bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Improvement in Hepatic Steatosis After Cushing’s Syndrome Treatment Is an Early Sign of Metabolic Recovery
Authors: Hamimi Ahmed , Sater Zahraa Abdul , McGlotten Raven , Matta Jatin , Pierce Annie , Abd-elmoniem Khaled , Ouwerkerk Ronald , Nieman Lynnette K , Gharib Ahmed M 
Published: May 2021

Abstract
Context: Cushing Syndrome (CS) is characterized by cortisol excess, impaired glucose tolerance, and obesity. As assessed by CT imaging, 20% of CS patients develop steatohepatitis (NASH). The gold standard test, liver biopsy, is associated with CS complications and cannot be used to confirm the diagnosis. This study evaluated the ability of magnetic resonance spectroscopy (MRS).
Objective: To identify the prevalence of NASH and its temporal changes in relation to other metabolic parameters in CS before and after successful treatment. Primary Outcome Measure: PDFF measured by MRS at 3T before, 6 and 12 months after Cushing’s syndrome treatment DESIGN: In this prospective IRB-approved study, 41 consecutive CS patients (44±1.8 y; 34(85%) females, 32.6±1.5 kg/m²; urine cortisol excretion 2242.7±1806.3 [3.5–45.0 mcg/24h]) underwent MRS before, 6 and 12months after successful treatment. PDFF was measured by MRS at 3T; NASH was defined as &gt;5% PDFF. Metabolic markers – glycohemoglobin (A1C) and body mass index (BMI) – were measured; Wilcoxon matched-pairs signed-rank test evaluated changes over time, and spearman rank test evaluated the correlation between variables. Results: At baseline, mean PDFF was 10.4±1.7 and correlated positively with BMI (r=0.5710, p&lt;0.0001). NASH was present in 32% of patients. After treatment, PDFF decreases were similar at 6 and 12 months (-52%, p=0.001 and -50%, p=0.02, respectively); rates of NASH declined to 13% and 11%. BMI decreased (-9%; p=0.0018 and -12%, p=0.0003) but without a statistically significant change overweight/obese status. A significant decrease in A1C followed at 12 months (-12%, p=0.0005).
Conclusions: MRS-PDFF is valuable for diagnosing NASH in Cushing Syndrome, which can affect a third of this patient population. Liver fat decreases by 6 months after normalization of cortisol and precedes the improvement of A1C. Indicating that liver insulin resistance due to fat accumulation has an essential role in diabetes pathophysiology in CS.
The Grave Hematologic and Hepatic Effects of Hyperthyroidism
Authors: Ahmad Sara Miriam , Jiang Bryan 
Published: May 2021

Abstract
Background: Hyperthyroidism can present with a myriad of symptoms including some rare, but morbid systemic manifestations. Here we present the case of a patient who presented with thyrotoxicosis, pancytopenia and cholestatic liver disease.
Clinical Case: A 37 year-old Hispanic female with no significant past medical history presented with weight loss, fatigue, jaundice and irregular menstrual cycles ongoing for 10 months. Upon presentation, vitals were notable for mild tachycardia. She had significant jaundice and a visibly enlarged thyroid gland, while no thyroid eye disease was noted. The patient was found to have a hemoglobin level of 6.5 g/dL (12.0 - 16.0 g/dL), white blood cell level of 2.3 K/uL (4.5 - 11.0 K/uL) and platelet count of 82 K/uL (150 - 400 K/uL). Alkaline phosphatase was elevated to 214 U/L (34.0 - 104.0 U/L) and total bilirubin was 8.7 mg/dl (0.2 - 1.2 mg/dL) with direct bilirubin of 5.4 mg/dL (0.0 - 0.2 mg/dL). Thyroid panel revealed an undetectable TSH and a free T4 of 5.58 ng/dL (0.61 - 1.18 ng/dL). Hematological work-up was negative for malignancy but did note severe iron deficiency. Hepatitis B and C virus, parvovirus B19 serology, magnetic resonance cholangiopancreatography, and autoimmune disease work-up all returned normal. Thyroid uptake scan showed diffuse uptake without nodular disease and a 24-hour uptake of 57% (normal 7-32%). Thyroid stimulating antibodies were positive at 115 IU/L (0.00-0.55 IU/L). Since all other work up was negative, it was concluded that her pancytopenia and cholestatic pattern of liver injury were likely due to hyperthyroidism with plan to do a bone marrow biopsy if she does not have improvement in blood cell counts. Patient was treated with radioactive iodine (RAI) ablation. A week after treatment she had further elevation in total bilirubin, whereas her blood counts had improved. It was decided to initiate methimazole with close monitoring of her liver function tests. Two months after treatment, her thyroid function improved and she was eventually transitioned to levothyroxine for post-ablative hypothyroidism. Bilirubin improved to normal range and her pancytopenia resolved without additional intervention. She had complete resolution of jaundice and started having regular menses 2 months after her RAI treatment.
