Feasibility of Imaging-Guided Adrenalectomy in Young Patients With Primary Aldosteronism

Many of the patients with primary aldosteronism (PA) are denied curative adrenalectomy because of limited availability or failure of adrenal vein sampling. It has been suggested that adrenal vein sampling can be omitted in young patients with a unilateral adrenal nodule, who show a florid biochemical PA phenotype. As this suggestion was based on a very low quality of evidence, we tested the applicability and accuracy of imaging, performed by computed tomography and/or magnetic resonance, for identification of unilateral PA, as determined by biochemical and/or clinical cure after unilateral adrenalectomy. Among 1625 patients with PA submitted to adrenal vein sampling in a multicenter multiethnic international study, 473 were ≤45 years of age; 231 of them had exhaustive imaging and follow-up data. Fifty-three percentage had a unilateral adrenal nodule, 43% had no nodules, and 4% bilateral nodules. Fifty-six percentage (n=131) received adrenalectomy and 128 were unambiguously diagnosed as unilateral PA. A unilateral adrenal nodule on imaging and hypokalemia were the strongest predictors of unilateral PA at regression analysis. Accordingly, imaging allowed correct identification of the responsible adrenal in 95% of the adrenalectomized patients with a unilateral nodule. The rate raised to 100% in the patients with hypokalemia, who comprised 29% of the total, but fell to 88% in those without hypokalemia. Therefore, a unilateral nodule and hypokalemia could be used to identify unilateral PA in patients ≤45 years of age if adrenal vein sampling is not easily available. However, adrenal vein sampling remains indispensable in 71% of the young patients, who showed no nodules/bilateral nodules at imaging and/or no hypokalemia. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01234220.

Adult Xp11.2 translocation renal cell carcinoma managed effectively with pazopanib

Xp11.2 translocation renal cell carcinoma (TRCC) is a rare and aggressive variant of renal cell carcinoma (RCC) when presenting in adults. We report a case of a man in his early 40s who was diagnosed with stage III Xp11.2 TRCC and underwent radical nephrectomy. Seven months following the surgery, an adrenal nodule and bilateral pulmonary nodules were discovered. He underwent cryoablation of the adrenal nodule and systemic treatment with daily pazopanib. He displayed stable disease for approximately 6 years. Following this period, multiple hospitalisations interrupted daily pazopanib therapy resulting in progression of disease. His regimen was then changed to ipilimumab and nivolumab, followed by current daily therapy with axitinib. The patient now shows stable disease in his 10th year after diagnosis. This case study demonstrates the efficacy of pazopanib for metastatic Xp11.2 TRCC and warrants further investigation to supplement the guidelines regarding the use of targeted therapy for TRCC.

Development of Deep Learning-Based Automatic Detection Algorithm for Adrenal Nodules on Contrast-Enhanced Abdominal CT Scans

Objective: Adrenal nodules are often incidentally detected on abdominal computed tomography (CT) scans due to their asymptomatic nature. We aimed to develop an automatic detection program for adrenal nodules on abdominal CT scans using deep learning algorithms. Methods: We retrospectively analyzed abdominal CT scans performed at two university-affiliated hospitals (n = 483 and n = 514, respectively) from 2006 to 2019. This dataset was randomly divided into training set (181 CTs without adrenal nodule and 362 CTs with adrenal nodule) and test set (291 CTs without adrenal nodule and 163 CTs with adrenal nodule). All CT scans were contrast-enhanced and the phase with the highest contrast between adrenal gland and adjacent normal tissues was selected for multi-phase CT. The core algorithm of our deep learning algorithm for adrenal nodule (DLAAN) was MULAN (Multitask Universal Lesion Analysis Network) algorithm whose backbone was a convolutional neural network. DLAAN was composed of two stages. The first stage was to detect the CT slice where normal adrenal gland or adrenal nodule were located. The second stage was for fine localization of adrenal nodule on the corresponding CT slice. The performance of DLAAN was evaluated using the area under the receiver operating characteristic curve (AUROC) for patient-level classification and free-response ROC for nodule-level localization. The figure of merit for free-response ROC was calculated as an average sensitivity when 0.5, 1, 2, and 4 false positives per slice were allowed. Results: The AUROC of DLAAN was 0.927 (95% confidence interval: 0.900–0.955). With a threshold probability of 0.9, the sensitivity and specificity were 86.5% and 89.0%, respectively. When left and right adrenal nodules were analyzed separately, the AUROC was 0.910 for left adrenal nodule and 0.957 for right adrenal nodule, respectively. The accuracy of DLAAN according to the size of adrenal nodule was 0.890, 0.734, 0.981, 1.00 and 1.00 for no adrenal nodule, adrenal nodule sized 1–2 cm, 2–3 cm, 3–4 cm and > 4 cm, respectively. The performance of DLAAN for the localization of adrenal nodule which was estimated by average sensitivity was 0.812. The number of CTs with at least one false positive nodule was 93/454 (20.5%). Conclusion: Our proof of concept study of deep learning-based automatic detection of adrenal nodule on contrast-enhanced abdominal CT scans showed high accuracy for both the classification of patients with or without adrenal nodule and the localization of adrenal nodule, although the performance of the algorithm decreased for small sized adrenal nodules. External validation with different CT settings and patient population is needed to assess the generalizability of our algorithm.

