bluuebunny/crossref_metadata_2025 huggingface dataset:
7112 A Case of Bilateral Adrenal Insufficiency Associated With Borderline Lupus and Antiphospholipid Syndrome
Authors: Hernandez Mendiola Karla Maria
Published: October 2024

Disclosure: K.M. Hernandez Mendiola: None.

Bilateral adrenal hemorrhage (BAH) is a rare condition leading to acute adrenal insufficiency with a mortality rate of 15%. Known etiologies include abdominal trauma, adrenal vein thrombosis, sepsis, shock, and anticoagulation. Systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) are uncommon conditions associated with BAH. We describe here a 79-year-old woman with a history of hypertension and a 23-year history of borderline SLE treated with hydroxychloroquine (HCQ) who presented at the ED with epigastric pain, diarrhea, and nausea. Six months before, HCQ was discontinued. The exam showed no abnormal findings, and an abdominal CT showed inflammation of the ascending colon. Augmentin was instituted, and the patient was sent home. After a week, the patient returned to the ED due to the persistence of symptoms, complaining of fatigue and right lower quadrant abdominal pain. Upon examination, the abdomen was soft but tender, with the CT suggesting pancolitis, while an MRI showed BAH. Laboratory findings included anemia, thrombocytopenia, elevated PT, low fibrinogen, and 11 mcg/dl cortisol. The patient was then admitted to the hospital, and hydrocortisone (HCT) therapy was initiated. After 12 hours of glucocorticoid initiation, cortisol level was 37 mcg/dl. On day 1, the patient remained hemodynamically stable. On day 2, a positive lupus anticoagulant was detected, with cortisol level dropping to 2 mcg/dl, warranting the continuation of HCT. From day 3 to 6, the patient suffered worsening coagulation and kidney functions. By day 7, an abdominal CT showed an extension of BAH. On day 8, the patient experienced a cerebral intraparenchymal hemorrhage and was transferred to the ICU, where, after two days passed away. The report presented here describes a catastrophic case of BAH associated with borderline SLE and APS in a patient who previously discontinued long-term treatment with HCQ, thereby enhancing the likelihood of a lupus flare-up. The adrenal glands are susceptible to thrombosis and hemorrhage due to their rich vascularity. In stress, the adrenals receive a significant blood volume, causing vascular congestion, potentially exceeding their capacity for venous drainage, and increasing the risk of hemorrhage. Autoimmune conditions, particularly SLE and APS, have been implicated in the etiology of adrenal hemorrhage. Antiphospholipid antibodies may bind to phospholipid-binding plasma proteins, promoting thrombosis in the adrenal vein by disrupting the coagulation fibrinolysis balance and the adrenal blood outflow, ultimately causing bleeding into the adrenal gland parenchyma. Although in this case, no cardiovascular collapse was observed, when unrecognized or undertreated, adrenal insufficiency complicating BAH can evolve into an adrenal crisis. Infections and medications that increase cortisol metabolism can also contribute to this complication.

Presentation: 6/3/2024
8769 A Case of Metastatic and Catecholamine Producing Bilateral Pheochromocytoma in a Patient with RET Gene Mutation
Authors: Amelia Mayers Raisa , Szafran-Swietlik Anna
Published: October 2024

Disclosure: R.A. Mayers: None. A. Szafran-Swietlik: None.

