bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Unusual Etiology of Graves’ Disease: Alemtuzumab
Authors: Santiago Carrion Ada Marie , Agosto-Vargas Yanerys 
Published: May 2021

Abstract
Cluster of differentiation 52 (CD-52) is a glycoprotein expressed on the surface of most lymphocytes and it is the most prevalent marker in T cells, B cells, natural killers and monocytes. Alemtuzumab, a CD-52 monoclonal antibody, is one of the initial therapies approved for patients with relapsing-remitting multiple sclerosis. It acts by inducing rapid and prolonged depletion of lymphocytes with a consequent immunosuppression. Although not clearly understood, Alemtuzumab has been associated with the development of autoantibodies. These have been reported to cause thyroid injury resulting in 10-15% incidence of new-onset Graves’ disease.
This is the case of a 38 year-old man with medical history of relapsing-remitting multiple sclerosis who came to the Endocrinology clinic to establish care due to abnormal thyroid function tests. Patient has received Alemtuzumab since the past two years. Three months prior to arrival, he was found with weight loss, hyperdefecation and tremors by his Neurologist. Patient was found with suppressed TSH for which Methimazole was commenced. Thyroid ultrasound showed normal size and homogenous right and left thyroid lobes, and no evidence of cystic or solid masses. Thyroid stimulating immunoglobulins were found elevated which correlated with Graves’ disease. Moreover, thyroid scintigraphy showed 34% radioiodine uptake at 24 hours indicating de novo synthesis of thyroid hormone in this patient with hyperthyroidism. As Alemtuzumab was identified as a precipitating cause of Graves’ disease, therapy was discontinued and plasmapheresis will be given for the treatment of relapsing-remitting multiple sclerosis.
Monoclonal antibody use has increased since the past decades. It has been well described in literature that monoclonal antibodies against programmed cell death receptor 1 (PD-1) and programmed cell death ligand 1 (PD-L1) may cause autoimmune thyroid disease. Nonetheless, it is important to recognize that other monoclonal antibodies may have similar adverse effects. Alemtuzumab is a monoclonal antibody and antineoplastic agent used for relapsing multiple sclerosis, some hematologic malignancies, and as an induction agent for solid organ transplantation. Its main effects include autoimmunity with thyroid being one of the most described targets. In these patients, expert clinicians should recognize the possibility of thyroid disease for prompt treatment which will improve quality of life.
Antineutrophil Cytoplasmic Antibodies in Patients Treated With Methimazole
Authors: Rosario Pedro Weslley , Andrade Gabriela Costa , Maia Flavia Coimbra Pontes 
Published: May 2021

Abstract
Introduction: Antithyroid drugs (ATDs) are widely used for the treatment of hyperthyroidism. Most side effects of these medications are mild and emerge within the first months of treatment. In contrast, antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis is a severe adverse event whose occurrence increases with increasing time of treatment. Vasculitis is more frequently associated with propylthiouracil than with methimazole, but the latter has also been related to the occurrence of ANCA and even to clinically manifest vasculitis. Many patients develop ANCA during treatment with methimazole but do not exhibit signs/symptoms of vasculitis. Objective: We previously reported a relatively high frequency (20%) of ANCA in patients exposed to methimazole but none of them exhibited clinical manifestations of vasculitis on that occasion. We continued to follow up these patients with ANCA and report here their evolution after 2 years. Methods: Seventeen patients exposed to methimazole were followed for 2 years after antibodies detection (ANCA). Results: Eight patients had ANCA but had not used methimazole for at least 6 months. During the following 24 months, continuing without ATD, none of the patients developed clinically apparent vasculitis. In the last assessment, five patients no longer had ANCA, while these antibodies persisted in three. Nine patients had ANCA and had been on methimazole for at least 6 months. The medication was not immediately discontinued in these patients when the antibodies were detected. After this detection, treatment with methimazole was continued in these patients for more 3 months (n = 1), 6 months (n = 2), 9 months (n = 1), 12 months (n = 2), 18 months (n = 2), and 24 months (n = 1). During the 2 years of follow-up after the detection of ANCA, none of the 9 patients developed signs/symptoms of vasculitis. In the last assessment, ANCA were negative in two patients who had received methimazole for more 3 and 6 months and who were therefore without receiving the drug for 21 and 18 months, respectively. The other 7 patients remained ANCA positive. Conclusion: Although vasculitis is necessarily associated with the presence of ANCA, the inverse frequency is undefined and appears to be low. Thus, measurement of ANCA would not be recommended in asymptomatic patients during methimazole treatment and immediate discontinuation of this drug, if these antibodies are detected eventually, may not be required. Reference: Antineutrophil cytoplasmic antibodies in patients treated with methimazole: a prospective Brazilian study. Andrade GC, Maia FCP, Mourão GF, Rosario PW, Calsolari MR. Braz J Otorhinolaryngol. 2019; 85:636-41.
