Toxic adenoma: to biopsy or not to biopsy?

Toxic adenoma nodules rarely harbour cancer. Fine-needle aspiration (FNA) is often not done because of the rarity of these lesions being cancer, the difficulty in interpreting cytology in hyperthyroid patients and the rare precipitation of thyrotoxicosis. We present two young, Caucasian female patients aged 29 and 13 years who were each diagnosed with a toxic nodule categorised as benign and indeterminate respectively. They underwent hemithyroidectomy after being rendered euthyroid, however their histology unexpectedly revealed differentiated follicular cancer. Despite thyroid cancer being rare in patients with toxic adenomas, it should be considered when planning treatment, especially if there are risk factors for cancer, or suspicious features on ultrasound examination. A review of the literature shows that compared with adenomas in euthyroid patients, patients in this group are generally younger and predominately female. If an FNA is considered, it should be performed after the patient is rendered euthyroid.

A Patient With Graves’ Disease And Thyroid-Associated Orbitopathy Undergoing Radioactive Iodine in Dr. Soetomo General Academic Hospital, Surabaya

Graves’ Disease (GD) is the most common etiology of thyrotoxicosis, followed by toxic multinodular goiter and toxic adenoma. GD can be managed with anti-thyroid drugs (ATDs), surgery, or radioactive iodine (RAI). Thyroid-associated orbitopathy (TAO) or Graves’ Ophthalmopathy (GO) affects 25%-50% patients with GD, and its presence usually dissuade clinicians to use RAI in treating hyperthyroidism. The presence of GO is a relative contraindication use of RAI in patients with GD, as RAI can worsen existing GO. Corticosteroid prophylaxis can be given to such patients to reduce likelihood of worsening of GO. However, patient with moderate to severe active GO is currently advised against undergoing RAI. Established guidelines recommend the use of corticosteroid prophylaxis in these patients. We reported a patients with GD and orbitopathy who was treated with RAI and was given steroid prophylaxis to prevent worsening of GO.

Hyperthyroidism Times 2: Dual Cause of Thyroid Hormone Excess

The most common etiology of Hyperthyroidism is due to circulating antibodies that are directed against the thyroid-stimulating hormone (TSH) receptor, known as Grave’s Disease (GD). Another cause is an autonomously functioning thyroid nodule over-producing hormones or Toxic Adenoma. The mechanism of these two pathologies are very distinct, but the question that arises is, can they coexist? This is a case of 44-year-old female who comes to the clinic referred by her ophthalmologist after been diagnosed with severe thyroid-associated orbitopathy currently on steroid therapy. Thyroid ultrasound has done previously showed enlarged homogenous thyroid gland with a single isoechoic nodule of 2.2x1.6x1.9cm with faint peripheral calcifications and vascularity. The patient was presenting with palpitations, heat intolerance, sweating, and discriminatory features such as double vision and left eye exophthalmos. On physical examination, there was no goiter or palpable thyroid nodules, but it was remarkable for left eyelid lag retraction and mild proptosis. Evaluation showed clinical and biochemical hyperthyroidism with TSH: 0.068 mU/ml (n:0.5-5.0mU/ml), FT4: 1.39ng/dl (n:0.87-1.85ng/dl), TSH receptor antibody: <1.10IU/L and thyroid-stimulating immunoglobulin: 0.54IU/L (borderline high). The patient was placed in antithyroid drugs and B-blockers for disease control. Afterward, the patient underwent a thyroid uptake scan reporting toxic adenoma on the left lobe, however even when the biochemical workup of GD is inconclusive, patient clinical findings are highly suggestive of it. Due to the risk of worsening orbitopathy with radioactive iodine therapy, patient was referred for surgical excision of toxic adenoma and total thyroidectomy was decided since residual thyroid tissue may expose the patient to circulating thyroid-stimulating immunoglobulin leading to hyperthyroidism recurrence and put her at risk of associated thyroid excess detrimental complications. Surgical specimen gross pathology biopsy reported the thyroid gland with hyperplastic changes of Grave’s Disease. Severe thyroid-associated orbitopathy was managed with decompression surgery but did not improve, for which an alternative therapeutic approach is decided with novel immunomodulatory agent and recent approved therapy, Teprotumumab. A monoclonal antibody that works on TSHR/IGF-1R signaling complex involved in Thyroid Eye Disease. Is unusual to see two different superimposing thyroid pathologies, but disease presentations can be atypical and can be present concomitantly. In this scenario, several factors must be taken into consideration when choosing an adequate therapy approach. Our case is an example that we need to individualize management options based on guidelines recommendations, patient’s clinical settings and decreased risks of future complications.

