bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atypical Carcinoid Tumor of the Mediastinum Presenting as Ectopic Cushing’s Syndrome
Authors: Medina Mora Luis Augusto , Siddiqui Raheel Sufian , Landry Ian , Cheng Kwan , Reich David Michael 
Published: May 2021

Abstract
Introduction: Ectopic Cushing’s syndrome (ECS) refers to Cushing’s syndrome (CS) that results from extra-pituitary secretion of adrenocorticotropic hormone (ACTH). Neuroendocrine tumors (NETs) are a rare cause of ECS, and their presence in the anterior mediastinum only represents 2-4% of all cases. We report a rare case of ECS in a patient with an atypical mediastinal carcinoid tumor.
Case Presentation: A 38-year-old male with a history of depression presented with generalized weakness, fatigue, and myalgia for one month. A one-week history of nausea and slight shortness of breath was reported. Physical exam and vital signs were unremarkable. Labs revealed hyperglycemia, hypokalemia, and metabolic alkalosis. A random serum cortisol was 47.7 mcg/dL (normal: 3-21 mcg/dL) and a 24-hour urine free cortisol was 7405 mcg/24 hours (normal: 3.5-45 mcg/24 hours). The morning serum cortisol after 8 mg dexamethasone at midnight, was 58.7 mcg/dL. Serum aldosterone and plasma renin activity were both undetectable. CT of the chest showed an anterior mediastinal mass measuring 9.0 x 10.3 x 6.1 cm accompanied by two large mediastinal lymph nodes. A PET CT confirmed the anterior mediastinal mass, which showed mild heterogeneous uptake and no evidence of metastatic disease. Core biopsy of mediastinal mass showed grade II neuroendocrine tumor/atypical carcinoid. Potassium, Spironolactone, Ketoconazole, and Metyrapone were used to control hypokalemia and hypercortisolemia. Trimethoprim-sulfamethoxazole (TMP-SMX) was started for Pneumocystis pneumonia prophylaxis. The patient underwent complete resection of the anterior mediastinal mass, thymectomy, and mediastinal lymph nodes dissection. Histopathology confirmed an atypical carcinoid in the mediastinal mass with negative margins. The rest of the thymus tissue and lymph nodes were negative for malignancy. ACTH and cortisol levels dropped significantly after surgery and the patient was discharged on oral hydrocortisone and TMP-SMX. At 4 weeks follow-up in the clinic, the patient was feeling much better and reported complete resolution of symptoms.
Discussion: ECS caused by an atypical carcinoid tumor is an extremely rare finding. Mediastinal NETs tend to have a poor prognosis due to their metastatic tendency and recurrence rates. Due to limited evidence in the medical literature, there’s much uncertainty and controversy regarding the best treatment of NETs. Standardized guidelines for the management of these atypical tumors are not well established. The primary mode of treatment is surgical resection of the ACTH-secreting tumor. However, in cases of advanced and metastatic tumors, surgical resection might not be sufficient and medical therapy with adrenal enzyme synthesis inhibitors may be needed. The use of neoadjuvant chemotherapy and/or radiotherapy remains unclear.
