bluuebunny/crossref_metadata_2025_split huggingface dataset:
What Lies Beneath? - Medullary Thyroid Cancer in Nodular Graves’ Disease
Authors: Wang Rongzhi , Vallepu Shirisha R , Chen Herbert , Nambron Rajasree 
Published: May 2021

Abstract
Background: Medullary thyroid carcinoma (MTC) accounts for 1%-2% of thyroid cancers in the United States (US). MTC originates from thyroid parafollicular C-cells, occurring either sporadically or hereditarily as part of type 2 multiple endocrine neoplasia (MEN) or familial MTC (FMTC). Hyperthyroidism is prevalent in approximately 1.2%, and Graves’ Disease (GD) is the most common cause of hyperthyroidism in the US. GD is an autoimmune disorder that results in increased thyroid hormone production due to the stimulation of TSH receptor by thyrotropin receptor antibodies (TRAb). Thyroid carcinoma in general is uncommon in GD patients, while MTC is extraordinarily rare. We report a case of sporadic MTC in GD, which is extremely rare. A recent publication stated that there were only 15 reported cases of MTC coexisting in GD until 2019. Clinical Case: A 62-year-old male with hypertension, diabetes and obesity presented to the endocrine surgery clinic with symptoms of diaphoresis, chest pain and fullness, shortness of breath, and palpitations. The patient had a brother with a pancreatic mass of unknown pathology and multiple family members with thyroid disease. On physical exam, there was a palpable non-tender left-sided nodule with no lymphadenopathy. His FT4 was 8.5 (0.76-1.46 ng/dL), TSH was &lt;0.006 (0.36-3.74 μIU/dL) and thyroid-stimulating antibody was 1.25 (&lt;0.10 IU/L). Ultrasound showed a multinodular goitre with a dominant nodule in the left lower pole measuring 2.3x1.9x1.5 cm. He was diagnosed with GD, treated with methimazole, and his symptoms improved. Subsequent nuclear medicine uptake scan showed diffusely increased uptake and a cold nodule in the left thyroid lobe. Repeat labs showed low TSH (&lt;0.01μIU/dL) and elevated FT4, CEA, calcitonin, PTH, metanephrine, and normetanephrine (1.04 ng/dl, 5.2 (3-5 ng/ml), 796 (&lt;18 pg/ml), 58.10 (18.40-88.00 pg/mL), 90 (&lt; OR = 57 pg/ml) and 222 (&lt; OR = 148 pg/ml), respectively). A thyroid fine-needle aspiration (FNA) was suggestive of MTC (Bethesda Category VI). Total thyroidectomy with left central lymph node dissection revealed a 2.5cm MTC confined in the left lobe with focal lymphovascular invasion. His postoperative course was uneventful, and CEA and calcitonin levels trended down (1.1 ng/ml and &lt;2 pg/mL, respectively). Conclusion: The coexistence of medullary thyroid carcinoma and Graves’ Disease is rare, incidental, with five-year survival rates lower than other thyroid cancers. A delayed diagnosis of MTC would be detrimental. Patients with thyroid nodules and GD are five times more likely to be diagnosed with thyroid carcinoma. Radiation, chemotherapy and thyroidectomy are standard treatment options for MTC, with total thyroidectomy being the preferred option. It is necessary to evaluate patients with GD for possible thyroid cancers, especially in the presence of nodules.
