bluuebunny/crossref_metadata_2025_split huggingface dataset:
“Relieving the Pressure” With Unilateral Adrenalectomy in a Case of Chronic Resistant Hypertension From Primary Aldosteronism
Authors: Brooks Danielle , Fernandez-Ranvier Gustavo , Rios Carlos , Shah Nirali A 
Published: May 2021

Abstract
Introduction: Primary aldosteronism is an under-recognized cause of resistant hypertension that is associated with an increased risk of cardiovascular disease and mortality. While surgical intervention may not lead to complete resolution of hypertension, partial success (defined by reduction in blood pressure and/or medications) can be achieved and future cardiovascular risks can be minimized. We present a case of a patient with primary aldosteronism whose chronic resistant hypertension improved significantly after unilateral adrenalectomy. Clinical Case: A 54-year-old female with resistant hypertension for 17 years and hypokalemia was diagnosed with primary aldosteronism. The patient had uncontrolled hypertension despite atenolol 50 mg, nifedipine XL 60 mg, triamterene-hydrochlorothiazide 37.5-25 mg, lisinopril 40 mg daily.
Laboratory evaluation was significant for plasma aldosterone concentration (PAC) 26.8 ng/dL (reference: 0.0–30.0 ng/dL), plasma renin activity (PRA) 0.168 ng/mL/hr (reference: 0.167–5.380 ng/mL/hr), PAC/PRA ratio 159.5, and potassium of 3.2 mmol/L (reference: 3.5–4.5mmol/L). Other workup showed plasma normetanephrines 128 pg/mL (reference: 0–145 pg/mL), metanephrines 25 pg/mL (reference: 0–62 pg/mL), and two normal midnight salivary cortisol tests. Saline infusion testing confirmed primary aldosteronism with a non-suppressed aldosterone level of 15.6 ng/dL (normal &lt;5 ng/dL). Abdominal imaging revealed two low-density right adrenal nodules consistent with adenomas and thickening of the left adrenal gland. The patient underwent adrenal vein sampling (AVS) with cosyntropin stimulation, which showed lateralization to the right adrenal. Despite adding clonidine 0.1 mg three times daily, hydralazine 25 mg three times daily and spironolactone 100 mg daily (which substituted triamterene-hydrochlorothiazide) after AVS, her blood pressure remained uncontrolled with blood pressure ranging from 150–180/90–110 mmHg. A laparoscopic right adrenalectomy was performed. Pathology revealed two adrenal cortical adenomas. At the one-month post-operative visit, her potassium was normal, PAC was 4.3 ng/dL, and blood pressure improved on a reduced regimen of atenolol, lisinopril, and nifedipine.
Conclusion: In patients with chronic uncontrolled hypertension due to primary aldosteronism, surgical intervention may not lead to complete resolution of hypertension but may lead to partial clinical success. Residual hypertension may be due to underlying vascular changes associated with long-term exposure to elevated aldosterone. The post-operative PAC in our case was less than 5 ng/dL suggesting biochemical cure and potentially reduced cardiovascular risk. This case emphasizes that adrenalectomy should be considered in resistant hypertension, even if complete clinical cure may not be attainable to reduce future cardiovascular events.
Non-Functioning Pheochromocytoma in a Patient With Von Hippel Lindau Syndrome (VHL): Case Report
Authors: Ricardo Gustavo Piech , Scalissi Nilza , Bueno Cristina Bellotti Formiga , Scalco Renata Da Cunha , Lima Jose Viana 
Published: May 2021

Abstract
Background: We report the case of a patient with VHL Syndrome with an adrenal lesion compatible with non-functioning pheochromocytoma and it’s diagnostic management. Case Report: JMN, female, 32 years old, referred for screening for VHL syndrome, after diagnosis in a sister, who has clear cell renal carcinoma (ccRCC), cerebellar hemangioblastoma and genetic analysis, by next generation sequencing (NGS), which identified the allelic variant germline pathogenic c. 256C&gt; T in heterozygosis in exon 1 of the VHL gene. The patient is asymptomatic and her physical examination is normal. Optic fundus examination with lesion suggestive of right hemangioblastoma. Family history: mother who died at 59 with a diagnosis of ccRCC, without genetic investigation. Maternal aunt diagnosed with VHL and involvement of the cerebellum, kidney and pancreas. Two brothers with genetic and clinical diagnosis of VHL syndrome, presenting pheochromocytoma and renal carcinoma. Laboratory tests: plasma metanephrine: 0.3 nmol/L (RV &lt;0.5nmol/L), plasma normetanephrine: 0.5 nmol/L (RV &lt;0.9nmol/L), chromogranin A 61 ng/mL (RV &lt;93 ng/ml). Genetic evaluation by NGS identified the pathogenic variant c. 256C&gt; T in heterozygosity in exon 1 of the VHL gene. Topographic examinations: magnetic resonance imaging (MRI) of adrenals with nodule in the left adrenal gland, hypersignal in T2, measuring 2.9 x 2.3 cm, suggestive of pheochromocytoma and whole body scintigraphy with metaiodobenzylguanidine (MIBG) positive in the left adrenal gland. She underwent resection of the tumor in the left adrenal, without complications. Anatomopathology compatible with pheochromocytoma with immunohistochemistry for ki67 &lt;3%. Currently, the patient is clinically stable and with periodic follow-up, as well as family members, performing screening for diseases associated with VHL. Conclusion: VHL syndrome is one of the possible causes of non-functioning pheochromocytomas and paragangliomas, and adrenal lesions with negative metanephrine levels do not exclude them; thus highlighting the importance of exams such as CT or MRI and functional topographic studies (whole body scintigraphy with MIBG and / or PETCT with Galio68DOTA) for their diagnosis.
