Normal Plasma Renin Research Articles

Renal pseudohypoaldosteronism type 1-an adult case series including a novel gene variant.

Renal pseudohypoaldosteronism type 1 (PHA1) is a rare disease affecting infants. Symptoms are failure to thrive, vomiting, and weight loss. It is caused by gene variants in NR3C2 by which the mineralocorticoid receptor is dysfunctional, and patients develop hyponatremia, elevated plasma aldosterone, and renin but have normal blood pressure. Little is known about PHA1 in adults. We present four adults with PHA1, their clinical, biochemistry, and genetic data. Clinical and biochemical data were collected from the medical files and clinical examination of the participants. Genetic testing was performed. Two adult dizygotic twins and their mother, as well as an adult man were included. One of the sisters and the man had had severe hyponatremia and been admitted several times as young infants, treated with sodium chloride and fludrocortisone. All had as adults elevated plasma aldosterone and normal sodium. The females now had normal plasma renin, but it was increased in the male. A novel genetic variant in NR3C2 was found in the twins and their mother (c.1816T>C, p.(Cys606Arg)). All had normal blood pressure and were asymptomatic. In adulthood, PHA1 seems to be asymptomatic and long-term consequences favorable.

6661 Critical Limb Ischemia - An Unusual Presentation Of A Pheochromocytoma

Abstract Disclosure: S. Hassan: None. Background: Pheochromocytomas can lead to vasoconstriction and its various clinical manifestations due to excess catecholamine release. Critical limb ischemia as a clinical manifestation of pheochromocytoma has been reported sparsely. Clinical Case: A 43 year old female with a past medical history of type 2 diabetes mellitus, Turner syndrome, and hypertension presented to the emergency department with acute on chronic left leg pain. She underwent workup with a CT angiography of the abdomen with runoff for evaluation of her vessels, which revealed an occlusion of her left superficial femoral artery with chronic stenosis of the right femoral system. Multiple unsuccessful attempts were made at revascularization of her left lower extremity, including femoropopliteal bypass, with eventual left above knee amputation, multiple fasciotomies, and angiogram and stenting of multiple vessels. The patient was on a combined OCP (norethindrone-ethinyl estradiol) for hormone replacement for Turner syndrome for the past 30 years, and did not have a personal or family history of clotting disorders. She underwent a hypercoagulable workup which was negative. Echocardiogram was negative for thrombi and was otherwise unremarkable. Incidentally discovered on her initial CT angiography was a heterogeneously enhancing right adrenal mass, which was further delineated on a dedicated CT of the adrenals, which showed a 3.7 cm right adrenal mass with pre-contrast Hounsfield units measuring 46. Biochemical workup revealed a normal plasma renin activity and aldosterone, plasma metanephrine elevated to 5.20 nmol/L (range 0.00 – 0.49 nmol/L), plasma normetanephrine elevated to 4.95 nmol/L (range 0.00 – 0.89 nmol/L), 24 hour urine metanephrine elevated to 3830 ug/d (range 36-229 ug/d), and 24 hour urine normetanephrine 1733 ug/d (range 95 – 650 ug/d). She reports a diagnosis of hypertension at age 36, with no secondary workup pursued; she had suboptimal control on three separate medications, lisinopril, metoprolol, and hydrochlorothiazide. Her blood pressure and heart rate were noted to be labile during her aforementioned surgery. Alpha blockade with doxazosin was started based on her significantly elevated plasma and urine metanephrines and normetanephrines, with improvement in her blood pressure control. She was not found to have a definitive cause of her critical limb ischemia; she was noted to have atherosclerosis in the vessels of her lower extremities, and her chronic oral contraceptive use may also have played a role. However, OCPs are often reported to cause venous rather than arterial thrombi. Therefore, it can be inferred that the catecholamine excess from her presumed pheochromocytoma caused vasoconstriction which may have played a role in the development of her critical limb ischemia. Conclusion: Catecholamine excess that is resultant from a pheochromocytoma may manifest as critical limb ischemia. Presentation: 6/1/2024

Abstract #1400950: Chiari I Malformation with Concomitant Nonfunctioning Pituitary and Adrenal Tumors

