bluuebunny/crossref_metadata_2025_split huggingface dataset:
Successful Management of Hyperthyroidism With Lithium and Radioiodine in a Patient With Previous Methimazole-Induced Agranulocytosis
Authors: Fantin Esther H , Goemann Iuri Martin 
Published: May 2021

Abstract
Introduction: Antithyroid drug (ATD) therapy is the first-line treatment of Graves’ hyperthyroidism. Agranulocytosis, although rare, is a life-threatening condition associated with ATD therapy. For patients who recovered from ATD-induced agranulocytosis, surgery or radioiodine (RAI) therapy are adequate options to restore the patient’s euthyroid state. Here we report a case of ATD-related agranulocytosis where lithium therapy was used before RAI to control thyrotoxicosis and prevent worsening of hyperthyroidism. Case Report: A 74-year-old female with a previous history of hypertension presented with a 2-month history of weight loss (12 lbs), palpitations and shortness of breath. She was afebrile with a heart rate of 110, a blood pressure of 149/80, a fine tremor and a moderate diffuse goiter. She had a normal eye exam. Laboratory evaluation demonstrated TSH &lt;0.01 uIU/mL (0.35-5.5), FT4 3.11 ng/dL (0.51-1.65) and TSH receptor antibody (TRAb) 40 (&lt;1,0 U/L), consistent with thyrotoxicosis due to Graves’ disease. She was started on methimazole (MMI) 15mg and metoprolol. After four weeks, symptoms resolved and thyroid function tests (TFT) improved. However, after two months of treatment, she was hospitalized for fever, diarrhea and abdominal pain. White blood cell count (WBC) was 650/μL, and neutrophil count was 90/μL. A diagnosis of gastroenteritis and agranulocytosis was made and MMI was stopped. After seven days, symptoms resolved, the neutrophil count was 2200/ul and TFT were acceptable (FT4 1.25, ng/dL TT3 1.67 ng/ml, TSH &lt; 0.02 uIU/mL). She was discharged without ATDs and a RAI dose of 20 mCi was scheduled. However, RAI therapy had to be postponed due to COVID-19 pandemic restrictions. After 3 weeks, TFT worsened and therapy with lithium carbonate 300 mg TID was started as the patient refused thyroidectomy. Lithium was initiated 12 days before RAI therapy and was maintained 7 days after the procedure. No side effects associated with lithium treatment were reported. TFT 7 days after RAI were FT4 1.43, ng/dL TT3 2.05 ng/ml and TSH &lt; 0.02 uIU/mL. One month later, the patient was euthyroid without need for thyroid medication and remains on follow up. Discussion: Serum thyroid hormone (TH) concentrations usually increase after RAI therapy for Graves’ disease, a worrisome fact in patients with increased risk for cardiovascular complications. Previous studies report that pre-RAI treatment with lithium prevents changes in serum TH concentrations and enhances RAI therapy’s effectiveness. Here, treatment with lithium was used to control thyrotoxicosis and prevent further increase in TH levels associated with RAI therapy. Lithium is particularly suitable for patients with ATD-related side effects before definitive therapy (radioiodine or thyroidectomy). The antithyroid effect of lithium in this setting should be further studied.
Thyroid Abscess Initially Presenting as Destructive Thyroiditis With Subsequent Hypothyroidism
Authors: Caseja Ahl Jeffrey , Wang Richard L , Nakhle Samer 
Published: May 2021

Abstract
Introduction: Due to its rich vascular supply and high iodine content infection of the thyroid gland is rare and is uncommonly associated with hyperthyroidism. We report a case of a thyroid abscess presenting with hyperthyroidism with subsequent hypothyroidism in an immunocompetent patient.
