bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcome of Teprotumumab Treatment for Graves Orbitopathy After Multiple Attempts at Orbital Decompression Surgery
Authors: Kabir Purnima , Lewis Chantal , Hendrix Joshua 
Published: May 2021

Abstract
Background: Graves’ Orbitopathy, also known as Thyroid Eye Disease (TED) is a severe ocular manifestation of Graves’ Disease. It manifests as an autoantibody mediated reaction to the thyroid hormone stimulating receptor (TSH-R), these receptors are closely linked with the insulin-like growth factor-1 receptors (IGF-1R). The TSH-R antibodies play a major role in the pathogenesis of TED. The activation of the TSH-R and IGF-1R on orbital fibroblasts and adipocytes lead to IGF-1 expression. This initiates inflammation, fibroblast proliferation and accumulation of glycosaminoglycans in the orbital tissue. Treatment modalities include glucocorticoids, orbital radiation and orbital decompressions. Recent understanding of the molecular basis of TED has resulted in targeted therapy with Teprotumumab, an inhibitory monoclonal antibody against IGF-1R. There is limited literature on the outcomes of Teprotumumab use after orbital decompression surgery.
Clinical Case: 43-year-old female presented with symptoms of diplopia, periorbital pain, dry eyes and tremor. Ocular exam: Vision was correctable to 20/20 in each eye, restricted motility, bilateral lid edema, lid retraction with superior scleral show and conjunctival injection. Clinical Activity Score &gt; 4. Diagnostic tests: TSH 0.00 undetectable (N:0.5-5.0mIU/L) FT4 3.19 (N:0.7-1.9ng/dL) TSI thyroid stimulating immunoglobulin 490% of baseline (N: 130% of baseline). Diagnosis of Graves’ disease with associated orbitopathy was made. In addition to medical management for Graves’ thyroid disease she was referred to ophthalmology. She was treated with high dose steroids for 4 weeks with no resolution of symptoms. She was then referred to an oculoplastic surgeon for bilateral orbital decompressions which resulted in mild improvement in diplopia but a residual proptosis. The decision was made to treat with teprotumumab, which had recently been FDA approved. Patient reported improved symptoms without complicating enophthalmos. Review confirmed improved proptosis on Hertel Exophthalmometry. The right eye improved from 22 mm to 16 mm and the left eye from 21 mm to 17 mm (N &lt;20.1 mm Caucasian females) with preserved visual acuity, improved lid retraction, resolved conjunctival chemosis and decreased periorbital pain after 6 doses of Teprotumumab therapy.
Conclusion: Graves’ orbitopathy can result in debilitating symptoms affecting quality of life. Targeted molecular therapy such as teprotumumab is an effective treatment even after orbital decompression.
Reference: Ting, M., Ezra, D.G. Teprotumumab: a disease modifying treatment for graves’ orbitopathy. Thyroid Res13, 12 (2020). https://doi.org/10.1186/s13044-020-00086-7
Preeclampsia and Thyrotoxicosis: A Case of Impending Storm
Authors: Wilson Marianne K , Hermayer Kathie L 
Published: May 2021

Abstract
Introduction: Preeclampsia is a complication of pregnancy defined by new onset hypertension after 20 weeks with proteinuria or new onset thrombocytopenia, renal or liver dysfunction, pulmonary edema or cerebral/visual symptoms. Hyperthyroidism in pregnancy is usually due to Graves’ disease, and if poorly controlled can increase the risk of preeclampsia and thyroid storm. In this case report we present a case of preeclampsia with impending thyroid storm treated successfully with medical therapy, delivery, and plasmapheresis. Case Description: A 40-year-old female who is 31 6/7 weeks pregnant presents with cough and dyspnea. She has no known thyroid disease. Her systolic blood pressure at presentation is &gt;160 mmHg. She is diagnosed with preeclampsia based on elevated spot protein/creatinine ratio (1.4 g/g) and persistent hypertension. A brain natriuretic peptide is elevated to 847 (reference range &lt;= 100 pg/ml). Complete blood count and comprehensive metabolic panel are normal, with exception of mild alkaline phosphatase elevation. A CT pulmonary angiogram is negative for pulmonary embolism but shows bilateral pleural effusions. She is started on intravenous antihypertensive medications and furosemide. Due to persistent tachycardia, thyroid function is checked and is notable for a thyroid stimulating hormone level of 0.05 (non-pregnant reference range 0.35 – 4.94 mIU/L), an elevated free T3 of 13.7 (non-pregnancy reference range 1.7 – 3.7 pg/ml), and an elevated free T4 &gt; 4 (non-pregnancy reference range 0.70-1.48 ng/dL). She is started on therapy for impending thyroid storm, including maximum doses of propranolol, propylthiouracil, hydrocortisone and saturated solution of potassium iodide. Her thyroid stimulating immunoglobulin is &gt; 500 (reference range &lt;= 122%) and TSH receptor antibody is &gt; 40 (reference range &lt;= 1.75 iU/L) leading to a new diagnosis of Graves’ disease. On hospital day three, she develops altered mental status and fetal bradycardia, warranting emergency cesarean section. On hospital day five she develops worsening confusion, abnormal liver function tests and increasing levels of free T4 and free T3. At this time, she is started on plasmapheresis therapy. Free T4 and free T3 values normalize after two rounds. Her medications are slowly weaned, and she is discharged from the hospital on methimazole 20 mg daily. Her baby is discharged after a brief hospital stay for sequela of prematurity. Discussion: While far less common than preeclampsia, thyrotoxicosis may present with similar symptomatology and can pose significant morbidity and mortality risk for pregnant patients. However, with prompt diagnosis and appropriate therapies, the disorder can be treated successfully and without lasting harm to the mother or fetus. For these reasons, it should remain on the differential for patients with symptoms of preeclampsia, and thyroid studies should be considered.
