Urinary Normetanephrine Research Articles

PMON283 A CASE OF INHALED FLUTICASONE INDUCED ADRENAL INSUFFICIENCY

Abstract Inhaled glucocorticoids (ICS) are recommended in all patients with persistent asthma. While relatively safe, ICS can occasionally cause systemic side effects including adrenal suppression, bone loss, and cataract formation. We describe a 53-year-old woman with adrenal insufficiency secondary to inhaled fluticasone. A 53-year-old woman was referred for evaluation of an incidental 5.5×2.7 cm left adrenal mass discovered on CT chest when she was hospitalized for an asthma exacerbation. She had asthma since the age of 20 and had intermittently been on oral steroids which were tapered off several months prior to her evaluation. Medications included fluticasone (230-21mcg/actuation inhaler) HFA 2 puffs twice daily, azithromycin, azelastine, calcium carbonate, cholecalciferol, esomeprazole, guaifenesin, magnesium, and montelukast. On exam vital signs were: BP 128/88, HR 95, BMI 41.13 kg/m2. She was obese with left > right supraclavicular fullness, mild dorsocervical fullness, slightly thinned skin, but no striae or proximal muscle weakness. Labs were initially sent to evaluate for an adrenal incidentaloma: A random morning (8 AM) cortisol was <0.5 mcg/dL (6-18 mcg/dL), plasma ACTH was 6pg/ml (7.2-63.3 pg/mL), 24 hour free urinary cortisol: < 1mcg/24 hours (2500 ml/ 24hr urine, urine creatinine 1.66g/24 hours). Urine and plasma metanephrines and normetanephrines were negative. FSH and LH were normal. A 250 mcg cosyntropin stimulation test was done showing a baseline cortisol of <0.5 mcg/dL and ACTH <3.0 pg/mL, cortisol levels of 2.7 mcg/dL and 3.2 mcg/dL at 30 and 60 minutes, respectively. Pituitary MRI was normal. She was diagnosed with adrenal insufficiency likely caused by an exogenous steroid. Since she had been off oral steroids for several months urinary steroid testing was performed revealing an elevated fluticasone metabolite: Fluticasone 17β-carboxylic acid >10,000 pg/nL (nl < 10 pg/nL). Hence inhaled fluticasone was determined to be the cause. Similar findings have been described in patients with HIV on anti-retroviral therapy (ART) where metabolism of inhaled steroids can be impaired resulting in hypothalamic-pituitary-adrenal suppression. Our patient was not on ART but may have a genetic variant resulting in delayed steroid clearance or enhanced susceptibility to HPA suppression, though fluticasone is known to accumulate in adipose tissue. She stopped fluticasone and several days later repeated urine testing revealing a urine Fluticasone 17β-carboxylic acid level of 96 pg/nL, two weeks later inhaled budesonide was initiated and over the course of three months her ACTH increased from 3.3 to 18.3 to 26.3 (pg/mL) and cortisol rose slightly from 0.9 to 3.2 to 3.7 mcg/dL. Conclusion Awareness of the potential systemic side effects of inhaled corticosteroids is important and patients should be kept on the lowest effective dose. Conversely, in the evaluation of patients with secondary adrenal insufficiency the possibility of inhaled corticosteroids playing a causative role should be considered. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

ODP054 The Impact of SGLT2-inhibitors on Renin-Aldosterone axis and Adrenal Incidentaloma's work up: Case study and literature review

Abstract Introduction SGLT2 inhibitors (SGLT2i) are being increasingly used in patients with Type 2 DM given their glycemic effects along with cardio-protective and reno-protective effects. SGLT2i exert these effects through various mechanisms, mainly through the RAAS (Renin-Angiotensin-Aldosterone System) with diuresis, leading to transient elevation of renin levels with minimal effect on aldosterone levels. We present a case where elevated aldosterone levels improved stoppage of SGLT2i. Case 52 year male with history of GERD and Sleep apnea who was referred for evaluation of right adrenal incidentaloma of 2 cm found on CT abdomen in 12/2019 as part of renal stone work up. Initial work up in 3/2020 showed elevated aldosterone of 87.1, renin of 2.3 with ratio of 37.9. Repeat work up in 7/2020 showed elevated aldosterone of 66 with renin levels of 2. High urine aldosterone of 64.7 was noted but urine sodium of 171 mg only. Urine metanephrine and normetanephrine levels were in the reference range. He was started on spironolactone considering hyperaldosteronism and mild hypertension, but developed hyperglycemia and type 2 diabetes mellitus which was initially treated with insulin and later switched to Jardiance. Follow up CT abdomen with adrenal protocol in 8/2020 showed stable right adrenal nodule, consistent with adrenal adenoma. His repeat aldosterone levels remained elevated at 70 with renin levels of 2.8 in 6/2021 after holding spironolactone for 2 weeks. Patient was advised to stop Jardiance as well as continue holding Spironolactone in 9/2021 and repeated labs showed an improvement in aldosterone levels of 43 in 10/2021 and 21 in 12/2021 with renin levels of 2.79 and 2.95 respectively. Discussion SGLT2 inhibitors are known to reduce heart failure hospitalization in the clinical trials. Use of SGLT2i leads to early diuresis with natriuresis and systemic RAAS activation rather than intra-renal RAAS activation. Effects are mainly mediated through transient natriuresis with volume depletion in short term, leading to RAAS activation with transient renin elevation but no significant effects on aldosterone levels, possibly due to other controlling factors like ACTH and K levels along with circadian rhythm. Our case presents unique scenario where elevated aldosterone with normal (non-suppressed) renin levels were noted in the context of adrenal incidentaloma work up and Jardiance use. Even though the improvement of aldosterone levels might be related to multiple factors but with increasing use of SGLT2i, much attention should be paid to the impact of these agents on renin-aldosterone axis and possible need of holding these agents if elevated renin-aldosterone levels are noted. Presentation: No date and time listed

ODP271 Primary Aldosteronism and Primary Hyperparathyroidism: A Report of Dual Endocrine Hypertension