Paraneoplastic Hypoglycemia Leading to Insulin Independence in a Patient With Type 1 Diabetes
Authors: Haeri Nami Safai , Mahmud Hussain , Korytkowski Mary T 
Published: May 2021

Abstract
Introduction: Hypoglycemia is a rare paraneoplastic manifestation of several non-islet cell tumors (NICT) that is rarely reported in individuals with diabetes. We report the first case of a patient with type 1 diabetes (T1D) and a recurrent gastrointestinal stromal tumor (GIST) who required discontinuation of all insulin therapy with continuous parenteral glucose infusions to avoid hypoglycemia.
Case: The patient is an underweight (BMI 14.9 kg/m2) 59-year-old female with a 24-year history of T1D treated with insulin pump therapy who was diagnosed with GIST in 2003. Following surgical resection with postoperative adjuvant therapy, she remained tumor free until 2012 when she had disease recurrence unresponsive to several tyrosine kinase inhibitors. In 2014, she reported frequent episodes of documented hypoglycemia despite continued reductions in basal insulin infusion rates. Laboratory testing following several hours of insulin discontinuation revealed undetectable insulin and C-peptide levels, low IGF-1, normal IGF-2, and an IGF-2: IGF-1 ratio of 7.86. Thyroid, kidney and adrenal tests were normal. Initiation of prednisone alone then in combination with octreotide did not abate the hypoglycemia. During a hospitalization for hypoglycemia, exogenous insulin therapy was discontinued and 10% dextrose infusions started. Attempts at weaning the dextrose infusions resulted in hypoglycemia, prompting insertion of a PICC line prior to discharge home with continuous 25% dextrose infusions at 40-60 mg per hour. Discussion: NICT hypoglycemia (NICTH) is characterized by excessive tumor production of IGF-2 or pro-IGF-2. The structure of IGF-2 is similar to insulin, allowing cross reactivity at the insulin receptor. IGF binding proteins (IGFBPs) are responsible for transporting IGF-2 in plasma. Abnormal processing of the gene for IGF-2 results in increased production of the more biologically active pro-IGF-2 that does not form a complex with IGFBP3 and is available to interact with insulin receptors. In patients with normal IGF-2 (chronic kidney disease, poor nutritional status), an IGF-2: IGF-1 ratio &gt;3 can be used to confirm NICTH. IGFBP-3 was not measured in this patient but it is likely this was low due to her poor nutritional status. The most definitive treatment for NICTH is resection of the tumor. Pharmacological management can be considered in patients who are not surgical candidates, but is not always successful as was observed in this patient. Conclusion:This is an unusual case of malignancy associated hypoglycemia in a woman with type 1 diabetes who required discontinuation of all insulin therapy as well as continuous dextrose infusions to achieve euglycemia and briefly maintain an acceptable quality of life over a period of several months.
