bluuebunny/crossref_metadata_2025_split huggingface dataset:
Paraneoplastic Eosinophilia (PNE): A Rare Finding in a Patient With Metastatic Medullary Thyroid Carcinoma
Authors: Jara Mark Anthony , Casteel Kelly N , Afshar-Kharghan Vahid , Subbiah Vivek , Wing Shane , Hu Mimi I-Nan 
Published: May 2021

Abstract
Introduction: Medullary thyroid cancer (MTC) is a rare tumor of neuroendocrine origin that co-secretes various peptides leading to diarrhea and vasodilation. Ectopic Cushing syndrome due to production of adrenocorticotropic or corticotrophin-releasing hormone is a well-recognized but uncommon paraneoplastic manifestation of advanced MTC. We report an extremely rare presentation of eosinophilia in a patient with MTC that correlated with disease progression. Case:
A 58-year-old woman with sporadic metastatic MTC harboring somatic RET M918T mutation developed metastatic disease to the liver, lung and bones 2 years after surgery for locally advanced disease. Calcitonin (Ctn) was 123 pg/ml and CEA was 2575 ng/ml. At that time, leukocytosis [WBC 30.8 K/ul (4-11k/ul)] and eosinophilia [eosinophil count 16.01 k/ul (0.04-0.40 k/ul)] were noted. She was asymptomatic. Extensive evaluation of hypereosinophilia ruled out hematological or infectious causes. The patient initiated vandetanib with a partial response (PR) with decrease in lung and liver metastases and a significant improvement of the paraneoplastic eosinophilia [eosinophil count 2.39 k/ul] after 10 weeks of treatment. After a year on treatment, there was progressive disease (PD) with increasing hilar and abdominal lymphadenopathy associated with increased eosinophilia of 4.34 K/ul. Vandetanib was discontinued. She was enrolled on a clinical trial with a highly potent and selective RET inhibitor. The patient achieved PR to study drug by the 2nd month on treatment and durable response for 30 months. The eosinophil count normalized [0.32 k/ul] 4 weeks after starting the new treatment. She developed PD in liver metastases associated with recurrent leukocytosis (WBC 58.6 K/ul) and eosinophilia of 28.13 K/ul. Ctn was 1646 pg/ml. CEA was 8722 ng/ml. Her bone marrow biopsy showed marked eosinophilia, focal MTC metastatic infiltrate, no increased blasts, and was negative for the BCR-ABL1 translocation and the FIP1L1-PDGFRA fusion. She was switched to a different RET Inhibitor but passed away 1 month after starting the new protocol. Discussion: Paraneoplastic eosinophilia should be considered after excluding other causes (e.g. infections, allergy, collagen, vascular or malignant hematopoietic diseases). Thyroid tumors producing colony-stimulating factors, associated with neutrophilia and/or eosinophilia have been described almost exclusively in patients with anaplastic thyroid cancer. This patient had a poorly differentiated MTC as evidenced by the disproportionally high CEA relative to Ctn. The course of the eosinophilia paralleled the clinical behavior of her disease. To our knowledge, this is only the 2nd report of eosinophil trends corresponding with MTC disease course, consistent with a paraneoplastic process. Conclusion: PNE is very rare in MTC and its presence suggests a poor prognosis.
