bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Testing Can Impact Clinical Decision Making and Therapeutic Approach in Thyroid Cancer
Authors: Garcia Gonzalo J Acosta , Praw Stephanie Smooke 
Published: May 2021

Abstract
We present the case of a patient with a thyroid nodule of indeterminate cytology on fine-needle aspiration (FNA) biopsy whose molecular profile significantly impacted clinical decision making and treatment.
A 77-year-old woman with a history of hyperthyroidism presented to our clinic for a second opinion regarding management of a recently discovered right thyroid nodule. Thyroid ultrasound (US) 6 months prior showed a 2.6 cm, heterogeneous nodule with peripheral vascular flow; not characterized based on ATA or TIRADS criteria. Family history was significant for papillary thyroid cancer in daughter at age 35 years. The patient had no history of head or neck irradiation. She had no compressive symptoms or manifestations of hyper or hypothyroidism.
FNA biopsy of the nodule was done twice in 4 months, and cytology was consistent with follicular lesion of undetermined significance (FLUS, Bethesda III) in both occasions. Repeat FNA biopsy at our institution showed follicular neoplasm (FN, Bethesda IV), and molecular testing using ThyroSeq v3 was positive for HRAS and TERT mutations, which conferred a &gt;95% risk of cancer. Patient was referred to Endocrine Surgery and total thyroidectomy was recommended based on nodule’s molecular profile and associated hyperthyroidism. No suspicious lymph nodes were noted on preoperative US. No gross local invasion observed intraoperatively. Surgical pathology showed intrathyroidal FN without invasion. However, given disparity between pathology findings and molecular markers, specimen was sent for outside blinded pathology review which concluded to be a follicular thyroid carcinoma with capsular invasion but no angiolymphatic invasion or extrathyroidal extension. Based on these findings, along with the known HRAS and TERT mutations, it was advised to proceed with radioiodine (RAI) remnant ablation. Patient was prepared with thyrotropin alfa and received 29 millicuries of RAI. Post-treatment scan showed focal neck uptake consistent with ablated thyroid tissue and no distant metastases. Patient had an excellent response to therapy, without evidence of biochemical or structural recurrence 2 years later.
Molecular testing of cytologically indeterminate thyroid nodules (Bethesda III, IV) has become an important tool to better refine risk of malignancy. Furthermore, the presence of certain mutations or mutation combinations, such as RAS and TERT co-occurrence, suggests a more aggressive behavior associated with worse outcomes. As a result, a more aggressive approach might be recommended. Our case illustrates how molecular testing can significantly influence therapeutic decisions such as extent of surgery, interpretation of surgical pathology and/or use of RAI. Further research is needed to determine if its routine use may lead to improved cancer-related outcomes or if it is cost-effective in the risk stratification of differentiated thyroid cancer.
Preoperative Amlodipine Is More Efficacious Than Prazosin in Preventing Intraoperative Haemodynamic Instability in Pheochromocytoma/Paraganglioma Patients: Interim Analysis of a Pilot Randomized Controlled Study
Authors: Memon Saba Samad , Jaiswal Sanjeet Kumar , Garg Robin , Barnabas Rohit , Goroshi Manjunath , Lila Anurag , Sarathi Vijaya , Dalvi Abhay , Garale Mahadeo , Hemantkumar Indrani , Patel Rajendra , Oak Shrikanta , Patil Virendra , Shah Nalini Samir , Bandgar Tushar Ramkrishna 
Published: May 2021

Abstract
Background: Preoperative blockade with α-blockers is recommended in patients with pheochromocytoma/paraganglioma (PPGL). The data on calcium channel blockade (CCB) in PPGL is scarce. We aim to compare the efficacy of CCB and α-blockers on intraoperative haemodynamic instability (HDI) in PPGL. Methods: In the interim analysis of this monocentric, pilot, open-label, randomized controlled trial, patients with solitary, secretory, and nonmetastatic PPGL were randomized to oral prazosin (maximum 30mg, n=9) or amlodipine (maximum 20mg, n=11). The primary outcomes were the episodes and duration of hypertension (SBP≥160mmHg) and hypotension (MAP&lt;60mmHg) and duration of HDI (hypertension and/or hypotension) as a percentage of total surgical time (from induction of anaesthesia to skin closure). Findings: The median (IQR) episodes (2 [1–3] vs. 0 [0–1], p 0·002) and duration of hypertension (19 [14–42] min vs. 0 [0–3] min, p 0·001) and intraoperative HDI duration (22·85±18.4% vs 2·44±2·4%, CI 8·68-32·14%, p 0·002) were significantly higher in the prazosin arm than the amlodipine arm whereas episodes and duration of hypotension did not differ between the two groups. There was no perioperative mortality whereas one patient had intraoperative ST depression on the electrocardiogram. The drug-related adverse effects were pedal edema (1 in amlodipine), dizziness (1 in prazosin), and tachycardia (6 in prazosin and 3 in amlodipine). Interpretation: Preoperative blockade with amlodipine was more efficacious than prazosin in preventing intraoperative HDI in PPGL. Larger studies that compare preoperative blockade with amlodipine and both competitive and noncompetitive α-blockers inPPGL patients of various biochemical phenotypes are warranted.
