A 45-year-old man presented to nuclear medicine for evaluation of hyperthyroidism with a desire for definitive radioiodine therapy. Thyroid scintigraphy using Tc-99m pertechnetate (Figure) was performed and revealed diffusely decreased uptake of the radiopharmaceutical compared to the salivary glands. No focal nodule was identified. The 24-hour I-131 uptake was 1.7%, which is below the normal range of 7.5% to 25%.
Diffuse decreased uptake of the radiopharmaceutical throughout the thyroid gland with a depressed 24-hour thyroid uptake value
Thyrotoxicosis is the state of symptoms and increased metabolism secondary to elevated thyroid hormone levels. Complementing clinical evaluation and serum lab values, thyroid scintigraphy is a useful tool in determining the cause of thyrotoxicosis.1
The differential diagnosis for thyrotoxicosis includes Graves’ disease and other syndromes that cause elevated thyroid hormones including subacute thyroiditis, iodine-induced thyrotoxicosis, factitious thyrotoxicosis, and even rarer conditions such as struma ovarii. Determining the underlying cause of thyrotoxicosis is essential to determining the appropriate treatment.1
Graves’ disease is an autoimmune disorder characterized by antibodies to the thyrotropin (also known as thyroid-stimulating hormone [TSH]) receptor that stimulate the thyroid gland to secrete thyroid hormones. Serum TSH levels are classically low due to the pituitary feedback loop. Typically, thyroid radiotracer uptake is increased diffusely on scintigraphy with elevated thyroid uptake values. Patients can be treated with I-131 radioiodine ablation, anti-thyroid medication, or surgery.1
Most patients with thyrotoxicosis have Graves’ disease. Graves’ disease is often seen in middle-aged females and presents with a variety of symptoms including weight loss, insomnia, anxiety, goiter, exophthalmos, and pretibial myxedema.2
Subacute thyroiditis is the most common cause of thyrotoxicosis in the setting of decreased radiotracer uptake on nuclear medicine studies. Subacute thyroiditis can be further classified as granulomatous thyroiditis (deQuervain’s thyroiditis), silent thyroiditis, and postpartum thyroiditis. Regardless of the subtype, thyroid inflammation results in the release of thyroid hormones with the expected symptoms of thyrotoxicosis. This elevation suppresses TSH and leads to a subsequent phase of hypothyroidism. Ultimately, the patient returns to a euthyroid state. Therefore, subacute thyroiditis is generally considered self-limiting, resolving within weeks to months, and nuclear medicine radioiodine therapies are not indicated.2 Management is usually handled by endocrinologists and/or primary care specialists, and treatment typically focuses on symptom relief.
Granulomatous thyroiditis is a type of subacute thyroiditis that follows a viral upper respiratory infection. Although not routinely sampled clinically, granulomas are found on histopathology.2 Patients with deQuervain’s thyroiditis present clinically with pain, fever and thyroid tenderness. A postviral inflammatory response causes inflammation of the thyroid follicles and release of stored thyroid hormones, producing thyrotoxicosis. The inflammation can cause pain and tenderness.3
The inflammation prevents the otherwise normal transport of iodine and pertechnetate into the thyroid cells, resulting in the typical scintigraphy findings of decreased uptake.1,4 Nonsteroidal anti-inflammatory drugs can provide symptomatic relief.1
Silent thyroiditis is a form of subacute thyroiditis typically found in elderly patients with possible arrhythmias and a nonenlarged thyroid. Patients do not typically present with thyroid pain.2 Silent thyroiditis is thought to be an autoimmune thyroiditis and a variant of Hashimoto’s thyroiditis.1
The pathogenesis of silent thyroiditis is lymphocytic infiltration of the thyroid follicles causing damage and release of thyroid hormones, producing thyrotoxicosis with identical clinical symptoms to Graves’ disease. The episode of hyperthyroidism resolves within weeks. The inflamed follicle cells are unable to organify iodine after the episode of inflammation, causing hypothyroidism and decreased radiotracer uptake on thyroid scintigraphy.5