RET mutation, observed in multiple endocrine neoplasia type 2 syndromes, is implicated in the development of pheochromocytomas of the kinase signaling cluster. Such tumors have lower metastatic risk and adrenergic production compared to the ones from the other clusters. We present a case of a metastatic, bilateral, small and biochemically active pheochromocytoma .This is the case of a 27-year-old man diagnosed with MEN 2A. He underwent total thyroidectomy due to medullary thyroid carcinoma at 2 years old. He was deemed cured and started on levothyroxine replacement. Since then, his plasma metanephrines by liquid chromatography-mass spectrometry and urine metanephrines done in a yearly basis as screening, were always within range of normality. Over the years, he developed substance abuse disorder with use of Kratom and methamphetamines and was admitted in a rehabilitation center multiple times in the last three years. During this time, the patient was reported to be slightly tachycardiac which was initially attributed to the use of substances. On the last year, an echocardiogram done as evaluation of his tachycardia showed an ejection fraction of 35%. Later, his annual metanephrine levels were markedly elevated (free metanephrine: 137 pg/mL and free normetanephrine : 157 pg/mL, normal ranges reported as less than 57 pg/mL and less than 148 pg/mL respectively). Abdominal tomography showed a right adrenal nodule of 1.2 cm and a left adrenal nodule of 1.6 cm, both with more than 10 Hounsfield Units. A Metaiodobenzylguanidine scan revealed a left adrenal nodule of 1.8 cm with diffuse radiotracer uptake, a right adrenal nodule of 1.2 cm with radiotracer activity and 3 subtle areas of focally increased radiotracer activity in the liver, two in left hepatic lobe and other in posterior right upper lobe. He underwent bilateral adrenalectomy with cortical sparring. Pathology results evidenced a left adrenal with a unifocal mass of 1.8 cm and a right adrenal with a mass of 1.2 cm , both without lymphovascular, capsular, local invasion or necrosis, a mitotic rate of 1-2 without atypical mitosis, not encapsulated with clean margins and positive for synaptophysin , chromogranin and S100 stains. An additional mass of 0.7 cm on the right adrenal gland was described with similar characteristics to the described before except for the involvement of the surgical margins. Currently on the literature there are different opinions regarding screening approach for pheochromocytomas in the presence of RET mutations. There are not strong recommendations regarding the use of imaging as a screening tool in this group of patients. It is important to consider that there are cases, as the one described in this report, that might present metastatic disease even with the presence of small pheochromocytomas that belong to the cluster of kinase signaling.

Presentation: 6/3/2024
7698 A case of Pheochromocytoma in a patient with severe aortic stenosis
Authors: Lane Chelsea , Aguirre Lina E , Azocar-Villalobos Jorge Luis , Dorin Richard I
Published: October 2024

Disclosure: C. Lane: None. L.E. Aguirre: None. J. Azocar-Villalobos: None. R.I. Dorin: None.

Background: Pheochromocytomas are rare neuroendocrine tumors derived from chromaffin tissue of the adrenal medulla and can secrete catecholamines. Pre-operative management of pheochromocytoma involves initiation of a- followed by b-adrenergic receptor blockade. In critical aortic stenosis (AS), adrenergic blockade may be complicated by decreased cardiac output and hypotension owing to dependence of venous return on maintenance of high afterload (1). We report a case of critical AS and incidentally discovered pheochromocytoma and describe our management strategy, which involved prioritization of aortic valve repair prior to adrenal surgery and multidisciplinary approach to initiation and titration of a- and b-adrenergic blockade prior to cardiac catheterization and transcutaneous aortic valve replacement (TAVR) procedures. Clinical Case: A 75-year-old Caucasian male with past medical history of obstructive sleep apnea, tobacco use, and cocaine use disorder was admitted with progressive dyspnea, decreased exercise tolerance, and involuntary weight loss of 18 kg over 3 months, and community acquired pneumonia. On admission, he was found to have critical aortic stenosis (valve area of 0.59 cm2, mean gradient 83 mmHg) and new HFrEF (EF 40-45%). CT chest demonstrated incidental right adrenal mass (5.6 x 5.0 x 4.7 cm) with central necrosis, HU units >10, and evidence of internal hemorrhage. Subsequent laboratory and functional imaging studies confirmed diagnosis of pheochromocytoma. Pre-procedural a-adrenergic blockade with doxazosin followed by beta-blockade was managed by a multidisciplinary team with ICU admission for monitoring and uncomplicated completion of cardiac catheterization and TAVR. Conclusions: Pre-procedural diagnosis of pheochromocytoma, multidisciplinary management, and intensive care setting for monitoring hemodynamic response to initiation and titration of a and b-adrenergic blockade appeared to be key factors in achieving uncomplicated completion of cardiac interventions prior to surgical resection of pheochromocytoma and critical AS. Successful TAVR was associated with marked improvement in hemodynamic status. Maintenance of b-adrenergic blockade to reduce myocardial contractility was critical to preservation of the prosthetic aortic valve and in preparation for planned robotic resection of the pheochromocytoma. References: 1. Feinstein I, Lee T, Khan S, Raleigh L, Mihm F. A case report of an open aortic valve replacement followed by open adrenalectomy in a patient with symptomatic pheochromocytoma and critical aortic stenosis. J Cardiothorac Surg. 2021 28;16(1):282. 2. Yang et al. Yang et al. BMC Anesthesiology (2023) 23:18