COVID-19 Infection Causing Atypical Thyroiditis
Authors: Katkar Rujuta Baban 
Published: May 2021

Abstract
Introduction: Coronavirus disease 2019 (COVID-19) has caused significant health burden across the world. Identification of factors contributing to severe disease is important to enable stratification of risk, optimize the reallocation of hospital resources, and guide public health recommendations and interventions. Subacute thyroiditis is an inflammatory thyroid disease characterized by neck pain and is usually preceded by an upper respiratory tract infection. It may be caused by a viral infection or a post-viral inflammatory reaction, and many viruses have been linked to the disease. We present case of atypical thyroiditis associated with COVID-19 infection. Case Report: 27-year-old female with no significant past medical history apart from recent COVID-19 infection is referred to endocrinology for evaluation of abnormal thyroid function test. Patient states around three months ago she was experiencing the symptoms like unintentional weight loss, nausea, palpitation, insomnia, anxiety, fatigue similar to symptoms she experienced 9 years ago while she was pregnant with her daughter so she thought she is pregnant again and visited her gynecologist. But patient had pregnancy test was done and she was found to be negative but her thyroid function test showed low TSH 0.32mIU/ml (0.47-4.68mIU/ml). Patient states around same time she was diagnosed with COVID-19 infection and she lost 5 pounds during that time but even after recovery from the infection she continued to lose weight and lost a total of 18 pounds in 3 months. Patient states during the time of COVID-19 infection she was having difficulty swallowing and painful swallowing but following infection patient denied any current difficulty swallowing or breathing, headache, vision changes, cold or heat intolerance, diarrhea or constipation, tremors, proximal muscle weakness, bulging of her eyes. Patient continue to have regular monthly menstrual cycles. Three months following infection patients repeat thyroid function tests were done and it showed normal TSH 0.56mIU/ml(0.47-4.68mIU/ml),free T4 1.05ng/dL(0.78-2.19ng/dL) and negative thyroid antibodies like TSI index&lt;1.0, Thyroid peroxidase Antibodies 1.4 IU/mL, Thyrotropin Receptor Ab &lt;1.00 IU/L. Patient also had normal thyroid ultrasound. Patient had complete resolution of hyperthyroid symptoms and did not require any medications. Conclusion: In conclusion, physicians should be engaged in close monitoring of thyroid disease in patients with suspected COVID-19, for timely detecting signs of disease progression. Finally, the presence of thyroid disease shall be regarded as an important factor in future risk stratification models for COVID-19.
Diagnostic Dilemma: A Case of Undetectable TSH
Authors: Mimms Remy , Sirisena Imali 
Published: May 2021

Abstract
Introduction: Under steady-state conditions, measurement of TSH is accepted as the best assessment of thyroid function. The widely used TSH chemiluminometric assays have very low limits of detection and can help distinguish between the various causes of subnormal TSH. However, when evaluating a patient with abnormal thyroid tests but without thyroid symptoms, an appraisal of the test should be considered.
