bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Opportunity Missed: Managing an Aggressive Adrenal Cortical Carcinoma
Authors: Jouneghani Nasrin Saleh , Al-Ramo Kathreen , White Wendy 
Published: May 2021

Abstract
Introduction: Adrenal cortical carcinoma (ACC) is a rare endocrine tumor with an incidence of up to 2 persons per million population. Complete surgical resection is the first-line therapy for localized tumors, while debulking surgery, radiation therapy, and/or chemotherapy may also be options for palliation in advanced ACC. Biochemical and radiographic evaluation of a newly discovered adrenal mass maximizes the opportunity for the patient to undergo a complete, margin-negative resection of the primary tumor, which is the most powerful determinate of long-term survival. Here we present the case of an extremely aggressive high grade adrenal cortical carcinoma that increased from 4 cm to 17 cm within 4 months, metastasizing to the lung, liver and left kidney prior to resection. Case summary: A 42-year-old woman presented to the Emergency Department (ED) with abdominal pain and was found to have hypokalemia and an incidental left adrenal mass measuring 4.9 x 4.6 cm. She was discharged home with instructions to follow up with her primary care physician for further workup. Unfortunately, she was lost to follow-up for 3 months. Her initial biochemical evaluation at follow-up did not show evidence of adrenal insufficiency or elevated metanephrines. A repeat outpatient CT chest abdomen pelvis revealed increased tumor size to 12.3 x 10.8 x 12.5 cm, with unclear renal vs adrenal origin, and multiple liver and lung metastases. She subsequently underwent left radical nephrectomy, adrenalectomy, splenectomy as well as a partial diaphragmatic resection 4 months after her initial ED presentation. The surgical specimen measured 17 x 11.5 x 8 cm. Endocrinology was consulted post-operatively to evaluate for relative adrenal insufficiency given hypotension & altered mental status. Further evaluation revealed new-onset hirsutism, male-pattern hair loss, proximal muscle weakness, and significant weight loss over the prior 3 months. Post-operative laboratory evaluation was significant for sustained hypokalemia of 2.4 mmol/L, 24 hour urine cortisol of 1326 mcg/24 hr (normal 3.5–45), as well as elevated DHEA-S of 994 mcg/dL (normal 27–240), and testosterone of 294 ng/dL (normal 10–75). Surgical pathology demonstrated a high-grade adrenal cortical carcinoma. Oncology was consulted and the patient was started on spironolactone for the hypokalemia, but declined any further therapy for her ACC and subsequently died 2 weeks later. Conclusion: This case illustrates how ACC can behave aggressively and further emphasizes the need for timely and complete biochemical evaluation of adrenal incidentalomas. This is particularly true with the presence of suspicious radiologic features such as size more than 4 cm and heterogeneous appearance. All patients with an adrenal incidentaloma should undergo biochemical and imaging evaluation, guided by thorough history-taking and physical exam, to ensure optimal outcomes.
An Overlooked Sequela of Long-Term Opioid Analgesic Use: A Case Report on Central Adrenal Insufficiency
Authors: Zhao Wei , Mohamed Issa , Humphries Derrek , Bankstahl Elizabeth 
Published: May 2021

Abstract
Background: Opioid use began to surge since late 1990s and has evolved into a full-fledge opioid epidemic. 2 million Americans aged 12 or older are estimated to have opioid use disorder. We hereby present a case of opioid-induced adrenal insufficiency (OIAI), an overlooked endocrinopathy in which chronic opioid use suppresses the hypothalamic-pituitary-adrenal axis.
Clinical Case: A 53-year-old African American female with past medical history of chronic pain syndrome presented with worsening fatigue and generalized weakness for a week, to the extent that she required full assistance to ambulate at home. Upon further inquiry, she also suffered from postprandial eipgastric pain and non-bloody diarrhea for several months. She has a 2-year use of Norco 10 mg/325 mg three times daily to manage her chronic pain. Her blood pressure was running low at 85/57 mmHg with no other abnormal vitals. Our first visual impression of her was a debilitated lady with low voice and slow body movements. Adrenal insufficiency was suspected and subsequently confirmed with low morning cortisol level (1.1 mcg/dL), low DHEAS level (25.3 mcg/dL) and subnormal response of cortisol (16.8 mcg/dL) to the cosyntropin stimulation test. Her ACTH level was less than 3 pg/mL. These laboratory findings were consistent with central adrenal insufficiency. Chronic steroid use, the most common culprit for adrenal insufficiency, was not found in her home medication list or prescription records. To further evaluate the underlying etiologies, we checked the pituitary hormones and found normal levels of LH, FSH, TSH, prolactin and IGF-1. Head CT 2 years prior was negative for any discernible mass. The suspicion for pituitary mass that markedly suppresses ACTH secretion only was reasonably low. The diagnosis of OIAI was made by excluding other causes. Endocrinology was consulted for the dosing of hydrocortisone. She improved physically after receiving hydrocortisone replacement therapy. Collaborative efforts were made to cut down her opioid dose.