Carney Complex With Endocrine Involvement Isolated to the Thyroid Gland
Authors: Williams Vanessa , Jabri Hadoun , Jakoby Michael G 
Published: May 2021

Abstract
Introduction: Carney complex is a rare autosomal dominant disorder characterized by pigmented lesions of skin and mucosae, endocrine neoplasms or overactivity, and myxomas of the heart, skin, and other organs. Most patients have at least two affected endocrine organs at time of diagnosis. We present a case of Carney complex with endocrine involvement limited to the thyroid gland. Case: A 48-year-old female was referred for evaluation of thyroid nodules incidentally discovered on imaging for submandibular salivary gland swelling. Ultrasound evaluation of the thyroid revealed numerous, bilateral nodules that were mostly cystic or spongiform, though some had irregular borders and microcalcifications. A brother with Carney complex had been diagnosed with papillary carcinoma, and the patient decided to undergo thyroidectomy. Fortunately, no thyroid carcinoma was found on postsurgical histopathology. Initial biochemical evaluation showed no evidence of hypercortisolemia (8 AM cortisol 1.7 mcg/dL on 1 mg dexamethasone suppression test; 24-h urine cortisol 26.1 mcg [reference: 4-50]), growth hormone excess (IGF-1 190 ng/mL [reference: 52-328]), or hyperprolactinemia (prolactin 10 ng/mL [reference: 2.74-26.72]). Imaging showed no pituitary or adrenal masses. The patient underwent total hysterectomy with bilateral salpingo-oophorectomy for endometrial cancer prior to referral. She was diagnosed with Carney complex at age 19 years, and her manifestations included atrial and ventricular myxomas, intraductal adenoma of the breast, multiple skin lesions (lentigines, blue nevi, and cutaneous myxomas), and myxomas of the external auditory canals. She is in a Carney complex kindred that includes her mother, two brothers, and a niece. Discussion: Carney complex is usually caused by inactivating mutations or large deletions in the protein kinase A type I alpha regulatory subunit (PRKAR1A) gene located on chromosome 17q22-24. Most mutations are inherited in an autosomal dominant manner, though approximately 30% of cases are due to de novo mutations. In a review of 365 cases, the median age at diagnosis was 20 years. Growth hormone adenomas or somatomammotroph hyperplasia occurs in approximately 75% of patients, and most have at least one additional endocrine abnormality including multinodular goiter, primary pigmented nodular adrenocortical hyperplasia, and testicular or ovarian masses. There is an approximately 10% chance of developing well differentiated thyroid carcinoma. Treatment for Carney complex is individualized depending on the patient’s presentation and includes excision or surgical removal of myxomas, neoplasms, and skin lesions, as well as regular evaluation for cardiac myxomas and endocrine overactivity. This case of Carney complex is unusual because the only endocrinopathy is multinodular goiter.
Cerebral Venous Sinus Thrombosis as a First Presentation of Glucagonoma
Authors: Alamri Bader Nasser , Rivera Juan Andres 
Published: May 2021

Abstract
Background: Glucagonoma is a very rare type of pancreatic neuroendocrine tumor (pNET) which represent about 2% of all pNETs (Yao et al.). Although glucagonoma can occur in multiple endocrine tumor syndromes (e.g., MEN-1), most cases are non-hereditary (John & Schwartz). The typical 4Ds presentation are diabetes (DM), depression, dermatosis, & deep vein thrombosis (DVT) (Cunha-Silva et al.). About 50% of glucagonoma patients have DVT during their disease course (Feingold et al.). Most reported DVT cases in glucagonoma are either lower limb DVT or pulmonary embolism (Teixeira, Nico & Ghideti; Castro et al.). To our knowledge, there is no report of a cerebral venous sinus thrombosis (CVST) as the first presentation for glucagonoma.
Clinical Case: A 67-year-old male with a history of psoriasis & benign prostatic hyperplasia presented to the emergency department with a diffuse headache. He was sent home with conservative management. Four days later, he developed acute left-sided weakness with numbness & facial droop. CT head with contrast revealed a superior sagittal sinus thrombosis extending into the right transverse & right sigmoid sinuses. Heparin infusion was initiated. Due to the extensive sinus vein thrombosis & lack predisposing conditions, a pan CT was done for possible malignancy. The scan showed a solid, well-defined, markedly enhancing lesion in the pancreatic tail, suggestive of a NET. At the same time, a new diagnosis of type 2 DM was made based on HbA1C of 11.8%. The patient denied any diarrhea, fever, abdominal pain or episodes suggestive of hypoglycemia. However, he endorsed night sweats with weight loss. His family history was significant for a brother who had a pNET that was resected. Endocrinology was consulted, & a workup for pNET was ordered. Chromogranin A (CgA) was elevated at 439.9 ng/ml (&lt;=82), while on PPI. 24-hour urine cortisol was normal. PTH, serum calcium, & the pituitary hormonal panel were all normal. hCG & CEA were normal. Given the new onset DM & DVT plasma glucagon was requested & came back elevated at 202 pg/ml (reference range 80 pg/ml). MRI showed an hypervascular T2 isointense lesion at the pancreas’ tail measuring 10 x 11 x 10 mm. A Ga68-DOTATATE PET scan was ordered. With this constellation of findings, we initiated somatostatin analog therapy while surgical resection was planned. We referred the patient to medical genetics.
