bluuebunny/crossref_metadata_2025 huggingface dataset:
The Difficulty of Post-Operative Surveillance of Calcitonin Negative Medullary Thyroid Cancer
Authors: Skutnik Emily , Kinney Rachel , Lopes Rebecca , Siu Chun , Magdaleno Angela , Perilli Gretchen
Published: May 2021

Background: As a differentiated thyroid tumor, medullary thyroid cancer (MTC) typically maintains the secretory function of the c-cells with resultant increase in serum calcitonin level along with frequent elevations in serum chromogranin A (CgA) and carcinoembryonic antigen (CEA).

Clinical Presentation: A 71-year-old female with history of multinodular goiter underwent a thyroid nodule biopsy after routine ultrasound surveillance revealed enlargement of two right lower lobe nodules compared with prior imaging. Fine needle aspiration (FNA) of one 3.1 x 1.9 x 2.7 cm right thyroid nodule revealed cellular material composed of spindle-shaped neoplastic cells, some of them with marked cytologic atypia, suspicious for a neuroendocrine tumor, specifically medullary thyroid carcinoma. A PET/CT scan was performed after injection of Gallium-68 dotatate radiotracer and revealed intense focal radiotracer activity in the approximately 2.5 x 2.1 cm right thyroid mid lower pole heterogeneous hypodense mass with tiny calcification inferiorly, consistent with the patient’s known tumor. There was no evidence of cervical octreotate avid metastatic lymphadenopathy and a chest x-ray showed no evidence of active pulmonary disease. The patient subsequently underwent a right partial thyroidectomy with isthmusectomy. Histopathology revealed a 2.8 x 1.9 x 1.9 cm neoplasm composed of spindle and polygonal cells growing in solid nests with neuroendocrine-type nuclei. Immunostains showed the tumor to be positive for AE1-AE3 cytokeratins, chromogranin, synaptophysin and CEA. It was focally positive for TTF-1 and calcitonin. Thyroglobulin and PAX-8 were negative. Using the AJCC 8th edition staging system, the tumor was staged a pT2Nx with margins uninvolved by carcinoma and no extrathyroidal extension or lymphatic invasion. Angioinvasion was present. Additional serum studies included a normal calcitonin value of <2.0 pg/ml (reference range 0-5.1 pg/ml), CEA 2.6 ng/ml (reference range <6.0 ng/ml), and a mildly elevated chromagranin A at 133 ng/ml (reference range 0-95 ng/ml). Plasma metanephrines, normetanephrines, vasoactive peptide, and glucagon levels were all unremarkable. Our patient’s surgical recovery was normal and two months later she remained asymptomatic without evidence of recurrence or metastasis.

Discussion: The diagnosis and post-operative surveillance of medullary thyroid cancer is challenging; even more complicated is the rare case of calcitonin-negative MTC. The cause of calcitonin-negative MTC remains unclear. Further studies are needed for the discovery and development of novel biomarkers for post-operative surveillance and evaluation of clinical relapse.
Will Real Time Visualization of Needle in Target Thyroid Nodules Minimize False Negative FNA Results?
Authors: Sekar Vijaykumar , Panjawatanan Panadeekarn , Syed Sofia Junaid
Published: May 2021