Thyroid Angiosarcoma Complicated by Neck Hematoma
Authors: Larsen Dana , Yanagisawa Robert 
Published: May 2021

Abstract
Background: Primary angiosarcoma of the thyroid is a rare, aggressive thyroid malignancy most typically found in the Alpine regions of Europe. We present a case of non-Alpine thyroid angiosarcoma complicated by recurrent surgical bed hematoma.
Case: An 81-year-old Albanian man presented with two months of dyspnea and hemoptysis and was found to have a large thyroid mass, multiple subcentimeter pulmonary nodules, and a left pleural effusion seen on CTA of the chest. He had a suppressed TSH &lt; 0.008 uIU/mL (n 0.400-4.200 uIU/mL) on presentation with a normal free T4 (1.36 ng/dL; n 0.80-1.50 ng/dL) and total T3 (107 ng/dL; n 87-178 ng/dL). Labs from 3 years prior were consistent with prior subclinical hyperthyroidism: TSH 0.28 uIU/mL, free T4 1.35 ng/dL, and free T3 3.98 pg/mL (n 2-4.4 pg/mL). A thyroid ultrasound was performed and showed multiple bilateral thyroid nodules, the largest of which was 6.0 x 7.8 x 5.4 cm in the right lower pole. He had no compressive symptoms and was clinically euthyroid. FNA of the nodule was non-diagnostic and cytology of the pleural fluid was negative for malignancy. He underwent a bronchoscopy which showed blood clots without endobronchial lesions, VATS with pleural biopsy, and right hemithyroidectomy. Pathology showed high grade epithelioid malignancy arranged in solid, variably discohesive nests and sheets, associated with vague vasoformative features and hemorrhage. Immunostains were diffusely and strongly positive for ERG as well as CD31 and AE1/3, but negative for PAX-8, TTF-1, and thyroglobulin, supporting a diagnosis of angiosarcoma. The remainder of the thyroid tissue was non-neoplastic with multinodular hyperplasia. After initial discharge, he re-presented on post-op day 10 with bleeding from the surgical site. CT of the neck showed extensive hematoma (10.3 x 5.0 x 8.7 cm) and he was taken back to the OR for evacuation. Residual tumor tissue found along the R carotid artery was determined to be the culprit. Over the next month the patient remained admitted for supportive transfusions, and palliative radiation to the pulmonary nodules and the residual tumor was initiated. His hospitalization was complicated by a proximal lower extremity DVT, which was treated with an IVC filter. Repeat chest imaging at six weeks showed new and progressive pulmonary nodules. Upon completion of 3 weeks of RT the patient was discharged debilitated, fatigued, and using supplemental oxygen. His family elected to pursue hospice care.
Conclusion: This case represents a rare, aggressive malignancy complicated by extrathyroidal extension and recurrent hematoma resulting in severe morbidity and precluding further systemic interventions. These highly vascular tumors likely present an elevated risk for postoperative hematoma which clinicians should recognize.
Toxic Thyroid Nodule: To FNA or Not?
