Radioactive Iodine Uptake Research Articles

PSAT321 Post-partum Thyroiditis Precipitated by SARS CoV-2 Infection-a Case Report

Abstract Introduction Postpartum thyroiditis is a form of destructive thyroiditis. It is thought to originate from an autoimmune mechanism that develops within one year of parturition. The condition results in inflammation of the thyroid resulting in damage to the thyroid follicles and release of previously stored thyroid hormone. There are only a handful of documented cases of postpartum thyroiditis associated with SARS CoV-2. Since the onset of COVID-19 a multitude of thyroid abnormalities have been associated with the virus. Case Summary A 33-year-old female, 5 months post-partum with a medical history significant for hypertension presents to the clinic for evaluation of hyperthyroidism. She tested positive for SARS-CoV-2 eleven days prior to delivering her child. Her pregnancy was only complicated by chronic hypertension. COVID-19 infection was symptomatic for mild respiratory symptoms. She had no history of hypo or hyperthyroidism prior to or during her pregnancy. At presentation, patient was largely asymptomatic with a physical exam significant only for sinus tachycardia. Laboratory tests done two weeks before her visit, were significant for a suppressed TSH <0.001 uIU/mL (reference range: 0.450- 4.50) and a mildly elevated Free T4: 1.84 NG/dL (reference range: 0.82-1.77) and T3: 139 NG/dL (reference range: 71-180). We repeated the tests and noted a recovering TSH of 0.110 uIU/mL; a low Free T4: 0.77 NG/dL and T3: 66 NG/dL. Thyroglobulin level was found to be elevated at 742.6 IU/mL (reference range 0.0-0.9). Thyroid Stimulating Immunoglobulin level was <0.10 IU/L (Normal- 0.00-0.55) and serum thyrotropin receptor Ab <1.10 IU/L (Normal- 0.00-1.75). Radioactive iodine uptake & scan was deferred as patient was breast-feeding at the time. As our patient was asymptomatic, she was prescribed only propranolol for her tachycardia. Discussion Documented cases of post-partum thyroiditis associated with SARS-CoV-2 infection are far and few. Post-partum thyroiditis is characterized by an initial thyrotoxic phase followed by hypothyroid phase and then a recovery period. Most patients are only mildly symptomatic during the initial hyperthyroid phase. At the time of referral to our clinic, the patient was already entering a hypothyroid state. She was asymptomatic at the time and therefore treated with expectant management only. COVID-19 has been identified as a cause of subacute post-infectious thyroiditis. It is known to be associated with a hyperinflammatory state characterized by a cytokine storm. Elevation of these cytokines can contribute to thyroid dysfunction. Conclusion It is hard to say whether our patient's acute thyroiditis was secondary to postpartum thyroiditis, subacute thyroiditis secondary to COVID-19 infection, or a combination of both factors. However, regardless of etiology it is important to note a possible correlation of post-partum thyroiditis in the setting of a SARS-CoV-2 infection. It is necessary to identify all cases of COVID-19 infection that can be associated with thyroid dysfunction. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

PSAT360 Thyrotoxicosis as a Delayed Response to Amiodarone

Abstract Introduction Amiodarone is often used in the treatment of cardiac dysrhythmia, but has been associated with toxicity of multiple organ systems including the thyroid. Patients treated with amiodarone can develop hypothyroidism or hyperthyroidism, also known as amiodarone induced thyrotoxicosis (AIT). AIT is further categorized into type I or type II depending on pathogenesis of the disease: type I resulting from increased hormone synthesis and type II resulting from glandular destruction. We report a case of a 68-year-old male patient who developed type II AIT approximately four years after cessation of Amiodarone therapy. Case Presentation A 64-year-old man initially presented to an outpatient endocrinology clinic for evaluation of incidental thyroid nodules. He had a normal thyroid function. His significant past medical history included atrial fibrillation/atrial flutter status post ablation. Thyroid ultrasound revealed bilateral subcentimeter nodules which remained stable over the subsequent two years. Approximately four years after establishing care, he presented to the endocrinologist again with weakness, decreased appetite, fatigue, and weight loss. Thyroid function testing revealed new onset hyperthyroidism with suppressed TSH, <0.01 mU/L (normal 0.5-5.0 mU/L), elevated FT4 4.5 ng/dL (normal 0.7-1.9 ng/dL) and elevated FT3, 7.4 pg/mL (normal 2.3-4.1 pg/mL). He had normal TSI, normal ESR, and no history of recent viral infection. Thyroid ultrasound showed stable subcentimetric nodules. Evaluation with radioactive iodine uptake (RAIU) scan was not possible due to recent contrast exposure during CT spine imaging. The patient was started on methimazole therapy with an assumptive diagnosis of toxic multinodular goiter. The dose was rapidly increased, within weeks, to 60mg daily, due to persistent severe hyperthyroidism. He was hospitalized twice for exacerbation of atrial fibrillation with rapid ventricular rate requiring cardioversion and augmentation of medical therapy. Further investigation revealed the patient had received amiodarone therapy for approximately three months, almost four years prior to his current presentation. A trial of 40mg prednisone daily was started in conjunction with methimazole for possible delayed type II AIT, resulting in a rapid improvement of symptoms and Free T4 levels. Once the patient's urinary iodine levels returned to normal, he underwent RAIU scan which revealed low uptake supporting the diagnosis of type II AIT. Methimazole therapy was stopped, and prednisone therapy was tapered down slowly and then discontinued over the course of three months, with complete resolution of hyperthyroidism. Conclusion This report reiterates the difficulties clinicians are often faced with when diagnosing and treating AIT, which, in our case, occurred four years after the discontinuation of amiodarone therapy. It highlights the importance of obtaining a history of remote amiodarone therapy, and considering steroids treatment for type II AIT, especially in patients with no clear other etiology and no response to high dose methimazole. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

PSAT335 Histopathological changes of the thyroid may be subtle yet important in Amiodarone induced thyrotoxicosis (AIT).

