bluuebunny/crossref_metadata_2025_split huggingface dataset:
Muscle Strength in Transgender Women After Long-Term Hormone Therapy: A Cross-Sectional Study
Authors: Alvares Leonardo A M , Santos Marcelo R , Souza Francis Ribeiro , Santos Lívia Marcela , Ramos Henrique A , Mendonca Berenice Bilharinho , Alves Maria-Janieire N Nunes , Costa Elaine Maria Frade , Domenice Sorahia 
Published: May 2021

Abstract
Introduction: Cisgender women (CW) are usually weaker than cisgender men (CM), but when the strength is expressed in relation to the body weight (BW) or fat free mass (FFM) it is observed that the difference disappears what suggests that the innate qualities of the muscle and its motor control mechanisms are similar in CW and CM. The effects of prior exposure to testosterone during puberty on the performance of transgender women (TW) undergoing physical effort are not well known. Objective: To evaluate muscular strength of TW in long-term gender affirming hormone therapy (GAHT). Methods: A cross-sectional study was carried out with 8 TW (average age of 34.0 yo, SD ±4.8), 8 CM and 8 CW matched by age and body mass index (BMI). All TW were non-gonadectomized subjects and were in estrogen plus cyproterone acetate therapy (average time of 15.6 years (SD ±8.7) of treatment). Mean total testosterone (ng/dL) levels of TW, CW and CM were 83.5, 20.5 and 480.5 at the time of the study, respectively. Hemoglobin levels of TW, CW and CM were 14,2 (range 13,5-14,9), 14,35 (range 12,8-14,7) and 15,35 (range 14,0-18,2), respectively BC was assessed by InBody 720. Handgrip strength tests were carried out using the Stoelting hand-held hydraulic dynamometer. Results: The mean maximum strength was 31,9 kg (SD±2.4) in TW, 29.2 kg (SD±4.4) in CW, and 47.5 (SD±8.6) in CM (TWvs.CW p=0.0743; TWxCM p&lt;0.0018; CWvsCM p&lt;0.001). Free fat mass (FFM) of TW was 55.56±6.88 kg, CW 38.98±4,09 kg, CM 64,98±6,29 kg (TWvsCW p&lt;0,0001; TWvsCM p=0,024; CWvsCM p&lt;0,0001). In the evaluation Median Strength/FFM, a mean of 0.54 was observed in the TW group, and 0.76 in the CW and CM (TWvsCW p=0.0157 and TWvsCM p=0.036, CWvsCM p&gt;0.9999). Discussion: The expression of muscle strength/FFM is the same in CM and CW, which suggests that the innate quality of the muscles as well as their motor control is similar in these groups, as showed in many data in the literature. However, the analysis of this ratio in TW showed a significant lower rate than the other groups. Conclusion: After GAHT muscle strength of TW is equal of CW. There is a decrease in the functionality of the muscular unit in producing strength in this group of TWs since strength decreased disproportionately to muscle mass which leads us to believe that there are important functional changes in intracellular oxidation mechanism.
Anxiety and Fear During the Covid-19 Pandemic: A Web-Based Survey of Thyroid Cancer Survivors
Authors: Graves Claire E , Goyal Neha , Levin Anna , Nuno Miriam A , Kim Jina , Campbell Michael J , Shen Wen T , Gosnell Jessica Erin , Roman Sanziana , Sosa Julie Ann , Duh Quan-Yang , Suh Insoo 
Published: May 2021

Abstract
Background: The coronavirus (COVID-19) pandemic has led to rapid changes in our society and healthcare system. Cancer patients and survivors may be disproportionately affected by these changes, including decreased access to healthcare, increased infection risk, and economic challenges. We sought to determine the effects of the pandemic on thyroid cancer survivors’ quality of life. Methods: An anonymous web-based survey was administered in collaboration with ThyCa: Thyroid Cancer Survivors’ Association, consisting of questions about (1) demographics, (2) thyroid cancer clinical characteristics, (3) attitudes toward and impact of COVID-19, and (4) the Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item profile. The survey was linked on the ThyCa homepage. PROMIS measures were scored using item response theory models with a T-score metric relative to U.S. reference data via the HealthMeasures Scoring Service (https://www.healthmeasures.net). T-scores were analyzed using Mann-Whitney U, Wilcoxon signed-rank, Kruskal-Wallis, and Spearman’s rank correlation tests. Results: From 5/6/2020 - 10/8/2020, 505 participants accessed the survey, and all completed surveys by U.S.-based thyroid cancer survivors were analyzed (n=378, 75%). Mean age was 53 years, 89% were female, 90% were white, 74% had papillary thyroid cancer, 97% had surgery, and 70% received radioactive iodine. The vast majority agreed or strongly agreed (83%) that their lives were very different during COVID-19, as was the way they interacted with their doctors (79%). Less than half (43%) agreed or strongly agreed that they were satisfied with the amount of information from their doctor’s office regarding COVID-19 changes. Compared to previously-published PROMIS data for this population, T-scores were significantly higher in the domain of anxiety/fear (57.8 vs. 56.5, p&lt;0.01) and lower for ability to participate in social roles and activities (46.2 vs. 48.1, p&lt;0.01). Younger age was weakly correlated with greater anxiety/fear (Spearman’s rho=-0.38, p&lt;0.01), and greater anxiety/fear was associated with pending treatment (p&lt;0.01), lower cancer stage (p=0.01), and female sex (p=0.02). Conclusions: During the COVID-19 pandemic, thyroid cancer survivors reported increased anxiety/fear and decreased social participation. In our efforts to care for patients both physically and mentally as the pandemic continues, we must better understand their fears and concerns and improve communication about potential changes to their care.
