Hypoaldosteronism Research Articles

SUN-167 Treatment Considerations for a Healthy Pregnancy in Women with Classical Congenital Adrenal Hyperplasia (CAH)

Background:CAH is caused by an enzyme deficiency involved in cortisol synthesis leading to an increase in ACTH. Increased ACTH causes elevated levels of steroid hormone precursors & chronic stimulation of the adrenal glands resulting in hyperplasia. The most common form of CAH is due to 21OH deficiency (21OHD) with the classic, salt-wasting form causing glucocorticoid & mineralocorticoid deficiency & androgen excess.Poorly controlled CAH causes increased production of androgens & progesterone & decreased fertility. Fertility in woman with 21OHD can be challenging due to decreased sexual interest & anatomical abnormalities. Despite these challenges, the pregnancy rate is not significantly lower in women with well controlled 21OHD. However, as these patients are uncommon recommendations for pregnancy can be challenging for endocrinologists.Clinical Case:A 27-year old G0P0 female with classic, salt losing CAH presented to discuss pregnancy. Her medications were hydrocortisone 10mg qAM & 5mg qHS & fludrocortisone 0.1mg daily. She denied symptoms of dehydration, nausea, vomiting, dizziness, or fatigue.She was diagnosed with CAH while in-utero & started on steroid therapy after birth. She did not require any surgical genital reconstruction. Menarche occurred at age 11 and she had regular menses every 35-40 days, with no evidence of excessive androgen exposure including excess body hair, deepening of her voice, or cliteromegaly.On physical exam she was normotensive & had no evidence of virilization or cushingoid features. She exhibited minor darkening of the palmar creases. Her labs were significant for free testosterone of 9.1 pg/ml (0.2-5.0 pg/ml), total testosterone of 115 ng/dl (2-45 ng/dl), ACTH of 780 pg/ml (6-50 pg/ml), androstenedione of 636 ng/dl (41-262 ng/dl), & 17 OHP of 1560 ng/dl (15-290 ng/dl).Her hydrocortisone dose was increased to 20 mg qAM & 10 mg qHS & fludrocortisone 0.1mg daily was continued. Our objectives were to normalize the androgen level & suppress serum progesterone to less than 2 nmol/L. If the objectives were not reached she would be converted to prednisone BID.Conclusion:Endocrine providers are the primary resource for fertility recommendations for 21OHD patients & must understand the challenges in this very rare group of patients. Collaboration with the perinatologist is crucial for success.The goals of preconception endocrine assessment in a patient with classic CAH are to adjust hormone therapy to ensure optimal endocrine milieu for conception & risk assessment of having a child affected with 21OHD. The patient will need a higher dose of fludrocortisone during the later part of pregnancy. Counseling that stress doses of glucocorticoids for intercurrent illness and during labor and delivery are required for both the patient and the obstetrician.

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.

MON-LB038 Isolated Hypoaldosteronism Due to Autoimmune Adrenalitis in a Patient With Autoimmune Polyglandular Syndrome

BACKGROUNDAt the initial presentation of autoimmune adrenal insufficiency, most patients present with hormonal deficiencies from all three layers of adrenal cortex. However, isolated aldosterone deficiency causing a true partial adrenal insufficiency in the setting of autoimmune adrenalitis remains underrecognized.CASE REPORTA 67-year old female patient with a known history of diabetes mellitus type 1 since the age of 13 and morphea, presented with progressively worsening symptoms of confusion and hallucinations, fatigue, and loss of appetite over the past 5 years. During this time, she has had frequent and recurrent episodes of mild intermittent hyponatremia with hyperkalemia requiring intravenous fluids and ingested salt tablets, especially when she felt more symptomatic. On her initial evaluation here, she presented with hyponatremia (125 mmol/l, n: 135-145 mmol/l), low osmolality (264 mOsm/kg, n: 275-295 mOsm/kg), and normal potassium level (3.6 mmol/l, n: 3.6-5.2 mmol/l). Further investigations drawn at the same time revealed a low aldosterone (<4 ng/dL), normal renin (5.3 ng/mL/hr, ref 2.9-10.8), normal serum cortisol level (and normal response to Cortrosyn stimulation), though all in the setting of positive antibodies against 21-hydroxylase. Pan-imaging revealed no evidence of malignancy that can be causing ectopic SIADH production. Additional testing showed presence of auto antibodies contributing to pernicious anemia and thyroid disease. Treatment was started with fludrocortisone 0.1 mg tablet daily and she was advised to take the salt tablets only if she has any symptoms. The patient’s symptoms have resolved 8 months since this diagnosis, with normalized sodium and potassium levels.CONCLUSIONAutoimmune primary adrenal insufficiency usually affects all three layers of the adrenal cortex, where patients present with deficiencies in cortisol and aldosterone. Isolated hypoaldosteronism has rarely been reported, however because it can cause life-threatening hyponatremia, it is an important entity to recognize. It is important to work up in such patients as they may be in the initial stages of autoimmune Addison’s disease and can progress to developing cortisol deficiency, though the time course to this progression is not well known.