Conclusion: The etiology of pancytopenia has been thought to be multifactorial with consumption of nutrients (including iron, manifesting as iron deficiency anemia), stimulation of erythropoiesis and sequestration of blood cells due to splenomegaly. Thyroid associated hepatic dysfunction has been proposed to be secondary to relative hypoxia in the perivenular regions and the direct toxic effect of thyroid hormone on hepatic tissue. In patients with concurrent hepatic disease and thyrotoxicosis, it is reasonable to consider treatment with thionamides with close monitoring, if other etiologies for hepatic disease are ruled out.
Thyroid Paraganglioma- An Unusual Head and Neck Tumour
Authors: Sim Sing Yang , Al-Mrayat Ma’en 
Published: May 2021

Abstract
Paragangliomas are neuroendocrine tumour originating from the neural crest-derived paraganglia with majority arising from the head and neck. (1)Thyroid paraganglioma are exceedingly rare neuroendocrine tumours accounting for &lt;0.1% of thyroid malignancy (1)
We present a 57 years old gentleman who was referred to ENT surgeon following discovery of a two month history of lump on his left neckIt has not changed in size and not caused any symptoms such as anxiety, sweats, palpitations, dizziness or unexplained headaches. He has a Past medical history of epilepsy following a Road traffic accident 28 years ago leaving him seizure prone. He has no family history of neuroendocrine tumours His ultrasound scan of his thyroid gland showed a 25 x 23 x 15mm lesion lying anteriorly within the left thyroid lobe. There are two highly reflective foci which could represent microcalcification. It was classified as U5 lesion He proceeded with fine needle aspiration which confirmed carcinoma of the left thyroid gland with no clear differentiation between follicular or papillary carcinoma. He undergone a total thyroidectomy and left central level VI lymph node dissection His histology confirmed a thyroid paraganglioma staining strongly positive for neuroendocrine markers (Synaptophysin and chromogranin) while S-100 shows positivity in the sustentacular cells. He was referred for genetic testing which demonstrate no evidence of mutation in FH, SDHAF2, SDHB/C/D, RET, MAX, TMEM127 and VHL gene. He was commenced on levothyroxine replacement at a dose of 150micrograms OD. His urine metanephrines is 178.1pmol/L (0-510), urine normetanephrines 192.9pmol/L (0-1180) and 3-methoxytyramine &lt;75pmol/ L (0-180) (all normal). His MRI neck revealed no synchronous tumour. He continues to be followed up under our endocrine clinic.
Conclusion: Due to the rarity of these tumours, their natural history is mostly unknown. Nevertheless, postoperative surveillance should include plasma or urinary metanephrines and ultrasonography.
References: 1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3824793/
Thyroid Storm: A Diagnostic Conundrum
Authors: Maharaul Mashrutee S , Raghuwanshi Maya P , Umar Rehan , Pishdad Reza 
Published: May 2021

Abstract
Thyroid storm is a life threatening complication of hyperthyroidism which comes with multi-system involvement and is associated with a mortality of 8-25% despite modern advancements in treatment and supportive measures.
A 47 year old woman with past medical history of hypertension and morbid obesity presented to the emergency room with 3 week history of shortness of breath and chest pain associated with productive cough, bilateral leg swelling, orthopnea and palpitations. Upon evaluation, she was in moderate respiratory distress, restless, tachypneic and tachycardic. She had bilateral proptosis and visible jugular venous pulsation along-with bibasilar crackles and pitting edema bilaterally. Lab tests revealed BNP 539 pg/ml and D-Dimer 6401 ng/ml. ECG showed atrial flutter, Chest X-Ray showed bilateral pleural effusions, and CT Chest was negative for pulmonary embolism but revealed anterior mediastinal mass, differential of which included thymoma or teratoma. She was admitted to CCU for aggressive diuresis, control of heart rate and was started on anticoagulation. A review of medical records from outside hospital revealed patient was hyperthyroid 8 months ago, however, was not on any medications. Given a Burch-Wartofsky score &gt;70, she was started on IV hydrocortisone and cholestyramine for severe thyrotoxicosis. Endocrinology was consulted and added PTU to management. TFTs revealed a TSH 0.006 IU/ml, FT4 4 ng/dL and T3 2.5 ng/ml. Bedside ECHO showed LVEF of 14% with global hypokinesis and thyroid ultrasound revealed an enlarged, heterogenous thyroid with a solid, isoechoic, calcified left lobe nodule measuring 0.8 x 0.4 x 0.5 cm. Her serum TSI and thyrotropin receptor antibodies were elevated at 17.20 IU/L and 20.20 IU/L, respectively. She responded to treatment and was discharged on metoprolol, losartan, spironolactone, and furosemide for new-onset heart failure, apixaban for atrial flutter, and PTU and cholestyramine for hyperthyroidism, with Cardiology and Endocrinology follow-ups.
