bluuebunny/crossref_metadata_2025_split huggingface dataset:
Choriocarcinoma Induced Thyrotoxicosis in a Male Adult
Authors: Radovanovic Natasa , De Castro Alicia , Cao Yenong , Ammana Hima Reddy , Kwak Leigh 
Published: May 2021

Abstract
Introduction: Germ cell tumors normally occur in the gonads but may be found in extragonadal sites (due to abnormal migration of germ cells during embryogenesis). Metastatic choriocarcionomas are non-seminomatous germ cell tumors which overproduce beta Human Chorionic Gonadotropin (hCG). Rarely, thyrotoxicosis can be driven by germ cell tumor-mediated hCG excess. This hormone binds to the TSH receptor with reduced potency compared to intact TSH. Paraneoplastic thyrotoxicosis, driven by extremely high levels of hCG, is a rare condition which can be associated with choriocarcinomas. Case Presentation: We present a case of 29-year-old man with metastatic extragonadal choriocarcinoma under active treatment with oxaliplatin, paclitaxel, gemcitabine (2 cycles completed), right upper lobe resection and whole brain radiation. He was admitted for small bowel obstruction and persistent tachycardia which prompted evaluation of thyroid function. His initial labs were remarkable for TSH &lt;0.01 mclU/mL (0.27-4.20 mclU/mL), FT4 of 6.38 ng/dL (0.93-1.70 ng/dL), total T3 261 ng/dL (75-170 ng/dL), and beta hCG 578,259 mlU/ML (0-2 mlU/ML). His most recent round of chemotherapy was 7 days prior to admission. He was started on atenolol and methimazole but his FT4 rapidly declined, hence methimazole was stopped after one dose of 40 mg. Sevenfold decrease in FT4 to 0.93 ng/dL correlated with fivefold decrease in beta hCG levels to 98,921 mlU/ML. A week later his FT4 increased to 2.42 ng/dL along with increase of beta hCG to 448,116 mlU/ML. At this point he developed multiple complications due to progressive metastatic disease including acute urinary retention, shortness of breath, abdominal pain, tachycardia, acute anemia and thrombocytopenia, anxiety and was started on methimazole as part of palliative treatment for symptom relief. Unfortunately, he passed away three weeks after initial presentation of thyrotoxicosis due to widespread disease. Discussion: Choriocarcinoma is very rare and aggressive germ cell tumor especially in males. Unfortunately, the widespread nature of choriocarcinomas at the time of diagnosis is a major main reason for poor prognosis. Clinical manifestations of thyrotoxicosis associated with choriocarcinoma such as tachycardia, anxiety, tachypnea are variable and often can overlap with constitutive symptoms in widespread malignancy. Even if a definitive cure of choriocarcinoma is not attainable, recognizing an associated paraneoplastic thyrotoxicosis can provide an important pathway to provide palliative symptom relief.