Hyponatremia and Hyporeninemic-Hypoaldosteronism in a Pediatric Intensive Care Unit Patient

Hyponatremia is one of the most commonly encountered electrolyte abnormalities encountered in the pediatric world. Defined as a serum or plasma sodium less than 135 mEq/L, the etiology of hyponatremia is one that can typically be determined by performance of a thorough history. However, occasionally the etiology of a patient’s hyponatremia is more elusive and determined only after laboratory evaluation. We present a 6-year-old girl with a complex medical history including spinal muscular atrophy, tracheostomy and ventilator dependence, who was admitted to the pediatric intensive care unit for treatment and evaluation of seizures with hyponatremia that was initially thought to be due to syndrome of inappropriate anti-diuretic hormone or cerebral salt wasting. However, during her hospital course, it was determined that the hyponatremia was more indicative of a rarer and much less common cause of hyponatremia, hyporeninemic-hypoaldosteronism. The physiological factors controlling serum sodium are reviewed, the etiologies of hyponatremia are presented and the treatment of hyporeninemic-hypoaldosteronism is discussed. J Med Cases. 2020;11(4):100-102 doi: https://doi.org/10.14740/jmc3457

Therapeutic Renin Inhibition in Diabetic Nephropathy-A Review of the Physiological Evidence.

The purpose of this systematic review was to investigate the scientific evidence to support the use of direct renin inhibitors (DRIs) in diabetic nephropathy (DN). MEDLINE was searched for articles reported until 2018. A standardized dataset was extracted from articles describing the effects of DRIs on plasma renin activity (PRA) in DN. A total of three clinical articles studying PRA as an outcome measure for DRIs use in DN were identified. These clinical studies were randomized controlled trials (RCTs): one double-blind crossover, one post hoc of a double-blind and placebo-controlled study, and one open-label and parallel-controlled study. Two studies reported a significant decrease of albuminuria associated with PRA reduction. One study had a DRI as monotherapy compared with placebo, and two studies had DRI as add-in to an angiotensin II (Ang II) receptor blocker (ARB). Of 10,393 patients with DN enrolled in five studies with DRI, 370 (3.6%) patients had PRA measured. Only one preclinical study was identified that determined PRA when investigating the effects of aliskiren in DN. Moreover, most of observational preclinical and clinical studies identified report on a low PRA or hyporeninemic hypoaldosteronism in DM. Renin inhibition has been suggested for DN, but proof-of-concept studies for this are scant. A small number of clinical and preclinical studies assessed the PRA effects of DRIs in DN. For a more successful translational research for DRIs, specific patient population responsive to the treatment should be identified, and PRA may remain a biomarker of choice for patient stratification.

SUN-067 Severe acute hyponatraemia in a patient with Sjogren's syndrome

Sjogren's syndrome is an auto-immune rheumatological condition associated with joint pains, dry eyes and mouth. It has previously been associated with syndrome of inappropriate anti-diuretic hormone (SIADH) (de Villiers, Willem & Klemp, P., 1991) and with hyporeninaemic hypoaldosteronism (Onozaki, Akira et al.) as potential causes of hyponatraemia, however the literature is sparse. Sjogren's syndrome is associated with other renal diseases diagnosed on biopsy such as renal tubular acidosis, glomerulonephritis and interstitial nephritis. This case explores a patient with a more severe episode of hyponatraemia in the context of background renal salt wasting and strong immunological and clinical evidence of Sjogren's syndrome. The information from this case report was gathered retrospectively from the patient's case notes and test results with their explicit consent. The patient was admitted under the medical team generally unwell with acute confusion in July of 2018. They were normally completely well, only taking lansoprazole (a proton pump inhibitor) and ramipril (an angiotensin converting enzyme inhibitor (ACE-I)) for hypertension. They were found to have a serum sodium of 109mmol/l and were given 2.7% sodium chloride intravenously. Renal function, measured with creatinine, was stable at the patient's baseline throughout the admission. The patient was then taken to an intensive care setting and further tests showed a urinary sodium of 64 mmol/l, a urinary osmolality of 476 and serum osmolality of 237 mosm/kg H20. This was felt to be due to renal salt wasting or potentially SIADH. There were no suspicious lung lesions on x-ray imaging despite the patient being an active smoker. The patient improved clinically and biochemically with fluid restriction to 1.5L daily and sodium rose to 131mmol/l over 6 days of this management. Cortisol was in the normal range and urinary sodium fell to 24mmol/l. The patient had been complaining of joint pains and dry mouth and eyes from before admission and further outpatient tests showed positive anti-CCP antibodies, strong positive to anti-Ro and anti-La antibodies and increased IgG. They were seen by rheumatology in the next 9 months who diagnosed Sjogren's syndrome with palindromic rheumatism of the hand joints. Tests in October 2019 show a persistently low serum sodium at 129mmol/l and a urinary sodium of 71mmol/l. Serum osmolality is now normal at 278 mosm/kg H20 and osmolality of urine is 553 mmol/kg. Renin and aldosterone levels are now normal. The patient is now clinically well with no symptoms of hyponatraemia and is not on any specific treatment for Sjogren's syndrome. The onset of symptoms associated with Sjogren's syndrome coincided with the acute severely hyponatraemic episode described above. Tests are consistent with renal salt wasting or SIADH which is not commonly described in existing literature. An association between hyponatraemia and Sjogren's may help to shed light into the effects of Sjogren's on the kidney. Whilst it has been associated with intersitial nephritis, renal tubular acidosis or glomerulonephritis (Goules et al. 2019) the association with acute, severe hyponatraemia has been less described. In this patient there is suspicion for ongoing hyponatraemia caused by Sjogren's syndrome given recent test results, the definite mechanism of which is unclear.

