bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Unusual Case of a Rapidly Enlarging Thyroid Gland in a Patient With Pendred Syndrome
Authors: Maler Neal , Levin Ellis R 
Published: May 2021

Abstract
Pendred syndrome is a genetic condition that is characterized by sensorineural hearing loss, abnormalities of the vestibular system, and goiter. In patients with Pendred syndrome, goiter tends to develop in late childhood or early adulthood and the literature details a progressive enlargement of goiter in these individuals. Here we report the case of a 26 year old female with Pendred syndrome and congenital deafness who presented with a rapidly enlarging thyroid gland over 1 week with associated symptoms of dysphagia, dyspnea, insomnia, and diaphoresis. Thyroid function tests at the time showed no abnormalities. Diagnostic thyroid ultrasound was performed and showed enlarged, multinodular goiter and bilateral thyroid nodules measuring 1.2 cm and 1.1 cm in the right and left thyroid lobe, respectively, with TI-RADS 2 classification. The patient had a thyroid core biopsy performed showing benign appearing thyroid follicles without any evidence of malignancy. After approximately one month following the initial presentation, the patient reported resolution of her goiter and associated symptoms without intervention. To our knowledge, this is the first case in the literature detailing a rapidly enlarging goiter in a patient with Pendred Syndrome, with subsequent resolution of signs and symptoms.
Thyroid Storm Treated With Nonconventional Therapy
Authors: Tashdjian Caroline , Shiu Paul , Kaur Tarandeep 
Published: May 2021

Abstract
Background: Thyroid storm is a rare sequela of thyrotoxicosis with mortality rate of 10-30%. Management of thyroid storm is heavily dependent on thionamides. Cholestyramine and potassium iodide (SSKI) are used as adjunctive therapy and not as the sole treatment for storm. We present a case of thyroid storm treated with cholestyramine and SSKI. Clinical Case: A 45 year old male with past medical history of atrial fibrillation, congestive heart failure, hypertension, substance abuse and grave’s disease presented to the emergency department (ED) for diarrhea. During the course of ED, patient went into atrial fibrillation with rapid ventricular rate. Chest X-ray showed pulmonary edema. Labs were: TSH &lt;0.0025 mIU/L (0.35-4.94 mIU/L) and free T4 3.52 ng/dl (0.7-1.40 ng/dl). Patient was noncompliant with methimazole. Upon admit, ACLS was initiated due to hypoxia and transferred to ICU for ventilator and pressor support. Wartofsky score was 60, suggestive of thyroid storm. Management included methimazole 20mg every 4hours, hydrocortisone 100mg every 8 hours, cholestyramine 4mg every 6 hours, and SSKI 250mg every 6 hours for thyrotoxicosis and amiodarone infusion for afib. Despite normal liver enzymes on admit, day 3 AST increased to 2740 U/L (5-34) and ALT 2684 U/L (0-55). Methimazole was stopped due to potential hepatotoxicity. Day 3 free T4 remained high at 4.16 ng/dl and patient remained critically ill. Plasmapheresis was offered as methimazole was stopped and patient was hemodynamically unstable to undergo surgery. However, family declined this intervention; SSKI and cholestyramine were continued. Free T4 was monitored over the course of treatment; by day 5 free T4 trended down to 1.93 ng/dl. SSKI was eventually stopped on day 8 of treatment as free T4 had normalized and cholestyramine reduced to 4mg twice daily. By day 15, free T4 was 0.8 ng/dl, so cholestyramine was stopped. Due to clinical improvement, patient was weaned off the ventilator and pressor support along with hydrocortisone. Liver enzymes normalized by Day 17. Patient was restarted on methimazole 5mg daily before discharge. Discussion: Thyroid storm is associated with varying degree of liver dysfunction, which can pose a challenge to treatment. In our case, acute fulminant liver failure was multifactorial in the setting of shock, thyroid storm and potential drug toxicity. Thus, thionamides were contraindicated. Radioactive iodine treatment was contraindicated due to use of amiodarone. Plasmapheresis and emergent thyroidectomy could not be done. Thus, nonconventional therapy was used and patient responded well to treatment. This case emphasizes the use of cholestyramine along with SSKI as an effective treatment in patients who are critically ill the setting of a thyroid storm, especially when thionamides are contraindicated and other avenues of treatment are limited.
Thyroid Storm With Concurrent Covid-19 Infection in a Pediatric Patient
Authors: Nicksic Victoria Brocksmith , Logel Santhi , Srinivasan Shardha , Mann Elizabath , Rehm Jennifer Leigh 
Published: May 2021

