bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of a Novel DICER1 Germline Mutation in Thyroid Follicular Adenoma Using Whole Exome Sequencing
Authors: Cheon Chong Kun
Published: May 2021

Backgrounds: DICER1 protein is a member of the ribonuclease III family of proteins that cleaves non-coding small RNA precursors to generate mature miRNAs, which in turn regulate gene expression post-transcriptionally. Thyroid abnormalities are frequently observed in DICER1 syndrome with multinodular goiter present in families in which a germline DICER1 mutation is segregating. Recently, we identified a germline DICER1 mutation in a family with multiple tumors using whole exome sequencing (WES). Methods and Materials: Following informed consent, WES of peripheral blood DNA was carried out on affected individual. Sanger sequencing was performed to confirm the DICER1 variant detected by WES and to assess her family for mutation in the same DICER1 exon (exon 20). Results: An 8 year-old girl presented with abdominal mass. Laparoscopic radical nephrectomy was done due to Wilms tumor. At age 12, palpable mass on the right thyroid lobe was found, and right hemithyroidectomy was performed. She was diagnosed with follicular adenoma, and she started to take levothyroxine. At age 13, palpable thyroid mass on the left thyroid lobe was identified, and total thyroidectomy was performed due to progressively enlarged remnant thyroid gland with multiple nodules. The pathological result was adenomatous goiter with a cystic change. During the evaluation, a 1.5cm follicular cyst in the left ovary, 0.7cm cystic lesion in the right middle lobe of the lung, and air-trappings in both lungs were observed. We performed WES which revealed a novel heterozygous missense mutation, c.3506C>G(p.S1169*) in exon 20 of the DICER1 gene. During the follow-up, she showed a severely enlarged right kidney with multiple septated cysts. Right total nephrectomy was done due to hemorrhage progression in cysts and biopsy revealed cystic nephroma. Continuous renal replacement therapy was applied after right nephrectomy, and maintenance hemodialysis was applied. Conclusions: We identified a novel DICER1 germline mutation in a family with thyroid follicular adenoma, Wilms tumor, and contralateral progressive cystic nephroma which is the first report in Korea.
Molecular Testing Can Impact Clinical Decision Making and Therapeutic Approach in Thyroid Cancer
Authors: Garcia Gonzalo J Acosta , Praw Stephanie Smooke
Published: May 2021

We present the case of a patient with a thyroid nodule of indeterminate cytology on fine-needle aspiration (FNA) biopsy whose molecular profile significantly impacted clinical decision making and treatment.

A 77-year-old woman with a history of hyperthyroidism presented to our clinic for a second opinion regarding management of a recently discovered right thyroid nodule. Thyroid ultrasound (US) 6 months prior showed a 2.6 cm, heterogeneous nodule with peripheral vascular flow; not characterized based on ATA or TIRADS criteria. Family history was significant for papillary thyroid cancer in daughter at age 35 years. The patient had no history of head or neck irradiation. She had no compressive symptoms or manifestations of hyper or hypothyroidism.

FNA biopsy of the nodule was done twice in 4 months, and cytology was consistent with follicular lesion of undetermined significance (FLUS, Bethesda III) in both occasions. Repeat FNA biopsy at our institution showed follicular neoplasm (FN, Bethesda IV), and molecular testing using ThyroSeq v3 was positive for HRAS and TERT mutations, which conferred a >95% risk of cancer. Patient was referred to Endocrine Surgery and total thyroidectomy was recommended based on nodule’s molecular profile and associated hyperthyroidism. No suspicious lymph nodes were noted on preoperative US. No gross local invasion observed intraoperatively. Surgical pathology showed intrathyroidal FN without invasion. However, given disparity between pathology findings and molecular markers, specimen was sent for outside blinded pathology review which concluded to be a follicular thyroid carcinoma with capsular invasion but no angiolymphatic invasion or extrathyroidal extension. Based on these findings, along with the known HRAS and TERT mutations, it was advised to proceed with radioiodine (RAI) remnant ablation. Patient was prepared with thyrotropin alfa and received 29 millicuries of RAI. Post-treatment scan showed focal neck uptake consistent with ablated thyroid tissue and no distant metastases. Patient had an excellent response to therapy, without evidence of biochemical or structural recurrence 2 years later.

Molecular testing of cytologically indeterminate thyroid nodules (Bethesda III, IV) has become an important tool to better refine risk of malignancy. Furthermore, the presence of certain mutations or mutation combinations, such as RAS and TERT co-occurrence, suggests a more aggressive behavior associated with worse outcomes. As a result, a more aggressive approach might be recommended. Our case illustrates how molecular testing can significantly influence therapeutic decisions such as extent of surgery, interpretation of surgical pathology and/or use of RAI. Further research is needed to determine if its routine use may lead to improved cancer-related outcomes or if it is cost-effective in the risk stratification of differentiated thyroid cancer.
Preoperative Amlodipine Is More Efficacious Than Prazosin in Preventing Intraoperative Haemodynamic Instability in Pheochromocytoma/Paraganglioma Patients: Interim Analysis of a Pilot Randomized Controlled Study
Authors: Memon Saba Samad , Jaiswal Sanjeet Kumar , Garg Robin , Barnabas Rohit , Goroshi Manjunath , Lila Anurag , Sarathi Vijaya , Dalvi Abhay , Garale Mahadeo , Hemantkumar Indrani , Patel Rajendra , Oak Shrikanta , Patil Virendra , Shah Nalini Samir , Bandgar Tushar Ramkrishna
Published: May 2021