Primary Thyroid Lymphoma: Could Surgery Be Avoided
Authors: Laukiene Romena , Miseviciute Karolina 
Published: May 2021

Abstract
Background: Primary thyroid lymphoma is a rare thyroid disease that makes up only 1 to 5% of all thyroid oncological disorders. The average patient with primary thyroid lymphoma is a woman in her sixth or seventh decade with a history of Hashimoto’s thyroiditis. Clinical Case: 28-year-old woman complained of hoarseness, rapidly enlarging mass of the neck. She was referred to an otorhinolaryngologist by her family physician who suspected upper airway pathology. Otorhinolaryngologist observed swelling of patients’ larynx and prescribed treatment for suspected bacterial larynx infection. Symptoms kept worsening despite of treatment and patient was referred to an endocrinologist for a consultation. Blood lab tests were unremarkable. Ultrasound of the thyroid was performed which revealed a large (4,5 cm), hypoechoic, solid, homogenous node with Doppler signs of increased intranodular vascularity. Additionally, enlarged submandibular salivary gland lymph nodes on both sides of the neck were observed. FNAC (fine-needle aspiration cytology) was performed to diagnose possible thyroid malignancy, however findings showed atypia of undetermined significance (3rd category of Bethesda classification), to differentiate from lymphocytic thyroiditis. Because of high risk of malignancy, it was decided to perform thyroidectomy. During surgery, urgent intraoperative biopsy revealed undifferentiated thyroid carcinoma. As radical tumor extirpation due to prominent surrounding fibrosis was impossible, then only one side lobectomy was performed. Final histological examination revealed large B cell lymphoma, phenotype: CD20+, BCL6+, MuM1+, CD21+, cMyc-, BCL2-, CD10-, CD30-, Ki-67 up to 97%. More accurate disease staging was performed post-operatively, PET scan and computed tomography revealed disseminated primary thyroid lymphoma. Final diagnosis was Stage IV primary large B cell lymphoma of the thyroid. Patient was treated with chemotherapy according to Rx7-CHOP14x6 (Rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) protocol. The treatment was tolerated well, 3 months after, complete remission of the disease was observed. During outpatient visits patient remained in remission for all 5 years of planned regular check-ups. Conclusion: This case demonstrates the diagnostic challenge of primary thyroid lymphoma. In the presence of rapidly enlarging thyroid mass, thyroid lymphoma is not usually suspected. FNAC as golden standard of thyroid malignancy often does not allow differentiation of this pathology. In this case, a core biopsy could have helped to make correct preoperative diagnosis and to avoid unnecessary surgery.
Responses to the First Radioactive Iodine Treatment After Targeted Therapy for Aggressive Papillary Thyroid Cancers
Authors: Soe Myat Han , Chiang Janet , Kang Hyunseok , Liu Chienying 
Published: May 2021

Abstract
Introduction: Tall cell variant (TCV) and columnar cell variant (CCV) are aggressive variants of papillary thyroid cancer (PTC) and they are overrepresented in radioactive iodine (RAI) refractory cases. Studies have reported using BRAF and/or MEK inhibitors to restore iodine avidity in patients with iodine refractory disease. There is much less experience of using targeted therapy pre-emptively to enhance iodine uptake for aggressive variants and advanced disease prior to the first RAI treatment (RAI-T). We present three patients with these variants and describe their responses to the first RAI-T after targeted therapy.
Case 1: 64-year-old male with CCV-PTC and areas of poor differentiation (pT3aN1bM1) has somatic BRAF V600E, TERT and AJUBA mutations. Thyroglobulin (TG) 6 weeks post surgery was 21 ug/L, with negative TG antibodies (TGAb). PET-CT revealed FDG avid superior mediastinal lymphadenopathy and lung metastases. He received dabrafenib for 6 weeks followed by his first RAI -T(153 mCi) after thyroid hormone withdrawal (THW). Pre- and post-therapy scans showed uptake in the neck, right superior mediastinum and lung metastases. Three months post RAI, TG decreased to 5.1 ug/L. Chest CT revealed stable mediastinal lymphadenopathy and decreased size of lung metastases.
Case 2: 41-year-old male with TCV-PTC containing areas of focal squamous differentiation and poor differentiation (pT4aN1bM1) has somatic BRAF V600E and TP53 mutations. PET-CT showed FDG avid neck lymph nodes and lung metastases. TG 8 weeks after surgery was 1.5 ug/L, TGAb 31.19 IU/L. He was treated with dabrafenib and trametinib for 4 weeks followed by his first RAI-T (150mCi) after THW. Pretreatment scan showed uptake in the thyroid bed and cervical lymph nodes. Post-therapy scan revealed additional uptake in the lung metastases. Chest CT 3 and 9 months after RAI-T revealed stable paratracheal lymph node and lung metastases. TGAb decreased to 7.04 IU/L; TG was 2.2 ug/L.