Abstract
Title: Thyroid Storm with Concurrent COVID-19 Infection in a Pediatric Patient
Background: A 16-year-old boy with recently diagnosed hyperthyroidism developed acute worsening of palpitations, tremor, diaphoresis, and shortness of breath in the setting of COVID-19 infection. There is increasing evidence of a relationship between COVID-19 and thyroid disease possibly due SARS-COV-2 use of ACE2 and the transmembrane protease serine 2 (TMPRSS2), which are highly expressed in the thyroid gland, to infect host cells.1
Clinical Case: Patient was diagnosed with hyperthyroidism after presenting to PCP with tremor, palpitations, and weight loss with a TSH &lt;0.02 mIU/L and FT4 6.86 ng/dL on day 0. No treatment was initiated and he was referred to outpatient endocrinology clinic. On day 2, he developed mild URI symptoms which improved by day 4.
On day 5, he developed acute worsening of tremor, palpitations, and weakness and presented to the ED where he was febrile to 38.4 C, tachycardic to 161 BPM, and hypertensive to 139/91 mmHg. Initial laboratory evaluation was significant for TSH &lt;0.02 mIU/L, FT4 6.64 ng/dL and COVID-19 nucleic acid amplification test positivity. FT3 was &gt;20.0 pg/mL and TRAB was 20.68 IU/L consistent with Graves’ disease. He met diagnostic criteria for thyroid storm with a score of 45 points using the Burch and Wartofsky scoring system based on the presence of thermoregulatory dysfunction (10 points), cardiovascular dysfunction (25 points) and precipitant history (10 points). Patient was admitted to a pediatric ICU and started on methimazole 20 mg every 8 hours, potassium iodide 250 mg every 8 hours, propranolol 40 mg every 8 hours, and hydrocortisone 50 mg every 8 hours with resolution of fever, tachycardia, and hypertension. He was noted to have left ventricular hypertrophy with progressive, asymptomatic ST elevation/nonspecific repolarization changes on electrocardiogram (ECG). Echocardiogram was normal. B-natriuretic peptide and serial troponin were normal. On day 6, inflammatory markers and coagulation studies were reassuring against concurrent multisystem inflammatory syndrome in children. Potassium iodide was discontinued on day 6 and hydrocortisone was discontinued on day 8.
Repolarization abnormalities persisted throughout his admission with appearance of prominent U waves and borderline QT prolongation, however no significant arrhythmias were noted. On day 9 FT4 was 1.99 ng/dL and FT3 was 4.8 pg/mL; he was discharged home in stable condition Conclusion: This is the first reported case of COVID-19 infection as presumed precipitant of thyroid storm in a pediatric patient with cardiac findings.
[1] Scappaticcio, L., Pitoia, F., Esposito, K., Piccardo, A., & Trimboli, P. (2020). Impact of COVID-19 on the thyroid gland: an update. Reviews in endocrine & metabolic disorders, 1–13. Advance online publication. https://doi.org/10.1007/s11154-020-09615-z
Thyroid Storm: A Rare Paraneoplastic Syndrome in an Infant With Hepatoblastoma
Authors: Vyas Neha , Neto Arino , Carakushansky Mauri , Gurnurkar Shilpa 
Published: May 2021

