Abstract
Hyperthyroidism is recognized as a cause of pulmonary hypertension (PH). Exercise stress echocardiography (ESE) can assess changes in cardiovascular function during exercise and plays an important role in the noninvasive evaluation of patients with suspected PH. We herein report a case involving a 51-year-old woman with exertional dyspnea who was diagnosed with Graves' disease. Resting transthoracic echocardiography showed normal left ventricular systolic and diastolic function, no significant valvular disease, and a tricuspid regurgitation pressure gradient (TRPG) of 34 mmHg. ESE revealed an elevated maximum TRPG of 61 mmHg during exercise, associated with dyspnea. We presumed that the cause of exertional dyspnea was PH associated with hyperthyroidism. Following treatment with thiamazole, euthyroid status was achieved and her symptoms improved. Post-treatment ESE showed improvement, with a maximum TRPG of 38 mmHg during exercise. ESE has the potential to identify PH associated with hyperthyroidism and to serve as a noninvasive tool for monitoring the therapeutic course after treatment.
Learning objective
Pulmonary hypertension (PH) should be suspected in patients with hyperthyroidism who present with unexplained exertional dyspnea. Exercise stress echocardiography (ESE) can noninvasively reveal masked PH and should be considered in patients with hyperthyroidism and exertional dyspnea when resting echocardiography does not identify a clear cause. ESE can also be used to monitor the therapeutic course of PH following treatment for hyperthyroidism.
Keywords: Pulmonary hypertension, Hyperthyroidism, Exercise stress echocardiography
Introduction
Hyperthyroidism affects the cardiovascular system, contributing not only to heart failure and atrial fibrillation but also to pulmonary hypertension (PH). Previous studies have shown that the prevalence of PH in patients with hyperthyroidism is approximately 30 %–50 % [1]. Although right heart catheterization (RHC) remains the gold standard for diagnosing PH, it is an invasive procedure and typically requires hospitalization. Transthoracic echocardiography (TTE), a noninvasive method, is commonly used to assess the probability of PH. However, the diagnostic accuracy of resting TTE is relatively low for the detection of PH [2]. By contrast, exercise stress echocardiography (ESE) allows for dynamic evaluation of cardiovascular function under physiological stress and plays an important role in the noninvasive assessment of patients with suspected PH [3]. We herein present a case of PH associated with hyperthyroidism that was successfully diagnosed and monitored until improvement using ESE.
Case report
A 51-year-old woman presented to our hospital with exertional dyspnea, fatigue, palpitations, tremors, and sweating. Her exertional dyspnea had appeared 6 months before and gradually progressed. Her medical history included depressive disorder and she had taken an antidepressant (fluvoxamine 150 mg/day). She did not have diabetes, hypertension, or dyslipidemia. She was a former smoker (30 pack-years). On physical examination, her blood pressure was 132/78 mmHg, heart rate 73 beats/min, peripheral oxygen saturation 98 %, and body mass index 23.1 kg/m2. There were no cardiac murmurs, no swelling or tenderness of the thyroid gland, and no signs of ophthalmopathy.
Laboratory results showed a hemoglobin level of 12.3 g/dL and a B-type natriuretic peptide level of 44.1 pg/mL. Thyroid function tests revealed an elevated free T4 level of 3.94 ng/dL and free T3 level of 17.3 ng/dL, with a suppressed thyroid-stimulating hormone level of <0.005 mIU/L. Both thyroid-stimulating hormone receptor antibodies and thyroid peroxidase antibodies were positive. Chest radiography revealed a cardiothoracic ratio of 47 % with no signs of pulmonary congestion. Electrocardiography showed sinus rhythm.
TTE demonstrated a left ventricular (LV) ejection fraction of 73 %, an LV end-diastolic diameter of 45 mm, a left atrial volume index of 32 mL/m2, a septal e′ of 9.6 cm/s, a lateral e′ of 12.8 cm/s, an average E/e′ of 6.7, a tricuspid regurgitation peak velocity (TRV) of 2.9 m/s, and a tricuspid regurgitation pressure gradient (TRPG) of 34 mmHg. No significant valvular disease was noted. Regarding right ventricular (RV) size and function, TTE showed an RV end-diastolic area of 19.4 cm2, an RV end-systolic area of 11.4 cm2, an RV fractional area change of 40.8 %, a tricuspid annular plane systolic excursion of 27.7 mm, and an S′ of 20.4 cm/s.