Presentation of Pheochromocytoma, Papillary Thyroid Cancer and Hyperparathyroidism in Three Family Members
Authors: Ashorobi Damilola , Mandal Kaushik , Liao Huijuan , Kumar Salini Chellappan 
Published: May 2021

Abstract
Introduction: Although rare, one of the most common inherited disorders is multiple endocrine neoplasia. It is an autosomal dominant disorder that predisposes individuals to certain endocrine abnormalities depending on which type. The type 2A is a combination of medullary thyroid cancer, hyperparathyroidism, and pheochromocytoma which have been explained to be due to a mutation in the RET proto-oncogene. This abstract present a case of a patient with hyperparathyroidism whom family members also have pheochromocytoma and papillary thyroid cancer. Case description: A 45 year-old Hispanic male came to the endocrinology clinic complaining of constipation and headache. He has a personal history of non-toxic multinodular goiter and underwent right sided thyroidectomy in 2015 with pathology report showing follicular adenoma. He is currently on thyroid replacement therapy. He is clinically and biochemically euthyroid with TSH of 2.29 IU/ml. Physical examination was unremarkable. His labs were pertinent for calcium 11.5mg/dl, parathyroid 245.7pg/ml, creatinine of 1.5mg/dl. Two years ago, parathyroid was 189.5pg/ml and calcium was 11mg/dl, 1.5 year ago parathyroid level was 235.5pg/ml, calcium was 11.4mg/dl, urine calcium 9.3mg/dl, 24hr urine calcium 286.4mg, calcitonin &lt;2pg/ml, vitamin D 23ng/ml, 1,25 vitamin D 53ng/ml. In 2017, Sestambi scan showed equivocal focus of faint parathyroid activity in the region of the mid to lower left thyroid lobe versus faint residual thyroid activity and in 2019, scan showed no definite parathyroid adenoma. Surgical intervention was recently recommended due to patient’s DEXA scan showing osteoporosis of the femoral neck. The family history of this patient is pertinent for two sisters; one with pheochromocytoma and the other with papillary thyroid cancer. One of the sisters is a 60 years old diagnosed with pheochromocytoma at 51. Her free normetanephrine level was 682pg/ml and total metanephrine was 727pg/ml at time of diagnosis. Her MRI report showed right adrenal mass measuring 3.5x2.8cm. Laparoscopic right adrenalectomy was done and pathology confirmed pheochromocytoma which was RET negative. She still follows up with endocrinology and calcitonin, chromogranin A and plasma metanephrines have been normal. The second sister is now 53 years old diagnosed with papillary thyroid cancer at age 27 and had total thyroidectomy with pathology confirming papillary thyroid cancer. Discussion: Based on the clinical presentation of these family members, the most likely explanation is familial inheritance. This pattern of inheritance cannot be explained by MEN 2A or 2B due to the absence of medullary thyroid cancer. It has also been reported that this unusual presentation could be a variant of MEN 2A.[i] Due to the family history, close follow up is required to monitor for the possible development of other endocrinopathies in the future.
Recurrent Pheochromocytoma, as Component of Multiple Endocrine Neoplasia
Authors: Dominguez Hydelene Beray , Pacheco Elizabeth P , Jimeno Cecilia , Lantion-Ang Franceslina C , Hernandez Edrome , Chiu Harold Henrison Chang 
Published: May 2021

Abstract
Background: Pheochromocytoma is a rare neuroendocrine tumor from the adrenal medulla’s chromaffin cells that secrete catecholamines. The mainstay of treatment is surgery. Although rare, it has a recurrence rate of 6.5-16.5% even after adequate surgical removal with a notable increase in prevalence among genetic syndromes, extra-adrenal tumors, larger tumor size, and younger age of diagnosis. Case: A 23-year-old Filipino male with no known familial disease presented with episodic headache, palpitations, diaphoresis, and resistant hypertension. Two masses in the left adrenal gland, with the larger one measuring 6.0cm x 5.0cm x 3.0cm, were surgically removed. Histologic examination revealed pheochromocytoma. Post-operatively, there was the normalization of urinary metanephrines and the resolution of the signs and symptoms. He was lost to follow-up and returned five years later with an abdominal ultrasound demonstrating a right adrenal mass. He had no accompanying signs and symptoms; the physical examination was unremarkable. On workup, biochemical testing revealed two 24-hour urinary metanephrine levels were markedly elevated, 14.49 and 19.97 (NV:0-1mg/24 hours). Calcitonin: 644 (NV:0-18pg/ml) and carcinoembryonic antigen (CEA): 23.52 (NV:&lt;5ng/ml) were also elevated. Mild hypercalcemia was noted with elevated intact PTH 101.74 (NV:0-65pg/ml). Parathyroid scintigraphy was normal. The neck ultrasound showed multiple bilateral thyroid nodules, with the largest measuring 1.2cmx0.9cm (TIRADS IV). The abdominal CT scan showed two well-defined, homogenous right adrenal masses, with the largest measuring 6.3cm x 5.6cm x 7.4cm. He underwent right adrenalectomy, and histopathology showed pheochromocytoma with Pheochromocytoma of the Adrenal Scale Score (PASS) of 3. One month later, he underwent total thyroidectomy with neck dissection and inferior parathyroid gland resection. Histopathology confirmed medullary thyroid cancer with nodal metastasis and parathyroid adenoma. The patient recovered well without complications. Biochemical tests normalized eight weeks post-surgery. The presence of synchronous recurrent pheochromocytoma, medullary thyroid cancer (MTC), and primary hyperparathyroidism is consistent with multiple endocrine neoplasia 2A (MEN2A) syndrome. Conclusion: Lifelong follow-up is essential in patients treated for pheochromocytoma despite the complete removal of the adrenal masses due to recurrence risk. Recurrence should likewise raise the suspicion of MEN2, a genetic syndrome. In addition, the pheochromocytoma has malignant characteristics, and the MTC has metastases to the cervical lymph nodes. Early detection and prompt intervention are essential for the treatment of the disease.