Background: Preoperative blockade with α-blockers is recommended in patients with pheochromocytoma/paraganglioma (PPGL). The data on calcium channel blockade (CCB) in PPGL is scarce. We aim to compare the efficacy of CCB and α-blockers on intraoperative haemodynamic instability (HDI) in PPGL. Methods: In the interim analysis of this monocentric, pilot, open-label, randomized controlled trial, patients with solitary, secretory, and nonmetastatic PPGL were randomized to oral prazosin (maximum 30mg, n=9) or amlodipine (maximum 20mg, n=11). The primary outcomes were the episodes and duration of hypertension (SBP≥160mmHg) and hypotension (MAP<60mmHg) and duration of HDI (hypertension and/or hypotension) as a percentage of total surgical time (from induction of anaesthesia to skin closure). Findings: The median (IQR) episodes (2 [1–3] vs. 0 [0–1], p 0·002) and duration of hypertension (19 [14–42] min vs. 0 [0–3] min, p 0·001) and intraoperative HDI duration (22·85±18.4% vs 2·44±2·4%, CI 8·68-32·14%, p 0·002) were significantly higher in the prazosin arm than the amlodipine arm whereas episodes and duration of hypotension did not differ between the two groups. There was no perioperative mortality whereas one patient had intraoperative ST depression on the electrocardiogram. The drug-related adverse effects were pedal edema (1 in amlodipine), dizziness (1 in prazosin), and tachycardia (6 in prazosin and 3 in amlodipine). Interpretation: Preoperative blockade with amlodipine was more efficacious than prazosin in preventing intraoperative HDI in PPGL. Larger studies that compare preoperative blockade with amlodipine and both competitive and noncompetitive α-blockers inPPGL patients of various biochemical phenotypes are warranted.
Thyroid Angiosarcoma Complicated by Neck Hematoma
Authors: Larsen Dana , Yanagisawa Robert
Published: May 2021

Background: Primary angiosarcoma of the thyroid is a rare, aggressive thyroid malignancy most typically found in the Alpine regions of Europe. We present a case of non-Alpine thyroid angiosarcoma complicated by recurrent surgical bed hematoma.

Case: An 81-year-old Albanian man presented with two months of dyspnea and hemoptysis and was found to have a large thyroid mass, multiple subcentimeter pulmonary nodules, and a left pleural effusion seen on CTA of the chest. He had a suppressed TSH < 0.008 uIU/mL (n 0.400-4.200 uIU/mL) on presentation with a normal free T4 (1.36 ng/dL; n 0.80-1.50 ng/dL) and total T3 (107 ng/dL; n 87-178 ng/dL). Labs from 3 years prior were consistent with prior subclinical hyperthyroidism: TSH 0.28 uIU/mL, free T4 1.35 ng/dL, and free T3 3.98 pg/mL (n 2-4.4 pg/mL). A thyroid ultrasound was performed and showed multiple bilateral thyroid nodules, the largest of which was 6.0 x 7.8 x 5.4 cm in the right lower pole. He had no compressive symptoms and was clinically euthyroid. FNA of the nodule was non-diagnostic and cytology of the pleural fluid was negative for malignancy. He underwent a bronchoscopy which showed blood clots without endobronchial lesions, VATS with pleural biopsy, and right hemithyroidectomy. Pathology showed high grade epithelioid malignancy arranged in solid, variably discohesive nests and sheets, associated with vague vasoformative features and hemorrhage. Immunostains were diffusely and strongly positive for ERG as well as CD31 and AE1/3, but negative for PAX-8, TTF-1, and thyroglobulin, supporting a diagnosis of angiosarcoma. The remainder of the thyroid tissue was non-neoplastic with multinodular hyperplasia. After initial discharge, he re-presented on post-op day 10 with bleeding from the surgical site. CT of the neck showed extensive hematoma (10.3 x 5.0 x 8.7 cm) and he was taken back to the OR for evacuation. Residual tumor tissue found along the R carotid artery was determined to be the culprit. Over the next month the patient remained admitted for supportive transfusions, and palliative radiation to the pulmonary nodules and the residual tumor was initiated. His hospitalization was complicated by a proximal lower extremity DVT, which was treated with an IVC filter. Repeat chest imaging at six weeks showed new and progressive pulmonary nodules. Upon completion of 3 weeks of RT the patient was discharged debilitated, fatigued, and using supplemental oxygen. His family elected to pursue hospice care.

Conclusion: This case represents a rare, aggressive malignancy complicated by extrathyroidal extension and recurrent hematoma resulting in severe morbidity and precluding further systemic interventions. These highly vascular tumors likely present an elevated risk for postoperative hematoma which clinicians should recognize.
Toxic Thyroid Nodule: To FNA or Not?
Authors: Kasina Siva Kumar , Hayward Erin E , Lal Geeta , Correia Marcelo
Published: May 2021

Background: ATA guidelines recommend evaluation of hyperthyroidism with radioiodine scan and consideration of FNA for non-toxic nodules with suspicious sonographic features. However, there is no standard evidence-based approach to performing ultrasound in patients with toxic nodules. Recent studies have shown increased rates of thyroid cancer in patients with hyperthyroidism and has been shown to demonstrate aggressive histologic features. Clinical Case: A 41-year-old female presented to primary care provider for annual physical exam, found to have intermittent bigeminy and enlarged thyroid on exam. EKG notable for multiple premature ventricular complexes. Evaluation revealed suppressed TSH <0.01 µIU/mL (0.27-4.20), normal free T4 1.27 ng/dL (0.80-1.80), slightly elevated free T3 4.84 pg/mL (2.57-4.43) and elevated TSI 238% (<122). Methimazole was started for treatment of hyperthyroidism. Thyroid sonogram was ordered for abnormal exam, that showed 2.7 cm TIRADS 4 left thyroid nodule with microcalcifications. I-131 uptake values were 20% and 49% at 4-hours and 24-hours, respectively. Technetium-99M scan showed toxic autonomous nodule in the left thyroid lobe corresponding to the one seen on sonogram. The remainder of the thyroid gland showed heterogeneously suppressed uptake. FNA of the thyroid nodule was done due to the presence of microcalcifications and the cytopathology was suspicious for papillary carcinoma. She underwent total thyroidectomy with central neck dissection involving pre-tracheal and paratracheal lymph nodes (level VI). Pathology showed 1.4 cm papillary carcinoma with lymphovascular space invasion and multifocal papillary microcarcinomas in the left thyroid lobe, 0.2 cm papillary microcarcinoma in right thyroid lobe, metastatic papillary carcinoma in 2 out of 5 lymph nodes, largest metastatic deposit 0.1 cm in the largest dimension with no extra nodal extension. There was also follicular hyperplasia noted consistent with Graves’ disease. Post-operatively, she had thyrogen-stimulated adjuvant RAI treatment, dose 107.4 mCi. Post therapy scan did not show evidence of distant metastases. Conclusion: This case demonstrates the identification of a metastatic papillary thyroid carcinoma based on suspicious ultrasound features requiring total thyroidectomy, central neck dissection and adjunct radioactive iodine in a patient with hyperthyroidism from co-existent toxic thyroid nodule and Graves’ disease.
Undifferentiated Thyroid Carcinoma With Anaplastic Features in a 78-Year-Old Filipino Female: A Case Report
Authors: Sarigumba Marion Bagaloyos , Isidro Maria Jocelyn Capuli
Published: May 2021