Thyroid disease is a common illness affecting 9 to 15 percent of the adults. Thyrotoxicosis refers to the clinical syndrome of hyper-metabolism due to excessive amount of circulating thyroid hormones. The incidence of thyroid storm is 0.57 to 0.76 per 100,000 people per year in the US. It most commonly occurs in women and is more common in patients with underlying Grave’s Disease. The exact underlying mechanism that leads to thyroid storm is not well understood but adrenergic activation seems to have a major role. Our patient had long standing untreated hyperthyroidism with a solid nodule which led to the crisis. The most common cause of death is cardiopulmonary failure and hence treatment should be initiated as soon as diagnosis is suspected owing to high mortality.
Awareness of thyroid pathology affecting the heart is important to remember in evaluating the etiology of heart failure in patients.
Thyroid Storm: A Dreaded Complication of Percutaneous Tracheostomy
Authors: Pradeep Pallavi , Kazi Mohammed Hussain 
Published: May 2021

Abstract
Background: Thyroid gland may be manipulated during tracheostomy. Although uncommon, this may result in potentially life-threatening thyroid storm especially in patients with underlying thyroidal illness. Plasmapheresis maybe used as a treatment modality for these patients.
Clinical Case: A 65-year-old Hispanic male was admitted to the hospital for acute exacerbation of heart failure and pneumonia. Medical history was significant for atrial fibrillation. He had been on amiodarone for 2 years, which was discontinued 2 months ago when he was diagnosed with amiodarone indued thyrotoxicosis (AIT). He was never started on any treatment for AIT. Lab work on admission was significant for undetectable TSH, fT4 of 4.4 ng/ml (RR: 0.8-1.5 ng/ml) and fT3 of 4pg/ml (RR: 2.2- 4.0 pg/ml). TSH receptor antibody was negative. Thyroid ultrasound showed mildly atrophic gland with no nodules. Methimazole, cholestyramine and hydrocortisone were initiated, and TFTs were trending down. Hospital course was complicated by cardio-respiratory failure requiring mechanical ventilation. After a short-term improvement in his clinical status, patient underwent percutaneous tracheotomy due to failure to wean from mechanical ventilation. On POD1, he was found to be tachycardic and febrile with Burch-Wartofsky score of 55, which was highly suggestive of thyroid storm. fT4 was &gt;8ng/ml and fT3 was 11.4pg/ml. He did not respond to maximal doses of thionamides, steroids and b-blocker. Thyroidectomy was considered, but patient was deemed to be high risk for any surgical intervention. Plasmapheresis was initiated for 5 days. TFT started trending down and patient improved clinically. On POD 14, fT4 was 2.1ng/ml, fT3 was 3.8 pg/ml.
Conclusion: This case highlights a rare complication of tracheostomy in a patient with known history of AIT. Studies have shown that there can be a significant increase in serum thyroid hormone levels after tracheostomy, even in euthyroid patients. There may even be a role of performing tracheostomy with thyroidectomy in non-euthyroidal patients. Use of plasmapheresis for thyroid storm is recommended by American Society of Apheresis when first line medical therapy fails. It maybe particularly effective in AIT as amiodarone and its active metabolite are highly bound to plasma proteins. To our knowledge, this is the first case of thyroid storm with a history of AIT, which was precipitated by tracheostomy, and successfully treated with plasmapheresis.
References: 1. Esen E, Karaman M, Deveci I, Tatlıpınar A, Tuncel A, Sheidaei S, Esen S. Analysis and comparison of changing in thyroid hormones after percutaneous and surgical tracheotomy. Auris Nasus Larynx. 2012 Dec;39(6):601-5.2. Muller C, Perrin P, Faller B, Richter S, Chantrel F. Role of plasma exchange in the thyroid storm. Ther Apher Dial. 2011 Dec;15(6):522-31.