Conclusion: DVT is a common presentation in glucagonoma & a major cause of mortality. The possible mechanism appears to be related to increased secretion of factor X by pancreatic alpha cells (Lobo et al.). Although DVT is not unusual, an extensive CVST as the first presentation in glucagonoma has not been reported. In this case, & in addition to unexplained DVT, the new diagnosis of DM in an elderly patient raised the suspicion of secondary causes. Such a presentation should encourage clinicians to broaden the differential diagnoses, including pNET.
Composite Pheochromocytoma With Ganglioneuroblastoma: A Case Report
Authors: Pastor Paola M Lockhart , Wong Beatrice Y , Stefan Simona 
Published: May 2021

Abstract
Introduction: A composite pheochromocytoma (PC) is an adrenal tumor that is often diagnosed post-operatively on histopathology. PCs are unique in that it is a combination of typicalpheochromocytoma and neural crest derived tumors. The incidence is reported to be less than 3%of adrenal neoplasms. The most common co-existing tumor within a PC is a ganglioneuroma. Wepresent a rare case of PC containing ganglioneuroblastoma (PC-GNBL) in a woman withoutsignificant biochemical manifestation of excess catecholamine production. Case Report: A 63-year-old woman with a prolonged history of uncontrolled hypertension on 4 oral anti-hypertensive medications (Amilodipine 10mg daily, Valsartan/HCTZ 320/25mg daily andClonidine 0.1mg/24h patch) and uncontrolled type 2 diabetes on insulin was diagnosed with a1.5x1.8x1.5cm right adrenal incidentaloma 2 years prior on CT imaging for abdominal pain. Hormonal evaluation was notable for plasma free metanephrine of 66 (&lt;57pg/ml),normetanephrine 229 (&lt;148pg/ml), and total metanephrines of 295 (205 pg/ml). However, 24-hour urine metanephrine evaluation was normal on two occasions: metanephrine 121 and 168mcg/24h (90-315), norepinephrine 237 and 336 mcg/24h (122-676) and total metanephrines 358and 504mcg/24 h (224-832). Hyperaldosteronism and hypercortisolism were ruled out. Follow-up CT scan 14 months later demonstrated growth of the right adrenal nodule to 1.7x2x2cm with49% washout. She underwent laparoscopic right adrenalectomy without perioperativecomplications. Pathology was consistent with a PC-GNBL. The PASS score was 7, consistentwith malignant pheochromocytoma. Within weeks of surgery, she had marked clinicalimprovement. Blood pressure was controlled on one anti-hypertensive and Hgb A1c decreased to7.1% from 11% without requiring insulin. CT abdomen/pelvis 6 months post-operatively did notshow evidence of metastasis. She was referred for genetic testing. Conclusion: This case highlights an unusual presentations of pheochmocytoma. It’s important to recognizethat resistant hypertension can present without episodic headaches, diaphoresis, palpitations, andwithout biochemical evidence of catecholamine excess. Composite PCs are indistinguishableclinically or radiologically from ordinary pheochmocytomas. These exceedingly rare mixedtumors are only diagnosed via surgical pathology. To date, there are only a few cases reported inthe medical literature of co-existing PC-GNBL tumors. Due to the scarcity of composite PCscases, important information regarding its presentation and prognosis are unknown. It remains tobe seen whether the GNBL part of the tumor changes the prognosis of the tumor. However, inour case, the clinical status of our patient improved.