Abstract Background Primary aldosteronism (PA) is one of the common causes of secondary hypertension. Primary hyperparathyroidism (PHPT) is a less common etiology of secondary hypertension. The concomitance of both PA and PHPT is very rare, with a possible bilateral positive feedback loop between the adrenal cortex and the parathyroid gland[1]. Clinical case: A 64-year-old female was referred to the endocrine clinic for secondary hypertension assessment. She was diagnosed with hypertension 30 years earlier, poorly controlled on three antihypertensive medications, nifedipine 90 mg daily, lisinopril 40 mg daily, and atenolol 50 mg daily. She started experiencing muscle cramps two years prior to the referral and was found to be hypokalemic on multiple occasions, with potassium ranging between 2.5 to 3 mmol/L. She also had multiple admissions to the emergency department for hypertensive urgencies within the last year. Family history was positive for poorly controlled hypertension in the patient's mother. Physical examination showed class I obesity with a BMI of 31, but otherwise unremarkable. Workup showed elevated aldosterone concentration of 38 ng/dl and suppressed renin concentration (<1 pg/ml) with an aldosterone/renin ratio of 38. Overnight dexamethasone suppression test was normal (cortisol of 1.5 mcg/dl, suppressed ACTH of 5.5 pg/ml, and appropriately elevated dexamethasone of 324 ng/dl). 24-hour urine metanephrine and normetanephrine levels were normal. Imaging showed bilateral adrenal adenomas of about 13-14 mm in widest diameter, with an average density of 10 Hounsfield units. Adrenal venous sampling revealed hyperfunctioning left adrenal with normal right adrenal. The left adrenal gland was removed laparoscopically, and blood pressure normalized postoperatively on the single antihypertensive agent (lisinopril). Interestingly, during the initial workup, the patient also had elevated calcium of 11 mg/dl and low phosphate at 2.5 mg/dl. In addition, parathyroid hormone (PTH) was elevated at 103 and 95 pg/ml on two occasions, with normal 25-OH vitamin D levels. 24-hoururine calcium was 240mg/dl, and creatinine in urine was 76.4 mg/dl. The calcium creatinine clearance ratio was 2.5%. Diagnosis of primary hyperparathyroidism was made. She had no renal stone, chronic kidney disease, or fractures, with a normal DEXA scan. There was no current indication for parathyroidectomy, and the patient continued to be followed up in the clinic. Clinical lesson: Recent evidence shows cross-talk between the adrenal cortex and parathyroid gland. Our patient may represent such a case, with concomitance of two rare endocrinopathies resulting in difficult-to-control hypertension [1,2]. Thus it is essential to investigate multiple etiologies of secondary hypertension. Reference: Brown JM, Vaidya A. Interactions between adrenal-regulatory and calcium-regulatory hormones in human health. Curr Opin Endocrinol Diabetes Obes . 2014;21(3): 193-201. doi: 10.1097/MED. 0000000000000062 Maniero C, Fassina A, Guzzardo V, et al. Primary hyperparathyroidism with concurrent primary aldosteronism. Hypertension. 2011 Sep;58(3): 341-6. doi: 10.1161/HYPERTENSIONAHA.111.173948. Epub 2011 Aug 8. PMID: 21825220. Presentation: No date and time listed

PSAT031 Dietary Influence (smoothies) on Measurements of Plasma and Urinary Metanephrines in a Patient with Hypertension.

Abstract Introduction Pheochromocytoma can be diagnosed by fractionated plasma and urinary metanephrines. However, these tests have several diagnostic issues. Drugs, such as tricyclic antidepressants, and diets both can affect biochemical testing. We report a patient who was consuming a catecholamine rich diet in the form of smoothies which resulted in falsely elevated metanephrines. Case history A 37-year-old female was seen in 2021 for evaluation of secondary hypertension. Patient had a history of intermittent palpitations but denied headaches or excessive sweating. She was taking amlodipine 5mg daily and potassium chloride 20mg daily. Significant past medical history included a partial nephrectomy for renal cell cancer at the age of 35 years. She denies family history of pheochromocytoma or MEN 2. Vital signs showed HR 70/min, BP 138/80 mm Hg. Examination of the heart, lungs and abdomen was normal. Skin exam revealed no bruises or abdominal striae. Labs revealed normal CBC, serum K 3.4, aldosterone 20.1 ng/dL (ref 0.0 - 30.0), renin 1.165 ng/mL/hr (0.167-5.360). Following 1-mg dexamethasone suppression test, serum cortisol was 1.0 mcg/dL. Plasma normetanephrine 113.8 pg/mL (0.0 - 110.1), metanephrine 26.1 pg/mL (0.0 - 88), 24-hour urine metanephrines 465 mg/24hr (74 - 297), normetanephrine 963 mg/24hr (105 - 354). Due to the discordant values between the plasma and urinary metanephrines, a detailed history was taken which revealed that her diets included smoothies, consisting of pineapple juice, bananas, papaya, mango, and sea moss. She drank 15 ounces 3 times per week. Additionally, she was also consuming 1 cup of pistachios and 1 cup of elderberries daily. Patient was counseled to stop drinking the smoothies, and eating pistachios and elderberry. Six weeks later her 24-hour urine metanephrines and normetanephrines returned at 80 mcg/24 hrs and 243 mcg/24 hrs, respectively. Additionally, CT of the adrenal glands confirmed normal adrenal glands. Conclusion Previous studies have shown that catecholamines from dietary sources can dramatically affect plasma as well urinary concentrations of the 3-O methylated metabolites of catecholamines. In our patient, consumption of catecholamine rich foods such as bananas, oranges, pineapples, and possibly elderberry may have contributed to the false positive results. Additionally, the discrepancy between the baseline plasma and urine metanephrines, the normal adrenal glands on CT and normalization of the metanephrines after discontinuing the smoothie diets confirmed that the false positive laboratory values indeed resulted from dietary influence. It is recommended that a detailed dietary history be taken prior to ordering laboratory testing for catecholamine-secreting tumors. Possible interfering medications and catecholamine rich foods should be discontinued, if possible, before biochemical testing to avoid false positive results. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

LBSAT62 Incidental Diagnosis Of Pheochromocytoma With Left Ventricle Hypertrophy And Bradycardia In A Normotensive Patient

