Thyroid Research and Practice

ORIGINAL ARTICLE
Year
: 2013  |  Volume : 10  |  Issue : 1  |  Page : 8--11

Hyperthyroidism - A reversible cause of pulmonary hypertension: A prospective echo cardiographic study


Babul H Reddy1, Sharath A Reddy2, Jayanthy Ramesh3, Rakesh K Sahay3,  
1 Department of Endocrinology, ESI Hospital, Sanathnagar, Hyderabad, India
2 Department of Cardiology, Sunshine Hospital, Behind Paradise Hotel, Secunderabad, India
3 Department of Cardiology, Osmania General Hospital, Hyderabad, India

Correspondence Address:
Babul H Reddy
Flat No-507, Emerald Block, My Home Jewel, Madinaguda, Hyderabad - 500 049, Andhra Pradesh
India

Abstract

Aim: To determine the prevalence of pulmonary hypertension (PHT) related to hyperthyroidism and its outcome with treatment. Materials and Methods and Results: We performed serial echocardiographic examinations in 25 consecutive patients with hyperthyroidism (20 females, five males) to estimate pulmonary artery hypertension at baseline and were repeated once an euthyroid state was achieved (mean 6 months after initiation of anti-thyroid treatment). Results were compared with 15 age- and sex-matched healthy controls. All hyperthyroid patients had normal Left Ventricular systolic function and 14 patients (56%) had PHT with Pulmonary arterial systolic pressure of at least 35 mmHg. There were no significant differences in the clinical characteristics of hyperthyroid patients with or without PHT. Nonetheless, those with PHT had significantly higher Cardiac Output PASP, peak trans-mitral early diastolic flow velocity (E), and ratio of E to early diastolic mitral annular velocity (E1). Among the 14 hyperthyroid patients with PHT, 10 (40%) had pulmonary arterial hypertension (PAH) with normal E/E1, and 10 (16%) had pulmonary venous hypertension (PVH) with elevated E/E1. These hemodynamic abnormalities and PHT were reversible in patients with PAH or PVH after restoration to a euthyroid state. Conclusion: In patients with hyperthyroidism and normal LV systolic function, up to 56% had PHT due to either PAH with increased CO (40%) or PVH with elevated LV filling pressure (16%). More importantly, hyperthyroidism-related PHT was largely asymptomatic and reversible after restoration to a euthyroid state.



How to cite this article:
Reddy BH, Reddy SA, Ramesh J, Sahay RK. Hyperthyroidism - A reversible cause of pulmonary hypertension: A prospective echo cardiographic study.Thyroid Res Pract 2013;10:8-11


How to cite this URL:
Reddy BH, Reddy SA, Ramesh J, Sahay RK. Hyperthyroidism - A reversible cause of pulmonary hypertension: A prospective echo cardiographic study. Thyroid Res Pract [serial online] 2013 [cited 2021 Oct 18 ];10:8-11
Available from: https://www.thetrp.net/text.asp?2013/10/1/8/105839


Full Text

 Introduction



Hyperthyroidism is a common endocrine disorder that is associated with prominent cardiovascular manifestations. Because of its hyper dynamic circulatory effect exacerbate pre-existing cardiac disease or cause denovo cardiovascular abnormalities, such as atrial fibrillation and heart failure. Recent studies also suggest a potential link between hyperthyroidism and pulmonary hypertension (PHT). [1]

In contrast to idiopathic primary or secondary PHT, hyperthyroidism-related PHT appears to have a good prognosis; pulmonary arterial pressure often normalizes after successful treatment of hyperthyroidism. The prevalence and natural course and pathogenic mechanisms of hyperthyroidism-related PHT remain unclear, as there is a scarcity of data on this issue.

The purpose of this study was thus to investigate the natural course and clinical outcome of PHT related to hyperthyroidism and to determine the serial hemodynamic changes of PHT related to hyperthyroidism using echo cardiographic measurements.

 Materials and Methods



This prospective study included consecutive hyperthyroid patients came to our outpatient Clinic from May 2007 to 2008, for treatment of hyperthyroidism.

Exclusion criteria

Pre-existing cardiovascular disease or symptomatic heart failure at presentation like significant valvular heart disease, coronary artery disease, dilated or hypertrophic cardiomyopathy, and congestive heart failure, etc. Any history of pulmonary thromboembolism or significant pulmonary disease; presence of autoimmune connective tissue disease, prior anti-thyroid therapy and/or beta adrenergic blockers at the time of referral.

Patients' data prospectively collected and included history of smoking, drug history, electrocardiography (ECG), chest X-ray, and laboratory results, including serum T3, T4, Thyroid Stimulating Hormone levels, anti Thyroid Peroxidase antibodies. We performed serial echocardiographic examinations in 25 consecutive patients with hyperthyroidism (20 females, five males) to estimate PHT at baseline and were repeated once an euthyroid state achieved (mean 6 months after initiation of anti-thyroid treatment [3-12 months]). Results were compared with 15 age- and sex-matched healthy controls.