The patient was diagnosed with Graves' disease. The cause of her exertional dyspnea was not considered to be left heart failure because TTE showed normal LV systolic and diastolic function, no significant valvular disease, and an E/e′ ratio within normal limits. The borderline elevated TRPG suggested the possibility of PH. To investigate the cause of the exertional dyspnea, ESE was performed using a semi-supine bicycle ergometer (Angio CPET EC; Lode B.V., Groningen, the Netherlands). ESE revealed an elevated maximum TRV of 3.9 m/s, a TRPG of 61 mmHg, and an estimated mean pulmonary artery pressure (mPAP) of 39 mmHg, calculated using the following formula: estimated systolic pulmonary artery pressure (TRV^2 × 4) × 0.6 + 2 [4] (Table 1, Fig. 1A). These findings were consistent with exertional dyspnea. The ΔmPAP/Δcardiac output (CO) slope was 5.76 mmHg/L/min−1. The E/e′ ratio did not significantly increase during exercise. Neither ST-T change nor regional LV wall motion abnormality was observed during exercise and we ruled out coronary artery disease. These results suggested the potential presence of PH associated with hyperthyroidism. The patient began treatment for hyperthyroidism with thiamazole 15 mg/day.
Table 1.
Exercise stress echocardiography before and after treatment for hyperthyroidism.
| Before treatment |
After treatment |
|||||
|---|---|---|---|---|---|---|
| Rest | 50 W | 75 W | Rest | 50 W | 75 W | |
| Systolic BP, mmHg | 129 | 156 | 133 | 127 | 143 | 153 |
| Diastolic BP, mmHg | 74 | 86 | 89 | 81 | 92 | 83 |
| Heart rate, bpm | 71 | 108 | 130 | 58 | 88 | 107 |
| SpO2, % | 98 | 99 | 98 | 97 | 96 | 96 |
| LVEF, % | 72.8 | 72.2 | 81.5 | 69.7 | 73.4 | 70.1 |
| Stroke volume, ml | 88 | 89 | 73 | 58 | 63 | 64 |
| Cardiac output, L/min | 6.2 | 9.6 | 9.5 | 3.4 | 5.5 | 6.8 |
| TMF E, cm/s | 66 | 83 | – | 51 | 80 | – |
| A, cm/s | 86 | 92 | – | 67 | 96 | – |
| e′ average, cm/s | 11.0 | 13.3 | – | 9.9 | 14.8 | – |
| E/e′ average | 6.0 | 6.2 | – | 5.2 | 5.4 | – |
| TRV, m/s | 2.7 | 3.5 | 3.9 | 2.4 | 3.1 | 3.1 |
| TRPG, mmHg | 29 | 49 | 61 | 23 | 38 | 38 |
| mPAP, mmHg | 20 | 31 | 39 | 16 | 25 | 25 |
| ΔmPAP/ΔCO, mmHg/L/min−1 | – | – | 5.76 | – | – | 2.65 |
A, late diastolic mitral inflow velocity; BP, blood pressure; CO, cardiac output; E, early diastolic mitral inflow velocity; e′, early diastolic mitral annular velocity; LVEF, left ventricular ejection fraction; mPAP, mean pulmonary artery pressure; SpO2, peripheral oxygen saturation; TMF, transmitral flow; TRPG, tricuspid regurgitation pressure gradient; TRV, tricuspid regurgitation peak velocity.
Fig. 1.
Tricuspid regurgitation peak velocity (TRV) measured by continuous wave Doppler echocardiography during exercise. Maximum TRV was (A) 3.9 m/s before treatment for hyperthyroidism and (B) 3.1 m/s after treatment.