Abstract Introduction Pheochromocytoma is a rare catecholamine secreting tumor. It can be associated with multiple endocrine neoplasia type 2(MEN 2), neurofibromatosis type 1 and von hippel-lindau syndromes(1). Case 36 year old afro american male with no pervious medical or surgical history. Drinks alcohol occasionally. no regular medications or known allergies. Family history is positive for mother with hypertension. He was referred to endocrinology clinic after incidental finding of a left adrenal mass in CT scan. The CT abdomen and pelvis with contrast showed heterogenous enhancing mass in the left adrenal gland of 5.5×4.1×5.3centimeters compressing the anterior margin of left kidney with necrotic and cystic foci. Review of systems was negative, denied headache,palpitations, seizure, sweating and weight loss. Physical examination was remarkable for bradycardia with heart rate of 50BPM. Laboratory work up was significant for high plasma metanephrine 2070 pg/ml normal less than 88, normetanephrine 1983pg/ml normal less than 110, chromogranin A 1259ng/ml normal less than 101.8, 24hr urine metanephrine 13342ug/24hr normal between 58 and 276 and 24hr urine normetanephrine 6596 ug/24hr normal between 156 and729. Thrombocytosis and macrocytic RBCs.12 Lead electrocardiogram showed sinus bradycardia 50BPM with left ventricle hypertrophy Sokolow-Lyon criteria. MRI abdomen showed 4.9×3.8×5.3 centimeters solid mass in the left adrenal gland. MIBG Scan showed intense radiotracer accumulation in the left adrenal gland. He was kept on alpha blockers for three weeks and beta blocker was added in the last week with intravenous fluids on the day of surgery. He underwent uneventful left laparoscopic adrenalectomy. Histopathology showed a 6cm focal non neoplastic pheochromocytoma in the left adrenal gland with negative surgical margins. Genetic test for MEN2A/B-RET was negative. Conclusion pheochromocytoma has a variable clinical presentations. The classis triad of episodic headache, sweating and palpitations is infrequent. It can present with electrocardiogram changes of left ventricle hypertrophy without high blood pressure. Rare cases have bradycardia. The secreted interleukins and inflammatory markers can cause thrombocytosis. Treatment is surgical resection with preoperative alpha and beta blockage. Long term follow up is recommended for the recurrence(2).

PSAT027 An Incidentally-Discovered Retro-Cardiac Paraganglioma Presenting as NSTEMI

Abstract Introduction/Background Paragangliomas are rare tumors arising from extra-adrenal chromaffin tissue (1,2). The majority of paragangliomas occur in the head and neck, with the heart representing an uncommon site (3). We present a rare case of a patient who was incidentally found to have a hypersecretory retro-cardiac paraganglioma. Clinical Case A 72-year-old woman with a history of hypertension, hyperlipidemia, migraines, and prior cerebrovascular accident presented to the Emergency Department with sudden, substernal, pleuritic chest pain. She described weeks of a "fluttering sensation" in the chest with one episode of syncope. She denied shortness of breath or diaphoresis. Vitals were normal and EKG did not demonstrate ischemia. Troponin uptrended and the patient was admitted due to concern for non-ST-elevation myocardial infarction (NSTEMI). She promptly underwent cardiac catheterization which revealed non-obstructive coronaries and a left atrial mass with blood supply from the right coronary artery and the left circumflex artery. Cardiac MRI demonstrated an extracardiac, interpericardial 42×24×37 mm mass below the left atrium without aggressive features, and delayed homogenous enhancement with dynamic perfusion, suggestive of a paraganglioma. Biochemical evaluation demonstrated elevated free plasma normetanephrines of 5.5 nmol/L (normal: < 0.90 nmol/L) and normal free plasma metanephrines. Chromogranin-A was elevated at 454 ng/ml (normal: <93 ng/ml). 24-hour urine total urine metanephrines were markedly elevated at 1438 mcg/24h (normal: 180-646 mcg/24h) with mainly urine normetanephrines of 1390 mcg/24h (normal: 148-560 mcg/24h). The patient's TSH, free T4, and total T3 were normal. PET/CT scan was negative for metastatic disease. The patient denied a family history of paraganglioma or pheochromocytoma. She was seen in follow-up with Cardiac Surgery, who felt the resection would be technically difficult, but that there were no other alternatives. The patient's procedure was postponed due to a COVID-19 surge and patient was begun on alpha- and beta-blockade, instead of pure alpha-blockade with phenoxybenzamine, in view of her recent history of NSTEMI. Conclusion We present a rare case of an incidentally-found cardiac mass, discovered during cardiac catheterization, with biochemical and radiographic evaluations concerning for a retro-atrial paraganglioma. Cardiac paragangliomas can present with a range of symptoms, from hypertension to different obstructive symptoms, including ischemia, depending on the tumor's location. The secretory activity of cardiac paragangliomas can also vary; the literature reports that about 31% are biochemically active (2). Though rare, our case highlights the importance of understanding the atypical presentation and evaluation of cardiac paragangliomas.

ODP621 Hypertension with Hypokalemia in Pregnancy? Think "Cushing's Syndrome"

Abstract Introduction Pregnancy is uncommon in women with Cushing's syndrome (CS) as hypercortisolism and hyperandrogenism suppress gonadotropins leading to anovulatory cycles. Such pregnancies carry a higher rate of fetal morbidity and mortality. Therefore, it is of paramount importance to diagnose and treat CS in pregnancy. The diagnosis of CS in pregnancy is challenging due to the physiologic changes of the hypothalamic-pituitary-adrenal axis during pregnancy. We describe a case of CS in pregnancy that was a successfully treated with surgery. Case description An asymptomatic 39-year-old pregnant female patient with gestational hypertension was admitted to the hospital after she was found to have uncontrolled hypertension (while on 3 anti-hypertensive medications) and severe hypokalemia with potassium level of 2.8 mEq/L. She was 14 weeks pregnant at the time. She has a family history of primary aldosteronism in her father successfully treated with adrenalectomy at the age of 60. Her work up included blood work (done at 13: 42) which showed sodium level of 146 mEq/L, plasma aldosterone concentration of <1 ng/dL, plasma renin activity of 1.0 ng/mL/hr, total testosterone of 46 ng/dL, DHEA-S of 31 mcg/dL, plasma metanephrines <50 pg/mL, 24-hour urine metanephrines 70 ug, 24-hour urine normetanephrines 164 ug/24 hrs, ACTH 5 pg/mL, and cortisol 28.2 mcg/dl. MRI abdomen without contrast showed a 3.5×3.0×4.2 cm left adrenal nodule consistent with adenoma. Patient was diagnosed with non-ACTH dependent subclinical CS based on her elevated cortisol and low ACTH levels. She underwent left laparoscopic adrenalectomy and was discharged on oral hydrocortisone. Pathology showed adrenal cortical adenoma. Her blood pressure normalized shortly after surgery and her anti-hypertensive medications were stopped. Discussion Pregnancy is associated with multiple changes in the hypothalamic-pituitary-adrenal axis making diagnosis of CS in pregnancy challenging. Those changes include increased Cortisol binding globulin production leading to increased serum cortisol level and lack of suppression with Dexamethasone beside placental production of CRH and ACTH, all leading to increased salivary and urinary free cortisol levels, as well. This case of hypertension and hypokalemia in pregnancy presented a diagnostic dilemma. Furthermore, the clinical presentation was confounded by a family history of primary aldosteronism. However, the low serum ACTH level highly suggested the diagnosis of CS. Unfortunately, there are no pregnancy-specific guidelines for the diagnosis of CS. The dexamethasone suppression test is not recommended as it often yields false-positive results. The use of urinary free cortisol and late-night salivary cortisol is recommended, and the diagnosis is established when results are three to four times the upper limit of normal. ACTH levels <10 pg/ml are suggestive of adrenal CS. MRI without contrast can be used for imaging. To date, there have been over 260 reported cases of CS in pregnancy with more than half of them being. Presentation: No date and time listed

