High Prevalence of Autoimmune Thyroid Disease in Pulmonary Arterial Hypertension

doi:10.1378/chest.122.5.1668

Chest

Volume 122, Issue 5, November 2002, Pages 1668-1673

https://doi.org/10.1378/chest.122.5.1668 Get rights and content

Study objectives

An association between thyroid disease and pulmonary arterial hypertension (PAH) has been reported, yet the pathogenetic relationship between these conditions remains unclear. Because immune system dysfunction may underlie this association, we sought to determine the prevalence of autoimmune thyroid disease (AITD) in patients with PAH.

Design and setting

Prospective observational study at a single academic institution.

Patients

Sixty-three consecutive adults with PAH (ie, sustained pulmonary artery systolic pressure, > 25 mm Hg) were evaluated for clinical, biochemical, and serologic features of AITD.

Measurements

Thyroid gland dysfunction was determined by clinical examination for goiter, and by biochemical measurements of thyrotropin and free thyroxine. Immune system dysfunction was determined by serologic measurements of antibodies to thyroglobulin and thyroid peroxidase. First-degree family history of AITD also was ascertained in order to investigate for genetic clustering of autoimmunity.

Results

Thirty-one patients (49%; 95% confidence interval [CI], 37 to 62%) received diagnoses of AITD. Eighteen patients were newly diagnosed, and 9 patients required the initiation of pharmacologic treatment. There was no chronologic relationship between the diagnosis or treatment of PAH and that of AITD. Sixteen patients (25%; 95% CI, 15 to 36%) had 24 first-degree family members with AITD.

Conclusions

Approximately half of the patients with PAH have concomitant AITD. These two conditions may be linked by a common immunogenetic susceptibility, and the elucidation of this association may advance the understanding of the pathophysiology and treatment of PAH. Systematic surveillance for occult thyroid dysfunction in patients with PAH may prevent the hemodynamic exacerbation of right heart failure.

Section snippets

Materials and Methods

The Stanford University Human Subjects Committee approved this study, and each patient gave written informed consent before participating. We enrolled 63 consecutive adult (age, > 18 years) patients who had received a diagnosis of PAH and had received continuing care at the Stanford Hospital Chest Clinic between August 1999 and December 2001. PAH was diagnosed by right heart catheterization findings of sustained mean pulmonary arterial pressures of > 25 mm Hg at rest and was categorized

Results

The mean age of the cohort was 47 years (range, 19 to 79 years), there were 53 women and 10 men, and PAH had been diagnosed for a mean duration of 2.7 years (range, 0.1 to 11.5 years). At the time of the initial thyroid function evaluation, 15 patients were receiving continuous IV epoprostenol (Flolan; GlaxoSmithKline; Research Triangle Park, NC) by infusion therapy, 2 patients were taking subcutaneous uniprost (Remodulin; United Therapeutics; Silver Spring, MD), and 1 patient was a heart-lung

Discussion

PAH results from complex, poorly understood interactions between genetic factors and environmental triggers. Genetic studies identified bone morphogenetic protein receptor-II mutations in patients manifesting familial and sporadic PPH.²⁹^,³⁰ Additional genetic factors potentiating immune dysfunction also may be involved, since the following features of autoimmune disease are commonly observed in PAH patients: marked female gender predominance³¹^,³²; distinctive human leukocyte antigen haplotypes³³

