Adrenal Cortical Adenoma Research Articles

Autophagy-Related Proteins Are Differentially Expressed in Adrenal Cortical Tumor/Pheochromocytoma and Associated with Patient Prognosis.

The aim of this research was to evaluate the expression and concomitant implications of LC3A, LC3B, beclin-1, and p62, which are key components of autophagy in human adrenal gland tumors. Tissue microarray was made for 321 cases of adrenal gland tumor (adrenal cortical adenoma (ACA): 115, adrenal cortical carcinoma (ACC): 17, and pheochromocytoma (PCC): 189). Immunohistochemical staining was performed for beclin-1, p62, LC3A, and LC3B, and the results were compared with the patients’ clinicopathologic parameters. LC3A, LC3B, beclin-1, and LC3B isolated single positive cells (ISPC) positivity rates were higher in PCC than in adrenal cortical tumor (ACT), whereas p62 positivity was lower in PCC than in ACT. The proportion of positive LC3B (ISPC) was higher in ACC than in ACA. In addition, the proportion of cells positive for p62 and LC3B (ISPC) was significantly higher in PCCs with a GAPP score of ≥3. In univariate Cox analysis, p62 positivity (p = 0.014) and the presence of p62 (ISPC) (p = 0.001) were associated with shorter disease-free survival in PCC. Moreover, p62 positivity was predictive of shorter overall survival (OS) in patients with PCC by multivariate analysis (relative risk, 6.240; 95% CI, 1.434–27.15; p = 0.015). Differences were found in the expression of autophagy-related proteins according to adrenal gland tumor types. Compared to ACT, the proportion of LC3A, LC3B, beclin-1, and LC3B (ISPC) positivity was higher in PCC, whereas p62 positivity was lower. Similarly, p62 positivity in PCC was associated with patient prognosis of OS.

Expression of Glucose Metabolism-Related Proteins in Adrenal Neoplasms

Purpose: The aim of this study was to investigate the expression patterns of glucose metabolism-related proteins and their clinicopathologic implications in adrenal cortical neoplasms (ACN) and pheochromocytoma (PCC). Methods: Immunohistochemical staining was performed to evaluate glucose metabolism-related proteins (GLUT1, CAIX, hexokinase II, G6PDH, PHGDH, and SHMT1) in 132 ACN cases (115 adrenal cortical adenoma [ACA] and 17 adrenal cortical carcinoma [ACC]) and 189 PCC cases. Results: Expression levels of GLUT1 in tumor cells ([T]; p < 0.001), GLUT1 in stromal cells ([S]; p < 0.001), G6PDH (p < 0.001), and SHMT1 (p = 0.002) were higher in ACN than in PCC. GLUT1 (T; p = 0.045) and PHGDH (p = 0.043) levels were higher in ACC than in ACA. In a univariate analysis of ACN, GLUT1 (T; p = 0.017), CAIX (S; p = 0.003), and PHGDH (p = 0.009) levels were correlated with a shorter overall survival (OS). GLUT1 (T; p = 0.001) and PHGDH (p < 0.001) were related to a shorter OS in PCC. GLUT1 (T) positivity (p = 0.043) in ACN predicted a poor OS in a multivariate Cox analysis. In PCC, high GAPP score (p = 0.026), GLUT1 (T; p = 0.002), and PHGDH (p < 0.001) were independent prognostic factors for poor OS. Conclusions: The adrenal gland tumors ACN and PCC had different expression patterns of glucose metabolism-related proteins (GLUT1, G6PDH, and SHMT1), with higher expression levels in ACN than in PCC. GLUT1 and PHGDH were significant prognostic factors in these adrenal neoplasms.

