bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiofrequency Ablation: A Novel Treatment Option for Neck Recurrence in Medullary Thyroid Carcinoma
Authors: Aljammal Jules , Ahmad Shahzad , Hussain Iram , Zulfiqar Fizza 
Published: May 2021

Abstract
Background: Medullary thyroid carcinoma (MTC) is an aggressive cancer with cervical lymph node metastases typically found at presentation. The recurrence rate after resection is high (~ 50%)(1), and patients often need multiple surgeries. Radiofrequency ablation (RFA) has been used in treatment of recurrent thyroid cancer when surgery is contraindicated or declined by patients in both Asia and Europe (2). We present the first case of an MTC recurrence treated successfully with RFA in North America.
Clinical Case: A 43-year-old female with sporadic metastatic MTC, status post total thyroidectomy and multiple neck surgeries, presented with elevated calcitonin level of 630 pg/mL (normal: &lt; 10 pg/mL). Neck ultrasound showed left tracheoesophageal groove mass, measuring 12 mm X 12 mm X 17 mm, consistent with metastatic MTC on cytopathology with calcitonin washout of 16590 pg/mL (normal: &lt; 10 pg/mL). She had no dysphagia, shortness of breath or hoarseness of voice. Computed tomography (CT) scan of chest confirmed presence of mass, in proximity with left recurrent laryngeal nerve. Serial imaging showed rapid enlargement, with concern for impending aerodigestive tract invasion. Surgical intervention had a high risk of vocal cord paralysis due to the lesion’s location. A multidisciplinary tumor board agreed that thermal ablation aimed at shrinking the mass, as a bridge to systemic therapy, would be the best option. RFA was performed as an outpatient with conscious sedation, after informed consent and observing standard aseptic techniques. Under continuous ultrasound guidance, D5W was injected into left tracheoesophageal groove behind the mass and a continuous infusion of D5W at 15 mL/hr was maintained to protect the nerve from thermal injury. Using a trans-isthmic approach, an 18 G monopolar RFA probe with 5 mm active tip was advanced into the malignant mass and ablation was performed with 35 W power until the entire mass was hyperechoic. Vocal response was monitored throughout the procedure and voice remained normal after RFA. A neck ultrasound at her 6 months follow-up showed ablated lesion measuring 7 mm X 11 mm X 10 mm, representing a 68.6% reduction in volume. Repeat CT scan thorax showed disappearance of mass in left neck region.
Conclusion: RFA is a minimally invasive and effective treatment for recurrent cervical MTC lesions, and a viable alternative to surgery, as shown in our case. Future studies should focus on long term follow-up and comparison with surgery with regards to safety and efficacy.
References: 1.Skoura E. Depicting medullary thyroid cancer recurrence: the past and the future of nuclear medicine imaging. Int J Endocrinol Metab. 2013;11(4):e8156. 2.Garberoglio R, Aliberti C, Appetecchia M, Attard M, Boccuzzi G, Boraso F, et al. Radiofrequency ablation for thyroid nodules: which indications? The first Italian opinion statement. J Ultrasound. 2015;18(4):423-30.
Relationship Between rhTSH Administration and Thyroid Cancer Progression: A Case Report
Authors: Mejia Maria G , de Bogotá, C Hospital San José , Veronesi Luz Amaya , Concha Diana Carolina 
Published: May 2021

Abstract
Introduction: The relationship between the administration of recombinant TSH (rhTSH) and the progression of thyroid cancer has been described in some case reports (1). There are scant data suggesting that rhTSH acts as a growth factor that stimulates metastatic tumor expansion. Case Report: A 55 year old male patient who 3 years ago reported an evident mass at cervical level. The ultrasound documented a large thyroid mass with an endothoracic component. The FNA reported BETHESDA IV, suspicious for follicular neoplasia. Extension studies showed lytic left parietal bone lesion and liver metastatic compromise. The pathology of the total thyroidectomy showed a follicular carcinoma with a micronodular pattern and capsular invasion, of 19x9x7 cm, vascular and esophageal involvement T4BN0M1. He was sent to radioiodine therapy with 100 MCI with previous suspension of LT4 (Preablative TGL&gt; 300 ng / ml (&lt;50 ng / ml) Abs-TGL 2 IU / ml (&lt;2 IU / ml) TSH 31.3 mIU / L (0.37-4.7 mIU / L) and body scan documenting uptake of the radiotracer at the left parietal, the anterior costal grating, and liver. A second dose of iodine was applied, with 150 MCI after stimulation with thyrotropin (Preablative TGL&gt; 300 ng / ml, Abs-TGL 1.76 IU / ml, TSH 83 mIU / L) Immediately after the administration of rhTSH, the patient described the appearance of alopecic plaques on the scalp, sensation of mass at the right upper quadrant of the abdomen and bone pain in the right rib cage and at the right hip, which progressively worsened the following days until they were incapacitating. The scan report showed a new uptake in dorsal vertebrae, the MRI showed new bone injury at the innominate bone, as well as increase in the sum of its maximum dimensions by 22%, indicative of progression. The cerebral angio-MRI showed hypervascularized metastasis at the left parietal level. Bone scintigraphy documented foci of hyper uptake in both parietals, manubrium and sternal body, 5-8 right anterior costal arches, right scapula, both humeral heads, vertebral bodies T3-T5-T7L4, right acetabulum, left proximal femur and the entire length of the right femur. The clinical and imaging worsening of the bone lesions after the application of rhTSH was striking, for this reason radiotherapy and embolization of the liver lesion was performed. The patient was not a candidate for neurosurgical management due to the vascular component of the cranial lesions. Conclusion: rhTSH is a very well-tolerated method that avoids symptoms associated with severe hypothyroidism. However, it has been associated with neoplastic progression. This is one of the few cases documented in the literature where there is a direct association between the administration of rhTSH and the progression of bone metastases.