Congenital Adrenal Hyperplasia: Diagnostic Features in a Limited Resource Country, Senegal

Introduction: Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive diseases characterized by enzymatic deficiencies in the biosynthesis of adrenal steroids. The most common 21-hydroxylase deficiency is characterized by a cortisol deficiency and an excess of androgens, with or without aldosterone deficiency. In our countries, in the absence of neonatal screening, the diagnosis is most often late leading to life-threatening complications. The aim of this study was to describe the diagnostic features of CAH at the Albert Royer National Children’s Hospital (ARNCH) in Dakar. Patients and method: We conducted a retrospective, descriptive study carried out at the pediatric endocrinology department of ARNCH from 2015 to 2019. All children aged under 15 with a form of CAH were included. Socio-demographic data, family history, clinical and biochemical data at presentation were collected. Patients were noted as presenting with Disorder of Sexual Development (DSD) with dehydration, DSD without dehydration, dehydration without DSD, precocious puberty. The Prader’s scale was used to determine the degree of external virilization. These data were entered and analyzed with Epi Info version 7.2. Results: A total of 32 patients were included, representing 74.41% of the causes of disorder of sexual development (DSD) and 84.21% of the causes of adrenal insufficiency. These were 27 girls (84.37%) and 5 boys (15.63%). The mean age was 19 ± 34.6 months. DSD was the main finding (87.5%). It was associated with dehydration in 22 cases (68.75%). 21-hydroxylase deficiency represented 93.75% of the cases with salt wasting in 73.33% of the cases. Conclusion: The diagnosis of CAH was delayed leading to life-threatening adrenal crises. In the absence of neonatal screening for CAH in Senegal, there is a need to train healthcare workers to recognize neonates with DSD early and refer them timeously for specialist care.

Aldosterone deficiency type 1 due to mutation of the CYP11B2

Aldosterone deficiency type 1 due to mutation of the CYP11B2

Evolving Adrenal Dysfunction After Bilateral Adrenal Infarction: A Case Report

To describe a case of sequential bilateral adrenal infarction and hemorrhage resulting in an unusual pattern of adrenal function over time. A 50-year-old male with autoimmune antiphospholipid syndrome (APS) presented to the emergency room with severe abdominal pain. Diagnostic studies performed included contrast-enhanced computerized tomographic (IV-CT) imaging of abdomen and pelvis, and laboratory assessment of the hypothalamic-pituitary-adrenal axis. IV-CT of abdomen and pelvis on day 1 showed acute left adrenal gland infarction; cortisol level was 19.9 μg/dL and serum sodium was 133 mEq/L. The patient subsequently developed hyponatremia and hypotension. Repeat IV-CT of abdomen and pelvis on day 3 showed hemorrhagic conversion of the left infarcted adrenal gland and a new right adrenal gland infarction. Cosyntropin stimulation test (CST) confirmed primary glucocorticoid insufficiency. Plasma renin activity and the serum aldosterone level were within normal limits with normokalemia. At 7-month follow-up, CST demonstrated cortisol and aldosterone deficiency. Adrenal infarction is a rare complication of APS but is the most common endocrine complication. Evidence of bilateral adrenal infarction on imaging does not predict the type of adrenal dysfunction that might ensue, as demonstrated in this case. Thorough evaluation of glucocorticoid, mineralocorticoid, and androgen deficiency should be conducted both at the time of the event and in follow-up.