Functional and non-functional types of adrenal tumors: a case series

Adrenal gland masses could be classified into functional, malignant, or benign. An adrenal cortical adenoma is one of the most common incidentalomas found with either functional or non-functional type. Pheochromocytoma is a neural crest cell origin tumor associated with catecholamine production. A classic triad of headache, sudden episodic perspiration, and tachycardia marked a pheochromocytoma. We report three patients with adrenal tumors. First, a 52-year-old woman with complaints of pain in the left flank suggests a left kidney tumor. The patient has an increased blood pressure intraoperatively. Adrenal cortical adenoma was found postoperatively. The second case is an Indonesian male 27-year-old with pain in the upper right abdomen. Intraoperative, the patient also has an escalation in blood pressure. Antihypertensive drugs are also used in this patient. Postoperatively, a pathology result of pheochromocytoma was revealed from this patient. The third case, adrenal myelolipoma, was suspected in a 48-year-old male and underwent surgery because of tumor growth. Later, a histopathological examination revealed myelolipoma of the adrenal. Management of adrenal tumor should be done individually based on each patient. In the first and second cases, blood pressure was unstable intraoperatively and was managed using several drugs, and was stable at follow-up. In the third case was no hemodynamic problem. In the case of an adrenal tumor, management tailoring should be based on the individual patient.

Incidentally discovered myelolipomatous adrenal adenomas, including six cases presenting with hypercortisolism

Most adrenal incidentalomas are non-functioning adenomas that require no treatment. The presence of a myelolipomatous component of adrenal incidentalomas is a rare, but well-known occurrence in both hyperplastic and neoplastic lesions of the adrenal cortex. Although the improvements in abdominal imaging have increased identification of myelolipomatous adrenal cortical adenomas radiologically, due to the rarity of this lesion, the clinical pathological features of these lesions are unclear and can sometimes cause diagnostic difficulty. Eleven patients had surgeries at The University of Texas MD Anderson Cancer Center. Four additional cases were provided from an external collaborator. Of the 15 cases, there were 5 male and 10 female patients, with a median age of 52 years (mean 54 years, range 28–84 years). Clinical presentation included adrenal incidentaloma (n = 9), Cushing syndrome (n = 4, including 1 as a part of Carney complex), and subclinical Cushing syndrome (n = 2, including 1 with bilateral macronodular adrenal hyperplasia). In this study, we present the clinicopathologic features of fifteen myelolipomatous adrenal adenomas, the largest series published thus far.

“Relieving the Pressure” With Unilateral Adrenalectomy in a Case of Chronic Resistant Hypertension From Primary Aldosteronism

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 <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.

Persistent Hyperkalemia Post-Adrenalectomy for Aldosterone-Producing Adenoma

Abstract Background:Post-operative hypoaldosteronism due to chronic suppression of the renin-aldosterone axis of the contralateral gland can be complicated with hyperkalemia. We describe a case of persistent hyperkalemia post adrenalectomy for aldosterone-producing adenoma. Clinical Case: A 47-year-old male was first diagnosed with hypertension in 2011. He was investigated for secondary hypertension after hospital admission in 2019 for hypertensive urgency and symptomatic hypokalemia (potassium, K 1.9–2.3 mmol/L, n = 3.5–5.0). Subsequent laboratory investigation revealed elevated serum aldosterone (3565 pmol/L, n &amp;lt; 103) with an aldosterone renin ratio of 115 (n &amp;lt; 35). A confirmatory test with saline loading showed an unsuppressed serum aldosterone level of 1840 pmol/L. Adrenal CT reported a 4.1-cm, heterogeneous left adrenal lesion. A diagnosis of primary aldosteronism was made, and he underwent laparoscopic left adrenalectomy in July 2020. Histopathology examination was consistent with adrenal cortical adenoma. Both potassium supplementation and spironolactone were stopped immediately postoperatively. Two weeks later, he developed symptomatic hyperkalemia (K 6.0 mmol/L), requiring hospital admission, and started on potassium binder. Throughout clinic follow-ups, potassium remained high (K 5.4–6.1 mmol/L), despite low potassium diet and potassium binder. His case was co-managed with the nephrology team and given a trial of frusemide and sodium bicarbonate to normalize his potassium. However, after 4 months, he remained hyperkalemic. Repeated serum aldosterone was not elevated (&amp;lt;103 pmol/L). He was then started on fludrocortisone and finally managed to achieve serum potassium normalisation (K 4.1–4.5 mmol/L). Conclusion: This case highlights the importance of monitoring potassium levels in all patients after adrenalectomy, particularly those with clinical risk factors. Retrospective studies by Park et al and Fischer et al reported that a long duration of hypertension, impaired preoperative renal function, older age, and large adenoma size represent risks for developing hyperkalemia postoperatively, whereas the use of mineralocorticoid receptor antagonists preoperatively does not prevent hyperkalemia. Treatment includes a low potassium diet, a high sodium diet, adequate hydration, potassium binder, frusemide, and fludrocortisone. In some cases, hyperkalemia may be prolonged, necessitating long-term fludrocortisone therapy, up to 11–46 months².