Background: Anaplastic thyroid carcinoma (ATC) accounts for 0.8-9.8% of all thyroid cancers globally with a median survival from diagnosis of 5 months.

Clinical Case: A 78-year-old Filipino female sought consult due to a rapidly progressive anterior neck mass. This started as a centimeter-sized nodule initially noted three months prior. Two months after, there was gradual enlargement to a fist-size, movable mass, hard in consistency associated with dysphagia and hoarseness of voice. On consult, neck ultrasound revealed an enlarged right thyroid with a mass in the right lobe (TI-RADS 5), multinodular with no lymphadenopathy. Furthermore, a CT scan of the neck was done to evaluate for other structural causes of dysphagia showing no intrathoracic extension. Patient was advised surgery but was lost to follow up due to lockdown from COVID-19. In the interim, patient was admitted for aspiration pneumonia. IV antibiotics were initiated and urgent surgery was advised to relieve patient of respiratory compromise. Patient was airlifted to a tertiary care center for further management. Baseline thyroid function tests were normal. Repeat neck imaging showed interval increase in the hypodense mass measuring 6x9x8 cm (from 3x4x5 cm) (APxWxCC) extending to the hypopharynx and laryngeal vestibule with mass effect to the trachea and esophagus. A multidisciplinary meeting was done to establish goals of care. On the 3rd hospital day, a tracheostomy with incisional biopsy and frozen section was done which revealed round to spindle cell neoplasm with anaplastic features. No further surgical resection was done and specimen was sent for immunohistochemical staining. Long term enteral access was secured during the same operation. Final histopathology showed undifferentiated thyroid carcinoma with anaplastic features and no definite lymphovascular invasion. Immunohistochemical markers were negative for CD3, CD20, Thyroglobulin, TTF-1, PAX8, Calcitonin and Pancytokeratin which reveal loss of tumor antigenicity, consistent with the histopathologic diagnosis. Metastatic work-up revealed varisized pulmonary, subpleural and hepatic nodules with lymphangitic carcinomatosis. Patient was staged as IVC (T4N1M1). Patient was referred for radiation to maximize local control, to complete 33 fractions of 200 cGy on the thyroid mass and received one cycle of Paclitaxel before discharge. Concurrent chemoradiation was continued and completed 29 cycles of radiation and 2 cycles of Paclitaxel which significantly reduced the tumor size. However, the patient succumbed to acute coronary syndrome on her third admission.

Conclusion: There is currently no consensus first-line treatment modality available worldwide. Although the diagnosis and treatment of ATC is considered medically urgent, end-of-life planning must be given high priority in order to optimize the quality of the patient’s remaining life.
Xeroderma Pigmentosum: An Uncommon Risk Factor for Aggressive Follicular Thyroid Carcinoma
Authors: Pattison Jillian
Published: May 2021

Introduction: Follicular thyroid carcinoma (FTC) is the second most common thyroid cancer, which typically presents in an older populations, and carries a near 100% 5-year relative survival rate if diagnosed prior to cancer spreading outside of the thyroid. Clinical Case: A 26-year old female presented to emergency room with persistent jaw pain, despite course of antibiotics prescribed by dentist. She has a past medical history of xeroderma pigmentosum (XP) with over 130 surgeries for malignant skin lesions, as well as benign multinodular goiter for which she underwent total thyroidectomy at the age of 18, with pathology reporting benign tissue and follicular adenoma. Emergency room imaging of maxillofacial/sinus incompletely captured a mass in the left paratracheal region, extending into the lumen of the trachea. Patient was then transferred to University Hospital for further evaluation. Dedicated neck imaging confirmed 4.6cm mass in expected area of thyroid gland, invading into left tracheal wall, cervical esophagus, and hypopharynx. Additional imaging revealed numerous pulmonary nodules, and a 4mm enhancing focus of left superior temporal gyrus. Nuclear positron emission tomography imaging revealed regions of hypermetabolic activity in the left maxillary sinus, the facial nodules, cervical lymph nodes, and mass like region of hypermetabolic activity in the thyroid bed. Biopsy confirmed follicular thyroid parenchyma, concerning for follicular carcinoma. Patient then underwent mass resection and tracheostomy. Some thyroid tissue was left on contralateral side to malignancy due to adjacency to only functional recurrent laryngeal nerve. Pathology following surgery confirmed follicular thyroid carcinoma, with evidence of angioinvasion. Thyroglobulin mass spectrometry prior to surgery was 302 ng/mL. Conclusion: While it is well known that patients with XP suffer from early development of mucocutaneous and ocular cancers in sun-exposed areas, these patients also have increased risk for multinodular goiter as well as internal malignancies. Furthermore, treatment of any internal malignancy is limited due to inability for patients with XP to be treated with radiation. Providers for patients with XP should have very low thresholds to investigate all new symptoms aggressively, maximizing chances of diagnosing malignancies in early stages.
Zebra Case of Papillary Thyroid Cancer in MEN-2 Syndrome
Authors: Gaballa Salem
Published: May 2021