Introduction: Prevalence of thyroid nodules in the adult population based on detection by ultrasonography is about 20-76% of which only 5% account for thyroid cancer. All patients with a suspected thyroid nodule either on physical examination or noted incidentally on other imaging should be evaluated with thyroid ultrasound. Any thyroid nodule >= 1 cm on ultrasound should be investigated with FNAC. Ultrasound guided FNAC techniques are used to reduce false negative results. We present a patient with suspicious finding on initial thyroid ultrasound and subsequent negative FNAC presenting a few years later with papillary thyroid cancer. Case Presentation: A 32 y.o. female with history of thyroid nodule and thyroiditis presented to the endocrine clinic for follow-up of her thyroid nodule. 5 years ago, she was diagnosed with thyroid nodule, which was found on an ultrasound scan for workup of her dysphagia. The thyroid ultrasound then showed diffusely heterogeneous thyroid gland with an ill-defined area of decreased echogenicity in the right lobe and left superior lobe and possible nodule in the lower pole left thyroid. Blood work showed TSH of 1.71 (n 0.34-3.00 uIU/ml) and thyroid peroxidase antibody levels was 27.8 (n < 9.0 IU/ml). A CT scan of neck with contrast was done and no concerning mass was seen. The patient had a follow-up ultrasound after 8 months which showed small bilateral thyroid lesions, somewhat ill-defined. The patient had an FNA biopsy of the right thyroid nodule: the results were consistent with a benign follicular nodule. A follow-up thyroid ultrasound was done in a year, and the findings were unchanged. The patient came back 3 years later for follow-up with complaints of a new palpable nodule in the neck. Ultrasound showed unchanged right thyroid nodule and some new cervical adenopathy. The ultrasound showed a 2.2 cm heterogeneous lymph node with punctate echogenic foci along the right lateral margin of the right internal jugular vein at the level of the thyroid gland, Subsequently FNA biopsy of the right cervical node and right thyroid node were done. The cells from lymph nodes were positive for malignancy and cells from the right thyroid nodule were atypical. Overall the appearance was consistent with papillary thyroid carcinoma. Subsequently the patient underwent total thyroidectomy and right modified lymph node dissection and the pathology results came back as multifocal papillary thyroid cancer right side 1.2 cm and left side 0.4 cm, with metastasis to 2 lymph nodes. Conclusion: The reported false negative rate of ultrasound-guided FNAC is variable. Success of US-FNA depends on experience of operator and cyto-pathologist and the intrinsic nature of the nodule. Malignancy rates of only 1-2% are reported with repeat FNA in prior benign nodules. Good FNA techniques and real-time visualization of needle in target nodules can further decrease false negatives.
“Fueling the Fire” - Irish Sea-Moss Resulting in Jod-Basedow Phenomenon in a Patient With Grave’s Disease
Authors: Khalifa Maram , Aftab Hassaan B , Kantorovich Vitaly
Published: May 2021

Background: Jod-Basedow phenomenon is a rare cause of thyrotoxicosis due to excess iodine intake. Herbal supplements containing sea-moss have high iodine amount which may precipitate thyrotoxicosis in patients with underlying Grave’s disease or autonomous thyroid nodules. Clinical Case: A seemingly healthy 28-year-old female presented to the ED with chief complaint of fatigue with associated anxiety, palpitations and weight loss. On admission her temperature was 100.4 F, pulse 126 bpm and blood pressure 116/56 mmHg. Exam was unremarkable for thyroid goiter or orbitopathy. Labs revealed WBC count 3.4 x103/µL (ref range 4.0-11.0) with neutropenia, hemoglobin 4.3 g/dL (11.7-15.7), platelet 49 x103/µL (150-450). Liver transaminases (AST, ALT, and alkaline phosphatase) were elevated with levels up to 4 times the upper limit of normal. She was diagnosed with hemolytic anemia secondary to severe Vitamin B12 deficiency due to pernicious anemia. TSH was <0.01 mIU/L (0.27-4.20), free T4 2.46 ng/dL (0.8-1.9) and total T3 139 ng/dL (76-181). The patient subsequently endorsed remote history of hyperthyroidism diagnosed 7 years ago however she could not recall the underlying etiology or the name of medication she was treated with. She reportedly stopped this medication after 1 month due to developing goiter. She also endorsed intermittent use of store-bought supplement of Irish sea moss and bladderwrack in last 2 years. Further workup revealed elevated TSI and TBII antibody titers establishing diagnosis of Grave’s disease. Thyroid ultrasound showed normal sized heterogeneous hypervascular gland with no nodules. I-123 thyroid uptake and scan showed diffuse moderately elevated radioiodine uptake of 16.8% and 40.8% at 4 and 24 hours, respectively. Thionamide therapy was withheld due to concern of neutropenia and transaminitis. She was treated with beta-blocker after which her vital signs normalized. Labs 1 week after stopping sea moss showed TSH 0.01 mIU/L and free T4 1.4 ng/dL. Conclusion: Irish sea moss is a readily available herbal supplement with high, variable amounts of iodine. Despite little scientific evidence, it is often marketed to improve goiter amongst other health benefits. The recommended daily iodine intake per the FDA is 150 mcg. Higher amounts are expected to initially cause a short-lived suppression of thyroid function; the Wolff-Chaikoff effect, followed by “escape” and accelerated production of thyroid hormone in abnormal thyroid gland, known as Jod-Basedow phenomenon. In our case, the patient unknowingly worsened her underlying Grave’s disease due to the Jod-Basedow effect. Of note, apparantly she had a longer than expected course of Wolff-Chaikoff effect preceding the thyrotoxic state due to sporadic irregular intake of sea moss. Discontinuing sea moss led to clinical and biochemical improvement of hyperthyroidism without requiring thionamide therapy.
Amiodarone Induced Thyrotoxicosis in the Setting of End Stage Cardiomyopathy
Authors: Anderson Karolina , Baum Howard B A
Published: May 2021

