bluuebunny/crossref_metadata_2025_split huggingface dataset:
Graves’ Disease Presenting After 25 Years of Stable Thyroid Hormone Replacement Therapy
Authors: Wyne Kathleen 
Published: May 2021

Abstract
Background: Autoimmune thyroid disease may present with a wide range of symptoms. When the presentation is hyperthyroidism due to Graves’ Disease the symptoms generally subside over the subsequent two years but may recur at any time months to years later. When the initial presentation is hypothyroidism that person usually remains hypothyroid, requiring thyroid hormone replacement therapy for the rest of their life. Clinical Case: 67 year old woman presenting with hyperthyroidism after 25 years of stable dose thyroid hormone replacement therapy (THRT). She recalls being diagnosed with hyperthyroidism in her late 30s. She did not take any medication at that time. She is very clear that she was not treated with radioactive iodine or surgery. She recalls presenting with fatigue and weight gain about 2 years later at which time she was initiated on thyroid hormone replacement therapy. After multiple dose changes in the first few years she was stabilized on 90 mg daily of Armour thyroid. After more than 20 years on this dose the hyperthyroid symptoms recurred. Her symptoms persisted after decreasing then, ultimately, stopping the Armour Thyroid. Evaluation for causes of hyperthyroidism revealed the presence of both TRAb and TSI antibodies that have decreased in titer but are now still present more than 4 years after the diagnosis of hyperthyroidism. Symptoms have been controlled over this time period with low dose (5-10 mg/day) methimazole. Conclusion: Hypothyroidism is very common in women, with Hashimoto’s Thyroiditis as the usual etiology. When patients on thyroid hormone replacement therapy (THRT) present with symptoms of hyperthyroidism they are usually managed with dose reduction. However, complete cessation of THRT is unusual, especially after more than 10-20 years of therapy. Dose reduction of more than 50% without contributing factors such as significant weight loss should prompt measurement of TRAb and/or TSI to evaluate for Graves’ Disease regardless of the duration of the THRT.
Graves’ Disease Induced Severe Hypercalcemia
Authors: Lugo Lopez Zahira Marie , Penna Laurianne El Musa , Ortiz Arnaldo Nieves , Rivera Ivan Augusto , Diez Andrea del Toro , Bossolo Alex N Gonzalez , Garcia Michelle Marie Mangual 
Published: May 2021

Abstract
Introduction: Hyperthyroidism is a well-known non-parathyroid hormone-mediated cause of hypercalcemia. Hypercalcemia associated with thyrotoxicosis is usually asymptomatic. Increased osteoclastogenesis is one of the mechanisms underlying this etiology. Hyperthyroidism is associated with mild to moderate levels of hypercalcemia in approximately 20% of patients, but severe hypercalcemia is rare. We report a case of a male with Grave’s disease-induced symptomatic severe hypercalcemia. Clinical Case: A 36-year-old male with type 2 diabetes mellitus and arterial hypertension who was transferred from another institution to our Emergency Department due to suspected primary hyperparathyroidism for Endocrinology Services evaluation. Family history is non-contributory. Patient reports palpitations, irritability, and unintentional weight loss of approximately fifty pounds in nine months. One month ago, he started with constipation, anxiety, depression, abdominal discomfort, nausea, and vomiting for which decided to seek medical attention. Physical examination was remarkable for tachycardia, dry mucous membranes, and goiter. Laboratory tests showed lipase 69 U/L (13-60U/L), albumin-corrected calcium 14.3 mg/dL (8.8-10.3mg/dL), phosphorus 3.30 mg/dL (2.4-4.2mg/dL), magnesium 1.58 mg/dL (1.8-2.2mg/dL), creatinine 1.38 mg/dL (0.90-1.30 mg/dL), alkaline phosphatase 77 IU/L (43-115IU/L), iPTH 4 pg/mL (11-67pg/mL), PTHrp &lt;0.4 pmol/L (≤4.2pmol/L), 25-OH vitamin D 32.1 ng/mL (30-100ng/mL), 1,25-dihydroxyvitamin D &lt;5.0 pg/mL(19.9-79.3pg/mL), hemoglobin 11.6 g/dL (14-18g/dL), negative serum and urine protein electrophoresis, TSH 0.003 uIU/mL (0.45-5.33 uIU/mL), free T4 2.80 ng/dL (0.71-1.85ng/dL), total T3 2.57 ng/mL (0.80-2.00ng/mL), TSI: 486% (&lt;140%), urine calcium 24hr 525mg/day (100-300mg/day). Thoracic and abdominopelvic CT scan without contrast was unremarkable for masses, adenopathies, osseous lesions, or acute abdominal processes. Patient was treated with IV isotonic saline and methimazole 10mg oral daily with resolution of symptoms. Finally, diagnosed with Graves’ disease as the cause of hypercalcemia after ruling out other etiologies. He was discharged home with calcium levels 10.8 mg/dL, normal renal function, methimazole, and follow up with Endocrinology Services. Conclusion: This is a case of an atypical presentation of hyperthyroidism-induced symptomatic hypercalcemia. It is important to consider hyperthyroidism in the differential diagnoses of severe hypercalcemia. Prompt suspicion is essential due to the effective treatments available for Graves’ disease. Early treatment of hypercalcemia is important for quick resolution of symptoms and decreased associated mortality.