SAT-069 A Case of Congenital Hypoaldosteronism Due to Aldosterone Synthase Deficiency Misdiagnosed as Classic Congenital Adrenal Hyperplasia

Background: The clinical presentation of congenital hypoaldosteronism due to aldosterone synthase (aka corticosterone methyloxidase; CMO) deficiency varies with age and infants present with signs/symptoms of isolated mineralocorticoid deficiency. Classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) is characterized by combined glucocorticoid, mineralocorticoid deficiency and androgen excess. Clinical Case: A 6.8 y/o Female was referred for genetic testing for classic 21OHD CAH. Past History: Birth weight/length: 7.9 lbs/20 inches at term, uncomplicated pregnancy. Normal female genitalia. She presented within the 1st week of life with poor feeding and poor weight gain. Newborn screen - normal. Inpatient admission at 1 month for failure to thrive. Initial workup significant for Na 127 mg/dL (135 - 145), K 6.5 mg/dL (3.4 - 5.3), mildly elevated random 17hydroxyprogesterone (17OHP) 241 ng/dL (32 - 139) and cortisol 11.6 mcg/dL. She was diagnosed with CAH and initiated on hydrocortisone and fludrocortisone therapy. Medications: Hydrocortisone 2.5 mg twice daily (6.3 mg/m2/day), fludrocortisone 50 mcg daily. Family History: Non-contributory, mid-parental height 154.9 cm. Physical exam: Height 115.6 cm (20th %ile), weight 19.8 kg (18th %ile), BP 109/65 mmHg (95th/ 84th %ile). Well-appearing with no cushingoid features. Genital/pubertal exam: Prepubertal, normal female external genitalia. Laboratory tests: ACTH stimulation test was performed which showed - 0min: 17OHP 19 ng/dL, Cortisol 8 mcg/dL; 60min: 17OHP 155 ng/dL (<1000), Cortisol 23.4 mcg/dL (normal response >18), ruling out the diagnosis of classic 21OHD CAH. Hydrocortisone was discontinued. Further workup (holding fludrocortisone for 48hrs) showed mildly elevated plasma renin activity 3.5 ng/mL/hr (0.8 - 2), low aldosterone 1.8 ng/dL (3.5 - 124), normal 18-hydroxycorticosterone 11 ng/dL (6 - 85). 18-hydroxycorticosterone/aldosterone ratio 6.1 (ratio <10) - suggesting the diagnosis of CMO type I deficiency (1). Targeted genetic testing for CYP11B2 revealed a novel homozygous frameshift alteration in exon 3: p.Phe157Serfs*108 (c.451_469dup), a pathogenic variant predicted to lead to protein truncation and loss of function. Conclusions: This case demonstrates that the clinical presentation of isolated mineralocorticoid deficiency often overlaps features of combined glucocorticoid and mineralocorticoid deficiency. Normal newborn screen along with absence of virilization in a female infant should alert a clinician to consider isolated mineralocorticoid axis defects. The gold standard ACTH stimulation test should be performed to rule out classic CAH and avoid unnecessary glucocorticoid replacement and its long-term side effects. Reference: 1. Root AW, Disorders of aldosterone synthesis, secretion, and cellular function. Curr Opin Pediatr. 2014 Aug;26(4):480-6.

SAT-090 Autonomic Dysfunction and Hypoaldosteronism Before and After CABG: Case Report and Literature Review

INTRODUCTION: The sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) are the cornerstones of cardiovascular adaptation.Autonomic dysfunction produces symptoms that overlap with hypofunction of the RAAS, namely hypoaldosteronism. The simultaneous presence of both disorders is not uncommon, especially in patients with CAD undergoing CABG surgery. Objective: This is the case of a patient with recurrent episodes of syncope and severe bradycardia, found to have both hyporeninemic hypoaldosteronism and carotid sinus hypersensitivity. We describe those interrelated phenomena and their association with CAD and CABG surgery. Case presentation: Our patient is a 63-year-old male with a history of hypertension (On Bisoprolol, Valsartan and Hydrochlorothiazide) and hyperlipidemia presenting for coronary artery bypass grafting for triple vessel disease. On the day of admission, the patient lost consciousness briefly and was transiently hypotensive (60/30 mm Hg) with a heart rate of 65 bpm. He reported having had similar self resolving episodes in the past at times of emotional stress. The next day, the patient underwent CABG surgery that was uneventful. Four hours later he developed another episode of unprovoked hypotension that resolved with the administration of neosynephrine. On postoperative day 3, while removing the central line from the right IJ vein, he lost consciousness and had a cardiac pause of 5 seconds. His blood pressure was 70/45 mm Hg. He regained consciousness immediately afterwards upon leg elevation. A carotid massage resulted in a 7 seconds cardiac pause, confirming the presence of carotid sinus hypersensitivity, necessitating the insertion of a pacemaker. However the patient lost consciousness again the next morning despite a normal functioning device. Endocrinology work up was initiated to rule out adrenal insufficiency. It revealed an undetectable aldosterone level with a low-normal renin level, ie hyporeninemic hypoaldosteronism.No hyponatremia, hyperkalemia, renal insufficiency or hypocortisolism were noted. Patient was started on fludrocortisone 0.1 mg daily, and his hemodynamics improved.He remained free of symptoms with normal electrolytes and vital signs on follow up since then. Conclusion: This case describes coexistence of hyporeninemic hypoaldosteronism and carotid sinus hypersensitivity. Although both entities might seem unrelated, a review of the literature and the physiology of cardiovascular hemodynamics revealed that CAD leads to autonomic dysfunction, which can present as carotid sinus hypersensitivity as in our case. In turn, the impaired adrenergic function blocks the activation of renin, leading to hypoaldosteronism and hypofunctioning RAAS. CABG surgery unmasked those interrelated entities. Patient was treated successfully with pacemaker placement and fludrocortisone replacement.

