bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low Rate of Guideline Adherence for the Diagnosis and Management of Adrenal Incidentalomas in the Nova Scotia Health Authority Central Zone
Authors: Pipe Stephanie , Costa Andreu , Siddiqi Ferhan 
Published: May 2021

Abstract
Background: Adrenal incidentalomas are prevalent and clinically significant, yet are often overlooked by clinicians. The objective of this study was to retrospectively examine the adherence to American College of Radiology (2017) and European Endocrine Society (2016) guidelines for the diagnosis and management of adrenal incidentalomas within a centre servicing a population of over 400,000. Methods: Relevant computed tomography (CT) and magnetic resonance (MR) scans from February 17th, 2019 to December 18th, 2019 were consecutively reviewed for the presence of adrenal incidentalomas. Radiographic reports and original imaging were reviewed to evaluate the completeness of reporting. A chart review was conducted to determine if biochemical investigations for cases were undertaken and whether referral to Endocrinology was made. Reports were checked for the inclusion of an addendum recommending Endocrinology referral. Results: A convenience sample of 148 cases were included in the study, with 176 distinct adrenal incidentalomas identified. Where relevant, attenuation values were provided for 20% of cases, and follow-up imaging was recommended in 59% of cases. Of the 124 cases where biochemical investigation was deemed appropriate, a complete work-up was conducted in 4% of cases, and 11% were referred to Endocrinology. Follow-up imaging was ordered appropriately in 36% of cases, and no cases had inappropriate follow-up imaging. The addendum was included for 19% of cases, and it did not impact biochemical investigation rates but did improve Endocrinology referral rates. Conclusions: There is poor adherence to guidelines for the diagnosis and management of adrenal incidentalomas within our study population. This poor adherence would be an ideal target for quality improvement initiatives, in order to minimize missed functional and malignant adrenal masses.
Should Mode of Presentation Influence Interpretation of Thyroid Nodule Ultrasounds?
Authors: Stevens Lisa , Davoren Peter M 
Published: May 2021

Abstract
Background: The American College of Radiology (ACR) TI-RADS is a standardized scoring system for thyroid ultrasound reports providing recommendations on the need for fine needle aspirations (FNAs) independent of patient presentation. Aim: The aim of this audit was to determine if the initial presentation of the patient should be considered during the work-up of thyroid nodules. Methods: Data was collected from electronic medical records on 133 patients who underwent thyroid FNAs (165 FNAs in total) and 98 patients who had thyroid surgery for the management of thyroid nodules at Gold Coast University Hospital from Jan 1st 2019 – Dec 31st 2019. Patient presentation, adequacy of the ultrasound report and FNA results were recorded. These results were aligned with final diagnosis after surgery. Results: 98 patients underwent surgery and 29 (29.6%) were found to have malignant nodules, including 12 (12.2%) with microcarcinomas. Of the 29 malignancies, 16 patients presented with a palpable neck lump. Conclusions: Our data suggests a palpable neck lump is a significant factor in determining the risk of malignancy. It may be possible to adjust the current TI-RADS algorithm used to interpret thyroid ultrasounds to include patient presentation. This would reduce unnecessary testing and burden on the healthcare system.