Risk of Mental and Sleep Disorders After the Diagnosis of Adrenal Adenomas: A Population-Based Cohort Study
Authors: Singh Sumitabh , Zhang Catherine , Atkinson Elizabeth , Achenbach Sara , Ebbehoj Andreas , Li Dingfeng , Kaur Ravinder Jeet , Stricker Nikki H , Mielke Michelle , Bostwick J Michael , Rocca Walter A , Bancos Irina 
Published: May 2021

Abstract
Background: Adrenal adenomas are incidentally diagnosed in 7% of adults undergoing abdominal imaging. Mild autonomous cortisol secretion is present in 50% of adrenal adenomas, and even “nonfunctioning” adrenal adenomas demonstrate abnormal steroid profile. We aimed to 1) investigate the prevalence of mental and sleep disorders in patients with adrenal adenomas and to 2) determine the risk of mental and sleep disorders after the diagnosis of adrenal adenoma in patients compared to the referent subjects from the same population Methods: Using a medical records linkage system, we identified adult patients living in the Olmsted County, MN diagnosed with an adrenal adenoma during 1995–2017. Patients with overt hormone excess were excluded. Every patient with adenoma was matched by sex and age to a referent subject from the same population. Subjects were followed until death or end of the study. Mental health related comorbidities and sleep disorders were assessed at baseline and during follow up. Results: Our cohort included 1004 patients with adrenal adenomas and 1004 referent subjects (58% women, median age of 63 years). Patients were more likely to smoke (70% vs 54%, p &lt;0.001) and had a higher BMI (30 kg/m2 vs 28 kg/m2, p &lt; 0.001). Within 5 years prior to the index date (diagnosis of adenoma), and after adjusting for BMI and smoking, patients demonstrated a higher prevalence of depression (Odds ratio, OR of 1.3 (CI95% 1.1–1.6), p=0.02), anxiety (OR of 1.4 (CI95% 1.1–1.8, p=0.003), substance abuse disorders (OR of 2.4 (CI 95% 1.7–3.4), p&lt;0.001), but not insomnia (OR of 1.2 (CI95% 0.9–1.7) and sleep related breathing disorders (OR of 1.3 (CI 95% 0.9–1.7). During follow-up, starting 1 year after the diagnosis, patients demonstrated a higher risk of new onset depression (HR of 1.9, CI95%1.5–2.4), anxiety (HR of 1.5,CI95% 1.2–1.9), schizophrenia (HR of 1.7, CI95% 1.2–2.4), and substance abuse disorders (HR of 1.6, CI95% 1.2–2.0). Risk of sleep disorders 1 year after diagnosis was also high for insomnia (HR of 1.4, CI95% 1.1–1.9), sleep-related breathing disorders (HR of 1.8, CI95% 1.4–2.3), hypersomnias of central origin (HR of 2.0, CI95%1.04–3.96), parasomnias (HR of 2.4, CI95%1.2–4.7), and sleep-related movement disorders(HR of 1.9, CI95%1.3–2.6). Conclusion: Patients with adenomas are at increased risk for mental and sleep disorders, possibly explained by the underlying subtle cortisol secretion. Further prospective studies with an in-depth characterization of both hormonal secretion and mental/sleep disorders are needed. Reversibility or improvement of mental health and sleep disorders with adrenalectomy should be investigated.
Graves’ Disease After Hematopoietic Allogeneic Bone Marrow Transplant in a Patient With Sickle Cell Disease
Authors: Alameri Majid 
Published: May 2021

Abstract
Endocrinopathies are among the most recognized late complications post hematopoietic stem cell transplant (HSCT). Dysfunctions of hormonal axes including the hypothalamus, pituitary, gonads, thyroid and adrenals reported. Moreover, thyroid dysfunctions including thyroiditis, hypothyroidism and hyperthyroidism has been reported to develop 8-32 months after HSCT.