A Case for Lithium Pretreatment Prior to Radioactive Iodine Ablation in Grave’s Disease
Authors: Thakkar Aditi , Chen Constance Lee 
Published: May 2021

Abstract
Radioactive iodine ablation (RAIA) therapy with Iodine-131 (I-131) is an established treatment for grave’s thyrotoxicosis. However, there is 10 to 20% chance of treatment failure. Lithium, a drug used to treat bipolar disorder, has significant effects on thyroid function. The most clinically relevant is the inhibition of thyroid hormone release. It is also known to inhibit colloid formation, and is involved in blocking organic iodine as well as thyroid hormone release from the thyroid gland without an effect on radioiodine uptake. This leads to increased radioiodine retention in the thyroid gland. Here, we present a case which exemplifies this action of lithium. A 46 year old male with a history of atrial fibrillation and grave’s disease presented to the endocrine clinic. TSH was &lt;0.01 and FT4 was 36. RAI uptake (RAIU) scan showed diffusely increased uptakes with 4 and 24 hour values of 61.2 and 54.6 %. He subsequently underwent RAI ablation with 18 mCi of I 131. He then presented three years later with persistent hyperthyroid symptoms. TSH &lt;0.01 and FT4 4.3. RAIU showed 24-h thyroid uptake of 41%. Patient opted for a second treatment with RAIA and was treated with 30 millicuries of I 131. He however continued to have clinical and biochemical evidence of thyrotoxicosis and was started on methimazole (MMI). Although he was biochemically euthyroid on MMI, he continued to complain of hyperthyroid symptoms such as palpitations, tremors and weight loss. When methimazole was briefly held six months after initiation, TSH was undetectable and FT4 had increased from 0.83 to 1.42. He subsequently underwent a third RAIU off MMI which showed normal 4 and 24 hour uptake, measuring 15.7% and 28% respectively. Patient subsequently opted for third trial of RAI ablation with lithium pretreatment. He declined surgery. He was started on lithium 900mg/day for 6 days, starting on the day of RAI ablation. He underwent RAI ablation with 45 mCi I-131. Patient tolerated the procedure well with subsequent tests indicating hypothyroidism requiring levothyroxine supplementation. Patient’s hyperthyroid symptoms resolved. Several factors affect the efficacy of radioiodide therapy for hyperthyroidism including the short persistence of radioiodide in the thyroid gland. In hyperthyroid Graves’ patients, radioactive iodide uptake is enhanced due to presence of TSH receptor antibody, however, radioiodide is also rapidly discharged because of its increased turnover. Lithium can significantly reduce the release of iodine from the thyroid gland and thus increase iodine retention. There is evidence to suggest that adjuvant lithium can increase thyroidal radioiodine uptake in patients with a low baseline RAIU (&lt; 30%). This case demonstrate that lithium can be used safely prior to RAI therapy in cases of RAI ablation failure even with low baseline RAIU.
A Case of HCG-Mediated Hyperthyroidism Related to Metastatic Choriocarcinoma
Authors: Sovich Samantha C , Garg Dave K , Yu Run 
Published: May 2021

Abstract
Introduction: We present a clinical case of a non-seminomatous germ cell choriocarcinoma producing human chorionic gonadotrophin (HCG) and inducing hyperthyroidism.
Clinical Case: A 21-year-old male with recently diagnosed metastatic non-seminomatous germ cell choriocarcinoma presented with persistent tachycardia and anxiety. At diagnosis, his β- human chorionic gonadotrophin (β-HCG) was elevated to 6,435 mIU/mL (normal &lt;1 in male) and thyroid-stimulating hormone (TSH) was within normal limits. At presentation, however, his β-HCG increased to 103,229 mIU/mL, TSH was suppressed &lt;0.02 mcIU/mL (normal 0.3-4.7), and free thyroxine was elevated (FT4) 2.6 ng/dL (normal 0.8-1.7). His thyrotoxicosis improved with initiation of methimazole; however, his TSH remained undetectable due to persistently elevated β-HCG levels. His course was complicated by hemorrhagic shock and acute liver injury in the setting of a presumed intraluminal gastric metastasis, necessitating the discontinuation of methimazole. He was continued on steroids to try to minimize T4 to T3 conversion, but ultimately his thyroid hormones uptrended. He became stable enough to tolerate 5 days of chemotherapy, after which his FT4 quickly normalized. Unfortunately, he continued to suffer from vasodilatory shock and ultimately passed away.
Discussion: It has been demonstrated that HCG can bind to the TSH receptor and has thyrotropic activity. The development of hyperthyroidism requires HCG levels &gt;200,000 mIU/mL that are sustained for several weeks (1). It is unknown what the prevalence of hyperthyroidism is in choriocarcinoma, but it has been shown to greatly increase when serum HCG levels are greater than &gt;50,000 mIU/mL (2).
Conclusion: Hyperthyroidism can be difficult to recognize in patients suffering from cancer as many of the typical symptoms can also be seen with active malignancy. Patients with HCG-secreting tumors should be evaluated for hyperthyroidism and may benefit from treatment until the underlying cause can be managed.