A Case of Iatrogenic Cushing’s Syndrome
Authors: Del Toro Diez Andrea , Garcia Michelle Marie Mangual , Garcia-Mateo Jose M , Sanchez Ernesto Jose Sola 
Published: May 2021

Abstract
Cushing’s syndrome (CS) is considered a rare disease. The most common cause is the exogenous use of glucocorticoids (GCs), which are often given within a controlled medical setting, but their factitious use is rare. Factitious CS is more common in females, young patients, those with psychiatric disorders, and those with contacts within the medical field. The diagnosis of CS is challenging because some features are non-specific and commonly present in the general population, such as obesity, depression, diabetes, hypertension (HTN), and low bone mineral density (BMD). A high suspicion is warranted. We present the case of a 47-year-old man with HTN, obesity, dyslipidemia, obstructive sleep apnea, and low BMD who complained of increased appetite, significant weight gain, fatigue, sleepiness, muscle weakness, and occasional facial flushing. Medications include Hydrochlorothiazide, Furosemide, Losartan, Atorvastatin, and Teriparatide. Vital signs were normal and body mass index was 41.9 kg/m2. He had a round face, central obesity, and wide purple striae in his abdomen. Dual-energy X-ray absorptiometry scan showed low BMD at spine. Laboratories revealed a glycated hemoglobin of 6.1%, late-night salivary cortisol of &lt;0.03 mcg/dL, 24-hour urine free cortisol of 22.5 mcg/24hr, morning cortisol of 0.01 ug/mL, ACTH 23.5pg/mL, and dehydroepiandrosterone sulfate (DHEA-S) 35 mcg/dL. Our patient persistently denied use of exogenous GCs, but a urine synthetic GC screen disclosed a positive result for dexamethasone; levels at 1.1 mcg/dL. After an exhaustive conversation, our patient confessed to using over-the-counter dexamethasone 4mg to treat occasional muscle aches. ACTH is usually suppressed in factitious CS, but this was not our patient’s case, giving the appearance of ACTH-dependent hypercortisolism. This can lead to unnecessary diagnostic and therapeutic approaches. An unsuppressed ACTH could be due to an unreliable ACTH immunoassay or intermittent, instead of continuous, ingestion of GCs. A suppressed DHEA-S level, as seen in our patient, may provide the clue to exogenous GC use as the cause of CS. Our case is also rare because our patient is male, older, and not related to the medical field. Hypercortisolism must be detected and treated early due to its high morbidity and mortality. Several features may be reversed with treatment. The possibility of hypothalamic-pituitary-adrenal (HPA) axis suppression due to prolonged use of GCs, resulting in adrenal insufficiency (AI) should be considered. The prevalence of GC-induced AI ranges from 14–63%, with the highest risk in those with Cushingoid features and those receiving a dose equivalent to prednisone 20mg daily for more than three weeks. Sudden withdrawal of GCs should be avoided to prevent adrenal crisis. A tapering regimen should be adopted with subsequent biochemical testing of the HPA axis once GCs have been reduced to a physiologic dose.