Phenotypic Differences in Thyroid Immune Related Adverse Events Following Treatment With Immune Checkpoint Inhibitors
Authors: Muir Christopher Alan , Menzies Alexander M , Clifton-Bligh Roderick John , Long Georgina V , Scolyer Richard A , Tsang Venessa 
Published: May 2021

Abstract
Background: Thyroid toxicity is common following immune checkpoint inhibitor (ICI) treatment. Published studies estimate the incidence at 10-20%, although rates vary widely between different ICIs. The etiology of ICI-associated thyroid immune related adverse events (irAEs) is unknown & not all patients develop a classic thyroiditis-like presentation of transient hyperthyroidism followed by a hypothyroid phase. Only small observational cohorts have been reported & the clinical & biochemical features of thyroid irAEs have not been well characterized. The current study aimed to describe thyroid irAEs in a large cohort of patients with melanoma. Methods: We reviewed outcomes in a prospective cohort of adult patients undergoing ICI treatment for advanced melanoma. Thyroid function was measured at baseline & at regular intervals during treatment. Thyroid irAEs were defined as new biochemical thyroid dysfunction developing over the course of routine follow-up. Results: Thyroid irAEs occurred in 518 of 1246 (42%) patients. Median follow-up was 11.3 months. Multiple patterns of thyroid-irAEs were observed, such as hyperthyroidism (subclinical or overt) in 31%, hypothyroidism in 8%, & euthyroid hyperthyroxinemia, hypothyroxinemia & isolated low FT3 syndrome each in 1% of participants. Thyroid irAEs were more frequent following combination (CTLA-4 + PD-1) ICI treatment (56%) than following PD-1 (38%) or CTLA-4 (25%) based monotherapies (p=0.001). The severity of thyroid irAEs differed by ICI, with higher rates of overt (vs. subclinical) thyroid dysfunction following combination ICI treatment (47%) relative to PD-1 (37%) & CTLA-4 (19%) monotherapies (p=0.001). Younger age (OR 0.88 per 10-yrs; 95% CI 0.81-0.96), female sex (OR 1.62; 95% CI 1.27-2.08) & combination ICI-treatment (vs. CTLA-4, OR 3.76, 95% CI 2.49-5.75; vs. PD-1, OR 1.90, 95% CI 1.45-2.49) were associated with higher odds of thyroid irAE. Time to onset of thyroid dysfunction was shorter in patients with overt hyperthyroidism relative to other types of thyroid irAE (log rank p=0.001). Overt hyperthyroidism was associated with increased irAEs in other organ systems (colitis, hepatitis, etc), increased irAE severity & increased multi-system irAEs than euthyroid patients or patients with other subtypes of thyroid irAE (p=0.003). Overt hyperthyroidism was also associated with improved progression free survival (HR 0.57; 95% CI 0.39-0.84; p=0.005) & overall survival (HR 0.68; 95% CI 0.49-0.94; p=0.02). No benefit to cancer survival was observed with other thyroid irAE subtypes. Conclusions: Thyroid irAEs were common. Combination ICI treatment resulted in more frequent, more severe, & earlier onset thyroid irAEs. Of thyroid irAE subtypes, overt hyperthyroidism was uniquely associated with increased immune responsiveness, as evidenced by higher incidence of extra-thyroidal irAEs & improvements in cancer survival.
A Subtype of Papillary Thyroid Carcinoma Bone Metastasis With Excellent Response to RAI-Therapy
Authors: Vodopivec Danica M , Reddy Niyoti , Lee Stephanie L 
Published: May 2021

Abstract
Introduction: Bone metastases from differentiated thyroid cancer are generally resistant to radioactive iodine (RAI) therapy and are associated with poor prognosis, except for RAI-avid bone metastases with no structural correlate on imaging studies. Case: A 59 y/o woman presented for the evaluation of non-toxic multinodular goiter. Thyroid US showed a 2.7 cm nodule meeting FNAB criteria and no suspicious cervical lymph nodes. Cytology reported a Bethesda IV category with ThyroSeq V3 positive for chromosomal copy number alterations and a high Na+/I− symporter (NIS) expression (27%) with an ~ 60% probability of cancer. The patient underwent left lobectomy with isthmusectomy without neck dissection. Surgical pathology showed a 3.5 cm papillary thyroid carcinoma with extensive angioinvasion (≥4 vessels), negative margins, no ETE, and did not contain a BRAF V600E mutation. Completion thyroidectomy, in anticipation of RAI treatment, showed no additional tumor. Post-operative Tg after 6 weeks was unexpectedly high at 69 ng/mL (negative Tg Ab, TSH 5.7 uIU/ml) which prompted a rhTSH I-123 RAI WBS with SPECT/ CT and a diagnostic chest CT to uncover possible distant metastases. There was RAI uptake in the thyroid bed and right anterolateral 9thrib without a CT correlate (no osteolytic lesion) but with a signal abnormality on MRI. She was categorized as T2NxM1, 8th Edition AJCC Stage IVB, and ATA high risk. She was treated with 148.3 mCi I-131. Unfortunately, 6 months later the Tg was elevated and rising (Tg 38.4 ng/mL, negative Tg Ab, TSH 0.05 uIU/ml). A second diagnostic I-123 WBS with SPECT/ CT showed a new recurrence in the neck but no uptake in the rib lesion on planar images or other distant sites. Because of the unusually high Tg without any RAI-avid metastatic disease, an 18-FDG PET/CT was ordered to search for non-RAI avid disease. This showed disease confined to the neck and increased sclerosis of the rib lesion without increased FDG-uptake consistent with treated disease status post-RAI. There were no other distant hypermetabolic lesions. The left thyroid bed lesion was biopsied and consistent with Bethesda VI cytology and she will soon undergo left central neck dissection with tumor resection. Discussion: RAI-avid bone metastases without structural correlate on high-resolution imaging are a subtype of bone metastases located in the marrow. They do not present as the typical lytic lesions from cortical destruction. They often resolve following RAI treatment, do not cause skeletal-related complications, and do not significantly affect prognosis. The combination of high NIS expression and increased vascularity in the bone marrow (as opposed to the protected microenvironment in the bone cortex) makes them vulnerable to RAI treatment. Recognition of this subset of bone lesions may prevent overtreatment with high doses of RAI treatment and avoid the use of bisphosphonates or external beam radiation.
