Thyrotoxicosis presenting as pulmonary hypertension

Case report

A 45-year-old woman presented with a 4-month history of progressive dyspnea on exertion; orthopnea; exertional chest pain; and weight loss of 15.9 kg (35 lb), most of which occurred during the previous month. On examination, her height was 150 cm (59 in) and weight was 63 kg (138.9 lb).

The patient had a 3-year history of hypertension and was receiving propranolol (20 mg twice daily) and lisinopril/hydrochlorothiazide (10/12.5 mg daily).

Her blood pressure was 130/80 mm Hg, pulse rate was 100 beats per minute, temperature was 37°C (98.6°F), and respiration rate was 16 breaths per minute. Cardiovascular examination revealed an elevated jugular venous pressure, right ventricular heave, and hyperdynamic left ventricular impulse. Chest auscultation showed a regular rhythm, with a 2/6 systolic murmur over the left sternal border. The patient's lungs were clear to auscultation.

An echocardiogram revealed a left ventricular ejection fraction of 0.65, with a severely enlarged right atrium. The pulmonary systolic pressure was 65 mm Hg.

A ventilation-perfusion (V./Q.) scan was performed for a workup of pulmonary hypertension. During the procedure, however, the patient had severe dyspnea and hemoptysis. Her pulse rate increased to 170 beats per minute (Figure 1 and Table 1).

Pulmonary embolism was suspected, and the patient underwent a CT scan of the chest, which was negative for pulmonary pathology. Physical examination was significant for diffuse pulmonary crackles. The patient was admitted to the ICU and required ventilatory support. A Swan-Ganz catheter was placed, and the cardiac output was 7.93 L/min.

Laboratory findings revealed a thyrotropin (TSH) level of less than 0.06 µIU/mL, a total thyroxine (T₄) level of 31.9 µg/dL (normal, 4.7 to 11.4 µg/dL), and a free T₄ level of more than 6 ng/dL (normal, 0.71 to 1.85 ng/dL).

A thyroid scan showed diffuse uptake of the radioactive isotope of iodine (¹²³I), which is consistent with the diagnosis of Graves disease (Figure 2).

The patient was given intravenous b-blockers and propylthiouracil via a nasogastric tube. Her hemodynamic parameters improved, and she was weaned from ventilatory support. She continued to receive oral b-blockers and propylthiouracil until definitive ablation with ¹³¹I was achieved (Table 2).

Discussion

Few cases of thyrotoxicosis as the underlying cause of pulmonary hypertension have been reported in the literature.^1,2 Thyrotoxicosis is a known cause of high-output cardiac failure and can result in pulmonary hypertension. Our patient initially presented with signs and symptoms consistent with pulmonary hypertension. Her thyroid was not appreciably enlarged initially, and a thyroid bruit was never heard. The thyroid progressively enlarged after hospitalization, and the patient subsequently had mild exophthalmos, for which definitive ablation with ¹³¹I was performed.

The presentation of hyperthyroidism can vary widely. Graves disease is the most common cause and occurs about 10 times more frequently in women than in men.³ The classic triad of Graves disease includes hyperthyroidism, goiter, and exophthalmos.

Age can strongly influence clinical findings of Graves disease. Thyroid enlargement occurs in 85% to 95% of patients younger than 50 years^4,5 and in 50% of patients older than 70 years. Atrial fibrillation is more likely in patients older than 70 years and is unlikely in patients younger than 50 years. Graves ophthalmopathy occurs in 30% of patients, and although presentation time varies, it usually occurs within 3 months of onset.^6,7

Atypical presentations of Graves disease can occur. For example, one case presented solely as heart failure before the more classic manifestations of Graves disease appeared.⁸ Other cases of Graves disease have presented solely as pulmonary hypertension.

•Pulmonary hypertension: Primary pulmonary hypertension is defined as a mean pulmonary arterial pressure of more than 25 mm Hg, with the exclusion of secondary causes such as left-sided cardiac disease, obstructive and restrictive lung disease, and chronic thromboembolic disease.^9,10

Systemic illnesses are rarer causes of pulmonary hypertension. The incidence of primary pulmonary hypertension is increased in conditions such as HIV infection and liver cirrhosis and is associat-ed with the use of anorectic sympathomimetic agents and with cocaine inhalation.¹⁰

Dyspnea is the most common symptom of pulmonary hypertension. Angina occurs in about one third of patients.¹¹ Other signs and symptoms include fatigue and syncope. Physical examination findings include a left parasternal heave, increased jugular venous pressure, and a systolic ejection murmur. Peripheral edema occurs in more severe cases.