Abstract Background Amiodarone is an effective antiarrhythmic for several cardiac arrhythmias. Due to its high iodine content and long half-life with direct toxic effects on the thyroid gland, it is known to cause a spectrum of thyroid dysfunction. AIT type 1, a form of iodine-induced hyperthyroidism, and AIT type 2, a drug induced destructive thyroiditis, pose a diagnostic and therapeutic challenge. Since the physical and psychological consequences of long-term therapy with either condition are too large to ignore, it is crucial to differentiate between the two types. Histopathologic findings in AIT includes disrupted follicles filled with desquamated vacuolated epithelial cells, foamy macrophages, scattered lymphocytes, involution changes and fibrosis. However, these changes may be subtle in patients who have been treated with long term high dose steroids, but helpful in establishing either AIT 1 or 2. Case A 56-year-old man with a history of cardiomyopathy with an ejection fraction of 30% and atrial flutter treated previously with six months of amiodarone, presented for a routine appointment found to be in atrial flutter with rapid ventricular rate. The patient was off amiodarone therapy for ∼ 6 months prior to current presentation. The patient was referred to the ER where initial vital signs were remarkable for heart rate in the 140s. Exam was remarkable for mild tremor of the outstretched bilateral hands. Labs were remarkable for TSH of 0.01 ulU/ml (0.27-4.20), Free T4 of 2.2 ng/dl (0.93-1.70), Free T3 of 5.9 pg/ml(2.3-4.2). Thyroid ultrasonography revealed a heterogeneously enlarged thyroid gland with no increased vascularity, and 2.4 cm isthmus nodule of a TI-RAD-3. Thyroid stimulating immunoglobulins (TSI) of 96 (<140%), and thyroid peroxidase (TPO) of 2IU/ml (<9). Thyroid radioactive iodine uptake (RAIU) revealed a severely decreased uptake in the setting of amiodarone use. Mixed AIT was suspected and patient was placed on titrated dose of Methimazole (MMI) and Prednisone. Approximately three weeks later, patient was discharged on MMI 40 mg TID and Prednisone 60 mg daily. He had a close outpatient follow up with further titration of prednisone to 80 mg daily. Due to prolonged nature of disease, he was subsequently referred for total thyroidectomy. Histological examination revealed subtle changes including desquamated follicular epithelial cells and intrafollicular foamy macrophages. The thyroid architecture was maintained and no inflammatory infiltrates of fibrosis were noted. These findings are consistent with AIT type 2. Conclusion AIT is a challenging diagnosis, and in medically refractory cases, total thyroidectomy is a curative option. The pathological findings in a patients treated with prolonged steroids may dampen inflammation of AIT2, and therefore careful histologic examination and monitoring of inflammatory markers may help to consolidate diagnosis. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

LBSAT314 Diagnosis And Management Of A Rare Case Of Marine-Lenhart Syndrome

Abstract Introduction Marine-Lenhart syndrome is defined as Graves’ disease with co-existing toxic thyroid nodules. Approximately 25% to 30% of patients with Graves’ disease have accompanying nodules. More than 95% of these nodules are hypoactive, and thus, only a tiny percentage are hyperactive. In these patients, Graves’ disease and toxic nodules both contribute to thyrotoxicosis11. Here we present a case that details this syndrome's diagnosis, management, and treatment complication. Clinical Case A 68-year-old female presented to the primary care physician's office with complaints of anxiety and heat intolerance. Three years before this visit, the patient was diagnosed with Graves’ disease. She had achieved remission after one year of methimazole therapy. During the office visit, the patient was in sinus tachycardia at 112 BPM. There were no signs of exophthalmos on examination, and the thyroid was not palpable. Further testing revealed thyrotoxicosis with suppressed TSH of <0. 01 mcIU/mL (0.36-3.74) and elevated free T4 of 2.49 ng/dL (0.76-1.46). Thyrotropin receptor antibody (TRAb) was positive at 2.60 IU/L (0. 00-1.75). The patient was started on atenolol. Although TRAb was positive, thyroid ultrasound and radioactive iodine uptake scan (RAIU) were ordered to look for alternative diagnoses. The thyroid ultrasound showed four nodules in the left lobe, the largest of which was 1.8×1.5×1.3 cm. RAIU showed increased 24-hour uptake of 45% and three areas of increased focal uptake in the left thyroid lobe consistent with toxic nodules. Definitive treatment was needed due to both toxic nodules and Graves’ disease. The patient agreed to radioiodine ablation therapy (RAI) and received a dose of 21 uCi. One month after receiving RAI, the patient complained of worsening anxiety and heat intolerance. On repeat testing, TSH was <0. 01mcIU/mL, and free T4 was 4.78 ng/dL. The patient developed radiation thyroiditis and was given methimazole 10mg daily for two weeks. Three weeks after the course of methimazole, the patient became hypothyroid and was managed with 88 mcg of levothyroxine daily with no symptoms. Conclusion Common causes of hyperthyroidism are Graves’ disease or autonomous functioning thyroid nodules per the American Thyroid Association12. However, in hyperthyroid patients, Marine-Lenhart syndrome should be considered, especially those with thyrotoxicosis recurrence. This diagnosis steers management away from antithyroid drugs and toward RAI or thyroidectomy. For patients treated with RAI, antithyroid medications should be included as an adjunct therapy to reduce post-radiation thyroiditis. References 1 Cakir, Mehtap. "Marine-Lenhart Syndrome.," Journal of the National Medical Association 97, no. 7 (July 2005): 1036-38.12 Ross, Burch, et al., Thyroid. Oct 2016, 26(10): 1343-1421. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