Presentation: 6/1/2024
7764 A Case of Primary Hyperaldosteronism With Negative Imaging Findings -Diagnostic Approach and Outcome in a Decade
Authors: Datta Gupta Uma , Al-Ghuraibawi Muthanna , Abdulhussein Roua , Panigrahi Kalpana , Deribe Zewge
Published: October 2024

Disclosure: U.D. Gupta: None. M. Al-Ghuraibawi: None. R. Abdulhussein: None. K. Panigrahi: None. Z. Deribe: None.

Distinguishing between the various subtypes of primary hyperaldosteronism (PHA) poses a clinical challenge. Nevertheless, it is notable that primary hyperaldosteronism is a prominent contributor to secondary hypertension, accounting for less than 1% of cases. The triad of hypertension, hypokalemia, and metabolic alkalosis demands screening for PHA. While bilateral adrenal hyperplasia and aldosterone-producing adenomas (APA) are common, rarer forms like unilateral adrenal hyperplasia and glucocorticoid-responsive aldosteronism can also occur. In our case, a 61-year-old patient has been diagnosed and treated for primary hyperaldosteronism for last 10-years. Presently, the patient is undergoing management for blood pressure with a medication regimen comprising Amiloride, Nifedipine, Minoxidil, Atenolol, and Eplerenone over the past decade. No abnormal findings were observed in the computed tomography or magnetic resonance imaging of the adrenal gland, and adrenal venous sampling test results were non-conclusive. The patient has exhibited favorable outcomes with medications, also subsequent imaging has not revealed the presence of an adrenal mass. This case is presented as unique due to its atypical presentation, characterized by the absence of anatomical lesions in the adrenal gland and non-conclusive sampling test results. Nevertheless, the patient responded positively to treatment, supported by the diagnostic significance of preliminary lab tests for primary hyperaldosteronism (aldosterone level: 20.5; plasma renin activity: 0.19, initially aldosterone levels were 17 and 7 before and after saline infusion). Notably, literature acknowledges that the aldosterone-producing adenomas (APAs) can be very small, sometimes <3 mm in diameter, and lesions <1 cm may be overlooked on CT scans. The limitation of adrenal venous sampling (AVS) is the challenge in obtaining good sample due to technical difficulties and variations in local expertise, success rates in AVS may vary. This case exemplifies the diagnostic complexities encountered in primary hyperaldosteronism cases, where imaging and adrenal venous sampling, though frequently recommended, may pose challenges. In conclusion, we share insights from this case and its treatment outcome. Clinically, a thorough assessment of symptoms, along with laboratory results, is crucial for diagnosis and treatment and further categorization may be challenging without imaging and adrenal venous sampling.

Presentation: 6/3/2024
7988 A Case of Spontaneous Pituitary Hemorrhage in Late Pregnancy
Authors: Poudyal Dinesh , Prince Grace L
Published: October 2024

Disclosure: D. Poudyal: None. G.L. Prince: None.

