Papillary Thyroid Cancer with Bilateral Adrenal Metastases

Introduction

Papillary thyroid carcinoma is the most common type of thyroid malignancy (88%) and has an excellent prognosis (1). It typically remains confined to the thyroid or may metastasize to regional lymph nodes. Distant organ metastasis is rare, most commonly involves the lungs (40% to 80%) and bone (6% to 36%), and has a poor prognosis. Other distant metastases are rare and may involve the brain, liver, adrenal glands, and skin (2).

Metastasis of papillary thyroid cancer to abdominal organs is extremely rare. Whole body scintigraphy with ¹³¹I is useful during follow-up to detect persistent disease, especially in high- or intermediate-risk patients. Adrenal uptake of ¹³¹I resulting from metastatic thyroid cancer has been described in four patients, including papillary thyroid cancer (two patients) (3,4), an undefined thyroid cancer originating from follicular cells (one patient) (5), and follicular thyroid cancer (one patient) (6). However, a literature review showed no previously reported case of bilateral adrenal uptake in patients with thyroid cancer who had whole body scintigraphy with ¹³¹I (7). We treated a patient with aggressive metastatic papillary thyroid cancer who had ¹³¹I uptake in both adrenals on ¹³¹I scintigraphy and bilateral adrenal lesions on abdominal computed tomography (CT) scans.

Patient

A 47-year-old woman presented for evaluation because of severe right upper arm pain and weakness. Magnetic resonance imaging (MRI) of the thoracic spine showed a compression fracture at the third thoracic vertebra associated with a soft tissue mass (Fig. 1A). A CT-guided biopsy of the mass showed metastatic papillary thyroid carcinoma. Ultrasonography of the neck showed an enlarged right thyroid lobe with cervical lymphadenopathy. A high resolution CT scan of the chest showed multiple bilateral pulmonary nodules (Fig. 1B). A whole body bone scintigraphy with technetium Tc 99m methylene diphosphonate showed only uptake at the third thoracic vertebra.

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FIG. 1.

A 47-year-old woman who had metastatic papillary thyroid cancer. Initial treatment included thyroidectomy, external beam radiation therapy to the thoracic spine, and ¹³¹I. (A) Magnetic resonance imaging (MRI) of the thoracic spine before treatment showed a compression fracture of the third thoracic vertebra associated with a soft tissue mass (arrow). (B) High-resolution computed tomography (CT) scan before treatment showed pulmonary metastases.

The patient was treated with total thyroidectomy and lymph node dissection. Histologic evaluation of the thyroid tumor (3 cm long×5 cm wide) showed a classic variant of papillary thyroid carcinoma of the right thyroid lobe (Fig. 2A). There was no tall cell, columnar, or diffuse sclerosing variant to suggest aggressive tumor biology. There was lymphovascular and capsular invasion, and four lymph nodes contained metastatic papillary thyroid carcinoma (Fig. 2B).

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FIG. 2.

(A) Histology from the right thyroid lobe with papillary thyroid cancer. Hematoxylin and eosin (400×) microphotograph of papillary carcinoma showing papillary formation, lined by hyperchromatic enlarged nuclei with inconspicuous nucleoli, focal nuclear overlap with nuclear grooves, and focal clearing of the chromatin. (B) Histology from a local lymph node metastasis. Hematoxylin and eosin (40×) microphotograph of metastatic papillary carcinoma in the lymph node.

The lesion at the third thoracic vertebra was not operable and was treated with external beam radiation therapy from the first to fourth thoracic vertebrae. After withdrawal of thyroid hormone for 4 weeks, serum thyrotropin (TSH) was 51 mU/L, the stimulated thyroglobulin was 1426 ng/mL (Table 1). The patient was treated with ¹³¹I (9.6 GBq). The posttherapy whole-body scintigraphy showed radioactive iodine uptake in the thyroid bed, the third thoracic vertebra, and right pulmonary nodules (Fig. 3A). An abdominal CT scan showed normal adrenal glands (Fig. 4A). The patient was treated with a suppressive dose of levothyroxine (125 μg once daily).

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FIG. 3.

Serial whole-body scans after treatment with ¹³¹I. (A) After the first ¹³¹I treatment, there was increased uptake in the thyroid bed (T), the thoracic spine (Th3), and right pulmonary metastasis (P). There was no increased uptake in the abdomen. (B) After the third ¹³¹I treatment, there was increased uptake in both lungs and the third thoracic vertebra (Th3). Faint uptake was noted in the right upper abdomen (arrow) and was interpreted as a sign of physiologic bowel activity. (C) After the fourth ¹³¹I treatment, there was focal uptake in both adrenal glands (arrows), with greater intensity in the right compared to the left adrenal gland. There was increased uptake in the thyroid bed (T), the third thoracic vertebra (Th3), and in the lungs (P).