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Hypothyroidism has been shown to have several effects on organs, including derangements in the coagulation system, impairing endothelial function, but data on the importance of hypothyroidism in the pathogenesis and development of chronic thromboembolic pulmonary hypertension (CTEPH) are limited. This report presents an updated review of the prevalence and prognosis of hypothyroidism in patients diagnosed with CTEPH, including a detailed retrospective description of the series. The descriptive case series included 34 adult patients diagnosed with CTEPH, of whom 11 patients were diagnosed with hypothyroidism. The prevalence of hypothyroidism in CTEPH was found to be 32.35%. All patients with hypothyroidism had NYHA functional Class II-III. Hemodynamic values obtained through right heart catheterization (RHC) showed that patients with hypothyroidism had significantly higher mean pulmonary arterial pressures (mPAP), with a mean of 56.91 mm Hg vs 43.93 mm Hg (p = 0.026), and the PVR in dynes/sec/cm5 was 932 vs 541 (p = 0.027). Significant differences in PVR were found in wood units (WU) 11.91 vs 7.11 (p = 0.042). The mean level of brain natriuretic peptide (BNP) between both groups was 797.3 pg/mL for patients with hypothyroidism vs 262.02 pg/mL in patients with euthyroidism (p = .032). Hypothyroidism may significantly affect patients' clinical and hemodynamic outcomes in patients with CTEPH. Hypothyroidism as a risk factor in the evaluation and treatment of these patients is vital to optimize outcomes in CTEPH; further research is warranted whether hypothyroidism therapies could alter such outcomes.
Associations of exposure to metal and metal mixtures with thyroid hormones: Results from the NHANES 2007–2012
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Disrupted thyroid homeostasis plays a role in neurocognitive dysfunction and metabolic disorders. Since individuals are exposed to multiple metals simultaneously, it is important to assess the effects of metal mixtures on thyroid hormone status. This study aimed to investigate the associations of metal mixtures and individual metals with thyroid hormone levels.
Data included 2399 men and 1988 women from the 2007–2012 National Health and Nutrition Examination Survey (2007–2012). Thyroid hormones measured included total triiodothyronine (T3), total thyroxine (T4), free forms of T3 (FT3) and T4 (FT4), and thyroid stimulating hormone (TSH). We included twelve metals (arsenic, barium, cobalt, cesium, molybdenum, antimony, thallium, tungsten, and uranium from urine; cadmium, lead, and mercury from blood) in traditional linear regression models controlling for 12 metals simultaneously and in quantile-based g-computation (QGC) to assess the relative contribution of each metal as well as the overall association with thyroid hormones as a metal mixture.
There were associations of the total metal mixture with thyroid hormones for T3 (beta: −0.023, 95% CI: −0.04, −0.01, in women), T4 (beta: −0.03, 95% CI: −0.05, −0.01, in men; beta: −0.026, 95% CI: −0.04, −0.01, in women), and the T3:T4 ratio (beta: 0.026, 95% CI: 0.01, 0.05, in men). Arsenic had negative contributions to T3 and T4. Cadmium had a positive contribution to T4 but negative contributions to T3 and T3:T4. Lead had a positive contribution to T3 and T3:T4, but a negative contribution to T4.
Multiple metals as a mixture were associated with thyroid hormone levels. Arsenic, cadmium, and lead were individually associated with multiple thyroid hormones. Examination of associations of metal mixtures and individual metals with thyroid hormones can contribute to an understanding of thyroid hormone homeostasis and provide evidence for developing intervention and guidance for health promotion.
Acute Right Ventricular Heart Failure: An Uncommon Case of Thyrotoxicosis
2018, American Journal of the Medical Sciences
Right ventricular failure can be secondary to right ventricular ischemia, pulmonary or tricuspid valvular disease, myocardial shunts, cardiomyopathy, acute and chronic pulmonary hypertension, myocarditis and pericardial disease and it generally carries a poor prognosis. Thyrotoxicosis is a clinical state resulting from high thyroid hormone action in tissues generally due to high thyroid hormone levels. The association between severe hyperthyroidism and high-output heart failure is well-known. Less widespread is the concept that hyperthyroid patients, irrespective of coexisting diseases and through mechanisms not fully elucidated, are at higher risk for pulmonary hypertension and right heart failure, both reversible with the achievement of euthyroidism and associated with a good prognosis. We describe the case of a 44-year-old woman with right ventricular failure and moderate pulmonary hypertension in the setting of thyrotoxicosis, which resolved rapidly after antithyroid treatment. The potential mechanisms underlying this condition will also be discussed.
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Citation Excerpt :
Graves’ disease, Hashimoto’s thyroiditis, and the presence of thyroid autoantibodies are all associated with pulmonary arterial hypertension (PAH). A prospective study of patients with PAH who underwent a comprehensive evaluation for thyroid function noted an autoimmune thyroid disease prevalence of 49%.1 A cohort study of patients with Graves’ disease noted a linear correlation between thyrotropin receptor antibody levels and echocardiographic estimates of pulmonary vascular pressures.2
Diagnostics in Children and Adolescents with Suspected or Confirmed Pulmonary Hypertension
2017, Paediatric Respiratory Reviews
We provide a practical approach on the initial assessment and diagnostic work-up of children and adolescents with pulmonary hypertension (PH). Transthoracic echocardiography (TTE) often serves as initial study tool before invasive cardiac catheterization. Misinterpretation of TTE variables may lead to missed or delayed diagnosis with devastating consequences, or unnecessary invasive diagnostics that have inherited risks. In addition to clinical and biochemical markers, serial examination of patients with PH using a standardized TTE approach, determining conventional and novel echocardiographic variables, may allow early diagnosis and treatment in paediatric PH. Cardiac magnetic resonance imaging and computed tomography represent important non-invasive imaging modalities, that together with TTE may enable comprehensive assessment of ventricular function and pulmonary hemodynamics. Invasive assessment of haemodynamics (ventricular, pulmonary) and testing of acute vasoreactivity in the catheterization laboratory is still the gold standard for the diagnosis of PH and pulmonary hypertensive vascular disease (PHVD) in children and for the initiation of specific PH therapy. We suggest the regular assessment of prognostic TTE variables as part of a standardized approach for initial diagnosis of children with PH. Overreliance on any single TTE variable should be avoided as it detracts from the overall diagnostic potential of a standardized TTE examination for PH.
Relationship Among Pulmonary Hypertension, Autoimmunity, Thyroid Hormones and Dyspnea in Patients With Hyperthyroidism
2017, American Journal of the Medical Sciences
Previous studies have reported conflicting results regarding the mechanisms underlying the pathophysiology of pulmonary hypertension (PHT) in patients with hyperthyroidism. Therefore, in this study, we investigated the association between PHT and thyroid-stimulating hormone (TSH) receptor antibody, thyroid peroxidase antibody, thyroglobulin antibody, TSH, fT3, fT4 and dyspnea during daily activities in a large population of patients with hyperthyroidism.
A total of 129 consecutive patients with hyperthyroidism, 37 with hypothyroidism and 38 euthyroid controls were enrolled in this study. The modified medical research council scale was used for the assessment of dyspnea in daily activities. All the patients and euthyroid controls underwent transthoracic echocardiography for the assessment of PHT.
Mild PHT was present in 35%, 36%, 13.5% and 5% of the patients with Graves׳ disease, toxic multinodular goiter, hypothyroidism and euthyroid controls, respectively. Pulmonary vascular resistance (PVR) was higher in hyperthyroid patients with PHT than in those without PHT. Moreover, a significant positive correlation was found between modified medical research council scale and pulmonary artery systolic pressure as well as PVR in patients with hyperthyroidism. No association was found between PHT and serum TSH receptor antibody, thyroid peroxidase antibody, thyroglobulin antibody, TSH, fT3 and fT4 levels.
Mild PHT is present in a significant proportion of patients with hyperthyroidism, regardless of etiology. PVR appears to be the main cause of PHT in patients with hyperthyroidism, and neither autoimmunity nor thyroid hormones are associated with PHT in these patients. Mild dyspnea during daily activities in patients with hyperthyroidism may be related to PHT; however, severe dyspnea requires further evaluation.