PSAT346 Persistent Fluctuation Between Hypothyroidism and Hyperthyroidism in a Patient with Both Hashimoto's Thyroiditis and Graves’ Disease: Challenges in Diagnosis and Treatment Approach

Abstract Introduction The two most common autoimmune disorders affecting the thyroid gland, namely Graves’ disease and Hashimoto's thyroiditis, represent opposite ends of the same spectrum. They can rarely co-exist in the same patient (1) leading to an unpredictable clinical course and pose a therapeutic challenge, necessitating close monitoring. We present a unique case of a female who switched multiple times between a hypothyroid and hyperthyroid state due to the co-existence of both Hashimoto's thyroiditis and Graves’ disease. Case Description A 78-year-old Caucasian female was diagnosed with hypothyroidism in 2011 by her primary care physician and was started on levothyroxine 50 mcg daily. The TSH level prior to initiation of levothyroxine therapy is unknown, but the first documented TSH level while on therapy in June 2012 was 0.347 uIU/ml (0.45-4.50), free T4 1.1 ng/dl (0.8-1.8) and free T3 3.4 pg/ml (2.3-4.2). Levothyroxine was lowered to 25 mcg daily but repeat TSH was 0.01 uIU/ml in February 2013 and the levothyroxine was discontinued. The TSH level rose to 7.35 uIU/ml in December 2014 and levothyroxine was restarted. However, subsequent dose reduction was required followed by discontinuation due to persistently suppressed TSH levels and the TSI antibody during that time was elevated at 24.10 IU/L (0.00-0.55). Patient established care at our endocrinology clinic in 2019. Initial laboratory findings showed suppressed TSH <0.005 uIU/ml (0.30-4.00), elevated free T3 4.72 pg/ml (2.00-4.40), normal free T4 1.70 ng/dl (0.80-1.80) and elevated TSI antibody 15.50 IU/L. Radioactive iodine uptake scan showed high normal 24 hour uptake at 32% (10-35%) with mild heterogeneous distribution of the radiotracer throughout both lobes of the gland with diminished uptake in the right lower lobe, which corresponded to a 1.3 cm nodule that was biopsied and reported to be Bethesda category II. Patient was initiated on methimazole 5 mg daily. In June 2019, labs showed elevated TSH 6.91 uIU/ml, low free T4 0.74 ng/dl and free T3 2.01 pg/ml. Methimazole was held, and labs repeated after a few weeks, did not change significantly. In September 2020, levothyroxine 25 mcg daily, was initiated due to fatigue symptoms and an elevated TSH 10.61 uIU/ml with low FT4 0.8 ng/dl. Patient did not follow up for a while after that. In December 2021, levothyroxine was increased to 50 mcg daily in response to an elevated TSH 12.91 uIU/ml. The TPO and TSI antibodies remain elevated at 210 IU/ml (0-34) and 9.08 IU/L respectively. Conclusion Our case highlights the diagnostic and therapeutic challenges encountered when both Hashimoto's thyroiditis and Graves’ disease co-exist in the same patient. Reference (1) Alvin Mathew A, Papaly R et al. Elevated Graves’ Disease-Specific Thyroid-Stimulating Immunoglobulin and Thyroid Stimulating Hormone Receptor Antibody in a Patient With Subacute Thyroiditis. Cureus 13(11): e19448. doi: 10.7759/cureus.19448 Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

PSAT327 Can Cannabis Use Lead to Central Hypothyroidism

Abstract Background Marijuana has been legalized for medical use in 36 states and for recreational use in 18 states. Its effects on thyroid function and hypothalamic-pituitary-thyroid axis in humans is not known. Clinical Case 72 years old male presented to his primary care physician with occasional difficulty swallowing. He reported fatigue for 4-5 years, trouble falling asleep for 2 months, weight gain 8 pounds over last few weeks, occasional diarrhea, and intermittent episodes of heat intolerance. His past medical history included controlled type 2 diabetes mellitus, recurrent herpes simplex infection, arthritis of hip joints, short-term memory loss, anemia, carpal tunnel syndrome and benign prostatic hyperplasia. Medications included glimepiride, lisinopril, acyclovir, tamsulosin, finasteride, escitalopram. He had been smoking marijuana regularly since he was a teenager. He denied using any other supplements. His physical exam was normal with stable vital signs and normal BMI. His labs showed a low TSH (0.096 mcIU/mL, n: 0.358-3.8 mcIU/mL), normal free T4 (0.90 ng/dL, n: 0.76-1.46 ng/dL), normal total T3 (70 ng/dL, n: 60-180 ng/dL). Review of his labs showed low TSH for last 4 years progressively getting worse with normal free T4 levels. TSH-receptor antibody and TPO Antibody level were negative. His white cell count, hemoglobin and platelets were normal. His electrolytes, kidney function and liver function tests were also normal. Thyroid Ultrasound showed 2 small sub-centimeter hypoechoic nodules in the left thyroid lobe. Two years ago, a radioactive Iodine scan showed normal iodine uptake. A recent radioactive iodine uptake scan showed generalized decreased iodine uptake with no evidence of graves’ disease or toxic multinodular goiter. Conclusion Currently there are no controlled studies on the effect of marijuana use on thyroid function in humans. A cross-sectional analysis using National Health and Nutrition Examination Survey (NHANES) from 2007 to 2012 showed recent marijuana use was significantly associated with lower levels of TSH but was not associated with thyroid dysfunction (1). This study suggests that marijuana use is associated with low TSH levels. This could be due to hypothalamic suppression of TSH or may indicate a protective role against hypothyroidism. Older studies in rodents showed that cannabis exposure may lead to suppression of TSH and hypothalamic function (2). The data related to human subjects is scarce. Therefore, pathophysiologic mechanisms are speculative, although animal data support potential mechanism of hypothalamic suppression.