Most True Adrenal Incidentalomas Lack Proper Evaluation

Abstract Although the majority of true adrenal incidentalomas are benign and non-functional, appropriate workup is critical to rule out cancers as well as metabolic and cardiovascular diseases such as Cushing’s syndrome, primary aldosteronism (PA), and pheochromocytoma (PCC). The AACE/AAES and ENSAT guidelines recommend that all adrenal incidentalomas be evaluated for worrisome radiographic features and that all patients have initial biochemical work up to evaluate for hypercortisolism and pheochromocytoma as well as primary aldosteronism if hypertensive. Despite this, adrenal incidentalomas often are not evaluated properly leading to delayed diagnoses and potential complications from dysregulated hormone production. To determine if true adrenal incidentalomas are managed properly in our hospital system, we conducted a retrospective chart review. All CT scans (chest or abdomen) of adult patients conducted at the University of Colorado Hospital system between August 2011 and December 2016 were assessed (N=86,771). Of these, 305 scans identified true adrenal incidentalomas. CT scans done for patients with genetic conditions predisposing to adrenal nodules or done for an indication suggestive of adrenal disorder were excluded. From the 305 patient scans, 347 adrenal nodules were identified. Most patients (N=263, 86%) had one adrenal nodule; 42 (14%) had multiple nodules. Mean age of the cohort was 60±12.58 years old (range 21–88), and the majority were female (60.7%). The nodules had a mean size of 2.23±1.42 cm, range 0.5–11.2 cm. Most nodules were identified on CT scans with contrast (79%, N=241). Of the 64 scans (21%) done without contrast, 43% of the nodules had non-contrast enhanced (NCE) Hounsfield units (HU) less than 10, suggesting benign adenomas. Thirty-nine nodules (57%) had NCE HU greater than 10; eight of those were surgically removed (4 metastases from other primary cancers; 2 PCC; 2 lipid poor adrenal cortical adenomas). Most nodules were not biochemically evaluated. Only 64 of the 305 patients (21%) were tested for hypercortisolism (1mg ODST in 35; 24hr UFC in 29). Of those, three (0.1%) were diagnosed with Cushing’s syndrome. Only 82 patients (27%) were evaluated for PCC with plasma and/or 24hr urine metanephrines. Of these, 10 were diagnosed with PCC (3.3%). Only 24 patients (7.9%) were screened for PA with serum aldosterone and plasma renin activity, and four (1.3%) were positive. Taken together, of the 305 patients with adrenal incidentalomas, only 29 (9.5%) met guideline recommendations for biochemical work up for both hypercortisolism and PCC. Of those, 10 had a history of hypertension, yet only 5 were evaluated for PA. In summary, less than 10% of true adrenal incidentalomas had the proper biochemical evaluation. This suggests there are likely missed functional nodules leading to delayed or missed diagnosis possibly contributing to cardiovascular and metabolic consequences.