PMON42 A unique case of Norepinephrine secreting Head and Neck Paraganglioma

Abstract Introduction Head and neck Paragangliomas (HNPGLs) are rare, slow growing neuroendocrine tumors arising from parasympathetic and sympathetic paraganglia in the head and neck region. Traditionally, HNPGLs were presumed to be rarely secretory compared to thoracoabdominal sympathetic PGLs(<5%) and most of them are thought to be identified due to compressive symptoms or incidentally on imaging performed for screening in genetically predisposed individuals. However, most recent evidence has suggested that >10% of HNPGLs can be secretory although data has also shown that typically catecholamines. Case Presentation A 55-year-old man presented to the emergency room with worsening headaches, right sided neck pain and dizziness. Physical examination revealed multiple cranial neuropathies including right facial weakness with ipsilateral lagophthalmos, tongue atrophy, dystonic and atrophic sternocleidomastoid muscle, and vagal deficit. Blood pressure was markedly elevated at 227/108 mmHg. Computed tomography scan of head and neck revealed a large bony destructive lesion involving the right skull base measuring 9.0×7.0 cm, with involvement cervical vertebral bodies, as well as ventriculomegaly suggestive of obstructive hydrocephalus with mass effect on the brain stem and cerebellum. History revealed knowledge of this skull base mass for 13 years. Initially the mass was 3.2 cm in the largest dimension with elevated 24-hour urine normetanephrine 1113 mcg/day, Ref: 50-650 mcg/day and dopamine 667 mcg/day Ref: 60-440 mcg/day. He didn't seek further medical care at that time due to his family's opposition to traditional medicine. Magnetic resonance imaging upon this admission revealed 9.0×6.0×5.5 cm expansile, hypervascular, destructive mass at the right skull base with pronounced mass effect and brainstem compression with significant narrowing at the foramen magnum. 24-hour urine normetanephrines were significantly elevated at 4229 mcg/day, ref: 114-865 mcg/day, as well as elevated plasma Normetanephrine at 11.58 nmol/L, ref: 0.00-0.89 nmol/L, and urine Dopamine 10,071 mcg/day, ref: 71-485 mcg/day. Antihypertensive treatment was initiated with alpha blockade followed by additional beta blockade. After multidisciplinary discussion, the decision was made to pursue external radiation therapy given the considerable risk associated with the surgery due to location and vascularity. Genetic testing is pending at the time of abstract submission. Conclusion Recent evidence has suggested that >10% HNPGLs can be secretory as opposed to previous assumption that they are rarely secretory. Norepinephrine is the most common catecholamine secreted by HNPGL and dopamine is very rare. We present a unique case of HNPGL when surgery was deferred for more than a decade due to opposition to traditional medicine resulting in a large norepinephrine and dopamine secreting tumor (10 times the upper limit of normal) and multiple compressive cranial neuropathies. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

ODP280 A Unique Case of Coexisting Paraganglioma, Primary Hypoaldosteronism and Primary Hyperparathyroidism in a Single Patient

Abstract Introduction To date, case reports have shown an association between paraganglioma and primary hyperaldosteronism, and primary hyperparathyroidism with primary aldosteronism, but not for all three of the aforementioned endocrinopathies combined. Clinical Case A 54-year-old woman with history of uncontrolled HTN, hypokalemia, DM2, CKD stage III, Takotsubo cardiomyopathy and primary hyperparathyroidism presented to the hospital with back pain. CT scan showed a 4.3 cm necrotic retroperitoneal mass. Due to her labile blood pressure, ranging from 194/102 mmHg to 106/60 mmHg, endocrinology was consulted for evaluation of secondary hypertension. Plasma normetanephrines were 3447 pg/mL (n ≤ 57 pg/mL), 24-hour urine normetanephrines 5954 mcg/24 hours (n 122-676 mcg/24 hours) and 24-hour urine norepinephrines 476 mcg/24 hours (n 15-100 mcg/24 hours). 24-hour urine cortisol and 24-hour urine metanephrines were within normal limits. Plasma aldosterone level and plasma renin activity (PRA) were 19 ng/dL and 0.78 ng/mL/h (n 0.25-5.82 ng/mL/h),. However, the patient was also taking spironolactone and telmisartan which interfered with results, and withdrawal of interfering medications was considered unsafe. 68Ga-DOTATATE PET/CT showed mild uptake in a left para-aortic mass. Genetic testing did not show pathogenic mutations of AP2S1, CASR, MEN1, NF1, RET, SDHA, SDHAF2, SDHB, SDHC, TMEM127 or VHL genes. The patient was started on doxazosin and underwent successful removal of the left retroperitoneal mass consistent with paraganglioma. Six months later, surveillance testing showed normalization of fractionated plasma metanephrines and of 24-hour urine metanephrines. However, due to blood pressure of 152/100 mmHg and K of 2.8 mmol/L (n 3.5-4.7 mmol/L), concern was raised for primary hyperaldosteronism. After potassium repletion, labs showed plasma aldosterone of 37 ng/dL, PRA of 0.2 ng/mL/h (n 0.25-5.82 ng/mL/h) and ARR of 185 with potassium of 4.1 mmol/L (n 3.5-4.7 mmol/L) consistent with primary hyperaldosteronism. MRI of adrenal glands showed a left adrenal gland that was thickened and nodular but without discrete nodules > 1 cm. The patient was referred for adrenal vein sampling. Five years previously, the patient had been diagnosed with primary hyperparathyroidism, with PTH of 188.5 pg/mL (n 14-64 pg/dL), Calcium of 10.6 mg/dL (n 8.5-10.1 mg/dL) and GFR of 39. Pre-operative imaging with MRI neck had shown enlargement of two parathyroid glands. She had undergone two-gland parathyroidectomy with intraoperative PTH decrease of > 50% and normalization of calcium. However two weeks later, her PTH returned to pre-operative levels (with normal 25(OH)D) and continues to remains elevated. This has been attributed to underlying secondary hyperparathyroidism from her chronic kidney disease. Conclusion To our knowledge, this is a unique case of combined paraganglioma, primary hyperaldosteronism and primary hyperparathyroidism, as thorough literature review has not shown such a coexistence in the past. Presentation: No date and time listed