Introduction: The occurrence of papillary thyroid cancer in patients with familial medullary thyroid cancer (FMTC) is extremely rare and underreported. Case Presentation: A 51-year-old caucasian female with no past medical history who presented to primary care physician for her annual visit. She denied any complaints. Vital signs were unremarkable. Physical examination was remarkable for large left thyroid nodule without cervical lymph nodes enlargements. Family history was significant for metastatic MTC of her two sisters (at the age of 55, 60) and her niece at age of 21. She previously declined genetic testing. Labs were unremarkable including serum calcium of 8.3 mg/dL. Thyroid function panel revealed a TSH of 2.1 μU/mL, Free T4 of 1.4 ng/dL, Thyroid peroxidase (TPO) antibody of <6 IU/mL. Neck ultrasonography revealed a mid-left thyroid hypoechoic nodule of 1.8 ×1.5 cm, without cervical lymph nodes enlargements. Fine needle biopsy revealed a papillary thyroid cancer, follicular variant. The diagnosis confirmed by two university pathologists, without any evidence of MTC. Genetic testing revealed a germline mutation in RET oncogene exons 13. Further labs revealed normal metanephrines of 12 pg/mL and normal normetanephrine of 31 pg/mL, normal serum calcitonin was less than 2 pg/mL (0-5), normal serum CEA was 2.5 ng/mL (0-5), elevated anti- thyroglobulin (anti-TG) antibodies of 1234 iu/mL (0-0.9), and elevated thyroglobulin of 50 ng/mL (1.5-38.5). The patient was referred to ENT for total thyroidectomy. Further, she was treated with radioactive iodine ablation by 155 mCi of iodine 131. Follow up whole body thyroid scan revealed no evidence of residual or recurrence. The patient was treated with 112 mcg levothyroxine with a target of TSH less than 0.1. On six months follow up, repeated neck ultrasonography revealed no remnant of thyroid tissue. Follow up Thyroglobulin (TG) was less than 0.1 ng/mL, TSH 0.05 μU/mL, FT4 of 1.98 ng/dL, and calcitonin was still less than 2 pg/ml. Genetic testing of her daughters (24, 31) revealed germline mutations in RET-oncogene exons 13 and was referred for prophylactic thyroidectomy. Discussion: FMTC is an inherited syndrome characterized by the presence of only MTC without hyperparathyroidism or pheochromocytoma and is considered a variant of MEN2A. Most cases of MEN2A have been attributed to mutations in the intracellular portion of RET, and somatic mutations in RET have been identified in 50% of cases of sporadic FMTC. We recommend in patients with germline RET mutations and a family history of MTC, the diagnosis of papillary thyroid cancer should be confirmed by two pathologists, and patients should be tested for serum calcitonin, serum calcium, and metanephrines/normetanephrine levels. Genetic testing of first-degree relatives of FMTC at an early age is essential in guiding major management decisions such as the timing of prophylactic thyroidectomy.
A Case Report on Methimazole-Induced Cholestatic Jaundice in an Elderly Man With Hyperthyroidism
Authors: Ng Jennifer Lourdes , Ramos Celeste Ong
Published: May 2021

Background: The early detection and diagnosis of the causes of jaundice in a hyperthyroid patient taking antithyroid medications are paramount for the appropriate management of these patients. Clinical Case: A 72 year old male is admitted due to septic shock secondary to pneumonia and funguria, acute kidney injury secondary to sepsis, type 2 diabetes mellitus, uncontrolled and Graves’ disease with thyroid nodules (Tirads 4). On physical examination, he has icteresia and generalized jaundice. Methimazole was started 12 days ago. Initial tests were consistent with a cholestatic pattern of jaundice: slightly elevated alanine aminotransferase 70 U/L (16-63), aspartate aminotransferase 84 U/L (15-37) and significantly elevated alkaline phosphatase 662 U/L (46-116), total bilirubin 12.16 mg/dl (0.20-1.0), conjugated bilirubin 11.29 mg/dl (0-0.20) and unconjugated bilirubin 0.87 mg/dl (0-0.80). He has hypoalbuminemia and normal prothrombin time. He has negative anti-Smith antibody, anti-ribonucleoprotein, anti-mitochondrial antibody, and positive anti-nuclear antibody 1:160 speckled pattern. Hepatitis Profile showed chronic hepatitis A infection. Upper Abdomen Ultrasound showed ill-defined border in the left hepatic lobe; intrahepatic ducts and common bile duct are not dilated; gallbladder is contracted with no evident intraluminal echoes. Whole Abdomen with 4-phase Dynamic Liver CT Scan showed multiple ill-defined hypoattenuating lesions in the entire liver parenchyma; intrahepatic ducts, common bile duct, and pancreatic duct are not dilated; and gallbladder is normal in size without intraluminal calculus with possible metastases at spleen, left adrenal gland and tail of pancreas. He has normal AFP and elevated CEA. Methimazole was discontinued at admission and was started on Hydrocortisone 100 mg/IV every 8 hrs. Repeat liver profile panel showed decreasing trends after 4 days of holding methimazole. Repeat fT4 after 6 days of high dose hydrocortisone showed a decrease from 3.09 ng/dl to 1.98 ng/dl (0.89-1.76). Hydrocortisone was continued and tapered accordingly. Plans for RAI discussed. Conclusion: This case emphasizes the need to be vigilant for the very rare but serious adverse events of antithyroid medications.
A Million Reasons for Hyperthyroidism. Reporting a Case of Thyrotoxicosis in a Setting of Metastatic Choriocarcinoma
Authors: Ahmed Ali Samim , Siraj Elias Said
Published: May 2021