References: (1) Hershman, Jerome M. “Physiological and Pathological Aspects of the Effect of Human Chorionic Gonadotropin on the Thyroid.” Best Practice & Research Clinical Endocrinology & Metabolism, Baillière Tindall, 19 May 2004, www.sciencedirect.com/science/article/abs/pii/S1521690X0400020X.(2) Oosting, S F et al. “Prevalence of paraneoplastic hyperthyroidism in patients with metastatic non-seminomatous germ-cell tumors.” Annals of oncology: official journal of the European Society for Medical Oncology vol. 21,1 (2010): 104-8. doi:10.1093/annonc/mdp265
A Case of Thyrotoxic Periodic Paralysis
Authors: Mahali Lakshmi Priyanka , Pechman Amanda 
Published: May 2021

Abstract
Introduction: Thyrotoxic periodic paralysis (TPP) is an uncommon disorder characterized by simultaneous thyrotoxicosis, hypokalemia, and paralysis. It is a rare complication of hyperthyroidism with a prevalence of 1 in 100,000. It has a higher prevalence in young Asian males, with much fewer cases reported in Hispanic patients. The majority of cases are seen in hyperthyroidism due to Grave’s disease, however other causes of thyrotoxicosis have been associated with TPP. Hypokalemia occurs when thyroid hormone stimulates the sodium-potassium-ATP pump by binding to the thyroid response elements upstream of the genes for this pump, increasing its activity and thereby causing a transcellular shift of potassium into the intracellular fluid. Attacks usually begin with proximal muscle weakness of the lower extremities and may progress to tetraplegia, with the degree of muscle weakness corresponding to serum potassium levels. Interestingly, no correlations with serum T3 or T4 levels have been found.
Clinical Case: A 38-year-old Hispanic man with a history of GERD presented to the emergency department with an inability to move his extremities. Initial labs were significant for profound hypokalemia to 2.0 mEq/L (3.5-5) and hyperthyroidism, with TSH&lt;0.05 uU/mL (0.3-4.2) and free T4 2.4 ng/dL (0.6-1.5). Additional workup revealed a positive thyroid stimulating immunoglobulin and a positive thyrotropin binding inhibitor, and thyroid ultrasound demonstrated a hyperemic thyroid with numerous subcentimeter hypoechoic nodules, all of which was suggestive of Grave’s disease. His symptoms resolved with potassium repletion, suggesting thyrotoxic periodic paralysis secondary to hyperthyroidism. Upon further evaluation, the patient endorsed several months of hyperthyroid symptoms such as tremors, heat intolerance, and weight loss. He also endorsed alcohol use, a high carbohydrate diet, and recent life stressors, a combination of which likely precipitated his thyrotoxic periodic paralysis. He was discharged on methimazole 10 mg daily and propranolol 40 mg BID, with a decrease in his free T4 and improvement in his symptoms. He has been educated to avoid alcohol consumption and high-carbohydrate meals to avoid precipitating another episode of periodic paralysis, and once his hyperthyroidism is under better control he plans to undergo radioactive iodine ablation (RAI) for definitive management.
Conclusions: Thyrotoxic periodic paralysis is a rare but dangerous complication of hyperthyroidism, and should be considered in the differential diagnosis when young individuals present with otherwise unexplained hypokalemia and paralysis. Acute management is potassium repletion, long term management involves treatment of thyrotoxicosis and avoiding precipitating factors, and definitive therapy is RAI or thyroidectomy.
A Killian-Jaimeson Diverticulum Masquerading as a Thyroid Nodule
Authors: Patel Reema , Abdulla Maha , Rao Jianyu , Elliot Abemayor , Cheung Dianne 
Published: May 2021

Abstract
Background: A Killian-Jaimeson diverticulum is a rare outpouching in the cervical esophagus, just below the cricopharyngeus muscle, that can be easily mistaken for a thyroid nodule on ultrasonography (1).
Clinical Case: A 65-year-old woman underwent a thyroid ultrasound after her primary care physician noted left-sided thyromegaly. The ultrasound described a 33 mm solid, hypoechoic, wider-than-tall nodule in the left mid gland with an obscured posterior margin as well as macro- and microcalcifications. Given the size and highly suspicious features on ultrasound, she was referred to endocrinology clinic for a fine needle aspiration (FNA). She underwent ultrasound-guided FNA of what appeared to be the previously described thyroid nodule. Surprisingly, the pathology report noted degenerative changes with amorphous debris and possible foreign materials (vegetable or food) without any thyroid tissue. She was sent for an MRI neck, which showed the left neck mass communicating with the esophagus, favoring a left lateral projecting Killian-Jamieson esophageal diverticulum with internal debris. She was referred to head and neck surgery. Given only minimal symptoms of dysphagia, there are no current plans for surgery.
Conclusion: This case illustrates the possibility of mistaking a Killian-Jaimeson diverticulum as a thyroid nodule. Recognition of this rare disease process in the differential diagnosis of thyroid nodules with high risk ultrasound characteristics may prompt more advanced imaging with MRI or CT, and lead to an accurate diagnosis prior to subjecting patients to unnecessary and potentially harmful FNAs (2).