Her symptoms improved after starting treatment. Her thyroid hormone levels normalized within 1 month (free T4 level of 0.98 ng/dL). Follow-up ESE was performed at euthyroid status, 9 months after initiating thiamazole. The follow-up ESE showed improvement in maximum TRV to 3.1 m/s, TRPG to 38 mmHg, and estimated mPAP to 25 mmHg during exercise (Table 1, Fig. 1B), all within normal limits for pulmonary artery pressure during exercise [4]. The ΔmPAP/ΔCO slope had decreased to 2.65 mmHg/L/min−1. Because the PH improved following treatment for hyperthyroidism, we concluded that the PH was caused by hyperthyroidism.
At the time of writing, the patient was undergoing routine follow-up, and she had experienced no recurrence of exertional dyspnea for 4 years.
Discussion
We are not able to accurately distinguish whether the cause of her symptoms was hyperthyroidism or PH. However, we speculate that her symptoms were mainly caused by PH, because PH findings in ESE were not identified after her symptoms improved. PH associated with hyperthyroidism is generally reversible [5]; therefore, all patients with hyperthyroidism who present with exertional dyspnea should be screened for PH. A previous case report indicated that delayed treatment of PH associated with hyperthyroidism may lead to refractory PH [6]. Therefore, early recognition of PH in the context of hyperthyroidism is crucial.
Hyperthyroidism affects the cardiovascular system by increasing the heart rate, enhancing LV contractility, reducing systemic vascular resistance, and elevating CO [5]. However, hyperthyroidism does not necessarily cause increased heart rate, as in our case. A previous study showed that heart rate >90 bpm was present in only 47.2 % of the patients with hyperthyroidism [7]. Another previous study showed that mean heart rate in hyperthyroidism patients with PH was 84.9 ± 12.9 bpm [8]. Thyroid hormone reduces systemic vascular resistance and increases renin and aldosterone secretion, leading to a decrease in afterload and an increase in preload. Thyroid hormone also directly enhances myocardial contractility. These combined effects increase CO, resulting in hyperdynamic status [5]. The resulting hyperdynamic circulation may induce endothelial shear stress, endothelial dysfunction, intimal proliferation, vascular remodeling, and vasoconstriction in the pulmonary arteries, ultimately contributing to the development of PH [1].
The diagnosis of PH can be made using TTE, although RHC remains the gold standard for confirming PH. In most previous studies of PH associated with hyperthyroidism, the diagnosis was based on TTE findings without hemodynamic confirmation by RHC. PH in the context of hyperthyroidism was commonly defined as a pulmonary artery systolic pressure of >35 mmHg as measured by TTE [9]. However, resting TTE has limited accuracy in detecting PH, especially when TRV is <3.4 m/s [2].
ESE can evaluate changes in cardiovascular function during exercise and plays an important role in assessing patients with suspected PH [3]. Assessing pulmonary vascular resistance is more sensitive than simply estimating pulmonary artery pressure during exercise. The ΔmPAP/ΔCO slope, which reflects the dynamic pulmonary vascular resistance curve, is a simple and reliable variable for characterizing pulmonary hemodynamic changes during exercise. A steeper ΔmPAP/ΔCO slope indicates a higher risk for the development of PH [10]. Exercise-induced PH due to pulmonary arterial disease is defined on ESE as a ΔmPAP/ΔCO slope of >3.0 mmHg/L/min−1 or an mPAP of ≥30 mmHg [4]. ESE can reveal masked PH in patients whose exertional dyspnea cannot otherwise be explained. In addition, ESE is considered safe, with the incidence of serious complications—such as severe arrhythmia or myocardial infarction—reported to be ≤0.2 % [4]. ESE is easily reexamined to assess PH after treatment. Although supine ergometer is not available as an ESE method in all facilities, six-minute walk test can be performed without requiring special equipment and is universally available as an alternative ESE method [4].
In conclusion, we have reported a case of PH associated with hyperthyroidism, identified by ESE. Following treatment for hyperthyroidism, ESE demonstrated improvement in PH. ESE has the potential to noninvasively detect PH associated with hyperthyroidism and to monitor the therapeutic course of PH after treatment.
Consent statement
Written informed consent was obtained from the patient.
Declaration of competing interest
The authors declare that there is no conflict of interest.
Acknowledgment
None.
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