The Difficulty of Post-Operative Surveillance of Calcitonin Negative Medullary Thyroid Cancer
Authors: Skutnik Emily , Kinney Rachel , Lopes Rebecca , Siu Chun , Magdaleno Angela , Perilli Gretchen 
Published: May 2021

Abstract
Background: As a differentiated thyroid tumor, medullary thyroid cancer (MTC) typically maintains the secretory function of the c-cells with resultant increase in serum calcitonin level along with frequent elevations in serum chromogranin A (CgA) and carcinoembryonic antigen (CEA).
Clinical Presentation: A 71-year-old female with history of multinodular goiter underwent a thyroid nodule biopsy after routine ultrasound surveillance revealed enlargement of two right lower lobe nodules compared with prior imaging. Fine needle aspiration (FNA) of one 3.1 x 1.9 x 2.7 cm right thyroid nodule revealed cellular material composed of spindle-shaped neoplastic cells, some of them with marked cytologic atypia, suspicious for a neuroendocrine tumor, specifically medullary thyroid carcinoma. A PET/CT scan was performed after injection of Gallium-68 dotatate radiotracer and revealed intense focal radiotracer activity in the approximately 2.5 x 2.1 cm right thyroid mid lower pole heterogeneous hypodense mass with tiny calcification inferiorly, consistent with the patient’s known tumor. There was no evidence of cervical octreotate avid metastatic lymphadenopathy and a chest x-ray showed no evidence of active pulmonary disease. The patient subsequently underwent a right partial thyroidectomy with isthmusectomy. Histopathology revealed a 2.8 x 1.9 x 1.9 cm neoplasm composed of spindle and polygonal cells growing in solid nests with neuroendocrine-type nuclei. Immunostains showed the tumor to be positive for AE1-AE3 cytokeratins, chromogranin, synaptophysin and CEA. It was focally positive for TTF-1 and calcitonin. Thyroglobulin and PAX-8 were negative. Using the AJCC 8th edition staging system, the tumor was staged a pT2Nx with margins uninvolved by carcinoma and no extrathyroidal extension or lymphatic invasion. Angioinvasion was present. Additional serum studies included a normal calcitonin value of &lt;2.0 pg/ml (reference range 0-5.1 pg/ml), CEA 2.6 ng/ml (reference range &lt;6.0 ng/ml), and a mildly elevated chromagranin A at 133 ng/ml (reference range 0-95 ng/ml). Plasma metanephrines, normetanephrines, vasoactive peptide, and glucagon levels were all unremarkable. Our patient’s surgical recovery was normal and two months later she remained asymptomatic without evidence of recurrence or metastasis.
Discussion: The diagnosis and post-operative surveillance of medullary thyroid cancer is challenging; even more complicated is the rare case of calcitonin-negative MTC. The cause of calcitonin-negative MTC remains unclear. Further studies are needed for the discovery and development of novel biomarkers for post-operative surveillance and evaluation of clinical relapse.
Will Real Time Visualization of Needle in Target Thyroid Nodules Minimize False Negative FNA Results?