References: (1)Braga M. Ringel M. Cooper DS. Sudden Enlargement of Local Recurrent Thyroid Tumor after Recombinant Human TSH Administration. J Clin Endocrinol Metab. 2001; 86(11):5148–51.
Biopsy Confirmed Subacute Thyroiditis Associated With COVID-19
Authors: Maldonado Francisco Javier López , Cota Arreola Rene Arturo 
Published: May 2021

Abstract
Subacute thyroiditis is a transient inflammatory disease of the thyroid associated with anterior neck pain, and systemic symptoms. The diagnosis is generally reserved for a specific type of thyroiditis characterized by granulomatous inflammation and the presence of giant cells. We hereby present a case of a woman with a COVID-19 diagnosis, and a compatible biopsy result for subacute thyroiditis.
On 06/03/2020, a 28 year old woman with previous history of ankylosing spondylitis managed with certolizumab pegmol, presented with fatigue, headache, odynophagia, and fever (38.1°C). 2 days later an oropharyngeal swab (PCR) for SARS-CoV-2 turned out positive. On the 4th day the fever spiked to 39°C with added malaise. Acetaminophen 1 gr PO TID was prescribed. The patient denied dyspnea, and thorax CT-Scan was normal. Complete remission was achieved in 3 weeks. On 08/01/20 she returned to work after a negative swab test. On 08/04/20, she presented with fever (38.7°C), malaise, distal tremors, anorexia, tachycardia, myalgias, arthralgias, and fatigue. 2 days later anterior neck pain that radiated to the jaw, and diffuse goiter was noticed. A thyroid function panel reported Total T4: 24 µg/dL (4.5-12.5), fT4 5.2 ng/dl (0.8-1.8), TSH: 0.001 mUI/L (0.37-4.7), thyroglobulin 135 ng/ml (3-42). TPO-Ab &lt;35 IU/mL and TgAb &lt;20 IU/mL.
A neck US showed increased volume in the right lobe with multiple hypoechoic regions on both lobes, and diminished vascularization at color Doppler. I-131 scan showed no uptake. A biopsy of the right lobe reported fibrosis with inflammatory infiltrate composed of lymphocytes, plasma cells, histiocytes, and scarce neutrophils. Some cells with epithelioid appearance and a multinucleated giant cell were also found. Residual thyroid follicles showed colloid depletion and degenerative changes to the epithelium, which was consistent with a diagnosis of subacute thyroiditis.
Treatment was initiated with prednisone 10 mg PO QD, propranolol 20 mg PO BID for 2 weeks, and acetaminophen 1 gr PO TID PRN. Fever and pain were intermittent for 6 weeks, but the rest of the symptoms subsided within 2 weeks. On 11/15/20, the patient attended a check-up with lab results that were consistent with hypothyroidism, negative IgM, and positive IgG SARS-CoV-2. Replacement therapy with levothyroxine 88 mcg per day was initiated.
This case, which confirms the diagnosis of subacute thyroiditis via biopsy, among the others reported worldwide suggests that there’s an increased risk for women for subacute thyroiditis associated with COVID-19. Further research is needed to confirm risk factors for the development of the disease.