Amiodarone is a class III antiarrhythmic agent which has effects of myocardial depolarization and repolarization. Due to its many side effects including thyroid dysfunction, its use is limited to life-threatening arrhythmias. The thyrotoxicosis can be from the iodine content of amiodarone or its direct toxicity on the thyroid gland. Because of the long half-life, causing amiodarone to have effects for months, medical management can be challenging, and thyroidectomy may be indicated. This is a 76-year-old man with a history of systolic heart failure with reduced ejection fraction (15%), on milrinone after cardiac resynchronization therapy, and recurrent ventricular tachycardia on amiodarone. He was admitted after his ICD device fired. During initial admission, his TSH was <0.015mcunit/mL and FT4 was 2.34ng/dL. Due to concern for amiodarone induced thyrotoxicosis (AIT), he was started on methimazole, prednisone, and cholestyramine. FT4 decreased from 2.34ng/dL to 2.23ng/dL and he discharged on methimazole 30mg daily and prednisone 20mg daily with plans to taper. He was seen outpatient with continued improvement in his FT4 to 2.09ng/dL. He was then seen again and found to have a rising FT4 to 2.22ng/dL and his regimen of prednisone was reinitiated at 10mg daily and methimazole increased to 40mg daily. Despite the medication changes, he continued to have an elevation in his FT4 up to 3.00ng/dL at which point he returned to the hospital for further evaluation and was given methimazole 60mg TID, prednisone 20mg daily, and restarted cholestyramine. With his significant cardiovascular risk, aggressive medical management was attempted prior to surgical evaluation. After his thyroid function failed to respond to medical intervention, multidisciplinary discussion was had with patient, family, and physician teams regarding surgical intervention versus continued long-term monitoring. Family elected to pursue surgery. Thyroidectomy was performed by an experienced endocrine surgeon successfully and his FT4 and T3 decreased appropriately requiring him to be initiated on levothyroxine supplementation. AIT can be separated into Type I, in which there is an increase in synthesis of T4 and T3 with amiodarone providing increasing substrate, and Type II in which there is destructive thyroiditis, releasing excess T4 and T3. In the United States, approximately 5% of individuals who are on amiodarone therapy develop hyperthyroidism, majority being Type II. If possible, amiodarone should be discontinued in Type I AIT, but there is no clear evidence for discontinuation in Type II. Medical management includes thionamides for Type I AIT and glucocorticoids for Type II AIT. Patients who are refractory to drug therapy should be treated with thyroidectomy. The advantages of a surgical procedure

with careful cardiovascular monitoring overall outweigh the morbidity and mortality of uncontrolled thyrotoxicosis.
Amiodarone-Induced Hypothyroidism Initially Presenting as Decompensated Heart Failure and Hyponatremia
Authors: Ayesh Hazem , Burmeister Cameron , Beran Azizullah , Akpunonu Basil
Published: May 2021

Introduction: Amiodarone is an effective antiarrhythmic, but it is associated with altering thyroid function, ranging from thyrotoxicosis to hypothyroidism. In this study, we discuss amiodarone-induced hypothyroidism (AIH) presenting with hyponatremia and myxedema.

Case Presentation: A 75-year-old Caucasian man with a history of ischemic heart disease with an ejection fraction of 55-60% was seen in the ED with complaints of worsening lower limb edema and shortness of breath. Associated symptoms of constipation, generalized weakness, daytime sleepiness, and increased urinary frequency were noted. He was recently diagnosed with atrial fibrillation with a CHA₂DS₂-Vasc score of 5 and started on amiodarone nine months ago. He weighed 235 lbs with a BMI of 33.85 and vital signs are as follows: blood pressure 90/64, heart rate 64, respiration rate 13, and a temperature of 36.6 °C. Physical examination revealed a well-developed man in mild distress and slightly lethargic, with a palpable thyroid gland, heart sounds revealed an irregularly irregular heart rate, elevated JVD, bilateral rales, and bilateral pitting edema. Labs showed mildly low HB of 11.7, low Na of 125 mmol/L, elevated creatinine at 1.67 mg/dl, low urine osmolality at 270 mOsm/kg, and BNP of 24 with negative troponin. Chest x-ray showed cardiomegaly. TSH was elevated at 93 uIU/mL and low free T4 at less than 0.25 ng/dL with a negative anti-TPO. A diagnosis of amiodarone-induced hypothyroidism was made, and the patient was started on increased furosemide and levothyroxine 25 mcg daily. Significant improvement was noted in mental status, sodium level, and volume status within three days; and the patient was discharged home on 50mcg of levothyroxine.