Authors: Sekar Vijaykumar , Panjawatanan Panadeekarn , Syed Sofia Junaid 
Published: May 2021

Abstract
Introduction: Prevalence of thyroid nodules in the adult population based on detection by ultrasonography is about 20-76% of which only 5% account for thyroid cancer. All patients with a suspected thyroid nodule either on physical examination or noted incidentally on other imaging should be evaluated with thyroid ultrasound. Any thyroid nodule &gt;= 1 cm on ultrasound should be investigated with FNAC. Ultrasound guided FNAC techniques are used to reduce false negative results. We present a patient with suspicious finding on initial thyroid ultrasound and subsequent negative FNAC presenting a few years later with papillary thyroid cancer. Case Presentation: A 32 y.o. female with history of thyroid nodule and thyroiditis presented to the endocrine clinic for follow-up of her thyroid nodule. 5 years ago, she was diagnosed with thyroid nodule, which was found on an ultrasound scan for workup of her dysphagia. The thyroid ultrasound then showed diffusely heterogeneous thyroid gland with an ill-defined area of decreased echogenicity in the right lobe and left superior lobe and possible nodule in the lower pole left thyroid. Blood work showed TSH of 1.71 (n 0.34-3.00 uIU/ml) and thyroid peroxidase antibody levels was 27.8 (n &lt; 9.0 IU/ml). A CT scan of neck with contrast was done and no concerning mass was seen. The patient had a follow-up ultrasound after 8 months which showed small bilateral thyroid lesions, somewhat ill-defined. The patient had an FNA biopsy of the right thyroid nodule: the results were consistent with a benign follicular nodule. A follow-up thyroid ultrasound was done in a year, and the findings were unchanged. The patient came back 3 years later for follow-up with complaints of a new palpable nodule in the neck. Ultrasound showed unchanged right thyroid nodule and some new cervical adenopathy. The ultrasound showed a 2.2 cm heterogeneous lymph node with punctate echogenic foci along the right lateral margin of the right internal jugular vein at the level of the thyroid gland, Subsequently FNA biopsy of the right cervical node and right thyroid node were done. The cells from lymph nodes were positive for malignancy and cells from the right thyroid nodule were atypical. Overall the appearance was consistent with papillary thyroid carcinoma. Subsequently the patient underwent total thyroidectomy and right modified lymph node dissection and the pathology results came back as multifocal papillary thyroid cancer right side 1.2 cm and left side 0.4 cm, with metastasis to 2 lymph nodes. Conclusion: The reported false negative rate of ultrasound-guided FNAC is variable. Success of US-FNA depends on experience of operator and cyto-pathologist and the intrinsic nature of the nodule. Malignancy rates of only 1-2% are reported with repeat FNA in prior benign nodules. Good FNA techniques and real-time visualization of needle in target nodules can further decrease false negatives.
“Fueling the Fire” - Irish Sea-Moss Resulting in Jod-Basedow Phenomenon in a Patient With Grave’s Disease
Authors: Khalifa Maram , Aftab Hassaan B , Kantorovich Vitaly 
Published: May 2021

Abstract
Background: Jod-Basedow phenomenon is a rare cause of thyrotoxicosis due to excess iodine intake. Herbal supplements containing sea-moss have high iodine amount which may precipitate thyrotoxicosis in patients with underlying Grave’s disease or autonomous thyroid nodules. Clinical Case: A seemingly healthy 28-year-old female presented to the ED with chief complaint of fatigue with associated anxiety, palpitations and weight loss. On admission her temperature was 100.4 F, pulse 126 bpm and blood pressure 116/56 mmHg. Exam was unremarkable for thyroid goiter or orbitopathy. Labs revealed WBC count 3.4 x103/µL (ref range 4.0-11.0) with neutropenia, hemoglobin 4.3 g/dL (11.7-15.7), platelet 49 x103/µL (150-450). Liver transaminases (AST, ALT, and alkaline phosphatase) were elevated with levels up to 4 times the upper limit of normal. She was diagnosed with hemolytic anemia secondary to severe Vitamin B12 deficiency due to pernicious anemia. TSH was &lt;0.01 mIU/L (0.27-4.20), free T4 2.46 ng/dL (0.8-1.9) and total T3 139 ng/dL (76-181). The patient subsequently endorsed remote history of hyperthyroidism diagnosed 7 years ago however she could not recall the underlying etiology or the name of medication she was treated with. She reportedly stopped this medication after 1 month due to developing goiter. She also endorsed intermittent use of store-bought supplement