We report a 27-year-old male with sickle cell disease diagnosed at age of 5. He had multiple painful vasoocclusive sickle crises treated with blood transfusions, folic acid and rituximab. At age of 21, he presented with sudden right sided weakness and slurred speech. Further investigations, including magnetic resonance imaging of brain revealed occlusion of the left middle cerebral artery resulting in ischemic infarction. Subsequently, he had multiple red blood cell exchange transfusions on regular basis. He remained with residual weakness and slurred speech after rehabilitation. Bone marrow transplant was recommended as a curative treatment for his sickle cell disease by haematology team. A year later, he underwent a geno-identical allogeneic bone marrow transplantation harvested from his brother. He remained well for 22 months post-transplant without any evidence of graft versus host disease. 23 months post-transplant, he presented with loose motions, 2 kg wight loss and fine tremors. He was referred to endocrine department for further workup. Physical examination revealed a small smooth goitre. He had discrete exophthalmos of his left eye without any signs of active inflammation. Thyroid function tests confirmed diagnosis of Graves’ disease with TSH&lt;0.01 milli IU/L, Free T4=23.9 pmol/L, and TSH receptor antibodies of 3.79 IU/ml. Ophthalmological consultation suggested 6 months of selenium supplementation (200 mcg/day) with regular follow up. There has been no family history of autoimmune diseases or thyroid disorders. He started carbimazole (CMZ) 30 mg daily. His symptoms improved within 8 weeks, with normalization of Free T4 and Free T3 (TSH remained suppressed). 18 months later, he remained asymptomatic on carbimazole. He had recurrence of hyperthyroidism symptoms after 4 weeks trail of stopping carbimazole with elevation of Free T4 and Free T3. Carbimazole was restarted and he has been offered other treatment modalities of Graves’ disease. He elected to undergo total thyroidectomy. His sickle cell and blood counts remained stable during follow up period. Conclusion: Transplanted patients carries a life-long risk for developing endocrinopathies post initial transplant therapy. Acknowledging the wide spectrum of post-transplant endocrinopathies, an individualized case based periodic screening can be helpful to improve health outcomes of such patients. Because of the usual late presentation of such endocrine complications, transplanted patients might need life-long endocrine follow-up.
Hashimoto’s Thyroiditis Associated Thyroid Eye Disease:A Success Story of Teprotumumab
Authors: Jamal Issra 
Published: May 2021

Abstract
Background: Thyroid-associated eye disease is more common in patients with Graves’ disease. However, patients with Hashimoto’s may also be affected by thyroid-associated eye disease in up to 6% of patients. Clinical Case: 44 year old female patient with history of Hashimoto’s thyroiditis presented to the clinic for her hypothyroidism and evaluation of thyroid eye disease. The patient was experiencing episodes of bilateral and unilateral inflammation of her eyes described as redness, dryness, bulging of the eyes. She was evaluated by ophthalmology and was diagnosed with thyroid eye disease and was prescribed a course of steroids with partial improvement of the symptoms. Orbital MRI was ordered and it showed symmetrical enlargement of the inferior rectus muscles bellies bilaterally with the left being slightly more enlarged than the right, retro orbital fat pad was grossly inflamed. TPO was elevated,TSI and TRAb were negative. Patient continued to have frequent flare ups with suboptimal response to steroid therapy. A discussion about starting Teprotumumab was made due to lack of optimal response to steroids and worsening of her symptoms and therapy was started. Patient did develop significant hyperglycemia, but she did not have recurrent flare ups. Studies have found that Thyroid-associated eye disease was present in up to (6%) of Hashimoto’s thyroiditis patients, those with thyroid-associated eye disease tended to be older, have a longer duration of Hashimoto’s thyroiditis, heavy smokers, and were less likely to present with another associated autoimmune disease. TSAb was positive in 5.5% in the patients with Hashimoto’s and thyroid-associated eye disease. Teprotumumab ([IGF-1] receptor inhibitor) was approved for the treatment of Graves’ orbitopathy by the (FDA) in 2020. Conclusion: Hashimoto’s thyroiditis associated thyroid eye disease is a rare clinical presentation. Teprotumumab is a new FDA approved treatment for thyroid eye disease that was successful in treating the symptoms and prevented flare ups in this patient. Careful monitoring of side effects is recommended.
References: Kahaly GJ et al Thyroid stimulating antibodies are highly prevalent in Hashimoto’s thyroiditis and associated orbitopathy. J Clin Endocrinol Metab. March 10, 2016\Krassas GE, Wiersinga WM. - Thyroid eye disease: current concepts and the EUGOGO perspective. Thyroid International. 2005;4:3–4. Teprotumumab for Thyroid-Associated Ophthalmopathy. Smith TJ, Kahaly GJ, Ezra DG, Fleming JC, Dailey RA, Tang RA, Harris GJ, Antonelli A, Salvi M, Goldberg RA, Gigantelli JW, Couch SM, Shriver EM, Hayek BR, Hink EM, Woodward RM, Gabriel K, Magni G, Douglas RS SO N Engl J Med. 2017;376(18):1748.