ODP039 Giant Cystic Pheochromocytoma and GIST in a Patient With NF-1

Abstract Introduction Neurofibromatosis-1 (NF-1) is a genetic condition known to be associated with pheochromocytoma. We report a case of giant cystic pheochromocytoma in a patient with NF-1 and hypertensionincidentally found to have gastrointestinal stromal tumor (GIST) at operation. Clinical case: A 60-years old woman presented with a 5-week history of left sided abdominal lump. Her history is significant for NF-1, flank surgery age 5 and hypertension managed by amlodipine. Examination revealed a large nontender left upper quadrant abdominal mass crossing the midline. Computed tomography showed a20. 0×13.1×21.1 cm septate cystic and/or necrotic lesion arising from the left retroperitoneum versus adrenal gland, displacing the kidney anteromedially. Plasma free metanephrine was 3.38 nM (0-0.49) normetanephrine 3.47 nM (0-0.89),urine metanephrine 2605 mcg/day (36-229), urine normetanephrine 1215 mcg/day (95-650). There were no prior images or screens for pheochromocytoma. After preoperative blockade with phenoxybenzamine, open left adrenalectomy was performed. Intraoperative blood pressure fluctuated significantly. Exophytic firm nodules were incidentally noted and removed from the jejunum. Pathology revealed a22.5×21. 0×11.9 cm pheochromocytoma weighing 3058.9 g and five 0.2-0.7 cm gastrointestinal stromal tumors, spindle type. One-month postoperative metanephrine was 0.16 with normetanephrine 0.53 nM. The blood pressure remained normal without antihypertensives. Discussion Giant cystic pheochromocytomas are rare and may be silent. In populations with NF-1 the prevalence of pheochromocytoma is 0.1-7.7% and GIST 1.2% 1–3 . Their co-existence is seen less frequently. Recommendations for pheochromocytoma screening in NF-1 vary, from only hypertensive or symptomatic patients to routinely every 3 years 2–5 . There is no screening test for GIST 1 . Our patient presented at age 60 with the rare combination of clinically giant unilateral cystic pheochromocytoma, with incidental GIST in the setting of NF-1 and hypertension . Conclusion Routine screening for pheochromocytoma in patients with NF-1, especially those with hypertension may lead to earlier diagnosis and treatment.

ODP052 Recurrent Pheochromocytoma Concerning For Surgical Seeding From Prior Partial Adrenalectomy

Abstract Introduction Surgery for a sporadic pheochromocytoma does not always lead to long-term cure, even in patients with a benign tumor, with an estimated recurrence rate of 3% (1). We present a patient with a history of pheochromocytoma s/p partial adrenalectomy 10 years prior found to have recurrence not within the adrenal parenchyma, but in the prior resection bed and diaphragm, concerning for seeding of the surgical bed from prior surgery. Clinical Case A 56-year-old man with a history of pheochromocytoma s/p a laparoscopic left partial adrenalectomy 10 years prior, with no detected rupture of the capsule at time of surgery, presented with symptoms of palpitations and anxiety. The patient had previously tested negative for SDHB, SDHD, MEN2, and VHL. Repeat labs were concerning for recurrence: 24-hour urine normetanephrines 1192 μ g (156-729 μ g) and metanephrines 204 μ g (58-276 μ g), plasma normetanephrine 479.4 pg/mL (0. 0-136.8 pg/mL), metanephrines 38.2 pg/mL (0. 0-88. 0 pg/mL), and chromogranin A 129. 0 ng/mL (0. 0-101.8 ng/mL). MRI with contrast showed a mildly enhancing mass in the left adrenalectomy postsurgical bed with no changes noted in the liver, and an I-123 MIBG scan showed focal uptake in the left adrenal gland corresponding to the mass seen on MRI as well as heterogeneous uptake in the left hepatic lobe. A DOTATE PET scan done prior was negative. The patient underwent laparoscopic left adrenalectomy; the left adrenal gland was dissected and the patient was found to have multiple satellite lesions along the left diaphragm which were excised. On pathology, immunostains were positive for chromogranin and synaptophysin. Multiple nodules of pheochromocytoma/paraganglioma were seen involving the soft tissue of the diaphragm (<0.1-0.6 cm) and the periadrenal soft tissue and prior resection bed (<0.1-2.5 cm), with no tumor seen within the residual adrenal parenchyma. The tumor extended to the cauterized tissue edges and no lymphovascular invasion was seen. No necrosis, no increased mitotic activity, no atypical mitotic figures were noted, and Ki-67 proliferation index was <1%. Testing done six weeks postoperatively showed plasma normetanephrine 49.9 pg/mL, metanephrine <10 pg/mL, and chromogranin A 87.9 ng/mL. Repeat genetic testing was negative for SDHB, SDHD, VHL, and MEN2. One year postoperatively, the patient's blood pressures are well-controlled on a small dose of doxazosin, kept on as a prophylactic measure. Conclusion This case demonstrates a rare presentation of recurrent pheochromocytoma found in the diaphragm, periadrenal tissue, and surgical bed from a prior partial adrenalectomy, concerning for recurrence in setting of surgical seeding from prior surgery. This case highlights the importance of perhaps considering a total adrenalectomy rather than partial when possible. Reference: (1) Holscher I, et al. Recurrence Rate of Sporadic Pheochromocytomas After Curative Adrenalectomy: A Systematic Review and Meta-analysis. J Clin Endocrinol Metab. 2021 Jan 23;106(2): 588-597. Presentation: No date and time listed