Abstract
Background: Graves disease (GD) is the most common cause of pediatric hyperthyroidism. Thyroid storm (TS) is a rare initial manifestation of GD and is typically triggered by an underlying stressor such as infection, trauma or surgery in a patient with underlying GD and poorly controlled hyperthyroidism. Clinical Case: A previously healthy 21-month-old Hispanic male presented to our ER due to concerns of acute abdominal pain. He was noted to have diffuse abdominal tenderness, unremitting anxiety and mild exophthalmos. Vital signs revealed tachycardia and hypertension. Initial lab evaluation was suggestive of primary hyperthyroidism (TSH&lt;0.02 mcU/mL, n 0.5-4.5 mcU/mL, and free T4 at 5.8 ng/dL, n 0.8-2 ng/dL). His Burch-Wartofsky point scale score was 45, indicating high likelihood of TS. He was aggressively treated with methimazole, potassium iodide and propranolol. Five days later, there was a significant improvement in symptoms and labs (TSH&lt;0.02 mcU/mL, n 0.5-4.5 mcU/mL, and free T4 2.3 ng/dL, n 0.8-2 ng/dL) and he was discharged home on methimazole and propranolol. Interestingly, all thyroid autoantibodies were negative including TSI, TRAb, anti-thyroglobulin and anti-TPO antibodies. His thyroid function continued to improve and propranolol was discontinued. Three weeks after his initial hospital admission, he developed a diffuse urticarial rash and the methimazole was held and propranolol restarted. Within a few days, he developed persistent fevers for which he was readmitted. His
total T4 at that time was elevated at 23 mcg/dL (n 4.5-11 mcg/dL) and because the rash was improving, methimazole was restarted. In the following weeks, the patient continued to have intermittent fevers, diffuse waxing and waning rash, decreased activity, and reduced appetite. He was seen by his pediatrician who noted hepatomegaly. Abdominal CT and ultrasound revealed a liver mass (11 x 10 x 10 cm) and a 7 mm peripherally placed pulmonary nodule in the left lower lobe. The patient was admitted to the hematology/oncology unit for further evaluation. He was found to have an elevated alpha-fetoprotein level (AFP) of 43,051 ng/mL, n&lt;6 ng/mL, which was concerning for hepatoblastoma (HB) that was confirmed by tissue biopsy. He was subsequently initiated on neoadjuvant chemotherapy. Methimazole dose requirements gradually decreased with eventual discontinuation 1 week after initiation of chemotherapy. He has remained clinically euthyroid off methimazole for almost 3 months with normal thyroid function. Conclusion: We report an unusual case of transient hyperthyroidism that initially presented as TS in a 21 month old male who was subsequently diagnosed with HB. Paraneoplastic syndromes (PNS) may occur with any tumor. Hyperthyroidism is occasionally associated with non-seminomatous germ-cell tumors with elevated HCG. We believe this is the first report of pediatric thyroid storm as a PNS in HB.
Thyrotoxic Periodic Paralysis: A Rare Presentation of Graves’ Disease
Authors: Shrestha Bishow Chandra , Sherpa Chheki , Rijal Swarup sharma , Magaji Vasudev , Singh Vinita 
Published: May 2021

Abstract
Background: Thyrotoxic periodic paralysis (TPP) is a rare but serious thyroid emergency characterized by hypokalemia, acute onset flaccid paralysis & thyrotoxicosis. Typically, seen in an Asian male with untreated hyperthyroidism symptoms, who awakens at night or in the early morning with flaccid ascending paralysis. This is precipitated by exercise, alcohol or carbohydrate rich meal. TPP is widely reported & studied in Asian population. Its prevalence is about 2 % in Asian hyperthyroid patients. However, incidence is 0.1-0.2% in non-Asian hyperthyroid patients.
Clinical Case: 33-year-old Caucasian male with celiac disease and no thyroid disease sought emergency care for complaints of sudden onset severe weakness in all extremities. He reported 20-pound unintentional weight loss, intermittent palpitations and low-grade fever. He noticed leg cramps with numbness and unable to move his extremities. At initial evaluation, he had acute flaccid paralysis and tachycardia. Initial laboratory studies showed potassium at 1.9 mmol/l, Magnesium at 1.8, suppressed TSH &lt;0.005 uIU/ml with elevations in free T4 at 2.43 ng/dl and total T3 at 1.9 ng/ml. CT and MRI head were normal. Patient’s aldosterone level was normal. The patient’s paralysis and hypokalemia resolved after potassium replacement. Thyroid stimulating immunoglobulin was elevated and increased vascularity suggestive of Grave’s disease noted on thyroid Ultrasound. Methimazole and propranolol were initiated. His neurological workup was negative. After resolution of paralysis and hypokalemia he was discharged home. Since our patient presented with severe hypokalemia, flaccid paralysis and hyperthyroidism, that resolved promptly with potassium replacement, hence likely diagnosis of thyrotoxic periodic paralysis.
Discussion: Thyrotoxic periodic paralysis is potentially reversible and mostly seen with Graves’ disease among Asian population. Early diagnosis & treatment prevents life threatening complications. Differential diagnosis of TPP includes familial periodic paralysis, Guillain-Barre Syndrome & acute intermittent porphyria. Diagnosis is based on family history, characteristic presentation, hyperthyroidism with low serum potassium level. Possible mechanism is increased sodium-potassium ATPase activity in the skeletal muscle membrane leading to intracellular shift of potassium causing hypokalemia and muscle inexcitability. Treatment includes potassium replacement, nonselective beta-blocker and definitive treatment of hyperthyroidism, to prevent further episodes.
Thyrotoxicosis: A Primary Cause of Arrhythmias and Acute Heart Failure
Authors: Omotosho Yetunde Bernice , Farooqi Aneeba , Bakar Ayla , Jeelani Hafiz 
Published: May 2021