Thyrotoxic Periodic Paralysis in Young Caucasian Male
Authors: Panthi Sujata , Bhattacharya Rajib Kumar 
Published: May 2021

Abstract
Background: Thyrotoxic periodic paralysis (TPP) can be a medical emergency as delay in diagnosis can lead to life-threatening arrhythmia. Periodic paralysis is more prevalent in the Asian population. We report a case of thyrotoxic periodic paralysis in a young Caucasian male.
Case: A 24-year-old male with a past history of Graves’ disease, hypertension, and asthma was brought to the hospital due to leg weakness and fall. He was initially diagnosed with Graves’ disease 2 years ago. The patient could not take methimazole or metoprolol due to the affordability issue for the last 18 months. On presentation, he fell on the floor while attempting to stand up from the couch. He could not stand up or pick his cell phone. He remained on the floor for 2-3 hrs. A review of the system was positive for palpitation and fatigue and negative for diarrhea, weight loss, anxiety, sleep problem, and dry eyes. On arrival, he had a pulse of 100/min, BP of 157/85 mmHg with rest of vitals signs normal. Motor strength on bilateral lower extremities were 2/5. Upper extremity strength was normal. No thyromegaly or thyroid bruit was noted in the exam. The rest of the physical exam was normal. Labs showed Potassium 1.9 with a normal reference range (RR) of 3.5 - 5.1 mmol/l. His TSH was &lt; 0.01 (RR 0.35 - 5.00 MCU/ML), Free T4 was 5.0 (RR 0.6- 1.6 NG/DL), Total T3 was 425 (RR 87 - 180 NG/DL) and CK was 70 (RR 35- 232 U/L). EKG showed sinus rhythm at 90 bpm with no PR, T/ST, or QT abnormalities. He was given IV potassium and was also started on methimazole 10mg TID and metoprolol. His weakness and tachycardia were improved the next day. We discussed with him the options of medical management vs. surgery. He underwent a total thyroidectomy. Biopsy showed nodular hyperplasia consistent with graves’ disease.
Discussion: Thyrotoxic periodic paralysis (TPP) is characterized by hypokalemia and episode of acute muscle weakness in lower extremities in the setting of hyperthyroidism. The pathophysiology of TPP remains uncertain. Hyperthyroidism is a hyperadrenergic state in which beta-2-adrenergic stimulation in muscle cells directly induces cellular K+ uptake by increasing cAMP, leading to activation of Na/K ATPase. The increase in the influx of intracellular K+ leads to hypokalemia and skeletal muscle weakness. Some studies show pathophysiology can be different in Caucasians compared to the Asian population that there could be abnormalities in Na and K channels other than Na/K ATPase. Potassium replacement should be done with caution as hypokalemia is due to intracellular shift and rebound hyperkalemia is common during the management. Beta-blocker may reverse adrenergic overstimulation of Na/K ATPase. It can help rapidly improve paralytic symptoms.
The Prevalence of Adrenal Insufficiency in Kidney Transplant Recipients
Authors: Martin-Grace* Julie , Tomkins* Maria , Kennedy Carmel , Enroe Olive Mc , Heverin Karen , Srinivasan Shari , Little Dilly , Conlon Peter , De Freitas Declan , Denton Mark , Magee Colm , O’Seaghdha Conall , O’Reilly Michael William , Thompson Chris John , Sherlock Mark 
Published: May 2021

Abstract
Long term glucocorticoid therapy is a key component of immunosuppression for kidney transplant recipients (KTR), leading to a significant cumulative glucocorticoid exposure in this cohort. However, assessment of adrenal function and steroid education do not feature in clinical practice guidelines for KTR. This study aims to investigate the prevalence of adrenal insufficiency (AI) in KTR on maintenance prednisolone and develop a simple screening algorithm to identify patients at highest risk of AI. 67 KTR receiving prednisolone were recruited, with a median age of 52 yrs (IQR 39–64) and median time since transplantation of 79 months (IQR 46–146). Patients with known hypothalamic-pituitary-adrenal axis pathology, exposure to oral oestrogens or impaired graft function (creatinine &gt;170 umol/l) were excluded. Participants underwent a short synacthen test [SST, Roche Elecsys II immunoassay, pass cortisol &gt; 430 nmol/l, CV assay 1.8-2,1%)], assessment of lifetime glucocorticoid exposure and an assessment of metabolic health.72% (n=48) of participants failed the SST(30 min cortisol &lt; 430nmol/l). Participants with AI had a higher daily prednisolone dose (4.9 vs 