View all citing articles on Scopus

Presented in part as a poster at the American Association of Clinical Endocrinologists 10th Annual Meeting and Clinical Progress, San Antonio, TX, May 2, 2001.

This research was supported by a grant from the Vera M. Wall Center for Pulmonary Vascular Disease at Stanford University and by National Institutes of Health grants DK07217-24 and HL07708-10 (to Dr. Chu), and GCRC M01-RR00070.

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Chest

Clinical Investigations: Pulmonary HypertensionHigh Prevalence of Autoimmune Thyroid Disease in Pulmonary Arterial Hypertension

Study objectives

Design and setting

Patients

Measurements

Results

Conclusions

Section snippets

Materials and Methods

Results

Discussion

Lancet

Chest

Rheum Dis Clin North Am

J Am Coll Cardiol

Mayo Clin Proc

Chest

Chest

Chest

Am J Med Sci

Am J Med

Lancet

Am J Hum Genet

Chest

J Am Coll Cardiol

Am J Med

Hepatology

Appetite-suppressant drugs and the risk of primary pulmonary hypertension: International Primary Pulmonary Hypertension Study Group

N Engl J Med

Diagnosis and assessment of pulmonary hypertension. Primary pulmonary hypertension

Hypothyroidism and primary pulmonary hypertension: an autoimmune pathogenetic link?

Ann Intern Med

Epoprostenol-associated thyropathy in PPH patients [abstract]

Am J Respir Crit Care Med

Fetal and neonatal hyperthyroidism

Thyroid

Reversible pulmonary hypertension in neonatal Graves disease

Ir Med J

The pathology of intrauterine thyrotoxicosis: two case reports

Obstet Gynecol

Hyperthyroidism and pulmonary hypertension

J Intern Med

Clinical Investigations: Pulmonary Hypertension
High Prevalence of Autoimmune Thyroid Disease in Pulmonary Arterial Hypertension