Metastatic Adrenocortical Carcinoma Co-Secreting Multiple Steroid Hormones

Background: Adrenocortical carcinoma is a rare disease which may be complicated by co-secretion of multiple steroid hormones. Clinical Case: A 53- year-old female was discovered to have 1 cm left and 1.7 cm right adrenal nodules by Chest CT scan in 2004. She had a follow-up abdominal CT scan in 2011 revealing enlargement of the left adrenal mass to 5.7 cm and a stable 1.8 cm right adrenal nodule. A laparoscopic left adrenalectomy was performed in 2012 and the surgical pathology diagnosis was benign adrenal hyperplasia. In 5/2016 the patient developed left abdominal pain and a CT scan revealed a 1.7 cm mass in the left adrenalectomy surgical bed, a 1.4 cm nodular density adjacent to the left diaphragm and the stable 1.8 cm right adrenal nodule. 6/2016 lab tests: 24 hr urinary cortisol 15 ug/24 hr (<50 μg/24hr), aldosterone 8.7 ng/dL (<31 ng/dL), renin activity 0.7 ng/ml/hr (0.5–4 ng/mL/hr) and DHEA-S 94 ug/dL (32–240 μg/dL). A re-examination of the 2012 surgical pathology resulted in an addendum diagnosis of an adrenal cortical neoplasm of indeterminate malignant potential. In 1/2018 she underwent an exploratory laparotomy with surgical resection of the 1.7 cm mass in left paracolic gutter and biopsy of numerous small retro-peritoneal and multiple liver lesions. Pathology revealed metastatic adrenocortical carcinoma with low grade mitotic activity (3 mitoses per 10 HPF) and intermediate grade Ki-67 (15–25%). 5/2018 lab results: 1. aldosterone 20 ng/dL, 2. renin activity 0.2 ng/mL/hr and 3. testosterone 34 ng/dL (<75 ng/dL). Mitotane was started in 06/2018 but was discontinued in 9/2018 due to side effects. In 3/2020 she was hospitalized for generalized weakness and was discovered to be severely hypokalemic K+ 1.5 mmol/L (3.6–5.2 mmol/L) with an aldosterone of 300 ng/dL and renin activity of 0.1 ng/mL/hr. She was treated with IV KCl to correct her hypokalemia and was discharged on oral KCl 20 meq bid and spironolactone 50 mg bid. She was readmitted to the hospital on 10/12/2020 after a near-syncopal event and lab tests revealed a K+ of 1.4, aldosterone 508 ng/dL, renin activity 0.7 ng/mL/hr, AM cortisol 13.6 μg/dL (5–20 ug/dL), testosterone 161 ng/dL, and DHEA-S 377 ug/dL, indicating co-secretion of multiple steroid hormones. Her hypokalemia was treated with IV KCl and her spironolactone dose was increased to 100 mg bid. Conclusion: This case report details the rare occurrence of an adrenocortical carcinoma which was hormonally silent but eventually metastasized and became hormonally active, co-secreting multiple steroid hormones with a predominance of aldosterone. Serial adrenal hormone lab profiles are important for optimal management of patients with this disease.