References: (1) Kim HK, Lee JI, Jang HW, et al. Characteristics of Killian-Jamieson diverticula mimicking a thyroid nodule. Head Neck. 2012;34(4):599-603. doi:10.1002/hed.21575. (2) Bonacchi G, Seghieri M, Becciolini M. Killian-Jamieson diverticulum: real-time sonographic findings. J Ultrasound. 2016;19(4):295-298. Published 2016 Apr 21. doi:10.1007/s40477-016-0208-3.
A Rare Phenomenon of Hashimotos Thyroiditis Converting to Graves Disease
Authors: Caseja Ahl Jeffrey , Nakhle Samer 
Published: May 2021

Abstract
Introduction: Hashimotos thyroiditis and Graves disease are two distinct autoimmune disorders of the thyroid. Conversion of hypothyroidism to hyperthyroidism is even more rare. We report a case of an established Hashimotos thyoiditis patient who converted into Graves disease.
Case Description: 67-year old female with a past medical history of iron-deficiency anemia, dyslipidemia, and depression presented with a six-month history of fatigue, cold-intolerance, hair loss, and weight gain in September of 2015. Laboratory tests confirmed diagnosis of Hashimotos thyroiditis with an elevated TSH 80.7 (0.40-4.50 mIU/L), FT4 0.2 (0.8-1.8 ng/dL), and positive thyroid antibodies TPO 24 (0.0-8.9 IU/mL). She was started on Levothyroxine 88 mcg daily. Gradually she had a decreased requirement of Levothyroxine; from February 2016 to March 2017 she maintained a normal TSH range while on 50 mcg/day with resolution of her symptoms.
The patient was then lost to follow-up until she presented in the clinic in September 2018 with complaints of several weeks of easy fatigability, 10lb-weight loss, and periorbital edema. She was found to have a suppressed TSH 0.01, and elevated FT4 2.3, and FT3 8.4 (2.3-4.2 pg/mL). Her Levothyroxine 50 mcg/day was discontinued for four days and labs were repeated which still showed suppressed TSH and elevated FT4 and FT3. She was found to have a positive TRAB and a positive TSI which are consistent with hyperthyroidism. Thyroid ultrasound was performed which showed a heterogeneous thyroid gland with increased vascularity, confirming the diagnosis of Graves disease. She was started on Methimazole 10 mg daily. Her Methimazole dose was adjusted according to her thyroid function test until she had a total thyroidectomy in October 2019. She was started on levothyroxine post-operatively and as of March 2020 is on Levothyroxine 50 mcg/daily.
Conclusion: Despite the rarity of Hashimotos thyroiditis converting to Graves disease, it is possible that those affected can be encountered by primary care providers and hospitalists and could easily be mistaken for over-replacement of levothyroxine. Close monitoring of the patient along with regular thyroid function tests will be required for ongoing follow-up.
Selective Serotonin Reuptake Inhibitors Increase Urinary Free Cortisol in Patients with Carney Complex and Primary Pigmented Nodular Adrenocortical Disease
Authors: Chrysavgi Kamilaris Crystal Dawn , Sinaii Ninet , Stratakis Constantine A 
Published: May 2021

Abstract
Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of ACTH-independent Cushing syndrome predominantly associated with Carney Complex (CNC), a multiple endocrine neoplasia syndrome primarily caused by inactivating defects in PRKAR1A. PPNAD, which has neuroendocrine features, demonstrates cortisol production in response to serotonin as well as increased expression of tryptophan hydroxylase type 2, a serotonin synthesizing enzyme, and the serotonin (5-HT) receptors types 4, 6, and 7. This creates an autocrine/paracrine serotonergic regulatory loop that activates cortisol production. PPNAD can be diagnosed through a 6-day Liddle test (LT) showing a paradoxical increase of &gt;50% from baseline in 24-h urinary free cortisol (UFC) on the 2nd day of high-dose dexamethasone administration (Day 6). Selective serotonin reuptake inhibitors (SSRIs) inhibit the reuptake of serotonin and are widely used for the treatment of depression. We performed a retrospective cohort study of patients with CNC and PPNAD that underwent a LT to evaluate the effect of SSRIs on UFCs, with the hypothesis that SSRI use leads to an exaggerated increase in UFC through presumed activation of the described serotonergic regulatory loop. Of the 34 patients (4–65 y) with CNC and PPNAD that underwent a LT at our institution between 2004 and 2018, 4 took an SSRI during testing. No differences were observed between the SSRI (S) group and the non-SSRI (NS) group in baseline UFCs and the percent increase in UFC on D6. Specifically, the median (IQR) baseline UFC in the S group was 36 (13–252) mcg/24h (nl 4–56) vs 35 (13–98) mcg/24h in the NS group (P=0.95). The percent change in UFC was 208 (93–683)% in the S group and 185 (28–364)% in the NS group (P=0.89). However, there was a difference for overall UFC measurement (across days 1–6 of the LT) in the S group vs the NS group (P=0.03). Age &lt;18 vs 18+ and sex did not have an effect on the outcomes (P=0.17 and P=0.74, respectively). Thus, we conclude that though the percent change in UFC during the LT was similar in both groups, there was a significant difference in overall UFC in the S group when compared to the NS group. These data support an effect of SSRIs and serotonin on UFC and consequently cortisol production in PPNAD. This interesting observation has to be confirmed in more patients with CNC and PPNAD to further elucidate the effects of SSRIs on cortisol production in patents with PPNAD-caused Cushing syndrome, as this may have significant diagnostic and therapeutic implications.