Is Metformin Use Associated With Decreased Thyroid Cancer Risk in Patients With Acromegaly?
Authors: Kadioglu Pinar , Sulu Cem , Tay Kubilay , Guzel Suleyman , Sahin Serdar , Durcan Emre , Ozkaya Hande Mefkure 
Published: May 2021

Abstract
Context: Acromegaly has long been blamed to portend an increased risk for benign and malignant thyroid neoplasia. Growth hormone (GH) and consequent insulin-like growth factor 1 (IGF-1) hypersecretion are implicated in cancer promotion. Metformin, a biguanide derived from the French lilac, is gaining considerable interest because of its plausible anti-tumor properties. Besides, metformin has been shown to inhibit somatotroph proliferation and decrease GH secretion in in vivo studies. Patients with acromegaly have high incidence of diabetes and were thereof treated with metformin. We hypothesized metformin use may be linked to decreased thyroid cancer incidence in patients with acromegaly. Study Design and Methods: The medical records of 508 patients with acromegaly followed at our tertiary referral center between 1969 and 2019 were retrospectively reviewed. The inclusion criteria were having a follow-up duration for at least 12 months and being regularly screened for nodular thyroid disease and thyroid cancer by ultrasonography as indicated in respective guidelines. Patients with acromegaly were evaluated based on ongoing or prior history of metformin use or thyroid cancer diagnosis. Metformin exposure was defined as use of metformin for at least 12 months on a regular basis between initial date of acromegaly and time prior to cancer diagnosis date. Considering the long patency period of cancer of interest, we excluded exposures in the year immediately prior to index cancer date. We evaluated the effect of metformin exposure on risk of thyroid cancer using Kaplan-Meier analysis. Results: Final analysis included 377 patients with acromegaly. Mean age at acromegaly diagnosis was 41.6 ± 11.7 and 60.5% of the patients were female. Three hundred twenty-two patients (85.4%) had undergone transsphenoidal surgery as primary therapy, 73 patients (19.4%) needed radiotherapy and 178 patients (46%) received post-operative medical therapy. Median follow-up duration was 73.5 months (IQR [31.0-137.7]). One hundred twenty patients (31.9%) had an ongoing or prior use of metformin, and total of 19 patients (5%) had thyroid
cancer. Age at acromegaly diagnosis, gender distribution, baseline GH and IGF-1 levels, pituitary tumor size and invasiveness, biological aggressiveness, curative therapy options, treatment responses didn’t differ between metformin users and non-users, as well as between those having and not having thyroid cancer. Kaplan-Meier estimates for 1 year, 3 years and 5 years of metformin exposure showed decreased probability of thyroid cancer incidence (p&lt;0.05 for all). Conclusion: Although our results imply decreased thyroid cancer risk upon metformin exposure, prospective study designs with larger cohorts are obliged in order to fully elucidate the effect of metformin use on thyroid cancer.
Concurrent Papillary and Follicular Thyroid Cancer Presenting as Shoulder Pain
Authors: Santiago Carrion Ada Marie , Agosto-Vargas Yanerys 
Published: May 2021

Abstract
Differentiated thyroid cancer arises from thyroid follicular epithelial cells. It accounts for more than 90% of thyroid cancers. In areas of sufficient iodine nutrition, about 85% of differentiated thyroid cancers are papillary, 10% are follicular and 3% are Hurthle cell carcinomas. The coexistence of different types of thyroid cancer in a single patient is a rare condition.