Conclusions: OIAI is a longstanding overlooked condition in chronic opioid users of which clinicians should raise their awareness. The estimated prevalence of OIAI ranges from 9% to 29% depending on the daily dosage and total duration of opioid use. The case reports of OIAI, however, are only a few. Patients with OIAI could present with fatigue, weight loss, gastrointestinal symptoms, headache or muscular aches. Not only does OIAI impair patients’ quality of life and potentially escalate their opioid dosage by inexperienced prescribers, it also leads to catastrophic adrenal crisis following acute insults. The challenge clinicians face is to uncover the clinical clues suggesting OIAI, which are often hidden in a myriad of symptoms caused by chronic pain and other co-morbidities. Timely diagnosing OIAI is thus never more important in the midst of the unprecedented opioid epidemic.
An Unusual Case of Bilateral Adrenal Hyperplasia
Authors: De Castro Alicia , Comi Richard J , Crawford Andrew Robert , Radovanovic Natasa , Ammana Hima , Kwak Leigh 
Published: May 2021

Abstract
Background: Thrombocytopenia, anasarca, fever, reticulin fibrosis/renal failure, and organomegaly (TAFRO) syndrome is a variant of Castleman Disease, which is a rare lymphoproliferative disease that can be life threatening. Diagnosis is often delayed because of its nonspecific presentation. Bilateral adrenal hyperplasia has been a reported complication, however the majority of cases reported have been in Asian patients. Prior accounts of elevated ACTH in TAFRO have been in the context of adrenal insufficiency.
Clinical Case: A 28-year-old Caucasian male with a history of multiple sclerosis was seen in the ED with abdominal pain. On presentation, he was afebrile and normotensive. Physical exam was notable for cervical lymphadenopathy and abdominal tenderness. There was no facial rounding/plethora, bruising, abnormal striae, or proximal muscle weakness. He had normal blood counts, serum chemistry and liver function. An abdominal CT scan showed marked bilateral adrenal hyperplasia with pre-aortic, peri-aortic and retroperitoneal lymphadenopathy. An 8AM serum cortisol was 14.1 mcg/dl (4.8–19.6 mcg/dl) and adrenocorticotrophic hormone (ACTH) was elevated at 152 pg/ml (7.2–63 pg/ml). A repeat serum 8AM cortisol following low dose dexamethasone suppression test (LDDST) was 14.7 mcg/dl, however at that point the patient had developed new fevers and thrombocytopenia. Blood pressure, blood glucose and potassium remained normal. An MRI of the brain showed a normal appearing pituitary gland. An extensive infectious and rheumatologic evaluation was negative, and he underwent an inguinal lymph node biopsy which showed nodal expansion with histiocytes, consistent with TAFRO. High dose methylprednisolone and Siltuximab (an IL-6 inhibitor) were started, and his fever and abdominal pain resolved. He was discharged home on oral prednisone.
Conclusion: We describe a case of bilateral adrenal hyperplasia with elevated ACTH and non-suppressed cortisol on LDDST suggestive of ACTH-driven cortisol excess. However, interpretation of his LDDST is made difficult in the context of persistent fevers. Although we cannot definitively exclude pathologic hypercortisolism at this time, given his lack of suggestive features such as proximal muscle weakness, abnormal striae or hypokalemic alkalosis, his over-all presentation was more consistent with hyperplasia secondary to TAFRO rather than an underlying pathologic hypercortisolism. Adrenal hyperplasia has been noted in TAFRO, however its pathogenesis remains poorly understood. TAFRO should be added among the differentials for bilateral adrenal hyperplasia to facilitate early diagnosis and treatment.
References: Ducoux G, et al. Thrombocytopenia, Anasarca, Fever, Reticulin Fibrosis/Renal Failure, and Organomegaly (TAFRO) Syndrome with Bilateral Adrenal Hemorrhage in Two Caucasian Patients. Am J Case Rep. 2020;21:e919536.
