bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Thionamide Paradox: Thyrotoxicosis With Neutropenia as Initial Presentation of Grave’s Disease
Authors: Celis Valentina , Manzano Alex 
Published: May 2021

Abstract
Hyperthyroidism typically presents with symptoms such as tremors, palpitations, weight loss, heat intolerance and anxiety. Although rare, anemia, leukopenia or thrombocytopenia may develop as an unusual manifestation of thyrotoxicosis. Hematologic derangements have been reported as a side effect of antithyroid drugs (ATD) as well, and while ATD associated agranulocytosis is uncommon, it is a life-threatening condition.
A 49-year-old Hispanic female with history of iron deficiency anemia came to the emergency department (ED) with a chief complaint of palpitations. Also reported fatigue, myalgias, headache and anxiety of 1 week duration. Upon​ arrival to the ED she was tachycardic, appeared anxious and diaphoretic. Physical examination revealed a very discrete, non-tender goiter. Bloodwork showed hemoglobin 9.1 g/dL (12.0-16.0), WBC 2.30 c/µ​L (4.8-10.8),​ ANC 1.04 c/µ​L​ (1.80-7.20), ALC 0.88 c/µ​L​ (1.20-4.0), PLT 209 c/µ​L​ (150-450). TFTs were pertinent for TSH 0.007 UIU/mL (0.35-3.74), free T4 5.11 ng/dL (0.76-1.46) and total T3 555 ng/dL (60-181). She received initial treatment with hydrocortisone 300 mg and PTU 300 mg. She was admitted and started on propranolol 40 mg TID and prednisone 20 mg daily, but further doses of ATD were initially held due to concerns for her marked leukopenia. She subsequently became acutely psychotic with psychomotor agitation, visual and auditory hallucinations. CT of the brain revealed no acute abnormalities. She was started on olanzapine 2.5 mg daily for hyperthyroidism induced psychosis, along with methimazole 20 mg daily, KI (Lugol solution) 0.35 mL BID and cholestyramine 4g BID. Further workup of leukopenia showed no dysplastic​ cells on​ peripheral smear, normal vitamin B12 and folate levels, and negative HIV. She displayed marked improvement, denied ongoing hallucinations after 72 hours of initiating ATD, and WBC subsequently normalized. Thyroid workup was diagnostic for GD with positive TRAB and TSI. She was discharged in stable condition on methimazole 40 mg daily.
Agranulocytosis is a rare side effect of ATD (prevalence ~0.5%) and average time of onset is usually within 2-3 months after starting therapy. Although the majority of cases of hematologic alterations in GD are seen as a complication of ATD, our patient presented with the peculiarity that leukopenia (with both neutropenia and lymphopenia) was associated to untreated hyperthyroidism. This case illustrates the fact that in patients presenting with hyperthyroidism and leukopenia, treatment with ATD has proven to result in achievement of euthyroid state along with a sustained improvement in blood cell levels. Despite its rarity, agranulocytosis has become essentially ingrained to ATD amongst medical professionals. Clinicians should be aware that neutropenia is an uncommon feature of uncontrolled hyperthyroidism and feel confident with initiating ATD in this setting.
Thyroid Abscess After FNA Biopsy: A Case Report
Authors: Purdy Nicholas , Jodie Reider , Kevin Stavrides 
Published: May 2021

Abstract
Introduction: FNA biopsy of thyroid nodules is a common bedside procedure that rarely causes serious complications. Thyroid abscess is a rare complication of FNA that requires prompt diagnosis and treatment. We present a case of a thyroid abscess occurring 4 weeks after FNA in a 46 year old female, treated successfully with surgery.
Clinical Case: A 46 year old woman with history of acne presented with dysphagia, right sided neck pain and swelling 4 weeks after FNA of a 4.8cm right thyroid nodule with benign cytology. On physical examination, the right thyroid lobe appeared larger and was tender to palpation. The patient was afebrile. Laboratory evaluation was significant for acutely low TSH 0.06 uIU/mL [0.50 - 6.00 uIU/mL], thrombocytosis 547 K/uL [140 - 400 K/uL] and marked elevated sedimentation rate 98 mm/hr [0 - 20mm/hr]. Interestingly, she had a normal leukocyte count of 9.8 K/uL [4.00 - 10.80 K/uL]. US imaging showed acute increase in size of the right thyroid nodule to 7.6cm. CT neck confirmed a large, partially cystic right thyroid mass and further showed mass effect on surrounding structures and mild stranding in the subcutaneous fat. The patient elected for surgical treatment rather than repeat FNA with drainage of fluid components. Right thyroid lobectomy was planned but converted to surgical abscess drainage with subtotal thyroidectomy due to intense inflammatory changes in the neck. A large amount of purulent material was drained and sent for cultures, which grew multiple Staphylococcus species and Propionibacterium acnes. Surgical pathology showed granulation and connective tissue including skeletal muscle tissue with marked active chronic inflammation, micro abscess formation, few multinucleated giant cells, and fibrosis. Following surgery, TSH normalized, and the patient reported immediate improvement in symptoms of neck fullness, pain, and dysphagia. She was discharged home on post operative day one with a two week course of oral Augmentin 875mg twice daily. 6 weeks post operatively the patient remains symptom free in her usual state of health.