This is the case of a 56 year-old man with medical history of arterial hypertension who presented to clinics with right shoulder pain. Imaging of the right shoulder showed a osteolytic lesion involving the right humerus with associated cortical disruption consistent with pathological fracture secondary to metastatic disease. Bone biopsy showed papillary thyroid carcinoma. Subsequently, ultrasound-guided fine needle aspiration biopsy to a right lobe nodule was performed, which confirmed the presence of papillary thyroid carcinoma. There was also evidence of cervical lymph node involvement. Patient proceeded to total thyroidectomy with neck dissection, and surgical pathology revealed the presence of 2.5 cm right lobe papillary carcinoma and 1.5 cm left lobe follicular carcinoma. Postoperatively, he was found with persistent elevated thyroid-stimulating hormone (TSH) and elevated quantitative thyroglobulin with elevated thyroglobulin antibodies. Patient received therapeutic radioiodine (I-131) for ablation of thyroid cancer. Whole body iodine scan demonstrated residual functioning thyroid tissue within post-thyroidectomy bed, with or without residual carcinoma, and large expansile uptake lesion involving the right humeral head and neck. Therefore, patient will receive a second dose of radioactive iodine. He has been started on thyroid hormone replacement with a goal of TSH &lt;0.1 uIU/mL for high risk American Thyroid Association (ATA) stratification, and has remained clinically euthyroid.
Thyroid carcinoma is the most common endocrine malignancy and one of the most rapidly increasing cancers in the United States. This increase in incidence is largely due to incidental detection on diagnostic imaging. Here we present an uncommon case of two distinct thyroid malignancies occurring simultaneously in a patient presenting with a pathological fracture. Synchronous occurrence of two types of differentiated thyroid cancer is a rare event, and has only been reported in case series. Bone metastasis from differentiated thyroid cancer can occur in 2-13% of patients. Despite the therapy for papillary thyroid carcinoma and follicular thyroid carcinoma remain the same, proper identification will lead to prompt therapy and increased survival. Physicians should be aware of this variety.
Hurthle Cells Adenoma With Distant Metastases Refractory to Radioiodine
Authors: Rosario Pedro Weslley , Mourão Gabriela Franco 
Published: May 2021

Abstract
Introduction: Adenoma of the thyroid is defined as an encapsulated follicular tumor that is well delimited in relation to the adjacent parenchyma and whose cells do not exhibit the nuclear alterations of papillary thyroid carcinoma (PTC), and in the absence of capsular and vascular invasion. Adenoma, including the of Hurthle cells, is considered a benign tumor. No additional treatment is recommended after resection of the tumor. Case: A 64-year-old man was submitted to total thyroidectomy because of a nodule measuring 3.5 cm with indeterminate cytology (predominance of Hurthle cells). Histology revealed an Hurthle cells adenoma of 3.2 cm. The tumor did not exhibit vascular or capsular invasion, the cells did not contain nuclei of PTC, and no necrosis or mitoses were observed. Five years after surgery, serum thyroglobulin (Tg) was elevated (25 ng/ml) during euthyroidism (TSH 0.6 mUI/l) and in the absence of anti-Tg antibodies. Serum calcitonin was undetectable. The patient developed a progressive increase in Tg and neck ultrasonography (US), chest computed tomography (CT), and FDG-PET/CT were performed. US revealed atypical lymph nodes (the largest with 12 mm) and cytology showed abundance of Hurthle cells. Chest CT detected multiple nodules, the largest measuring 15 mm, and FDG-PET/CT revealed areas of cervical and pulmonary uptake corresponding to the lesions seen on US and CT. The patient received 100 mCi radioactive iodine and post-therapy whole-body scanning showed mild uptake only in the thyroid bed. The patient continues to show progressive increase in Tg (last measurement &gt; 1,000 ng/ml), as well as progression of metastases. He remains under follow-up and on therapy with tyrosine kinase inhibitor. The histology result was revised by two pathologists with broad experience in thyroid pathology who confirmed the initial findings compatible with adenoma. Conclusion: The present case shows that, although rare, Huthle cells tumors can develop metastases even when the tumor is &lt; 4 cm and unequivocally without nuclei of PTC or capsular and vascular invasion, thus considered benign (adenoma). As observed in this case, these metastases can be macrometastases, distant, and refractory to radioiodine. Reference: Lloyd RV, Osamura RY, Klöppel G, Rosai J, ed. WHO Classification of Tumours of Endocrine Organs. 4th edition Lyon: IARC; 2017