Chiari I malformation (CM1) is a rare finding with an incidence ranging from 3.3 to 8.2 per 100000. CM1 has been described with growth hormone secreting pituitary adenomas, and with EPAS1 gain-of-function mutation syndrome with multiple paragangliomas/pheochromocytomas, somatostatinoma, and polycythemia. There is only one case report in the literature describing a nonfunctional pituitary adenoma with CM1. We describe the first reported case of a patient with CM1 with concomitant nonfunctional pituitary and adrenal incidentalomas. A 45-year-old female with history of diet-controlled diabetes and HTN presented with a two-week history of bilateral upper extremity weakness and paresthesia, along with gait instability. She had reduced motor power in the upper extremities on physical exam. MRI cervical spine demonstrated a cervicothoracic syrinx, cerebellar tonsillar ectopia consistent with CM1. MRI brain showed diffuse enlargement of the pituitary gland measuring 16 x 14 x 13 mm bulging into the suprasellar cistern and minimally abutting the inferior aspect of the optic chiasm. MRI lumbar spine revealed a left adrenal gland nodule measuring 1.5 x 2.0 cm. Endocrine hormonal evaluation showed normal prolactin, follicle stimulating and luteinizing hormone, estradiol, free T3, free T4, and IGF-I levels. Aldosterone level was high in supine position with normal plasma renin activity initially with normal levels on repeat testing. Plasma free metanephrine, normetanephrine, testosterone levels were also normal. Patient was started on dexamethasone in anticipation of surgery. Patient underwent suboccipital craniectomy, C1 laminectomy, coagulation of cerebellar tonsils and expansile duraplasty for CM1. Patient did well postoperatively and dexamethasone was tapered off. Postoperative follow up after patient had been off steroids for three weeks showed normal levels of all pituitary and adrenal hormones, including normal dexamethasone suppression test. While CM1 is a rare finding, pituitary adenomas are relatively common. In cases of concomitant occurrence of CM1 and growth hormone secreting pituitary adenoma, over-secretion of growth hormone has been proposed as a mechanism to precipitate symptoms of CM1 by causing hypertrophy of connective and ligamentous tissue in the skull base and of the cranio-cervical canal. Our patient had normal IGF-1 levels with a nonfunctional pituitary adenoma raising the question whether there is some other underlying mechanism, possibly a genetic predisposition, that contributed to the concomitant occurrence of CM1 with pituitary and adrenal tumors. Whether these tumors become functional in the future remains to be seen.

LBSAT65 Search For A Duplicitous Pheochromocytoma

Abstract Introduction Pheochromocytomas are discovered during work up of adrenal incidentalomas and can be biochemically and clinically silent. We present a case of a patient who presented with typical "adrenergic spells" suggestive of pheochromocytoma but negative biochemical testing and non-confirmatory imaging findings. Case Report 39-year-old male presented with 4 weeks history of episodes of throbbing headaches, palpitations, sweating. He was found to be hypertensive, blood pressure of 220/110 mm Hg. Losartan was initiated, but symptoms persisted. Work-up for endocrine causes of hypertension revealed normal plasma renin activity 1.123 ng/ml/hr (0.167 to 5.380) and undetectable aldosterone level <1 ng/dl (0. 0-3. 0), mildly elevated random plasma normetanephrine 270 pg/ml (0-210), normal plasma metanephrines 49 pg/ml (0-88). Low-dose dexamethasone suppression test showed unsuppressed morning cortisol of 2.1ug/dl, undetectable ACTH <5 pg/ml, dexamethasone level 486 ng/dl. 24 urinary cortisol and 2 midnight salivary cortisol samples failed to confirm the diagnosis. 24-hr urine studies showed mildly elevated 24-hr normetanephrine 735 ug/24 hr (156-729), normal 24-hr metanephrines 197 ug/L (58-276), normal 24 hr epinephrine and dopamine levels. Repeat testing revealed normal plasma metanephrines levels and mildly elevated plasma normetanephrine levels 287 pg/ml (less than twice above the upper limit of normal). Dopamine and Chromogranin A levels were undetectable. Abdominal CT showed 2 cm round soft tissue density 42HU in right adrenal gland. Left adrenal gland contained 3 nodules measuring 11, 15 and 16 mm–all with density <10HU. MRI findings for the 2.2 cm right adrenal nodule was without significant drop in signal intensity on the in and out of phase sequences appearing moderately T2 hyperintense and T1 hypointense. Differential included atypical/fat poor adenoma, pheochromocytoma, or metastasis. On GA 68 Dotatate PET-CT this 2.2cm adrenal nodule had minimal to low radiotracer uptake. Since a pheochromocytoma could not be ruled out, patient was started on alpha blockade. Preoperative genetic testing was negative for common mutations associated with pheochromocytoma/paraganglioma syndromes. Patient underwent laparoscopic right adrenalectomy. Histopathology report confirmed 2.8 cm pheochromocytoma with a low PASS (2/20) and low GAPP score. Conclusion and Discussion Patients with borderline nor metanephrine elevations represent a diagnostic and therapeutic dilemma. The patient presented with adrenergic paroxysms strongly suggestive of underlying pheochromocytoma. Labs and imaging were not typical for pheochromocytoma and were indeterminate. Given strong clinical suspicion for a pheochromocytoma, we decided to proceed with adrenalectomy after pre-treatment with alpha blockers. Final histopathologic report confirmed the diagnosis of pheochromocytoma. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Hypocortisolism in a dog caused by bilateral pheochromocytoma