PSAT011 Biochemically Silent Pheochromocytoma in an Asymptomatic Patient with a Unilateral Lipid Poor Adrenal Adenoma

Abstract Introduction Pheochromocytomas are rare catecholamine-secreting tumors arising from the adrenal medulla, which can occur in asymptomatic patients. Diagnosis is primarily through biochemical evidence of catecholamine over secretion, however, in rare cases catecholamine levels are within normal limits. These are known as "biochemically silent" pheochromocytoma. The lack of biochemical evidence makes diagnosis particularly challenging in cases presenting as adrenal incidentalomas. We present a patient with a left adrenal incidentaloma, initially identified 10 years ago which has been slowly growing and gradually becoming biochemically active. This case illustrates how radiologic findings can alert providers to the presence of pheochromocytoma and the importance of not immediately attributing mild biochemical abnormalities to medications. Case A 50-year-old Caucasian female presented to the clinic for evaluation of a left adrenal incidentaloma discovered 10 years ago. Past medical history is significant for hypothyroidism, dyslipidemia, anxiety and depression. Patient had undergone surveillance of the adrenal nodule both radiographically and biochemically since its discovery. First available imaging is a CT Abdomen/Pelvis in 2016 that noted a 1.7cm left adrenal nodule with unenhanced attenuation value of 25.6 HU. Most recent CT Abdomen/Pelvis in June 2021 reported a 2.6cm mixed density enhancing left adrenal gland nodule with less apparent macroscopic fat, concerning for a lipid poor adenoma. Biochemical work up done previously was reported to be non-functional. In 2018, elevated 24-hr urine normetanephrine of 859mcg/24h (88-649mcg/24h) and elevated 24-hr urine total metanephrines of 955mcg/24h (182-739mcg/24h) were noted. No intervention was done at that time. In August 2021, elevated plasma normetanephrine of 308.6 pg/ml (0-136.8pg/ml), elevated urine 24hr norepinephrine of 165mcg/24h (0-135mcg/24h), and elevated urine 24 hr urine normetanephrine of 1015mcg/24h (131-612mcg/24h) were noted. Rest of the biochemical work up was negative for hyperaldosteronism, hypercortisolemia and hyperandrogenemia. Although elevations were noted in the above values, they were <2 fold and the patient was also taking Effexor which can falsely elevate the normetanephrine levels. However, given the increasing size of the lipid poor adenoma, the patient was referred for endocrine surgery evaluation. She was preoperatively placed on doxazosin and underwent laparoscopic surgical removal. Pathology was consistent with a 2.4cm pheochromocytoma. Postoperatively, plasma metanephrines and normetanephrines were within normal limits. Subjectively, patient reports improvement of her hot flashes, insomnia and anxiety. Conclusion This case emphasizes the importance of surveillance for a lipid poor adrenal nodule. Providers should have a high level of suspicion for pheochromocytoma in patients with a lipid poor adenoma even if they are biochemically silent. A knowledge of medications causing falsely elevated catecholamine levels is necessary, however, these should be considered along with other clinical and radiological findings. Early diagnosis is important, if pheochromocytoma remains unrecognized it can lead to high morbidity and mortality. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Adrenalectomy for Pheochromocytoma: Complications and Predictive Factors of Intraoperative Hemodynamic Instability.

Surgery is the treatment of choice for pheochromocytoma. However, this surgery carries a risk of hemodynamic instability (HDI). The aim of this study was to report complications associated with this procedure, to identify risk factors for HDI during surgery, and its impact on postoperative outcomes. The charts of all patients who underwent adrenalectomy for pheochromocytoma in two academic centers between 2006 and 2020 were retrospectively reviewed. The primary outcome was HDI defined by a systolic blood pressure >160mmHg or a mean blood pressure <60mmHg intraoperatively. The secondary outcomes of interest were the total duration of HDI, the occurrence of intraoperative arrhythmia, perioperative cardiovascular events, and postoperative complications. 205 patients were included. HDI occurred intraoperatively in 155 patients (75.6%) but only 6 (3.2%) experienced arrhythmia. Thirty-eight postoperative complications were reported (18.6%) but only nine were ≥3 according to Clavien-Dindo (4.4%). There were 10 postoperative cardiovascular events (5.7%). Patients with intraoperative HDI had higher rates of postoperative complications (21.3% vs 10%; P = .07), major postoperative complications (5.8% vs 0%; P = .12) and cardiovascular events (6.5% vs 0%; P = .12). Factors associated with intraoperative HDI in univariate analysis were age (OR = 8.14; P = .006), high blood pressure preoperatively (OR = 2.16; P = .04), tumor size (OR = 15.83; P = .0001), and urinary normetanephrine level (OR = 9.33; P = .04). In multidisciplinary centers, the overall morbidity of adrenalectomy for pheochromocytoma is low. HDI during adrenalectomy for pheochromocytoma is highly prevalent but rarely associated with major cardiovascular events. There might be a link between HDI and postoperative cardiovascular events.

Pre- and peri-operative characteristics, complications and outcomes of patients with biochemically silent pheochromocytomas; a case series.

Pheochromocytomas are rare tumors and biochemically silent ones with normal catecholamine levels are even rarer. Up to date, biochemically inactive pheochromocytomas are poorly investigated. We aimed to systematically assess the pre- and peri-operative characteristics and the outcomes of patients with these tumors who had been treated and followed-up in 2 tertiary centers. Clinical, laboratory and imaging data, treatment outcomes and follow-up of biochemically silent pheochromocytoma patients were recorded. Ten patients (5 men) [median age at diagnosis 52.5 years (24-72)] were included. Adrenal masses were incidentally discovered in all patients except from one who presented with pheochromocytoma-related manifestations. Twenty-four-hour urine metanephrine and normetanephrine levels were in the low-normal, normal and high-normal range in 4, 4 and 2 patients and in 1, 6 and 3 patients, respectively. Tumors were unilateral [median size 46 mm (17-125)] and high density on pre-contrast CT imaging or high signal intensity on T2-weighted MRI scans were found in all cases. Pre-operatively, 5 patients were treated with phenoxybenzamine [median total daily dose 70 mg (20-100)]. Intra-operatively, 4 patients developed hypertension requiring vasodilator administration and 8 developed hypotension; vasoconstrictors were required in 5 cases. One patient, not pre-operatively treated with phenoxybenzamine, developed Takotsubo cardiomyopathy. During a median 24-month (12-88) follow-up period, one patient had disease progression. The majority (90%) of patients with biochemically silent pheochromocytomas developed hemodynamic instability during adrenal surgery. In patients with biochemically silent adrenal lesions and a high suspicion index for pheochromocytoma based on tumor imaging characteristics, pre-operative alpha-blockade treatment may be advisable.