Primary Hyperaldosteronism From Adrenocortical Adenoma Presenting as Seizures and Stroke

Background: Primary hyperaldosteronism, which is unregulated secretion of aldosterone from the adrenal gland, is a common cause of resistant hypertension. Hyperaldosteronism can lead to life threatening cardiovascular and neurological complications emphasizing the crucial need for timely identification and management. We present a case of a young patient who suffered complications as a result of primary hyperaldosteronism. Clinical Case: A 35 year old female with a past medical history of resistant hypertension on four anti-hypertensive medications, primary hyperaldosteronism with known adenoma, CKD stage III, and hyperlipidemia presented to the hospital due to multiple seizures. She was found to be encephalopathic and required intubation for respiratory failure. Her systolic blood pressure was elevated to 250 mmhg. CT scan of the head showed a small left temporal hemorrhage and an MRI brain was revealing of bilateral thalamic infarcts. No neurosurgical intervention, antiplatelet or anticoagulation was recommended. She was admitted to the ICU and started on nitroprusside infusion. CT scan of the abdomen showed a 17 mm right adrenal nodule unchanged from prior imaging. Due to concern for pheochromocytoma, she was started on alpha blockade and subsequently beta blockade therapy. After stabilization of patient’s blood pressure, extubation, and improvement in mental status, she was discharged on new anti-hypertensive medications including spironolactone given her hypokalemia. Further endocrine evaluation was pursued. Work up included urine and plasma catecholamines which were not indicative of pheochromocytoma. Morning cortisol level was within normal limits. Plasma aldosterone level was 30, plasma renin was 0.90 with an aldosterone/renin ratio of 33 suggestive of primary hyperaldosteronism. Though the patient had known primary hyperaldosteronism with an adenoma, she had poor follow up and did not comply with initial recommendation of surgical removal of adenoma prior to her stroke. After medical stabilization following her stroke, a laparoscopic right adrenalectomy was performed. Pathology showed an adrenal cortical adenoma with no evidence of pheochromocytoma. Post-surgical systolic blood pressures were less than 120 mmhg. She was able to come off of spironolactone with plans to gradually discontinue other antihypertensive medications. Conclusion: This case emphasizes the importance of testing for primary hyperaldosteronism particularly in young patients with resistant hypertension. Furthermore, primary hyperaldosteronism should be considered as an underlying etiology for young patients who suffer from strokes particularly in the setting of hypertension. Given the reversibility of primary aldosteronism from an adrenocortical adenoma with surgery, life threatening complications such as cerebrovascular accidents can be prevented.

Cushing’s syndrome manifesting as chronic insomnia caused by adrenal cortical adenoma with incidental pituitary microadenoma: a case report

Background: Cushing’s syndrome is condition caused by excessive glucocorticoid with insomnia as one of its neuropsychiatric manifestation. Cushing’s syndrome may be caused by excessive adrenocorticotropin hormone (ACTH-dependent), for example from ACTH producing pituitary tumors, or by overproduction of cortisol by adrenocortical tumors. In this report, we presented a case with Cushing’s syndrome manifesting as chronic insomnia with adrenal cortical adenoma and pituitary microadenoma.Case presentation: A 30-year-old woman was consulted from the Neurologic Department to the Internal Medicine Department with the chief complaint of insomnia and worsening headache since 6 months prior to the admission. She had undergone head MRI and abdominal CT scan previously and was found to have both pituitary microadenoma and left adrenal mass. From the physical examination she had clinical signs of Cushing’s syndrome like Cushingoid face and purplish striae on her stomach. Midnight cortisol serum examination was done initially and showed high level of cortisol. High dose dexamethasone suppression test or DST (8 mg overnight) was later performed to help determine the main cause of Cushing’s syndrome. The result failed to reach 50% suppression of cortisol serum, suggestive that the Cushing’s syndrome was not ACTH-dependent from the pituitary but potentially from overproduction of cortisol by the left adrenal mass. Therefore, left adrenalectomy was performed and the histopathological study supported the diagnosis of adrenal cortical adenoma.Conclusion: Chronic insomnia is a very important symptoms of Cushing’s syndrome that should not be neglected. The patient had both microadenoma pituitary and left adrenal mass thus high dose DST test (8 mg overnight) needed to be performed to differentiate the source of Cushing’s syndrome. The result showed only little suppression therefore the pituitary microadenoma was not the source of Cushing’s syndrome and more suggestive from the adrenal etiology.

Expression of Glutamine Metabolism-Related and Amino Acid Transporter Proteins in Adrenal Cortical Neoplasms and Pheochromocytomas.