Hyperthyroid Manifestation in Beta HCG Secreting Tumor
Authors: Oktavia Nani , Pratiwi Chici , Mokoagow Muhammad Ikhsan , Epriliawati Marina , Nasaruddin Jerry , Kshanti Ida Ayu 
Published: May 2021

Abstract
Background: Serum β-Human Chorionic Gonadotropin (HCG) levels can be increased not only in pregnancy but also in various malignancies such as germ cell malignancy, lung cancer, ovarian cancer, and breast cancer. The alpha subunit of HCG and TSH are homologous, so β-HCG can cross-react with the TSH receptors and induce hyperthyroidism. High level of β-HCG serum can lead to hyperthyroidism, which can aggravate the patient’s malignant manifestations.
Case Presentation: A 33-year old woman admitted to our hospital with chief complaint general weakness one week before admission. The patient was 8 week-pregnant and the transabdominal ultrasound showed a gestational sac and she had also a positive urine β-HCG test. The patient had slight vaginal bleeding 1 month ago. The physical examination revealed tachycardia, pale conjunctiva, and multiple nodules in both breasts. On laboratory examination, we found low level of Hb 6.7 (n 11.7 - 15.5 g/dl), serum iron 18 (n 65 - 175 mg/dL), TIBC 164 (n 253 - 435 mg/dL), and ferritin 1971(n 4.63-204 mg/dL), positive urine β-HCG, potassium 2.5 (n 3.1 - 5.1 mmol/L). On transvaginal and transabdominal ultrasound examination, there was no gestational sac in the uterine cavity and there are no abnormalities in other gynecology organs. The chest X-ray showed a nodule in the upper right lung suggestive of metastasis with thickening of the soft tissue of the left mammary region suggestive of a left breast mass. We also found a consistent positive result of urine β-HCG, though it had passed four weeks after the occurrence of vaginal bleeding. Finally, the serum β-HCG examination was carried out and showed an increased result, 290,398 (n &lt;5 mIU/ml). The chest CT showed a heterogeny mass (mixed iso-dense and hypodense) that enhanced contrast on the inferior lobe of left lung (4.1 cm x 12.1 cm x 14.1 cm), a mass on apical segment of right lung, subpleural nodule, a mass on the right kidney, spleen, and mediastinal lymphadenopathy. The patient had packed red cell transfusion and after the Hb level reached 11 mg/dl, she still had tachycardia, so we examined the TSHs level. TSHs was found to be low at 0.014 (n 0.48-4.17 mg/dL), and FT4 increased to 2.82 (n 0.89-1.76 mg/dL). Thyroid ultrasound showed small simple cysts in both inferior thyroid pools, no solid mass and no increased vascular flow to the thyroid parenchyma. The patient was then thought to have hyperthyroid manifestation due to β-HCG secreting tumor. She was had methimazole and propranolol therapy, and a lung biopsy was planned.
Conclusion: Trophoblastic and non-trophoblastic tumors that secrete high level of β-HCG can induce hyperthyroid manifestations, particularly if the level was more than 20,000 mIU/mL
Hyperthyroidism and Immune Thrombocytopenia (ITP) Overlap Presenting as Hypoxic Ischemic Encephalopathy in a 38-Year-Old Filipino Female: A Case Report
Authors: Sarigumba Marion Bagaloyos , Cating-Cabral Monica Therese B 
Published: May 2021

Abstract
Background: The coexistence of these two conditions can mimic severe sepsis in critically ill patients which may leave severe thyrotoxicosis unrecognized. Its higher incidence in Asian population suggests a possible genetic propensity.