Rare Case of Thyroid Storm Masked by Diabetic Ketoacidosis
Authors: Nachawi Noura , Repp Anita Lopes 
Published: May 2021

Abstract
Introduction: Diabetic ketoacidosis can be triggered many other clinical conditions. In this case we describe uncommon presentation of diabetic ketoacidosis in the setting of thyroid storm. Clinical Case: An 82-year-old woman with history of type 2 diabetes treated with Insulin and Metformin presented with multiple falls preceded by fatigued and decreased oral intake for two weeks. On initial presentation, she was noted to have hyperglycemia and labs consistent high anion gap metabolic acidosis and positive serum and urine ketones suggesting diabetic ketoacidosis. Investigations were negative for any triggering infections. Diabetic ketoacidosis resolved with intravenous fluids and Insulin. However, patient remained consistently tachycardic. Repeated thyroid workup showed declining TSH (from 0.66 to 0.12 mIU/mL) (n: 0.270 - 4.200 mIU/mL), free T4 of 4.3 ng/dL (n: 0.9 - 1.7 ng/dL) and free T3 of 9.7 ng/dL (n: 79 - 165 ng/dL), thyroid peroxidase antibodies and thyroid stimulating immunoglobulin were both elevated of 293 IU/mL (n: &lt;5.6 IU/mL) and 7.2 IU/L (n: &lt;0.55 IU/L) respectively. Thyroid ultrasound showed several nodules in the isthmus and left lobe with multiple nodules with largest one measuring 1 X 2.3 cm. Treatment with Methimazole and Prednisone was initiated with good response. On follow up with endocrinology, repeated TSH was 28 mIU/mL and her Methimazole dose was reduced. Due to patient wishes of being conservative in management, no thyroid radioiodine uptake scan to evaluate the nodules.
Conclusion: Literature review shows several similar case reports of newly diagnosed thyrotoxicosis manifested by DKA in known type 1 and type 2 diabetic and obscured by other confounding conditions including pericarditis, flu syndrome, psychosis and cellulitis ultimately delaying diagnosis and treatment of thyroid storm. Fortunately, none of these cases were associated with adverse outcome. By presenting this case we emphasis on including thyroid function test as part of initial work up of diabetic ketoacidosis to avoid any potential adverse outcomes.
