A Rare Case of a Toxic Thyroid Nodule Found in a Hypothyroid Patient on Levothyroxine Therapy

Introduction: A hyperfunctional thyroid nodule can lead to symptoms of overt or subclinical hyperthyroidism but the association between a hyperfunctional thyroid nodule and hypothyroidism has not been well reported. We present a patient with a prior history of hypothyroidism previously controlled on Levothyroxine who later presented with an enlarging hot nodule. Case Presentation: A 62-year-old female with a history of factor V Leiden, hypothyroidism on levothyroxine therapy, and a meningioma presented to an outpatient clinic with complaints of fatigue, constipation, and 37-pound weight loss in one year. She was diagnosed with hypothyroidism 7 years ago after delivering her third child, but the underlying cause of her disease was unknown. She began taking levothyroxine 50mcg every morning after her diagnosis. She reported compliance and proper pill taking technique. Physical examination revealed a palpable thyroid nodule. The patient had a previous work up for thyroid nodules with a thyroid uptake and scan a few years prior, which showed a 1.42 x 0.96 x 1.87 cm hot nodule at the right middle lobe with a 24-hour uptake of 15.3%. The patient was asymptomatic at that time and thyroid function tests were within normal limits. She was instructed to continue taking levothyroxine. Repeat RAI Uptake scan at the time of her presentation to our office again showed the right middle lobe hot thyroid nodule with an increased 24-hour uptake of 27.5%. Ultrasound showed bilateral thyroid nodules and a hypervascular solid nodule measuring 2.28 x 1.27 x 1.9 cm that has increased in size. Lab work at this visit revealed a TSH of 0.329 uIu/mL, and free T4 of 1.25 ng/dL. Due to her low TSH and clinical presentation, the levothyroxine was discontinued. Anti-thyroid peroxidase antibodies were obtained to assess for Hashimoto’s Thyroiditis but were found to be normal. The patient was later referred to an endocrine surgeon for a total thyroidectomy. Conclusion: Although uncommon, hyperfunctional nodules in hypothyroid patients can create a confusing clinical picture with overlapping symptoms of underactive and overactive thyroid disease. It has been reported that patients with Hashimoto’s Thyroiditis can have hot nodules and coexisting hypothyroidism but the prevalence of hyperfunctional nodules in hypothyroid patients without Hashimoto’s Thyroiditis, as in this case, is not well-documented. Patients with hypothyroidism are treated with Levothyroxine but if coexisting hyperfunctional nodules are not detected, the patient may develop thyrotoxicosis. Clinicians should be aware of this rare but potentially life-threatening clinical condition.

Malignancy risk of hyperfunctioning thyroid nodules compared with non-toxic nodules: systematic review and a meta-analysis

Background Hyperfunctioning or hot nodules are thought to be rarely malignant. As such, current guidelines recommend that hot nodules be excluded from further malignancy risk stratification. The objective of this systematic review and meta-analysis is to compare the malignancy risk in hot nodules and non-toxic nodules in observational studies. Methods Ovid MEDLINE Daily and Ovid MEDLINE, EMBASE, Scopus, and Web of Science databases were searched. Observational studies which met all of the following were included: (1) use thyroid scintigraphy for nodule assessment, (2) inclusion of both hyperfunctioning and non-functioning nodules based on scintigraphy, (3) available postoperative histopathologic nodule results, (4) published up to November 12, 2020 in either English or French. The following data was extracted: malignancy outcomes include malignancy rate, mapping of the carcinoma within the hot nodule, inclusion of microcarcinomas, and presence of gene mutations. Results Among the seven included studies, overall incidence of malignancy in all hot thyroid nodules ranged from 5 to 100% in comparison with non-toxic nodules, 3.8–46%. Odds of malignancy were also compared between hot and non-toxic thyroid nodules, separated into solitary nodules, multiple nodules and combination of the two. Pooled odds ratio (OR) of solitary thyroid nodules revealed a single hot nodule OR of 0.38 (95% confidence interval (CI) 0.25, 0.59), toxic multinodular goiter OR of 0.51 (95% CI 0.34, 0.75), and a combined hot nodule OR of 0.45 (95% CI 0.31, 0.65). The odds of malignancy are reduced by 55% in hot nodules; however, the incidence was not zero. Conclusions Odds of malignancy of hot nodules is reduced compared with non-toxic nodules; however, the incidence of malignancy reported in hot nodules was higher than expected. These findings highlight the need for further studies into the malignancy risk of hot nodules.

