Thyroxine Replacement Therapy Reduces Hypothyroidism-Linked Pneumonia Risk

Patient undergoing thyroid examination
The doctor holds the results of a thyroid ultrasound examination of a girl. Thyroid diseases, nodular goiter, cancer
Researchers sought to evaluate the relationship between hypothyroidism and the risk of developing pneumonia.

Hypothyroidism is associated with an increased risk of pneumonia, but thyroxine replacement therapy may lower this risk, according to research published in Family Practice.

Through a nationwide, population-based, retrospective cohort study pulling data from Taiwan’s Longitudinal Health Insurance Database, researchers sought to evaluate the relationship between hypothyroidism and the risk of developing pneumonia. The population included cohorts with and without hypothyroidism; the hypothyroid cohort included adults aged 20 and older diagnosed with hypothyroidism between 2001 and 2014.

The primary study outcome was occurrence of pneumonia during the study period.

The total study population included 19,498 patients (patients with hypothyroidism, n=9749, matched 1:1 with control group participants without hypothyrodism). Baseline characteristics were well balanced between groups in terms of age, sex, and comorbidities.

The investigators identified more pneumonia events among patients with hypothyroidism compared with those without (18.2% vs 13.6% of events). Incidence rates were 29.2 and 21.3, respectively, representing 1775 and 1329 events with 60,735 and 62,483 person-years. Comparisons made after propensity score matching saw cumulative incidence curves that demonstrated a higher incidence of pneumonia in the hypothyroid cohort.

Over a 4-year follow-up period, sensitivity analyses showed similar results; people with hypothyroidism had a “significantly higher risk” of pneumonia compared with those without (crude hazard ratio [HR], 1.32; 95% CI, 1.18-1.48; adjusted HR [aHR], 1.41; 95% CI, 1.26-1.58).

The investigators also evaluated pneumonia incidence rates in patients undergoing thyroxine replacement therapy compared with those without; incidence rates were 28.1 and 31.2 individuals per 1000 person-years, respectively. The cohort with hypothyroidism demonstrated an increased pneumonia risk among those who did or did not receive thyroxine replacement therapy compared with the cohort without hypothyroidism (aHR, 1.30; 95% CI, 1.20-1.42 vs aHR, 1.54; 95% CI, 1.40-1.69). Cumulative incidence curves demonstrated a higher pneumonia risk in patients who were not receiving thyroxine replacement therapy.

Data were also stratified by age and sex, with results showing that hypothyroidism was significantly associated with a higher pneumonia risk in both younger and older patients (younger than 65 years: aHR, 1.34; 95% CI, 1.22-1.47; 65 years and older: aHR, 1.39; 95% CI, 1.24-1.55). In analyses stratified by sex, pneumonia risk was increased in the hypothyroid group regardless of sex (men: aHR, 1.46; 95% CI, 1.27-1.67; women: aHR, 1.36; 95% CI, 1.25-1.48).

Data were also evaluated based on a sampling period before and after the introduction of the pneumococcal polysaccharide vaccine (2001-2007 and 2008-2014). Risk results were similar in each time period (2001-2007: aHR, 1.40; 95% CI, 1.27-1.53; 2008-2014: aHR, 1.37; 95% CI, 1.21-1.54).

Study limitations include the use of diagnoses relying on ICD-9-CM codes rather than direct clinical evaluations, possible information biases due to ICD-9-CM code misclassifications, and an inability to evaluate laboratory data for patients due to data anonymization.

“We found that hypothyroidism was an independent risk factor for developing pneumonia,” the researchers wrote. “Thyroxine treatment attenuated the increased risk of pneumonia.”

“Additional prospective cohort studies, which include thyroid function tests and a more accurate clinical diagnosis of pneumonia based on radiological findings, are needed to confirm the effects of hypothyroidism and [thyroxine replacement therapy] on the risk of developing pneumonia,” they concluded.


Huang HK, Wang JH, Kao SL. Risk of developing pneumonia associated with clinically diagnosed hypothyroidism: a nationwide population-based cohort study. Fam Pract. Published online April 27, 2021. doi:10.1093/fampra/cmab027