AbstractWe present a 12‐year‐old French bulldog with muscle weakness, epigastric pain, weight loss, high systolic blood pressure and cardiac arrhythmias. Physical and laboratory examination revealed no abnormalities. On a computed tomography scan, severely enlarged adrenals were found, and endocrine and biochemical evaluations excluded hypercortisolism and hyperaldosteronism. Urinary metanephrine and normetanephrine/creatinine ratios were elevated, compatible with a diagnosis of pheochromocytoma. Symptomatic treatment with phenoxybenzamine was started and resulted in normalisation of a systolic blood pressure and reduction of arrhythmias. However, the onset of anorexia, vomiting and clinical deterioration prompted exploration of the adrenocortical reserve through an adrenocorticotropic hormone stimulation test, which confirmed glucocorticoid deficiency. Mineralocorticoid deficiency was ruled out by normal plasma aldosterone concentration and renin activity. Finally, an elevated endogenous plasma adrenocorticotropic hormone concentration defined the primary origin of the hypocortisolism. Clinical resolution occurred with prednisolone supplementation. This is the first report of hypocortisolism in a dog caused by a bilateral pheochromocytoma.

Primary hyperaldosteronism without suppressed renin

Primary Hyperaldosteronism characterizes elevated plasma and urinary aldosterone with suppression of plasma renin activity. Suppression can be due to sodium retention which is aldosterone dependent and extracellular volume expansion. Here a 29 year old male presented with uncontrolled hypertension, on work up he was diagnosed to have primary Hyperaldosteronism with normal plasma renin level. So with the available medical data on the patient as well as the publications on aldosterone/renin association in primary hyperaldosteronism was reviewed here to explain the rare finding.

A case of atypical reninoma with mild hypertension and normal plasma renin activity but elevated plasma renin concentration

BackgroundReninoma is a rare, benign renal neoplasm. Typical clinical features include severe hypertension, secondary hyperaldosteronism, hypokalaemia and metabolic alkalosis caused by the overproduction of renin.Case presentationA 25-year-old lean Chinese woman with no family history of hypertension was hospitalized for stage 1 hypertension that gradually developed over two years. Endocrine investigation showed hyperreninemia without hyperaldosteronism and hypokalaemia. Interestingly, although the patient had an elevated plasma renin concentration (PRC), her plasma renin activity (PRA) was in the normal range. Abdominal contrast-enhanced computed tomography (CT) scanning revealed a solid, low-density, renal cortical mass with delayed enhancement. Selective renal vein sampling (SRVS) was performed, and a lateralization of the renin secretion from the left kidney was found. Enucleation of the tumour led to a rapid remission of hypertension and hyperreninemia. Based on pathological findings, the patient was diagnosed with reninoma. Immunohistochemical staining of the tumour was positive for Renin, CD34, Vimentin, and synaptophysin (Syn) and negative for somatostatin receptor 2 (SSTR2) and chromogranin A (CgA).ConclusionsReninoma can present as mild hypertension without hyperaldosteronism and hypokalaemia. The clinical features of reninoma may depend on the degree of activation of the renin-angiotensin-aldosterone system (RAAS). PRC should be incorporated in the differential diagnosis of secondary hypertension.

