A Rare Cause of Thyrotoxicosis: Metastasis of Ovarian Clear Cell Carcinoma to the Thyroid Gland

Abstract

Metastases to the thyroid gland are rare, accounting for up to 2% of all thyroid malignancies. Ovarian cancer metastasizing to the thyroid is exceedingly uncommon, with only a few cases reported in the literature. We present the case of a 36-year-old female individual with a history of metastatic ovarian clear cell carcinoma and known thyroid metastasis who presented with shortness of breath, dysphagia, and palpitations. Laboratory evaluation revealed undetectable thyroid-stimulating hormone (TSH), elevated free thyroxine (fT4) and triiodothyronine (fT3), and markedly increased serum thyroglobulin levels. A computed tomography (CT) scan of the neck demonstrated diffuse thyroid infiltration with compressive features. The patient was diagnosed with thyrotoxicosis and treated with methimazole, prednisone, and metoprolol. To our knowledge, this is the first reported case of ovarian clear cell carcinoma with thyroid gland metastasis presenting with concomitant thyrotoxicosis. Although thyroid metastases are rare and typically nonfunctional, they should be considered in patients with known malignancy who develop new thyroid dysfunction, particularly when biochemical or imaging findings are atypical for thyroiditis or autoimmune thyroid disease. Recognizing this entity is important, as timely distinction from more common causes of thyrotoxicosis can guide appropriate, patient-centered management.

Introduction

Secondary thyroid cancer is a rare clinical entity, accounting for up to 2% of all thyroid malignancies [1]. Despite the thyroid gland's rich vascular supply, its microenvironment is typically inhospitable to metastatic tumor cell implantation and proliferation [2]. The most common primary sources of metastases to the thyroid include the kidney, lung, breast, and gastrointestinal tract [3]. In contrast, metastases originating from primary ovarian cancer are exceedingly rare, with only 3 cases reported in the literature to date [4-6].

Secondary thyroid cancers are often asymptomatic or present with nonspecific symptoms. Most cases are identified incidentally during surveillance imaging for distant metastases [7]. When present, symptoms typically include a painless neck mass or compressive features such as dysphagia or hoarseness. The subtle clinical presentation often poses a diagnostic challenge, as these lesions are frequently indistinguishable from primary thyroid malignancies or benign nodular disease without histopathologic confirmation. Although these tumors are generally nonfunctional, thyroid dysfunction is rarely observed [3].

Here, we report a unique case of metastatic ovarian clear cell carcinoma to the thyroid gland, which unusually presented with clinical thyrotoxicosis.

Case Presentation

A 36-year-old female patient with a history of metastatic ovarian clear cell carcinoma presented with a 2-day history of dysphagia, shortness of breath, palpitations, nausea, and vomiting. Her initial presentation occurred 5 years prior with 4 months of pelvic pain. Transvaginal ultrasound (US) revealed a 12.7-cm cystic mass originating from the left ovary, and her serum cancer antigen 125 (CA-125) level was elevated at 80 U/mL (SI: 80 kU/L) (reference range, 0-35 U/mL [SI: 0-35 kU/L]). Pelvic magnetic resonance imaging (MRI) demonstrated a large complex cystic mass with solid components in the right adnexa (Fig. 1A).

Figure 1.

(A) Pelvic magnetic resonance imaging (MRI), sagittal view, demonstrates an 11.0 × 12.3 × 11.0 cm complex cystic mass with solid components arising from the left adnexa. (B) Positron emission tomography–computed tomography (PET-CT), axial view, reveals increased fluorodeoxyglucose (FDG) uptake in the inferior pole of the left thyroid lobe, concerning for metastatic disease. (C) Contrast-enhanced computed tomography (CT) of the neck, axial view, shows a diffusely enlarged thyroid gland replaced by multiple hypoattenuating lesions consistent with metastatic ovarian carcinoma.