Clinical Case: A 63-year-old South Asian man was referred to endocrinology for evaluation of a non-detectable TSH (&lt;0.01 µIU/mL) that was reproduced on repeat testing, both using Siemens ADVIA Centaur TSH3-UL immunoassay. The patient was clinically euthyroid and denied taking biotin supplements. Testing of thyroid hormone showed normal values for free T3, total T3, free T4, and total T4. Additional labs included normal studies for free thyroxine by equilibrium dialysis, thyroid stimulating immunoglobulin, and heterophilic antibodies. Thyroid uptake and scan showed uniform uptake of 5.1% and 15.1% at 2-hours and 24-hours, respectively, with no dominant nodules. Hypothalamic-pituitary hormonal testing and MRI pituitary were both normal as well. When TSH testing was repeated on a separate platform, Roche’s eCLIA immunoassay, detectable values were obtained (TSH 6.48 µIU/mL).
Conclusions: Testing of serum TSH by commercially available immunoassays is based on the sandwich method in which one antibody binds to the β-subunit of TSH and the other to the α-β interface. Most assays use monoclonal antibody pairs to achieve high selectivity. Immunoassay tests are prone to interferences, particularly by way of altering the measurable concentration of the analyte or by altering antibody binding (1). In this case, the presence of detectable TSH depended on the platform by which it was measured. This finding suggests a TSH-β variant with impaired immunoreactivity but functionally normal bioactivity. Such a mutation has been previously reported to occur five times more frequently among South Asian individuals than the general population (2). Genetic testing was offered to the patient to confirm this suspicion but was declined.
It is incumbent on the clinician to reconcile a test result that is discordant with the clinical presentation. Having a fundamental understanding of the principles of the testing platform can assist in identifying potential sources of error. Failing to recognize a possible interference can lead to unnecessary healthcare expenditures, misdiagnosis and inappropriate management, potentially at a cost to the patient’s wellbeing. When faced with an undetectable TSH with otherwise normal thyroid hormones and unremarkable clinical picture, it is best to repeat the TSH test using a different available platform.
References: (1)Favresse J et al. Endocr Rev. 2018;39(5):830-850(2)Pappa T et al. Thyroid. 2015 Aug;25(8):869-76
Graves Disease in Infancy
Authors: Beliard Kara A , Shyamkumarb Srinidhi , Yau Mabel , Mintz Cassie , Rapaport Robert 
Published: May 2021

Abstract
Background: Graves disease (GD) is the most common cause of hyperthyroidism worldwide. The usual age of presentation is between 20-30 years, and it is more common in females. Transient hyperthyroidism does occur in infants born to mothers with GD, however, the novo GD in infants is extremely rare. We are aware of only four cases of GD in children under the age of 2 years old previously reported in the literature, with the youngest being of 18 months. Although rare, the complications can be devastating, so identifying and treating GD in infants is vital. We describe an infant who presented at 12 months of life with poor weight gain.
Patient Findings: A 12-month old female patient presented with weight loss, tachycardia, diaphoresis and hypertension. She had a palpable thyroid gland without ocular changes. She was found to have an undetectable Thyroid Stimulating Hormone (TSH) with an elevated free T4 of 2.1 ng/dL (normal 0.80 - 1.50 ng/dL). She was stabilized in the intensive care unit with beta-blocker and methimazole. The diagnosis of GD was subsequently confirmed with an extremely elevated elevated Thyroid Stimulating Immunoglobulins (TSI) titer of 263 Iu/L (normal 0.00-0.55 IU/L), her TSH receptor gene was normal. At 34 months of age, her TSI titer is still elevated at 34 IU/L and she still requires methimazole to maintain a euthyroid state. She is growing and developing appropriately.
Conclusion: To our knowledge, this report describes the youngest child to be diagnosed with GD in the English literature. Only four patients between the ages of 18 - 24 months have been described. Autoimmune diseases are rare in infants, the reason for which GD developed at such a young age remains unclear. Clinical signs and symptoms of hyperthyroidism in infants can be subtle and easily missed: increased growth velocity, failure to gain weight, autonomic changes, and irritability. Most patients have an enlarged thyroid gland, and some have ocular changes. The major long-term complications of undiagnosed hyperthyroidism include craniosynostosis and permanent neurocognitive damage. A high index of suspicion is needed for the recognition and prompt treatment of GD in infants, leading to better clinical outcome.