Background: Pituitary apoplexy (PA), caused by hemorrhage into the pituitary gland, is rare. The prevalence in pregnancy is also quite rare, with PA complicating 1 in 10,000 pregnancies. PA usually occurs in patients with pre-existing pituitary adenomas. Spontaneous pituitary hemorrhage (PH) causing PA in the absence of a known adenoma or other precipitating factors is less frequently described. Presenting symptoms of PA are non-specific and can pose diagnostic challenges, yet PA must be managed urgently and decisively due to the risk of life-threatening hormonal deficiencies that can ensue. Physiologic changes in pregnancy pose additional challenges in evaluating and managing patients with possible PA. Here we present a case of spontaneous PH during the third trimester of pregnancy in the absence of pre-existing pituitary pathology or known precipitants. Case presentation: A 31-year-old female, G2P1, with an uncomplicated first pregnancy, presented with acute-onset headache and vision loss at 36 weeks gestation. Her symptoms resolved spontaneously in 45 minutes. MRI brain without contrast showed hemorrhage within the left aspect of the pituitary gland, a mildly displaced infundibulum, but no mass effect on the optic chiasm. MRI brain obtained 1 year prior for headache was unremarkable. Lab work showed an 8AM cortisol of 19 ug/dL (Ref range 3.7 - 19.4 ug/dL), and a total T4 of 11.3 ug/dL (Ref 4.9 - 11.7 ug/dL). Ultimately, interpretation of her cortisol testing was limited by: elevated cortisol-binding globulin in the high-estrogen state of pregnancy, elevated cortisol production by an intact hypothalamic-pituitary-adrenal (HPA) axis during the latter portion of pregnancy, and the lack of validated cutoff values for 8AM serum cortisol levels during pregnancy. In light of these factors and the risk of undiagnosed adrenal insufficiency (AI), she was treated empirically with oral hydrocortisone. Subsequently, she had an uneventful vaginal delivery, supported by stress dosing of her steroids. Postpartum, she had a normal 8AM cortisol level of 14 ug/dL, and she was noted to quickly begin breastfeeding without incident. Conclusion: PA remains a critical diagnosis that cannot be missed in patients presenting with concerning symptoms and signs, in order to identify and treat life-threatening hormonal deficiencies. Pregnancy poses unique challenges in diagnosing hormonal deficiencies such as AI due to normal physiologic changes affecting the HPA axis as well as other pituitary axes. Therefore, the benefit of empiric hydrocortisone treatment likely outweighs any associated treatment risk in cases with consistent symptomatology and radiographic findings.

Presentation: 6/2/2024
8479 A Challenging Case of Hypercortisolism in an Adult Patient With McCune Albright Syndrome
Authors: Chary P Kesavan , Jasim S
Published: October 2024

Disclosure: P. Kesavan Chary: None. S. Jasim: None.

Background: McCune Albright Syndrome (MAS) is a rare genetic disorder that occurs due to a spontaneous post-zygotic missense mutation in the GNAS gene resulting in activating gain of function mutations in G-proteins. MAS classically presents as a triad of café-au-lait skin pigmentation, fibrous dysplasia of bone, and precocious puberty. However, continuous autonomous stimulation of endocrine glands can also result in various other endocrinopathies. We present a rare case of hypercortisolism due to bilateral multinodular adrenal hyperplasia (BMAH) in an adult patient with MAS. Case Report: A 38 year old female had MAS, clinically manifested by precocious puberty, renal phosphate wasting with rickets and osteomalacia, fibrous dysplasia of bone with history of multiple fractures, growth hormone excess, and multinodular thyroid status-post total thyroidectomy. A surveillance CT abdomen showed bilateral (right 3.8 x 1.3 cm and left 1.0 x 0.9 cm) adrenal adenomas with low intrinsic attenuation and washout. On diagnosis, the patient had an AM cortisol of 32.5 ug/dL (6.2-19.4 ug/dL) after a low-dose dexamethasone suppression test (DST), and an AM cortisol of 27.3 ug/dL after a high-dose DST. Late night salivary cortisol was 0.518 ug/dL (<0.010-0.090 ug/dL), 24-hour urine cortisol was 78 ug/24hrs (6-42 ug/24hrs), and ACTH was <1.5 pg/mL (7.2-63.3 pg/mL). The patient was initially asymptomatic and monitored for a few months, but subsequently developed easy bruising, recurrent skin infections, and irritability. The patient declined surgical intervention and was initiated on Osilodrostat. Shortly after medication initiation, she was hospitalized for perforated diverticulitis, hypokalemia, and hypomagnesemia. During hospitalization, AM Cortisol was 49 mcg/dL (4.8-19.5 mcg/dL) and 24-hour urine cortisol was 1023 mcg/24hrs (normal range 3.5-45 mcg/24hrs; the patient’s level prior to admission was 170-190 mcg/24hrs). Osilodrostat was held and the patient was initiated on Etomidate infusion. Once plasma cortisol levels normalized, she resumed Osilodrostat prior to discharge. The patient subsequently tried multiple medical therapy options before undergoing a bilateral adrenalectomy as a definitive treatment choice. Conclusion: The gain of function mutations in MAS result in autonomous endocrine gland function that can manifest clinically as various endocrinopathies. While the most common endocrinopathies in MAS are precocious puberty, hyperthyroidism, and pituitary dysfunction, active surveillance is critical to monitor for less common presentations such as hypercortisolism. This is the first report of adrenal Cushing’s in an adult patient with MAS.