Clinical Case: A 34-year old female with no past medical history presented with an enlarging neck mass associated with worsening, non-radiating throat pain of three-week duration associated with dysphagia. She reports 15-lb weight loss and palpitations. On presentation vital signs were within normal range. Physical examination revealed a diffusely tender anterior neck mass. Her thyroid function tests revealed TSH 0.01 uIU/mL (0.358-3.74), FT4 2.4 ng/dL (0.76-1.46), TSI &lt;0.10 IU/L (0.00-0.55), TPO 12 IU/mL (0-34). Laboratory workup was also significant for leukocytosis, thrombocytosis, and hyponatremia. Thyroid ultrasound revealed a large, irregularly shaped, multiloculated fluid collection involving both lobes measuring 6.4 x 4.8 x 2.0 cm. She was started on Vancomycin and Ampicillin/Sulbactam, Metoprolol, and Methimazole. Needle aspiration of 30 cc of purulent material was performed with culture showing a heavy growth of streptococcus constellatus sensitive to penicillin. After a 4-day inpatient stay, she was discharged with Amoxicillin/Clauvanate as well as Methimazole 10mg BID. Ten days after being discharged, the patient again presented to the emergency department with complaint that the neck mass had increased in size. CT neck showed a 5.1 x 2.8 x 0.8 cm lobulated fluid collection. CT-guided drainage was performed, cytology and wound culture were found to be unremarkable. Thyroid function tests revealed she was hypothyroid with TSH 31.157 uIU/mL and FT4 of 0.72 ng/dL. Upon discharge, Methimazole was discontinued and she was started on Levothyroxine 75 mcg daily. Due to failure of prior antibiotics, she received a 14-day course of IV Ceftriaxone. Outpatient follow-up eight weeks later showed she was euthyroid on Levothyroxine 75 mcg with ultrasound revealing small thyroid gland with resolution of the abscess.
Conclusion: Hyperthyroidism in the setting thyroid abscess is secondary to destructive thyroiditis. As there is no increase in thyroid hormone synthesis, there is no role for treatment with antithyroid medication. Symptomatic control with beta-blocker, surgical drainage, and IV antibiotics are recommended for cases of thyroid abscesses. If infection persists or extensive necrosis develops, thyroidectomy may be indicated. Hypothyroidism can be a consequence of destructive thyroiditis as was seen in this patient.
Thyroid Hormone Resistance With Concurrent Papillary Thyroid Cancer
Authors: Pahwa Dhivya , Shanik Michael Howard 
Published: May 2021

Abstract
Introduction: Thyroid hormone resistance is a genetic mutation resulting in decreased receptor responsiveness. We present a case of thyroid hormone resistance with concurrent papillary thyroid cancer.
Clinical Case: A 34-year-old man with a history of papillary thyroid carcinoma status post total thyroidectomy and radioactive iodine. He had transferred his care after moving to our area. He presented with persistently elevated TSH despite ongoing treatment with Levothyroxine 400 mcg daily. Upon presentation the patient reported intermittent palpitations and tremor. Vital signs revealed height of 74 inches, weight of 235 pounds, blood pressure of 112/64, and heart rate of 48. Physical examination revealed a well -healed scar on the neck without palpable lymphadenopathy. Bloodwork revealed TSH of 15.28 mIU/L and Free T4 of 2.8 ng/dL. The patient was maintained on Levothyroxine 400 mcg daily and educated on proper administration of the medication. Two months later, bloodwork revealed a TSH of 9.22 mIU/L with a Free T4 of 3.3 ng/dL. MRI of the pituitary revealed a 4mm hyper-intensity which likely represented a microadenoma. Resistance Thyroid Hormone (RTH) Mutation analysis was ordered which revealed a heterozygous mutation for the Thyroid Hormone Receptor (THR)-Beta gene. The mutation was detected at pArg438His indicating a single nucleotide substitution leading to the replacement of arginine by histidine at the p.438 of the translated protein on exon 10. The patient was maintained on Levothyroxine at 400 mcg daily.
Discussion: Thyroid hormone resistance describes a constellation of symptoms from decreased tissue responsiveness to thyroid hormones. Literature reveals the prevalence of THR to be 1 in 40,000 individuals. It occurs due to mutation on the thyroid hormone receptor, most often found on the alpha or beta subunit. Frequently patients present with tachycardia and hyperactivity but it can also present with symptoms suggestive of hypothyroidism and goiter. Risk factors include family history of RTH mutation often with an autosomal dominant inheritance pattern. Patients with an elevated Free T4 with a non-suppressed TSH should be investigated with a genetic analysis of Resistance Thyroid hormone. A positive mutation would confirm the diagnosis. Close monitoring of symptoms as well as thyroid function tests should guide treatment. The concurrent diagnosis of thyroid hormone resistance in conjunction with papillary thyroid carcinoma in our patient is unique and makes management a challenge. The literature reveals few cases reported.