Background: Human chorionic gonadotropin (hCG) induced transient hyperthyroidism is often seen during pregnancy. Other rare causes of beta hCG induced hyperthyroidism include trophoblastic tumors (hydatidiform mole and choriocarcinoma) and in men, germ cell tumors. The mechanism for hCG induced thyrotoxicosis lies in the structural similarity between TSH and hCG molecules leading to the direct stimulation of the TSH receptors. In regard to treatment, while gestational thyrotoxicosis is usually mild, self-limited and does not need medications, the hyperthyroidism of trophoblastic tumors may require antithyroid medications in addition to treating the underlying tumor. Thionamide use is reserved for moderate to severe cases of hyperthyroidism and for presurgical optimization. In our case report, we present a 22-year-old African American female with choriocarcinoma induced thyrotoxicosis requiring thionamide therapy. Clinical Case: A 22-year-old African American female presented to our emergency room after a witnessed generalized tonic-clonic seizure. Her brain CT scan showed a 4 CM mass concerning for AVM malformation with a subsequent brain MRI confirming parenchymal hematoma with surrounding vasogenic edema. Past medical history was significant for molar pregnancy managed with dilation and curettage followed by laparotomy to remove the pelvic mass. Given her history of molar pregnancy, pelvic ultrasound was performed which showed complex heterologous structure of uterine origin concerning for malignancy. Additional imaging studies of the lung, brain, abdomen and pelvis were performed, which showed possible metastasis to the lung, adnexa, and to the brain. Her clinical exam showed heart rate of 130 beats/min with a normal rhythm, fine tremors, aphasia, and a decrease grip strength in her right upper extremity. Her thyroid gland was slightly enlarged with no tenderness. Laboratory tests showed hCG of >1,000,000 mIU/mL, TSH of < 0.01mcU/mL, free T4 of 5.1ng/dL. Her TPO and TSI were negative. With a diagnosis of hyperthyroidism due to trophoblastic disease, she was treated with methimazole and propranolol resulting in rapid clinical and biochemical improvement. Later, left frontal craniotomy and hematoma evacuation was performed with histology confirming the diagnosis of metastatic choriocarcinoma. She was later transferred to a specialized center where she received chemotherapy. Her hCG subsequently dropped down to 699 mIU/mL. Conclusion: We report a rare case of metastatic choriocarcinoma causing symptomatic hyperthyroidism. The diagnosis is made by excluding other common causes of hyperthyroidism and it should be considered in females of childbearing age. Methimazole is an effective agent to control the hyperthyroidism while waiting for treatment of the underlying cancer.
A Rapidly Enlarging Thyroid Nodule- Aspergillus Abscess
Authors: Sheu Ivana , Idriss Almoatazbellah M
Published: May 2021

Introduction: Acute suppurative thyroiditis is a rare thyroid disorder with high mortality often due to bacterial or fungal infection. Here we present a case of a rapidly enlarging thyroid nodule in the setting of disseminated aspergillosis.

Case: A 31 year old female with lupus on immunosuppressants first presented with weakness to the emergency department with workup finding multiple pulmonary, intracranial and vertebral lesions and a left thyroid nodule. On thyroid ultrasound the nodule was solid, hypoechoic, 1.5x2.3x2.7cm with irregular margins and no echogenic foci. Thyroid function tests: Total T3 52ng/dL (80-210ng/dL), Free T4 2.26ng/dL (0.6-1.12ng/dL), TSH 0.015µIU/mL (0.45-4.12µIU/mL). The patient was started on voriconazole for disseminated aspergillosis with plan for outpatient thyroid workup. However with further brain lesion growth, the patient was readmitted with incidental finding of thyroid nodule developing into a multiloculated, septated, fluid filled 5x2.9x4cm lesion after 3 months. Fine needle aspiration of the thyroid lesion resulted in negative bacterial and fungal cultures, no malignant cells, positive fungal elements consistent with aspergillus on cytology. The patient was continued on antifungal therapy (switched to cresemba due to voriconazole side effects) with thyroid lesion regression to 2.4x0.6x1.3cm at 6 months and 1.8x1.1x1.6cm at 12 months. Her thyroid function test normalized ~ 1 month after initial set of labs and the patient remained clinically euthyroid throughout her course.

Discussion: Thyroid infections are limited due to the thyroid’s high iodine content, capsular encasement and rich vascularity. Acute suppurative thyroiditis (AST) due to aspergillus is a rare finding that can present solo or as a part of disseminated infection especially in immunocompromised individuals. Early presentation is often asymptomatic with possible thyroid function test abnormalities that self resolve in a couple weeks. Occasionally patients present with obstructive symptoms or findings of thyroid storm. Diagnosis is done through fine needle aspiration or autopsy, with treatment options including surgery, antifungals or both. Due to the high mortality of fungal AST, with improved outcomes with early diagnosis, it is important to consider AST as a part of the differential diagnosis in immunocompromised patients with systemic illness.
Alemtuzumab-Induced Hypothyroidism Presenting in Pregnancy - the First 2 Reported Cases
Authors: Scott Rebecca , Cornish Emily , Williams Daivd
Published: May 2021

Introduction: Alemtuzumab is a monoclonal antibody that improves outcomes in patients with relapsing-remitting multiple sclerosis. It binds to CD52 and causes a profound depletion of B and T lymphocytes. Autoreactive T cells often form as the immune system repopulates, causing autoimmune thyroid dysfunction in approximately 35% of patients. Alemtuzumab has been associated with new-onset hyperthyroidism during a subsequent pregnancy. Here, we present the first two cases of alemtuzumab-induced hypothyroidism diagnosed in pregnancy. Diagnosing and treating de novo thyroid dysfunction in pregnancy is essential for optimal fetal development and maternal wellbeing.