SUN-478 Poorly Differentiated Thyroid Cancer Arising from a Hyperfunctioning Nodule Treated with I-131

Thyroid nodules are a common clinical problem with an incidence of up to 1% in men and 7–15% of cases representing thyroid cancer. Current American Thyroid Association guidelines do not recommend cytologic evaluation of hyperfunctioning nodules as they rarely harbor malignancy. We present a case of a hyperfunctioning nodule which years after ablation was diagnosed as a poorly differentiated thyroid cancer. A 38 year old male had a 4cm thyroid nodule discovered in 1994. Nuclear Medicine (NM) imaging revealed a warm nodule though patient was euthyroid. Biopsy was benign with good sample. Nodule was followed with serial ultrasound (US) and TSH. In 2008 he became hyperthyroid. Scan showed hot nodule and he was given 27.3 mCi I-131 with normalization of the TSH. In 2013 patient again developed hyperthyroidism. NM imaging showed a hot nodule. After 29.5 mCi I-131 he became hypothyroid requiring levothyroxine. Intermittent US showed stability. In early 2019 nodule was 3.7cm, solid and hypoechoic but more heterogeneous. Despite TIRADS recommendation that nodule no longer be followed by US, FNA was performed and revealed Bathesda IV cytology. Gene classification with Thyroseq revealed a TERT mutation. On total thyroidectomy pathology demonstrated a 4.5cm poorly differentiated carcinoma thought to be of follicular origin. Tumor was partially encapsulated with multiple areas of vascular invasion and extensive tumor necrosis. Tumor was present at inked margin but no extrathyroidal extension was noted. There was a <1mm metastasis noted in 1 peri-isthmus lymph node. One month post operatively thyroglobulin was 123.5 ng/mL. I-123 whole body scan demonstrated bilateral uptake in the region of the thyroid suggesting adenopathy; there were similar findings on FDG-PET scan but no adenopathy was identified on US or the CT portion of the PET. Patient was treated with 129mCI of I-131 with focally intense activity in the lower neck on post treatment scan but nothing elsewhere. Follow up lab testing is pending. Though thyroid nodules are a common clinical problem, there are only isolated case reports of hyperfunctioning nodules being later found to have thyroid cancer. One retrospective series of over 6000 patients found a thyroid cancer prevalence of 0.15% in hyperthyroid patients treated with I-131.i Poorly differentiated thyroid cancer is thought to occur as a mutation from a differentiated cancer. Here, we present a novel case of the 25 year course of a benign, hyperfunctioning nodule later mutating into an aggressive poorly differentiated cancer. We hypothesize that this nodule mutated late in the course as it was clearly benign on initial biopsy and had a benign course until recent events. This case supports periodic screening of hyperfunctioning nodules after ablation, especially if the nodule does not shrink significantly after I-131. Endnotes i Angusti T et al. The Journal of Nuclear Medicine 41(6):1006–1009.

Marine-Lenhart Syndrome: Case Report, Diagnosis, and Management

The coexistence of thyroid functioning nodules and Graves’ disease is called Marine-Lenhart syndrome. This condition is estimated to occur in 0.8-2.7% of patients with Graves’ disease with few cases reported in the literature. Criteria for the diagnosis are not well defined. Here, we present a case of hyperthyroidism characterized by the presence of stimulating TSH receptor antibodies and severe bilateral exophthalmos. A thyroid uptake and scan revealed an elevated 24-hour iodine-131 uptake and a discrete hot nodule in the upper pole of the right lobe which was also observed with a thyroid ultrasound. The patient was diagnosed with Marine-Lenhart syndrome complicated by thyroid eye disease and was treated with methimazole followed by thyroidectomy and orbital decompression. We review the existing literature and propose criteria for the diagnosis and treatment of this condition.

Follicular Carcinoma Masquerading as a Hot Nodule in a Pediatric Patient

Autonomous functioning thyroid nodules (AFTNs) are generally considered to be benign entities, with malignancy found in about 1 per cent considered to be rare in the general population. Because of this low rate, fine needle aspiration is generally not recommended, and these lesions are most often treated with radioactive iodine, medication, or surgery. However, AFTNs are exceedingly rare in the pediatric population and the optimal treatment is not defined. We present a 14-year-old female patient with an AFTN treated with surgical resection and found to contain a follicular carcinoma with capsular invasion.