Mitotane in the Treatment of Adrenocortical Carcinoma: Metabolic and Endocrine Disruption

Abstract Background: Mitotane is a well-known adrenocytolitic agent resulting in adrenal insufficiency. However, little is known about its multiple and complex metabolic and endocrine effects. Clinical Case: Patient is a 6 year 9 month old female who presented with acne, pubic hair and rapid weight gain. Initial evaluation showed elevated testosterone (64 ng/dL), 17-OH-progesterone (236 ng/dL), DHEA-S (922 mcg/dL), and random cortisol (30.9 mcg/dL) with suppressed ACTH (<2.0 pg/mL). She had an inappropriate lack of suppression after a 1 mg overnight dexamethasone suppression test (cortisol 49 mcg/dL, nl <2 mcg/dL). Abdominal CT showed large necrotic-appearing right adrenal mass (10.7x8.8x15 cm) with no metastasis. Surgical excision was complicated by intraoperative rupture. Pathology confirmed stage III right adrenal cortical carcinoma. Patient was started on etoposide, cisplatin, doxorubicin, and mitotane as adjuvant therapy. 6 days after surgery, her DHEA-S and cortisol levels were undetectable. She was started on glucocorticoid replacement therapy with hydrocortisone at 18 mg/m2/day. Due to severe nausea, she was switched to dexamethasone 5 mg/m2/day (245 mg/m2/day dose equivalent to hydrocortisone). However, the patient developed hypotension, increased nausea and emesis and was switched back to hydrocortisone. The patient’s clinical course was complicated by hyperlipidemia with total cholesterol 215 mg/dL, HDL 48 mg/dL and LDL 150 mg/dL, as well as central hypothyroidism with low FT4 (0.8 ng/dL) and an inappropriately low normal TSH (0.31 mcIU/mL). She was started on levothyroxine with a final dose of 2.6mcg/kg/day to achieve euthyroid state. Mineralocorticoid deficiency has been reported in a small number of case reports of mitotane use. Our patient continues to demonstrate adequate mineralocorticoid function based on her normal electrolytes, aldosterone and plasma renin activity level. Conclusion: Mitotane exerts multiple clinically relevant metabolic and endocrine effects. Patients treated with mitotane should be monitored for complications including mineralocorticoid deficiency, central hypothyroidism, and hyperlipidemia. Dexamethasone must be avoided because of the rapid inactivation by CYP4503A4 leading to adrenal crisis. Typical glucocorticoid replacement dose must be doubled due to induction of CYP3A4 activity that leads to glucocorticoid inactivation.

Prospective Screening for Primary Aldosteronism in Patients With Suspected Obstructive Sleep Apnea.

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The effect of the components of the renin-angiotensinaldosterone system on the development of diabetic nephropathy in type 1 diabetes (review)

One of the key roles in the development of diabetic nephropathy belongs to the renin-angiotensin-aldosterone system (RAAS), which is involved in the regulation of hemodynamics, systemic and intrarenal pressure, production of profibrogenic and growth factors, vascular remodeling. At the end of the twentieth century, local (tissue) RAAS elements from renin to aldosterone were found in tissues and target organs (including kidneys). Tissue RAAS plays a leading role in the development of vascular complications of diabetes mellitus (DM): cardiovascular disease, diabetic nephropathy, and retinopathy. It is this fact that explains in many ways the pathogenetic role of RAAS in the defeat of target organs even with normal or low plasma renin activity (ARP). RAAS activation occurs long before the clinical signs of diabetic nephropathy, which makes it possible for earlier prevention and correction of initial changes in the study of its components, as well as reducing disability and the output of patients in chronic kidney disease. Given the tendency to “rejuvenate” diabetes mellitus, the lability of the course of the disease in childhood, the high hormonal activity in this group of patients, and, therefore, the greater the risk of complications, the timely diagnosis of the initial manifestations of DN is of high relevance and relevance.

The renin secretion profile under the influence of sleep deprivation and the neuropeptides CRH and GHRH

It is already known that during normal sleep plasma renin activity (PRA) shows oscillations with decreases during rapid-eye-movement (REM) sleep and increases during non-REM (NREM) sleep. We also know that renin correlates positively with slow-wave sleep (SWS). Sleep deprivation is known to enhance significantly SWS and slow wave activity (SWA, known as δ power).Based on these findings we addressed the question whether and to which extent sleep deprivation may affect the synchronization found between PRA and REM sleep during normal sleep and whether this synchronization is affected by other sleep regulating factors. To investigate these questions we compared sleep EEG and sleep-related free renin levels in 48 normal women and men 19–69 years old between nights before and after 40 h of sleep deprivation. During the recovery night, four bolus injections of either GHRH, CRH or placebo were injected via long catheter around sleep onset. When compared to baseline after each of the treatments SWS, SWA and renin levels increased. The characteristical oscillation profiles of renin during normal sleep were also preserved after sleep deprivation. Similar to normal sleep our data support also a distinct link between nocturnal renin secretion and SWS after sleep deprivation and that independent of the applied treatments.