Discussion: This case illustrates the need to constantly investigate the etiology of decompensated heart failure, especially when new medications with potential culprit side effects are noted or suspected. Amiodarone which is helpful in the management of atrial fibrillation has been known to cause thyroid dysfunction as hypo or hyperthyroidism. What is not widely known is that these endocrine dysfunctions can occur just a few weeks after therapy initiation.

Conclusion: We recommend that patients who started on amiodarone be monitored for thyroid dysfunction; especially when they present with deterioration in the cardiac function or show symptoms of endocrinopathy.
Coexistence of Thyroid Hormone Resistance and Autoimmune Thyroid Disease: Not a Mere Coincidence
Authors: Gnanapragasam Helen Prathiba , Idupuganti Amrutha , Bhat Salman Zahoor
Published: May 2021

Introduction: The coexistence of thyroid hormone resistance and autoimmune thyroiditis was initially thought to be a chance event. In a large cohort study, Barcoff et al. demonstrated an increased likelihood of thyroid autoantibodies in patients with thyroid hormone resistance (RTH). We report a unique case to epitomize the coexistence of these two conditions and discuss the postulated mechanisms.

Clinical Case: A 22-year-old woman with a history of Hashimoto’s thyroiditis, attention deficit hyperactivity disorder, and migraine presented to the endocrinology clinic with symptoms of weight loss, fatigue, decreased appetite, and heat intolerance for 4 months. She was diagnosed with Hashimoto’s thyroiditis at age 12 with elevated TSH only and had been on levothyroxine 25 mcg since diagnosis. Physical exam demonstrated a body mass index of 34.14 kg/m2, blood pressure of 138/91 mmHg, pulse of 77 bpm, and an enlarged palpable thyroid gland. Laboratory investigations revealed elevated thyroid peroxidase (TPO) antibody at 234 IU/mL (<9) and thyroglobulin Antibody at 3 IU/mL (<1) with elevated free T4 of 3.76 ng/dL (0.61-1.36), elevated total T4 of 21.58 mcg/dL (6.09-12.23), increased T3 uptake of 51.2% uptake (32-48.4), and upper normal TSH of 3.99 uIU/mL (0.44-5.33). Elevated free T4 was confirmed by the equilibrium dialysis method at 6.2 ng/dL (0.9-2.2) with upper normal TSH at 3.77 uIU/mL. Thyroid ultrasound demonstrated thyromegaly and hypervascularity of the gland. TSH secreting pituitary adenoma was ruled out with a normal alpha subunit of 0.2 ng/ml (0.1-0.6) and molar ratio of the alpha subunit to TSH ratio <1 along with a normal pituitary MRI. She was not taking other medications or supplements. She was diagnosed with thyroid hormone resistance and is undergoing genetic testing to differentiate the THRB genetic mutations from Non-TR-RTH. Her symptoms improved after discontinuing her levothyroxine.

Clinical Lesson: Our case highlights the importance of evaluating thyroid disorders properly before starting treatment and illustrates the coexistence of autoimmune thyroiditis with thyroid hormone resistance. Barcoff et al. demonstrated that there was an increased likelihood of thyroid autoantibodies with odds ratio = 2.36 (p = 0.002) in a large patient cohort with RTH, compared to their unaffected first-degree relatives. However, since there was no correlation in increased antibody with increased age and the duration of the disease, the proposed hypothesis did not substantiate chronic TSH stimulation inducing autoimmune response. The proposed mechanism is that the elevated TSH in RTH stimulates the immune system at the TRα level which was demonstrated in murine models with increased activation of thymic function in correlation with TSH level. More research is needed to understand the underlying mechanism of their coexistence.
How to Stop a Thyroid Storm When the Liver Is Bad: A Case Report and Literature Review
Authors: Saleh Ahmed Osman , Gul Wajiha , Hamad Mohammad Khair Ahmad Ibraheem , Naem Emad
Published: May 2021

Introduction: Patients with thyroid storm and resistance or contraindications to conventional medications may receive plasmapheresis until they have the definitive therapy.