Background Glutamine metabolism is considered an important metabolic phenotype of proliferating tumor cells. Objective The objective of this study was to investigate the expression of glutamine metabolism-related and amino acid transporter proteins in adrenal cortical neoplasms (ACNs) and pheochromocytomas (PCCs) in the adrenal gland. Methods A tissue microarray was constructed for 132 cases of ACN (115 cases of adrenal cortical adenoma and 17 cases of adrenal cortical carcinoma) and 189 cases of PCC. Immunohistochemical staining for glutamine metabolism-related proteins GLS1 and GDH and amino acid transporter proteins SLC1A5, SLC7A5, and SLC7A11 as well as SDHB was performed and compared with clinicopathologic parameters. Results The expression levels of GLS (p < 0.001), SLC7A5 (p = 0.049), and SDHB (p = 0.007) were higher in ACN than in PCC, whereas the expression levels of SLC1A5 (p < 0.001) and SLC7A11 (p < 0.001) were higher in PCC than in ACN. In ACN, GLS positivity was associated with a higher Fuhrman grade (p = 0.009), and SLC1A5 positivity was associated with SDHB positivity (p = 0.004) and a clear cell proportion < 25% (p = 0.010). SDHB negativity was also associated with tumor cell necrosis (p = 0.007). In PCC, SLC7A11 positivity was associated with nonnorepinephrine type (p = 0.008). In Kaplan-Meier analysis, patients with GLS positivity (p = 0.039) and SDHB negativity (p = 0.005) had significantly shorter overall survival in ACN. In PCC patients with a GAPP score ≥ 3, GLS positivity (p = 0.001) and SDHB positivity (p = 0.001) were associated with shorter disease-free survival, whereas GLS positivity (p = 0.004) was also associated with shorter overall survival. Conclusions The expression of glutamine metabolism-related and amino acid transporter proteins in ACN and PCC is distinct and associated with prognosis.

A case series of adrenal lesions in a tertiary care hospital

Introduction: Adrenal lesions as such are very rare conditions, which are incidentally detected through an imaging procedure, performed for reasons unrelated to adrenal dysfunction or suspected dysfunction and are known as adrenal incidentalomas.1 Its prevalence ranges from 1.4% to 2.9% worldwide. We report a series of three cases of adrenal lesions received at our hospital between the years 2011 and 2016. Case series: In a series of three cases, we found that there was one case of Adrenal cortical adenoma, one case of nodular hyperplasia of adrenal gland and one case of adrenocortical carcinoma. Majority of the tumors were seen in the age group of 20-40 years with male preponderance and only 42.8% were detected coincidentally on imaging. Conclusion: The three cases are reported here for their rarity of presentation. Keywords: Adrenal tumours, Adrenal incidentaloma, Adrenocortical carcinomas.

Adrenal-Renal Fusion with Adrenal Cortical Adenoma and Ectopic Adrenal Tissue, Presenting as Suspected Renal Mass: A Case Report

Adrenal-renal fusion with adrenal cortical adenoma is a rare anomaly with only a few cases described in the literature. Imaging-based identification of this anomaly remains a diagnostic challenge, making it difficult to differentiate upper pole renal malignancy from adrenal cortical adenoma. We describe a case of a 62-year-old woman with an upper pole cystic renal mass on imaging, who underwent robotic partial nephrectomy. Intraoperatively the renal mass was found to be an adrenal-renal fusion anomaly, with ectopic adrenal tissue. Adrenal-renal infusion of an adrenal cortical adenoma was confirmed on final pathology. Due to lack of imaging-based diagnosis, this condition should be considered in the differential for upper pole renal masses.

Predicting malignancy in patients with adrenal tumors using 18 F-FDG-PET/CT SUVmax.