Clinical Case: A 38-year-old Filipino female sought consult due to changes in behavior. Two months prior, patient had persistent heavy menstrual bleeding but refused work-up. There was progressive weakness and pallor in the interim but no consult was done until she had an aggressive behavior hitting everyone she sees. Patient has Graves disease, maintained on methimazole 15 mg/day and propranolol 30 mg/day. Patient was advised to undergo radioactive iodine therapy but was lost to follow-up for 2 years. Likewise, no medication adjustment nor monitoring of biochemical parameters was done during the same period. On admission, patient was disoriented, tachycardic and febrile. She was generally pale with petechiae on the extremities and blood clots on her lips. Internal examination of the introitus revealed fresh blood with clots. Pregnancy test was negative. Initial laboratory evaluation revealed severe anemia (3.3 g/dl) and thrombocytopenia (3000/uL). Peripheral smear showed mild anisocytosis of red blood cells with no blasts nor atypical lymphocytes and platelet clumps seen. Patient received 1 unit platelet apherese and 2 units packed red blood cells (PRBC) and was started on broad spectrum antibiotic. Neurologic evaluation was negative for craniopathies. Baseline cranial CT scan was not done due to absence of lateralizing signs and was managed as a case of hypoxic ischemic encephalopathy from severe blood loss. Patient was biochemically hyperthyroid with TSH 0.065 uIU/ml, FT4 2.67 ng/dl and 10-fold elevated anti-TPO. Methimazole was then resumed at 20 mg/day and propranolol at 30 mg/day. Neck ultrasound showed an enlarged thyroid with diffuse parenchymal disease. Furthermore, patient had negative Coombs test, normal fibrinogen and procalcitonin. Patient was weakly positive for ANA at 1:160 dilution but negative for other markers in the lupus panel. Consistent with ITP, patient was started on IV hydrocortisone. In the interim, patient had less vaginal bleeding but with persistent bicytopenia which required multiple platelet and PRBC transfusions. A bone marrow biopsy was contemplated. However, on the 7th hospital day, patient had sudden onset of right sided paresthesia with dysarthria and hematomas on extremities. MRI of the brain revealed a large intraparenchymal hemorrhage and patient eventually succumbed to it.
Conclusion: Bone marrow dysfunction secondary to the hyperthyroid state may explain the lack of response to standard therapy of ITP. There is short platelet lifespan, which is rather metabolic in nature, from increased reticuloendothelial phagocytic activity by upregulation of Fc receptor activity in patients with hyperthyroidism.
Hyperthyroidism: A Rare Cause of Cerebral Venous Thrombosis
Authors: Arguinchona Joseph , Pinjala Anusha , George Andrea 
Published: May 2021

Abstract
Background: Cerebral venous thrombosis (CVT) accounts for &lt;1% of strokes. In most cases, there is a predisposition to hypercoagulability; however, in about 30% of cases there is no identifiable etiology. Risk factors include pregnancy, puerperium, oral contraceptives, and coagulopathies and rarely hyperthyroidism. To the best of our knowledge there is no reported cases of CVT in uncontrolled hyperthyroidism with no underlying hypercoagulable disorder. We present a case where a woman developed CVT in the setting of uncontrolled hyperthyroidism. Clinical Case: A 24 year-old Caucasian woman was diagnosed with hyperthyroidism during 1st trimester of pregnancy based labs and was treated with propylthiouracil (PTU) 150 mg bid. At 34 weeks of pregnancy her FT4 normalized and PTU was discontinued. Three and half months post-partum she presented with left frontal headache, photophobia, phonophobia and transient visual loss on the right. Physical exam revealed right homonymous hemianopia without meningismus and an enlarged thyroid. Vitals showed BP 108/57 mm of Hg, HR 162 beats/min, RR of 23/min. CT head without contrast showed 8 mm focal hyperdensity along the left tentorium projecting at the left occipital lobe. She developed seizures after admission. MRI brain with and without contrast showed diffusely small left transverse and sigmoid sinus with a focal area of dural sinus thrombosis. MRI venogram of head