Asymptomatic Pheochromocytoma With Delayed Resection Due to Covid-19 and Persistent Postoperative Hypertension
Authors: Menon Trisha , Sinha Avani G 
Published: May 2021

Abstract
Background: Pheochromocytoma is promptly treated by surgical removal and usually results in resolution of hypertension. This case discusses an asymptomatic patient with two new malignancies-breast cancer and pheochromocytoma- who had positive outcomes despite delayed resection of pheochromocytoma due to COVID-19, but with a persistence of postoperative hypertension.
Clinical Case: A 60 year old woman with newly diagnosed breast cancer presented for workup of an adrenal mass found on PET scan. An abdominal contrast CT-scan demonstrated a left 3.2 cm indeterminant adrenal mass. Initial laboratory testing demonstrated positive 24 hour urine metanephrines (metanephrine 951 mcg/24hr, n &lt; 400 mcg/24hr for HTN and normetanephrine 1302 mcg/24hr, n &lt; 900 mcg/24h for HTN) and plasma metanephrines (normetanephrine 826 pg/mL, n &lt; 145 pg/mL and metanephrine 391 pg/mL, n &lt; 62 pgmL), suggestive of pheochromocytoma. An MIBG scintigraphy showed tracer uptake in the left adrenal gland, suspicious for pheochromocytoma. The patient was started on alpha then beta blockade with plan for removal, but due to the COVID-19 pandemic, surgery was delayed. In the interim, breast cancer therapy was adjusted to avoid complications or symptoms from the possible pheochromocytoma. The patient had always been asymptomatic, even during the physical and emotional stress of cancer and chemotherapy. She only had a diagnosis of uncontrolled hypertension for four years prior to presentation, treated with Valsartan-Hydrochlorothiazide, with average systolic BP of 140–180, and diastolic BP of 80–100. With the addition of Doxazosin and Metoprolol, the patient’s BP improved, with all readings &lt; 120/90. A left adrenalectomy was performed nearly six months after initial presentation, with final pathology report demonstrating moderately differentiated pheochromocytoma, with clean surgical margins. The patient remained hypertensive for months after the procedure, with initial systolic (SBP) readings of 150–160, and diastolic (DBP) readings of 90–100. However, follow up plasma metanephrine levels were normal (normetanephrine 165 pg/mL n &lt; 191.8 pg/mL and metanephrine 22.1 pg/mL n &lt; 88 pg/mL). The patient was then started on Amlodipine and Valsartan, with most recent SBP readings in the 130s.
Conclusion: This case demonstrated a clinically asymptomatic patient with persistent postoperative hypertension and normal plasma metanephrines, which has been demonstrated only in a minority of patients. Additionally, pheochromocytoma needs to be promptly removed if possible; this case demonstrated successful resection and clinical course despite the delay for this urgent surgery due to COVID-19.
Bilateral Familial Pheochromocytoma: Difficulty of Diagnosis and Management
Authors: Doghri Sohaib Khamal , Echchad Lamya , Azriouil Manal , Rifai Kaoutar , Iraqi Hind , Gharbi Mohamed Hassan El 
Published: May 2021

Abstract
Introduction: Bilateral pheochromocytoma is a rare tumor, often seen in the context of a family illness. The majority of pheochromocytomas are sporadic, but they can also occur within the framework of genetic diseases (10%): MEN2, VPL, NF1, familial paraganglioma (mutation of SDHB)⋯ In the context of a familial genetic disease, the pheochromocytoma can be either unilateral or bilateral, benign in 95% of cases and malignant in 5%. It still poses several problems related to its diagnosis, genetic aspects, especially in the absence of a family history. And the criteria of malignancy, given the non-existence to date of a certain & universal criterion that judges the malignancy of the tumor. We present through this article the exceptional case of “bilateral familial pheochromocytomas with strong suspicion of malignancy”.
Clinical Case: A 29-year-old lady, hypertensive since 4 years, admitted for exploration of severe secondary hypertension. She reports a triad of menard and severe lumbar pain, the somatic examination shows hypersensitivity of the flanks, a BP of 240/120 mmhg. the abdominal CT scan confirmed by an MRI show a right adrenal mass of 5 cm & another left of 1 cm, of suspicious appearance (irregular contours, areas of necrosis, heterogeneity, spontaneous density at 35 HU, a wash out at 33% with presence of L4 spinal angioma and peri-aortic lymph nodes. urinary methoxylated derivatives (UMD) returned high. The genetic study was positive VPL (on various radiological tests, there was just a spinal angioma) We retained the diagnosis of familal bilateral pheochromocytoma. In front of the clinical & radiological signs of malignancy, we decided to do: a right total adrenalectomy & a left partial adrenalectomy. Unfortunately, the blood pressure didn’t drop, and UMD were still positive; the anatomopathological study shows a pheochromocytoma with a PASS score estimated at 3 (benign!) Faced with conflicting clinical-radiological and histological data, we decided to total adrenalectomy without lymph node dissection and to closely monitor the progress. the post Op blood pressure was normalized and the UMD returned negative.