18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG-PET/CT) parameters may help distinguish malignant from benign adrenal tumors, but few have been externally validated or determined based on definitive pathological confirmation. We determined and validated a threshold for 18 F-FDG-PET/CT maximum standard uptake value (SUVmax) in patients who underwent adrenalectomy for a nonfunctional tumor. Database review identified patients with 18 F-FDG-PET/CT images available (training cohort), or only SUVmax values (validation cohort). Discriminative accuracy was assessed by area under the curve (AUC), and the optimal cutoff value estimated by maximally selected Wilcoxon rank statistics. Of identified patients (n = 171), 86 had adrenal metastases, 20 adrenal cortical carcinoma, and 27 adrenal cortical adenoma. In the training cohort (n = 96), SUVmax was significantly higher in malignant versus benign tumors (median 8.3 vs. 3.0, p < .001), with an AUC of 0.857. Tumor size did not differ. The optimal cutoff SUVmax was 4.6 (p < .01). In the validation cohort (n = 75), this cutoff had a sensitivity of 75% and specificity 55%. 18 F-FDG-PET/CT SUVmax was associated with malignancy. Validation indicated that SUVmax ≥ 4.6 was suggestive of malignancy, while lower values did not reliably predict benign tumor.

A Case of Hemorrhage of Non-functional Adrenal Cortical Adenoma in a Patient who was Receiving Anticoagulant Therapy

A Case of Hemorrhage of Non-functional Adrenal Cortical Adenoma in a Patient who was Receiving Anticoagulant Therapy

Long Noncoding RNA Expression in Adrenal Cortical Neoplasms.

Long noncoding RNAs (lncRNAs) consist of nucleic acid molecules that are greater than 200 nucleotides in length and they do not code for specific proteins. A growing body of evidence indicates that these lncRNAs have important roles in tumorigenesis. Separating adrenal cortical adenomas from carcinomas is often a difficult problem for the surgical pathologist. This is especially true when only small needle biopsies are available for examination. We used in situ hybridization (ISH) analysis to study normal adrenal cortical tissues and adrenal cortical tumors to determine the role of specific lncRNAs in tumor development and classification. The lncRNAS studied included metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), psoriasis susceptibility-related RNA gene induced by stress (PRINS), and HOX antisense intergenic RNA myeloid 1 (HAM1). We constructed a tissue microarray (TMA) for the studies and also analyzed a subset of cases by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Two 1-mm duplicate cores of normal adrenal cortex (NAC) (n= 23), adrenal cortical adenomas (ACAs) (n= 95), and adrenal cortical carcinomas (ACCs), (n= 20) were used on the TMA. The results of ISH were analyzed by image analysis. ISH showed predominantly nuclear expression of lncRNAs in adrenal cortical tissues. MALAT1 showed more expression in ACCs than in NAC and ACA (p< 0.05). PRINS had higher expression in NACs and ACAs than in ACCs. The lncRNAs MALAT1, PRINS, and HAM1 are all expressed in normal and neoplastic adrenal cortical tissues. MALAT1 had the highest expression in ACC compared to ACAs and may have a role in ACC development.

Pediatric adrenal incidentaloma

Abstract Adrenal incidentalomas are a rare finding in children. In adults, adrenal incidentalomas are often found during imaging or postmortem. When incidentally discovered in adults, the principles of management focus on estimating risk of malignancy, with subsequent treatment plans developed accordingly. Unfortunately, these guidelines are not applicable to children due to the difficulty in differentiating benign and malignant adrenal masses on imaging. For this reason, most pediatric adrenal masses are surgically excised. We present the case of a 14-year-old male who had imaging for nonspecific abdominal pain and was found to have a left-sided retroperitoneal mass suspicious for a retroperitoneal teratoma. Given the proximity to the adrenal gland, a hormonal workup was nonetheless performed with no evidence of abnormal hormonal activity noted. During laparoscopic intervention, this lesion was found to be originating from the adrenal gland raising suspicion for an adrenal mass and a laparoscopic left adrenalectomy was performed. Histology of the mass revealed a heterogenous mass with components concerning for adrenal cortical adenoma, myelolipoma and adrenocortical carcinoma. A more in-depth analysis of the mass using expert opinion revealed a diagnosis of adrenal cortical adenoma with hyaline myxoid stroma and secondary involutional features.