Reference: DynaMed. (2018, November 30). Thyroid Hormone Resistance. Retrieved October 2, 2020, from https://www-dynamed-com.arktos.nyit.edu/topics/dmp~AN~T912485
Igata M, et al. Coexistence of resistance to thyroid hormone and papillary thyroid carcinoma. Endocrinol Diabetes Metab Case Rep. 2016;2016:160003. doi:10.1530/EDM-16-0003
Thyroid Tuberculosis Causing Fever of Unknown Origin in a Patient With Multinodular Goiter
Authors: Rauf Mohammad Talha , Nhan Winnie , Daneshvar Farah 
Published: May 2021

Abstract
Introduction: Tuberculosis (TB) involving the thyroid gland is rare and typically results in hypothyroidism. Here we report a case of thyroid TB that presented with hyperthyroidism. Clinical Case: A 54-year-old woman with a history of hyperthyroidism due to toxic multinodular goiter presented to the emergency department with fever of unknown origin associated with sore throat, non-productive cough, night sweats, diarrhea, and right anterior neck pain that worsened with coughing. Her fevers were intermittent, ranging from 38 to 39 degrees Celsius, and would subside with acetaminophen. She reported that her symptoms had started after getting a thyroid [Tc-99m] pertechnetate scan and 24 hour [I-131] sodium iodide uptake study a month prior. The scan at the time revealed hyperfunctioning thyroid nodules in the lower lobes bilaterally. The 24-hour uptake was 20.2% which is within the normal range of 7 to 30%. TSH on presentation was 0.01 mIU/L (Normal range 0.3-5.50 mIU/L), free T4 was 2.05 ng/dL (Normal range 0.76 -1.7 ng/dL), and free T3 was 5 pg/mL (Normal range 1.9-3.9 pg/mL). Exam revealed a multinodular goiter, which was firm with mild tenderness, and no cervical lymphadenopathy. Infectious workup was unremarkable other than a positive interferon-gamma release assay. As for TB risk factors, the patient immigrated to the United States from Albania about 13 years prior. The patient denied any known TB exposure, neither had she been treated for TB. Radiograph and computed tomography (CT) of the thorax were unremarkable other than re-demonstration of the multinodular goiter. Fluorodeoxyglucose-18 positron emission tomography (FDG-PET), which was performed to identify any focus of active TB, had revealed intense, infiltrative, heterogeneous FDG uptake of the nodular thyroid gland with reactive level 3 and 4 cervical lymph nodes. Also, the scan revealed hyper-metabolic hilar, pre-tracheal, and sub-carinal lymph nodes which could represent latent TB. Further workup for any other foci of active TB including broncho-alveolar lavage, sputum cultures, lumbar puncture, and bone marrow biopsy were unremarkable. Thyroid ultrasound revealed 2 right sided and 3 left sided thyroid nodules, mostly solid and hypoechoic. Fine needle aspiration of nodules revealed benign follicular nodules bilaterally, however the left aspirate contained loose aggregates of histiocytes consistent with non-necrotizing granulomas. Acid-fast bacilli stain of the aspirate was negative. The patient was started on therapy for active TB with isoniazid, rifampin, pyrazinamide, and ethambutol. Six weeks after treatment her fevers had resolved. Conclusion: Thyroid TB should be considered when the severity of symptoms cannot be explained by the degree of hyperthyroidism alone in patients with increased risk of TB. Additionally, TB in the thyroid can be challenging to identify in a patient with known underlying thyroid disease.