Case Presentation: A 42 years old lady with no past medical history was brought by the EMS with palpitations, shortness of breath, vomiting, and profuse diarrhea. She was found to have an atrial flutter with low blood pressure, received synchronized cardioversion, but unfortunately, she developed ventricular tachycardia, tonic-clonic seizure and went to pulseless electrical activity (PEA). Upon examination, the patient was intubated, heart rate of 200 beats/min, blood pressure of 80/60 on vasopressors. She had exophthalmos and icteric eyes. Neck examination revealed palpable goiter. There was bibasal fine cracked and mild lower limb edema. Laboratory showed FT4 39 (11.6-21.9 pmol/L), FT3 5 (3.7- 6.4 pmol/L), and TSH <0.01 (0.3-4.2 mIU/L). Burch- Wartofsky’s score was 55/140. Her presentation was suggestive of Graves’ disease with thyroid storm. Further labs showed high liver enzymes, high INR, ammonia as well as high creatinine.

She was started on IV hydrocortisone and cholestyramine. Thionamides were contraindicated due to liver impairment.

Extracorporeal membrane oxygenation (ECMO) was initiated for cardiopulmonary support and continued for 6 days. TSH receptor antibodies result was pending, thus a thyroid uptake scan was done while the patient connected to ECMO to confirm the diagnosis. Thyroid scan showed increased uptake suggestive of grave’s disease despite iodine contrast received for CT scan chest two days back. After 5 sessions of plasmapheresis, FT3 2.8, and FT4 30, Lugol’s iodine started and she underwent total thyroidectomy. She was successfully extubated and thyroxine replacement was started after normalization of thyroid hormones

Discussion: The raised liver enzymes (shock liver) were a barrier to thioamides. With the contraindication to antithyroid medications, plasmapheresis was a rapid and safe option before thyroidectomy. The mechanism of plasmapheresis is to eliminate thyroid hormones, TSH-receptor antibodies, and cytokines. The current guidelines lack clear indications, the timing of initiation, and patient selection for plasmapheresis.

Conclusion: Plasmapheresis should be considered as a stabilising measure, especially when patients cannot tolerate conventional medications. Plasmapheresis leads to rapid decline in thyroid hormone levels, providing a window to treat definitively with thyroidectomy.
Improvement of Treatment Resistant Depression in a Patient With Primary Hypothyroidism and Thr92Ala5’ Type 2 Deiodinase Gene Polymorphism With Multiple Daily Doses of Triiodothyronine
Authors: Ahmed Ziyan , Sherin Rinsha P V , Fonseca Tatiana De Lourdes , Hoang Thanh Duc , Shakir Mohamed K M
Published: May 2021

