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Hyperthyroidism and a thyroid nodule
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A 51-year-old female with uterine fibroids, menorrhagia and iron deficiency anemia was referred to the endocrine clinic for abnormal thyroid function tests.
She had no prior history of thyroid disease or head and neck radiation. She had no family history of thyroid disease or thyroid cancer. She noted increasing fatigue with occasional palpitations while walking. She denied neck mass, anterior neck pressure or dysphagia.
Stephanie L. Lee
Her thyroid was mildly enlarged at 30 g with a 2.5 cm nodule in the right lobe. The nodule was firm to palpation, mobile and nontender. An ultrasound was performed in the clinic that showed a slightly enlarged thyroid with a heterogeneous, mildly hypoechoic echotexture but without significant vascular flow by Doppler. The thyroid parenchyma had a microcytic change consistent with a chronic thyroiditis.
A hypoechoic nodule in the inferior lateral right lobe was identified. This taller-than-wide nodule measured 2.9 cm x 2 cm x 1.8 cm (longitudinal x anteroposterior x transverse) with an irregular and undulating border (Figure 1).
Doppler analysis showed there were intranodular microcalcifications and macrocalcifications and grade 3/4 intranodular vascularity. No significant adenopathy was identified medial or lateral to the great vessels.
Biopsy, iodine uptake, labs
At this first visit, an ultrasound-guided fine needle aspiration biopsy was performed of the right nodule. While waiting for the cytology results, a 4-hour I-123 radioactive iodine uptake and scan was performed.
Figure 1. Thyroid ultrasound: A. Transverse image of the lower right thyroid lobe showing a taller-than-wide, very hypoechoic thyroid nodule with macrocalcifications (red arrows) and a cluster of microcalcifications (yellow arrow). TR= trachea. CA=carotid artery. B. Sagittal image of the right thyroid lobe. The hypoechoic nodule has an undulating margin (blue arrows), macrocalcifications (red arrow) and microcalcifications (yellow arrows). The surrounding thyroid parenchyma is hypoechoic and heterogeneous with microcytic change consistent with a chronic thyroiditis (THY).
The scan showed homogeneous uptake in a mildly enlarged gland with a photopenia area in the inferior lateral right lobe (Figure 2). The thyroid uptake was elevated at 21.5% at 4 hours (expected is 5%-15%). The results are consistent with Graves’ disease with a cold right inferior lateral nodule.
Laboratory testing showed hyperthyroidism with a thyroid-stimulating hormone level of 0.01 mIU/L (normal range, 0.35-4.9), thyroxine level of 9 mcg/dL (normal range, 5-11.4), triiodothyronine uptake of 30.1% (normal range, 21-38), free T4 index of 2.7 (normal range, 1-4), and T3 of 170 ng/dL (normal range, 80-160). Her thyroid peroxidase antibody was normal at 1 IU/mL (normal range, <5) with an elevated thyroid-stimulating immunoglobulin of 208% baseline (normal range, <140). The cytology was consistent with a papillary thyroid carcinoma.
Unanticipated scenario
The 2009 American Thyroid Association guideline for thyroid nodules and cancer suggests the first step after the detection of a thyroid nodule is to measure TSH followed by a thyroid ultrasound to confirm the presence of a nodule.
If the TSH is normal or elevated, an ultrasound-guided biopsy should be performed. If the TSH is suppressed, a nuclear thyroid scan is performed, and if the nodule is cold or less iodine avid than the surrounding thyroid parenchyma, then an ultrasound-guided biopsy of the nodule is recommended.
When the nodule has an increased uptake compared with the surrounding thyroid, the risk for thyroid malignancy in this toxic thyroid adenoma is extremely low, but not zero, and biopsy is not routinely recommended. This patient with a thyroid nodule and hyperthyroidism did not have a toxic adenoma but a nonfunctional nodule in a Graves’ gland.
Figure 2. Radioactive Iodine thyroid scan: 4 hours after the oral administration of 455 mcCi I-123, the patient had thyroid scintigraphy scan and thyroid uptake. The right thyroid lobe was slightly larger than the left lobe. The anteroposterior view shows a large area of photopenia in the inferior right thyroid lobe. The isotope uptake was homogeneously increased with an elevated 4-hour uptake of 21.5% (normal, 5%-15%). A photopenic area in the inferior right lobe was identified that correlates with the location of the nodule on thyroid ultrasound. The appearance is consistent with Graves’ hyperthyroidism with a cold, non-iodine avid nodule in the right inferior lobe. Photos courtesy of Stephanie L. Lee, MD, PhD.
In this situation, the ultrasound appearance with a very hypoechoic, taller-than-wide nodule with intranodular vascularity, irregular margins, and micro- and macro-calcifications has sensitivity for thyroid cancer of more than 91.9%. If the patient had waited 1 to 3 weeks that is typical for our hospital to schedule a thyroid scan and uptake before her biopsy, it would have prevented an expeditious diagnosis of cancer.
This is a reminder that even the best written evidence-based guidelines cannot anticipate every clinical scenario, and clinical judgment and experience should also help guide the diagnostic course. My fellows have asked me whether I would have biopsied this nodule if it was autonomous on nuclear scan, and the answer is still yes. The large multicenter trial by Moon showing the high specificity for cancer with these ultrasound characteristics did not exclude nodules that were iodine avid. The OR of cancer for the following features are shown in Table 1.