Predictive Accuracy of Delta Cortisol on Recovery of Adrenal Function in Patients With Drug Induced Cushing’s Syndrome With Secondary Adrenal Insufficiency
Authors: San Bo Bo 
Published: May 2021

Abstract
There is a growing concern upon the finding of many drug induced Cushing’s syndrome because of inadvertent use of glucocorticoids (GC) either prescribed or as alternative medicine in Myanmar. These patients are presenting with diversity of clinical problems ranging from hypertension, diabetes to acute adrenal crisis due to hypothalamic-pituitary-adrenal (HPA) axis suppression and secondary adrenal insufficiency (AI). The present study aimed to assess the delta cortisol (the degree of cortisol increments) during the first short Synacthen test (SST) as a factor predictive of adrenal function recovery in patients with drug induced Cushing’ syndrome with secondary AI and to determine the proportion of patients who recovered from AI within six-month follow-up. This was a hospital based prospective analytical study that enrolled a total of 52 patients with drug induced Cushing’s syndrome with secondary AI from January 2018 to June 2019. Secondary AI is defined by morning basal serum cortisol ≤ 400 nmol/L with Synacthen stimulated peak cortisol level ≤ 550 nmol/L and serum ACTH &lt; 60 pg/ml. The follow-up SSTs were performed at three-month and six-month after first SST, and the patients with morning basal serum cortisol &gt; 400 nmol/L (or) Synacthen stimulated peak serum cortisol &gt; 550 nmol/L during follow-up SSTs are defined as recovered adrenal function group. In this study, a total of 52 patients were treated with modified regimen of physiological dose of prednisolone with tapering schedule or stress dose GC based on the basal serum cortisol levels up to six months. Among them, nearly half (n=25 / 48.1%) of the patients with drug induced Cushing’s syndrome with secondary AI achieved normal adrenal function within six-month follow-up. It was found that mean values for delta cortisol were not statistically significant between recovered and non-recovered groups, 118.6 nmol/L (SD 72.3) and 97.2 nmol/L (SD 64.2) respectively. The delta cortisol during the first SST could not predict strongly (AUC - 0.6, 95% CI - 0.44 to 0.76, P = 0.2) the recovery of adrenal function in patients with drug induced Cushing’s syndrome with secondary AI and it was inconsistent with previous studies. The older age of the patients, oral route of administration of drugs causing Cushing’s syndrome and comorbid hypertension were found to be more significant in the non-recovered group. In conclusion, the present study did not support the evidence that the delta cortisol during the first SST could predict adrenal function recovery in patients with drug induced Cushing’ syndrome with secondary AI.
Reference: (1) Baek et al., 2016; Recovery of Adrenal Function in Patients with Glucocorticoids Induced Secondary AI. Endocrinol Metab.31, pp. 153–160. (2) Pofi et al., 2018; The Short Synacthen Test Can Be Used to Predict Recovery of HPA Axis Function. J Clin Endocrinol Metab.103(8), pp. 3050–3059.
Leukocytosis and PTHrP-Mediated Hypercalcemia: Ominous Signs in an Indolent Thyroid Nodule
Authors: Gerwer Johanna Elizabeth , Thomas Robert L , Orosco Ryan K , Choe Charles , McCowen Karen C 
Published: May 2021

Abstract
Introduction/Background: Anaplastic thyroid cancer is a rare thyroid malignancy with a bad prognosis. There are few systemic markers, as thyroglobulin is not usually synthesized in these poorly differentiated malignancies. Clinical Case - Diagnostic Evaluation, Treatment, and Follow Up: A 70-year old man presented in 2016 with a right thyroid nodule, slowly growing since 2012. The nodule was 10cm on neck CT and ultrasound showed a hyperechoic mass with central hypoechoic area, and coarse calcifications. Fine needle biopsy showed a follicular neoplasm. By 2019, neck CT showed enlargement of the nodule to 13 cm. Repeat thyroid biopsy was benign. Lobectomy was recommended due to size but not performed. In 2020, he developed neck discomfort and painful thigh swelling. WBC was significantly elevated at 27,000 (4000-10000) /mm3. Ultrasound showed no evidence of necrosis or abscess in the nodule. WBC rose progressively to 96,000/mm3 (ANC 94,200). CT chest showed further enlargement of the thyroid mass, a soft tissue shoulder mass and lung nodules suspicious for metastases. Laryngoscopy revealed a distorted larynx from external compression, and possible vocal-fold involvement (motion impairment) without airway compromise. Biopsy of the shoulder mass, lung nodule, and thigh masses all showed metastatic anaplastic thyroid cancer. Full infectious disease evaluation and molecular testing for BCR-ABL and JAK2 mutations were negative. Thus, leukocytosis was determined to be reactive in the setting of malignancy. Serum calcium of 14.7 mg/dL (8.5 - 10.6mg/dL) prompted hospital admission. Bone metastases were not visible on imaging. Hypercalcemia was treated effectively (to 8.3mg/dL) with IV fluids, calcitonin and IV bisphosphonates. Workup revealed suppression of PTH to 4 pg/mL (15-65 pg/mL) and low 25 Vitamin D of 21 ng/mL (30-80ng/L). Subsequently PTHrP was elevated at 53.4 pmol/L (&lt;2.3pmol/L) and 1,25 Vitamin D inappropriately normal at 48.9 pg/mL (20- 79.3pg/mL), suggested humoral hypercalcemia of malignancy. The patient declined further treatment beyond hospice care. Clinical Lesson/Conclusion: Significant, sudden leukocytosis and hypercalcemia prompted further evaluation of his long-standing apparently benign thyroid nodule leading to a diagnosis of anaplastic thyroid cancer. Presumably this mass had been a follicular thyroid cancer, misdiagnosed on cytology, that subsequently de-differentiated. There are uncommon reports of leukocytosis complicating anaplastic thyroid cancer, where elevated GCSF and IL-6 were noted. We suspect this same etiology here. Hypercalcemia is extremely rare other than one report of PTHrP-secreting anaplastic thyroid cancer. Thus, high, rising calcium and PTHrP levels may reflect level of disease activity in anaplastic thyroid cancer.
Medullary Carcinoma of Thyroid Due to GLP-1 Receptor Agonist
Authors: Vemula Hasitha , Villanueva Fiorella Sotomayor , Nguyen Huong Diem , Mohan Akhila , Potluri Sriravali 
Published: May 2021

Abstract
Introduction: The first GLP-1 receptor agonist (GLP-1 RA) was approved for the treatment of type 2 Diabetes mellitus in 2005. This class has gained popularity due to its anti-glycemic effect, weight loss and reduction in Cardiovascular disease outcomes1. The effects of this drug class on human thyroid cells are not well known. We hereby report a case of a woman who developed medullary carcinoma of thyroid (MTC) after using Dulaglutide.
CaseA 63-year-old female with T2DM for 3 years, taking dulaglutide for 2 years, who presented with a lump in the neck. She had no personal or family history of MEN 2 syndrome, radiation exposure or cancer. Examination showed a 2cm firm nodule in the left lower neck. Thyroid ultrasound revealed a large nodule in the left upper lobe of thyroid. Lab work showed TSH of 1.55mIU/L (0.27-4.2 mIU/L) and serum calcitonin level of 1903 pg/ml (0.0-5.1 pg/mL). FNA biopsy of the nodule showed MTC. She tested negative for RET MEN 2 gene mutation. She underwent total thyroidectomy and neck dissection. Pathological examination confirmed MTC. Post-op calcitonin improved to 2.1 pg/ml.
Discussion: GLP-1 RAs provide glycemic control by many mechanisms, including increase in insulin secretion, reduction in postprandial glucagon secretion, delaying gastric emptying, increasing satiety and weight loss. Although they have proved effective in T2DM management, the potential effects on thyroid C-cells should not be ignored. Several in-vitro studies have shown GLP-1 receptors on the rat thyroid tissue C-cells. Stimulation of these receptors resulted in increased production of calcitonin in a dose dependent manner and increased risk of C-cell tumor formation at 104 weeks. Studies initially done by Knudsen et al2 showed that this effect was not seen in humans due to lower expression of GLP-1 receptors in human thyroid tissue C cells. However, a study conducted by Gier et al showed the expression of GLP-1 receptor in some patients with C-cell hyperplasia as well as papillary and medullary carcinoma3. FDA adverse event reporting system database suggested an increased risk of thyroid cancer associated with GLP-1 RAs. It is unclear whether dulaglutide contributed to the development of MTC in this patient. She had not had a baseline calcitonin level prior to the initiation of dulaglutide. The consequence of long-term use of GLP-1 RAs in the thyroid gland in humans still remains unknown and further studies to determine if they increase the risk of MTC are warranted.
References: 1. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2016;375(4):311. Epub 2016 Jun 13. 2. Glucagon-like Peptide-1 receptor agonists activate rodent thyroid C-cells causing calcitonin release and C-cell proliferation. Endocrinology. 2010;151(4):1473. Epub 2010 Mar 3. Glucagon Like Peptide-1 Receptor Expression in the Human Thyroid Gland