Introduction: The augmentation pharmacologic therapy used in patients with treatment-resistant depression (TRD) includes drugs such as lithium, buspirone, triiodothyronine (LT3) and other drugs. We report a patient with TRD and primary hypothyroidism who responded to a combination of LT3, given in divided doses, and levothyroxine (LT4), rather than LT4 alone, even though the serum TSH levels were in the normal range with these treatments. Interestingly, the patient had a Thr92Ala5’ type 2 deiodinase polymorphism. Case Report: A 54-year old male presented to our emergency room with suicidal ideation 8 years ago. The patient had severe depression and developed uncontrollable urges to surf the internet, generally prohibited sites, approximately 3 months prior to his visit to the emergency room. He had noted a 12-lbs weight gain, cold intolerance, dry skin, and excessive sleepiness for 3 months. Patient was admitted to the psychiatry ward and laboratory testing showed a serum TSH 180 µIU/mL, FT4 0.48 ng/dL, total T3 46 ng/mL, and TPO antibody 278 IU/mL. A thyroid ultrasound was consistent with Hashimoto’s thyroiditis. A diagnosis of major depressive disorder and primary hypothyroidism was made. He was started on citalopram (20 mg/day) and levothyroxine (175 mcg/day). The Beck Depression Scores (BDS) during the initial weeks was 37.5 ± 5.1 (Mean ± SD) (normal 0-9) with corresponding TSH 164 ± 133 µIU/mL, FT4 0.70 ± 0.25 ng/dL, and total T3 61 ± 7.9 ng/mL. Two weeks later the dose of citalopram was increased to 40 mg/day and then buspirone 10 mg/day was added. At the end of 11 months the BDS was 27.81 ± 2.1 with a corresponding TSH 1.5 ± 0.1 µIU/mL. After 4 months, 7.5 mg of aripiprazole was added. After 11 months of treatment, he was treated with a combination of LT4 + LT3 (5 mcg once daily) and TSH became 0.76 ± 0.1 µIU/mL with a corresponding BDS of 18.0 ± 1.9. Twelve months later, the patient was switched back to LT4 alone and during LT4 treatment the BDS score was 24.2 ± 22.2 with a TSH of 1.44 ± 0.11. Nine months later patient was changed to LT4 + LT3 (5 mcg three times daily) and his BDS score was 10.3 ± 1.2 with a TSH of 0.72 ± 0.09 µIU/mL. When he was on LT4 + LT3 TID he was able to discontinue all the antidepressant drugs and he had no urge to surf on internet. His depression was controlled by over-the-counter antidepressant drugs (S-adenosylmethionine and rhodiola). A genetic test confirmed Thr92Ala5’ type 2 deiodinase polymorphism. Discussion and Conclusion: In our patient, there was a good correlation between the BDS improvement and the serum T3 levels (r: -0.7 p-value: 0.01). Thus, in patient with Thr92Ala5’ type 2 deiodinase polymorphism TID T3 dosing may significantly improve depression. Additional studies are needed.
Management of Atrial Flutter in Thyroid Storm
Authors: Lanham Theresa N , Morgan Farah Hena
Published: May 2021

Introduction: Thyroid storm, life-threatening hyperthyroidism, commonly presents with tachyarrhythmias. We present a case of hyperthyroid-induced atrial flutter, refractory to beta-blockade, successfully treated with electrical cardioversion (CV) while biochemically hyperthyroid.

Case Description: A 49-year-old female with history of asthma and no family or personal history of thyroid disease presented with new-onset atrial flutter and heart failure. The patient endorsed weight loss, hot flashes, anxiousness, tremors, and palpitations. She denied gastrointestinal symptoms or visual changes. She was afebrile with normal mentation. Heart rate was found to be 260 beats per minute (bpm) in atrial flutter. Exam demonstrated bilateral lower extremity edema, and profound exophthalmos. Labs were remarkable for thyroid stimulating hormone (TSH) <0.01 [ref: 0.27-4.2] uIU/mL, free T4 4.5 [ref: 0.8-1.8] ng/dL, free T3 15.5 [ref: 2.0-4.4] pg/mL, thyroid stimulating immunoglobulin (TSI) of 379 [ref: <140] % and a thyroid receptor antibody (TRab) of 10.02 [ref:<=2.0] IU/L. White blood cell count and liver function tests were normal. Chest x-ray (CXR) showed bilateral pulmonary edema and ultrasound showed an enlarged heterogeneous hypervascular thyroid gland. The patient was initially started on Methimazole 30 mg daily and Metoprolol 25 mg every six hours but on day two, the patient was transitioned to Propylthiouracil (PTU) 250 mg every 6 hours given continued atrial flutter and concern for thyroid storm given Burch-Wartofsky score was 50. She was also given potassium iodide for three days. Cardioversion was deferred, as it was felt that the severity of thyrotoxicosis would limit success. On day six, TFTs were improved with a free T4 of 2.2, free T3 3.6. On day 8, because of continued tachycardia >130 bpm with limitation of beta-blockade due to hypotension, she underwent a cardioversion which was successful. On discharge, free T4 was 1.7 and she was transitioned to Methimazole 40 mg daily.