MON-399 Congenital Adrenal Hyperplasia Newly Diagnosed in an Octogenarian

Relevance: The most common form of congenital adrenal hyperplasia (CAH) is 21-hydroxylase deficiency, in which a block in cortisol biosynthesis shifts precursors to pathways that make excess adrenal-derived androgens. We report a rare case in which a new diagnosis of CAH due to 21-hydroxylase deficiency occurred in an octogenarian. Clinical case: An 82 year old man presented for evaluation of persistent headache, anorexia, and unintentional weight loss. He was found to have acute worsening of chronic hyponatremia and hyperkalemia with presenting sodium and potassium levels of 121 and 5.8 mEq/L, respectively. He had increased skin pigmentation, but no hypotension or orthostasis. These findings prompted evaluation of his HPA axis. His AM cortisol was 11.9 mcg/dL (6.7-22.6) and ACTH was 1,036 pg/dL (7.2-63.3). After cosyntropin stimulation, his cortisol remained 10.8 at 30 minutes and 10.5 at 60 minutes. DHEA-S was 34.1 mcg/dL (20.8 - 226.4), Renin was 11.5 ng/mL/hr (0.2-5.4) and Aldosterone was < 1.0 ng/dL (0-30). Further hormonal testing showed an AM testosterone 788 ng/dL (264-916), which was higher than expected given the normal age related decline in testosterone. LH was 3.9 mIU/mL (1.2-8.6), FSH was 4.9 mIU/mL (1.3-19.3) and prolactin was 15.4 ng/mL (4.0-15.2). Oral hydrocortisone was initiated: 10mg in the morning and 5mg in the afternoon, in addition to florinef 0.1mg daily. By hospital day 4, his hyperkalemia and hyponatremia had normalized, his headaches resolved, and his appetite improved. Review of a prior CT chest/abdomen/pelvis (done for unintentional weight loss) demonstrated normal adrenal glands with no evidence of malignancy, hemorrhage, enlargement, or atrophy. 21-hydroxylase antibodies were undetectable. On further history, the patient disclosed that adrenarche occurred at age 6. He had short stature in his youth and was treated with growth hormone injections. He and his wife had difficulty conceiving and he was told of low sperm motility but ultimately had three children by natural conception. An insidious presentation of CAH was suspected based on this history and the high normal testosterone levels in this octogenarian. After uninterrupted treatment with hydrocortisone for two weeks, 17-hydroxy progesterone was 800 ng/dL (27-199), his ACTH improved to 660 and his testosterone decreased to 494. A 21-hydroxylase mutational analysis is pending. Conclusions: Classical CAH is typically diagnosed in infancy or youth in the setting of adrenal insufficiency with/without salt wasting, ambiguous genitalia in female infants or virilization. Although atypical to go undiagnosed for decades, non-classic CAH should be considered as a cause of aldosterone and cortisol deficiency, even among elderly patients, who present with signs and symptoms concerning for adrenal insufficiency. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

MON-359 Primary Adrenal Insufficiency Secondary to Chronic Use of Posoconazole: A Case Report