Case 3: 33-year-old female with invasive TCV-PTC (pT3bN1aM1) has a somatic BRAF V600E mutation. CT chest showed multiple scattered lung nodules up to 4mm. Ten weeks post surgery, TG was 0.1 ug/L, TGAb 5.21 IU/ml. Patient received 1 month of dabrafenib and trametinib followed by his first RAI-T(125 mCi) after THW. Pre- and post-therapy scans revealed uptake in the neck and left supraclavicular areas, without uptake in lung nodules. Three months post RAI, chest CT revealed stable lung nodules. TG was 0.1 ug/L, and TGAb was 5.16 IU/L. Neck ultrasound showed no disease.
Conclusion: These three patients with aggressive variants of PTC have advanced disease, and all were found to have a BRAFV600E mutation on genomic analysis. They tolerated BRAF targeted inhibition as an attempt to enhance iodine uptake preemptively with various responses to their first RAI-T. More studies will be needed to determine if this strategy will improve outcomes for these patients.
A Case of TSH-Secreting Pituitary Adenoma With Unusual Positive Staining for SF1
Authors: Robinson Kathleen , O’Neill Brian 
Published: May 2021

Abstract
Background: TSH-secreting pituitary adenomas are the rarest functional pituitary tumors. While they are often plurihormonal, SF1 positivity (indicating gonadotroph lineage) is unusual. Here we present the rare case of a patient with TSH-secreting pituitary adenoma with staining positive for TSH, GH, prolactin, SSTR2A, PIT-1, and SF1.
Clinical Case: Patient is a 42 year-old male with a history of hypogonadotropic hypogonadism (lost to follow-up), who presented with a 5 day history of nausea and vomiting. Vitals were notable for tachycardia to 108 BPM, with BMI 14.8 kg/m2. On physical exam he had enlarged right hemi-thyroid and exophthalmos. Labs were notable for TSH 12.55 μIU/mL (0.27-4.20), Free T4 &gt;7.77 ng/dL (0.80-1.80), Free T3 29.02 pg/mL (2.57-4.43), 8am cortisol 0.9 μg/dL (6.0-18.4), FSH 0.6 μIU/ml (1.5-12.4), LH 0.8 μIU/mL (1.7-8.6), PRL 8.5 ng/mL (4.0-15.2), total testosterone &lt;5 ng/dL (249-836), and IGF-1 88.9 ng/mL (94.4-223.0). MRI showed large lobulated pituitary mass extending into the suprasellar region with mass effect and thyroid US showed enlarged almost completely cystic right hemi-thyroid. The patient was started on methimazole 30mg BID, prednisone 40mg daily, and cabergoline 0.5mg weekly (he declined octreotide). FT4 and FT3 remained significantly elevated despite escalation of cabergoline to 0.5mg 5 days weekly, so the patient was admitted two months after his initial presentation for plasmapheresis followed by thyroidectomy. His hospital course was complicated by post-op meningitis and DI, both successfully treated. Surgical pathology was notable for patchy expression of TSH with rare cells expressing GH and prolactin, SSTR2A positivity, strong nuclear positivity for PIT-1 with negative T-PIT staining, and unusual positivity for SF1. At follow-up he is clinically euthyroid and stable without use of LT4 or HC therapy. Repeat TSH, FT4, ACTH, cortisol, and testosterone are pending. He declines chemotherapy, radiation, and octreotide. Conclusion: This is a rare case of TSH-producing adenoma demonstrating SF1 positivity in addition to TSH, GH, PRL, and PIT-1 expression, in the absence of excess gonadotroph secretion. When such tumors secrete multiple hormones, this has been used as evidence to support the argument that such tumors arise from a stem cell population(1). However, the implications for our patient remain unclear.