Clinical Cases: Case A: A 28-year-old woman conceived 26 months after alemtuzumab therapy. Prior to pregnancy, routine TFTs showed euthyroidism. At 17 weeks’ gestation she presented with fatigue, and blood tests confirmed overt hypothyroidism (TSH >100mIU/L (<4IU/L), fT4 3.7pmol/L (9-15pmol/L)). TRABs were positive. She was treated with levothyroxine, and TFTs normalised by 38 weeks’ gestation. Serial fetal ultrasounds showed constant growth velocity and no fetal goitre or tachycardia. The baby was born at term with birthweight on the 30th centile. On day 5 postpartum, the baby had a normal TSH of 3.1mIU/l (0.27-4.20mIU/l) but elevated fT4 of 31.5pmol/L (12-22pmol/L), which fell spontaneously to 22.0pmol/L by day 11.

Case B: A 37-year-old woman conceived 19 months after alemtuzumab therapy. Prior to pregnancy, routine TFTs had been within normal limits. However at 5 weeks’ gestation, blood tests showed overt hypothyroidism (TSH 47.9mIU/L (<4iU/L)), fT4 8.8pmol/l (10-16pmol/L)). Her only symptom was fatigue. TRABs were elevated. She was treated with levothyroxine, and TFTs normalised by 16 weeks’ gestation. Serial fetal ultrasound scans showed constant growth velocity and no fetal goitre or tachycardia. The baby was born at term with birthweight on the 25th centile. On day 1 postpartum, the baby had a normal fT4 (16.5pmol/l)but elevated TSH 13.02mIU/L, which normalised spontaneously by day 11 tp 1/64mIU/l.

Conclusion: To optimise pregnancy outcomes, we recommend that women previously treated with alemtuzumab should be screened monthly for thyroid dysfunction during a subsequent pregnancy. The neonatal team should be alert to transient neonatal thyroid dysfunction, which, like spontaneous alloimmune neonatal thyroid disease, appears to settle spontaneously. References: Garrahy et al. JCEM, 2019, 104 (9), 3624-3625Thakar et al. JCEM 2019, 104 (9), 3626-3627
An Unusual Cause of Thyrotoxicosis and Gynacomastia
Authors: McDonnell Tara Muire , Donald Darran Mc , Behan Lucy-Ann , Gibney James
Published: May 2021

We describe the case of a 24 year old man with metastatic non-seminomatous germ cell tumour who presented with hyperthyroidism and gynaecomastia associated with elevated human chorionic gonadotrophin(HCG). Following a 3 month history of gynaecomastia, flank pain, nausea and 7kg weight loss, the patient attended the emergency department with persistent vomiting. Initial laboratory investigations reported TSH <0.05mU/L (normal range 0.3-4.3) and free T4 29.5pmol/L (12-22), TPO antibodies negative, FSH <1 and LH 1 U/l, testosterone >52 nmol/L (9-29.0), bioactive prolactin 1048mU/L (63-245), SHBG 110.6 nmol/l (18.3-54.1), and oestradiol 3935pmol/L (<223). Clinical examination revealed bilateral tender gynaecomastia and supraclavicular lymphadenopathy. Testicular examination identified a left testis irregularity that was confirmed on ultrasound. Chest Radiograph revealed multiple bilateral opacities measuring up to 6 cm. Initial urine HCG was negative when tested on two occasions; however given suspicion for a HCG-secreting tumour, serum HCG was measured and reported as 503,944 IU/ml (<5) and AFP 17.6 IU/ml (0-5.0). The negative urine HCG is believed to be due to “hook effect”. CT revealed bulky retroperitoneal lymphadenopathy measuring 13 cm consistent with metastatic spread from the non-seminamatous germ cell tumour of testicular origin. Up front chemotherapy protocol with 4 cycles cisplatin based therapy was initiated given his disease burden and degree of symptoms. Radical orchidectomy was deferred until after chemotherapy - at which time germ cell tumour was only identified on immunohistochemistry staining. Over the 2 months following chemotherapy, all endocrinopathies resolved with corresponding reduction of HCG to 65.0 IU/ml. Symptoms of hyperthyroidism abated with treatment and his TFTs were biochemical normal. Oestrogen level also normalised with treatment. HCG-induced hyperthyroidism is a rare cause of hyperthyroidism. Endocrine manifestations occur in <5% germ cell tumour presentation but should be considered particularly when multiple endocrine abnormalities are present.
COVID-19 Induced Myxedema Madness
Authors: Tal Noa , Veriker Robbie , Averbukh Yelena
Published: May 2021

Background: Corona Virus Disease 2019 (COVID-19) pandemic was first reported in December 31st, 2019 in Wuhan, China. The clinical presentation is variable, including a variety of neuropsychiatric related symptoms. Myxedema Madness is a rare and severe neuropsychiatric complication of hypothyroidism manifested as psychosis.

Case Presentation: A 25-year-old female with past medical history significant for treated Papillary Thyroid Cancer, presented with near syncopal event associated with weakness, lower extremity swelling, constipation, cold intolerance and dry skin. The patient was not compliant with her thyroid replacement therapy. Upon collateral history taken from the patient’s mother; the patient became dysphoric and tearful. On examination, patient had slightly decreased blood pressure and non-pitting edema on lower extremities. On neurological evaluation she exhibited forgetfulness and retardation of speech and motoric activity. Lab was remarkable for TSH greater than 100 uU/mL (reference range 0.30-4.20 uU/mL), FT4 0.4 ng/dL (reference range 0.6-1.5 ng/dL), and FT3 0.7 pg/mL (reference range 2.3-4.2 pg/mL). Patient tested negative for COVID-19 PCR. She was started on her home dose of Levothyroxine 150 mcg daily. Patient was discharged home after she was assessed by a psychiatrist, with no further interventions. Three days later, the patient was readmitted for confusion, disorientation and memory loss. Patient was found to be positive for COVID-19 PCR and negative for SARS-CoV-2 antibodies. She was found to be disoriented with paranoid delusions. Laboratory studies showed negative urine drug screen, syphilis and NMDA antibodies. CSF analysis were within normal ranges. Brain Magnetic resonance imaging was only positive for pituitary hyperplasia. Patient was started on T4 and T3 replacement therapy (Levothyroxine 50 mcq Intravenous, Liothyronine 5 mcg daily orally, respectively) followed by Risperdal 1 mg nightly. After

significant improvement in her mood and delusions, patient was discharged home on Levothyroxine 150 mg daily and Risperdal 1mg for two weeks. Patient and family members were counseled on medications compliance. In a two-week follow-up visit, patient reported to be compliant with medications and improvement of mood. She denied hallucination or delusions. Her lab work was significant for TSH 5.57 uU/mL, FT4 1.3 ng/dL and FT3 3.2 pg/mL.