Severe Thyrotoxicosis Following Topical Iodine Application

Background: Exposure to iodine can lead to iodine-induced hyperthyroidism in patients with underlying thyroid disease. Clinical Case: A 67 year-old woman with a history of nontoxic multinodular goiter and atrial fibrillation presented with fatigue, palpitations, weight loss, and tremor. Laboratory evaluation demonstrated new-onset profound biochemical hyperthyroidism (FT4 > 7.77 ng/dL, n 0.8 – 1.8 ng/dL; FT3 >27.0 pg/mL, n 2.0-4.4 pg/mL). She was treated with beta-blocker, high doses of methimazole, and cholestyramine while further evaluation was pursued. She declined SSKI due to reported iodine allergy and steroids due to concerns about impact on wound healing following recent hip arthroplasty. TSI and TRAb were negative, and thyroid ultrasound showed stable nodules at 1.7cm. Pelvic ultrasound and MRI were obtained due to concern for non-thyroidal etiology, and revealed a 3.7cm septated cystic ovarian lesion, raising suspicion for struma ovarii. Whole body scan to localize site of thyroid hormone production could not be obtained due to high risk of clinical deterioration off methimazole, as she had persistent clinical and biochemical thyrotoxicosis on high doses (up to 90mg/day). She ultimately required 3 sessions of plasma exchange to lower her thyroid hormone levels, and then underwent bilateral salpingo-oophorectomy. Final pathology revealed mucinous cystadenoma without ectopic thyroid tissue. Post-operatively, her thyroid hormone levels were persistently elevated but improved compared to pre-operative levels, allowing for brief cessation of methimazole and completion of whole body scan. Imaging demonstrated a single focus of radioactive iodine uptake in the lower right thyroid lobe, correlating with the dominant 1.7 cm nodule on prior ultrasound, consistent with a toxic adenoma. Additionally, she was found to have an elevated urine iodine level (1200 mcg/24 hours, n 75 – 851 mcg/24 hours). Patient endorsed low iodine diet due to allergy history, and denied recent contrasted imaging study, dietary supplements, or amiodarone use. Upon further inquiry, she recalled using povidone-iodine solution to care for her surgical site post-arthroplasty, approximately a week before the onset of her initial symptoms. Her clinical presentation was ultimately attributed to toxic adenoma, with severe thyrotoxicosis exacerbated by iodine load. She underwent total thyroidectomy and is doing well on levothyroxine post-operatively. Conclusions: Topical iodine administration can contribute to iodine-induced hyperthyroidism in patients with underlying thyroid disease, and its use should be carefully considered in these patients. When evaluating a patient with new thyrotoxicosis, a detailed history of oral, IV, and topical iodine use should be obtained.

Assessment of Factors Affecting the Treatment Efficacy of Radioactive Iodine (I-131) Therapy in Patients with Hyperthyroidism

Objective: Hyperthyroidism is an increase in hormone production in the thyroid gland and the exposure of tissues to the hormones of the thyroid glands in the circulation. The most common causes encountered are Graves’ Disease, Toxic Multinodular Goiter and Toxic Adenoma. The purpose of radioactive iodine treatment is to make patients become euthyroid or hypothyroid. Despite adequate treatment, hyperthyroidism persists or reccurs in some patients. The aim of our study is to investigate the factors affecting the efficacy of radioactive iodine treatment in hyperthyroidism. Methods: In this retrospective study, relevant clinical and laboratory data were recorded in database of Kayseri Training and Research Hospital, Endocrinology and Metabolism Diseases Outpatient Unit between 2013-2016. Results: A total of 79 cases including 17 (21%) male, and 62 (79%) female patients were enrolled in the study. There were 33 (42%) Graves’ disease 9 (11%) Toxic Multinodular Goitre and 37 (47%) Toxic Adenoma patients when grouped according to diagnoses. Mean age was 56.5 ± 16,80. Development of hypothyroidism or euthyroidism were accepted as efficient treatment, hyperthyroidism or recurrence were considered as treatment failure. In 71 (89%) patients, treatment efficiently resulted in hypothyroidism or euthyroidism, whereas in 8 (11%) patients, the treatment failed due to recurrence or persistent disease. Treatment was 100 % effective in Toxic Multinodular Goitre and Toxic Adenoma groups, while it was effective in 75.7 of patients with Graves’ Disease. Patients who did not use antithyroid drugs recovered faster than patients who did. Conclusion: Radioactive iodine therapy is an efficient treatment in patients with hyperthyroidism. It was determined that 1 mm increase in nodule size decreased the treatment efficacy by 1.07 times (p<0,05). However, there are many factors that affect the efficacy of this treatment. To elucidate these factors and improve clinical practice, prospective long-term studies providing more reliable data with larger samples needed.

