancer. Both hypothyroidism and hyperthyroidism cause respiratory muscle weakness and decrease pulmonary function. Hypothyroidism reduces respiratory drive and can cause obstructive sleep apnea or pleural effusion, while hyperthyroidism increases respiratory drive and can cause dyspnea on exertion. Compression of the trachea, which may be positional, can occur with nodular goiters and thyroid cancer, and the latter can metastasize to the lungs.
HYPOTHYROIDISM
Depressed ventilatory drive — Some patients with hypothyroidism have alveolar hypoventilation [1]. In the extreme case of myxedema coma, there can be marked hypercapnia [2]. Severe hypothyroidism is associated with marked depression in hypoxic ventilatory drive and hypercapnic ventilatory drive, whereas less severe hypothyroidism (T4 [levothyroxine] replacement therapy stopped for three weeks) causes a moderate reduction in hypoxic ventilatory drive (figure 1 and figure 2) [3,4]. In one small study, the depression in hypoxic ventilatory drive, but not hypercapnic ventilatory drive, significantly improved with T4 therapy [3]. In another study, parenteral thyroid hormone replacement therapy for one week improved hypoxic and hypercapnic ventilatory responses in the subset of hypothyroid patients with pretreatment blunted responses [4].
Respiratory muscle weakness — Skeletal muscle myopathy occurs with hypothyroidism [5]; in animal studies, the proportion of type 1 fibers of the diaphragm and intercostal muscles decreased four weeks after total thyroidectomy [6]. Respiratory muscle strength is reduced in patients with hypothyroidism and improves with treatment; the reduction is caused by both a myopathy and neuropathy. In a study of six patients, maximal expiratory and inspiratory pressures were reduced and improved with treatment [7]. In a study of 43 hypothyroid patients, respiratory muscle weakness correlated with the degree of hypothyroidism [8]. The degree of weakness is usually mild to moderate, but there have been case reports of patients with marked weakness [9]. With treatment, respiratory muscle strength improves [8,9].
Pulmonary function — Changes in spirometry in hypothyroidism include mildly lower forced vital capacity (FVC) and lower forced expired flow [10]. Vital capacity improves with T4 treatment [8,9]. Nonobese hypothyroid patients have normal lung volumes, whereas obese hypothyroid patients have moderate reductions in lung volumes.
Carbon monoxide diffusing capacity (DLCO) may be low and increase during treatment; in one study, the mean value was 63 percent of the predicted value before and 93 percent during [1]. The reasons for the low DLCO and its improvement are unclear.
Cardiopulmonary exercise performance is also reduced with hypothyroidism [10] and improves with treatment [11]. In a study of patients with newly diagnosed hypothyroidism, besides lower FVC and DLCO, hypothyroid patients had worse maximal exercise testing parameters including oxygen consumption (62 versus 100 percent), minute ventilation (38.9 L versus 69.3 L), tidal volume (1.05 L versus 2.18 L), and oxygen pulse (89.5 versus 131), with higher breathing reserve (62.5 versus 39.3 percent) [10]. The effects of hypothyroidism on mitochondrial metabolism and skeletal muscles may contribute to exercise intolerance [12].
Respiratory failure — Hypothyroidism should be considered in patients with respiratory failure who are difficult to wean. In a study of 121 ventilator-dependent patients, four were found to have severe hypothyroidism [13]; weaning was aided by treatment with T4.
Pleural effusions — Pleural and also pericardial and peritoneal effusions can occur in patients with severe chronic hypothyroidism [14,15]. The effusions are exudates, indicative of increased capillary permeability [16]. Among patients with hypothyroidism, however, most pleural effusions have causes other than the hypothyroidism alone [17].
Obstructive sleep apnea — Obstructive sleep apnea is more common among patients with hypothyroidism. In one study of 11 patients with newly diagnosed hypothyroidism, nine had marked sleep apnea [18], with 72 episodes per hour; the number decreased to 13 episodes per hour after treatment with T4 for 3 to 12 months, without weight loss (figure 3). A study from Taiwan [19] found a lower incidence of obstructive sleep apnea among newly diagnosed hypothyroid patients (5 of 20); unsuspected hypothyroidism was present in 2 of 65 (3 percent) patients with newly diagnosed obstructive sleep apnea. Possible mechanisms for obstructive sleep apnea in patients with hypothyroidism include depressed ventilatory drive and narrowing of the airway due to enlargement of the tongue, pharynx, or larynx due to mucinous edema (myxedema).
Pulmonary hypertension — Thyroid dysfunction, primarily mildly elevated thyroid-stimulating hormone (TSH) consistent with subclinical hypothyroidism, is common among patients with idiopathic pulmonary hypertension [20,21], and autoimmune thyroid disease has been found increased among patients with pulmonary hypertension [22,23].
Pulmonary fibrosis — In a systemic review, hypothyroidism was associated with increased likelihood of fibrosis of the liver, heart, and lung [24]. The mechanisms of how hypothyroidism could promote fibrosis are uncertain; proposed mechanisms include extracellular matrix accumulation, mitochondrial dysfunction, and associated autoimmune processes.