A left salpingo-oophorectomy was performed, and histopathology confirmed ovarian clear cell carcinoma. Cytology from pelvic washing revealed malignant cells, and the patient was diagnosed with stage IC3 ovarian clear cell carcinoma. She received 6 cycles of carboplatin and paclitaxel chemotherapy, after which CA-125 levels decreased to 5 U/mL (SI: 5 kU/L). A post-treatment computed tomography (CT) scan of the chest, abdomen, and pelvis showed no evidence of disease. Surveillance included CA-125 monitoring every 3 months.

Three years later, her CA-125 level rose to 63 U/mL (SI: 63 kU/L). CT imaging showed a 6.3-cm left paraaortic lymph node and multiple enlarged mesenteric lymph nodes. A CT-guided biopsy confirmed recurrent clear cell carcinoma. The patient underwent 6 additional cycles of chemotherapy with carboplatin, paclitaxel, and bevacizumab. A subsequent positron emission tomography (PET)-CT scan revealed persistent paraaortic lymphadenopathy and new focal fluorodeoxyglucose (FDG) uptake in the inferior pole of the left thyroid lobe (Fig. 1B). US-guided core biopsy of the thyroid nodule confirmed metastatic ovarian clear cell carcinoma.

Diagnostic Assessment

On physical examination, the patient was tachycardic with a regular rhythm, and her thyroid was diffusely enlarged without tenderness. Electrocardiography revealed sinus tachycardia with a heart rate of 157 beats per minute. Laboratory evaluation demonstrated an undetectable serum thyroid-stimulating hormone (TSH) level, elevated free thyroxine (fT4) level of 2.7 ng/dL (SI: 34.75 pmol/L) (reference range, 0.7-1.5 ng/dL [SI: 9.01-19.31 pmol/L]), and elevated free triiodothyronine (fT3) level of 11 pg/mL (SI: 16.9 pmol/L) (reference range, 1.7-3.7 pg/mL [SI: 2.61-5.7 pmol/L]). Her thyroglobulin (Tg) level was markedly elevated at 13 559 ng/mL (SI: 13 559 μg/L) (reference range, < 55 ng/mL [SI: < 55 μg/L]). Thyroid-stimulating immunoglobulin (TSI) and thyroid peroxidase antibody (TPOAb) levels were within normal limits.

Chart review confirmed that the patient had not received intravenous iodinated contrast for at least 4 weeks. A radioactive iodine uptake scan demonstrated diffusely decreased uptake (<1%; reference range, 10%-35%) with an enlarged thyroid gland containing multiple hypoattenuating masses, causing tracheal narrowing and esophageal compression (Fig. 1C). Brain MRI revealed a 2.4-cm mass in the left posterior occipital lobe, consistent with metastatic disease. Flexible nasolaryngoscopy showed bilateral vocal cord paralysis with minimal airway patency.

Treatment

The Burch-Wartofsky score was calculated as 35 (10 points for gastrointestinal symptoms and 25 points for a heart rate >140 beats/min; 25-44 = suggestive of impending thyroid storm), consistent with severe thyrotoxicosis [8]. Given concern for severe thyrotoxicosis, the patient was started on methimazole 5 mg daily, prednisone 40 mg daily, and metoprolol 100 mg twice daily. This regimen led to resolution of tachycardia and improvement in gastrointestinal symptoms. Due to concerns for airway compromise, a tracheostomy was performed to secure the airway. Endocrine surgery was consulted for potential thyroidectomy; however, surgery was not recommended given the diffuse metastatic disease and the limited life expectancy. The patient subsequently underwent palliative neck radiotherapy, which resulted in symptomatic relief of dysphagia and neck discomfort.

Outcome and Follow-Up

Following comprehensive goals-of-care discussions, the patient elected to transition to hospice care.

Discussion

Metastatic disease to the thyroid gland is an uncommon clinical entity, comprising approximately 1% to 2% of all thyroid malignancies [1]. Despite the thyroid gland`s rich vascularity, it is an infrequent site of metastasis, likely due to its high oxygen and iodine content, colloid-rich environment, and rapid arterial blood flow, which may inhibit tumor implantation and growth [2]. Metastatic involvement of the thyroid from ovarian cancer is exceedingly rare, with only a few cases reported in the literature, and even fewer arising from ovarian clear cell carcinoma [4-6].