Conclusion: Both psychosis secondary to COVID-19 and Myxedema Madness are rare conditions. Appropriate and timely supplementation of thyroid hormone facilitated speedy return of patient’s cognitive and psychiatric functions to appropriate baseline. This case report may increase physician’s awareness for potentially increased susceptibility of patients with severe hypothyroidism to neuropsychiatric manifestations of COVID-19.
COVID19 Associated Painful Subacute Thyroiditis
Authors: Bhargava Pooja , Steenkamp Devin Warren
Published: May 2021

Objective: Physicians should be aware that thyroiditis is a potential sequela of COVID-19 infection. Discussion: A 49-year-old female without any prior history of thyroid dysfunction presented with clinical and biochemical hyperthyroidism after a diagnosis of COVID-19 illness four months ago. At the time of thyroiditis diagnosis: free T4 was 1.52 ng/dL (normal, 0.76-1.46 ng/dL), TSH <0.005 uIU/mL (normal, 0.358-3.74 uIU/mL), Thyroglobulin antibodies 2 IU/mL (normal, <=1 IU/mL), TPO antibody 1 IU/mL (normal, <9 IU/mL), ESR 5 mm/hr (normal, 0-20 mm/hr). Thyroid US showed no nodules or evidence of autoimmune thyroid disease or abnormal vascular flow. A radioactive iodine uptake test was performed through the primary care office. The test demonstrated symmetric, uniform radiotracer uptake in the right and left lobe. 24-hour uptake was low at 0.1% (normal 15-25%) indicating thyroiditis. Patient features consistent with the diagnosis of subacute thyroiditis include suppressed TSH, diffuse tenderness on thyroid palpation, absent TPO/TG antibodies, and suppressed I-123 RAI uptake (<1%) on 24-hour scan. Conclusion: There is limited data surrounding thyroid disease and COVID-19. It has been suggested that a possible sequela of COVID-19 is thyroiditis. Physicians caring for recovering COVID-19 patients should be aware of possible painful subacute thyroiditis and to check thyroid studies in persons with symptoms of thyrotoxicosis post-COVID-19.
Discordant Thyroid Function Tests in Patients With HIV: A Case Report and Discussion of Diagnostic Approach
Authors: de Souza Tamara Gizelle , Hannoush Zeina Carolina
Published: May 2021

Background: TFT patterns correlate directly with clinical symptoms in most patients with thyroid disease. However, some patients have TFTs which are at odds to clinical findings, posing a diagnostic challenge. Such cases warrant careful evaluation with a structured, rational approach to avoid misdiagnosis and mistreatment.

Clinical Case: A 48-year-old female liver transplant recipient with HIV presented with an asymptomatic multinodular goiter, low TSH and low/normal fT4. Her medications were nadolol, Bactrim, ursodiol, azithromycin, tacrolimus, efavirenz, emtricitabine, tenofovir and zolpidem. Thyroid US showed 3 dominant nodules with benign pathology on FNA. Uptake scan showed diffuse increased uptake consistent with Grave’s disease. She tried MMI for one year, then opted for RAI ablation and was started on LT4 with titration of dose. fT4 remained low/normal regardless of receiving LT4, MMI or no therapy over the following eight years. TSH was appropriately suppressed from 1.42 to 0.160 (0.45 - 4.500 mIU/L) when LT4 weekly dose was increased from 175 mcg to 350 mcg. On lower dose LT4 (150 mcg to 250 mcg weekly) her fT4 stayed low, 0.50 - 0.74 (0.82 - 1.777mg/dL) with normal TSH of 0.73 - 1.42. She remained clinically euthyroid throughout. Serial yearly thyroid US showed no significant change. Pituitary hormonal work-up (IGF-1, FSH, LH, ACTH, estradiol and cortisol) was appropriate for age. fT4 by direct dialysis assay was low with normal TSH. tT4, T3 uptake, rT3, TBG and TPO Ab were normal. HAMA antibodies were negative. LT4 was stopped and she remains clinically euthyroid with low fT4 0.56 and normal TSH 1.73.

Conclusion: The pattern of low fT4 with normal TSH is uncommon. Potential causes that were systematically evaluated include non-thyroidal illness, central hypothyroidism and assay interference. Normal pituitary function and appropriate TSH suppression while on LT4 ruled out central hypothyroidism. Her overall profile suggested fT4 assay interference. Commonly known interference factors were ruled out; biotin, HAMA Ab, pregnancy, renal failure, TBG excess, familial dysalbuminemic hyperthyroxiemia and trans-thyretin-associated hyperthyroxidemia. Direct dialysis is the gold standard fT4 assay but does not detect agents displacing T4 from TBG. It is less commonly recognized that low fT4 with normal TSH has been described amongst clinically euthyroid persons with HIV, at a prevalence of 1.3%–6.8%. Low fT4 is associated with didanosine, stavudine, and ritonavir, but not her anti-virals. The significance of low fT4 in patients with HIV is unclear, because they do not have a higher rate of hypothyroid symptoms. In the absence of clinical hypothyroidism, such as in this patient, LT4 treatment is not recommended. This case uniquely spans eight years and therefore offers valuable insight into the appropriate work-up, management and long-term natural history of low fT4 in persons with HIV.
Factitious Total Triiodothyronine(T3) Elevation in a Euthyroid Patient With Paraproteinemia
Authors: Mandal Kaushik , Asharobi Damilola , Kumar Salini Chellappan , Liao Huijuan , Resenthal David
Published: May 2021