Graves’ Thyrotoxicosis and Fulminant Myopericarditis: A Clinical Dilemma!
Authors: Jain Meenu , Puchalski Adam , Hodge MaryBeth 
Published: May 2021

Abstract
Myocarditis is a rare presentation of Graves’ disease, fulminant myocarditis is even rarer. We report a woman with Graves’ disease with fulminant myopericarditis as the presenting clinical feature. A 23-year-old healthy woman presented with acute onset pleuritic chest pain, palpitations, diaphoresis, heat intolerance, and dyspnea. There was no history of fever, upper respiratory tract infection, diarrhea, or weight loss. Physical exam revealed sinus tachycardia and palpable non-tender thyroid. Blood work was pertinent for TSH &lt;0.01uIU/ml(0.3-4.5), free T4 2.8ng/dl(0.6-1.5), free T3 &gt; 32.6pg/ml (2.4-4.2) and positive TSI (thyroid-stimulating immunoglobulin) 12.4 IU/L (&lt;0.54). She had a diffusely enlarged vascular thyroid on ultrasound, all findings consistent with hyperthyroidism due to Graves’ disease. Electrocardiogram showed sinus tachycardia with diffuse PR depression and ST-segment elevation, troponin was 0.85 which increased to 17.5 within 12 hours, an echocardiogram showed normal ejection fraction (EF) with mild pulmonary hypertension but no pericardial effusion. She improved symptomatically with beta-blockers, methimazole, and colchicine but unfortunately had a witnessed ventricular fibrillation cardiac arrest in the next 12 hours with return to spontaneous circulation achieved after 90 minutes of bystander cardiopulmonary resuscitation. Coronary angiogram revealed normal coronaries with post-cardiac arrest EF of 5%. She subsequently developed acute respiratory distress syndrome secondary to massive pulmonary hemorrhage requiring extracorporeal mechanical support for worsening cardiogenic shock, succumbing to her illness a few hours later. Graves’ disease affects 0.5% of the population and causes hyperthyroidism in 50-80% of cases. Thyrotoxicosis may be associated with supraventricular arrhythmias and cardiomyopathy due to long-standing untreated hyperdynamic heart failure, but myopericarditis is an unusual presentation of Graves’ thyrotoxicosis with fulminant myopericarditis being even rarer. Fulminant myocarditis can present with ventricular tachyarrhythmias and can rapidly deteriorate into shock which may be difficult to distinguish from other causes of cardiogenic shock such as acute coronary syndromes or stress-induced cardiomyopathy. Myopericarditis associated with Graves’ is thought to be due to autoimmunity against functional TSH receptors identified in human cardiomyocytes. Fulminant myocarditis is a common cause of sudden cardiac death in young healthy adults, which is also the same population that gets Graves’ disease. It is critical to recognize the unusual presenting features of Graves’ disease such as fulminant myopericarditis, as timely aggressive intervention can reduce the risk of sudden cardiac death.