Our case is unique for multiple reasons. First, it demonstrates a rare metastatic pattern in a patient with advanced ovarian clear cell carcinoma, a histologic subtype known for its aggressive behavior and relative resistance to chemotherapy [9]. Second, the presentation with thyrotoxicosis is highly unusual and was not described in the previous cases [4-6]. Most metastatic lesions to the thyroid are nonfunctional and do not disrupt thyroid hormone dysfunction. Daroszewski et al proposed that thyrotoxicosis in the setting of nonfunctional thyroid cancer can be the result of the destruction of the thyroid follicles by a rapidly enlarging malignancy and releasing the preformed thyroid hormones to the circulation [7]. In our patient, the combination of suppressed TSH, elevated fT4 and fT3, elevated Tg, negative thyroid autoantibodies, and diffusely reduced radioactive iodine uptake were consistent with destructive thyroiditis secondary to metastatic infiltration.

The differential diagnosis for new-onset thyrotoxicosis in a patient with known malignancy is broad and includes painless (silent) thyroiditis, Graves disease, medication-induced hyperthyroidism (eg, tyrosine kinase inhibitors), and metastatic involvement [10]. While painless thyroiditis is a relatively more common cause of thyrotoxicosis and can present with elevated Tg levels, the Tg elevation is usually more modest and rarely reaches extreme values [11, 12]. In contrast, our patient's Tg level was profoundly elevated at 13 559 ng/mL (SI: 13 559 μg/L). Furthermore, the absence of thyroid autoantibodies, including TPOAb, argues against painless thyroiditis, making it less likely in this case [13].

The management of thyroid metastases is largely individualized and depends on the extent of disease, symptoms, and the patient's overall prognosis. Surgical resection may be considered in selected patients with isolated thyroid metastasis or in cases with compressive symptoms. If surgical resection is not an option, as in our case, palliative interventions such as corticosteroids, and palliative radiotherapy may provide meaningful relief of compressive symptoms.

This case highlights an exceptionally rare presentation of metastatic ovarian clear cell carcinoma to the thyroid gland with concomitant thyrotoxicosis. Although thyroid metastases are uncommon and typically nonfunctional, they should be considered in patients with known malignancy who develop new thyroid dysfunction, specifically when laboratory and imaging findings are atypical for more common causes of thyroiditis and autoimmune thyroid diseases. Recognition of this entity is important, as timely differentiation from more common causes of thyrotoxicosis can guide appropriate management. Ultimately, multidisciplinary management, including symptom-directed therapy and timely goals-of-care discussions, plays a central role in optimizing quality of life in patients with advanced metastatic disease.

Learning Points

• Metastasis to the thyroid gland is rare, accounting for only 1% to 2% of all thyroid malignancies, despite the thyroid's rich vascular supply. Ovarian clear cell carcinoma rarely metastasizes to the thyroid, with very few reported cases in the literature.

• Metastatic thyroid involvement is typically nonfunctional, but in rare cases, it may cause destructive thyroiditis and thyrotoxicosis.

• A markedly elevated thyroglobulin level in the absence of thyroid autoantibodies and low radioactive iodine uptake should raise suspicion for destructive thyroiditis or metastatic infiltration.

Contributors

All authors made individual contributions to authorship. B.C. and A.B. were involved in the clinical care of the patient and preparation of the manuscript. All authors reviewed and approved the final draft.

Abbreviations

CA-125

cancer antigen 125

CT

computed tomography

fT3

free triiodothyronine

fT4

free thyroxine

MRI

magnetic resonance imaging

Tg

thyroglobulin

TPOAb

thyroid peroxidase antibody

TSH

thyrotropin (thyroid stimulating hormone)

US

ultrasound

Funding

No public or commercial funding.

Disclosures

None declared.

Informed Patient Consent for Publication

Signed informed consent was obtained from the patient.

Data Availability Statement

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.