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FIG. 4.

Serial CT scans of the abdomen. (A) After the first treatment with ¹³¹I, both adrenal glands appeared normal (arrows). (B) After the third treatment with ¹³¹I, a right adrenal lesion was noted (2 cm×3 cm; horizontal arrow). The left adrenal gland appears enlarged compared to the CT shown in (A) (vertical arrow). (C) After the fourth treatment with ¹³¹I, right (5 cm×6 cm) and left (2 cm×3 cm) adrenal lesions were noted (arrows).

The patient was followed for 3 years and was treated with three additional therapeutic doses of ¹³¹I (9.2 GBq per treatment); the doses were limited to 9.2 GBq to minimize the risk of pulmonary toxicity. All therapies were obtained after withdrawal of levothyroxine for 4 weeks. After thyroid hormone withdrawal, the TSH levels ranged from 51 to 97 mU/L and the thyroxine (T₄) levels were between 2 and 5 pmol/L (reference range 22–24 pmol/L; Table 1). Whole-body iodine scans were performed 10 days post ¹³¹I therapy. After the third ¹³¹I dose, the whole-body scintigraphy showed increased uptake in both lungs and the third thoracic vertebra; faint uptake was noted in the right upper abdomen and was interpreted as a sign of physiologic bowel activity (Fig. 3B). Abdominal CT scanning showed a right adrenal lesion (Fig. 4B). After the fourth ¹³¹I dose, the whole-body scan showed increased uptake in both adrenal glands, with greater intensity in the right compared to the left adrenal gland; there was increased uptake in the thyroid, the third thoracic vertebra, and both lungs (Fig. 3C). A repeat abdominal CT scan showed bilateral adrenal lesions (Fig. 4C). The left adrenal lesion (2 cm×3 cm) was enhanced and solid, and the right adrenal lesion (5 cm×6 cm) was cystic (8 Hounsfield units); both left and right adrenal glands had enlarged since the previous CT scan, consistent with bilateral adrenal metastasis.

Tissue biopsy of the adrenal masses was not obtained. Despite additional radioactive treatment and full TSH suppression (TSH 0.01 mU/L), the patient's disease progressed at all metastatic sites, with persistently elevated thyroglobulin levels; the stimulated thyroglobulin at the last radioactive iodine therapy was more than 5000 ng/mL (Table 1).

Discussion

This patient had bilateral adrenal metastases from papillary thyroid cancer. Bilateral adrenal metastases from papillary thyroid cancer are rare. Adrenal metastasis secondary to thyroid cancer was described previously in six patients, including four patients who had increased iodine uptake on whole body iodine scintigraphy (3 –6), one patient who had metastasis noted on a fluoro-deoxyglucose positron emission tomography (PET) scan (8), and one patient who had metastasis noted after adrenalectomy (9).

Optimal treatment of papillary thyroid cancer includes thyroidectomy, adjuvant ¹³¹I ablation therapy, and long-term TSH suppression with levothyroxine. Lifelong follow-up is needed and may include neck ultrasonography, measurement of stimulated and nonstimulated thyroglobulin levels, whole body scintigraphy with ¹³¹I, CT, MRI, and fluoro-deoxyglucose PET scans.

In whole-body ¹³¹I scintigraphy, iodine uptake in the abdomen is a common finding and may represent normal bowel activity. However, in a high-risk patient, iodine uptake may be an early sign of metastatic disease, as in the present patient. Delayed views and correlation with anatomic studies such as CT, MRI, single-photon emission CT, or PET-CT may help distinguishing normal physiologic iodine uptake from adrenal metastasis. The prognosis of patients with papillary thyroid cancer and distant metastasis is worse in older patients (age >45 years), multiple organ involvement, higher tumor stages, aggressive histologies, and a loss of the ability to concentrate ¹³¹I (10).

In summary, the present patient with advanced papillary thyroid cancer had the unusual finding of bilateral, rapidly growing adrenal metastases, confirmed with bilateral adrenal ¹³¹I uptake on whole-body scintigraphy and abdominal CT scans. The patient had a poor response to repeated radioactive iodine therapy after thyroidectomy. Elevated abdominal uptake of ¹³¹I in a high-risk patient may be an early sign of abdominal metastatic disease.