Refractory Postsurgical Hypothyroidism in Nephrotic Syndrome
Authors: Rendon Casey 
Published: May 2021

Abstract
62-year-old female with a history of thyroid cancer of unknown type s/p thyroidectomy 30 years prior to presentation, who had 2 months of worsening generalized edema and increasing need of dose escalation of her oral thyroid replacement by her PCP. Despite increasing her thyroxine dose multiple times and adding Armour thyroid based on increasing TSH and decreasing FT4 on outpatient labs, her edema continued to get worse. She presented to the Emergency Department. She takes no other medications. Symptoms include malaise, cold intolerance, weight gain, hair loss, bloating without constipation,“feeling foggy” and that her memory seemed a bit “off”, and she felt her mood was more “sensitive”, and she had atypical non-exertional chest discomfort. On exam she was was bradycardic to 56 and hypertensive to 175 systolic, had faint bibasilar crackles were present bilaterally, had significant pitting edema of the bilateral lower extremities, 3+ up to the level of her abdomen, as well as pitting edema of her bilateral upper extremities, and no periorbital edema was seen. Her neurologic exam was non-focal. Outpatient labs included TSH 178, free T4 0.35, albumin 1.2, and BNP level of 57. Her liver and kidney function tests were normal. Hospital labs included a normal CBC, chemistry with an albumin of 2.2 and normal range liver and kidney function. Thyroid function tests included a very high TSH level of 141, low free T4 level of 0.37, and a free T3 toward the lower end of normal. Lipid panel showed severe hypercholesterolemia. Urine studies showed microhematuria as well as the equivalent of proteinuria to the level of 10 grams per day. HIV was negative and complement levels were within normal limits. CXR, renal US, transvaginal US, and CT chest/abdomen/pelvis were performed to investigate the proteinuria and potential secondary causes of the proteinuria, all of which were unremarkable for acute or pertinent findings. Pathology results from a kidney biopsy showed membranous nephropathy. The patient initially received IV steroids and IV thyroxine as well as an albumin infusion. She was quickly transitioned to oral thyroxine due to her stability on presentation. She was given a statin and ACE inhibitor as well as IV Lasix. And she was discharged on thyroxine, with Armour thyroid being discontinued. She had severe hypothyroidism in a patient dependent on exogenous thyroid hormone which was exacerbated by severe proteinuria due to a new-onset nephrotic syndrome. Her hospital course uneventful. She responded well to intravenous diuretics. After her diagnosis of membranous nephropathy, Nephrology recommended continued conservative treatment due to her normal renal function and improving edema with outpatient follow up. She only received a single dose of IV thyroxine and remained stable after switching to oral thyroxine.
The Diagnostic Accuracy of Dehydroepiandrosterone Sulfate in Diagnosing Adrenal Insufficiency
Authors: Suresh Malavika , Gruber Lucinda , Bancos Irina 
Published: May 2021

Abstract
Background: Evaluation for adrenal insufficiency (AI) includes dynamic testing that is cumbersome, expensive, and may not always be accessible. Our objective was to evaluate the diagnostic accuracy of dehydroepiandrosterone sulfate (DHEAS) in diagnosing AI.
Methods: This is a single-center retrospective study of patients evaluated for AI between July 10th, 2012 to January 7th, 2020 who underwent Cosyntropin stimulation testing (CST) or Insulin tolerance test (ITT), and had baseline measurement of DHEAS. Diagnosis of adrenal insufficiency was based on peak cortisol of &lt;18 ug/dL during either CST or ITT.
Results: We identified 491 patients (379 [77.2%] women, median age 42 years [range 18–84]) who met inclusion criteria. Primary adrenal insufficiency (PAI) was diagnosed in 16 (3%) patients, secondary adrenal insufficiency (SAI) was diagnosed in 211 (43%) patients, and AI was excluded in 264 (54%) patients. CST was performed in 478 (97%) patients, ITT was done in 45 (9%) patients, with 32 patients having both CST and ITT performed. Using a peak cortisol of &lt;18 mcg/dl during CST to diagnose AI, ROC analysis of DHEAS demonstrated an area under the curve of 0.79, p&lt;0.0001. A DHEAS cutoff of 100 mcg/dL excluded AI with a sensitivity of 93%, specificity of 41%, and a false negative rate of 3%. A DHEAS cut-off of 25 mcg/dl diagnosed AI with a false positive rate of 9% (Sensitivity 57% and specificity 85%). Notably, of 32 patients who had both CST and ITT performed, the diagnosis of AI was concordant in only 5 patients, while additional 27 patients had discordant results (26 were diagnosed with SAI based on ITT, but with a normal CST, and 1 patient was diagnosed with AI on CST but not on ITT). When excluding the 27 patients with discordant results, the overall performance of DHEAS in diagnosis of AI based on CST has not changed.
Conclusion: DHEAS is a valuable baseline diagnostic test for AI. DHEAS &gt;100 mcg/dl predicts a normal response during CST with a false negative rate of 3%, while DHEAS &lt;25 mcg/dl is reflective of underlying adrenal insufficiency and predicts an abnormal CST with a false positive rate of 9%. In these situations, CST can be avoided.