A Frame-Shift for IGF-1R in Breast Cancer and Metastasis
Authors: Obr Alison E , Lemenze Alexander , Maingrette Krystopher , Ciliento Virginia , Chang Yun-juan , Bulatowicz Joseph J , Wood Teresa L 
Published: May 2021

Abstract
Although, IGF-1R historically has been considered a target for inhibition to treat breast cancer patients, recently, we have identified low levels of IGF-1R are associated with worse overall patient survival and basal-like, triple-negative breast cancer (TNBC). Our findings present a frame-shift for the function of IGF-1R in breast cancer. To elucidate how loss of IGF-1R function impacts aggressive breast cancers, we have integrated the use of human patient data with mouse models where IGF-1R has been deleted or dysregulated. Single cell RNA-sequencing (scRNAseq) analyses from mouse mammary tumors with decreased IGF-1R has revealed expansion of macrophage populations within the tumor consistent with our previous data identifying IGF-1R attenuation promotes an immune evasive tumor microenvironment. Further analysis of the epithelial cell populations identified expansion of the basal and luminal progenitor cells in tumors with reduced IGF-1R. Gene expression alterations in these populations includes enrichment of pathways necessary for cell invasion, cell adhesion, and metastasis. We have further defined how reduced tumor epithelial IGF-1R promotes metastasis by utilizing tail vein injection (TVI). Micrometastatic lesion numbers were similar in animals injected with tumor epithelial cells from control and tumor models with decreased IGF-1R. In contrast to primary tumor-induced metastases, IGF-1R attenuation in dissociated tumor cells decreased metastatic cell proliferation in TVI lungs. Moreover, we observed alterations in expression of several cadherins in tumors with decreased IGF-1R; E-cadherin gene and protein levels are decreased, while P-cadherin gene and protein levels are increased. In vitro cell adhesion assays revealed epithelial cells from tumors with attenuated IGF-1R had reduced adherence to matrix and cell-cell contacts. We have aligned the scRNAseq data from mouse mammary tumors with decreased IGF-1R with human data gene profiles from patient tumors with low IGF-1R and have identified common pathways that are necessary for promoting tumor metastasis including EMT, cell adhesion, and cell cycle. Correlation with the human patient data suggests the mouse models with attenuated IGF-1R reflect similar biology to human patients with low IGF-1R expression. Furthermore, we have uncovered a function for IGF-1R in maintaining proper cell-cell adhesion in the primary tumor supporting the conclusion that dysregulated IGF-1R favors metastatic extravasation of tumor epithelial cells.
A Novel Steroidogenic Factor-1 Antagonist, OR-449, as a Targeted Therapy for Adrenocortical Cancer
Authors: Crowe Paul , Fox Ray , Tao Haiyan , Eastwood Emily , Raheja Neil , Ribeiro Raul , Thacher Scott 
Published: May 2021

Abstract
Adrenocortical carcinoma (ACC) is a rare cancer with an annual incidence of 0.7-2.0 cases per million in the US and EU. Surgical resection combined with adjuvant chemotherapy remains the primary treatment for patients with advanced disease. Although surgery is an option for most patients, oftentimes cases presenting with locally advanced or metastatic disease are not candidates for surgical resection. Furthermore, the non-specific adrenolytic and highly toxic FDA-approved chemotherapy drug, mitotane, is only marginally effective in adult and pediatric ACC. Steroidogenic factor-1 (SF-1 or NR5A1), an orphan nuclear receptor that is essential for the growth and development of the adrenal gland, is highly expressed in adult and pediatric ACC. Moreover, SF- is the major, active transcription factor in ACC (1,2). To address the unmet need for a targeted therapy in ACC, we identified potent small molecule SF-1 antagonists that block SF-1 transcriptional activity through the SF-1 ligand-binding domain (IC50 = 15-20 nM in a CHO cell reporter assay). In short-term dissociated cell cultures established from SJ-ACC3 (3), a pediatric ACC patient-derived tumor xenograft (PDX), OR-449 and a related SF-1 antagonist, OR-907S, blocked DNA synthesis as measured by inhibition of EdU incorporation in SF-1+ cells (IC50 = 500-600 nM, &gt;80% efficacy at 10 μM) whereas OR-907R, the 100-fold less potent enantiomer of OR-907S, is nearly inactive. OR-449, which has &gt;20% oral bioavailability and a long plasma half-life (&gt; 9 h) in mouse, rat and dog, inhibited growth of SJ-ACC3 tumors grown in immunocompromised mice following daily oral dosing (30 mg/kg) for 4 weeks. SF-1-responsive genes, both down- and up-regulated, identified by RNAseq (by comparison of OR-907S and OR-907R in SJ-ACC3 dissociated cell culture), also responded to OR-449 in SJ-ACC3 xenografts following 7 days of dosing, indicating transcriptional regulation of SF-1 by OR-449. Importantly, in an exploratory 2-week mouse safety study, OR-449 showed no adverse effects when dosed up to 100 mg/kg. Taken together, these findings suggest that SF-1 antagonists could provide a safe and effective targeted therapy for ACC. References: (1) Mohan, et al., Curr. Opin. Endocrinol. Metab. Res., 2019; 8:72; (2) Corces, et al., Science, 2018; 362:eaav1898; (3) Pinto, et al., Clin. Cancer. Res., 2013; 19:1740.