The Burden of Illness of Congenital Adrenal Hyperplasia (CAH) in Adults: Results: of a Structured Literature Review
Authors: Woods Matthew Stephen , Coope Helen , Maskin Kamran , Parviainen Lotta Elisabet , Porter John , Withe Michael , Sabar Uzmah 
Published: May 2021

Abstract
Objectives: Congenital adrenal hyperplasia (CAH) is a group of rare autosomal-recessive disorders that arise from genetic deficiencies in key enzymes involved in cortisol synthesis. The burden of CAH has never been comprehensively reviewed; this literature review was conducted to summarise the existing burden of illness evidence available for these patients. Methods: A structured, comprehensive literature review was conducted to identify articles describing the burden and treatment landscape of CAH. Literature databases (MEDLINE, Embase, the Cochrane Library and EconLit), websites and conference proceedings were searched. Searches were performed in 2016 and updated in June 2020; eligible articles presented evidence for patients with CAH or paediatric patients with adrenal insufficiency (AI), for ≥1 topic of interest (epidemiology; natural history; clinical characteristics; humanistic, caregiver and economic burden; treatment options; or clinical guidelines). The evidence presented here focusses on the humanistic and economic burden of CAH in adults. Results: A total of 3,711 citations were identified and 336 were included; 84 references reported humanistic or economic burden data relevant to adult patients with CAH. 51 publications were identified reporting patient symptoms, comorbidities and cardiometabolic risk factors; 38 reporting on the impact of CAH on health-related quality of life (HRQL); 5 reporting patient views and 2 reporting economic burden associated with CAH. Compared to the general population, adult patients with CAH were found to be significantly shorter, have poorer bone health, increased levels of obesity, impaired male and female fertility, higher blood pressure and cholesterol levels, have more psychiatric and neurological disorders and have poorer cognitive performance. Adult patients with CAH were also found to have greater insulin resistance and higher levels of type 2 diabetes (T2D). CAH patients are also at risk of adrenal crisis, which contributes to excess mortality. The reported HRQL in adults with CAH varies, with increased impairment observed in more severe forms of CAH, and challenges due to living with a chronic disease impacting HRQL varying according to sex. “Sick day rules” where patients need to double or triple treatment doses, have a significant impact on patients’ HRQL and also have an impact on patients’ resource use, with a UK study reporting that CAH patients will implement these rules 171 times over their lifetime, and be hospitalised for adrenal crises on 11 occasions. CAH was also found to have a significant economic impact, with significantly higher annual healthcare costs compared to matched controls (p=0.007 for patients aged 18–40 years; p&lt;0.001 for patients aged ≥40 years). Conclusions: This comprehensive review highlights that CAH in adults is associated with a significant humanistic and economic burden.
Percutaneous Ethanol Injection as Treatment for Thyroid Cystic Nodules
Authors: Rios Paola , Ambut Jonathan , Manzano Alex 
Published: May 2021

Abstract
Background: Thyroid cystic nodules are common and frequently benign. Aspiration of thyroid cyst decreases compression symptoms and volume. However, they commonly recur, and usually, surgery is required for definitive treatment. A less invasive approach, done less frequent, is percutaneous ethanol injection (PEI), which has shown fewer recurrences than simple aspiration and is well-tolerated with few side effects. We present 2 patients that where treated in our clinic with PEI.
Clinical Case: 41-year-old female with a history of primary hypothyroidism on Levothyroxine, with neck discomfort, and no risk factors for thyroid cancer had a cystic thyroid nodule 1.5 x 1.8 x 2.8 cm over the right thyroid lobule. Cytology results reported as Bethesda II. One year later, her thyroid nodule was 1.9 x 2.6 x 3.3 cm. Underwent FNA and 6 cc of dark brown liquid was drained from the cyst which was reported again as Bethesda II. The patient was monitored with thyroid ultrasound after a year, and the cystic nodule was 2.2 x 2.9 x 3.1 cm. PEI was decided as the next approach. After six cc was aspired, 0.5 cc of desiccated ethanol was injected into the remained cystic. Eight months after PEI, cystic size was 0.7 x 0.9 x 0.8 cm. The second case is a 40-year-old female who presented complaining of neck discomfort without changes in her voice. The patient did not have any risk factors for thyroid cancer. Thyroid ultrasound was done, which showed a 2.3 x 2.7 x 3.3 cm cyst on her right thyroid lobe. PEI was arranged and 9 cc of dark fluid was aspirated with a posterior injection of 0.5 cc of desiccated ethanol. Symptoms resolved, and the patient was lost to follow up. Five years later, she was seen again. Neck ultrasound showed a cyst of 0.4 x 0.6 x 0.8 cm on her right thyroid lobe. Neither of the two patients had a side effect associated, and the procedure was well tolerated.
Conclusions: Percutaneous ethanol injection is a good alternative in the treatment for cystic thyroid nodules due to decrease in cystic size, which we observed that continued for five years of follow up in one of our patients. These will avoid frequent cystic aspiration secondary to recurrence or invasive surgical management.