Postpartum thyroiditis is another form of subacute thyroiditis manifesting weeks to months after delivery, with patients having a mildly enlarged thyroid gland.2 Postpartum thyroiditis occurs in up to 5% of pregnancies.1
The thyrotoxicosis in postpartum thyroiditis is mild, typically self-limiting, and resolves within weeks. Histology reveals lymphocytic infiltration of thyroid tissue, similar to silent thyroiditis.5 A transient hypothyroidism follows the episode of thyrotoxicosis in postpartum thyroiditis and can potentially be permanent requiring clinical monitoring.1
Iodine-induced thyrotoxicosis is most commonly secondary to treatment with the antiarrhythmic drug amiodarone, which contains 75mg of iodine per 200mg tablet. A similar process can be seen with iodinated contrast. Radiotracer uptake decreases as the radiotracer competes for uptake with the relatively large pool of stable iodine.1 Amiodarone thyrotoxicosis occurs in 3% of patients treated with amiodarone, and the risk of amiodarone-induced thyrotoxicosis is directly proportional to dosage.6 Treatment is medical and nuclear medicine radioiodine ablation is not indicated.1
Factitious thyroiditis is manifested as elevated serum thyroid hormone secondary to ingesting exogenous thyroid hormone in euthyroid patients, usually for weight loss. TSH is suppressed and iodine uptake is decreased, resulting in diffusely decreased radiotracer uptake. Treatment is to cease ingestion of exogenous thyroid hormones.1
Struma ovarii is hyperthyroidism secondary to a rare, typically benign, teratomatous ovarian tumor that secretes thyroid hormones. The excess thyroid hormone suppresses TSH levels and decreases scintigraphic radiotracer uptake. Treatment is tumor excision.1
In this case, although the patient presented clinically with symptoms indistinguishable from Graves’ disease, the thyroid uptake and scan did not support this diagnosis. Therefore, other causes of hyperthyroidism that would have decreased thyroid activity on nuclear medicine studies were considered. Among the differentials discussed above, the final diagnosis is largely based on clinical history, as tissue sampling is not routinely performed. In this case, a diagnosis of a subacute thyroiditis was made.
The most important duty of the imager is to recognize and alert the clinician of diagnostic possibilities other than Graves’ disease as the cause of the hyperthyroid state. Nuclear medicine radioiodine therapies for hyperthyroidism are indicated for Graves’ disease and hyperfunctioning nodule(s). Performing a radioiodine therapy in this patient would have been inappropriate given 1) the self-limiting nature of most cases of subacute thyroiditis, making a permanent ablation of the thyroid gland unnecessary; and 2) the extremely low 24-hour thyroid uptake value that would require an unreasonably high dose of I-131 for a successful ablation.
Because it is common, Graves’ disease is the initial primary diagnostic consideration in patients with thyrotoxicosis. However, clinicians and imagers must be cognizant of other causes of thyrotoxicosis as the treatments are different. Encountering a hyperthyroid patient with depressed findings on scintigraphy suggests a process other than Graves’ disease. Subacute thyroiditis, as well as other rarer causes of thyrotoxicosis, are uncommon but are important disease processes for imagers to be aware of to avoid inappropriate and ineffective radioiodine therapies.
Sabbagh M, Vollman DP, Viglianti BL. Decreased Thyroid Activity in a Patient with Hyperthyroidism. J Am Osteopath Coll Radiol. 2018;7(1):29-31.
Mathieu Sabbagh, D.O.,1 Dennis P. Vollman, D.O.,1 Benjamin L. Viglianti, M.D., Ph.D.2,3
1 Department of Radiology, Garden City Hospital, Garden City, MI
2 Department of Radiology, University of Michigan, Ann Arbor, MI
3 Nuclear Medicine Service, Veterans Affairs (VA) Medical Center, Ann Arbor, MI