Intravascular Lymphoma in Patient With Celiac Disease With Multi Glandular Involvement
Authors: Alam Mustafa , Horani Mohamad Hosam 
Published: May 2021

Abstract
Case Presentation: The patient is a 60 year old male with a past medical history of celiac disease, paroxysmal Afib, iron deficiency, and CAD who presented with lightheadedness, dizziness, and fatigue. Notable workup revealed that the patient had Afib with RVR, a TSH of 0.189, Free t4 0.51an LDH of 2726, hemoglobin of 8.7, AST of 155, ALT of 19, WBC of 4.5, and serum iron of 20. The patient’s cardizem dose was adjusted and repeat transthoracic echocardiogram was unremarkable compared to history. The patient presented again with complaints of abdominal distension, postural dizziness, occasional night sweats, and fevers. Repeat workups revealed pancytopenia, proteinuria, hypotension, and anasarca most pronounced in the lower extremity and scrotum. Ultimately, a kidney biopsy revealed an intravascular B cell non-Hodgkin lymphoma (IVBCL). Notable repeat labs include a CRP of 44 and a failed ACTH stimulation test. A brain MRI revealed a 6mm pituitary microadenoma. The patient placed on an R-CHOP regiment and is scheduled for repeat MRI to rule out pituitary involvement.
Discussion: IVBCL’s are a rare form of diffuse B cell lymphoma and remain a diagnostic challenge due to the variety of involved systems including skin, CNS, and endocrine. IVBCL is also known to not produce a mass or lymphadenopathy. Celiac disease is a known risk factor for non-Hodgkin’s lymphoma. A literature search reveals a few case reports with common themes of increased LDH and inflammatory markers, anemia, and hepatic and renal dysfunction. Postural hypotension can also be a presenting symptom due to IVBCL’s ability to infiltrate neurovascular tissue to cause autonomic neuropathy. However, in this case, the patient’s history of primary adrenal insufficiency makes this unlikely. Hypothyroidism secondary to pituitary and thyroid involvement was suspected due to TSH level suppressed enough for central hypothyroidism. Repeated MRI showed resolution of Pituitary Microadenoma post Chemo therapy.
Sylvain Raoul Simeni Njonnou, Bruno Couturier, Yannick Gombeir, Sylvain Verbanck, France Devuyst, Georges El Hachem, Ivan Theate, Anne-Laure Trepant, Virginie De Wilde, Frédéric-Alain Vandergheynst, “Pituitary Gland and Neurological Involvement in a Case of Hemophagocytic Syndrome Revealing an Intravascular Large B-Cell Lymphoma”, Case Reports in Hematology, vol. 2019, 6 pages, 2019. https://doi.org/10.1155/2019/9625075
Catassi C, Fabiani E, Corrao G, et al. Risk of Non-Hodgkin Lymphoma in Celiac Disease. JAMA. 2002;287(11):1413
Khan MS, McCubbin M, Nand S. Intravascular Large B-Cell Lymphoma: A Difficult Diagnostic Challenge. J Investig Med High Impact Case Rep. 2014 Mar 6;2(1):2324709614526702.
Pearce C, Hope S, Butchart J. Intravascular lymphoma presenting with postural hypotension. BMJ Case Rep.
Published 2018 Jan 29.