Stemness regulation of the adrenal mixed corticomedullary tumorigenesis-a case-control study

Mixed corticomedullary tumor is an adrenal tumor intermixed with cortical and medullary cells. It is extremely rare with unclear tumorigenesis. We reported a 32-year-old female, manifested with typical Cushing’s syndrome and hypertension, to be diagnosed with right huge adrenal mixed corticomedullary tumor (8.8 cm). Right adrenalectomy was done to document the tumor intimately admixed with adrenal cortical adenoma and pheochromocytoma by biochemistry and immunohistochemistry. A case-control study was designed to explore the tumorigenesis of mixed corticomedullary tumor by whole exome sequencing. Expression of the stemness markers was controlled by a tissue array of 80 adrenal tumors. Overall, 1559 identical variants coexisted in parts of adrenal cortical adenoma and pheochromocytoma, which mainly (85.8%) originated from germline mutations. These enriched mutations were engaged in stemness control, coherent with substantial expression of the stemness markers (SOX2, CD44 and OCT4) in both parts. The differential stemness expressions were demonstrated in other adrenal tumors as well. The germline mutations were also enriched in signaling involving cancer proliferation, hypoxia inducible factor-1, focal adhesion and extracellular matrix receptor interaction. Somatic mutations affecting mitogen-activated protein kinase signaling, glycolysis and the citrate cycle were found in some tumor elements. This is the first study to verify the rare mixed corticomedullary tumor by molecular and genetic evidence to link with its phenotype. Germline mutations involving the stemness regulation and cancer proliferative signaling may drive intermixed tumor formation. Somatic mutations related to glycolysis and the citrate cycle may contribute to greater tumor outgrowth.

The Effect of Extracellular Calcium Metabolism on Aldosterone Biosynthesis in Physiological and Pathological Status.

Primary aldosteronism (PA) was reported to frequently harbor not only cardiovascular diseases but also some metabolic disorders including secondary calcium metabolic diseases. Recently, the potential association between aldosterone producing cells and systemic calcium metabolism has been proposed. For instance, PA is frequently associated with hypercalciuria or hypocalcemia, which subsequently stimulates parathyroid hormone (PTH) secretion. This altered calcium metabolism in PA patients could frequently result in secondary osteoporosis and fracture in some patients. On the other hand, extracellular calcium itself directly acts on adrenal cortex and has been also proposed as an independent regulator of aldosterone biosynthesis in human adrenals. However, it is also true that both PTH and vitamin D pathways stimulate endocrine functions of adrenal cortical adenomas to co-secret both aldosterone and cortisol. Therefore, it has become pivotal to explore the potential crosstalk between aldosterone and systemic calcium metabolism. We herein reviewed recent advances in these fields.

SAT-196 The Use of 11C-metomidate PET-CT to Detect Unilateral Primary Hyperaldosteronism

BackgroundIdentifying causative adrenal lesions presents a significant diagnostic burden for physicians and radiologists. We describe the use of radiolabelled metomidate to lateralise primary hyperaldosteronism.Case presentationA 52-year old Chinese man with a 5-year history of hypertension was referred for hypokalemia [K 2.7 mmol/L (3.6 - 5.0)]. He had been on Telmisartan 80 mg and Amlodipine 10 mg daily and blood pressure at home ranged 110-120 / 70-80 mmHg. There was no history of poor oral intake, persistent diarrhea or vomiting, and he was not on any other prescription or alternative medications. There was no significant family history of hypertension or sudden cardiac death. Clinic blood pressure was 140/84 mmHg. There were no features suggestive of Cushing’s syndrome.Repeat biochemical tests confirmed hypokalemia (K 3.1 mmol/L), and associated raised bicarbonate 37.3 mmol/L [19 - 29]. Magnesium and creatinine were normal. Aldosterone-renin Ratio was elevated at 8.1 (serum Aldosterone 611 pmol/L [97.3 - 834.0], active renin 2.7 pg/ml [1.8 – 59.4]). Post-saline infusion, non-suppressible serum aldosterone levels of 1137 pmol/L was demonstrated, consistent with autonomous aldosterone production.A computed tomography of the adrenal revealed a 2.3 cm x 1.9 cm nodule on the left adrenal gland consistent with lipid rich adenoma.Adrenal vein sampling (AVS) under continuous synacthen infusion was performed. Adrenal to peripheral cortisol ratio was ≥10 for either adrenal veins, confirming cannulation of the adrenal veins. Aldosterone-cortisol ratios showed lateralization to the left adrenal gland (lateralization ratio of 10.35). There was contralateral suppression of the right adrenal gland with ratio of 0.41. 11C-Metomidate PET-CT scan demonstrated a maximum standardised uptake value (SUVmax) of 26.8 over the left adrenal nodule, while the SUVmax of the right adrenal gland was 16.2. Ratio of the left to right adrenal gland SUVmax was 1.65 (above the threshold of 1.25); and was concordant with AVS. This confirmed that the patient had a left functional adrenal adenoma responsible for hyperaldosteronism.Our patient underwent a left adrenalectomy, and histology was consistent with adrenal cortical adenoma. Prior to surgery he required 72 mmol/l of potassium supplementation daily to maintain K levels of 3.3 – 4.0 mmol/L. Two weeks post-operatively, he was normokalemic (K 4.9 mmol/L) without potassium supplementation. Serum aldosterone normalized to 159.3 pmol/L (active renin 9.3 pg/ml). Blood pressure is well controlled on amlodipine 5mg daily.ConclusionTargeted molecular imaging such as 11C-Metomidate PET-CT could aid localisation of functional adrenal disease to guide definitive surgical management. In the future, this could obviate the need for invasive and technically complex procedures like AVS.