Conclusion: Thyroid abscess following FNA is a rare occurrence with few reported cases in the literature. Because of its rarity, diagnosis and treatment may be delayed, resulting in a life-threatening emergency. Both repeat needle aspirations and surgical management, combined with culture directed antibiotics, are acceptable methods for treatment. Immunocompromise, not present in our patient, is the main risk factor reported for thyroid abscess. Propionibacterium and Staphylococcus commonly cause acne, which may have increased our patient’s risk of infection. Our case highlights the importance of maintaining a high level of clinical suspicion for abscess in patients who develop neck pain and swelling following FNA, even in the absence of significant risk factors, in order to facilitate prompt diagnosis and treatment.
Transient Thyrotoxicosis in Molar Pregnancy
Authors: Jancuska Ashley , Hendrickson Chase Dean , Rhee Chanhaeng 
Published: May 2021

Abstract
Introduction: Thyroid function abnormalities commonly occur in pregnancy. Due to the structural homology between beta-human chorionic gonadotropin (beta-hCG) and thyrotropin (TSH), some of these changes may be physiologic, while others can be from pathologic causes. Molar pregnancies represent a unique etiology, as beta-hCG levels are often markedly elevated due to trophoblastic hyperplasia and can cause hyperthyroidism. Case Description: A 20-year-old pregnant female presented at 18 weeks estimated gestational age for persistent nausea and vomiting, which had worsened over the past one to two weeks. She also noted palpitations and heat intolerance. On initial presentation, her heart rate was 145 beats per minute, blood pressure was 135/86 mmHg, oxygen saturation was 98% on room air, and temperature was 98.3 F. Exam was notable for sinus tachycardia; no thyromegaly, palpable thyroid nodules, lower extremity edema, or tremors were appreciated. Transvaginal ultrasound was performed, and an approximately 17-week fetus with no cardiac activity was identified; an enlarged and hydropic placenta and bilateral theca lutein cysts were also seen on imaging, concerning for a partial molar pregnancy. Laboratory data revealed plasma beta-hCG &gt;1,000,000 mIU/mL. Due to her symptoms and tachycardia that were refractory to intravenous hydration, thyroid function tests (TFTs) were assessed: TSH of 0.01 uIU/mL and free T4 (FT4) 6.85 ng/dL. She was started on methimazole and beta blockade in the pre-operative period. She received mifepristone and underwent dilatation and evacuation. Histopathology was consistent with a partial mole, given the presence of fetal somatic differentiation. Beta-hCG and FT4 levels rapidly trended down in the post-operative setting, and methimazole was discontinued. Levels were monitored closely after discharge. Atenolol was stopped when her TFTs normalized. Approximately six weeks after surgery, her TSH was 0.523 uIU/mL and FT4 was 0.70 ng/dL. Three months after surgery, the beta-hCG level had decreased to 4 mIU/mL. Discussion: In North America, the incidence of hydatidiform moles is approximately 100 per 100,000 pregnancies. Hydatidiform moles compromise two distinct entities: complete moles and partial moles, which are distinguishable based on karyotype and histopathological features. In molar pregnancies, the trophoblastic tissues, which produce hCG, are hyperplastic; thus, markedly elevated hCG levels can be seen. Due to its structural similarity to TSH, beta-hCG can activate TSH receptors and drive production of thyroid hormone, which can subsequently result in a thyrotoxic state. Surgical management of the mole is key, as the hyperthyroidism usually resolves with uterine evacuation, though hCG levels must be monitored closely afterwards to ensure gestational trophoblastic neoplasia does not develop.