Unlikely Coexistence of Sporadic Pheochromocytoma and Bilateral Macronodular Adrenal Hyperplasia: A Challenge to Manage

Background: The incidence of bilateral macronodular adrenal hyperplasia (BMAH) is unknown, but growing in an era of increased utilization of imaging. Coexistence of BMAH and pheochromocytoma has not previously been reported. Clinical Case: A 63-year man presented with enlarging left chest-wall mass found to have a poorly differentiated sarcoma. Staging PET/CT identified a hypermetabolic 2.0 cm left adrenal nodule with SVU of 16.6 concerning for metastasis. Hormonal evaluation included dexamethasone suppression test with 7AM serum cortisol of 24.7 ug/dL (<1.8 ug/dL) without dexamethasone level, serum ACTH <5.0 pg/mL (7.2–63 pg/mL), plasma metanephrine of <0.20 nmol/L (0–0.49 nmol/L), and plasma normetanephrine of 0.76 nmol/L (0.00–0.89 nmol/L). Biopsy of this left adrenal nodule was consistent with pheochromocytoma. By history, he lacked any classical symptoms of pheochromocytoma. Repeat testing demonstrated only slight elevations in normetanephrine (1.3 nmol/L and 1.2 nmol/L); he remains asymptomatic at follow-up 4 months later. However, history and exam revealed central obesity, thin skin, type 2 diabetes mellitus on insulin, and hypertension controlled on three agents concerning for Cushing’s. Repeat evaluation showed AM cortisol of 17.9 ug/dL (<1.8 mcg/dL) with dexamethasone level of 917 ng/dL (180–550 ng/dL), ACTH of 6.4 pg/mL with concordant cortisol of 23.1 ug/dL, and 24 hour urine collection with 0.98 L volume, creatinine of 0.58 g/24h (1–2 g/24hr), and urinary free cortisol of 67 ug/24h (3.5–45) altogether suggesting ACTH-independent hypercortisolism. On review of CT abdomen, he has bilateral adrenal nodules measuring >1cm with bilateral gland enlargement consistent with BMAH. Resection of his left adrenal gland was not pursued due to cormorbidities as well as biochemically-silent nature of his pheochromocytoma. To manage his hypercortisolism, he was recently initiated on osilodrostat after completing radiation therapy for his chest-wall sarcoma. Conclusion: This is the first case demonstrating clinical, biochemical, and imaging results consistent with bilateral macronodular adrenal hyperplasia and hypercortisolism also found to have a clinically and biochemically silent, biopsy proven pheochromocytoma. This is also a unique use of osilodrostat to manage BMAH.

SAT-190 Are Pet Scans Needed in Evaluating Lipid Rich Adrenal Adenomas?

Introduction Adrenal glands are highly vascularized organs and can be the foci of metastatic disease. Incidentally discovered adrenal nodules should be evaluated with CT or MRI imaging and biochemical testing. Metastatic lesions do not have a specific clinical presentation or imaging features but are suspected when there is attenuation greater than 10 HU, presence of calcification, hemorrhage, or abnormal enhancement signals in CT scan or MRI. However, malignant lesions can be present along with benign ones as described here. Clinical Case A 74-year-old female initially presented with uncontrolled hypertension in 2002, at which time she was found to have a left adrenal incidentaloma. MRI/MRA of the abdomen with and without gadolinium contrast showed a 2.5 x 2.6 cm left adrenal nodule, described as a benign lipid rich adrenal adenoma. Biochemical testing revealed no evidence of pheochromocytoma, hyperaldosteronism, or hypercortisolism. Follow-up CT scan in 2003 showed the left adrenal nodule was slightly larger (3.0 x 2.5 cm) but remained lipid rich (<10 HU). There was also a new sub-centimeter nodule in the left medial-posterior limb with similar appearance. In the interim, she was diagnosed with a melanoma on her back in 2003, which was resected without any evidence of invasion. In 2004, abdominal MRI with and without gadolinium contrast showed stable left adrenal nodules. As she continued to have persistent hypertension, uncontrolled with several medications, biochemical work-up for pheochromocytoma, hyperaldosteronism, and hypercortisolism was repeated and was again negative. Surveillance CT imaging in 2005 did not show any changes to her adrenal adenomas. In 2016, she presented to the emergency room with a hemorrhagic cerebrovascular accident. MRI of the brain was consistent with metastatic lesions. CT scan of the chest, abdomen and pelvis showed metastatic lesions in the lungs, liver, bone, and spleen. There was a new 8 mm right adrenal nodule noted with no changes in the left adrenal nodules. Biopsy of a subcutaneous chest wall nodule revealed metastatic melanoma. Thus, she was started on palliative immunotherapy with nivolumab. During her follow-up, she had a series of PET CT scans over a 6 month period, which showed increasing size (up to 4.3 cm) and FDG uptake in the left adrenal nodule. Surprisingly, the left adrenal nodule had a predominantly fatty density (mean of 5 HU) but with an area of hyperdensity which could represent either an adenoma with a coexisting metastatic lesion or angiomyolipoma. Biopsy of the left adrenal nodule revealed a metastatic melanoma. Conclusion This case describes a benign adrenal nodule coexistent with a metastatic lesion. As the patient had metastatic melanoma, a PET-CT was ordered. Melanoma is known to metastasize to the adrenal. This case serves to remind clinicians to perform a careful medical history as management and outcomes can be affected.