Cortisol attenuates inflammatory responses, contributes with glucose homeostasis, and enhances vascular smooth muscle tone augmenting blood pressure among other functions. The symptoms and signs of adrenal insufficiency (AI) depend upon acuity and degree of loss of the adrenal function, including whether mineralocorticoid production is preserved or not. A 65 years-old male with past medical history of mixed connective tissue disease developed 2 weeks of fever and was diagnosed with hemophagocytic lymphohistiocytosis for which he was placed on HLH-94 protocol (ectoposite and high dose pulse steroids). He was also found to have invasive murcomycosis initially treated with amphotericin and posacolonazole(PSO). Given the culture results, amphotericin was stopped and PSO 500mg daily was continued. The patient had a complicated hospital course and was discharged on 2mg of dexamethasone with a pertinent taper. He developed weakness and failure to thrive. His dexamethasone was increased to 3mg daily by his oncologist, and his PSO and chemotherapy was continued. Due to worsen fatigue and deconditioning the patient was brought to the Emergency Room. Upon arrival he was noticed to have persistent orthostatic hypotension despite intravenous fluids, hyponatremia and hyperkalemia (what is the potassium) suggestive of mineralocorticoid deficiency. Further endocrinology workup revealed plasma renin activity of 16.7ng/ml/hr (0.167-5.380) with a low aldosterone level of 1.6ng/dl (0.0-30). CT abdomen imaging showed intact adrenal glands bilaterally. Patient was diagnosed with PSO induced primary AI, he was placed on fludrocortisone with significant symptoms improvement and normalization of electrolytes and blood pressure. After a thorough literature review we found two case reports of iatrogenic Cushing in patients using Fluticasone and PSO, three cases of steroid induced secondary AI in patients treated with inhaled budesonide and PSO; and two cases of primary adrenal insufficiency in patients using PSO without steroids. PSO effects in the adrenal axis are rare, clinicians should be aware of their potential effects on the hypothalamic-pituitary-adrenal axis and pharmacologic interactions with steroids.

MON-268 A Rare Case of Primary Hypoaldosteronism in a Newborn

BACKGROUND: Primary aldosterone synthase deficiency (ASD) is a rare but potentially life-threatening cause of mineralocorticoid deficiency primarily due to a defect in CYP11B2, which encodes aldosterone synthase. There are two types of ASDs, both resulting in primary hypoaldosteronism, but due to differences in blockade of the terminal oxidation step, are distinguished by low 18-hydroxycorticosterone (18-OHC) in Type 1 and elevated 18-OHC in Type 2. With a wide variation in clinical severity and presentation, few cases of ASD have been reported. CLINICAL CASE: A 10-day old full term male infant born to unrelated parents of European descent presented with weight loss, poor feeding and dehydration, in the setting of hyponatremia (Na 127 mM, ref 131-145 mM) and hyperkalemia (K 8 mM, ref 3.2-6 mM). He had normal genitalia and no hyperpigmentation on exam. A cosyntropin stimulation test resulted in a cortisol of 19 μg/dL. Electrolytes transiently improved with normal saline but worsened after fluids were discontinued. Oral NaCl was initiated at a dose of 4 mEq/kg/day and titrated to 6 mEq/kg/day. Aldosterone levels while hyponatremic were inappropriately low (<35 ng/dL, ref <218 ng/dL) with elevated plasma renin activity (PRA) of 112 ng/mL/hr (ref 0.25-5.82 ng/mL/hr), consistent with primary hypoaldosteronism. On day 14 of life, fludrocortisone was started at 0.05 mg/day and increased to 0.2 mg/day until Na and K levels normalized. At 20 days of life he was discharged, only to return 3 days later with isolated hyperkalemia (K 6.4 mM), PRA elevation to 80 ng/mL/hr, and lethargy. Prior 18-OHC and corticosterone levels returned significantly low at <26 ng/dL and <40 ng/dL respectively, consistent with a diagnosis of Type 1 ASD. Subsequently, fludrocortisone was increased to 0.3 mg/day and NaCl to 8 mEq/kg/day. At 6 months, the infant continues to do well though growth velocity remains slightly impacted. However, due to suppressed PRA levels and hypertension on exam, fludrocortisone was reduced to 0.05 mg/day and NaCl to 4.5 mEq/kg/day. Given the rarity of Type 1 ASD, he was referred for genetic counseling to obtain molecular confirmation. CONCLUSION: This is a rare case of Type 1 ASD diagnosed in early infancy based on inappropriately low 18-OHC and aldosterone levels during times of hyponatremia or hyperkalemia requiring high doses of mineralocorticoid and salt replacement in the first few months of life. While ASD is generally considered less severe than CAH, it can present with recurrent dehydration, salt wasting and failure to thrive, and be lethal if not recognized promptly. Despite timely treatment, growth retardation can still occur. Long term follow-up is needed to better understand the natural history of ASD, though clinical severity may decrease with age. As it is not included in newborn screening, this case highlights the importance of suspecting ASD in infants with hyponatremia and hyperkalemia.

Neonatal adrenal insufficiency: Turkish Neonatal and Pediatric Endocrinology and Diabetes Societies consensus report.