References: (1) Tordjman et al. Plurihormonal Pituitary Tumor of Pit-1 and SF-1 Lineages, with Synchronous Collision Corticotroph Tumor: a Possible Stem Cell Phenomenon. Endocr Pathol. 2019 Mar;30(1):74-80.
A Rare Case of Anaphylaxis to Methimazole in a Patient With Graves’ Disease
Authors: Garg Dave , Garcia Gonzalo Acosta , Praw Stephanie Smooke 
Published: May 2021

Abstract
We present the case of a patient with Graves’ Disease (GD) who developed anaphylaxis to methimazole (MMI) necessitating hospitalization, emergent treatment and ultimately urgent total thyroidectomy. While the most common adverse reactions to thionamides include hepatotoxicity, agranulocytosis, pruritis, and urticaria, delayed anaphylaxis has been reported.
A 25-year-old woman was diagnosed with GD two years prior to presentation during an admission for syncope. She was started on MMI 10 mg twice a day and propranolol 10 mg three times a day, which she took for roughly one year until she ran out of medication and was lost to follow-up. She remained off MMI until she re-presented several months later grossly thyrotoxic, complaining of fatigue, heat intolerance, unintentional weight loss, blurry vision, and palpitations. Labs were significant for TSH &lt;0.02 mIU/L (normal 0.3-4.7), free T4 &gt;7 ng/dL (normal 0.8-1.7), free T3 &gt;2900 pg/dL (normal 222-383), and thyroid stimulating immunoglobulin (TSI) &gt;500 (normal ≤122).
She was restarted on propranolol and MMI 10 mg twice a day which was quickly increased to 20 mg twice a day. Two weeks after restarting MMI, the patient presented to the ER with a diffuse pruritic rash and was treated with antihistamines and steroids. She clinically improved and was discharged in stable condition. Two days later, her symptoms recurred along with flushing, facial/lip swelling, and dysphagia. She presented to our hospital with evidence of angioedema and difficulty breathing. Based on her presentation, anaphylaxis was diagnosed, and she was given intramuscular epinephrine. She was also started on glucocorticoids, H1/H2 blockers and montelukast and was admitted to the ICU for close monitoring. Over the next few days, her symptoms improved.
As there was no other recent novel exposure, her anaphylactic reaction was attributed to MMI. Given the life-threatening nature of the reaction, there was concern for trialing propylthiouracil (PTU) due to its known cross-reactivity with MMI. Thus, treatment with propranolol, steroids and potassium iodide was initiated with improvement in her thyroid labs. As the patient would be unable to tolerate anti-thyroid agents in the future, it was decided to pursue definitive treatment with total thyroidectomy given the presence of eye disease.
Anaphylaxis secondary to MMI is very rare, and less than a handful of cases have been reported. However, they seem to share two key features: their occurrence with higher doses of MMI (≥40 mg daily), and a delayed onset of presentation (2-4 weeks from exposure). The mechanism is unknown, although it is unlikely to be IgE-mediated given its time course. Current ATA guidelines recommend against using MMI or PTU in patients who have developed serious side effects to the other agent. Our case highlights the importance of close monitoring and timely follow-up after initiating anti-thyroid drugs.