The Prevalence of Tertiary Adrenal Insufficiency in Patients Receiving Topical Glucocorticoid Treatment for Oral Lichen Planus
Authors: Einarsdottir Margret J , Bankvall Maria , Robledo-Sierra Jairo , Rödström Per-Olof , Trimpou Penelope , Johannsson Gudmundur , Hasséus Bengt , Ragnarsson Oskar 
Published: May 2021

Abstract
Objective: Glucocorticoid (GC) treatment suppress the hypothalamic-pituitary-adrenal axis, which may lead to tertiary adrenal insufficiency. This study aimed to investigate the prevalence of tertiary adrenal insufficiency among patients with oral lichen planus treated with topical GC (clobetasol propionate) in the oral cavity, a standard treatment option for this condition.
Methods: In this cross-sectional study, we included 24 patients with oral lichen planus receiving long-term (&gt; 6 weeks) clobetasol propionate treatment. Adrenal function was assessed by measuring serum cortisol between 8–9 AM, after a withdrawal of treatment for 48 hours. For patients with serum cortisol concentrations below 280 nmol/L (10 µg/dL), a 250 µg corticotropin stimulation test was performed.
Results: Twenty patients had normal serum cortisol concentrations (range 280–621 nmol/L), whereas four patients had low serum cortisol concentrations (13, 45, 63, and 229 nmol/L, respectively). A corticotropin stimulation test revealed partial adrenal insufficiency in two patients (serum cortisol peak level 350 nmol/L and 360 nmol/L) and severe adrenal insufficiency in another two patients (serum cortisol peak level 150 nmol/L and 210 nmol/L).
Conclusion: In this small study, approximately 20% of patients receiving chronic topical GCs treatment for oral lichen planus had tertiary adrenal insufficiency. It is essential to be aware of this potential risk and to inform patients about the need for GC stress-doses during an intercurrent illness episode.
Urine Proteomic Analysis of Differences Between Patients With Hyperthyroidism Before and After Carbimazole Treatment
Authors: Masood Afshan 
Published: May 2021

Abstract
Background: Hyperthyroidism, characterised by increased circulating thyroid hormone (TH) levels, alters the body’s metabolic and systemic haemodynamic balance and directly influences renal function However, the underlying mechanisms and metabolic implications of these changes are not well understood. Objective: In the present study we aimed to study the changes occurring in the urinary proteome of patients with hyperthyroidism before and after treatment. The levels of the excreted proteins in the urine were studied using an untargeted 2D DIGE MALDI TOF proteomic approach with network analysis. Methods: The study included 9 age matched patients with mean age 38.6 ± 12.1 years with newly diagnosed hyperthyroidism. The patients were evaluated at baseline and after receiving treatment with carbimazole. Urine samples were obtained from the same patient at baseline (hyperthyroid state) with serum FT4 levels of 35.4 + 9.9 pmol/L and TSH 0.014 + 0.014 mIU/L (mean + SD), and post treatment with anti-thyroid drugs (euthyroid state) with levels of FT4 17.0 + 2.8 pmol/L and TSH 0.6 + 0.5 mIU/L (mean + SD).
Results: Alterations in the abundance of urinary proteins, analyzed by Progenesis software, revealed statistically significant differential abundance in a total of 40 spots corresponding to 33 proteins, 26 up and 7 down (≥1.5-fold change, ANOVA, p ≤ 0.05). The proteins identified in the study are known to regulate processes related to cellular metabolism, transport, acute phase response. The urinary proteins upregulated with hyperthyroidism included serotransferrin, transthyretin, serum albumin, ceruloplasmin, α1B glycoprotein, syntenin-1, nesprin, and glutamilnyl peptide cyclotransferase while the 3 notable down regulated proteins were plasma kallikrein, protein glutamine gamma-glutamyl transferase and serpin B3. Bioinformatic analysis using Ingenuity Pathway Analysis (IPA) identified dysregulation of pathways related to cellular compromise, inflammatory response, cellular assembly and organization and identified the involvement of the APP and AKT signaling pathways via their interactions with interleukins as the central nodes. Conclusion: The urine proteomic profiling between the hyperthyroid and euthyroid states demonstrates alteration in the protein levels involved in acute phase response and in maintaining an individual’s haemodynamic state.
A Case of Renal Cell Carcinoma and Pheochromocytoma Due to Germline Inactivating Mutation in Fumarate Hydratase (FH)
Authors: Reda Sarah Alicia , Japp Emily A , Si Qiusheng , Badani Ketan , Levine Alice C 
Published: May 2021

Abstract
A 60-year-old female with a history of well-controlled hypertension, prediabetes, status post hysterectomy for fibroids, presented for evaluation of hematuria and unintentional weight loss. She denied palpitations, headaches, tremors, and diaphoresis. Initial CT demonstrated a right renal mass suspicious for renal cell carcinoma and an adrenal mass. Magnetic resonance imaging (MRI) confirmed a hypervascular, right adrenal mass (6.7 x 6 x 5 cm) without loss of signal.