Significance of Discordant Results: between Confirmatory Tests in Diagnosis of Primary Aldosteronism
Authors: Fukumoto Tazuru , Umakoshi Hironobu , Ogata Masatoshi , Yokomoto-Umakoshi Maki , Matsuda Yayoi , Motoya Misato , Nagata Hiromi , Nakano Yui , Iwahashi Norifusa , Kaneko Hiroki , Wada Norio , Miyazawa Takashi , Sakamoto Ryuichi , Ogawa Yoshihiro 
Published: May 2021

Abstract
Context: Current clinical guidelines recommend confirmation of positive result in at least one confirmatory test in the diagnosis of primary aldosteronism (PA). Clinical implication of multiple confirmatory tests has not been established, especially when patients show discordant results. Objective: The aim of the present study was to explore the role of two confirmatory tests in subtype diagnosis of PA. Design: Retrospective cross-sectional study. Setting: The study was conducted at two referral centers. Participants and Method: We identified 360 hypertensive patients who underwent both captopril challenge test (CCT) and saline infusion test (SIT) and exhibited at least one positive result. Among them, we studied 193 patients with PA whose data were available for subtype diagnosis based on adrenal vein sampling (AVS). Main Outcome Measure: The prevalence of bilateral subtype on AVS according to the results of the confirmatory tests. Results: Of patients studied, 127 were positive for both CCT and SIT (double-positive), while 66 were positive for either CCT or SIT (single-positive) (n = 34 and n = 32, respectively). Altogether, 135 were diagnosed with bilateral subtype on AVS. The single-positive patients had milder clinical features of PA than the double-positive patients. The prevalence of bilateral subtype on AVS was significantly higher in the single-positive patients than in the double-positive patients. (63/66 [95.5%] vs. 72/127 [56.7%], P &lt; 0.01). Several clinical parameters were different between CCT single-positive and SIT single-positive patients. Conclusion: Patients with discordant results between CCT and SIT have a high probability of bilateral subtype of PA on AVS.
Inadvertent Excessive Soy Intake as Part of a Weight Loss Program Leading to Rapid Growth of Multinodular Goiter
Authors: Thrupthi Komandur , Leung Vivien 
Published: May 2021

Abstract
Background: Over the past few decades consumption of soy products has gained popularity in the U.S. in part due to reports of potential health and weight loss benefits. However, concerns have emerged regarding soy as a potential endocrine-disrupting chemical (EDC) leading to thyroid dysfunction amongst other health issues. Studies have shown a potential association of high soy intake with risk of hypothyroidism and simple goiter (1), but less is known regarding its impact on multinodular goiter. Clinical Case: A 33-year-old female originally from Bolivia without significant medical history presented to our endocrine clinic with complaints of right-sided neck swelling. The swelling was insidious in onset, had gradually increased in size over the past 3-4 months, and become uncomfortable. She denied dysphagia, cough, or shortness of breath. Prior to the onset of symptoms, she had enrolled in a commercial weight loss program. The diet program consisted of limiting caloric intake to multiple meal replacement bars during the day followed by a light dinner of fish and non-starchy vegetables. Examination revealed a palpable right-sided thyroid mass and enlarged thyroid gland. Lab work showed normal TSH, fT4, and T3 levels, positive anti-thyroid peroxidase antibody (anti-TPO Ab) 588 (&lt;=35.0 IU/ml), and negative thyroid-stimulating immunoglobulins (TSI). Ultrasound of the thyroid confirmed the presence of a 4 cm dominant right thyroid nodule and multinodular goiter. Subsequent fine-needle aspiration of thyroid nodule was consistent with benign nodular goiter. Upon further investigation, it was discovered that the meal replacement bars contained a significant amount of soy protein resulting in an excessive intake of 20-40 grams of soy protein daily. We discussed treatment options, and the patient declined thyroid surgery in favor of surveillance following discontinuation of the weight loss products. The patient was advised to consume a varied diet and given follow-up appointments for monitoring. Conclusion: Inadvertent excessive soy intake via meal replacement bars may have triggered the rapid growth of a multinodular goiter in our patient despite reported adequate dietary iodine intake. Soy products often contain isoflavones that may exert an adverse effect on the thyroid by inhibition of TPO, disruption of iodine metabolism, and/or estrogenic activity. We advise that caution be exercised with high soy protein consumption especially in patients with underlying risk factors for multinodular goiter. References: Messina, M. and Redmond, G., 2006. Effects of soy protein and soybean isoflavones on thyroid function in healthy adults and hypothyroid patients: a review of the relevant literature. Thyroid, 16(3), pp.249-258.