SUN-910 High Enhancement Washout by CT Imaging Does Not Exclude Pheochromocytoma/Paraganglioma: Review of Two Cases

Background: It is well known that delayed images from contrast-enhanced CT are useful in distinguishing adrenal adenomas from non-adenomas, with an absolute washout that exceeds 60% being most consistent with a lipid rich adenoma. We present two cases of an adrenal mass that met the criteria for a lipid rich adenoma by CT imaging, but found to be a pheochromocytoma (PCC) and paraganglioma (PGL). Clinical Case Case#1 An 82 yo woman presenting with tachycardia was found to have a 2.4 cm heterogeneously attenuating, left adrenal nodule with an absolute washout of 61% and a relative washout of 45%. The right adrenal was normal. Urinary catecholamine levels were elevated with an epinephrine (E) 38 mcg (2–24), norepinephrine (NE) 388 mcg (15–100), dopamine (DOPA) 175 mcg (52–480), metanephrine (MN) mcg 620 (90–315), normetanephrine (NMN) 1553 mcg (122–676) and vanillylmandelic acid 12.5 mg (< 6) on a 24h collection. Due to a cardiac resynchronization therapy device, an MRI could not be obtained. MIBG imaging was obtained and showed increased uptake in left adrenal gland, corresponding to the lesion identified on CT. The patient underwent laparoscopic adrenalectomy and the pathology confirmed a PCC. Case#2: A 74 yo man was found to have an incidental right adrenal nodule on CT imaging measuring 2.4 cm. Absolute washout was 83% and relative washout 68%. The left adrenal gland was normal. A follow up MRI obtained showed slight increase in T2 weighted images and no drop out on out of phase imaging, raising concern for a PCC. Urinary catecholamines were elevated including E 12 mcg (2–24), NE 280 mcg (15–100), DOPA 246 mcg (52–480), MN 175 mcg (90–315) and NMN 1298 mcg (122–676) on a 24-hr. collection. MIBG imaging further confirmed the diagnosis with increased uptake in the right adrenal gland. The patient underwent laparoscopic adrenalectomy then, converted to open right adrenalectomy through an anterior approach due to adherence of the tumor to the renal vein. The pathology revealed a PGL. Conclusion: PCC/PGL are rare but life-threatening neuroendocrine tumors that require early detection to reduce associated morbidities and mortality and improve surgical outcomes. CT is commonly used to characterize adrenal lesions and an absolute washout of >60% is most consistent with an adenoma. However, as demonstrated by these two cases, washout exceeding 60% can also be seen in non-adenomas, perhaps secondary to degeneration of the nodule causing necrotic or cystic changes or uncommonly, the presence of a high lipid content in the tumor [1]. Thus, when clinical suspicion is strong and/or there is a positive biochemical workup, confirmatory imaging should be considered to establish the diagnosis. References: [1] Blake, M. A., Kalra, M. K., Maher, M. M., Sahani, D. V., Sweeney, A. T., Mueller, P. R., ... & Boland, G. W. (2004). Pheochromocytoma: an imaging chameleon. Radiographics, 24(suppl_1), S87-S99.