Differentiating Recurrent Thyroiditis From Graves’ Disease on a Background of Lithium Use
Authors: Subbiah Kasi , Kumar Jesse , Sivappriyan Siva , Anandappa Samantha 
Published: May 2021

Abstract
A 26-year-old female presented with severe thyrotoxic symptoms 4 months post-partum following an uncomplicated pregnancy; investigations showed a FT4 39.4 pmol/L (n 12 – 22 pmol/L), FT3 8 pmol/L (n 3.1 – 6.8 pmol/L), FT4:FT3 ratio 4.9, TSH &lt;0.02 mU/L (n 0.27 – 4.2 mU/L), TSH receptor antibody (TRAb) &lt; 0.9 IU/L (n &lt; 0.9 IU/L) with normal blood flow on ultrasound doppler and a low (0.2%) Tc99 uptake isotope scan suggesting thyroiditis. 2 years previously she had an episode of thyroiditis (investigations showed FT4 31.2 pmol/L, FT3 7 pmol/L, FT4:FT3 ratio 4.4, TSH &lt;0.02 mU/L and imaging showed low (0.4%) Tc99 uptake) when on lithium 1gm/day for more than a year to treat bipolar disorder.
On recurrence, despite compliant treatment with Propranolol and Prednisolone 30mg once daily, thyroid function deteriorated and 2 months later repeat thyroid function testing showed a FT4 &gt; 100 pmol/L, FT3 30.2 pmol/L, FT4:FT3 ratio 3.3 and TSH &lt; 0.02 mU/L. A repeat Tc99 uptake scan showed increased uptake at 13% and ultrasound showed a very vascular bulky thyroid gland. These investigations were suggestive of either a rebound hyperthyroidism (post-thyroiditis) or Graves’ disease. At this stage, TRAb titers were repeated and were now elevated at 4.5 IU/L therefore carbimazole 40mg daily was started. Due to the severity of symptoms, she underwent urgent thyroidectomy. Histopathology showed features of diffuse hyperplasia of the thyroid gland with variably sized follicles lined by cuboidal epithelial cells and a mild patchy chronic inflammatory cell infiltrate in the stroma. Post thyroidectomy she is stable on L-thyroxine therapy.
Points for discussion:
1. Lithium is typically used as a mood stabilizer and as thyroid dysfunction is known to exacerbate mood disturbances it is vital that patients are appropriately screened, monitored and treatment is commenced promptly for thyroid disease.
2. Lithium can increase clinical manifestations of thyroid autoimmunity and may influence thyrotoxicosis either due to thyroiditis or Graves’ disease. Differentiating these etiologies is important from the treatment perspective.
3. FT4:FT3 ratios, TSH receptor antibodies, Tc99 uptake scans and ultrasound doppler of the thyroid will assist in diagnostic accuracy. However, in certain rare circumstances, during the recovery phase of thyroiditis, the Tc99 scan can demonstrate diffusely increased activity, which is representative of a rebound phenomenon thus posing a diagnostic dilemma.
4. Finally, TRAb titers may help differentiate the above, but sometimes may change from undetectable to high suggesting changes in thyroid autoimmunity.
Difficulties in Differential Diagnosis of Thyrotoxicosis: Clinical Case
Authors: Volkova Natalia I , Davidenko Ilya , Dzherieva Irina , Ganenko Lilia , Reshetnikov Igor , Sorokina Julya , Zibarev Alexander , Degtyareva Yulya , Chernova Anastasya , Gizatullina Gulnara 
Published: May 2021

Abstract
Introduction: Thyrotoxicosis (T) develops as a result of persistent excess of thyroid hormones (TH). There are two groups of diseases that are fundamentally different in pathogenesis. The first group includes those in which the production of TH increases. Diseases of the second group are accompanied by T caused by destruction of the thyroid gland tissue. Therapeutic approaches for different pathogenetic types of T are different, therefore, a careful differential diagnosis of T is necessary, even if at first glance the diagnosis seems obvious. Clinical Case: A 35-year-old patient consulted a physician complaining of weakness, weight loss by 11 kg in 1.5 months, tremors, palpitations, which first appeared about a month ago. The examination revealed TSH &lt;0.0083 mU/l (0.4-4.0), and an endocrinologist’s consultation was recommended. On examination, the thyroid gland is no larger than the distal phalanx of the subject’s thumb, BMI=24 kg/m2, HR=100 bpm, BP=115/80 mm Hg. Laboratory examination: TSH &lt;0.0083 mU/l, free T4 =28.29 pmol/l (9.0-19.05). Ultrasound of the thyroid gland: signs of diffuse changes in tissue, the total volume=16.8 ml3. For differential diagnosis of T, antibodies to TSH receptors were determined, the titer of which turned out to be slightly increased 1.43 IU / L (&lt;1). A diagnosis of Graves’ disease (GD) was made and treatment was prescribed (Tyrozol 30 mg, Bisoprolol 