ThyrotropinomA: Diagnosing a Rare Cause of Hyperthyroidism
Authors: Bhanot Monica , Hendrickson Chase Dean 
Published: May 2021

Abstract
Case: The patient is a 40-year-old male who presented for evaluation of hyperthyroidism with symptoms including palpitations, increased bowel movements, anxiety, and worsening tremor. With a family history of Graves’ disease and an ultrasound showing a hyperemic thyroid, there was initial suspicion for Graves’ disease. Although a radioactive iodine thyroid scan showed diffuse uptake that was elevated, 21.4% at 4 hours and 33.1% at 24 hours, lab evaluation appeared inconsistent with Graves’ disease revealing: TSH 1.65 µU/mL (upper limit of normal [ULN] 4.5), free thyroxine (FT4) 1.99 ng/dL (ULN 1.17), free triiodothyronine 6.16 ng/dL (ULN 3.98), thyroid stimulating immunoglobulin 92% (ULN 122), and thyroid receptor antibodies less than 1.0 IU/L (ULN 1.75). Lab results were reproducible with elevated FT4 even by equilibrium dialysis at 3.9 ng/dL (ULN 2.4) and high-normal TSH with serial dilution that ruled out assay interreference. Given these findings, our focus turned to rare causes of hyperthyroidism including thyrotropinoma and thyroid hormone resistance (RTH). Unique to the diagnosis of thyrotropinoma is an elevated serum α subunit in 50-85% of cases (1). Therefore, we obtained an α subunit level which was 0.35 ng/mL (ULN 0.55) with a molar ratio of 2.2 (ULN 2.4). Since the α subunit level was normal, the patient obtained genetic testing for mutations in the thyroid hormone receptor β gene seen in 85% of RTH cases (1). However, no sequence variants were identified. Since initial lab and genetic analyses were undifferentiating, additional tests were obtained including an insulin-like growth-factor 1 level of 209 ng/mL (ULN 237) and prolactin level of 10.1 ng/mL (ULN 20) which can be elevated in 30% of mixed thyrotropinoma cases (1). The first evidence to suggest a thyrotropinoma was a mildly elevated sex-hormone binding globulin at 102 nmol/L (ULN 80). Further evaluation with pituitary magnetic resonance imaging showed a 6-milimeter lesion. Although the pituitary lesion is suggestive of a thyrotropinoma, it is not definitive, as they are present in 20% of RTH cases (1). Therefore, with increased suspicion of a thyrotropinoma, we pursued the more robust T3 suppression test which showed 56% suppression of TSH consistent with a thyrotropinoma. The patient had pituitary surgery with pathology confirming weak immunoreactivity for TSH. Post-operatively, his symptoms improved and free thyroid hormones normalized.
Discussion: It is important to distinguish between thyrotropinoma and RTH as the treatment is different with 80% of thyrotropinoma cases achieving euthyroidism after surgery (1). In our case, the diagnosis was initially unclear thus it was important to broaden the lab and genetic evaluation considering the limitations of the studies. One such limitation is the α subunit may not be elevated in microadenomas as occurred in our case.
1. Beck-Peccoz et al. J Endocrinol Invest. 2019; 42:1401-6
Title: Case of Hyperthyroidism in a Patient on Anti-PD-1 (Programmed Cell Death Receptor-1 Blocking Antibody) Therapy Caused by Destructive Thyroiditis Followed by Graves’ Disease
Authors: Reddy Chandrika , Zena Mohsen 
Published: May 2021

Abstract
Introduction: Immune checkpoint inhibitor (ICI) related thyroid dysfunction such as destructive thyroiditis and hypothyroidism can occur with Anti-PD-1 therapy. Graves’ disease (GD) however is considered rare. We report a case of isolated hyperthyroidism in a patient on Pembrolizumab, Anti-PD-1 presenting initially as destructive thyroiditis and later transitioned to GD.
Case: 57 y.o lady was diagnosed with squamous cell carcinoma of cervix, stage 4 in 2016. She was noted to have asymptomatic goiter in 1997. PET scan in 02/2017 showed hypermetabolic activity in the right lobe nodule of 5.6 cm with maximum SUV of 9.8. Baseline TSH was in normal range in 04/2017. US guided fine needle biopsy of the nodule resulted as follicular neoplasm with 15-30%, risk of malignancy. Molecular test showed 40% risk of malignancy. Lobectomy was deferred. Pembrolizumab was initiated for advanced cervical cancer in 07/2018. Repeat PET in 10/2018 showed resolution of metastasis and right thyroid mass was stable. TSH remained in euthyroid range for 4 months until 11/ 2018. In 01/2019, her TSH was low and became undetectable in 03/2019 with high free T4 and total T3. She developed symptoms of hyperthyroidism. TSI was positive and TSHR Ab was negative. RAIU was low. No iodinated contrast study done prior to I123 scan. In 05/2019 to 08/2019, free T4 and total T3 was normal range with detectable but low TSH consistent with transient resolving thyroiditis. In 10/2019, thyroid hormones significantly increased with recurrence of hyperthyroidism. Both TSI and TSHR Ab were elevated confirming diagnosis of GD. Due to overt thyrotoxicosis, Methimazole (MMI) was initiated in 10/2019. She was briefly lost to follow up and stopped MMI. RAIU scan in 12 /2019 showed increased uptake consistent with GD. MMI was resumed in 04/2020. 06/2020 - 09/2020, MMI dose was titrated to achieve euthyroid state. In 09/25/2020, hypothyroidism was noted which improved with MMI dose reduction. Anti- TPO and Anti-Tg were negative. Pembrolizumab was stopped in 07/2020 due to dilated cardiomyopathy. She completed 2-year course of Pembrolizumab with advanced cervical cancer showing excellent response.