SUN-170 Adrenal Insufficiency Due to Adrenal Hemorrhage

Introduction: Antiphospholipid Syndrome (APS) can involve multiple organ systems but endocrine manifestations are rare. In most cases adrenal insufficiency (AI) is the first endocrine manifestation of APS. The prompt diagnosis of adrenal insufficiency is critical. We present a case of AI associated with antiphospholipid syndrome who was managed successfully. Case presentation: A 50-year-old man was admitted with deep venous thrombosis of the distal left femoral vein extending to the popliteal vein and was started on xarelto, but he developed pleuritic chest pain and dyspnea in 48 hours. CT scan confirmed a pulmonary embolism and patient was treated with heparin drip. Two days following heparin drip patient developed acute bilateral flank pain and hypotension; and CT abdomen showed 2 masses replacing the adrenal glands that were concerning for hematomas. Laboratory results: serum potassium 4.9 mmol/L, serum cortisol 3.3 mcg/dL (reference 7.2–19.4), ACTH level 319 pg/mL (reference 7–53), aldosterone <1.0 ng/dL (reference 0.0–3.0), and plasma renin activity 7.17 ng/ml/hr (reference, 0.15–3.95). Serum antiphospholipid antibody testing showed cardiolipin Ab Ig 140 GPL/mL (reference 0–14), cardiolipin Ab IgM 100 MPL/mL (reference 0–12) and cardiolipin Ab IgA >150 APL/mL (reference 0–11). Further testing showed beta-2 glycoprotein 1 Ab IgG 103 GPI units (reference 1–20), IgM 94 GPI units (reference 0–32), and IgA 150 GPI units (reference 0–25). His hypotension dramatically improved upon administration of IV hydrocortisone and the abdominal pain resolved in 3 days. Upon discharge he was placed on hydrocortisone and continued warfarin therapy. At a 6-week follow-up visit, patient was asymptomatic. Additional lab tests revealed normal plasma renin activity and aldosterone levels. Two years later an ACTH stimulation test confirmed persistent AI. Basal plasma ACTH level was 230 pg/mL (ref 5–50). Additionally plasma renin activity and serum aldosterone levels indicated no mineralocorticoid deficiency. An adrenal CT scan revealed significant long-term interval decrease in size of bilateral adrenals with hypo-attenuating focus in the right adrenal gland, favored to represent post hemorrhage changes without convincing evidence of underlying neoplasm especially given decrease in size compared to 4-years prior. Presently, patient is doing well on hydrocortisone and warfarin treatment. Conclusion: In all cases of adrenal hemorrhage and infarction with unknown etiology, screening with lupus anticoagulant and anticardiolipin antibodies is imperative. Recognition of this high mortality condition will allow for appropriate screening and confirmatory tests leading to prompt diagnosis and timely management.

SAT-363 Deletion of TASK Channels Selectively from the Zona Glomerulosa Causes Mild Angiotensin II-Independent Hyperaldosteronism with Elevated Blood Pressure in Mice

Overt dysregulation of the renin-angiotensin-aldosterone system (primary aldosteronism: APA and IHA) has long been known for its deleterious cardiovascular consequences. Recently, however, subclinical mild hyperaldosteronism was recognized as a significant risk factor for hypertension, and may represent an early stage in the disease spectrum. Previously, we developed mouse models of hyperaldosteronism by globally deleting subunits of the TWIK-related acid sensitive potassium channel (TASK). Global TASK-1 (Kcnk3) and TASK-3 (Kcnk9) KO mice markedly overproduce Ang II-independent (autonomous) aldosterone, that is not suppressed by high dietary sodium and is accompanied by low renin and elevated blood pressure. Here, we report a novel mouse model of mild hyperaldosteronism produced by the zona glomerulosa (zG)-specific deletion of TASK channels. To generate trigenic Cyp11b2Cre/+ :: Kcnk3f/f :: Kcnk9f/f mice (zG-TASK-KO), the Cyp11b2Cre/+ strain that expresses Cre-recombinase under the aldosterone synthase promoter was crossed with the Kcnk3f/f :: Kcnk9f/f strain. We confirmed restriction of Cre-expression to the zG layer by qRT-PCR and immunohistochemistry using a Cre-dependent reporter mouse (Gt(ROSA)26Sortm4(ACTB-tdTomato,-EGFP)Luo/J ). Despite normal plasma renin, zG-TASK-KO mice displayed a mild increase in 24-hr. urinary aldosterone excretion (11.8±0.8 KO vs 9.3±0.6 controls; ng/mg-aldosterone/creatinine, p<0.05) that was much less than the frank increase observed in global TASK-KO mice (42.6±6.9 ng/mg, aldosterone/creatinine, p<0.05). Hyperaldosteronism of zG-TASK-KO mice failed to normalize with AT1R antagonism (candesartan) or salt suppression (4% Na-diet). Twenty-four-hour blood pressure of conscious, freely behaving zG-TASK-KO mice was increased compared to control mice (systolic: 133.3±1.8 mmHg KO vs 122.7±1.2 mmHg controls, p<0.05) and failed to normalize with candesartan, but corrected with MR antagonism (spironolactone). This study demonstrates that a zG-specific channel defect can produce mild autonomous hyperaldosteronism sufficient to cause chronic aldosterone-driven and Angiotensin II-independent blood pressure elevation.