It is difficult to make a diagnosis of adrenal insufficiency in the newborn, because the clinical findings are not specific and the normal serum cortisol level is far lower compared to children and adults. However, dehydratation, hyperpigmentation, hypoglycemia, hyponatremia, hyperkalemia and metabolic acidosis should suggest the diagnosis of adrenal insufficiency. Hypotension which does not respond to vasopressors should especially be considered a warning. If the adrenocorticotropin hormone level measured simultaneously with a low serum cortisol level is 2-fold higher than the upper normal limit of the reference range, a diagnosis of primary adrenal insufficiency is definite. Even if the serum cortisol level is normal, a diagnosis of relative adrenal insufficiency can be made with clinical findings, if the patient is under heavy stress. The serum cortisol level should be measured using the method of ‘high pressure liquid chromatography’ or ‘LC mass spectrometry’. Adrenal steroid biosynthesis can be evaluated more specifically and sensitively with ‘steroid profiling’. Rennin and aldosterone levels may be measured in addition to serum electrolytes for the diagnosis of mineralocorticoid insufficiency. Adrenocorticotropic hormone stimulation test may be used to confirm the diagnosis and elucidate the etiology. In suspicious cases, treatment can be initiated without waiting for the adrenocorticotropic hormone stimulation test. In schock which does not respond to vasopressors, intravenous hydrocortisone at a dose of 50-100 mg/m2 or a glucocorticoid drug at an equivalent dose should be initiated. In maintanence treatment, the physiological secretion rate of hydrocortisone is 6 mg/m2/day (15 mg/m2/day in the newborn). The replacement dose should be adjusted with clinical follow-up and by monitoring growth rate, weight gain and blood pressure. Fludrocortisone (0,1 mg tablet) is given for mineralocorticoid treatment (2x0,5-1 tablets). A higher dose may be needed in the neonatal period and in patients with aldosterone resistance. If hyponatremia persists, oral NACl may be added to treatment. In the long-term follow-up, patients should carry an identification card and the glucocorticoid dose should be increased 3-10-fold in cases of stress.

Refractory Hypotension post Coronary Artery Bypass Graft Unmasking Hypoaldosteronism: Case Report and Literature Review

The sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) are the cornerstones of cardiovascular adaptation. The simultaneous presence of disorders involving both is not uncommon, especially in patients with coronary artery disease undergoing coronary artery bypass surgery (CABG). This is the case of a patient with both hyporeninemic hypoaldosteronism and autonomic dysfunction. This article describes his clinical course before and after CABG surgery, along with a literature review of those interrelated entities. Our patient is a 63-year-old male with a history of hypertension and hyperlipidemia presenting for CABG for triple vessel disease. On the day of admission, the patient had sudden unprovoked loss of consciousness along with hypotension and bradycardia. He reported having had similar episodes in the past at times of emotional stress. After stabilization, the patient underwent CABG surgery the next day and it was uneventful. Four hours later, he developed another episode of hypotension with bradycardia which resolved upon administration of fluids. On postoperative day 2, while removing the jugular line, he had loss of consciousness with 5 seconds pause recorded on his bedside monitor. A carotid massage confirmed carotid sinus hypersensitivity, which necessitated the insertion of a pacemaker. However, patient continued to have similar episodes despite a functioning device. Workup revealed hyporeninemic hypoaldosteronism with an undetectable aldosterone level, although patient was not diabetic, had normal cortisol level, and had no other risk factors for those findings. Patient was started on fludrocortisone 0.1 mg daily; his hemodynamics improved markedly, and his symptoms resolved permanently. Our patient has hyporeninemic hypoaldosteronism caused most likely by his autonomic dysfunction, rather than having of two separate entities. A review of the literature showed that primary autonomic insufficiency with reduced circulating norepinephrine levels prevent renin activation and subsequently aldosterone release, leading to hyporeninemic hypoaldosteronism. Coronary artery disease is a known cause of autonomic dysfunction and CABG surgery unmasks this entity, which explains the exacerbation of our patient’s symptoms during this phase.

An Update on Addison's Disease.