Do Not Miss MEN 1 Screening When Patients Are Newly Diagnosed With Pancreatic Neuroendocrine Tumor
Authors: Bai Ravisha , Izuora Kenneth E 
Published: May 2021

Abstract
Background: Multiple endocrine neoplasia type 1(MEN 1) is a rare genetic disorder characterized by the combined occurrence of parathyroid, pituitary, and duodeno-pancreatic neuroendocrine tumors (NETs) along with other characteristic tumors. Here, we present a patient with history of pancreatic NET who presented 2 years after her initial diagnosis with primary hyperparathyroidism and prolactinoma, consistent with MEN 1.
Case Report: A 60-year-old African American woman was admitted to our hospital with nausea, vomiting and headache for a week. On presentation, she was found to be hypotensive and tachycardic, both responded to IV fluids. Workup for infectious etiology came back negative. Her physical exam was benign except for dry oral mucosa, dry skin and epigastric tenderness. Laboratory evaluation showed serum calcium 11.8 mg/dL (8.4 - 10.2 mg/dL), which prompted further work up. Her PTH level was 1,079 pg/ml (8.5 - 72.5 pg/ml), Phosphorus 2.1 mg/dL (2.3 - 4.7 mg/dL), and 25 Hydroxy Vitamin D 10.2 ng/ml (7.4 - 44.0 ng/ml). Additional history and review of her records revealed she was hospitalized 2 years earlier with nausea, vomiting and abdominal pain. Then she was found to have esophageal and gastric ulcers on EGD. Endoscopic ultrasound revealed an 8 mm hypoechoic lesion in the body of pancreas found to be a pancreatic NET on biopsy. She had elevated gastrin level of 470 pg/ml (0 - 115 pg/ml) and was diagnosed with a gastrinoma. She was discharged on a PPI and was lost to follow up. Patient had no significant family history. Given her past history and current presentation, we assessed her pituitary hormonal function which was unremarkable except for prolactin level of &gt;1,000 ng/ml (post-menopausal 1.8 - 20.3 ng/ml). Pituitary MRI showed a 1.8 cm macroadenoma. The optic nerve and optic chiasm were normal. Based on her clinical presentation and radiologic findings, she was diagnosed with MEN 1. Her Calcium level trended down with IV hydration, and her presenting symptoms resolved. She was started on bromocriptine, pantoprazole and vitamin D and was discharged with out-patient appointments scheduled with gastroenterology and endocrinology clinics.
Conclusion: This case highlights the importance of having a high index of suspicion to prompt screening for MEN 1 in patients newly diagnosed with a pancreatic NET.
Early diagnosis and timely treatment of the associated disease conditions in MEN 1 can prevent significant morbidity and mortality associated with these conditions.
Hypoglycemia, Something Lost in Translation
Authors: Al-Naqeeb Ghadah , Neupane Rabin , Baral Neelam , Gao Faye , Steves Mark , Wexler Jason Adam 
Published: May 2021

Abstract
Introduction: Insulinoma is a rare neuroendocrine tumor that may occur sporadically or as part of multiple neuroendocrine neoplasia type 1, with an incidence of 4 per million per year. Given the nonspecific symptoms of hypoglycemia, the diagnosis of insulinoma may be delayed by months, years or even decades. Case Presentation: A 50 year-old Hispanic, Spanish speaking male with a history of hypertension presented with progressive epigastric pain, nausea and bilious vomiting for 2 days. Physical exam was notable for abdominal distention and tenderness. Initial labs showed white blood cells of 19.4 k/uL (4-10.8), glucose of 85 mg/dl (65-140). CT abdomen showed findings consistent with moderate grade small bowel obstruction and normal pancreas. The patient was managed conservatively with nasogastric tube placement and nothing per oral (NPO). Within 8 hours started experience sweating, restlessness, fingerstick glucose was 40 mg/dl. Upon questioning, he reported episodes of lightheadedness, sweating and shakiness 8 years prior to this hospitalization, and he recalled being told that he was hypoglycemic during prior hospitalizations at another institution. He stated he was told to drink juice upon experiencing such symptoms and no work up or diagnostic investigation was recommended. We