Profound Hypothyroidism 21 Days After Methimazole Initiation in a Patient With Graves’s Disease and Liver Cirrhosis
Authors: Hammami Safa , Schuff Kathryn Graham , Hettinger Barbara Diane 
Published: May 2021

Abstract
Introduction: Methimazole is the first line treatment of nonpregnant Grave’s disease (GD) patients with Grave’s ophthalmopathy. It usually results in euthyroidism within 4 to 12 weeks, and it is recommended to check FT4 every 4 to 6 weeks after initiation of therapy. We report a patient with GD who developed profound hypothyroidism 21 days after starting methimazole. Clinical Case: 51-year-old male with decompensated EtOH/NASH liver cirrhosis, Gilbert’s syndrome, and GD presented with severe hypothyroidism 21 days after initiating methimazole treatment. He initially presented to the emergency department (ED) with atrial fibrillation with a HR of 140 and found to have bilateral exophthalmos and lid lag. Labs: TSH &lt;0.01 uIU/L (normal range (nl) 0.27-4.20), FT4 2.6 ng/dl (nl 0.7-1.7), TT4 6.2 ug/dl (nl 4.5-12), TT3 125 ng/dl (nl 71-180), TBG 14 ug/ml (nl 13-39), TSI 344 IU/l (nl 0-0.5), AST 55 IU/L (nl 14-44), ALT 27 IU/L (nl 9-57), Alk Phosphatase 497 IU/L (nl 45-129), Tbili 7.1 mg/dl (nl 0.2-.1), and albumin 2.1 g/dl (nl 3.4-5). He was started on methimazole 40 mg daily and propranolol 20 mg BID. Three days later, FT4 decreased to 1.3 ng/dl, so methimazole was decreased to 20 mg day. Ten days later, FT4 was 0.2 ng/dl and methimazole was reduced further to 10 mg daily. Eight days later, he presented to the ED with severe lethargy and found to have HR of 38 and oral temperature (T) of 94. TSH was 3.49 uIU/L and FT4 &lt;0.1 ng/dl. Sixteen hours after 200 mcg IV levothyroxine, he had normal mental status, HR of 49, and T of 97.9. FT4 increased to 0.5 ng/dl within 48 hours of thyroxine initiation. Urine drug screen was only positive for tetrahydrocannabinol and other work up for severe lethargy and hypothermia was unremarkable. He was discharged on 100 mcg of PO levothyroxine. Conclusion: Only 21 days after starting methimazole, the patient developed severe lethargy associated with hypothermia, bradycardia, and undetectable FT4, with no alternative etiology and prompt response to IV levothyroxine, consistent with profound hypothyroidism. Although the half-life of T4 is shortened in hyperthyroidism, the particularly fast and profound effect of methimazole in this patient was unusual and likely due to a limited extra-thyroidal pool of thyroxine caused by low TBG level. As cirrhosis is usually associated with increased TBG level, he may have a contributing congenital etiology. Reduced levels of other T4 binding proteins, albumin and pre-albumin may also have contributed. Although methimazole clearance can be decreased in liver impairment, no dose adjustment is generally recommended, and even this would not have explained the observed rapid decrease in FT4 level. Methimazole should be used with caution and FT4 should be checked early and more frequently when treating hyperthyroid patients with liver disease and possible alteration in thyroid binding proteins.