Addison's disease - the traditional term for primary adrenal insufficiency (PAI) - is defined as the clinical manifestation of chronic glucocorticoid- and/or mineralocorticoid deficiency due to failure of the adrenal cortex which may result in an adrenal crisis with potentially life-threatening consequences. Even though efficient and safe pharmaceutical preparations for the substitution of endogenous gluco- and mineralocorticoids are established in therapy, the mortality in patients with PAI is still increased and the health-related quality of life (HRQoL) is often reduced.PAI is a rare disease but recent data report an increasing prevalence. In addition to the common "classical" causes of PAI like autoimmune, infectious, neoplastic and genetic disorders, other iatrogenic conditions - mostly pharmacological side effects (e. g., adrenal haemorrhage associated with anticoagulants, drugs affecting glucocorticoid synthesis, action or metabolism and some of the novel anti-cancer checkpoint inhibitors) are contributing factors to this phenomenon.Due to the rarity of the disease and often non-specific symptoms at least in the early stages, PAI is frequently not considered resulting in a delayed diagnosis. Successful therapy is mainly based on adequate patient education as a cornerstone in the prevention and management of adrenal crisis. A focus of current research is in the development of pharmacokinetically optimized glucocorticoid preparations as well as regenerative therapies.

Addison's disease in antiphospholipid syndrome: a rare complication.

SummaryAddison’s disease (AD) is the most common endocrine manifestation of antiphospholipid syndrome (APS), but it remains a very rare complication of the syndrome. It is caused by adrenal venous thrombosis and consequent hemorrhagic infarction or by spontaneous (without thrombosis) adrenal hemorrhage, usually occurring after surgery or anticoagulant therapy. We present a clinical case of a 36-year-old female patient with a previous diagnosis of APS. She presented with multiple thrombotic events, including spontaneous abortions. During evaluation by the third episode of abortion, a CT imaging revealed an adrenal hematoma, but the patient was discharged without further investigation. A few weeks later, she presented in the emergency department with manifestations suggestive of adrenal insufficiency. Based on that assumption, she started therapy with glucocorticoids, with significant clinical improvement. After stabilization, additional investigation confirmed AD and excluded other etiologies; she also started mineralocorticoid replacement. This case illustrates a rare complication of APS that, if misdiagnosed, may be life threatening. A high index of suspicion is necessary for its diagnosis, and prompt treatment is crucial to reduce the morbidity and mortality potentially associated.Learning points:AD is a rare but life-threatening complication of APS.It is important to look for AD in patients with APS and a suggestive clinical scenario.APS must be excluded in patients with primary adrenal insufficiency and adrenal imaging revealing thrombosis/hemorrhage.Glucocorticoid therapy should be promptly initiated when AD is suspected.Mineralocorticoid replacement must be started when there is confirmed aldosterone deficiency.Hypertension is a common feature of APS; in patients with APS and AD, replacement therapy with glucocorticoids and mineralocorticoids may jeopardize hypertension management.

Successful Use of Fludrocortisone in a Child with Refractory Cerebral Salt Wasting Syndrome: A Case Report and Review of Literature

Hyponatremia post-neurosurgical intervention can be dangerous and potentially life-threatening. Two of its most common causes are cerebral salt wasting (CSW) and syndrome of inappropriate anti-diuretic hormone release (SIADH). CSW is proposed to be secondary not only to the elevated levels of circulating atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) but inhibition of steroidogenesis in the zona glomerulosa of the adrenal cortex, thus resulting in mineralocorticoid deficiency. We present a two-year-old male who had developed acute hyponatremia secondary to CSW on post-operative day two after a sub-total resection of a low-grade juvenile pilocytic astrocytoma (WHO grade I). Fludrocortisone was successfully used to manage the refractory hyponatremia and alleviated the need to use very large amounts of oral sodium supplementation.

Aldosterone deficiency in mice burdens respiration and accentuates diet-induced hyperinsulinemia and obesity.

Aldosterone synthase inhibitors (ASIs) should alleviate obesity-related cardiovascular and renal problems resulting partly from aldosterone excess, but their clinical use may have limitations. To improve knowledge for the use of ASIs, we investigated physiology in aldosterone synthase-knockout (ASKO) mice. On regular chow diet (CD), ASKO mice ate more and weighed less than WT mice, largely because they hyperventilated to eliminate acid as CO2. Replacing CD with high-fat diet (HFD) lessened the respiratory burden in ASKO mice, as did 12- to 15-hour fasting. The latter eliminated the genotype differences in respiratory workload and energy expenditure (EE). Thus, aldosterone deficiency burdened the organism more when the animals ate carbohydrate-rich chow than when they ate a HFD. Chronic HFD exposure further promoted hyperinsulinemia in ASKO mice that contributed to visceral fat accumulation accompanied by reduced lipolysis, thermogenic reprogramming, and the absence of weight-gain-related EE increases. Intracerebroventricular aldosterone supplementation in ASKO mice attenuated the HFD-induced hyperinsulinemia, but did not affect EE, suggesting that the presence of aldosterone increased the body's energetic efficiency, thus counteracting the EE-increasing effect of low insulin. ASIs may therefore cause acid-overload-induced respiratory burden and promote obesity. Their use in patients with preexisting renal and cardiopulmonary diseases might be contraindicated.