Conclusion: Malignant familial bilateral pheochromocytoma is a very rare & very difficult entity to diagnose, manage & monitor. A good management requires serious collaboration between: endocrinologist, radiologist, urologist, pathologist
Careful Evaluation of Cosyntropin Dose in the Diagnosis of Adrenal Insufficiency
Authors: Musurakis Clio , Chitrakar Solab , Sharag Randa Eldin , Shrestha Ekta , Pethe Gauri , Qureshi Faisal 
Published: May 2021

Abstract
Introduction: The use of the 250μg cosyntropin dose or otherwise called high-dose ACTH test is the gold standard test for diagnosis of primary adrenal insufficiency. The 1μg dose test or the low-dose test is mostly reserved for diagnosis of secondary adrenal insufficiency. Careful consideration of the results produced during the diagnostic process is imperative to avoid mislabeling of patients with a disease that requires lifelong treatment.
Case Report: This is the case of a 45-year-old female with a history of asthma and psoriasis who presented with emesis. Home medications included monthly TNF-alpha inhibitor injections for psoriasis, triamcinolone acetonide topical spray and budesonide-formoterol inhaler. On admission, she also had nausea, chills and diaphoresis, as well as palpitations, lightheadedness, and shortness of breath. When she arrived at the ER, vitals were remarkable for low blood pressure. Labs were unremarkable except for CMP concerning for anion gap metabolic acidosis, hyponatremia, and hypokalemia. A random serum cortisol was 6.4 mcg/dL, which was relatively low. ACTH was within normal range. Due to concern for adrenal insufficiency, a 1μg cosyntropin test was performed which showed a peak cortisol concentration of less than 18 mcg/dL. As the response was assessed as suboptimal, endocrinology was consulted to offer a treatment plan for steroids. However, the test was repeated using the gold standard 250μg cosyntropin dose and the patient then showed an adequate response and she was not started on steroids.
Conclusions: This is a case that demonstrates how the 250 μg ACTH or high-dose stimulation test should be used for diagnosis of primary adrenal insufficiency (AI), as it is the gold standard. The 1 μg ACTH or low-dose stimulation test can be used for diagnosis of primary AI but only when the high dose test is not available. On the other hand, the 1 μg ACTH stimulation test has been shown to be more sensitive than the 250 μg test in diagnosing secondary adrenal insufficiency. When using the most appropriate test correctly, the clinician can only then offer the patient the best treatment strategies. Our patient did not require chronic replacement therapy. The steroids in this case could have harmed the patient as chronic administration could cause adrenal gland suppression.
Catecholamine-Producing Adrenal Schwannoma: A Rare Pheochromocytoma Imposter
Authors: Chiu Christine E , Angell Trevor E 
Published: May 2021

Abstract
Background:Adrenal schwannoma is a tumor of the adrenal medulla that poses a pre-operative diagnostic challenge due to its non-specific imaging findings and rarity. Even more uncommon are functional catecholamine-producing adrenal schwannomas (CPAS) that can lead to the clinical presentation of catecholamine excess. Here, we present a case of biochemically and histopathologically confirmed CPAS and provide a review of the existing cases in the literature.