Discussion: Thyroid storm has a mortality rate of 10-20%, often related to tachyarrhythmias which can be difficult to treat during a hyperthyroid state. Tachycardia should initially be treated with beta-blockade and antithyroid therapy. Amiodarone is avoided due to concern for worsening hyperthyroidism. A literature review suggests that electrical CV should not be attempted until a patient is euthyroid for four months, as a majority will spontaneously revert once thyroid levels normalize. Conversely, other studies have found that the rate of recurrence of atrial fibrillation between clinically hyperthyroid and euthyroid patients was not statistically significant, suggesting CV should not be delayed until a patient is euthyroid. This suggests that further studies need to be completed to better elucidate appropriate timing in hyperthyroid patient’s refractory to pharmacologic treatment alone.
Stopping Levothyroxine Therapy in Subclinical Hypothyroidism, Perhaps We Could Start a Trend
Authors: Albashaireh Arwa , Maraka Spyridoula
Published: May 2021

Introduction: Subclinical hypothyroidism (SCH) is diagnosed based on elevated thyrotropin (TSH) and normal thyroxine (FT4) levels. Previous guidelines recommended treatment of SCH with levothyroxine (LT4) when TSH is > 10 uIU/mL or if TSH <10 uIU/mL with symptoms suggestive of hypothyroidism, positive thyroperoxidase antibodies (TPO Ab) or evidence/risk factors of cardiovascular disease. There has been an increasing practice of LT4 prescription for SCH, which contributes to making LT4 the second most prescribed drug in the US. Case: This case reviews the course of a patient with SCH treated with LT4. A 68 year old woman with medical history of hyperlipidemia, osteoporosis, and non-toxic multinodular goiter was diagnosed with SCH due to Hashimoto’s thyroiditis based on TSH 9.59 uIU/mL (0.34 - 5.60), FT4 0.66 ng/dL (0.58 - 1.64), and +TPO Ab. The patient had similar thyroid function tests (TFT) 1 year ago. She reported symptoms of hair loss, dry skin, and fatigue. She decided to undergo a trial of LT4 50 mcg daily. Two months later, her TSH had normalized and she reported slight improvement of fatigue. After one year on LT4, the patient reported symptoms of anxiety and heat intolerance and decided to stop LT4. Laboratory work up revealed TSH 0.22 uIU/mL and FT4 1.03 ng/dL consistent with exogenous hyperthyroidism. At the time of her follow up, the patient had been off LT4 for about 3 weeks. She continued to have ongoing fatigue, but reported resolution of the hyperthyroid symptoms. She was advised to stay off LT4 and to have yearly TFT. Discussion This case illustrates that not only LT4 treatment for SCH did not result in apparent improvement of hypothyroid-related symptoms, but also caused iatrogenic hyperthyroidism. A recent meta-analysis of 21 randomized clinical trials including 2192 patients with SCH found that LT4 therapy is not significantly associated with improvement in general quality of life or thyroid-related symptoms. Additionally, there is evidence of potential harm associated with LT4 and added burden of lifelong management. In 2019, a new guideline panel issued a strong recommendation against thyroid hormones in adults with SCH. Patients who are already on LT4 therapy for SCH may benefit from LT4 deprescribing. Clinicians need to discuss with their patients if LT4 discontinuation is a reasonable consideration. Studies at low risk of bias assessing patient important outcomes after LT4 discontinuation are required imminently.
Storm’s a Brewing
Authors: Franquemont Stephanie , William Ronnie , Theckedath Boby
Published: May 2021