initiated a hypoglycemia investigation when he was NPO, when serum glucose level of 40 mg/dl. Labs showed insulin level 34 uIU/mL (3-19), free insulin 25 uIU/mL (3-19), C-peptide 3.32 ng/mL (0.81-3.85), beta hydroxybutyrate &lt;0.02 mmol/L (0.02-0.27) and proinsulin of 36.6 pmol/L (3-50) and hemoglobin a1C of 5% (3.8-5.6). Serum screening for hypoglycemic agents was negative. When MRI abdomen was negative for a pancreatic mass. We proceeded with advanced diagnostic imaging with endoscopic ultrasound (EUS) which showed a 26 mm x 19 mm ovoid, hypoechoic mass at the junction of the pancreatic body and tail. Tissue specimen obtained with fine needle aspiration showed grade 1 neuroendocrine neoplasm. The patient underwent distal pancreatectomy and splenectomy with suture repair of the small bowel and left wedge liver biopsy. The pathology showed a well-differentiated neuroendocrine tumor of the pancreas, positive for synaptophysin, chromogranin and CD56 and Ki-67 with proliferation index &lt;2% and no evidence of metastasis to the liver. The patient’s hypoglycemia resolved following surgery and rose to &gt; 200 mg/dL requiring us to begin insulin therapy during the hospital stay before ultimately discharging the patient on metformin for type 2 diabetes. Conclusion: Insulinoma is a rare but treatable neuroendocrine tumor. Early diagnosis is important to avoid adverse clinical events related to hypoglycemia. It is important to maintain a strong clinical suspicion in order to identify and pursue the cause of unexplained hypoglycemia to improve the quality of life of patients with this rare condition.
Metastatic Non-Functional Pancreatic Neuroendocrine Tumor in a Patient With a Pathogenic TSC1 Mutation
Authors: Sliwinska Aleksandra , McFadden David , Malchoff Carl D 
Published: May 2021

Abstract
Introduction: Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disorder caused by mutations in two tumor suppressor genes (TSC1 and TSC2) encoding proteins critical in cell growth and proliferation and is associated with an increased risk for benign and malignant tumors. Pancreatic neuroendocrine tumors (PNET) occur in 1.5-1.8% of patients with TSC. They have been primarily reported in TSC2, with only a few cases in the context of TSC1. We describe a non-functional metastatic PNET in a patient with a known pathogenic TSC1 mutation.
Case Description: A 49-year old female with a past medical history of bipolar disease, a family history of TSC1 in a daughter, a known pathologic TSC1 mutation (c.2356C&gt;T), and previous history of renal cell carcinoma (RCC) was evaluated for a pancreatic lesion with likely liver metastases. Two years prior to the presentation, a 10 mm pancreatic lesion was initially noted on the CT scan during a renal mass evaluation. Nephrectomy confirmed the RCC. Two years later, surveillance imaging revealed two new lesions in the liver, and the pancreatic lesion had enlarged to 1.3 cm. She denied symptoms suggestive of a functional PNET, and her physical exam was unremarkable. Gallium-68 dotatate (GA-68) PET/CT scan demonstrated avid lesions of both the pancreatic tail and left hepatic lobe. Biopsy of the 3 cm liver mass revealed a metastatic high-grade neuroendocrine carcinoma (mib-1 proliferation index of 15%) favoring a primary PNET. Immunohistochemical stains were positive for chromogranin A, synaptophysin, EMA, PAX 8, CK 20, and villin. Stains for CA 19-9 and CK 7 were negative. Biochemical testing suggested that the PNET was non-functional. Specifically, serum concentrations of gastrin, somatostatin, glucagon, glucose, C-peptide, proinsulin, pancreatic polypeptide, chromogranin A, and vascular endothelial growth factor were within normal limits. The patient underwent distal pancreatectomy and resection of the liver mass. Pathological specimens confirmed the diagnosis of a PNET. The patient remained asymptomatic and was monitored regularly with MRI and GA-68 PET/CT scans without further evidence of the disease for 1.5 years. Conclusions: We conclude that this patient harboring a c.2356C&gt;T TSC1 mutation developed a non-functional metastatic PNET. PNET is a likely component of TSC1.