Clinical Case: A 43-year old woman with a history of hypertension was incidentally found to have a 4 cm left adrenal lesion. Computed tomography of the mass demonstrated indeterminate enhancement and washout characteristics. Upon evaluation, she had episodes of palpitations and fatigue without headache or flushing. Her medications were notable for metoprolol, vortioxetine, and lisdexamfetamine. Laboratory results were notable for elevated 24-hour urine metanephrine and normetanephrine of 551 mcg/24hr (normal: 58–203 mcg/24hr) and 927 mcg/24hr (normal: 88–649 mcg/24hr) respectively. Due to the possibility of pheochromocytoma, the patient elected for surgery and underwent laparoscopic left adrenalectomy after pre-treatment with an alpha-1-antagonist. Pathology demonstrated a 4.8 cm well-circumscribed tumor arising from the adrenal medulla that showed mostly hypercellular areas of spindled cells with wavy nuclei and focal nuclear palisading along with hypocellular areas with loose edematous stroma with focal areas of calcification and microcyst formation. IHC of the tumor cells was diffusely positive for S-100 and SOX-10, consistent with adrenal schwannoma. Laboratory results approximately 2 months post-operative on the same medications demonstrated normalization of 24-hour urine metanephrine and normetanephrine, confirming CPAS. A search of PubMed was performed using the search terms “adrenal schwannoma,” which returned 41 reports, of which 2 confirmed CPAS. Of the 3 cases, including ours, patients had a mean age of 44 years old and M:F ratio of 1:2. Each of the 3 tumors were left-sided with sizes ranging from 4.8 cm to 7.7 cm, which were all surgically removed. In the two previously published reports, the reported pre-operative laboratory markers were serum catecholamines and urine catecholamines, respectively, but neither compared levels to a reference range. In all cases, catecholamine levels normalized following surgical removal.
Conclusion: Adrenal schwannoma is a rare entity in the differential diagnosis of non-functioning adrenal incidentaloma, but it should be considered for catecholamine-producing adrenal tumors as well. A summary of published cases suggests that these are typically large tumors with possible female predominance. This case is the first to document levels of catecholamine metabolite concentrations in CPAS.
Cushing’s Syndrome Associated With an Adrenal Cavernous Hemangioma
Authors: Khan Rind Jubran Afzal , Saeed Zeb Ijaz 
Published: May 2021

Abstract
Introduction: Adrenal cavernous hemangiomas are rare benign tumors that arise from vascular endothelium and are often discovered incidentally on abdominal imaging. The majority are nonfunctioning; however, we present a case of adrenal Cushing’s syndrome in a patient with a cavernous adrenal hemangioma.
Case: A 72-year-old woman was referred for an incidental right adrenal mass. On questioning, she endorsed abdominal pain, sixty-pound unintentional weight gain over five years, truncal obesity, and easy bruising. Past medical history was relevant for hypertension. Her surgical history was extremely complicated, having had a perforated peptic ulcer, open cholecystectomy complicated by injury to the right ureter, incisional hernia repair, appendectomy, and hysterectomy with bilateral salpingo-oophorectomy.
She was first noted to have a right adrenal mass on a CT done eight years ago, measuring 3.8 x 3.2 cm. A repeat CT abdomen and pelvis now showed this mass to be 6.5 x 6.3 x 8.1 cm with unenhanced Hounsfield units of 29.6. Radiographically, this was a heterogeneous, solid, and cystic appearing mass with peripheral brisk arterial enhancement areas, which appeared to fill in on delayed imaging. The enhancement pattern of the lesion was consistent with an adrenal cavernous hemangioma. An MRI of the abdomen also demonstrated similar peripheral nodular enhancement favoring an adrenal cavernous hemangioma.
Functional testing for the adrenal mass was undertaken. Morning cortisol was 23.4 mcg/dl with ACTH low at 5.3 pg/ml, and DHEA-S 3 mcg/dl. She failed to suppress with overnight 1 mg dexamethasone with AM cortisol of 3.6 mcg/dl. Midnight salivary cortisol levels were high at 0.237 mcg/dl and 0.419 mcg/dl while a 24-hour urine free cortisol was normal at 15.2 mcg/d. She tested negative for pheochromocytoma and primary aldosteronism.
The patient was deemed a poor surgical candidate due to her history of multiple prior abdominal surgeries and a BMI of 46. Therefore, she underwent an IR angioembolization of the right adrenal mass instead. On follow-up CT, there was no significant change in the size of the lesion; however the degree of rim enhancement was slightly decreased. Post procedurally, her a.m. cortisol remained high-normal at 18.3 mcg/dL.. She is currently enrolled in a study for medical treatment of Cushing’s syndrome.
Discussion: Adrenal cavernous hemangiomas usually present incidentally in the 6th-7th decade of life with a female predominance. These lesions are often asymptomatic; however, abdominal pain is the most common presenting symptom. The majority of adrenal cavernous hemangiomas are hormonally quiescent and mineralocorticoid excess and/or subclinical Cushing’s syndrome is exceedingly rare. Our patient is unique in her presentation of adrenal Cushing’s with this lesion and the novel use of angioembolization to decrease the size of this vascular tumor.