A Rare Case of Rhabdomyolysis in a Patient With Pembrolizumab Induced Hypothyroidism
Authors: Idriss Setana , Shaikhoun Mazin , Ramineni Srivyshnavi , Elnigomy Sheikan , Apedo Margaret 
Published: May 2021

Abstract
Introduction: Although reported in previous literature, Rhabdomyolysis due to hypothyroidism,without an obvious precipitating factor, is rare. We report a case of severe hypothyroidism leading torhabdomyolysis. Case Report: A 70-year-old man with a history of progressive weakness, myalgia x1 month, statinallergy, pancreatic adenocarcinoma, metastatic melanoma, and acquired hypothyroidism afterreceiving Pembrolizumab for 6 months. He was non-adherent to the levothyroxine, prescribed 1month before hospitalization. He presented to the ED after slipping from his bed onto the floor in aseating position and being unable to get up due to his weakness. Initially, he was afebrile, hypoxic,tachypneic, tachycardic, hypotensive, lethargic, oriented x2, and had a global muscular weakness. Labs were significant for CK of 10,180 (n &lt; 166 IU/L), TSH 136.18(n 0.34-5.6 mU/L), FT4 &lt; 0.25 (n0.6-1.10 ng/dl), FT3 1.4 (n 2.5-3.9 Pg/ml), AKI, leukocytosis, abnormal electrolytes and LFTs. IV fluidsand antibiotics failed to improve the patient’s clinical status in 48 hours. He was started on IVthyroxine and stress steroids with improved weakness and overall clinical picture. Discussion: 4.6 % of people have hypothyroidism per the United States National Health andNutrition Examination Survey. Rhabdomyolysis is defined as the rapid breakdown of skeletal muscle,which may also develop due to hypothyroidism. Most patients with hypothyroidism who developrhabdomyolysis are found to have a clear precipitating risk factor, such as the use of statins orstrenuous exercise. Still, none of these risk factors were present in this case. Our patient acquiredhypothyroidism after a few months of receiving Immunotherapy. It is reported that hypothyroidismoccurs in (9% to 18%) of patients receiving Pembrolizumab. Although the patient was prescribedthyroid replacement therapy, he was not adherent to the medication for 1 month prior topresentation. Although mechanical injury is reported to cause elevated CK levels, mostrhabdomyolysis cases are related to crush injuries. We believe that the fall was probably related tohis progressive generalized weakness due to his noncompliance with medical therapy leading tomyxedema coma and rhabdomyolysis. Conclusion: Screening for hypothyroidism in patients with elevated muscle enzymes should behighly considered since an early diagnosis. Prompt treatment of hypothyroidism is essential toprevent rhabdomyolysis and its consequence.
Acute Inflammatory Demyelinating Polyneuropathy (AIDP) Masked by Autoimmune Thyroiditis
Authors: Wirtshafter Stephanie , Iqbal Iqra 
Published: May 2021

Abstract
Hashimoto’s thyroiditis and Guillain-Barre syndrome (GBS) are autoimmune disorders that are both well-known in their own right. Hashimoto’s is one of the most common causes of primary hypothyroidism, and GBS involves immune mediated damage to the peripheral nervous system. The association between the two is a rare clinical entity. This case demonstrates that these entities can occur together and could be related in similar pathophysiology.
A 37 year old male presented with complaints of bilateral hand and feet numbness for one month. The numbness started in the hands, then involved the feet, and was mostly felt in tips of extremities. He also complained of weakness in arms and legs. Neurology exam showed bilateral patellar, ankle, and biceps hyporeflexia. Muscle strength was 5/5 in all extremities, but decreased grip strength was noted in the hands. Initial lab work including complete blood count, comprehensive metabolic profile and urinalysis were all in normal range. Computerized tomographic scan (CT) head was normal while CT abdomen/pelvis showed hepatic fatty infiltration. Other lab tests including HIV, syphilis, Hepatitis B, Hepatitis C, glycosylated hemoglobin A1c, lipid panel, anti-nuclear antibody, anti-neutrophil cytoplasmic antibodies, serum/urine protein electrophoresis, alcohol level, vitamin B1, B6, folate, copper, and creatine kinase were all negative or within normal range. Lab abnormalities included elevated thyroid stimulating hormone (TSH) of 20.2 mIU/l and low normal B12 level of 289 pg/ml. His triiodothyronine (T3) and thyroxine (T4) hormone levels were in normal range. A thyroid peroxidase antibody level came back as high as 966 IU/ml. A diagnosis of Hashimoto’s thyroiditis leading to subclinical hypothyroidism was made. Patient was discharged on vitamin B12 and 112mcg of Synthroid. Instead of getting better, he returned 1 week later with worsening numbness and tingling which was now ascending upward to bilateral knees and elbows. Meanwhile TSH improved to 10 mIU/l and vitamin B12 increased to 1162 pg/ml. A magnetic resonance imaging (MRI) of the cervical/thoracic spine was unremarkable. A lumbar puncture showed negative xanthochromia, 0 WBC, 0 RBC, 0 neutrophils, 0 lymphocytes, 0 monocytes, glucose 63 mg/dl, elevated protein of 57 mg/dl, and culture was negative. Guillain-Barre syndrome was then the working diagnosis, more specifically its most common subtype, acute inflammatory demyelinating polyneuropathy (AIDP). Patient received five days of intravenous immunoglobulins and his symptoms improved. He was then discharged to follow up with endocrinologist.
