When a ‘hot’ nodule is not a toxic thyroid adenoma

Issue: June 2009

ByStephanie L. Lee, MD, PhD, ECNU

A 43-year-old woman presented to an endocrine clinic for the evaluation of an enlarging goiter. The patient had complained of an enlarging neck over the prior 12 months with no compressive symptoms. A technetium-99m thyroid scan was interpreted as a cold left lower pole thyroid nodule and a hot thyroid nodule extending into the anterior mediastinum (figure 1A). An ultrasound in radiology revealed a multinodular goiter with a dominant 3 cm nodule in the left lobe. Radiology performed an ultrasound-guided fine-needle aspiration biopsy that contained insufficient cells for diagnosis.

Stephanie L. Lee, MD, PhD
Stephanie L. Lee

Over the next year, she noted that her neck continued to enlarge with mild symptoms of dysphagia when she consumed solid foods but not with liquids. Although she did not complain of cough or stridor, she complained of progressive worsening dyspnea on exercise. Finally, a chest radiograph revealed pulmonary nodules and a CT scan of the chest revealed a large thyroid mass in the left lobe and multiple pulmonary nodules <1 cm in diameter. She was referred to the endocrine clinic for the neck mass. Exam confirmed a firm, nonmobile mass in the left lobe of the thyroid that extended across the isthmus into the right lobe and multiple bilateral palpable firm lateral cervical neck nodes. Endocrine ultrasound revealed a hypervascular, hypoechoic 4 cm x 4 cm x 6 cm mass in the left lobe of the thyroid that extended across the isthmus. The caudal margin of the inferior poles of the left and right lobe was easily imaged above the sternal notch. Repeat FNA with ultrasound guidance by the endocrinologist nearly one year after the insufficient biopsy in radiology contained atypical cells consistent with a poorly differentiated thyroid carcinoma.

Figure 1 A&B: Thyroid Scintigraphy
Figure 1. Thyroid Scintigraphy. A. Technetium-99m thyroid scan. AP view shows trapping in the salivary glands (green arrows), thyroid and a mass inferior to the sternal notch marker (yellow arrow). B. I-123 thyroid scan. AP view with uptake in the thyroid and a mass inferior to the sternal notch. The poorly differentiated thyroid carcinoma was located in the inferior left lobe and isthmus. The cold nodule is indicated by an orange arrow.

All images courtesy of Stephanie L. Lee

Figure 2: Non-contrast CT scan of the neck and chest
Figure 2. Non-contrast CT scan of the neck and chest. Axial views of the neck show the large mass in the left lobe of the thyroid extended across the isthmus (orange arrow), an expansile mass in the manubrium (yellow arrow) and multiple pulmonary metastases (red arrows).

It was puzzling that there was a large area of technetium-99m trapping inferior to the sternal notch despite an absence of adenopathy or mass in the anterior mediastinum on the thorax CT scan (figures 1 and 2). The nuclear physician was adamant that it represented trapping by the large left thyroid mass. To confirm the iodine avidity and likelihood of metastatic disease, an iodine-123 thyroid scintigraphy with single photon emission computed tomography (SPECT) was performed that confirmed a cold nodule in the inferior pole of the left lobe of the thyroid extending into the isthmus and a separate mass inferior to the sternal notch (figures 1B, 3). Fusion of the SPECT images of the I-123 scan (figure 4) with the CT scan of the thorax confirmed a large 1.5 cm x 3 cm manubrial metastasis and not an extension of the mass into the anterior mediastinum. Laboratory testing showed normal thyroid function with a thyrotropin 1.23 uU/mL and free thyroxine 1.1 ng/dL with a thyroglobulin of 33,537 ng/mL with negative thyroglobulin antibodies. Thyroidectomy and bilateral neck dissections removed a 6-cm poorly differentiated follicular thyroid carcinoma with bilateral metastatic nodes in levels 6 and 3 bilaterally.

Figure 3 A, B & C: SPECT imaging of thyroid
Figure 3. SPECT imaging of the thyroid. I-123 thyroid scan with pseudocolorization. A. Anterior AP image showing the thyroid. B. More posterior AP image showing uptake into the manubrial mass. C. Sagittal reconstruction showing I-123 uptake in the thyroid is separate from the manubrial uptake.

Figure 4 A&B: Fusion of axial CT and SPECT images
Figure 4. Fusion of Axial CT and SPECT images. A. Axial images of the upper thorax showing the apical lung and the expansile lesion in the manubrium. B. Fusion of the CT scan with the axial SPECT I-123 images demonstrate that the manubrial mass an iodine-avid metastasis.

Postoperatively, her thyroglobulin fell to 18,068 ng/mL. She was considered for manubriumectomy to remove the large metastatic tumor because a tumor this size within bone — even if strongly iodine avid — is unlikely responsive to radioactive iodine therapy. However, the patient refused surgery. Since the manubrial tumor was not invasive and asymptomatic, a palliative dose of radioactive was planned. She was allowed to become hypothyroid, and four days before admission for radioiodine therapy she was admitted for a small amount of hemoptysis; a CT scan with contrast was ordered by the admitting physicians. Because of the large amount of iodine in the IV CT contrast, she was placed on triiodothyronine with a plan to treat in six weeks or when her urinary iodine levels decreased. Within 10 days she was admitted again for shortness of breath with a new left lower lobe pneumonia, elevated white blood cell count and fever. Her shortness of breath continued to worsen when a pleural effusion developed five days after admission that nearly obliterated her right thorax. Despite antibiotics and placement of a chest tube, the patient suddenly expired. An autopsy was refused by the family to determine cause of death.

Another part of this story is the tragic delay in diagnosis of this poorly differentiated thyroid carcinoma for one year, despite multiple visits for complaints of neck enlargement and shortness of breath. Insufficient biopsies occur in the hands of even the most experienced clinician, but they need to be repeated immediately with ultrasound guidance. The imaging lesson of this story is that clinicians must look at the images and not the reports. Despite discussing this case with a very experienced nuclear medicine physician, she was convinced that the technetium-99m trapping below the sternal notch was in the substernal extension of the tumor. Only after assessing by ultrasound and reviewing the CT images was it clear that the thyroid tissue did not extend below the clavicles. Radioactive iodine SPECT images fused with CT images allowed us to make the diagnosis of a sternal metastasis. Although it was suspected that she had pulmonary metastases, it had not been confirmed. However, the distant metastatic disease to bone confirmed her poor prognosis.

Radioiodine SPECT/CT scanning is extremely useful for accurate localization and assessment of regional and distant radioiodine uptake in residual thyroid remnant and metastases in nodes, lung or bones. In addition, radioactive iodine SPECT/CT is extremely useful to determine if physiological trapping of radioiodine is pathological or an unusual physiological variation.

Stephanie L. Lee, MD, PhD, is Associate Chief in the Section of Endocrinology, Diabetes and Nutrition and Associate Professor of Medicine at Boston Medical Center.

For more information:

Chen L. J Nucl Med. 2008;49:1952-1957.

Wang H. Clin Imaging. 2009;33:49-54.

Wong KK. Am J Roentgenol. 2008;191:1785-94.