ODP614 Two cases of Graves Disease Associated Hypokalemic Periodic Paralysis

Abstract Introduction Periodic paralysis (PP) is a rare neuromuscular disorder due to a defect in ion channels in muscle, characterized by episodes of painless muscle weakness or paralysis, which may be precipitated by heavy exercise or high-carbohydrate meals. Hypokalemic PP (HPP) is most common of the periodic paralyses, however is still very rare, with an estimated prevalence of 1 in 100,000. An acquired form of hypokalemic PP can be seen in thyrotoxicosis of any cause. We present 2 cases of HPP due to thyrotoxicosis. Case 1 27 year old Asian male presented to the ED due to sudden onset of acute weakness/near paralysis in lower extremities, with weakness of bilateral upper extremities. He was found to be hypokalemic with a potassium of 2.0 mmol/L (3.5-5.1). At the same time, he was also found to be hyperthyroid with a suppressed TSH of 0.03 uIU/Ml (0.35-5.5) and a free T4 2.2 ng/mL (0.5-1.3), Total T3 225 ng/Dl (70-204), Free T3 5.9 pg/mL (1.5-4.1). TSI antibodies elevated at 1.39 IU/L (<0.10). He was started on potassium supplements and methimazole. At a 3-month follow-up, patient reported no further episodes of weakness or paralysis. Case 2 23 year old White male presented to ED with severe muscle weakness and was found to have hypokalemia of 2 mmol/L (3.5-5.1). On further labs, TSH was undetectable at less than 0.01 uIU/mL (0.35-4.94), Free T4 2.81 ng/dL (0.61-1.82), Total T3 of 451 ng/dL(48-178), TSI antibodies were positive at 178%(</=122%). Nuclear uptake scan confirmed Graves’ disease with radioactive iodine uptake of 58.1% at 4 hours and 70% at 24 hours with homogenous uptake in the entire gland and no evidence of hot or cold nodules. He was started on methimazole and propranolol for tachycardia and palpitations and potassium supplements. Muscle weakness resolved on treatment methimazole. Discussion and conclusion We present two cases of HPP likely caused by Graves’ disease. Both patients presented with hypokalemia and further workup revealed underlying thyrotoxicosis. The exact mechanism behind HPP due to thyrotoxicosis is not well understood. It is proposed that excess thyroid hormone may predispose to paralytic episodes by increasing the susceptibility to the hypokalemic action of epinephrine or insulin. This condition has been most widely reported in Asian populations, in which the incidence is approximately 2% in contrast to non-asian population with incidence of 0.1 to 0.2%, and is more common in men. Treatment of thyrotoxicosis with restoration and maintenance of euthyroid state ceases attacks. To summarize, few case series report the association of HPP with Graves’ disease. These patients usually present acutely with severe muscle weakness or paralysis. In conclusion, in diagnosis of HPP, possibility of thyrotoxicosis should be considered, especially in the absence of family history of PP. Presentation: No date and time listed

PSAT349 New Onset of Grave's Disease In Background of Hashimoto's Thyroiditis, Autoantibodies Switch Phenomenon; A Case Report.

Abstract Introduction Hashimoto's thyroiditis and Grave's disease represent the two spectrums of same autoimmune thyroiditis. The evolution from Graves disease into Hashimoto's thyroiditis is the most common scenario. While the conversion from Hashimoto's thyroiditis into Grave's disease is a rare occurrence. Exact incidence of this conversion is unknown because of its rarity. We present the case of a young female who developed full blown grave's disease in background of hypothyroidism secondary to Hashimoto's disease. Case presentation 56 year old hispanic female with past medical history of osteoarthritis and Hashimoto's thyroiditis (TPO +ve) and euthyroid on levothyroxine 75mcg daily for past 6 years who presented to the Emergency Department with concerns of palpitations and dyspnea on exertion for 4 months. Patient denied any recent change of manufacture and dosage of levothyroxine and reported compliance to medication. Review of symptoms was positive for palpitations, dyspnea on exertion, sleep disturbances, reduced exercise tolerance and unintentional weight loss of 20 lbs over 4 months. Physical exam was notable for tachycardia to 130's at rest, hyper-dynamic precordium with non-displaced heaving apex beat, normal S1/S2, no murmurs/gallops/rubs, visible pulsations in neck bilaterally, pounding pulses throughout the extremities and tremors on out stretched hands; and was negative for exophthalmos, thyromegaly and pedal swelling. EKG showed only Sinus tachycardia; Initial lab work up showed TSH of <0.01mIU/l (0.5-1.5), free T3 of 14.50 pg/ml (1.8-4.6), free T4 of 5.5 ng/dl (0.9-1.8). Patient was educated; levothyroxine was held and she was started on atenolol 25mg daily for symptoms control. Further workup revealed Thyroid stimulating immunoglobulin (TSI) of 5.69 IU/L (0.0-0.55); thyroid receptor antibodies levels of 8.14 IU/L (0.0-1.75); TPO antibodies levels of 20.1 IU/L (<=34.9). Small right upper lobe nodule was found on prior thyroid USG with interval decrease in size on repeat imaging. Radioactive iodine uptake scan was delayed because patient underwent CT pulmonary angiogram at presentation to ED and pulmonary embolism was ruled out. Later scan showed thyromegaly with heterogenous uptake of 82% in both lobes in 24 hours. Patient was diagnosed with Grave's disease. Patient opted for radioactive iodine ablation therapy. Post ablation, her symptoms resolved completely; she developed hypothyroidism and was started on maintenance levothyroxine. Conclusion Conversion of Hashimoto's thyroiditis to Graves's disease is a rare phenomenon and in literature review, It has been postulated to be due to a combination of atypical destructive autoimmune thyroiditis and change of thyroid receptor antibodies from blocking (TRAb) to stimulating ones (TSAb), a phenomenon known as "switch" resulting in hyperthyroidism. It is important to note that treatment with thyroxine itself can induce this switch. Clinicians should suspect this possibility in a patient who suddenly becomes hyperthyroid in setting of hypothyroidism so that appropriate management could be offered. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