Intro: Thyroid storm is an often feared but overall rare complication of untreated hyperthyroidism. This severe presentation of thyrotoxicosis has multiple different treatment modalities with actual treatment directed by the patient’s clinical course. We present the case of a 34-year-old male who presents in thyroid storm. Case: A male presented to the emergency department in southern Arizona in July with complaint of dizziness and tachycardia after working outside in the sun all day. He was rehydrated with symptomatic improvement but had continued tachycardia. The patient refused admission and left the emergency department prior to his thyroid function tests resulting with a TSH of <0.02 and FT4 of 7.43. He had no apparent follow-up or further symptoms until he presented back to the emergency department approximately one year later at age 34. He presented the second time with shortness of breath and palpitations and was found to have atrial fibrillation with rapid ventricular rate >200, a TSH <0.02, and TSH of 6.59. He was tachypneic, but his temperature and blood pressure were within normal limits. He had a CTA of the chest that showed bilateral pulmonary infiltrates. He was started on intravenous metoprolol and diltiazem without resolution of his tachycardia, so an amiodarone drip was started. Hours later, the patient became hemodynamically unstable and went into cardiac arrest. Return of spontaneous circulation was obtained and the patient was intubated with post-arrest cooling protocol initiated. The patient was clinically diagnosed with thyroid storm, which was supported by an elevated Burch-Wartofsky score. Post-arrest treatment of thyroid storm was complicated by acute liver failure, systolic heart failure with ejection fraction <20%, and persistent tachycardia. The patient was treated with high dose methimazole, propranolol, potassium iodine drops, corticosteroids, and cholestyramine. Surgery was considered given the slow progression of medical treatment but no pursued due to cardiovascular risk. Plasmapheresis was considered but not available. The patient’s thyroid function was followed daily and improved over a week despite persistent tachycardia and delirium. Eventually, the patient was discharged home with daily methimazole 20mg and planned outpatient follow-up for definitive therapy. Discussion: This patient presented to the ED with evidence of thyrotoxicosis that was untreated for one year prior to returning with thyroid storm. This illustrates the ability of a young, otherwise healthy patient to compensate for a prolonged period with relatively few symptoms prior to decompensating. This also shows the importance of having a system in place to catch abnormal laboratory results even if the patient is no longer present in the facility; a project has already been completed to catch abnormal thyroid function testing at our facility in the future.
Sub-Acute Thyroiditis Presenting as Pyrexia of Uknown Origin
Authors: Bahl Suhani , Babu Priya Mohan , Capatana Florin , Khan Ishrat , Adlan Mohamed , Premawardhana Lakdasa D K E
Published: May 2021

Introduction: Pyrexia of unknown origin (PUO) is often a diagnostic challenge. Common causes currently reported include non-infectious inflammatory disorders (NIID) (30.6%), infections (23.1%), malignancy (10.7%) and miscellaneous (12.4%). However, 23.1% remain undiagnosed despite extensive investigations. Fever is a component of subacute thyroiditis (SAT) in 28-83% of subjects reported in the literature. But its presentation as a PUO is reported only in a handful of subjects.

Case Presentation: A 71-year-old Asian male presented with evening fevers of 2-3 weeks duration. He had no accompanying sweats, cough, breathlessness, or weight loss. He had a past history of TB, polio, hydatid cyst and hypertension for which he was on treatment. He was a teetotaler. Several family members living in his native land had active TB and he visited them often. Clinical examination at initial presentation was unremarkable. He interrupted investigations to go back to Asia, and became unwell for over 6 weeks with evening fevers and sweating, a weight loss of over 7 kg, and a poor appetite. At this point he had no neck pain, palpitations or bowel abnormalities. Clinical examination continued to be normal upon his return to the UK and in the Endocrine Clinic. Investigations: Investigations were done to exclude (a) infections - There was no growth of pathogenic organisms in repeated blood, urine and sputum cultures. Screening tests for TB, hepatitis, and glandular fever were negative. Blood screens for malarial parasites, amoebic and Brucella serology, and stools examination and culture were also negative. Echocardiography was normal. (b) Malignancy - Urine Bence Jones proteins and serum protein electrophoresis were normal. Bone marrow examination was suggestive of Leishmaniasis but a PCR test excluded this diagnosis. Humoral markers of malignancy were negative. CT scans of the thorax, abdomen and pelvis were normal and did not show any evidence of visceral abnormalities (c) NIID - CRP 120, ESR 130, with blood tests consistent with iron deficiency. Autoimmune screening for dsDNA, ANA, ANCA were negative. Upon return to the UK a PET/CT scan showed the diffuse tracer uptake in both thyroid lobes and changes consistent with a large left lobe. Free thryroxine was 28pmol/l (reference range 9-19.1), and TSH was undetectable (<0.004 mU/l). Thyrotrophin receptor antibodies were negative. Management and conclusion He was given carbimazole initially but this was stopped as he became severely hypothyroid. This hypothyroidism persisted for several months even after stopping carbimazole but reversed spontaneously. He therefore had a biphasic pattern of thyroiditis typical of SAT. There are only 9 previous cases reported of SAT presenting as PUO. Although SAT is a rare cause of PUO, early thyroid testing and if necessary, functional thyroid imaging should be considered in subjects with PUO to confirm it.
The Unusual Case of a Rapidly Enlarging Thyroid Gland in a Patient With Pendred Syndrome
Authors: Maler Neal , Levin Ellis R
Published: May 2021

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

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 <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

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 <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 <0.02 mIU/L, FT4 6.64 ng/dL and COVID-19 nucleic acid amplification test positivity. FT3 was >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

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<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<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<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

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 <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.