Presentation: 6/3/2024
8621 A Challenging Case of Preoperative Management of Pheochromocytoma Presenting With Recurrent Hypotension
Authors: Shripad Namratha , Arif Aneela , Osman Radwa
Published: October 2024

Disclosure: N. Shripad: None. R. Osman: None.

Introduction: Pheochromocytoma is a neuroendocrine tumor that clinically manifests due to the hypersecretion of catecholamines. Preoperative management typically involves alpha- and beta-adrenergic blockade. Patients commonly present with hypertension; however, in rare cases, patients may be hypotensive due to other comorbidities, posing a challenge to preoperative management. The following is a case of management of a pheochromocytoma with recurrent preoperative hypotension before the initiation of blood pressure-lowering agents. Case: A 47-year-old female presented to the hospital with dizziness and hypotension. The patient has a history of bilateral nephrectomy with left-sided adrenalectomy secondary to left-sided renal cell cancer and is hemodialysis-dependent. A right-sided pheochromocytoma was diagnosed a year ago on a follow-up CT scan done for monitoring renal cell cancer. The diagnosis was later confirmed with a DODATE scan and, eventually, a biopsy. Normetanephrine levels were between 581-735 pg/mL (0-88 pg/mL), with normal metanephrine levels. She denies having hyperadrenergic spells. She was started on metoprolol and doxazosin the year prior to presentation; however, she self-discontinued doxazosin after experiencing dizziness and palpitations on hemodialysis days. On admission, she was afebrile with a blood pressure of 103/66 mm Hg and a heart rate of 115 BPM. After an interdisciplinary decision was made for surgical resection, she was restarted on a lower dose of doxazosin (1 mg) and metoprolol was increased to the goal heart rate. Despite fewer hypotensive episodes on a reduced dose of doxazosin, the patient remained hypotensive on hemodialysis days. Salt tablets were started post-dialysis after clearance from nephrology, and an improvement in blood pressure was noted. She underwent a right adrenalectomy without receiving saline infusion before surgery due to concerns about volume overload. She was started on stress dose steroids due to her history of left adrenalectomy. She remained stable during and following surgery and did not require any vasopressor support. Discussion: Perioperative management of pheochromocytoma can be challenging in hypotensive patients and is poorly documented. Midodrine, an alpha-1 agonist that is typically used in dialysis-induced hypotension, is contraindicated in the setting of pheochromocytoma. We opted to manage our patient with a reduced dose of doxazosin and beta-blocker initially; however, with continued hypotensive episodes, the addition of salt tablets preoperatively on dialysis days helped to alleviate the hypotension. Although our patient did not require it, a preoperative overnight albumin infusion is a viable alternative to saline to prevent volume overload. Despite the limited literature, the patient was treated successfully through an interdisciplinary approach.