Background: We report a rare case of a patient treated with levothyroxine for hypothyroidism who also had paraproteinemia and was found to have a clinically inconsistent elevation of T3 by RIA. Clinical Case: A 72 Year old African American female with a history of hypothyroidism and IgG kappa Multiple Myeloma (MM) was admitted to the hospital for altered mental status. Her hypothyroidism had been well controlled for years on a stable dose of levothyroxine 0.075mg daily. Review of systems were negative pertinent to thyroid dysfunction. Family history: negative for thyroid disease. On physical exam, an elderly female clinically euthyroid without palpable thyromegaly but was confused and disoriented. Initial Vital signs: BP 117/67, HR 62, RR 14, T 98, SpO2 99% on room air. BMI 19. EKG: normal sinus rhythm, CXR: normal, TSH: 6.27 (0.55-4.78 uIU/mL), total T3: >600 (60-181ng/dL), total T4: 4.5 (3.2-12.6 ug/dL), FT4: 1.22 (0.89-1.76 ng/dL), hemoglobin: 6.6 (12-16 g/dL), hematocrit: 20.9 (38-47 %), Na: 132 (136-145 mmol/L), K: 4.0 (3.5-5.1 mmol/L), Cl: 104 (98-10/ mmol/L), BUN: 45 (20-31 mmol/L), creatinine: 2.8 (0.6-1.0 mg/dL), total protein: 10.1 (5.7-8.2 g/dL), albumin: 1.8 (3.4- 5.0 g/dL), A:G ratio: 0.22 (0.60-1.50 mmol/L). Serum protein electrophoresis revealed Gamma Globulin 5.8 (0.8-1.7 g/dL), Kappa 9270 mg/L (3.3 -19.4 mg/L) Lambda 9.3 (5.7-26.3mg/L), K/L 996.7 (0.26 -1.65), B2 - macroglobulin: 17.9 (ref: 600 with normal reverse T3 21(8-25 ng/dL). Conclusion: Rare cases of factitious elevations of thyroid hormone have been reported in patients with elevated abnormal IgG or IgA proteins having high binding affinity for thyroid hormone.[1] This hypothyroid patient was clinically and biochemically euthyroid except for a dramatic but clinically inconsistent elevated total T3. She also had multiple myeloma with paraproteinemia (IgG Kappa M spike). The few cases reported to date have shown factitious elevation of either or both total T4 and total T3. In our case the factitious elevation was limited to total T3. We alert clinicians to be aware of factitious elevation of thyroid hormones due to high affinity binding to immunoglobulins. In our case this caused spurious elevation of total T3, but not total T4, in a patient with multiple myeloma and an IgG kappa M spike paraprotein. Reference: 1: Marianna Antonopoulou, Arnold Silverberg, “Spurious T3 Thyrotoxicosis Unmasking Multiple Myeloma”, Case Reports in Endocrinology, vol. 2013, Article ID 739302, 3 pages, 2013. https://doi.org/10.1155/2013/739302
Gestational Thyrotoxicosis in a Patient With Hyperemesis Gravidarum
Authors: Alameddine Hind , Palani Gurunanthan , Zekarias Kidmealem
Published: May 2021

Untreated or inadequately treated overt hyperthyroidism in pregnancy can have devastating consequences for both mother and fetus. At the same time antithyroid drugs (ATDs) are known for their teratogenic effect and should be avoid when possible; once the diagnosis of hyperthyroidism is made in a pregnant woman, attention should be focused on determining the etiology of the disorder and whether it warrants treatment. Here, we report a case of hyperemesis gravidarum patient presenting with significant elevation of thyroid hormones and a review on diagnosis and management of gestational transient thyrotoxicosis. A 33-year-old female, G4P3 at 8 weeks pregnant admitted for nausea and vomiting. Thyroid labs showed TSH < 0.01 (Reference: 0.4-4.0mU/L) and free T4 is 3.53 (Reference: 0.76-1.46ng/dl). Patient was discharged on antiemetics with a diagnosis of hyperemesis gravidarum. She was re-admitted at 9 weeks pregnant with ongoing nausea and vomiting. She had palpitations, fatigue and reported 15 pound weight loss in 2 weeks. Past medical history included thyroid hormone abnormality noted during pregnancies of 2011 and 2017. Physical exam was significant for tachycardia and diffusely enlarged thyroid gland. Repeat labs showed TSH <0.01, free T4 5.81, total T3 of 317 (Reference: 60-181ng/dl). Thyroid ultrasound showed multiple nodules. Considering significant elevation in free T4 and total T3; empiric therapy with propylthiouracil was recommended. Patient declined anti-thyroid therapy. TSI and TRH antibodies came back later as negative. Patient was treated with enteral feeding for hyperemesis gravidarum. Thyroid labs 3 weeks later improved; FT4 down to 1.63 and TT3 down to 250. Patient delivered healthy baby at 40 weeks of gestation. Although the differential diagnosis of thyrotoxicosis in pregnancy includes any cause that can be seen in a nonpregnant patient, the most likely causes for hyperthyroidism in pregnancy are gestational thyrotoxicosis (GTT) with or without hyperemesis gravidarum or Graves’ disease. GTT is described as an hCG-mediated hyperthyroidism that occurs in the first trimester of pregnancy; it is generally asymptomatic with mild biochemical hyperthyroidism. Distinguishing true overt hyperthyroidism from GTT in a setting of hyperemesis gravidarum is challenging. The absence of clinical signs of hyperthyroidism and negative thyroid antibodies supports the diagnosis of GTT. T3 tends to be disproportionately elevated more than T4 in patients with overt hyperthyroidism. HCG level has not been found to be useful in distinguishing between GTT and GD. Overt hyperthyroidism is treated using anti-thyroid drugs (ATD) whereas supportive therapy without ATD is the accepted standard of treatment of patients with hyperemesis gravidarum and GTT. More studies addressing the best management of these group of patients is needed.