Subacute Thyroiditis After SARS-CoV-2 Infection Presenting With Pyrexia of Unknown Origin
Authors: Singh Santosh 
Published: May 2021

Abstract
Subacute thyroiditis(SAT) is associated with viral(destructive) or post-viral(inflammatory) origin.[1]The most common clinical characteristics of SAT are female sex preponderance, anterior neck pain and fever.[2,3] Heart rhythm disorders and silent cervical forms have been described in SAT associated with SARS-CoV-2 infection,which occurs 16 to 36 days after resolution of COVID-19.[1,3] Symptomatic improvement occurs in a few days after initiation of therapy with sterods or NSAID.[3] Pyrexia of Unknown Origin (PUO) is a very rare presentation of SAT.[2] Hereby, a case of SAT, presenting with painful neck swelling and persistent fever (5weeks duration), two weeks after resolution of COVID-19, is being discussed. The index patient was a 50-year old obese,normotensive, diabetic (10 years duration, HbA1c-6.6% on SU, metformin, sitagliptin and dapagliflozin) male. TSH was suppressed (0.02 mIU/L), FT4 (3.06 ng/dl, upper limit of normal-1.48ng/dl) and FT3 (3.9 pg/ml, upper limit of normal-3.71 pg/ml) were elevated. Total T4 and T3 were normal. HS-CRP was markedly elevated. IL-6 and TBG were not estimated. Cervical USG revealed diffuse hypoechogenecity of thyroid gland and thyromegaly. There was reduced uptake in thyroid scan (technetium). The patient became afebrile after 4 days of initiation of 30 mg prednisolone (tapered by 10 mg every 5 days). The initial tachycardia reverted to sinus rhythm with marked reduction of neck tenderness. This case highlights certain considerations for SAT associated with SARS-CoV-2 infection. Firstly, it can present with PUO (first case report). Secondly, it may be associated with normal total T4 and T3 which can happen due to reduced TBG consequent upon increased IL-6.[4] References: 1. Caron Philippe: Thyroid disorders and SARS-CoV-2 infection: From pathophysiological mechanism to patient management. Ann Endocrinol (Paris), 2020, Sept. 2. Fever of Unknown Origin as a Sole Presentation of Subacute Throiditis in an Elderly Patient. A Case Report with Literature Review. Raj R, Yada S, Jacob A et al: Hindawi Case Reports in Endocrinology, 2018, Article ID 5041724 3. Brancatella A, Ricci D, Latrofa F et al: Is subacute thyroidits an underestimated manifestation of SARS-CoV-2 infection? Insights from a case serie. J Clin Endocrinol Metab, 2020, Aug 11, dgaa537. 4. Bartaleno L, Brogioni S, Grasso L and Martino E: Increased serum interleukin-6 concentration in patients with subacute thyroiditis:relationship with concomitant changes in serum T4-binding globulin concentration. Journal of Endocrinological Investigation, 1993, 16, 213-218.
Tuberculous Thyroiditis Post COVID-19 Infection
Authors: Win Kyaw Zin , Hamidi Afshin , Sattar Alamgir , Karunakaran Abhijana 
Published: May 2021

Abstract
Thyroid tuberculosis (TT) is a rare disease and can be a diagnostic challenge. Here we highlight a case of TT following COVID-19 infection. A 38-year Myanmar immigrant female presented with nocturnal fever, fatigue, nausea, sore throat, appetite and weight loss for 1 week with dysphagia, neck swelling, dyspnea, and watery diarrhea. Medical history included renal transplant due to ESRD from IgA nephropathy, DM and treated latent TB with no prior or family history of thyroid disease. She had COVID 7 months ago, complicated by allograft rejection. She was tachycardic, febrile but not in acute distress. Neck exam revealed diffuse thyromegaly with tenderness on right lobe without bruit, palpable cervical lymphadenopathy nor tremors. Labs showed WBC 12.8x109/L (4.8-10), and ESR 50 ml/hr (20-40). On admission, she developed AKI and immunosuppressant meds were discontinued. She was started on broad-spectrum antibiotic. CT chest reported moderate loculated right pleural effusion with mid and lower lobe consolidation. Blood and urine culture, pleural fluid, sputum culture for acid-fast bacilli (AFB) and QuantiFERON-TB were negative. Upon persistent fever, RIPE therapy (rifampin, isoniazid, pyrazinamide, ethambutol) was started and stopped after 10 days due to transaminitis and negative TB PCR. Further labs showed TSH 0.04 mIU/ml (0.27-4.2), FT4 2.81 ng/dl (0.93-1.7), TT3 127 ng/dl (80-200), negative TPO and TSI. Endocrinology was consulted for thyroiditis. Ibuprofen and Propranolol were initiated with continuation of prednisone. Repeat thyroid labs normalized in 4 days. US thyroid noted diffuse, heterogenous thyromegaly without hypervascularity or abscess. CT neck showed diffuse thyromegaly 4.2x7.2x7.5 cm in size; right thyroid lobe extended to posterior clavicle with enhanced capsule, without discrete lymph node or vascularity changes, suggestive of thyroiditis. Fine needle aspiration (FNA) of left thyroid lobe drained 3 ml purulent fluid and AFB were seen on direct smear. She was diagnosed as TT, but unable to restart RIPE therapy due to worsening liver function. She expired after cardiac arrest due to intracranial bleeding and brain abscess. Thyroid tuberculosis is a rarely reported clinical entity. This is the first reported case of secondary TB (TT) in post-COVID infected patient from reactivation of latent TB. In our case, follicular destruction caused initial hyperthyroidism with later recovery. It can be difficult to distinguish subacute from suppurative thyroiditis due to TB. Imaging may not always show clear abscess formation. FNA is crucial for diagnosis, and drainage of any abscess. Anti-TB meds can be given, surgery is rarely required. TT should be considered in any immunocompromised patient with fever and neck pain. Imaging should also include evaluation for any CNS spread of TB. Early detection and treatment will help reduce significant morbidity and mortality.