ODP615 Emergence of Graves’ Ophthalmopathy in the Setting of Sudden Hypothyroidism: Possible Mechanisms Explored

Abstract Background Ninety percent of thyroid eye disease (TED) patients are hyperthyroid and at least 10% of TED occurs in the setting of euthyroidism or hypothyroidism. When Graves’ hyperthyroidism is diagnosed, 74% may not present with ophthalmopathy. Clinical Case A 58 year old woman diagnosed with Multinodular nontoxic goiter without nodule suspicious for malignancy was carefully monitored. No Levothyroxine treatment started. In 2017, patient had sudden onset of tremors, weight loss and palpitations. There were no signs of thyroid associated orbitopathy. Her TSH was <0. 009 uIU/ml (0.30-4) and FT4 29. 06pmol/L (10-22). Thyroid scan showed elevated 2- and 24-hours RAI uptake (as high as 80%) in both lobes. She was started on Methimazole but developed adverse reactions hence RAI (10 mci) was given. A month after RAI, she was rendered hypothyroid with of TSH 73.48uIU/ml (0.27-3.75), FT4 2.257pmol/L (8.8-44). She was maintained on Levothyroxine and remained euthyroid for four years. One year post RAI, ultrasound showed a small sized thyroid gland (right lobe: 3×0.6×1.5cm and left lobe: 2.2×0.3×1.3cm). May 2021, she followed up due to bulging eyes with scratchy sensation. She was noncompliant with Levothyroxine for several months. TSH was elevated to 46.19 uIU/ml (0.3-4. 00) and FT4 12.35 pmol/L (10.20-22.50). Levothyroxine dose was adjusted and repeat TSH was normal to 0.38 uIU/ml (0.30-4. 00) with FT4 of 22.40 pmol/L (10.20-22.50). Despite euthyroidism, there were progressive eye protrusion, conjunctival redness, pain and blurring of vision. TSHrAb was elevated to 21.62 U/L (N: <1 U/L). TSI was elevated to 6.59 IU/L (N: <0.10). . MRI of the orbit showed findings suggestive of Graves’ ophthalmopathy. She was started on Prednisone 60mg/day. Repeat TSHrAb was 9.85 U/L (<1U/L) after 3 weeks of steroids. Levothyroxine was stopped to check whether she had recurrence of Graves’ disease. When Levothyroxine was discontinued, there was worsening of eye disease and it was confirmed that patient was hypothyroid with TSH of 48.91 uIU/ml (0.55-4.78). Levothyroxine was resumed at 100mcg 1 tablet once daily and continued with Prednisone in tapering doses. Conclusion There were possible mechanisms that can lead to Graves’ ophthalmopathy in patients who had RAI and suddenly became hypothyroid. The rapid and protracted hypothyroidism caused increased secretion of TSH that stimulate antigen production by thyrocytes or induce proliferation in retro-orbital preadipocytes which express the TSH receptor. The protracted hypothyroidism can also be related to fluctuating TSHrAb post RAI. It was suggested that remission of TSH-receptor autoimmunity after RAI is less common. Clinicians should acquire baseline and monitoring of TSHrAb or ophthalmology consultation for all patients undergoing RAI regardless of whether they have eye signs or not. Maintenance of euthyroidism will help prevent emergence of Graves’ ophthalmopathy. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Thyroid Differentiation Scores (TDS, eTDS) in Radioiodine Resistant (RAIR) Papillary Thyroid Cancer (PTC) Patients

BRAF- and RAS-guided re-sensitization therapy of RAIR thyroid cancer distant metastasis (TCDM) currently leads to re-induction of RAI uptake in 50-60% of patients. There is an unmet need for better early identification of RAIR risk to increase re-sensitization success. We assessed the hypothesis that The Cancer Genome Atlas (TCGA) TDS (Agrawal et al, 2014) and the enhanced TDS (eTDS) (Dunn et al,2019) comprising mRNA expression of 16 and 48 thyroid-specific differentiation associated genes, respectively, of primary tumors could identify patients who later developed RAIR.

Relation between surgical oncologic quality indicators for papillary thyroid cancer.