HYPERTHYROIDISM
Increased ventilatory drive — Hyperthyroidism is associated with an increased ventilatory drive in response to hypoxemia and hypercapnia. With exercise, hyperthyroid patients are more dyspneic than normal subject controls for the same level of work, but there is no difference in dyspnea for the same level of ventilation [25]. Thus, increased ventilatory drive seems to account for dyspnea on exertion in hyperthyroid patients [25]. The mechanism for increased ventilatory drive is uncertain, but beta-adrenergic blockade reduces it to normal, suggesting that adrenergic stimulation plays a role [25].
Respiratory muscle weakness — Hyperthyroidism causes respiratory muscle weakness [26,27]. In a study of 20 hyperthyroid patients, both maximal expiratory and inspiratory pressures fell with increasing degrees of hyperthyroidism [27]. Respiratory muscle force increased to normal after treatment. Hyperthyroidism can also cause abnormalities in pulmonary function, with reductions in forced expiratory volume in 1 second (FEV1) and vital capacity that improves with treatment [27,28].
Pulmonary hypertension — Pulmonary hypertension, a known complication of neonatal thyrotoxicosis, has also been reported in adults with hyperthyroidism, with over 70 percent of cases occurring in women [29-32]. The mechanism of pulmonary hypertension in these patients is unclear, but pulmonary pressures drop with institution of medical therapy for the hyperthyroidism [29,30,33].
GOITER — Retrosternal goiters have the greatest part of their mass within the chest. They are found in 2 to 6 percent of patients undergoing thyroidectomy [34] and comprise 5 to 11 percent of all mediastinal tumors resected at thoracotomy [35]. Larger cervical or retrosternal goiters can cause tracheal compression with symptoms of cough, nocturnal dyspnea, wheezing, and stridor [36]. While most retrosternal goiters are in the anterior mediastinum, they can occur in the posterior mediastinum, as well [37]. The effect of goiters on flow-volume loop studies of upper airway patency can be positional, with findings of upper airway obstruction present only in the supine position [38,39]. (See "Clinical presentation and evaluation of goiter in adults", section on 'Obstructive symptoms' and "Flow-volume loops".)
Patients with large goiters causing symptoms related to pressure on the trachea, esophagus, or great vessels are usually treated by thyroidectomy, but radioiodine therapy will result in some decrease in goiter size. (See "Treatment of obstructive or substernal goiter".)
AUTOIMMUNE THYROID DISEASE — Patients with treated autoimmune hypothyroidism (Hashimoto's thyroiditis) have more pulmonary symptoms (cough, dyspnea, and sputum), heightened cough reflex sensitivity, increased airways responsiveness, and increased markers of sputum inflammation than controls [40]. In addition, significantly higher titers of thyroid peroxidase (TPO) antibodies have been found in women with than without asthma [41]. It is possible that the association of Hashimoto's thyroiditis and TPO antibodies with pulmonary symptoms may reflect a related autoimmune process that affects pulmonary function. Similarly, there may be an association between autoimmune thyroid disease and pulmonary hypertension. (See 'Pulmonary hypertension' above.)
THYROID CANCER AND THE LUNG — Thyroid cancer can metastasize to the lung. In a study of 1127 patients, 101 (9 percent) had pulmonary metastases [42]. The incidence of pulmonary metastasis was lowest in patients with papillary carcinoma (9 percent), compared with that in patients with follicular (13 percent) or Hürthle cell (25 percent) carcinoma. However, since papillary carcinoma is much more common, it was the most common cause of pulmonary metastases (69 percent), as compared with follicular carcinoma and Hürthle cell carcinoma.
Pulmonary metastases are often treated with radioiodine therapy [43,44]. It is unusual for there to be pulmonary damage with radioiodine therapy for lung metastases of thyroid cancer, but radiation pneumonitis can occur [43]. (See "Differentiated thyroid cancer: Radioiodine treatment".)
SUMMARY — Many thyroid diseases can lead to pulmonary problems, including hypothyroidism, hyperthyroidism, nodular goiter, and thyroid cancer.
●Hypothyroidism – Hypothyroidism reduces respiratory drive, causes respiratory muscle weakness, and can cause obstructive sleep apnea and pleural effusion. (See 'Hypothyroidism' above.)
●Hyperthyroidism – Hyperthyroidism is associated with an increased ventilatory drive in response to hypoxemia and hypercapnia, which is perceived by the patient as dyspnea, particularly with exertion. Hyperthyroidism may also cause respiratory muscle weakness and pulmonary hypertension. (See 'Hyperthyroidism' above.)
●Goiter – Larger cervical or retrosternal goiters can cause tracheal compression with symptoms of cough, nocturnal dyspnea, wheezing, and stridor. (See 'Goiter' above and "Clinical presentation and evaluation of goiter in adults", section on 'Obstructive symptoms'.)
●Thyroid cancer – Papillary, follicular, and Hürthle cell thyroid cancer can metastasize to the lung. (See 'Thyroid cancer and the lung' above.)
