A young pregnant woman with shortness of breath

RULING OUT PULMONARY EMBOLISM

2. Has pulmonary embolism been definitively ruled out at this point?

• Yes
• No

The answer is no. The negative ventilation-perfusion scan and normal D-dimer test in this patient are not enough to rule out pulmonary embolism. The diagnosis of pulmonary embolism should be based on the clinician’s estimation of the pretest probability of pulmonary embolism (which is based on presenting signs and symptoms), as well as on a variety of tests, including spiral computed tomography (CT), ventilation-perfusion lung scanning, and serum D-dimer testing. Signs and symptoms that may guide the clinician are chest pain (present in 70% of patients with pulmonary embolism), tachypnea (70%), cough (40%), shortness of breath (25%), and tachycardia (33%).² A history of pregnancy, malignancy, immobility, or recent surgery may also increase the pretest probability of pulmonary embolism. In many cases, one’s clinical suspicion is highly predictive and is useful in diagnosing pulmonary embolism.

The accuracy of the tests varies widely, depending on the pretest probability of pulmonary embolism. For instance, in a patient with a high pretest probability but a low-probability ventilation-perfusion scan, the true probability of pulmonary embolism is 40%, but in a patient with a low pretest probability and a low-probability scan, the probability is only 4%.

The Wells criteria can be used to calculate the pretest probability of pulmonary embolism. Given this patient’s tachycardia and clinical presentation, her pretest probability according to the Wells criteria indicates increased risk. However, because her D-dimer test, lower-extremity Doppler test, and ventilation-perfusion scan were normal, pulmonary embolism is less likely.³

However, if one’s clinical suspicion is high enough, further investigation of pulmonary embolism would proceed despite the encouraging test results.

CASE CONTINUED

The cardiology consult team notes that her beta human chorionic gonadotropin (beta-hCG) level is much higher than would be expected at 12 weeks of pregnancy, and so they are concerned about the possibility of a molar pregnancy. In addition, her level of thyroid-stimulating hormone (TSH, or thyrotropin) is markedly low.

HYPERTHYROIDISM IN PREGNANCY

3. Which of the following would not explain this patient’s markedly low TSH level?

• Graves disease
• Molar pregnancy
• TSH-secreting pituitary adenoma
• Gestational transient thyrotoxicosis
• Twin pregnancy

Hyperthyroidism (also called thyrotoxicosis) has many causes, including but not limited to Graves disease, pituitary adenoma, struma ovarii (teratoma), hCG-secreting hydatidiform mole, and thyroid carcinoma (which is rare).⁴ In most of these disorders, the TSH level is low while the levels of thyroxine (T₄), triiodothyronine (T₃), or both are high.

Symptoms of hyperthyroidism are the effect of elevated T₄ and T₃ levels on the target organs themselves. Common symptoms include fever, tachycardia, tremor, stare, sweating, and lid lag. Other symptoms include nervousness, delirium, hypersensitivity to heat, flushing, palpitations, fatigue, weight loss, dyspnea, weakness, increased appetite, swelling of the legs, nausea, vomiting, diarrhea, goiter, tremor, atrial fibrillation, and cardiac failure.⁴ In its extreme form, called thyroid storm, thyrotoxicosis can be life-threatening. The likelihood of an impending thyroid storm can be assessed by clinical variables such as the patient’s temperature and heart rate and whether he or she has heart failure or gastrointestinal manifestations.⁵

Graves disease, the most common cause of hyperthyroidism in pregnancy, is due to stimulation of TSH receptors by antibodies against these receptors. Graves disease is possible in this patient, but a subsequent TSH receptor antibody test is negative.

Pituitary adenomas are one of the few causes of hyperthyroidism in which the TSH level is high, not low. Therefore, this is the correct answer.

Gestational transient thyrotoxicosis is a nonautoimmune condition that results in transient hyperthyroidism of variable severity.⁶ Usually, it occurs in otherwise normal pregnancies without complications, but the initial manifestation is hyper- emesis.⁶ It can be differentiated from Graves disease by the absence of TSH receptor antibodies and by no history of thyroid disorder.⁷ Common symptoms of gestational transient thyrotoxicosis include weight loss (or failure to gain weight), tachycardia, and fatigue.

The reason for the transient rise in ^T4 may be that beta-hCG is structurally similar to TSH (and also to luteinizing hormone and follicle-stimulating hormone), so that it has mild thyroid-stimulating effects.⁷ Sustained high levels of beta-hCG may in time give rise to the manifestations of thyrotoxicosis.

Molar pregnancy also can cause hyper-thyroidism via elevated levels of beta-hCG. However, twin pregnancy is more common and can produce sustained levels of beta-hCG above 100,000 IU/L. In most cases of twin pregnancy, the TSH level is decreased and the T₄ level transiently elevated.⁶ The elevated beta-hCG and the subsequent thyrotropic manifestations are thought to be directly related, and symptoms resolve when beta-hCG levels go down.⁶

In most cases of hyperthyroidism in pregnancy, the acute condition can be managed by a short (≤ 2-month) course of a beta-blocker. In rare cases, propylthiouracil treatment may be required. Gestational transient thyrotoxicosis is not associated with detrimental outcomes.

Case continued

Our patient’s TSH level is low and her free T₄ and T₃ levels are elevated. Her high beta-hCG level may be stimulating the thyroid gland and may account for the low TSH value, as well as for her tachycardia, emesis, shortness of breath, and weight loss.

After an obstetric consult, it is determined that our patient has a viable pregnancy. However, further investigation with transvaginal ultrasonography reveals that she has two viable, single-placenta, intrauterine gestations, separated by a thin chorionic membrane.

Beta-hCG and free T₄ levels are significantly higher in twin pregnancies than in single pregnancies, especially in the early stages.⁶ In our patient, the twin pregnancy led to the elevated beta-hCG, which eventually manifested as thyrotoxicosis, which caused the shortness of breath, hyperemesis, weight loss, tachycardia, and nausea.

Shortness of breath in patients with thyrotoxicosis is well recognized but not well explained. It may be caused by decreased lung compliance, engorged capillaries in the lung, or left ventricular failure, as well as by chest pain due to increased myocardial demand or coronary artery vasospasm.⁴ The dyspnea is present at rest and during exertion, and the high metabolic rate is thought to lead to an inappropriate response of the ventilatory system.^3,8