Iodoral-Induced Iatrogenic Hypothyroidism
Authors: Kwak Leigh , Gruntmanis Ugis , De Castro Alicia , Radovanovic Natasa , Ammana Hima Reddy 
Published: May 2021

Abstract
Background: Iodine is essential for the formation of thyroid hormones. Therefore, the thyroid gland is generally able to maintain normal hormone synthesis despite changes in iodine availability. When there is an increase in iodide load, the thyroid gland is able to inhibit the formation of organic iodide via the Wolff-Chaikoff effect (WCE). This prevents the formation of large quantities of thyroid hormones, thus preventing hyperthyroidism1. Continued exposure to excess iodine is also overcome by the “escape” phenomenon and hormone synthesis resumes in a normal fashion2. However, some patients may lack this autoregulation and develop hypothyroidism. Clinical Case: An 86-year-old male with a history of subclinical hypothyroidism initially presented to his PCP for evaluation of cognitive decline. Workup revealed a TSH of 10 mcIU/mL (0.34 – 5.6 mcIU/mL), a normal FT4 and a negative TPOAb. It was subsequently revealed that the patient was started on Iodoral 12.5 mg daily, an iodine/potassium iodide supplement, 1 month prior to presentation by a naturopathic doctor. Prior to all this, his TSH had always ranged between 4 – 6 mcIU/mL for many years. It was recommended that he discontinue Iodoral and repeat thyroid labs in the future. Despite this, the patient continued on varying doses of Iodoral supplementation. Repeat labs obtained 8 months later revealed an elevated TSH of 99 mcIU/mL and a low FT4 of 0.43 ng/mL (0.6 – 2.6 ng/mL). Despite these numbers, he was asymptomatic and did not exhibit any overt signs of hypothyroidism. He was referred to Endocrinology and finally stopped taking Iodoral.7 weeks post-discontinuation, his repeat labs showed a resolution of hypothyroidism and return to his baseline subclinical disease with a TSH of 8.2 mcIU/mL and a normal FT4. A urine iodine/creatinine was normal at 244.2 ug/g (35 – 540 ug/g) indicating that there was no residual iodine excess from the Iodoral. Conclusion: As far as we are aware, we present the first reported case of Iodoral-induced iatrogenic hypothyroidism. As with past cases of iodine-induced hypothyroidism, our patient had underlying thyroid disease in subclinical hypothyroidism which could explain why he was unable to escape from the WCE. The half-life of Iodoral is unknown but it is generally understood that the effects of iodide are reversed between 2 to 4 weeks after withdrawal. Our patient did not repeat his thyroid function tests until 7 weeks post-discontinuation but did demonstrate a return to baseline with no other intervention. Reference: 1. Markou K, Georgopoulos N, Kyriazopoulou V, Vagenakis AG. Iodine-Induced hypothyroidism. Thyroid. 2001 May;11(5):501-10. doi: 10.1089/105072501300176462. PMID: 11396709.2. Torti JF, Correa R. Potassium Iodide. 2020 Oct 12. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan–. PMID: 31194460.