Laboratory Testing: elevated 24-hour urine vanillylmandelic acid (VMA) 17.5 mg/24 h (&lt;6), and urine normetanephrines 2276 ug/24 h (122-676) with normal urine metanephrines 158 ug/24 h (90-315). 24-hour urine free cortisol was normal. The patient underwent a right adrenalectomy and partial nephrectomy. Pathology confirmed a low-grade renal cell carcinoma (RCC) and a 6.8 cm pheochromocytoma (PCC). Genetic analysis revealed an inherited mutation in the fumarate hydratase (FH) gene, which is diagnostic of hereditary leiomyomatosis and renal cell cancer (HLRCC). Wildtype FH codes for an enzyme that converts fumarate to malate in the mitochondrial Krebs cycle. Inactivating mutations in FH trigger the hypoxia pathway by activating hypoxia-inducible factor (HIF) thereby promoting tumor growth and angiogenesis.
In PCC, 30-40% are hereditary and another 40-50% are found to have somatic mutations in 1 of 20 PCC susceptibility genes. Several autosomal dominant heritable syndromes, including Neurofibromatosis type 1 (NF-1), von Hippel-Lindau (VHL), Multiple Endocrine Neoplasia Type 2 (MEN 2), and Paraganglioma Syndromes Types 1–5, have an increased incidence of PCC, most of which modulate hypoxia pathways. FH mutations are similarly inherited in an autosomal dominant fashion and cause HLRCC.
HLRCC is associated with 75-80% risk for cutaneous and uterine leiomyomas, and a 10-16% risk for type II papillary renal cell carcinoma. The risk of RCC in patients with FH mutations is much greater than in the general population, where the prevalence is ~2% in those who lack the mutation. In one study, FH deficiencies attribute between 19-41% of all RCC cases. Rare families with PGL/PCC have also been found to carry this germline FH mutation. This FH mutation is associated with increased risk of metastasis in patients with PGL/PCC by a similar mechanism of carcinogenesis via the hypoxia pathway. Currently, there are no strict guidelines for surveillance in individuals with HLRCC, however, patients should have a yearly abdominal MRI, skin examination every 2 years, and an annual gynecological evaluation for leiomyosarcoma. Each first-degree relative should be offered genetic testing of the FH mutation, as 50% of relatives may carry the gene. This case underscores the importance of genetic workups in patients with PCC, especially if associated with other tumors.
Hypercalcemia in Pheochromocytoma: From MEN to VHL
Authors: Mittal Madhukar , Gupta Parul , Chaudhary Gautam R , Garg Mahendra K 
Published: May 2021

Abstract
Background: Co-occurrence of phaeochromocytoma and primary hyperparathyroidism is usually seen in patients of Multiple Endocrine neoplasia 2A(MEN2A) and is rare in Von Hippel Lindau disease (VHL). Parathyroid adenoma with pheochromocytoma in a genetically confirmed VHL has been reported only once till date (1). Clinical Case: A 30-year male was admitted for evaluation of hypertension and incidentally diagnosed adrenal mass on ultrasound. 9-years back, he was diagnosed as a case of VHL (right renal clear cell carcinoma, pancreatic cystadenoma, spinal hemangioblastoma and epididymal cysts). Right nephrectomy and pancreatic cyst excision had been done and past work-up for pheochromocytoma was normal. He also had been operated twice for recurrent renal calculi. Family history revealed surgery in mother for pancreatic mass. Current imaging revealed right adrenal mass (4.7*4.6 cm) with left renal cysts and calculi, pancreatic cysts and spinal- medullary hemangioblastoma and epididymal cysts. Fundus examination was normal. 24-hours urinary fractionated normetanephrines were elevated (2062 mcg/24 hours) and I131MIBG scan showed 4.7*4.6cm concentrating lesion in right renal fossa suggestive of right adrenal pheochromocytoma. However his biochemical evaluation revealed hypercalcemia (12.1 mg/dl), low phosphorus (3.2 mg/dl), low 25(OH) D (24.84 nmol/l), and raised PTH (121pg/ml). Ultrasound neck and Tc99m-Sestamibi localized left inferior parathyroid adenoma. DEXA scan showed severe osteoporosis. Genetic analysis confirmed VHL mutation in exon-1. Calcitonin and RET mutation were normal (ruled out MEN2A). Therapeutic approach was surgical excision of adrenal pheochromocytoma followed by parathyroidectomy. We report a case of pheochromocytoma with primary hyperparathyroidism (cause: left inferior parathyroid adenoma) in a patient of VHL (Renal clear cell carcinoma, pancreatic cystadenoma, epidydymal cysts and medullary and spinal hemangioblastoma). Hypercalcemia seen in patients of VHL is either due to bone metastasis/PTHrP/IL-6 secretion from RCC or due to PTHrP/PTH/calcitonin secretion from pheochromocytoma and rarely due to associated parathyroid adenoma. Literature search revealed four case reports of parathyroid adenoma with VHL. In only one of these, VHL had pheochromocytoma associated with parathyroid adenoma (1). Conclusion: Ours is the 2nd such case reported in literature of primary hyperparathyroidism in a genetically confirmed case of VHL with pheochromocytoma. This case highlights the overlap of tumorigenesis in two rare genetically divergent syndromes and importance of long-term follow-up for sequential development of new tumors. Reference: Arao T, Okada Yet al. A case of VHL disease with bilateral pheochromocytoma, renal cell carcinoma, pelvic tumor, spinal hemangioblastoma and primary hyperparathyroidism. Endocr J. 2002 Apr;49(2):181–8.