Abstract
Thyrotoxicosis results from excessive thyroid hormone and may occur in Graves’ disease, multinodular goiter, and thyroiditis. The association of hyperthyroidism with the worsening of pre-existing heart disease is very well recognized. Additionally, hyperthyroidism can also cause primary cardiac disease including arrhythmias and congestive heart failure. We present a 65-year-old female with a past medical history of intermittent palpitations who came to the emergency department with shortness of breath and bilateral lower extremity swelling. Physical exam revealed an anxious woman with bilateral proptosis, jugular venous distention, bibasilar crackles, and bilateral lower extremity edema. Laboratory data was significant for a brain natriuretic peptide level of 1,930. Chest x-ray revealed vascular congestion. Transthoracic echocardiogram showed an ejection fraction of 63% and diastolic dysfunction. She was admitted and received diuretics for acute heart failure. She developed atrial fibrillation with a rapid ventricular response, managed with a diltiazem infusion and anticoagulation. This event prompted thyroid evaluation which showed a thyroid-stimulating hormone (TSH) of 0.01mU/L, elevated free T4 at 3.37ng/dl, free T3 at 5.8pg/ml, positive Thyroid-stimulating immunoglobulins (TSI) 473%, and thyroid peroxidase (TPO) antibodies 158U/ml. Her symptoms improved after treatment with methimazole. The heart is susceptible to hyperthyroidism due to multiple thyroid hormone receptors on cardiac myocytes causing high sympathetic stimulation from an increased number of myocardial beta-cell receptors. Atrial fibrillation occurs in 10 to 20% of patients with hyperthyroidism and is prevalent among the elderly population. People 60 years and above with a low serum thyrotropin concentration are at a threefold higher risk of developing atrial fibrillation in the subsequent decade. Complications such as cerebrovascular accidents occur in about 14% of cases. About 6% of thyrotoxic individuals develop heart failure secondary to a tachycardia mediated mechanism, leading to an increased level of cytosolic calcium during diastole. This causes reduced ventricular contractility and diastolic dysfunction, often associated with tricuspid regurgitation. Graves’ disease is an autoimmune process characterized by hyperthyroidism due to circulating autoantibodies. TSI binds to and activates thyrotropin receptors, causing the increased synthesis of thyroid hormones. If left untreated, Graves’ disease can lead to severe thyrotoxicosis. Clinicians should be aware of this disease association and ensure thorough clinical investigation, prompt diagnosis, and treatment of thyrotoxicosis to avert these life-threatening events.
Thyrotropin-Secreting Pituitary Adenoma Successfully Treated With Cabergoline
Authors: Saand Aisha R , Flores Monica , Alqaisi Sura , Lashin Ossama 
Published: May 2021

Abstract
Background: Thyrotropin secreting pituitary adenomas (TSH-oma) account for less than 1% of pituitary adenomas and are a rare cause of hyperthyroidism. In this case, we describe the safe use of cabergoline with the subsequent achievement of euthyroid levels and the resolution of symptoms.
Clinical Case: A 67-year-old female with a presumed history of hypothyroidism for the last 3 years managed with Armour thyroid was referred for fatigue associated with palpitations, intermittent diarrhea, insomnia, and anxiety. Her TSH was noted to be suppressed at that time, and her Amour thyroid was changed to Levothyroxine 25 mcg daily, which was eventually stopped as her symptoms persisted. Follow-up thyroid function tests (TFTs) showed elevated TSH (8.60 µU/mL, reference range 0.340 - 5.600 µU/mL), and elevated free T3 (10.8 pg/mL, reference range 2.7-4.7 pg/mL) and free T4 (2.0 ng/dL, reference range 0.8-1.5 ng/dL) levels. Further laboratory workup including basal prolactin, LH, FSH, hCG α-subunit, IGF-1, and ACTH levels were within the normal range. Physical examination showed diffuse thyroid enlargement. An I-123 thyroid uptake and scan showed uniform uptake throughout the gland with no focal hyperintense areas. A dedicated pituitary MRI was performed and revealed an 8 mm microadenoma in the posterior left adenohypophysis. The patient wanted to avoid any invasive treatment and refused trans-sphenoidal surgery and medical therapy was chosen. Unfortunately, using a somatostatin analog as part of the standard medical treatment was not an option due to the high cost and lack of insurance coverage. For these reasons, a trial of cabergoline was started to suppress TSH secretion. Atenolol 25 mg daily was added temporarily for the management of her sympathetic symptoms. On periodic follow-up, her symptoms gradually subsided, and TFTs remained within normal limits. Treatment was continued for one year.
Conclusion: Clinical manifestations of hyperthyroidism with biochemical evidence of elevated thyroid hormone levels and TSH levels should raise a strong suspicion for central or secondary hyperthyroidism due to TSH secreting pituitary adenoma. Cabergoline might represent an effective alternative form of medical treatment for TSH-oma in certain situations where the first line therapeutic options are refractory, contraindicated, or declined.
Dio2-CreErt2 Knockin Model to Identify T3-Generating Cells That Express Type 2 Deiodinase in Tissues
Authors: Ng Lily , Liu Ye , Liu Hong , Forrest Douglas 
Published: May 2021