Presentation: 6/3/2024
7677 A Novel Cause of Resistant Hypertension: Paraganglioma and Conn's Syndrome
Authors: Belal H F , Minns R M , Chehade J M , Koch C A
Published: October 2024

Disclosure: H.F. Belal: None. R.M. Minns: None. J.M. Chehade: None. C.A. Koch: None.

Background: Concomitant hyperaldosteronism (PA) and pheochromocytoma (PHEO) are extremely rare causes of hypertension. We present a novel case of concurrent PA and paraganglioma (PARA). Clinical Case: A 37 year old Ghanaian female with prior history of hypertension presented on referral with asymptomatic resistant hypertension and hypokalemia. Patient had developed hypokalemia (2.7 mEQ/L, 3.5-5.1 mEQ/L) after caesarean section for pre-eclampsia; discharged with hydralazine, labetalol and nifedipine. Labs on initial consultation showed hypokalemia 2.7 mEQ/L (3.5-5.1 mEQ/L), elevated plasma aldosterone 133.4 ng/dL (0.0-30.0 ng/dL), renin 0.815 ng/mL/hr (0.167-5.38 ng/mL/hr), elevated norepinephrine 1139 pg/mL (0-874 pg/mL), elevated chromogranin A 175.6 ng/mL (0.0-101.8 ng/mL); normal epinephrine, dopamine, DHEAS. Twenty-four-hour urine (volume 2,700 ml): elevated normetanephrine 967 mcg/24 hr (131-612 mcg/24 hr); normal urine metanephrine and free cortisol. Adrenal CT and MRI revealed left adrenal lesion 1.3 x 1.2 x 1.1 cm (pre-contrast Hounsfield Unit 13, absolute washout 74%), adjacent extra-adrenal 1.8 x 1.6 x 1.6 cm lesion near left renal vein chain (MRI T2 hyperenhancement) and no right adrenal lesions. She was started on prazosin 1 mg qd, spironolactone 25 mg qd, telmisartan 40 mg qd and potassium chloride 20 mEq TID for three weeks prior to left adrenalectomy and left retroperitoneal mass resection. Pathology revealed left adrenal cortical adenoma and left retroperitoneal PARA (positive synaptophysin, chromogranin, S100; preserved SDHB expression; Ki67 index 2%). Postoperatively blood pressure was controlled with amlodipine alone. Postoperative plasma/24 hour urine aldosterone, metanephrine, catecholamine and plasma renin, potassium were all normal. Conclusion: This is the first case, to our knowledge, of extra-adrenal PARA and Conn's Syndrome. Mao et al reviewed 7724 adrenal masses and found fifteen cases of concurrent PA and PHEO, but no concurrent PA and PARA [1]. Hypokalemia is rare yet more common (87%) in concurrent PA/PHEO than PA alone (28%)[1]. Management of concurrent PA and PHEO is primarily focused on medical bridging to a surgical cure while conserving adrenal function. As our case demonstrates, while exceedingly rare, it is important to work up adrenal masses to ensure that concurrent lesions are not missed. We propose a potential mechanism for concurrent lesions of PHEO/PARA could be concurrent germline mutations in genes triggering PA and in genes triggering PPGL syndromes.2References: 1. Mao JJ, Baker JE, Rainey WE, Young WF, Bancos I. Concurrent Pheochromocytoma and Primary Aldosteronism: A Case Series and Literature Review. J Endocr Soc. 2021;5(8):bvab107. 2. Kimura N, Koch CA, et al. Extraadrenal paragangliomas. pp.190-195. in: Lloyd RV et all. (Eds). WHO classification of tumors of endocrine organs (4th edition). IARC, Lyon 2017

Presentation: 6/2/2024
6637 A Rare Case of a Possible Non-functional (Clinically Silent Biochemically Negative) Adrenal Pheochromocytoma
Authors: Kumar Babu Vedesh , Corwin Michael T , Olatunbosun Samuel T
Published: October 2024

Disclosure: V.K. Babu: None. M.T. Corwin: None. S.T. Olatunbosun: None.