Protocols for the workup of pulmonary hypertension have been published.¹¹ Chest radiography, electrocardiography, and transthoracic echocardiography (TTE) are the recommended initial studies when pulmonary hypertension is suspected.¹¹ Electrocardiography can screen for chamber enlargement and may show right ventricular hypertrophy, right atrial hypertrophy, and right-axis deviation. TTE is the most useful noninvasive test and can estimate pulmonary arterial pressures. It is also useful in excluding valvular disease.

If oxygen saturation is low and pulmonary embolism is suspected, V./Q. scanning and pulmonary angiography can be performed. High-resolution CT is recommended if interstitial lung disease is suspected. Pulmonary function tests can help differentiate obstructive from restrictive lung diseases.

•The link between thyroid disease and pulmonary hypertension: Thyroid disease and pulmonary hypertension may share a common autoimmune etiology. In addition, hyperthyroidism is associated with high-output cardiac failure.¹² In patients who have thyrotoxicosis, characteristic manifestations include sinus tachycardia, atrial dysrhythmias, and high-output cardiac failure.

Marvisi and colleagues¹³ evaluated 34 patients with hyperthyroidism and found a strong association between TSH values and pulmonary arterial pressures. Patients in a euthyroid state as a result of methimazole therapy had normal pulmonary arterial pressures.

It is recommended that all patients with primary pulmonary hypertension be screened for coexisting thyroid disease.¹⁴ Thurnheer and colleagues¹⁵ found 4 patients with hyperthyroidism and coincidental pulmonary hypertension. After therapy for hyperthyroidism, pulmonary arterial pressures decreased to normal levels.

Conclusion

Thyroid disease is associated with pulmonary hypertension. Because of this association, hyperthyroidism should always be considered in the differential diagnosis of a patient presenting with pulmonary hypertension.

Measurement of the TSH level is recommended in patients with pulmonary hypertension when cardiopulmonary conditions have been ruled out.

References:

1.

Nakchbandi IA, Wirth JA, Inzucchi SE. Pulmonary hypertension caused by Graves' thyrotoxicosis: normal pulmonary hemodynamics restored by (131)I treatment.

Chest

.

1999; 116:1483-1485.

2.

Ferris A, Jacobs T, Widlitz A, et al. Pulmonary arterial hypertension and thyroid disease.

Chest

.

2001;119:1980-1981.

3.

Felz MW, Stein PP. The many faces of Graves' disease. Part 1. Eyes, pulse, skin, and neck provide important clues to diagnosis.

Postgrad Med.

1999;106:57-64.

4.

Nordyke RA, Gilbert FI Jr, Harada AS. Graves' disease. Influence of age on clinical findings.

Arch Intern Med.

1988;148:626-631.

5.

Greenwood RM, Daly JG, Himsworth RL. Hyperthyroidism and the impalpable thyroid gland.

Clin Endocrinol (Oxf).

1985;22:583-587.

6.

Haddad G. Is it hyperthyroidism? You can't always tell from the clinical picture.

Postgrad Med.

1998;104:42-59.

7.

Burch HB, Wartofsky L. Graves' ophthalmopathy: current concepts regarding pathogenesis and management.

Endocr Rev.

1993; 14:747-793.

8.

O'Malley BP, Northover BJ, Woods KL. Heart failure in sinus rhythm as the sole manifestation of Graves' disease.

Postgrad Med J.

1986;62:1051-1053.

9.

Rubin LJ. Primary pulmonary hypertension.

N Engl J Med.

1997;336:111-117.

10.

Fishman AP. Clinical classification of pulmonary hypertension.

Clin Chest Med.

2001; 22:385-391.

11.

McGoon MD. The assessment of pulmonary hypertension.

Clin Chest Med.

2001;22: 493-508.

12.

Okura H, Takatsu Y. High-output heart failure as a cause of pulmonary hypertension.

Intern Med.

1994;33:363-365.

13.

Marvisi M, Brianti M, Marani G, et al. Hyperthyroidism and pulmonary hypertension.

Respir Med

.

2002;96:215-220.

14.

Kashyap AS, Kashyap S. Thyroid disease and primary pulmonary hypertension.

JAMA

.

2001;285:2853-2854.

15.

Thurnheer R, Jenni R, Russi EW, et al. Hyperthyroidism and pulmonary hypertension.

J Intern Med.

1997;242:185-188.