Discussion: Observed thyroid dysfunction with ICI, is transient destructive thyroiditis followed by hypothyroidism, which can be permanent. Our patient had an initial low RAIU indicating destructive thyroiditis along with, mildly elevated TSI suggestive of superimposed autoimmune process. The elevated TSI predisposed to later occurrence of GD likely precipitated by Pembrolizumab. MMI provided therapeutic benefit.
Conclusion: Less than 10 cases of GD with ICI and 5 cases of GD with Anti-PD- 1 have been reported. Our patient is a second case of persistent hyperthyroidism due to GD induced by Pembrolizumab. GD should be considered if hyperthyroidism persists or recurs in patients on ICI with destructive thyroiditis, which is mostly transient.
Use of Lugol’s Solution in the Management of Complex Graves’ Disease-a Small Case Series
Authors: Asefa Rufaro , Martin Allison Shane 
Published: May 2021

Abstract
Background: There are currently no clear guidelines for the peri-operative use of Lugol’s solution (LS) as an alternative to conventional anti-thyroid drug (ATD) therapy in patients with complex Graves’ thyrotoxicosis.
Clinical Cases: Case 1 is a 44- year-old woman who presented with symptoms of hyperthyroidism and a moderately enlarged goiter due to Graves disease. She was treated initially with Methimazole 45 mg, once daily which was reduced to 30 mg once daily after a week. She subsequently presented to the emergency department with severe anxiety, sore throat, and a high fever. A blood panel showed evidence of profound agranulocytosis due to Methimazole. Methimazole was stopped and she was treated with a 10-day course of LS followed by a semi-elective total thyroidectomy.
Case 2 is a 54-year-old old woman who presented with thyrotoxicosis due to Graves’ disease. She was started on Propylthiouracil (PTU) to which she developed hepatotoxicity and the decision was made to stop PTU. Methimazole was substituted to which she developed a severe desquamating rash hence it had to be stopped immediately. She was given a 10 day course of LS followed by semi-elective total thyroidectomy.
Conclusion: In both cases, hyperthyroidism was successfully treated with Lugol’s solution and their surgeries were uneventful with full recovery. Although beneficial, Lugol’s Solution may result in adverse effects such as severe hypothyroidism, escape hyperthyroidism and death. These cases highlight the need for evidence based treatment guidelines for the use of Lugol’s solution in complex hyperthyroid cases.
Identification of Cell Types that Express Dio3 Deiodinase, a Thyroid Hormone-Inactivating Enzyme, Using a Dio3-CreERT2 Reporter System
Authors: Liu Ye , Forrest Douglas 
Published: May 2021

Abstract
Background: Thyroid hormone promotes development, growth and metabolism. The level of thyroid hormone ligand (triiodothyronine, T3) in tissues depends not only on circulating levels but also upon tight regulation by activating and inactivating deiodinases within tissues. Type 3 deiodinase (Dio3) inactivates T3 and its precursor thyroxine (T4) and mediates many functions including in neurodevelopmental, sensory and reproductive systems. Dio3 is subject to genomic imprinting. Despite its critical functions, Dio3 is often expressed transiently and at low levels in restricted cell populations making it difficult to detect in natural tissues. Methods: To visualize Dio3 expression at cellular resolution, we derived a Dio3-CreERt2 knockin allele that expresses tamoxifen-dependent Cre recombinase from the endogenous Dio3 gene. When crossed with Ai6 reporter mice, Dio3-CreERt2-positive cells display fluorescent signals. When tamoxifen-treated at neonatal ages, Dio3-CreERt2 recapitulates endogenous Dio3 expression as previously reported in brain: in the bed nucleus of the stria terminalis and preoptic nuclei. In addition, we uncovered several positive cell groups in the hypothalamus, brain stem, pituitary and other tissues. Drastic differences were observed for Dio3-CreERt2 as a paternally versus maternally inherited allele, revealing imprinting effect in specific cell types. Dio3-CreERT2 activity is enhanced by T3 administration, in accordance with Dio3 as a T3-indicible gene. Conclusion: The Dio3-CreERT2 model sensitively reveals Dio3-expressing cell types in tissues. The model is useful for studying expression patterns, imprinting and lineage tracing of Dio3-positive cells during development and homeostatic challenges.