MON-387 Pheochromocytoma Masquerading as Vasomotor Menopausal Symptoms

Introduction Pheochromocytoma and paraganglioma are neuroendocrine tumors arising from chromaffin cells. There are approximately 500-1600 new cases of combined pheochromocytoma and paraganglioma in the United States per year. Most of the cases occur between the 3rd and 5th decade of life. Recent studies demonstrate that more than 50 percent of these tumors are asymptomatic. Case We present a 58 year old female with no significant past medical history, referred to endocrinology division for treatment of vasomotor symptoms of menopause. Her last menstrual period was 6 years ago. She had noticed generalized profuse diaphoresis, intermittent lightheadedness, anxiety and hot flashes that had started in perimenopause. The diaphoresis had limited her outside activities. She denied hypertension, tachycardia and headaches. She denied hormonal replacement therapy for menopausal symptoms and paroxetine had not helped her symptoms in the past. When evaluated in endocrinology, we reviewed her past records and noticed the presence of a right adrenal nodule on a CT abdomen from 2010. Biochemical evaluation showed elevated plasma normetanephrine at 1.9 (<0.90 nmol/l) with normal metanephrine at <0.20 (<0.50 nmol/l). 24 hour urine fractionated catecholamines and metanephrines results: Dopamine 121 (65-400 mcg), epinephrine 9.0 (<21 mcg), norepinephrine 170 (15-80 mcg), metanephrine 130 (<400 mcg), normetanephrine 1074 (<900 mcg) and total metanephrines 1204 (<1300 mcg). She had normal urinary cortisol, serum DHEA-S, serum aldosterone, plasma renin and serum calcium. MRI of adrenal glands reidentified a 1.7 cm right adrenal nodule suspicious for pheochromocytoma, that had doubled in size compared with prior images. Patient was prepared preoperatively with phenoxybenzamine and propranolol. She underwent right adrenalectomy and pathology was positive for pheochromocytoma. Four weeks post surgery, repeat plasma normetanephrine normalized at 0.28 (<0.90 nmol/l) and repeat 24 hour urine collection showed that norepinephrine normalized at 29 (15-80 mcg) and normetanephrine normalized at 285 (<900 mcg). Patient had complete resolution of presenting symptoms after adrenalectomy. Genetic testing is currently pending. Conclusion Our patient presented at 58 years old with symptoms masquerading as vasomotor menopausal symptoms that in retrospect predated perimenopause. Careful history, physical exam and past records review are important to best assist our patients. Adrenal nodules, independent of size, should undergo biochemical evaluation for hormonal excess, as per the Endocrine Society guidelines. Lack of typical symptoms of pheochromocytoma does not exclude this diagnosis as typical symptoms are seen with larger tumor size. Recent review studies demonstrate that more than half of pheochromocytoma cases are diagnosed serendipitously.

SUN-390 A Rare Case of Bilateral Macronodular Adrenal Hyperplasia Discovered Incidentally