4.2mg/day, p=0.002), a greater cumulative glucocorticoid exposure (289 vs 111 mg/kg, p=0.03) and lower estimated glomerular filtration rate (63 vs 81 ml/min/1.73m2, p=0.03) than those with intact adrenal function. There was no difference in duration of glucocorticoids post transplantation, previous transplant history, pre-transplant glucocorticoid exposure, immunosuppression regime, exposure to other glucocorticoid preparations, BMI and cortisol binding globulin concentration between those who passed or failed a SST. Participants with AI had a lower baseline cortisol (143 vs 303 nmol/l, p&lt;0.001), lower baseline serum ACTH (14 vs 20 pg/ml), a lower peak stimulated cortisol (325 vs 490 nmol/l, p&lt; 0.001) and lower cortisol response (139 vs 189 nmol/l, p=0.013) to synacthen testing than those with normal adrenal function. A morning cortisol of &lt;294 nmol/l predicted AI result with 100% sensitivity (95% CI 92–100%, p&lt; 0.001) and 63% specificity, therefore AI could be excluded if morning cortisol &gt;300nmol/l, reducing the need for stimulatory testing. Our results suggest KTR are at higher risk for AI than previously reported, highlighting a need for greater patient and physician awareness regarding AI. We suggest that KTR with a morning cortisol &lt; 300nmol/l are at high risk of AI, and dynamic testing should be considered for these patients.
Transdermal Absorption of Methimazole- a Cat’s Tale
Authors: Mittal Ashima , Gordon Murray B 
Published: May 2021

Abstract
Introduction: In modern civilization different kinds of animals live with us as pets. These pets have different diseases and are on medications. Close contact with animals can cause medication adverse reactions or may worsen pre-existing conditions in humans. Here we present an interesting case of hypothyroidism worsened by transdermal absorption of methimazole administered for feline hyperthyroidism. Case History: 66-year-old Caucasian female with past medical history of postoperative hypothyroidism s/p total thyroidectomy secondary to multinodular goiter due to Hashimoto’s thyroiditis with a 0.2 cm papillofollicular microcarcinoma and 0.7 cm follicular adenoma presented for follow up. She complained of weight gain, lethargy and dry skin for the past 4 months. She was on a stable dose of levothyroxine 112 mcg daily for the past year. She took her pill correctly and did not miss any doses. Her other medical problems were impaired fasting glucose, osteopenia and B12 deficiency. Her repeat thyroid function tests showed TSH 11.2 mc IU/ l (0.4 -4) (TSH - 0.538 mc IU/ L 6 months back), T4 - 6.8 mcg/ dl (4.5 - 12) (T4 8.9 6 months back). She had a measurable serum thyroglobulin of 0.4 ng/ml with antithyroglobulin antibody 11 IU/ml (&lt;115) consistent with some residual thyroid tissue despite her history of a “total thyroidectomy”. Due to recent worsening of her symptoms with elevated TSH on background of previous stable levothyroxine requirement, further detailed history was taken. She reported that her cat was suffering from hyperthyroidism, treated with methimazole 10 mg daily. The patient used to cut the pill in half with bare hands and fed it to her pet. She also used to handle wet methimazole that her cat coughed up. Her levothyroxine dose was continued at 112 mcg daily. The patient was advised to use gloves before feeding and wash her hands after feeding her cat. Her symptoms resolved after she took precautions and TSH normalized to 1.170 mc IU/ l with T4 7.6 two months later. Conclusion: Absorption of methimazole by transdermal administration has been shown in cats1. A study by Kasraee et al showed safety of a 5% topical methimazole application for treatment of post inflammatory hyperpigmentation in humans with no change in thyroid function tests2. Our case contradicts this study and indicates that methimazole might be absorbed transdermally in humans. To conclude, more studies are needed to study the effect of transdermal administration of methimazole in humans.
References: 1. Hill KE, Mills PC, Jones BR et.al. Percutaneous absorption of methimazole: an in vitro study of the absorption pharmacokinetics for two different vehicles. J Vet Pharmacol Ther. 2015;38(6):581-589. PMID: 25683868 2. Kasraee B et al. Safety of topical methimazole for the treatment of melasma. Transdermal absorption, the effect on thyroid function and cutaneous adverse effects. Skin Pharmacol Physiol. 2008;21(6):300-305. PMID: 18667842