Two Cases of Graves’ Hyperthyroidism Treated With Homeopathic Remedies Containing Herbal Extracts from Lycopus spp. and Melissa officinalis
Authors: Kaplan Daniel , Dosiou Chrysoula 
Published: May 2021

Abstract
Background: Plant extracts from species of Lycopus (bugleweed) and Melissa officinalis (lemon balm) have long been used as folk remedies in the treatment of hyperthyroidism1. In vitro studies have shown that extracts from bugleweed and lemon balm inhibit stimulation of thyroid hormone production by both TSH and Graves’ antibodies1. An in vivo study in rats showed that oral bugleweed extract alters extra-thyroidal T4 conversion2.
Case 1: A 64 year-old woman presented for routine examination and was found to have a TSH of 0.01 mIU/L on 6/6/2016. Labs the next month showed FT4 1.4ng/dL (0.8-1.8) and FT3 4.7pg/mL (2.3-4.2). TSI was elevated to 275% (Normal&lt;140%), consistent with Graves’. She did not have symptoms of hyperthyroidism. The patient’s cat had been treated for hyperthyroidism with Thyrosoothe (TS), a formulation containing extracts from bugleweed and lemon balm. After being diagnosed with hyperthyroidism, the patient began taking TS. On 9/12/16 the patient’s labs were improved with TSH 0.02mIU/L, FT4 0.88 ng/dL (0.8-1.8) and Total T3 86 (76-181). Three months later, the patient’s TSH was 1.89 with normal FT4, Total T3 and TSI. She took TS for 9 months. Her thyroid function tests have remained normal since starting TS, without the need for any other anti-thyroid medications.
Case 2: A 46 year-old female presented with periorbital edema in July 2018 and was referred to an ophthalmologist, who diagnosed her with thyroid eye disease. She was also complaining of palpitations and “jitteriness”. She was found to be hyperthyroid on labs and was treated with methimazole (MMI) between August 2018 and February 2019, requiring doses of up to 10mg BID. In March 2019 she stopped MMI due to transaminitis and began taking a thyroid tincture containing bugleweed and lemon balm extract. She has remained euthyroid on the herbal tincture, her transaminitis has resolved, and she has not required any further anti-thyroid medication. Her TSI, which was 0.84 IU/L (Normal&lt;0.55) in May 2019, normalized to 0.36 IU/L in June 2020, after 15 months on this tincture, which she is still taking.
Conclusion: In vitro and rat studies of bugleweed and lemon balm extract have demonstrated anti-thyroidal effects. This is the first report of the use of these plant extracts in the treatment of two patients with Graves’ disease, in whom it led to restoration of euthyroidism and normalization of TSI titers. Further study of the anti-thyroidal effects of bugleweed and lemon balm in humans is warranted to evaluate its potential role as an adjunctive therapy in Graves’ disease.References: 1. Auf’Mkolk, M., et al. “Extracts and Auto-Oxidized Constituents of Certain Plants Inhibit the Receptor-Binding and the Biological Activity of Graves’ Igs*.” Endocrinology, vol. 116, no. 5, May 1985, pp. 1687–93. 2. Winterhoff, H., et al. “Endocrine Effects of Lycopus Europaeus L. Following Oral Application.” Arzneim. Forsch., vol. I, no. 44, 1944.