2.5 mg per day). After 3 weeks, the patient noted an improvement in well-being, but weakness, tremor, an increase in free T4 (23.33 pmol/l) and total T3 (3.26nmol / l at a rate of 0.98-2.33) remained. The lack of achievement of the target values of TH levels was regarded as inadequacy of the received dose of Tyrozol, in connection with which it was decided to increase the dose to 40 mg per day. After 2 weeks, an increase in free T4 (27.26 pmol/L) and total T3 (3.84 nmol/L) remained. The lack of positive dynamics called into question the diagnosis of GD. With a more thorough collection of anamnesis, it was found that 1.5 years ago, the patient took amiodarone for 6 months as prescribed by a cardiologist (he does not remember the dose). In this connection, to establish the cause of T, scintigraphy was performed: revealed a weak accumulation of a radiopharmaceutical with diffuse uneven distribution. Based on the data obtained, amiodarone-induced T type 2 was verified. Treatment was corrected: Tyrosol withdrawal and Prednisolone administration, 40 mg/day with positive dynamics from treatment. Conclusion: Clinical case demonstrates how important it is to carefully collect the patient’s history and follow the algorithms for differential diagnosis. Errors in diagnosis lead to incorrectly prescribed treatment, lengthening the duration of symptoms, which affects not only the patient’s quality of life, but also reduces the level of his trust in medical professionals.
High-Dose Thyroid Hormone Replacement in Bexarotene-Induced Central Hypothyroidism
Authors: Mathews Tony , Gigliottie Benjamin 
Published: May 2021

Abstract
Background: Central hypothyroidism is a rare disorder characterized by a defect in thyroid hormone production by an otherwise normal thyroid gland due to decreased stimulation by TSH. Medications are an uncommon cause. Case Presentation: A 72-year-old man was referred for evaluation of a low TSH. He had a long history of hypothyroidism, euthyroid on levothyroxine, and was diagnosed with cutaneous T cell lymphoma (CTCL). Due to disease progression on dapsone, PUVA and TAR baths, he was started on bexarotene. Soon after, he developed recurrent symptoms of hypothyroidism including fatigue, cold intolerance, dry skin, and myalgias. Workup revealed a TSH of &lt;0.01 ulU/mL (0.27-4.20) with a free T4 of 0.6 ng/dl (0.9-1.7). After evaluation, his levothyroxine dose was increased. Repeat labs 3 months later showed a TSH of &lt;:0.01 with a free T4 0.8 ng/dl and T3 43 ng/dl (80-200). Over several months, levothyroxine titration to a supraphysiologic dose of 800 mcg daily was required, despite optimal administration, to normalize FT4. Given persistent hypothyroid symptoms and a low T3 level, liothyronine 5 mcg BID was added and resulted in clinical and biochemical euthyroidism. Clinical Lessons: Unlike in primary thyroid disorders, the TSH assay is unreliable in central hypothyroidism since values can be low, normal, or even mildly elevated; regardless, TSH has subnormal bioactivity. Ineffectual TSH leads to a low T4, which is a required for diagnosis. Bexarotene, a derivative of Vitamin A, is a retinoid X receptor (RXR) selective ligand approved for the treatment of CTCL. The exact mechanism of bexarotene-induced thyroid dysfunction is not clear, although it involves both central and peripheral effects. Bexarotene inhibits TSH gene expression by decreasing the activity of the thyrotropin β subunit gene promoter in a dose-dependent and thyroxine-independent manner; TSH levels drop as early as 4-8 hours after exposure. Bexarotene also directly lowers T4 and T3 levels, even in athyreotic patients, by negatively impacting deiodinase activity and hepatic conjugation. Stopping bexarotene is often not possible given its effectiveness in CTCL. Therefore, thyroid hormone should be initiated with the goal of achieving a normal FT4, although as the current case demonstrates, massively supraphysiologic doses and/or the addition of liothyronine may be necessary to achieve clinical euthyroidism.
The Majority of Inpatient Short Synacthen Tests Are Performed Incorrectly, Due to Imprecise Timing, Incorrect Sampling and Failure to Interrupt Steroid Administration
Authors: McCarthy Aonghus , McKenna Susan , Hall Keira , Niland Aileen , Boran Gerard P , Moran Carla M 
Published: May 2021

Abstract
Introduction: The short synacthen test (SST) is commonly used to assess adrenal function. Accurate timing and appropriate holding of exogenous steroids are essential to ensure correct interpretation of results.