Introduction: Asymptomatic adrenal masses are often discovered incidentally while testing for unrelated conditions. A very uncommon finding is thickening and increased nodularity of both adrenal glands, which can lead to the patient being diagnosed with subclinical Cushing's syndrome, Conn's syndrome, or both. Case presentation: A 45-year-old African-American man presented to the hospital with a one-month history of increased abdominal girth, bilateral lower extremity edema and shortness of breath, with progressive epigastric abdominal pain which prompted admission. His medical history was relevant for obesity, coronary artery disease and heart failure with reduced ejection fraction. On examination he had a blood pressure of 152/99 mmHg, was diaphoretic, and complained of constant epigastric pain. Multiple purple and pale striae were visible along his abdomen, and he had pitting edema in both lower extremities. His initial laboratory studies showed a potassium of 2.6 mEq/L. A CT scan of the abdomen was relevant for bilaterally enlarged and tortuous adrenal glands, which the patient had no previous knowledge of. Diuresis greatly improved his edema and shortness of breath. Additional laboratory tests showed persistent hypokalemia, normal plasma renin activity and aldosterone, elevated fasting cortisol, normal metanephrines in 24-hour urine collection, and low ACTH level. A suppression test done by administering dexamethasone 0.5 mg every 6 hours for 2 days, was able to suppress the elevated cortisol levels. He was started on spironolactone, and underwent MRI of the abdomen, which confirmed bilateral multinodular adrenal hyperplasia with no imaging characteristics of pheochromocytoma. The patient was discharged home once his clinical status improved. Laboratory studies done at follow-up appointments showed persistently elevated cortisol, normal aldosterone to renin ratio, normal levels of plasma metanephrines and suppressed levels of ACTH. He was also referred to surgery for eventual bilateral adrenalectomy. Discussion: Primary bilateral macronodular adrenal hyperplasia (BMAH) is a very rare cause of endogenous Cushing's syndrome, representing less than 2% of cases. It is characterized by enlarged adrenal glands containing pigmented nodules that secrete excess cortisol and/or aldosterone (1). BMAH is often an incidental finding in patients with subclinical hyper-cortisolism. A low level of plasma ACTH along with bilaterally enlarged adrenal glands on imaging suggest the diagnosis, and this is confirmed with a dexamethasone suppression test. Accurate detection is important for guiding management, which includes pharmacological therapy and bilateral adrenalectomy. Reference: 1. De Venanzi A, Alencar GA, Bourdeau I, Fragoso MCBV, Lacroix A. Primary bilateral macronodular adrenal hyperplasia. Curr Opin Endocrinol Diabetes Obes. 2014 Jun;21(3):177-84.

Triple-A syndrome: a wide spectrum of adrenal dysfunction

Triple-A or Allgrove syndrome is an autosomal recessive disorder due to mutations in the AAAS gene, which encodes a nucleoporin named ALADIN. It is characterized by a classical clinical triad: alacrima, achalasia and adrenal insufficiency, the canonic symptoms that are associated with progressive peripheral neuropathy. Only a few cohorts have been reported. The objective of the present study was to characterize the various spectra of adrenal function in Triple-A patients. A retrospective clinical and biological monitoring of 14 patients (10 families) was done in a single multidisciplinary French center. All had AAAS gene sequenced and adrenal function evaluation. Nine different AAAS mutations were found, including one new mutation: c.755G>C, p.(Trp252Ser). Regarding adrenal function, defects of the zona fasciculata and reticularis were demonstrated by increased basal ACTH levels and low DHEAS levels in all cases regardless of the degree of glucocorticoid deficiency. In contrast, mineralocorticoid function was always conserved: i.e., normal plasma renin level associated with normal aldosterone level. The main prognostic feature was exacerbation of neuropathy and cognitive disorders. These data suggest that, in Triple-A patients, adrenal function can be deficient, insufficient or compensated. In our cohort after the first decade of life, there does not appear to be any degradation of adrenal function over time. However, patients with compensated adrenal function should be informed and educated to manage a glucocorticoid replacement therapy in case of stressful conditions, with no need for systematic long-term treatment.

Striatin Gene Polymorphic Variants Are Associated With Salt Sensitive Blood Pressure in Normotensives and Hypertensives

Understanding the interactions between genetics, sodium (Na+) intake, and blood pressure (BP) will help overcome the lack of individual specificity in our current treatment of hypertension. This study had 3 goals: expand on the relationship between striatin gene (STRN) status and salt-sensitivity of BP (SSBP); evaluate the status of Na+ and volume regulating systems by striatin risk allele status; evaluate potential SSBP mechanisms. We assessed the relationship between STRN status in humans (HyperPATH cohort) and SSBP and on volume regulated systems in humans and a striatin knockout mouse (STRN+/-). The previously identified association between a striatin risk allele and systolic SSBP was demonstrated in a new cohort (P = 0.01). The STRN-SSBP association was significant for the combined cohort (P = 0.003; β = +5.35 mm Hg systolic BP/risk allele) and in the following subgroups: normotensives, hypertensives, men, and older subjects. Additionally, we observed a lower epinephrine level in risk allele carriers (P = 0.014) and decreased adrenal medulla phenylethanolamine N-methyltransferase (PNMT) in STRN+/- mice. No significant associations were observed with other volume regulated systems. These results support the association between a variant of striatin and SSBP and extend the findings to normotensive individuals and other subsets. In contrast to most salt-sensitive hypertensives, striatin-associated SSBP is associated with normal plasma renin activity and reduced epinephrine levels. These data provide clues to the underlying cause and a potential pathway to achieve, specific, personalized treatment, and prevention.