Metastatic Insulinoma Presenting After Bariatric Surgery in a Patient Subsequently Diagnosed With MEN 1
Authors: Poku Caroline A , Samarasinghe Shanika Prajani 
Published: May 2021

Abstract
Background: Hypoglycemia is a recognized complication of bariatric procedures due to changes in the gut hormonal milieu. Possible causes of hypoglycemia include dumping syndrome, nesidioblastosis and rarely insulinoma. MEN1 is a heritable disorder characterized by the occurrence of parathyroid, anterior pituitary and pancreatic islet cell tumors. Clinical Case: A 48 yo female with HTN, depression, PCOS, primary hyperparathyroidism s/p 3.5 gland parathyroidectomy 2008, facial angiofibroma 2011, obesity s/p gastric sleeve 2018, and a history of DMT2 presented with frequent episodes of hypoglycemia. DMT2 was diagnosed in 2003, but all DM drugs were withdrawn shortly after sleeve gastrectomy. One year after surgery, she started to develop primarily fasting hypoglycemia in the 40-50 mg/dl range confirmed on CGM. Symptoms included perioral numbness, diaphoresis and confusion which resolved with glucose tablets. She reported a 7 kg weight regain due to eating every 2 hours to minimize episodes but symptoms progressed. Family history was significant for HTN and DM. A 72 hour fast confirmed hyperinsulinemia with symptomatic hypoglycemia at a serum glucose of 37 mg/dl, a suppressed ß-hydroxybutyrate of 0.6 mmol/L, elevated proinsulin 7.7 ρmol/L and inappropriate normal c-peptide 0.8 ng/mL. The oral hypoglycemic panel was negative. A pancreatic protocol CT revealed a 1.2 cm heterogeneous arterial enhancing lesion in the body of pancreas, a 0.6 cm focus in the tail of pancreas, a 1.6 cm enhancing lesion in the liver and a 1.4 cm abdominal wall mass. Genetic testing was positive for MEN-1 and additional biochemical evaluation including VIP, gastrin and glucagon was negative. A pituitary MRI was unremarkable. She underwent an ex-lap, partial hepatectomy, distal pancreatectomy, splenectomy, and resection of the duodenal mass. The pancreas had multiple NETs, largest was 1.6 cm and stained positive for insulin. The liver mass demonstrated a metastatic well differentiated NET. The 1.7 cm duodenal mass was consistent with a leiomyoma. All surgical margins were negative, but focal lymphovascular and perineural invasion was identified with negative lymph nodes (0/27). She was diagnosed with a metastatic insulinoma with histopathology revealing a well differentiated neuroendocrine tumor G1, &lt;1mitosis/2mm2, Ki-67 less than 3%, stage pT1N0M1. Hypoglycemia resolved post-operatively. Conclusion: Hypoglycemia predominantly in the fasting state, worsening shortly after bariatric surgery, or refractory to dietary or medical management should be further evaluated to exclude insulinoma. Given her medical history, there was concern for MEN-1, thus prompting genetic testing. Unlike with sporadic cases, there is a higher rate of recurrence with MEN-1 associated insulinoma. Highly unusual is also the finding of metastatic disease, occurring only in 4- 14% of all insulinoma cases.