Thyrotoxicosis: a rare presentation of molar pregnancy

Background

Molar pregnancy is a relatively rare complication of gestation with an incidence reported in the USA to be 121 per 100 000 pregnancies.1 This complication occurs when there is an abnormal proliferation of trophoblastic tissue, resulting in a non-viable mass that often resembles grape-like structures. The major risk factors for molar pregnancy are prior gestational trophoblastic disease and increased maternal age, especially greater than age 45.1

The most common presenting symptom of molar pregnancy is vaginal bleeding. Hyperemesis gravidarum is a classic association, but presents less frequently than vaginal bleeding.2 An even rarer complication of molar pregnancy is thyrotoxicosis. Although increased thyroid function is often reported in gestational trophoblastic disease, only 5% of these cases show symptoms of hyperthyroidism. It is believed that an elevated hCG level >200 000 IU/L for several weeks is necessary for the development of thyrotoxicosis.3 Treatment is necessary to alleviate the patient’s symptoms and to prevent progression into thyroid storm. Thyroid storm is a lethal condition that, even when treated, has a mortality rate as high as 50%.4

We report a case of molar pregnancy in which the patient subsequently developed thyrotoxicosis. This case highlights the rare complications of molar pregnancy, and the importance of monitoring for clinical hyperthyroidism in this patient population. The case demonstrates how effective treatment of thyrotoxicosis in molar pregnancy not only alleviates the patient’s symptoms, but also helps to prevent progression into the highly lethal thyroid storm.

Case presentation

A 49-year-old woman, G8P7, with asthma and bipolar disorder presented to her primary care provider with nausea, vomiting and bilateral breast tenderness. At the visit, a qualitative urine pregnancy test was positive, revealing an unplanned pregnancy. The patient then began to experience intermittent vaginal spotting that eventually increased to soaking multiple pads throughout the day. This was associated with abdominal cramps that prompted her visit to the emergency room. She had seven uncomplicated vaginal deliveries in the past, the most recent of which was 10 years ago. She has no personal or family history of fibroids, cervical cancer or molar pregnancy.

On admission, the patient was haemodynamically stable with generalised abdominal tenderness on examination. According to her last menstrual period, the estimated gestational age was 15 weeks. She was admitted to the obstetrics and gynecology (OBGYN) team. Later that night, she developed a fever of 39.4°C associated with sinus tachycardia, diaphoresis and tremors in her extremities. On day 2 of admission, she was found to have laboratory data consistent with hyperthyroidism at which point the endocrinology team was consulted.

Investigations

Prior to the endocrinology consultation, the patient underwent a vaginal ultrasound that revealed an enlarged and irregular cystic-appearing endometrium without an intrauterine gestational sac (figures 1 and 2). β-hCG level was disproportionately elevated to 414 600 IU/L given the gestational age. These findings were concerning for molar pregnancy. Her thyroid studies showed an undetectable Thyroid-stimulating hormone (TSH) (<0.015 μIU/mL; first trimester reference range 0.60–3.40), elevated free T4 (3.73 ng/dL; first trimester reference range 0.8–1.2) and elevated free T3 (10.0 pg/mL; first trimester reference range 4.1–4.4). Blood cultures from the day she spiked a fever eventually grew Salmonella species. CT chest/abdomen/pelvis did not reveal a source of the infection, nor did it show evidence of metastases.

Figure 1

Transvaginal ultrasound showing lack of intrauterine sac and abnormal placental tissue with fluid-filled cysts in longitudinal view.

Figure 2

Transvaginal ultrasound showing lack of intrauterine sac and abnormal placental tissue with fluid-filled cysts in transverse view.

Differential diagnosis

The patient’s presentation and workup were consistent with molar pregnancy (nausea, vomiting, vaginal bleeding, ultrasound with no intrauterine sac but with cystic appearance, and significantly elevated hCG). Her laboratory studies showed a new hyperthyroid state (compared with baseline normal Thyroid function tests (TFTs) obtained a few years ago during psychiatric evaluation), and she experienced symptoms of tachycardia, heat intolerance, diaphoresis and tremors. Therefore, the leading differential was thyrotoxicosis secondary to molar pregnancy, as stimulation of TSH receptors by the beta subunit of hCG can cause increased production and release of thyroid hormones.5

Other causes of hyperthyroidism were also considered but deemed less likely clinically. The patient lacked a goitre, pretibial myxoedema, exophthalmos or lid lag to suggest Graves’ disease, although TSH receptor and thyroid peroxidase antibodies were not collected during the admission. She has no history of any thyroid disorders in the family. There was no preceding viral upper respiratory tract infection or neck tenderness to indicate subacute thyroiditis. Fibrinogen was mildly elevated to 558 mg/dL in the setting of concurrent salmonella bacteraemia. In painless (silent) thyroiditis, T4 is usually disproportionately elevated compared with T3, which was the opposite in this case.6 The patient’s home medications were reviewed, and no medications were found that are classically linked to thyroiditis. She does have a history of bipolar disorder, but it has been managed with olanzapine and fluoxetine without prior lithium use. There was no recent iodinated contrast media exposure prior to the development of her symptoms. A thyroid ultrasound was not obtained prior to her emergent intervention.

Infection, such as endometritis, was also on the differential before the blood cultures turned positive, given the fever and tachycardia. Although bacteraemia could explain these abnormal vital signs, it does not account for her other symptoms of heat intolerance and tremors. Besides an enlarged endometrium, the vaginal ultrasound did not show signs of endometritis. The patient also lacked productive cough or dysuria to suggest other infectious aetiologies.

Lastly, the patient had multiple admissions in the past with tachycardia that spontaneously resolved. Her tachycardia then was attributed to excessive caffeine consumption (drinking 4–6 cups of coffee in the morning), as well as frequent use of her albuterol inhaler. However, the patient currently only drinks one cup of coffee a day and has not used her albuterol inhaler in over 2 weeks. She also did not have significant anaemia or decreased urine output to suggest hypovolaemia as a cause of the tachycardia.

Treatment

After reviewing the patient’s case, the endocrinology team reached a consensus that the patient was suffering from thyrotoxicosis secondary to her molar pregnancy. The patient was scheduled for a suction dilation and curettage to evacuate the mole and remove the ultimate source of the β-hCG. On day 2 of admission, she was started on propranolol (not administered due to hypotension) and propylthiouracil (PTU) (500 mg loading dose, followed by 100 mg every 8 hours) to decrease sympathetic hyperactivity and thyroid hormone production, respectively. Although methimazole has a more rapid onset and better side effect profile than PTU, this patient also had significantly elevated free T3 levels, so PTU was chosen for its ability to prevent T4 to T3 conversion.7 After discussion with the OBGYN team, there was initially low suspicion for infection (before blood cultures resulted), so the patient was also started on intravenous hydrocortisone (300 mg loading dose, followed by 100 mg every 8 hours). The decision to start steroids was based on concern of thyroid storm occurring in the perioperative period. At the time the endocrinology team was consulted, the patient had a Burch-Wartofsky Point Scale score of 40, which suggests impending thyroid storm.4 Furthermore, steroids also help decrease conversion of T4 to the more active T3 hormone.8

Overnight, the patient became hypotensive and persistently tachycardic. Due to concerns of sepsis, the OBGYN team performed an emergent suction D&C early on day 3 of admission. Specimen was collecting during the procedure, and pathology revealed diploidy with negative p57 immunohistochemistry stain, consistent with a complete hydatidiform mole.