The Importance of Exclusion of Obstructive Sleep Apnea During Screening for Adrenal Adenoma and Diagnosis of Pheochromocytoma.

Context. As catecholamine elevation is a key element in the diagnosis of pheochromocytoma, more commonplace causes of sympathetic excess, such as obstructive sleep apnea (OSA), should be excluded as standard practice prior to diagnosis. This is essential to avoid misdiagnosis of adrenal incidentalomas identified in the estimated 42 million Americans with OSA, with greater than 4 million projected to undergo a computed tomography study annually. Case Description. A 56-year-old woman presented with a several year history of paroxysmal hypertension, palpitations, and diaphoresis. Abdominal/pelvic computed tomography performed during an unrelated hospitalization revealed a 2-cm left-sided adrenal nodule initially quantified at 37 Hounsfield units. Posthospitalization, 24-hour urine normetanephrine level was markedly elevated. Reassessment 2 weeks later revealed continued normetanephrine excess. Following normal thyroid function tests, morning cortisol, aldosterone, and plasma renin activity, laparoscopic adrenalectomy was performed. Surgical pathology identified an adrenal cortical adenoma. As paroxysms continued postoperatively, repeat 24-hour urine metanephrines were measured, demonstrating essentially unchanged normetanephrine elevation. Search for an alternate cause ensued, revealing OSA with progressive continuous positive airway pressure noncompliance over the preceding year. Regular continuous positive airway pressure therapy was resumed, and at the end of 7 weeks, 24-hour urine normetanephrine levels had declined. Conclusion. Pheochromocytomas are rare and sleep apnea is common. However, the overlap of clinical symptoms between these disorders is substantial, as is their ability to produce catecholamine excess. Thus, excluding uncontrolled or undiagnosed OSA in high-risk patients should be standard practice before diagnosing pheochromocytoma.

The renin–aldosterone axis in kidney transplant recipients and its association with allograft function and structure

The level of the renin-angiotensin-aldosterone system (RAAS) activity in kidney transplant recipients has not been extensively studied or serially profiled. To describe this axis and to determine its association with GFR change, interstitial expansion and end-stage renal disease (ESRD) we measured plasma renin activity (PRA) and plasma aldosterone levels annually for 5 years in 153 kidney transplant recipients randomly assigned to losartan or placebo. PRA and plasma aldosterone levels were in the normal range at all times and did not vary by immunosuppression regimen. Those on losartan exhibited higher PRA but similar plasma aldosterone levels. Neither baseline nor serial PRA or plasma aldosterone levels were associated with GFR decline, proteinuria or interstitial expansion. Losartan use, [HR 0.48 (95% CI 0.21–1.0), insignificant], and Caucasian donor, [HR 0.18 (95% CI 0.07–0.4), significant] were associated with less doubling of serum creatinine, death or ESRD. Hypertension, less than 3 HLA-matches, the combination of tacrolimus-rapamycin and acute rejection were associated with more events. Neither PRA nor plasma aldosterone levels were independently associated with this outcome. Higher serial plasma aldosterone levels were associated, however, with a significantly higher risk of ESRD, [HR 1.01 (95% CI 1.00–1.02)]. Thus, systemic RAAS is not overly activated in kidney transplant recipients but this may not reflect the intrarenal system. Importantly, plasma aldosterone levels may be associated with more ESRD.

Effect of upright posture on natriuresis, sympathetic nerve activity and atrial natriuretic peptide after acute saline infusion in young men with mild essential hypertension

Abnormal sodium excretion by the kidneys contributes to the pathogenesis of essential hypertension. We studied the effect of upright posture on natriuresis and hormone level after a saline infusion in 8 normotensive men (23±2years old<mean±SE>) and 14 men with mild essential hypertension (25±2years old) with normal plasma renin. All subjects were hospitalized and placed on a diet containing sodium chloride at 6g per day. Physiological saline was infused intravenously during 120min at a rate of 8.3mL·min−1, while we measured urinary sodium excretion (UNaV), endogenous creatinine clearance (CCr), renal blood flow (RBF), calculated from p-aminohippuric acid clearance and hematocrit, plasma noradrenalin concentration (PNE) and atrial natriuretic peptide concentration (PANP).