Echocardiographic examination

Two-dimensional, M-mode, Doppler flow, and tissue Doppler imaging studies were performed in all subjects using the System Philips IE33 machine with a 5-MHz transducer.

PHT was defined as PASP of at least 35 mmHg, based on the Venice clinical classification for PHT, an additional assessment of pulmonary capillary wedge pressure may allow distinction between pulmonary arterial hypertension (PAH) and pulmonary venous hypertension (PVH) in patients with concomitant left heart disease. Pulmonary capillary wedge pressure was estimated using a tissue Doppler imaging technique that determines the ratio of the trans-mitral early diastolic flow velocity (E) to the early diastolic mitral annular velocity (E').

Using these data, patients with PHT were then further classified as having either PAH (normal E/E') or PVH (high E/E'). All echocardiographic examinations were performed by a single an experienced operator.

Follow-up

All patients were assessed every 2-3 months in the outpatient clinic. A repeat clinical evaluation, ECG, laboratory measurements, and transthoracic echocardiography were performed at euthyroid state after initiation of anti-thyroid drugs.

Statistical analysis

Statistical comparisons were performed with Student's t-test. Changes in continuous variables at baseline and 6-month follow-up were analyzed with paired Student's t-test. Calculations were performed using SPSS software (version 10.0): a P value ≤ 0.05 was considered statistically significant.

 Results



Study population

The mean age was 40 years, and most were female (80%). All patients had suppressed TSH and elevated free T4 level. Graves' disease was the underlying etiology in 19 patients (78%) and multinodular goiter in 5 (20%), toxic adenoma in 1 (0.4%) patient. ECG revealed the presence of atrial fibrillation in four patients [Table 1].{Table 1}

All patients were treated with carbimazole.

Follow-up echocardiography was performed in all patients with PHT who had achieved a clinically and bio-chemically euthyroid state. (Mean 6 m [3-12 m]) After achieving euthyroid status, the mean PASP decreased from 47 ± 2-34 ± 2 mmHg (P ≤ 0.01), decrease in CO from 6.1 ± 0.5 to 4.5 ± 0.3 l/min (P ≤ 0.01), heart rate from 89 ± 5 to 77 ± 4 beats/min (P ≤ 0.01) and an increase in Total vascular resistance from 1319 ± 96 to 1710 ± 108 dynes-sec/cm -5 (P ≤ 0.01) [Table 2] and [Table 3] and [Figure 1], [Figure 2] and [Figure 3]. {Figure 1}{Figure 2}{Figure 3}{Table 2}{Table 3}

 Discussion



In patients with hyperthyroidism and normal LV systolic function, asymptomatic PHT as detected by echocardiography was observed in 56% of patients at presentation, pathogenesis could be either PAH (72%) or PVH (28%), Patients with PAH had significantly lower TVR and higher CO than patients with PVH.

In patients with PAH, the lack of a vasodilatory response of the pulmonary vasculature to thyroid hormone might not allow the pulmonary circulation to accommodate the increased CO and thus result in an elevated PASP. [2]

In contrast, patients with PVH had significantly lower E' than patients with PAH, suggesting early diastolic dysfunction, recent studies demonstrate that prolonged subclinical hyperthyroidism is associated with LV diastolic dysfunction. [3] Patients with PVH also tend to be older than patients with PAH (Leading to elevated LV filling pressure).

PHT resolved in all patients on achieving a euthyroid state. This suggests that hyperthyroidism directly contributed to the occurrence of PHT. Although hyperthyroidism has been proposed as a reversible cause of PHT, data on its incidence and pathogenesis is limited.

Previous studies show that up to 40-50% of patients with hyperthyroidism have elevated PASP (≥35 mmHg), although the potential mechanism of PHT was not explored. [4] Consistent with this finding, our study shows that upto 56% of unselected hyperthyroid patients had asymptomatic PHT. Pathogenesis of PHT exactly not known, proposed hypothesis were autoimmune mediated endothelial injury, [5] increased metabolism of nitric oxide by hyperthyroid state, hyperdynamic circulation, decreased surfactant synthesis [6] and sympathovagal imbalance. [7]

Limitations of this study

Invasive hemodynamic assessment was not performed, and precise measurements of CO, TVR, and LV filling pressure were not from obtained. We did not routinely perform additional investigations, such as markers for autoimmune connective tissue disease or imaging for pulmonary thromboembolism to exclude secondary PHT (Patients with established causes of secondary PHT were, nonetheless, excluded from study, and PHT resolved in all the patients after successful treatment of hyperthyroidism). Although patients with PHT reported no symptoms of heart failure, the impact of the development of PHT on exercise capacity was not objectively assessed. Sample size is small, large-scale studies are needed to confirm results.

 Conclusion



In patients with hyperthyroidism with normal LV systolic function, up to 56% have PHT due to either PAH with increased CO (40%) or PVH with elevated LV filling pressure (16%). Hyperthyroidism-related PHT was largely asymptomatic and reversible after restoration to an euthyroid state. So hyperthyroidism should be considered as the reversible cause of PHT.

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