Aims & Methods: We reviewed all SSTs performed on inpatients in our hospital over a 1-year period, in order to determine accuracy of testing.
Results: 42 patients (Male 15, Female 27), with mean age 68 years (range 43–90), underwent SST. The majority (39/42; 93%) of tests were requested by internal medicine physicians. The indications for testing were; suspected adrenal insufficiency (18), HPA axis suppression (9), fatigue (7), hyponatremia (5), suspected pituitary disease (2) and vomiting (1). 7 (44%) of the 16 patients taking steroids did not have medication appropriately held. 31 (74%) patients did not have serum ACTH measured prior to the test. 28 (66%) tests were not started at the correct time. Only 10 (24%) of the 30 minute samples were completed within the 25-35min sample window. The mean time between the 0min and 30min samples was 42mins (median 62mins; range 0-209mins). 12 (29%) tests involved an unnecessary 60min sample. 8 (19%) tests had no interpretation of results documented in the medical notes. 4 (10%) patients underwent repeat testing, necessitated by an incorrect first test.
Discussion: The vast majority of inpatient SSTs (33/42;79%) were performed suboptimally, with the most common errors pertaining to incorrect timing of the test, inaccurate sampling and inappropriate pre-test steroid administration. Considering these errors, some results may have been interpreted incorrectly. Repeat tests were recognised as required in 10% of patients, with associated inconvenience, cost and discomfort. Improved training and guidelines for performing SSTs should be available to hospital staff to ensure more accurate application of the test.
Epithelial Transcription Factor FOXA1 Regulates Prostate Cancer Immune Response
Authors: Brea Lourdes T , Wang Xiaohai , Yu Jindan 
Published: May 2021

Abstract
Background : While localized prostate cancer (PCa) can be mitigated by surgery and radiation, metastatic PCa remains a challenge to treat. Androgen deprivation therapies and androgen receptor (AR) pathway inhibitors are mainstay treatments for advanced PCa. Yet, resistance often develops leading to castration-resistant prostate cancer (CRPC). Forkhead Box A1 (FOXA1) is a pioneer transcription factor that plays pivotal roles in regulating AR activity and promoting epithelial differentiation. Studies have shown that FOXA1 is frequently downregulated in CRPC tumors. Congruently, FOXA1 loss is reported to induce aberrant AR signaling, epithelial-mesenchymal transition, and PCa de-differentiation. However, the role of FOXA1 in regulating PCa immune response, an area of much interest recently, has not been reported. CRPC has shown poor response to immune checkpoint inhibitors, due to its immunosuppressive nature. A better understanding of the tumor intrinsic mechanisms regulating PCa tumor immunity will inform the design of better targeted immunotherapeutic approaches. Methods: We performed RNA-seq, ChIP-seq, qPCR, western blot, and ELISA analyses to evaluate how FOXA1 regulates inflammatory response genes. We utilized an in vitro macrophage infiltration transwell assay, in which M2-like macrophages were added to the upper chamber and PCa cells were plated in the lower chamber, to examine how perturbations to PCa cells affect macrophage migration. Finally, we performed bioinformatic analyses of patient datasets to confirm the clinical relevance of FOXA1 repression of inflammatory genes in PCa. Results: Through integration of RNA-seq and ChIP-seq data, we uncovered a novel function of FOXA1 in suppressing inflammatory response pathways. In accordance, patient data analyses revealed that inflammatory response genes were upregulated in FOXA1-low PCa tumors. Mechanistically, we showed that FOXA1 proteins bound an intragenic enhancer of Hypoxia-inducible factor 1-alpha (HIF1A) gene to directly repress its expression, such that FOXA1 loss induced HIF1A upregulation. We further showed that Monocyte Chemoattractant Protein-1 (MCP-1/CCL2) became upregulated upon FOXA1 depletion in a HIF1A-dependent manner. This led to infiltration by immunosuppressive, tumor promoting M2-like macrophages. Inhibiting this HIF1A-CCL2 axis with a HIF1A inhibitor or CCL2 neutralizing antibody blocked macrophage infiltration. Future studies using immunocompetent mouse models are needed to confirm the effect of FOXA1 on macrophage infiltration in vivo and evaluate the preclinical potential of targeting the FOXA1-HIF1A-CCL2 axis in CRPC. Conclusion: This study proposes a novel role for FOXA1 loss in promoting macrophage infiltration via the HIF1A-CCL2 axis. Moreover, our findings suggest that targeting this axis may be a promising approach for the treatment of FOXA1-low CRPC tumors.