Background:It remains unclear how thyroid surgical oncologic quality indicators (TSOQIs) are related to each other, and how to best interpret and apply these measures within the context of surgical quality assurance. We aimed to examine the relation between 3 TSOQIs: postoperative serum thyroglobulin level, 24-hour radioactive iodine uptake (RAIU) and metastatic lymph node ratio (MLNR).Methods:We conducted a retrospective review of patients who underwent total thyroidectomy for treatment of papillary thyroid cancer (PTC) performed by a single high-volume thyroid surgeon at a tertiary referral centre between 2012 and 2017. To establish the strength of correlation between pairs of quality indicators and the MACIS (metastasis, age, completeness of resection, invasion and size) prognostic score, we performed tests of normality and used the Spearman correlation coefficient to determine the correlation of nonnormal data containing outliers.Results:A total of 139 patients with PTC were included in the study. Their mean MACIS score was 5.0 (standard deviation 1.5). Fifteen patients had high-risk thyroid cancer (MACIS score > 6.99). A weak correlation was found between serum thyroglobulin level and RAIU (rs = 0.27, p = 0.006) and a moderate correlation was found between serum thyroglobulin level and MLNR (rs = 0.40 p = 0.002). A weak correlation between serum thyroglobulin level and MACIS score was also observed (rs = 0.20, p = 0.05).Conclusion:Based on our findings, we propose that the postoperative serum thyroglobulin level represents the quality metric that has the most clinical utility because it is measurable in all patients and also correlates with both RAIU and MLNR. With further research, surgeons seeking to evaluate the oncologic quality of thyroidectomy performed for PTC may consider applying a quality indicator to their future practice.

Sinomenine Hydrochloride Promotes TSHR-Dependent Redifferentiation in Papillary Thyroid Cancer.

Radioactive iodine (RAI) plays an important role in the diagnosis and treatment of papillary thyroid cancer (PTC). The curative effects of RAI therapy are not only related to radiosensitivity but also closely related to the accumulation of radionuclides in the lesion in PTC. Sinomenine hydrochloride (SH) can suppress tumor growth and increase radiosensitivity in several tumor cells, including PTC. The aim of this research was to investigate the therapeutic potential of SH on PTC cell redifferentiation. In this study, we treated BCPAP and TPC-1 cells with SH and tested the expression of thyroid differentiation-related genes. RAI uptake caused by SH-pretreatment was also evaluated. The results indicate that 4 mM SH significantly inhibited proliferation and increased the expression of the thyroid iodine-handling gene compared with the control group (p < 0.005), including the sodium/iodide symporter (NIS). Furthermore, SH also upregulated the membrane localization of NIS and RAI uptake. We further verified that upregulation of NIS was associated with the activation of the thyroid-stimulating hormone receptor (TSHR)/cyclic adenosine monophosphate (cAMP) signaling pathway. In conclusion, SH can inhibit proliferation, induce apoptosis, promote redifferentiation, and then increase the efficacy of RAI therapy in PTC cells. Thus, our results suggest that SH could be useful as an adjuvant therapy in combination with RAI therapy in PTC.

TH1.9 Clinical relevance of postoperative elevated thyroglobulin antibodies in patients with differentiated thyroid cancer

Abstract Aims 20%–25% of patients with differentiated thyroid cancer (DTC) can have elevated thyroglobulin antibodies (TgAb). The study aimed to find any prognostic significance of elevated TgAb during follow-up. Methods 10-year retrospective study from a tertiary centre including 79 patients with raised TgAb after total/staged thyroidectomy for DTC. We identified patients with stable (7.6%), increasing (15%) and decreasing levels of TgAb (77.2%); groups 1, 2 and 3 respectively. During follow-up we analysed TgAb in subcategories by TgAb trend (&amp;gt;50% increase, &amp;lt;50% increase, &amp;gt;50% decrease, &amp;lt;50% decrease, positive to negative, negative to positive and stable levels), gender, age, surgery, autoimmune disease, histology, RAI uptake, distant metastasis, and recurrence. Results The incidence of raised TgAb levels was 33.2%, with female predominance. No connection was identified regarding other parameters; 11.4% had distant metastasis. The highest mean level of TgAb was in group 2 (1918.75IU/mL) and the lowest in group 3 (412.70IU/mL). The recurrence rate changed significantly between the 3 groups: 50% in group 1, 75% in group 2, and 25% in group 3 (p=0.002). Recurrence rates decreased to 15% in the subcategory where TgAb become undetectable from positive (p=00001). In patients with negative to positive trend or &amp;gt;50% increase, recurrence rates were 100% (p=0.041) and 70% (p=0.012) respectively. Conclusions Patients with increasing TgAb levels during follow up have a higher rate of recurrence distinctly for those with negative to positive and &amp;gt;50% increase. These categories of patients need closer follow-up.

Effect of Lugol's solution on 131I therapy efficacy in Graves' disease.