This subtle presentation of GBS/AIDP masked by Hashimoto’s thyroiditis and vitamin B12 deficiency suggests a close association of autoimmune etiology between these disorders. Although rare, endocrinologists should consider this rare association in cases of paresthesias with unexplained symptoms.
Amiodarone Induced Thyrotoxicosis: A Case of Refractory Disease Treated With Thyroidectomy
Authors: Mushref Malek , Tofil Kathrin Sandra , Hermayer Kathie Lynn 
Published: May 2021

Abstract
Amiodarone induced thyrotoxicosis (AIT) is a challenging diagnosis that affects 3-5% of patients taking amiodarone in the United States. Type I AIT is seen in patients with preexisting thyroid disease and is generally treated with thionamides while type II AIT represents a destructive thyroiditis that responds to glucocorticoids. A mixed type exists and is associated with higher mortality, especially in older adults with cardiovascular disease. Thyroidectomy is considered a last resort option for patients intolerant or refractory to medical treatment.
A 70 year-old male with a history of coronary artery disease, ventricular tachycardia (VT), and heart failure was referred to the endocrine clinic for abnormal thyroid function tests that showed TSH &lt;0.0023 uIU/mL (0.4-4.7), Free T4 2.51 ng/dL (0.7-1.48) and Free T3 5.37 pg/mL (1.71-3.71). He endorsed palpitations, excessive sweating, tremors, and reported taking amiodarone for 3 years prior to presentation. Vitals showed normal pulse and blood pressure. Thyroid autoantibodies including TSI and TBII were within normal limits. Thyroid ultrasound showed mild thyromegaly with normal vascularity and no nodules. AIT was suspected and he was started on methimazole 20 mg daily, prednisone 30 mg daily and continued on his home metoprolol 100 mg daily. Methimazole and prednisone were both up titrated in a week because his labs did not improve. One month later, he presented to the hospital with acute exacerbation of heart failure. His TFTs showed (TSH &lt;0.0021 uIU/mL, FT4 &gt;5.0 ng/dL, FT3 4.61 pg/mL). Thyroid RAIU showed severely decreased uptake secondary to the high iodine content of amiodarone. He remained thyrotoxic despite using higher doses of prednisone (60 mg daily) and methimazole (90 mg daily). He was changed to PTU (900 mg daily) and started on cholestyramine, with no improvement in overall status. Several weeks after admission, a total thyroidectomy was performed. His postoperative course was unremarkable except for hypoparathyroidism. He was clinically and biochemically euthyroid one week after his procedure. At 6 months follow up, he remained stable on levothyroxine 100 mcg/day but continued to require calcitriol and calcium supplementation.
We present an interesting case of mixed type AIT refractory to medical therapy associated with cardiovascular compromise. This case highlights the challenges in the diagnosis and management of such patients. Thyroid autoantibodies, thyroid ultrasound and RAIU were more indicative of Type II AIT, however, lack of response to high dose steroids was inconsistent with the diagnosis. While receiving the treatment for both Type I and II AIT, our patient had persistent clinical and biochemical thyrotoxicosis and required thyroidectomy. Although most AIT patients are treated medically, thyroidectomy is reserved for those most severe and refractory cases and is considered a viable option in such patients.