Authors: Kasina Siva Kumar , Hayward Erin E , Lal Geeta , Correia Marcelo 
Published: May 2021

Abstract
Background: ATA guidelines recommend evaluation of hyperthyroidism with radioiodine scan and consideration of FNA for non-toxic nodules with suspicious sonographic features. However, there is no standard evidence-based approach to performing ultrasound in patients with toxic nodules. Recent studies have shown increased rates of thyroid cancer in patients with hyperthyroidism and has been shown to demonstrate aggressive histologic features. Clinical Case: A 41-year-old female presented to primary care provider for annual physical exam, found to have intermittent bigeminy and enlarged thyroid on exam. EKG notable for multiple premature ventricular complexes. Evaluation revealed suppressed TSH &lt;0.01 µIU/mL (0.27-4.20), normal free T4 1.27 ng/dL (0.80-1.80), slightly elevated free T3 4.84 pg/mL (2.57-4.43) and elevated TSI 238% (&lt;122). Methimazole was started for treatment of hyperthyroidism. Thyroid sonogram was ordered for abnormal exam, that showed 2.7 cm TIRADS 4 left thyroid nodule with microcalcifications. I-131 uptake values were 20% and 49% at 4-hours and 24-hours, respectively. Technetium-99M scan showed toxic autonomous nodule in the left thyroid lobe corresponding to the one seen on sonogram. The remainder of the thyroid gland showed heterogeneously suppressed uptake. FNA of the thyroid nodule was done due to the presence of microcalcifications and the cytopathology was suspicious for papillary carcinoma. She underwent total thyroidectomy with central neck dissection involving pre-tracheal and paratracheal lymph nodes (level VI). Pathology showed 1.4 cm papillary carcinoma with lymphovascular space invasion and multifocal papillary microcarcinomas in the left thyroid lobe, 0.2 cm papillary microcarcinoma in right thyroid lobe, metastatic papillary carcinoma in 2 out of 5 lymph nodes, largest metastatic deposit 0.1 cm in the largest dimension with no extra nodal extension. There was also follicular hyperplasia noted consistent with Graves’ disease. Post-operatively, she had thyrogen-stimulated adjuvant RAI treatment, dose 107.4 mCi. Post therapy scan did not show evidence of distant metastases. Conclusion: This case demonstrates the identification of a metastatic papillary thyroid carcinoma based on suspicious ultrasound features requiring total thyroidectomy, central neck dissection and adjunct radioactive iodine in a patient with hyperthyroidism from co-existent toxic thyroid nodule and Graves’ disease.
Undifferentiated Thyroid Carcinoma With Anaplastic Features in a 78-Year-Old Filipino Female: A Case Report
Authors: Sarigumba Marion Bagaloyos , Isidro Maria Jocelyn Capuli 
Published: May 2021

Abstract
Background: Anaplastic thyroid carcinoma (ATC) accounts for 0.8-9.8% of all thyroid cancers globally with a median survival from diagnosis of 5 months.
Clinical Case: A 78-year-old Filipino female sought consult due to a rapidly progressive anterior neck mass. This started as a centimeter-sized nodule initially noted three months prior. Two months after, there was gradual enlargement to a fist-size, movable mass, hard in consistency associated with dysphagia and hoarseness of voice. On consult, neck ultrasound revealed an enlarged right thyroid with a mass in the right lobe (TI-RADS 5), multinodular with no lymphadenopathy. Furthermore, a CT scan of the neck was done to evaluate for other structural causes of dysphagia showing no intrathoracic extension. Patient was advised surgery but was lost to follow up due to lockdown from COVID-19. In the interim, patient was admitted for aspiration pneumonia. IV antibiotics were initiated and urgent surgery was advised to relieve patient of respiratory compromise. Patient was airlifted to a tertiary care center for further management. Baseline thyroid function tests were normal. Repeat neck imaging showed interval increase in the hypodense mass measuring 6x9x8 cm (from 3x4x5 cm) (APxWxCC) extending to the hypopharynx and laryngeal vestibule with mass effect to the trachea and esophagus. A multidisciplinary meeting was done to establish goals of care. On the 3rd hospital day, a tracheostomy with incisional biopsy and frozen section was done which revealed round to spindle cell neoplasm with anaplastic features. No further surgical resection was done and specimen was sent for immunohistochemical staining. Long term enteral access was secured during the same operation. Final histopathology showed undifferentiated thyroid carcinoma with anaplastic features and no definite lymphovascular invasion. Immunohistochemical markers were negative for CD3, CD20, Thyroglobulin, TTF-1, PAX8, Calcitonin and Pancytokeratin which reveal loss of tumor antigenicity, consistent with the histopathologic diagnosis. Metastatic work-up revealed varisized pulmonary, subpleural and hepatic nodules with lymphangitic carcinomatosis. Patient was staged as IVC (T4N1M1). Patient was referred for radiation to maximize local control, to complete 33 fractions of 200 cGy on the thyroid mass and received one cycle of Paclitaxel before discharge. Concurrent chemoradiation was continued and completed 29 cycles of radiation and 2 cycles of Paclitaxel which significantly reduced the tumor size. However, the patient succumbed to acute coronary syndrome on her third admission.