confirmed CVT. She was started on levetiracetam and low dose heparin drip. Further workup showed: TSH &lt;0.005 UIU/ml with FT4&gt;8 ng/dl, TSH receptor antibodies 11.10 (normal range 0.00 - 1.75 IU/L), thyroid peroxidase antibody &gt;1300 (normal range &lt;=59 u/ml), and thyroid stimulating antibodies 6.85 (0.00 - 0.55 IU/L) suggestive of Graves disease. She was initiated on PTU 200 mg Q8hrs, propranolol 80 mg Q8hrs and lugol’s iodine 5 drops Q8hrs. Hypercoagulable workup except for protein C and S returned unremarkable. Over the next several days, thyroid levels improved significantly. She was discharged home on warfarin and methimazole. Conclusion: The exact pathophysiology of CVT in hyperthyroidism remains unclear. Some proposed mechanisms include increased activity of pro coagulative plasma constituents including Von Willebrands Factor, Factor IX, X, antithrombin, and fibrinogen as well as an increased aPTT and a decrease in thrombolytic factors like t-PA. These changes result in an increased risk of thrombosis. This case demonstrates the potential development of CVT as a result of untreated overt hyperthyroidism. It highlights the importance of treatment and close follow up of Graves’ disease to prevent severe complications. Further studies need to be done to understand the process of coagulation in hyperthyroidism and this could allow clinicians to better identify hyperthyroid patients at risk for clotting.
Intrathyroidal Branchial Cleft Cysts Presenting as Bilateral Thyroid Nodules
Authors: Faisal Sobia , Rosenblatt Joseph 
Published: May 2021

Abstract
Introduction: Intrathyroidal brachial cleft cysts are a rare entity and are usually associated with Hashimoto’s thyroiditis. Etiology is not very clear at this point, but they are thought to arise from the ultimobranchial body remnant during embryogenesis of the gland versus originating secondary to chronic inflammation as a form of squamous metaplasia. They are a common finding in the lateral neck but not with the thyroid. We present a case of a suspicious appearing bilateral thyroid nodules which were found to branchial cleft cysts on biopsy.
Clinical Case: A 56-year-old woman presented to us for evaluation of thyroid nodules. Her past medical history was pertinent for endometrial cancer status post surgery and radiation, obesity, sleep apnea, hyperlipidemia and hypothyroidism. She was diagnosed with hypothyroidism around 30 years ago and had been on Levothyroxine since then. She was recently noted to have a low TSH level on routine labs done by her primary care provider and therefore her Levothyroxine dose was adjusted. She also underwent a thyroid ultrasound due to exam findings of a palpable thyroid nodule. The ultrasound revealed a suspicious 2.2 cm hypoechoic solid nodule with irregular margins and micro-calcifications in the left mid thyroid lobe. Additionally, she was also noted to have a 0.8 cm hypoechoic nodule with irregular margins in the right mid thyroid lobe. No concerning cervical lymphadenopathy was identified. She was hence referred to us for further evaluation. She denied having compressive symptoms and did not have history of head/neck radiation or family history of thyroid cancer. Both nodules were biopsied but were interpreted as non-diagnostic with insufficient follicular cells and colloid. She underwent repeat biopsy of both nodules which again was interpreted as non-diagnostic. After discussion with patient, given her suspicious ultrasound findings and inconclusive biopsy results she was referred to endocrine surgery for surgical evaluation. Shortly after she underwent total thyroidectomy with pathology consistent with bilateral benign branchial cleft like cysts associated with adjacent thyroid follicles undergoing squamous metaplasia admixed with chronic inflammation.
Conclusion: Pathogenesis of these intrathyroidal branchial cleft cysts is still unclear and not many similar cases have been reported in the literature so far. These commonly present as a painless mass but sometimes can also be an incidental finding. There are not a lot of specific details in the literature regarding imaging or pathology characteristics of these lesions therefore resulting in surgical intervention to reach a definitive diagnosis.