Lugol's solution could control thyroid function and suppress 131I uptake in hyperthyroidism. This study aimed to investigate the appropriate time to withdraw Lugol's solution before 131I therapy (RIT) in Graves' disease (GD) patients, and how this should influence 131I uptake and RIT outcome. Two groups (125 cases and 1805 cases) of GD patients received RIT, who were pre-treated with and without Lugol's solution (RI-CI group and RI group). The RI-CI group was further divided into the following sub-groups depending on the duration span between Lugol's solution withdrawal and RIT: sub-group A, 4-7 d (n = 49); sub-group B, 8-14 d (n = 41); and sub-group C, 15-30 d (n = 35). The highest radioactive iodine uptake rate (RAIUmax), effective half-life (Teff), TRAb, and free triiodothyronine (FT3) and free thyroxine (FT4) levels were compared, and therapeutic outcome was evaluated. There were no significant differences in RAIUmax, TRAb, and Teff among the four sub-groups (P > 0.05). Both FT3 and FT4 levels in sub-groups A and B were lower than those in group RI and sub-group C (P < 0.05). The outcome of non-hyperthyroidism (euthyroidism + hypothyroidism) in groups RI-CI and RI was significantly different at post-RIT month 1 and 3 (P < 0.05). However, intergroup differences at 6 and 12months were not significant (P > 0.05). Withdrawal of Lugol's solution 4-7 or 8-14 d before RIT does not influence 131I uptake and RIT efficacy in GD. Moreover, in order to avoid a rapid increase in thyroid hormone levels at the same time, Lugol's solution should be withdrawn 4-7 d before RIT.

The Iodine Rush: Over- or Under-Iodination Risk in the Prophylactic Use of Iodine for Thyroid Blocking in the Event of a Nuclear Disaster.

Iodine is an essential element for the production of thyroid hormones (THs). Both deficient and excess iodine intakes may precipitate in adverse thyroidal events. Radioactive iodine (RI) is a common byproduct of nuclear fission processes. During nuclear emergencies RI may be released in a plume, or cloud, contaminating the environment. If inhaled or ingested, it may lead to internal radiation exposure and the uptake of RI mainly by the thyroid gland that absorbs stable iodine (SI) and RI in the same way. A dose of radiation delivered to the thyroid gland is a main risk factor for the thyroid cancer development. The SI prophylaxis helps prevent childhood thyroid cancer. The thyroid gland saturation with prophylactic SI ingestion, reduces the internal exposure of the thyroid by blocking the uptake of RI and inhibiting iodide organification. However, negative impact of inadequate SI intake must be considered. We provide an overview on the recommended iodine intake and the impact of SI and RI on thyroid in children and adolescents, discussing the benefits and adverse effects of the prophylactic SI for thyroid blocking during a nuclear accident. The use of SI for protection against RI may be recommended in cases of radiological or nuclear emergencies, moreover the administration of iodine for prophylactic purposes should be cautious. Benefits and risks should also be considered according to age. Adverse effects from iodine administration cannot be excluded. Precise indications are mandatory to use the iodine for thyroid blocking. Due to this natural adaption mechanism it’s possible to tolerate large doses of iodine without clinical effects, however, a prolonged assumption of the iodine when not needed can be dangerous and may precipitate in severe thyroidal and non-thyroidal negative effects.

Machine learning identifies baseline clinical features that predict early hypothyroidism in patients with Graves' disease after radioiodine therapy.

Background and objective Radioiodine therapy (RAI) is one of the most common treatment solutions for Graves’ disease (GD). However, many patients will develop hypothyroidism as early as 6 months after RAI. This study aimed to implement machine learning (ML) algorithms for the early prediction of post-RAI hypothyroidism.Methods Four hundred and seventy-one GD patients who underwent RAI between January 2016 and June 2019 were retrospectively recruited and randomly split into the training set (310 patients) and the validation set (161 patients). These patients were followed for 6 months after RAI. A set of 138 clinical and lab test features from the electronic medical record (EMR) were extracted, and multiple ML algorithms were conducted to identify the features associated with the occurrence of hypothyroidism 6 months after RAI.Results An integrated multivariate model containing patients’ age, thyroid mass, 24-h radioactive iodine uptake, serum concentrations of aspartate aminotransferase, thyrotropin-receptor antibodies, thyroid microsomal antibodies, and blood neutrophil count demonstrated an area under the receiver operating curve (AUROC) of 0.72 (95% CI: 0.61–0.85), an F1 score of 0.74, and an MCC score of 0.63 in the training set. The model also performed well in the validation set with an AUROC of 0.74 (95% CI: 0.65–0.83), an F1 score of 0.74, and a MCC of 0.63. A user-friendly nomogram was then established to facilitate the clinical utility.Conclusion The developed multivariate model based on EMR data could be a valuable tool for predicting post-RAI hypothyroidism, allowing them to be treated differently before the therapy. Further study is needed to validate the developed prognostic model at independent sites.

Targeting GLI1 Transcription Factor for Restoring Iodine Avidity with Redifferentiation in Radioactive-Iodine Refractory Thyroid Cancers.

Simple SummaryThyroid cancers have an excellent prognosis by standard therapy of surgery followed by radioactive-iodine therapy. However, metastatic thyroid cancers do not response to radioactive-iodine therapy by losing iodine avidity. Therefore, reversing iodine avidity to metastatic thyroid cancers gives a new chance of applying radioactive-iodine therapy to the cancers. In the current study, we found that GLI1 knockdown can revert iodine non-avid thyroid cancers to iodine avid cancers by increasing expression of thyroid-specific proteins. Restoration of iodine avidity in thyroid cancers makes the cancers sensitive to radioactive-iodine therapy again. Therefore, the GLI1 can be a potential therapeutic target of radioactive-iodine resistant thyroid cancers.Radioactive-iodine (RAI) therapy is the mainstay for patients with recurrent and metastatic thyroid cancer. However, many patients exhibit dedifferentiation characteristics along with lack of sodium iodide symporter (NIS) functionality, low expression of thyroid-specific proteins, and poor RAI uptake, leading to poor prognosis. Previous studies have demonstrated the effect of GLI family zinc finger 1 (GLI1) inhibition on tumor growth and apoptosis. In this study, we investigated the role of GLI1 in the context of redifferentiation and improvement in the efficacy of RAI therapy for thyroid cancer. We evaluated GLI1 expression in several thyroid cancer cell lines and selected TPC-1 and SW1736 cell lines showing the high expression of GLI. We performed GLI1 knockdown and evaluated the changes of thyroid-specific proteins expression, RAI uptake and I-131-mediated cytotoxicity. The effect of GANT61 (GLI1 inhibitor) on endogenous NIS expression was also assessed. Endogenous NIS expression upregulated by inhibiting GLI1, in addition, increased expression level in plasma membrane. Also, GLI1 knockdown increased expression of thyroid-specific proteins. Restoration of thyroid-specific proteins increased RAI uptake and I-131-mediated cytotoxic effect. Treatment with GANT61 also increased expression of endogenous NIS. Targeting GLI1 can be a potential strategy with redifferentiation for restoring RAI avidity in dedifferentiated thyroid cancers.