Frequency of Pathological Types of Hyperthyroidism in Thyroid Scan Patients

Background: Hyperthyroidism is a common systemic disorder where Graves’ disease is known as the leading cause of the disease. Thyroid stimulating hormone, T4 and T3 antibody assay are usually performed for the diagnosis of the pathology. However, with uncertainty in the results and in order to estimate the magnitude and the exact cause of the disease, radioactive iodine uptake (RAIU) test is recommended. The aim of this study is to evaluate underlying pathology in the patients presenting hyperthyroidism using RAIU test results. Methods: This is a cross-sectional retrospective study conducted on the patients with hyperthyroidism referred to Shahid Madani Hospital in Khorramabad. Data regarding the biochemical analysis and RAIU test was collected from the records and a questionnaire based on demographic and clinical information was completed for each patient. Results: Of 137 patients presenting hyperthyroidism, 62.04% were presented with Graves’ disease, 24.08% with toxic multinodular goiter and 13.86% with toxic adenoma. 24-hour RAIU test showed that the percent of radioiodine uptake was most in toxic adenoma 67.7%, Graves’ disease 53.5% and multinodular goiter 39%, respectively. From the age-based analysis, we found that Graves’ was most common in 20-30 years old individuals 34%, multinodular goiter in 50+ aged individuals 36.3% and toxic adenoma was most prevalent in 30-40 and 50+ aged patients, 26.3% each. In our population of interest, 81.8% toxic multinodular goiter patients were females. Conclusions: Our study presents the outcome of RAIU tests in hyperthyroidism based on the underlying pathologies. We also conclude, in light of other findings, Graves’ disease is the most common cause of hyperthyroidism in our population.

Toxic Adenoma Mimicking Papillary Thyroid Carcinoma

Introduction/Objective A thyroid nodule requires multiple steps in the identification of its nature, which determines its management. In most cases, low TSH levels support a benign origin. However, examples of hyperfunctioning thyroid carcinoma have been reported. Recent observations show that the number of thyroid cancer increases with the prevalence in young patients. The ambiguity of some cases necessitates the use of a full range of diagnostic methods up to molecular cytological diagnostics. Methods We present a report on the case of an 11-year-old boy complaining of weight loss despite having a good appetite. Results The blood test showed free T4 1.51 (0.81 - 1.35 ng/dL), free T3 6.04 (3.31 - 4.88 pg/mL), and TSH 0.01 (0.662 - 3.90 mU/L). During sonography, the left thyroid lobe was almost completely replaced by an isoechogenic circumscribed mass with multiple colloid cystic spaces. No suspicious microcalcifications or abnormal cervical lymph nodes were identified. A thyroid scan revealed the presence of a toxic autonomously functioning thyroid nodule in the left lobe. Methimazole and propranolol were prescribed, with subsequent left hemithyroidectomy on 10/21/2019. Grossly, the left thyroid lobe was 3.4 x 2.5 x 2 cm. The sectioning revealed light brown homogeneous stroma with a well-defined yellow-tan nodule (1.1 x 1.1 x 1 cm) in the middle of the lobe. The specimen was entirely submitted for permanent fixation in formalin. Microscopically, an encapsulated nodule was seen with the follicular and focal papillary pattern; nuclear features strongly and multifocally suggested a diagnosis of papillary carcinoma. HBME1 and calcitonin immunostains were negative; CK19 immunostain was multifocally positive. Next-generation sequencing supported the diagnosis of toxic adenoma with atypical features. Conclusion Every case of thyroid neoplasm should be fully investigated using modern and high-tech technologies, regardless of the functioning state of the gland. Molecular testing is supportive, especially in ambiguous situations, which benefits the patient.