TAKOTSUBO SYNDROME REVEALING PHEOCHROMOCYTOMA

Objective: We report the case of 57-year old woman with no previously known cardiovascular disease. Design and method: Her conventional cardiovascular risk factors were type 2 diabetes (HbA1c&lt; 6.5%), hypertension and active smoking. She presented to the ER for thoracic pain, headache, sweating and tachycardia (150 bpm). Results: Blood analysis showed an elevation of cardiac biomarkers (Troponin 2035ng/l; BNP 541ng/l, Ddimers 19500ug/l), and acute renal impairment (creatinin 158umol/l) while EKG showed inferior NSTEMI. Echocardiography visualized typical takotsubo aspect with apical hypokinesia. Thoraco-abdominal CT-scan showed an important left adrenal tumor. Plasmatic and urinary metanephrine and normetanephrine were high. The patient benefited from adrenal surgery with an optimal result on blood pressure control. Conclusions: Although the association TTS-pheochromocytoma has already been described, it remains uncommon. Catecholamine excessive secretion mediates TTS cardiomyopathy having a negative impact essentially on apical segments increasing wall stress and pressure, but different ventricular segments may be concerned as individual adrenoreceptors distribution patterns vary. TTS diagnosis should legitimate pheochromocytoma screening when associated with labile hypertension.

Takotsubo cardiomyopathy in patients suffering from acute non-traumatic subarachnoid hemorrhage—A single center follow-up study

Takotsubo cardiomyopathy (TTC) is an important complication of subarachnoid hemorrhage (SAH), that may delay surgical or endovascular treatment and may influence patient outcome. This prospective follow-up study intended to collect data on the prevalence, severity, influencing factors and long-term outcome of TTC in patients suffering from non-traumatic SAH. Consecutive patients admitted with the diagnosis of non-traumatic SAH were included. Intitial assessment consisted of cranial CT, Hunt-Hess, Fisher and WFNS scoring, 12-lead ECG, transthoracic echocardiography (TTE), transcranial duplex sonography and collecting laboratory parameters (CK, CK-MB, cardiac troponin T, NT-proBNP and urine metanephrine and normetanephrine). Diagnosis of TTC was based on modified Mayo criteria. TTC patients were dichotomized to mild and severe forms. Follow-up of TTE, Glasgow Outcome Scale assessment, Barthel's and Karnofsky scoring occurred on days 30 and 180. One hundred thirty six patients were included. The incidence of TTC in the entire cohort was 28.7%; of them, 20.6% and 8.1% were mild and severe, respectively. TTC was more frequent in females (30/39; 77%) than in males (9/39; 23%) and was more severe. The occurrence of TTC was related to mFisher scores and WFNS scores. Although the severity of TTC was related to mFisher score, Hunt-Hess score, WFNS score and GCS, multivariate analysis showed the strongest relationship with mFisher scores. Ejection fraction differences between groups were present on day 30, but disappeared by day 180, whereas wall motion score index was still higher in the severe TTC group at day 180. By the end of the follow-up period (180 days), 70 (74.5%) patients survived in the non-TTC, 22 (81.5%) in the mild TTC and 3 (27%) in the severe TTC group (n = 11) (p = 0.002). At day 180, GOS, Barthel, and Karnofsky outcome scores were higher in patients in the control (non-TTC) and the mild TTC groups than in the severe TTC group. Takotsubo cardiomyopathy is a frequent finding in patients with SAH, and severe TTC may be present in 8% of SAH cases. The severity of TTC may be an independent predictor of mortality and outcome at 6 months after disease onset. Therefore, a regular follow-up of ECG and TTE abnormalities is warranted in patients with subrachnoid hemorrhage for early detection of TTC. The study was registered at the Clinical Trials Register under the registration number of NCT02659878 (date of registration: January 21, 2016).

P139 CARDIAC PARAGANGLIOMA: THE IMPORTANCE OF MULTIMODALITY IMAGING

Abstract Cardiac paraganglioma is a rare neuroendocrine tumour secreting norepinephrine and causing severe hypertension, palpitations, tachyarrhythmias; its precise location is very important because the compression of cardiovascular structures may result in ischaemia, arrhythmia and cardiac failure. Surgical resection represents the primary treatment modality. A 40–year–old young woman with history of hypertension, nocturnal tachycardia and sweats with elevated levels of urinary metanephrine underwent abdominal MRI angiography showing normal kidneys and adrenal glands while in the cardiac–mediastinal site a solid neoformation with contrast impregnation confirmed at subsequent chest CT scan with contrast medium and it appeared inseparable from superior vena cava and occupying the atrial chambers. Patient started therapy with an α–adrenoceptor blocker and underwent cardiac MRI documenting the intrapericardial site of the lesion infiltrating atrial septum and PET/CT scan revealing a large area of uptake of the analogue of somatostatin in the mediastinum typical for atrial paraganglioma. Subsequent angiography CT scan of the thoracic aorta and coronary CT scan showed no signs of infiltration on the great vessels and heart chambers but there was not a clear adipose cleavage plane and the mass appeared intensely vascularized by two large vessels arising from the circumflex artery and the isthmic aorta. After specialistic surgical evaluation the patient was treated with ligation of the afferent peduncle to the neoformation and biopsy of the tissue sample was performed. Post–procedure angiography CT scan showed the neoformation unchanged in size with the two unchanged afferent branches. Histological examination of the tissue sample concluded with arteriovenous hemangioma. One month after surgery elevated urinary normetanephrine levels persisted and the mass on echocardiogram was unchanged. Cardiac MRI after three months was unchanged and specialistic surgical evaluation did not suggest reoperation. Six months after surgery cardiac MRI showed mild increase in volume of the intrapericardial lesion and unchanged atrial septum infiltration. The multimodality imaging plays an important role in the diagnosis of cardiac paraganglioma. The arterial ligation, without the completely removal of the lesion, was not conclusive, the mass increased in size and the patient remained symptomatic. Surgical resection is necessary for the complete cure of the syndromes.