Immunotherapy-Induced Thyroiditis in Cancer Patients

Hyperthyroid patients may have increased or decreased radioiodine uptake on I-123 uptake and scan, which helps to differentiate the etiology of the hyperthyroid state. Thyroiditis is an uncommon complication of cancer immunotherapy and, in this situation, is likely secondary to an autoimmune response. The typical presentation of thyroiditis, regardless of the etiology, is elevated T4 and/or T3, low TSH and low radioactive iodine uptake. Herein we report a case of cancer immunotherapy-induced thyroiditis in a 34-year-old female diagnosed with right breast grade 2 invasive ductal carcinoma with ER and PR positive, Her2neu negative tumor markers. Due to her ER-positive tumor, 8-cycles of chemo-immunotherapy with Paclitaxel + Pembrolizumab were prescribed. The patient began to complain of intermittent palpitations halfway through her treatment, and her TSH after 6 cycles of treatment was &lt;0.01 U/ml. She had negative TSI or anti-TPO (Pre-treatment TSH- 1.54 U/ml) antibodies. I-123 thyroid uptake and scan demonstrated faint thyroid activity with very low I-123 uptake, consistent with thyroiditis. Her treatment was ultimately continued and continued close monitoring of thyroid function tests was recommended.

Endoscopic central lymph node dissection of thyroid cancer via chest-breast approach: results, indications, and strategies.

Surgery for thyroid cancer via endoscopic approach was still controversial. Herein, we report the indications, strategies for operative techniques, as well as results for endoscopic central lymph node dissection of thyroid cancer via chest-breast approach (ETCB-CLND). A retrospective analysis was conducted on the cases of DTC, whom underwent ETCB-CLND from January 2013 to June 2020. Three hundred and twenty-three cases underwent ETCB-CLND (endoscopic group) and 267 cases underwent open surgery (open group). General characteristic, surgical results, thyroglobulin (Tg), radioactive iodine uptake (RAIU), radioactive technetium uptake (RATU), radionuclide imaging of the thyroid residual area (RITRA), and radionuclide imaging of suspicious lymph nodes metastasis (RISLNM) were analyzed and compared between the two groups. The age of the endoscopic group were lower than that of the open group. The operation time of lobectomy in endoscopic group were longer than that in open group. The gender distribution (P = 0.831), operation time of total thyroidectomy (P = 0.311), intraoperative blood loss (P = 0.672), postoperative hospital stay (P = 0.852), tumor size (P = 0.259), number of cases of lymph node metastasis (P = 0.618), number of dissected lymph nodes (P = 0.681), number of metastatic lymph nodes (P = 0.723), and complications (P = 0.749) did not differ significantly between groups, nor did the surgical range (P = 0.661), Tg at 1month (P = 0.61) and 1year (P = 0.67) after surgery, before (P = 0.589) and after (P = 0.593) radioiodine therapy, RAIU-2h/24h (P = 0.906/0.582), RATU (P = 0.532), (99mTc 15min:P = 0.503; 131I 24h:P = 0.377; 131I 3d:P = 0.919), RISLNM (none: P = 0.887; central: P = 0.630; lateral: P = 0.659). The rational and normative application of the endoscopic technique in central lymph node dissection of DTC is safe, feasible, and consistent with the principle of radical tumor cure for selected cases by well-trained surgeons.

Functional imaging in thyroid cancer patients with metastases and therapeutic implications

Functional imaging plays a central role in the management of thyroid cancer patients.In patients with a differentiated thyroid cancer (DTC), radioactive iodine (RAI) is used mostly with a therapeutic intent, either post-operatively or as the first line systemic treatment in patients with known structural disease. A whole body scan is performed a few days after the RAI administration, and this procedure is very sensitive to detect all tumor foci with RAI uptake. PET/CT with 18F-FDG complements the use of RAI at the initial evaluation of patients with high-risk DTC, during follow-up in those with rising serum thyroglobulin levels over time, for the work-up of patients with documented structural disease and for assessing the efficacy of focal or systemic treatment modalities. 18F-FDG uptake is a prognostic indicator in all these clinical conditions. A dosimetric approach with 124I PET/CT showed encouraging results.Several functional imaging modalities are currently available for medullary thyroid carcinoma (MTC) patients. 18F-FDG-PET/CT may be sensitive in MTC patients with high FDG uptake that signals aggressive disease. 18F-DOPA is the most sensitive imaging technique to visualize small tumor foci, and is also highly specific in patients with a known MTC, but should be complemented by a CT scan of the chest and by a MRI of the liver to detect small metastases.