SAT-216 Retroperitoneal Paraganglioma: Case Report

Introduction: Paraganglioma (PGL) is a rare type of neuroendocrine neoplasm able to secrete neuropeptide and catecholamines. It can occur in any location between the neck and the pelvis. Most of the PGLs are diagnosed in the third to fifth decades and clinical presentation is variable and depends upon catecholamine secretion and tumor location. PGLs occur in the abdomen in 85% of cases. There are no unique imaging characteristics specific for PGLs, consequently, these tumors can be mistaken with other primary abdominal tumors. Clinical-Case: We present the case of a 65-year-old woman with history of hypertension (diagnosis at 40 years) and dyslipidemia. She denied family history of hypertension. In the context of a recent diagnosis of type 2 Diabetes Mellitus, she underwent abdominal ultrasound which revealed a large, heterogeneous nodular formation with partial liquid content, measuring 12x15 cm, adjacent to the left hepatic border. Abdominal CT scan revealed an intra-abdominal mass, with 14cm (largest diameter), showing intimate contact, with no cleavage plan with the posterior wall of the gastric fundus, suggesting Gastrointestinal Stromal Tumor. A left adrenal nodule with 3.3 cm was also present, rounded, hypoechogenic, with regular margins and homogeneous. Echoendoscopy with biopsy of the retro-gastric mass showed a neuroendocrine neoplasia. At this point she was sent to an endocrinologist. When questioned she referred headache, diaphoresis and anxiety complaints for 3 years. At examination, a painless abdominal mass in the epigastrium and left hypochondrium was found. Laboratory evaluation revealed urinary metanephrines 11738 (64-302) ug/day, urinary normetanephrines 5832 (162-527) ug/day, renin 15.5 (1-8.2) pg/mL, aldosterone 28.6 (10-160)ng/dL, cortisol after 1 mg dexamethason 1,18 µg / dl (less than 1,8ug/dl) and chromogranin A 36.6 nmol / L (less than 3nmol/l). MIBG scintigraphy revealed fixation only in the large known retroperitoneal mass. The patient underwent excision of the retroperitoneal mass and of the left adrenal gland without complications. The histological diagnosis revealed, respectively, paraganglioma and adrenal cortical adenoma. Four weeks after surgery laboratory results were normal (urinary metanephrines 202 ug/24h and normetanephrines 382.0 ug /day; Chromogranin A 2.60 nmol/l). The results of the genetic tests including SDHB, SDHD, SDHC, VHL and MAX were negative. Conclusion: This report emphasizes the necessity to include paraganglioma in the differential diagnosis and management of retroperitoneal tumors avoiding the risk of the biopsy in this kind of tumors.