Conclusion: There is currently no consensus first-line treatment modality available worldwide. Although the diagnosis and treatment of ATC is considered medically urgent, end-of-life planning must be given high priority in order to optimize the quality of the patient’s remaining life.
Xeroderma Pigmentosum: An Uncommon Risk Factor for Aggressive Follicular Thyroid Carcinoma
Authors: Pattison Jillian 
Published: May 2021

Abstract
Introduction: Follicular thyroid carcinoma (FTC) is the second most common thyroid cancer, which typically presents in an older populations, and carries a near 100% 5-year relative survival rate if diagnosed prior to cancer spreading outside of the thyroid. Clinical Case: A 26-year old female presented to emergency room with persistent jaw pain, despite course of antibiotics prescribed by dentist. She has a past medical history of xeroderma pigmentosum (XP) with over 130 surgeries for malignant skin lesions, as well as benign multinodular goiter for which she underwent total thyroidectomy at the age of 18, with pathology reporting benign tissue and follicular adenoma. Emergency room imaging of maxillofacial/sinus incompletely captured a mass in the left paratracheal region, extending into the lumen of the trachea. Patient was then transferred to University Hospital for further evaluation. Dedicated neck imaging confirmed 4.6cm mass in expected area of thyroid gland, invading into left tracheal wall, cervical esophagus, and hypopharynx. Additional imaging revealed numerous pulmonary nodules, and a 4mm enhancing focus of left superior temporal gyrus. Nuclear positron emission tomography imaging revealed regions of hypermetabolic activity in the left maxillary sinus, the facial nodules, cervical lymph nodes, and mass like region of hypermetabolic activity in the thyroid bed. Biopsy confirmed follicular thyroid parenchyma, concerning for follicular carcinoma. Patient then underwent mass resection and tracheostomy. Some thyroid tissue was left on contralateral side to malignancy due to adjacency to only functional recurrent laryngeal nerve. Pathology following surgery confirmed follicular thyroid carcinoma, with evidence of angioinvasion. Thyroglobulin mass spectrometry prior to surgery was 302 ng/mL. Conclusion: While it is well known that patients with XP suffer from early development of mucocutaneous and ocular cancers in sun-exposed areas, these patients also have increased risk for multinodular goiter as well as internal malignancies. Furthermore, treatment of any internal malignancy is limited due to inability for patients with XP to be treated with radiation. Providers for patients with XP should have very low thresholds to investigate all new symptoms aggressively, maximizing chances of diagnosing malignancies in early stages.