Abstract
Background: Thyroid hormone promotes many developmental and homeostatic functions. Apart from adequate circulating levels, the concentration of the active hormone T3 within tissues may be amplified by type 2 deiodinase (Dio2) by conversion from the precursor T4. Dio2 is critical in auditory development, bone maturation, brain function and control of the hypothalamic-pituitary-thyroid axis. Despite its crucial role, an obstacle to studying Dio2 is that the protein has a short half-life, is at low levels and is often transiently expressed, making it difficult to identify Dio2 in tissues at cellular resolution. Methods: We derived a Dio2-CreERt2 knockin mouse that expresses tamoxifen-dependent Cre recombinase from the endogenous Dio2 gene. When crossed onto Ai6 reporter mice, following tamoxifen treatment, Dio2-CreERt2 expression is detected as fluorescent signal in specific cells in brain regions, pituitary, and other tissues. We showed previously that Dio2 is essential for hearing with rising expression levels in the cochlea prior to onset of hearing. The Dio2-CreERt2 model identified positive cell types in the cochlear spiral ligament, septal divisions and modiolus around the sensory epithelium. Dio2-positive fibrocytes were adjacent to and extended projections around blood capillary networks, the source of T4 supply. Transcriptome analysis of isolated positive cells revealed bone lineage-related origins for many of these cells. Conclusion: The Dio2-CreERt2 model detects Dio2 expression sensitively at cellular resolution. In the cochlea, Dio2-positive cell types reside in vascularized support tissues, suggesting combined endocrine and paracrine-like control of the T3 supply. Analysis of cell origins suggests novel interactions between endocrine and skeletal systems in promoting T3 action required for hearing.
The Role of Nuclear Receptor Corepressors NCoR1 and SMRT on Physiologic Function in the Adult Mouse
Authors: Ritter Megan J , Amano Izuki , De Oliveira Lorraine Soares , Vella Kristen R , Hollenberg Anthony Neil 
Published: May 2021

Abstract
Thyroid hormone (TH) plays an essential role in maintaining homeostasis and regulating metabolism in all organ systems beginning with embryogenesis and continuing throughout life. TH action is mediated by the thyroid hormone receptor (TR), which is a nuclear receptor, and it’s coregulators. The nuclear receptor corepressor 1 (NCoR1) and the silencing mediator of retinoid and thyroid hormone receptors (SMRT) are two critical corepressors of the TR that inhibit gene transcription in the absence of TH. Repression is mediated by complexing with histone deacetylase 3 (HDAC3), which is stabilized by NCoR1 and SMRT. NCoR1 and SMRT are critical for maintaining metabolic homeostasis and act to mediate energy expenditure, insulin sensitivity, and body weight. We sought to elucidate the roles of NCoR1 and SMRT in maintaining global physiologic function in the adult mouse. In order to study the post-natal role of these corepressors, we used a tamoxifen-inducible Cre recombinase (UBC-Cre-ERT2) to knock-out (KO) NCoR1, SMRT, or NCoR1 and SMRT together in adult mice because global deletion of either corepressor during embryogenesis is lethal. Mice were injected with tamoxifen at 8 weeks of age to KO either NCoR1 (NCoR1-KO; NKO), SMRT (SMRT-KO; SKO), or both NCoR1 and SMRT (double KO; DKO) and metabolic parameters were analyzed. While postnatal deletion of either NCoR1 or SMRT did not impact mortality, KO of both NCoR1 and SMRT resulted in a rapidly lethal phenotype heralded by weight loss, hypoglycemia and hypothermia. Metabolic phenotyping confirmed a loss of body mass and in particular fat mass in addition to a reduction in energy expenditure and increase in fecal caloric density. Further analysis showed the rapid development of hepatosteatosis and disturbances in lipid metabolism with a profound increase in beta-oxidation. We also found a reduction in HDAC3 protein levels in the DKO mice but no rapidly lethal phenotype in HDAC3 KO mice. Overall, we show that NCoR1 and SMRT together are critical for life as their deletion results in a rapidly lethal phenotype. While NCoR1 and SMRT are required to stabilize the corepressor complex, including HDAC3, HDAC3 KO resulted in a distinct and separate phenotype.