Hereditary and Sporadic Pheochromocytoma: Comparison of Imaging, Clinical, and Laboratory Features.

BACKGROUND. A considerable fraction of pheochromocytomas initially suspected to be sporadic, whether or not symptomatic, are a result of germline mutations. OBJECTIVE. The purpose of this article is to compare imaging features between hereditary and sporadic pheochromocytomas. METHODS. This retrospective study included 71 patients (39 women, 32 men; median age, 48 years) who underwent adrenal pheochromocytoma resection from January 2002 to October 2021 after preoperative CT or MRI. Two radiologists independently reviewed examinations to assess features of the largest resected pheochromocytoma. Interreader agreement was assessed by prevalence-adjusted bias-adjusted kappa coefficients; a third radiologist resolved discrepancies for further analysis. Genetic testing was used to classify pheochromocytomas as hereditary or sporadic and to classify hereditary pheochromocytomas by germline mutation clusters. Symptoms associated with pheochromocytomas and preoperative biochemical laboratory values were recorded. Groups were compared using Kruskal-Wallis, Fisher exact, and chi-square tests, and false-discovery rate-adjusted p values were computed to account for multiple comparisons. RESULTS. Hereditary pheochromocytoma (n = 32), compared with sporadic pheochromocytoma (n = 39), was associated with younger median age (38 vs 52 years, p = .001) and smaller median size (24 vs 40 mm, p < .001). Interreader agreement for CT and MRI features, expressed as kappa, ranged from 0.44 to 1.00. Hereditary and sporadic pheochromocytoma showed no difference in frequency of calcifications, hemorrhage, cystic change/necrosis, or macroscopic fat on CT, or in frequency of hemorrhage, cystic change/necrosis, macroscopic fat, or microscopic fat on MRI (p > .05). When combining CT and MRI, cystic change/necrosis was observed in 35% of hereditary versus 67% of sporadic pheochromocytomas (p = .10). Hereditary pheochromocytoma, compared with sporadic, had lower frequency of symptoms (31% vs 74%; p = .004) and lower 24-hour urinary normetanephrines (1.1 vs 5.1 times upper limits of normal, p = .006). Among hereditary pheochromocytomas, cystic change/necrosis (when assessable on imaging) was present in 18% and 45% of those with cluster 1 (n = 11) and cluster 2 (n = 21) germ-line mutations, respectively. CONCLUSION. Hereditary pheochromocytomas, compared with sporadic, are detected at a younger age and smaller size, produce lower 24-hour urinary normetanephrines, are less often symptomatic, and may less frequently show cystic change/necrosis. CLINICAL IMPACT. Imaging findings may complement clinical and biochemical features in raising suspicion for a previously unsuspected germline mutation in patients with pheochromocytoma.

Abstract 92: Contemporaneous association of pheochromocytoma with Cushing's syndrome

Background: Pheochromocytomas are catecholamine secreting tumours of the adrenal gland. We report a rare case of adrenocorticotropic hormone-secreting pheochromocytoma.Case Report: A twenty-five-year-old male presented with excessive fatigue for one year. He had pain abdomen two weeks prior to the presentation. On examination, he was pale, emaciated, had tachycardia with normal blood pressure. Abdominal ultrasound revealed a right adrenal mass. There were no stigmata of Cushing's disease. His urinary metanephrine was 469.8 μg/24 hours, and nor-metanephrine was 3676.5 μg/24 hrs. Androstenedione, DHEA-S were normal. The 8 am cortisol was not suppressed with overnight 1mg dexamethasone. He had elevated ACTH (253.9 pg/mL). Calcium, phosphorous, prolactin levels were normal. He underwent laparoscopic resection of the tumour after adequate alpha and beta-blockade. The tumour measured 9x8.5x6 cm with no capsular or vascular invasion. Histopathology revealed tumour cells with round to irregular nuclei arranged in the Zellballen pattern. Tumour cells were diffusely positive for chromogranin A. Ki-67 index was 1-2%. Post-operatively 24-hour urinary metanephrine, normetanephrine and ACTH levels were normalized.Conclusion: This case report highlights the importance of complete biochemical evaluation in a patient with an adrenal mass even if biochemical evidence of pheochromocytoma is confirmatory.

Pseudo-pheochromocytoma due to obstructive sleep apnea: a case report.

SummaryObstructive sleep apnea (OSA) is a condition of intermittent nocturnal upper airway obstruction. OSA increases sympathetic drive which may result in clinical and biochemical features suggestive of pheochromocytoma. We present the case of a 65-year-old male with a 2.9-cm left adrenal incidentaloma on CT, hypertension, symptoms of headache, anxiety and diaphoresis, and persistently elevated 24-h urine norepinephrine (initially 818 nmol/day (89–470)) and normetanephrine (initially 11.2 µmol/day (0.6–2.7)). He was started on prazosin and underwent left adrenalectomy. Pathology revealed an adrenal corticoadenoma with no evidence of pheochromocytoma. Over the next 2 years, urine norepinephrine and normetanephrine remained significantly elevated with no MIBG avid disease. Years later, he was diagnosed with severe OSA and treated with continuous positive airway pressure. Urine testing done once OSA was well controlled revealed complete normalization of urine norepinephrine and normetanephrine with substantial symptom improvement. It was concluded that the patient never had a pheochromocytoma but rather an adrenal adenoma with biochemistry and symptoms suggestive of pheochromocytoma due to untreated severe OSA. Pseudo-pheochromocytoma is a rare presentation of OSA and should be considered on the differential of elevated urine catecholamines and metanephrines in the right clinical setting.Learning pointsObstructive sleep apnea (OSA) is a common condition among adults.OSA may rarely present as pseudo-pheochromocytoma with symptoms of pallor, palpitations, perspiration, headache, or anxiety.OSA should be considered on the differential of elevated urine catecholamines and metanephrines, especially in patients with negative metaiodobenzylguanidine (MIBG) scan results.