Zebra Case of Papillary Thyroid Cancer in MEN-2 Syndrome
Authors: Gaballa Salem 
Published: May 2021

Abstract
Introduction: The occurrence of papillary thyroid cancer in patients with familial medullary thyroid cancer (FMTC) is extremely rare and underreported. Case Presentation: A 51-year-old caucasian female with no past medical history who presented to primary care physician for her annual visit. She denied any complaints. Vital signs were unremarkable. Physical examination was remarkable for large left thyroid nodule without cervical lymph nodes enlargements. Family history was significant for metastatic MTC of her two sisters (at the age of 55, 60) and her niece at age of 21. She previously declined genetic testing. Labs were unremarkable including serum calcium of 8.3 mg/dL. Thyroid function panel revealed a TSH of 2.1 μU/mL, Free T4 of 1.4 ng/dL, Thyroid peroxidase (TPO) antibody of &lt;6 IU/mL. Neck ultrasonography revealed a mid-left thyroid hypoechoic nodule of 1.8 ×1.5 cm, without cervical lymph nodes enlargements. Fine needle biopsy revealed a papillary thyroid cancer, follicular variant. The diagnosis confirmed by two university pathologists, without any evidence of MTC. Genetic testing revealed a germline mutation in RET oncogene exons 13. Further labs revealed normal metanephrines of 12 pg/mL and normal normetanephrine of 31 pg/mL, normal serum calcitonin was less than 2 pg/mL (0-5), normal serum CEA was 2.5 ng/mL (0-5), elevated anti- thyroglobulin (anti-TG) antibodies of 1234 iu/mL (0-0.9), and elevated thyroglobulin of 50 ng/mL (1.5-38.5). The patient was referred to ENT for total thyroidectomy. Further, she was treated with radioactive iodine ablation by 155 mCi of iodine 131. Follow up whole body thyroid scan revealed no evidence of residual or recurrence. The patient was treated with 112 mcg levothyroxine with a target of TSH less than 0.1. On six months follow up, repeated neck ultrasonography revealed no remnant of thyroid tissue. Follow up Thyroglobulin (TG) was less than 0.1 ng/mL, TSH 0.05 μU/mL, FT4 of 1.98 ng/dL, and calcitonin was still less than 2 pg/ml. Genetic testing of her daughters (24, 31) revealed germline mutations in RET-oncogene exons 13 and was referred for prophylactic thyroidectomy. Discussion: FMTC is an inherited syndrome characterized by the presence of only MTC without hyperparathyroidism or pheochromocytoma and is considered a variant of MEN2A. Most cases of MEN2A have been attributed to mutations in the intracellular portion of RET, and somatic mutations in RET have been identified in 50% of cases of sporadic FMTC. We recommend in patients with germline RET mutations and a family history of MTC, the diagnosis of papillary thyroid cancer should be confirmed by two pathologists, and patients should be tested for serum calcitonin, serum calcium, and metanephrines/normetanephrine levels. Genetic testing of first-degree relatives of FMTC at an early age is essential in guiding major management decisions such as the timing of prophylactic thyroidectomy.
A Case Report on Methimazole-Induced Cholestatic Jaundice in an Elderly Man With Hyperthyroidism
Authors: Ng Jennifer Lourdes , Ramos Celeste Ong 
Published: May 2021

Abstract
Background: The early detection and diagnosis of the causes of jaundice in a hyperthyroid patient taking antithyroid medications are paramount for the appropriate management of these patients. Clinical Case: A 72 year old male is admitted due to septic shock secondary to pneumonia and funguria, acute kidney injury secondary to sepsis, type 2 diabetes mellitus, uncontrolled and Graves’ disease with thyroid nodules (Tirads 4). On physical examination, he has icteresia and generalized jaundice. Methimazole was started 12 days ago. Initial tests were consistent with a cholestatic pattern of jaundice: slightly elevated alanine aminotransferase 70 U/L (16-63), aspartate aminotransferase 84 U/L (15-37) and significantly elevated alkaline phosphatase 662 U/L (46-116), total bilirubin 12.16 mg/dl (0.20-1.0), conjugated bilirubin 11.29 mg/dl (0-0.20) and unconjugated bilirubin 0.87 mg/dl (0-0.80). He has hypoalbuminemia and normal prothrombin time. He has negative anti-Smith antibody, anti-ribonucleoprotein, anti-mitochondrial antibody, and positive anti-nuclear antibody 1:160 speckled pattern. Hepatitis Profile showed chronic hepatitis A infection. Upper Abdomen Ultrasound showed ill-defined border in the left hepatic lobe; intrahepatic ducts and common bile duct are not dilated; gallbladder is contracted with no evident intraluminal echoes. Whole Abdomen with 4-phase Dynamic Liver CT Scan showed multiple ill-defined hypoattenuating lesions in the entire liver parenchyma; intrahepatic ducts, common bile duct, and pancreatic duct are not dilated; and gallbladder is normal in size without intraluminal calculus with possible metastases at spleen, left adrenal gland and tail of pancreas. He has normal AFP and elevated CEA. Methimazole was discontinued at admission and was started on Hydrocortisone 100 mg/IV every 8 hrs. Repeat liver profile panel showed decreasing trends after 4 days of holding methimazole. Repeat fT4 after 6 days of high dose hydrocortisone showed a decrease from 3.09 ng/dl to 1.98 ng/dl (0.89-1.76). Hydrocortisone was continued and tapered accordingly. Plans for RAI discussed. Conclusion: This case emphasizes the need to be vigilant for the very rare but serious adverse events of antithyroid medications.