Skin Deep: A Rare Case of Thyrotoxic Periodic Paralysis in an African American Patient
Authors: Banerjee Ela 
Published: May 2021

Abstract
Background: Thyrotoxic Periodic Paralysis (PP) is a rare form of hypokalemic PP that occurs in association with hyperthyroidism, especially Grave’s disease. This disease is frequently seen in males and is particularly prevalent among Asians with an incidence rate of 2%. In non-Asian populations, the incidence among those with hyperthyroidism is even lower at 0.1 - 0.2% and therefore significantly rare in African populations. Inability to recognize this emergency in the non-Asian population can therefore result in potentially fatal outcomes. Case Presentation: A 27 year old African American male with a history of Grave’s disease presented to the emergency department (ED) with the inability to move his muscles. Patient was initially diagnosed with Grave’s disease in 2017 when he was found to have suppressed TSH with elevated TSI and started on methimazole 40mg daily. The patient ran out of methimazole about 2 weeks prior to presentation and woke up on the day of admission with extreme muscle weakness. At the outside hospital, he was found to have potassium of 1.5mEq/L,TSH of &lt; 0.1uL/ml and Free T4 of 3.4 ng/dL. He was given 1000 mg Propylthiouracil, stress dose hydrocortisone, propranolol and potassium replacement and then transferred to our ED for Endocrine evaluation. On assessment, he complained of nausea, vomiting, full body muscle weakness, tingling in his extremities and irritability. He denied any recent illnesses. On physical exam, Temperature 97.4 F, Respiration 18, Pulse 84, BP 157/72, O2 saturation 99%. His thyroid gland was enlarged however non-tender and without bruit. He had normal respiratory and cardiac exam. He was lying flat in bed and unable to raise his limbs against gravity and also unable to hold up his limbs when raised. He lacked his patellar and ankle jerk reflexes bilaterally. He was otherwise alert and oriented x 3. On labs, TSH was 0.004 uL/ml, Total T3 was 294 ng/dL, Free T4 of 3.01 ng/dL, Potassium was 2.1 mEq/L. His potassium was cautiously replaced and improved to 4.7 mEq/L later in the day, at which time, the patient was able move and sit up in bed. He was restarted on Methimazole 40mg daily for his thyroid disease and arranged for outpatient follow up. Discussion: Thyrotoxic PP is seen in a male-to-female ratio ranging from 17:1 to 70:1 and occurs at an average age of 20-40 years. Thyrotoxic PP is especially rare in the non-Asian population at an incidence rate of 0.1 - 0.2%. Nevertheless, in setting of ever-growing diversity due to immigration and inter-race relationships, it is difficult to predict one’s genetics based on the color of their skin. It is possible that our African American patient may have an Asian ancestor unbeknownst to him. Therefore, we must keep a broad differential regardless of one’s race so as to not miss timely diagnosis of medical emergencies which can result in reduced muscle strength, flaccid paralysis, respiratory failure, cardiac arrhythmias and eventual death.
Subacute Thyroiditis With Very Elevated Thyroglobulin Level in a Patient on Chronic Adalimumab Therapy
Authors: Jobira Beza , Saxon David , Greca Amanda La 
Published: May 2021

Abstract
Background: Viral infections are a well-recognized cause of subacute thyroiditis (SAT), but other etiologies are occasionally seen. Here we present a case of SAT in a patient receiving chronic tumor necrosis factor inhibitor (TNF-i) therapy. Serum thyroglobulin (Tg) levels in healthy individuals have been reported and range 1.40-29.2ng/mL in males and 1.50-38.5ng/mL. There are no known serum Tg levels of reference in SAT.
Clinical Case: A 43-year-old woman with a history of psoriasis treated with adalimumab presented to her primary care physician (PCP) 2 months after her mother had noticed the patient’s new goiter. Patient recalled upper respiratory infection symptoms lasting 1.5 weeks, and subsequent agitation, insomnia, and a low-grade fever preceding the development of goiter. She denied neck compressive symptoms aside from mild dysphagia. She has been treated with adalimumab 40mg subcutaneous injection weekly for psoriasis with good results for the past 3.5 years and was on norethindrone 0.35mg daily for contraception. Her thyroid exam with her PCP revealed a diffuse painless goiter and she was clinically euthyroid. Labs revealed a TSH 1.44mIU/L [0.45-5.33], TT3 104ng/dL [60-181], fT3 3.3pg/mL [2.3-4.2], fT4 0.83ng/dL [0.89-1.76], and Tg 288.7ng/mL [1.6-50]. Thyroid antibodies (Tg, thyroid peroxidase and thyroid stimulating immunoglobulin) were negative. She tested negative for COVID-19. The neck ultrasound showed an enlarged pseudonodular thyroid gland with a heterogenous parenchyma and diffuse hypervascularity bilaterally (right lobe, 7.4 x 2.8 x 3.0 cm; left lobe, 8.4 x 3.2 x 3.6 cm; isthmus, 9 mm). A month later, repeat labs showed TSH 1.56 mIU/L, TT3 85 ng/dL, fT4 0.74 ng/dL, and Tg 231.2 ng/mL. She was subsequently referred to Endocrine Clinic 4 months after her initial presentation. She had a persistent diffuse painless goiter, minimally decreased in size, and she remained clinically euthyroid. Labs included a TSH 1.75 mIU/L and fT4 0.78 ng/dL.
Conclusion: There are known associations of SAT with chronic TNF-i therapy in patients with psoriasis. Viral infections are an identified cause, but other triggers in chronic TNF-i therapy may exist. Serum Tg is elevated during SAT, but in this case Tg elevation was very significant. Although normal serum Tg levels are established in healthy individuals, there are no known reference values during SAT. Tg levels should not be used in acute illness period to evaluate illness severity or the resolution of SAT.