of Irish sea moss and bladderwrack in last 2 years. Further workup revealed elevated TSI and TBII antibody titers establishing diagnosis of Grave’s disease. Thyroid ultrasound showed normal sized heterogeneous hypervascular gland with no nodules. I-123 thyroid uptake and scan showed diffuse moderately elevated radioiodine uptake of 16.8% and 40.8% at 4 and 24 hours, respectively. Thionamide therapy was withheld due to concern of neutropenia and transaminitis. She was treated with beta-blocker after which her vital signs normalized. Labs 1 week after stopping sea moss showed TSH 0.01 mIU/L and free T4 1.4 ng/dL. Conclusion: Irish sea moss is a readily available herbal supplement with high, variable amounts of iodine. Despite little scientific evidence, it is often marketed to improve goiter amongst other health benefits. The recommended daily iodine intake per the FDA is 150 mcg. Higher amounts are expected to initially cause a short-lived suppression of thyroid function; the Wolff-Chaikoff effect, followed by “escape” and accelerated production of thyroid hormone in abnormal thyroid gland, known as Jod-Basedow phenomenon. In our case, the patient unknowingly worsened her underlying Grave’s disease due to the Jod-Basedow effect. Of note, apparantly she had a longer than expected course of Wolff-Chaikoff effect preceding the thyrotoxic state due to sporadic irregular intake of sea moss. Discontinuing sea moss led to clinical and biochemical improvement of hyperthyroidism without requiring thionamide therapy.
Amiodarone Induced Thyrotoxicosis in the Setting of End Stage Cardiomyopathy
Authors: Anderson Karolina , Baum Howard B A 
Published: May 2021

Abstract
Amiodarone is a class III antiarrhythmic agent which has effects of myocardial depolarization and repolarization. Due to its many side effects including thyroid dysfunction, its use is limited to life-threatening arrhythmias. The thyrotoxicosis can be from the iodine content of amiodarone or its direct toxicity on the thyroid gland. Because of the long half-life, causing amiodarone to have effects for months, medical management can be challenging, and thyroidectomy may be indicated. This is a 76-year-old man with a history of systolic heart failure with reduced ejection fraction (15%), on milrinone after cardiac resynchronization therapy, and recurrent ventricular tachycardia on amiodarone. He was admitted after his ICD device fired. During initial admission, his TSH was &lt;0.015mcunit/mL and FT4 was 2.34ng/dL. Due to concern for amiodarone induced thyrotoxicosis (AIT), he was started on methimazole, prednisone, and cholestyramine. FT4 decreased from 2.34ng/dL to 2.23ng/dL and he discharged on methimazole 30mg daily and prednisone 20mg daily with plans to taper. He was seen outpatient with continued improvement in his FT4 to 2.09ng/dL. He was then seen again and found to have a rising FT4 to 2.22ng/dL and his regimen of prednisone was reinitiated at 10mg daily and methimazole increased to 40mg daily. Despite the medication changes, he continued to have an elevation in his FT4 up to 3.00ng/dL at which point he returned to the hospital for further evaluation and was given methimazole 60mg TID, prednisone 20mg daily, and restarted cholestyramine. With his significant cardiovascular risk, aggressive medical management was attempted prior to surgical evaluation. After his thyroid function failed to respond to medical intervention, multidisciplinary discussion was had with patient, family, and physician teams regarding surgical intervention versus continued long-term monitoring. Family elected to pursue surgery. Thyroidectomy was performed by an experienced endocrine surgeon successfully and his FT4 and T3 decreased appropriately requiring him to be initiated on levothyroxine supplementation. AIT can be separated into Type I, in which there is an increase in synthesis of T4 and T3 with amiodarone providing increasing substrate, and Type II in which there is destructive thyroiditis, releasing excess T4 and T3. In the United States, approximately 5% of individuals who are on amiodarone therapy develop hyperthyroidism, majority being Type II. If possible, amiodarone should be discontinued in Type I AIT, but there is no clear evidence for discontinuation in Type II. Medical management includes thionamides for Type I AIT and glucocorticoids for Type II AIT. Patients who are refractory to drug therapy should be treated with thyroidectomy. The advantages of a surgical procedure
with careful cardiovascular monitoring overall outweigh the morbidity and mortality of uncontrolled thyrotoxicosis.