References: 1.Lodish, M. B., & Stratakis, C. A. (2010). Endocrine tumors in neurofibromatosis type 1, tuberous sclerosis, and related syndromes. Best practice & research Clinical endocrinology & metabolism, 24(3), 439-449.2.Dworakowska, D., & Grossman, A. B. (2009). Are neuroendocrine tumors a feature of tuberous sclerosis? A systematic review. Endocrine-Related Cancer, 16(1), 45.
The Diagnosis and Management of a Rare ACTH-Producing Neuroendocrine Tumor Causing Cushing’s Syndrome
Authors: Findlay Ryan , Gray Daryl , Shepherd Jessica , Joseph Mariamma , Hussain Nadeem , Laidley David , Van Uum Stan 
Published: May 2021

Abstract
A 57-year-old woman presented with a three-month history of worsening lethargy, weight gain, central adiposity, proximal muscle weakness, and hypokalemic hypertension. Initial investigations were consistent with ACTH-dependent Cushing’s Syndrome. 24-hour urine cortisol: 711nmol/day (normal&lt;275), cortisol after 1 mg dexamethasone suppression test 960nmol/L (normal&lt;50)), 2-day dexamethasone suppression cortisol: 575 and ACTH: 19 pmol/L. MRI sella was normal. She required several hospital admissions for worsening proximal muscle weakness and falls. She was started on ketoconazole and spironolactone. Basal insulin was started for dysglycemia. Petrosal vein sampling indicated ectopic ACTH production. CT scan of chest/abdomen/pelvis showed no intrathoracic or intra-abdominal abnormality. Thyroid ultrasound and whole-body octreotide scan showed no abnormalities. A Gallium 68-dotatate PET scan showed focal tracer uptake in the pancreatic tail suspicious for a well-differentiated neuroendocrine tumor (NET). MRI pancreas showed a slightly truncated pancreatic tail with no discrete lesion. We proceeded with Endoscopic Ultrasound (EUS) which revealed an irregular hypoechoic mass in the pancreatic tail. EUS–guided fine-needle biopsy (EUS-FNB) using a 22G SharkCore needle, revealed a neuroendocrine neoplasm staining positively for ACTH. She underwent distal pancreatectomy with pathology showing a 1.4cm well-differentiated NET, staining positive for ACTH with a Ki67 index of 10%. Postoperatively, her ketoconazole, spironolactone, and insulin were discontinued. Her dysglycemia, hypertension and other clinical symptoms gradually improved. Immediately post-operatively, her AM cortisol was 403 and her 24-hour urine cortisol was elevated 959nmol/day. Repeat AM cortisol and 24-hour urine cortisol one-month post-surgery were 392 nmol/L and 72 nmol/day respectively, confirming biochemical remission. Discussion: ACTH-producing pancreatic NETs are rare, accounting for less than 15% of reported cases of EAS. They are often aggressive, with 78.7% of reported cases having distant metastasis at diagnosis (1). They are associated with significant morbidity and mortality. Diagnosis and management can be difficult and require multiple investigations and multidisciplinary team involvement. In our case, we utilized endoscopic ultrasound to ensure a correct preoperative localization. We discuss the systematic approach for diagnosis and the management of an ACTH-producing pancreatic NET. References: 1. Maragliano R, Vanoli A, Albarello L, Milione M, Basturk O, et al. ACTH-secreting pancreatic neoplasms associated with Cushing syndrome: clinicopathologic study of 11 cases and review of the literature. Am J Surg Pathol. 2015 Mar;39(3):374-82. doi: 10.1097/PAS.0000000000000340. PMID: 25353285.