Introduction: Adrenal pheochromocytomas (pheo) are rare neuroendocrine tumors arising from the chromaffin cells of the adrenal medulla. Their incidence is around 0.8 per 100,000 patient years. They are usually sporadic, with about 40% having a pre-existing familial genetic disease. About 3% of adrenal incidentalomas prove to be pheo. They have a heterogenous presentation and are diagnosed by measuring urinary and plasma fractionated metanephrines (met) and catecholamines (catecho). The diagnosis becomes challenging in patients presenting with small tumors and normal levels of biochemical metabolites, as in our patient. Clinical Case: A 32-year-old male with no significant past medical history was referred to us with a left adrenal incidentaloma of 1.2 cm x 1 cm with 23 Hounsfield units during a non-contrast CT scan performed for abdominal pain. He denied spells of headaches, excessive perspiration, palpitations, history of hypertension, hypokalemia, history of kidney stones, fractures, muscle weakness, easy bruisability, new abdominal striae, change in weight, steroid use, or family history of endocrine tumors. MRI with adrenal protocol 3 months later showed a 1.2 cm x 1.4 cm left adrenal nodule that was markedly hyperintense on T2-weighted and hypointense on T1-weighted images without microscopic fat, suspicious for a pheo. It also demonstrated peripheral enhancement with progressive central filling on the delayed images without washout. Plasma met and catecho were normal: normetanephrines (normet) (45.2 pg/mL), met (36.4 pg/mL), epinephrine (epi) (34 pg/mL), norepinephrine (norepi) (295 pg/mL) and dopamine (<30 pg/mL). Subsequent 24-hour urine testing revealed normal met (155 mcg/day, 154 mcg/day), and normal normet (248 mcg/day, 236 mcg/day) on two separate occasions, and normal epi (9 mcg/L), norepi (36 mcg/day), and dopamine (228 mcg/day). The patient was subsequently referred to Endocrine Surgery for evaluation. Conclusion: Our patient likely has a non-functional pheo. Another possibility is an adrenal hemangioma, which would show discontinuous peripheral nodular enhancement in addition to progressive central filling. Patients with pheo less than 2 cm may present with normal biochemical testing. The size of a pheo is usually proportional to the levels of its biochemical metabolites. This case is unique because patients with a similar sized pheo are expected to have 3 times higher levels of plasma met and catecho, even if still within normal limits. It is important to take tumor size into consideration when interpreting labs to determine its functional status. This may help in determining the need for a pre-operative alpha blockade prior to adrenal surgery. A definitive diagnosis of a pheo’s non-functional status can only be confirmed after histopathological examination of the tumor tissue.

Presentation: 6/3/2024
12564 A Rare Case Of Pembrolizumab Induced Secondary Adrenal Insufficiency
Authors: Escano Volquez Lorena , Desai Prarthana
Published: October 2024

Disclosure: L. Escano Volquez: None. P. Desai: None.

Pembrolizumab is an immune check-point inhibitor that blocks the PD1 receptor and is currently used in the treatment of a vast variety of malignancies. Despite adrenal insufficiency (AI) already being documented as a rare but potential side effect, its diagnosis is usually delayed due to vague presentation, increasing the risk of deleterious outcomes. We present a case of secondary AI while on pembrolizumab in which diagnosis was delayed due to unspecific clinical picture.This is a 66-year-old male who presented to the hospital with decreased appetite, nausea and generalized weakness. Patient was seen a month prior with similar symptoms which were thought to be secondary to poor oral intake in the setting of underlying malignancy. Medical history remarkable for squamous cell carcinoma of the skin with recent lung metastasis for which he was started on pembrolizumab a year ago. On arrival to the emergency department, patient was hypertensive with BP 144/68 mmHg, HR 88, and RR 15. Orthostatic vitals were positive. Physical examination otherwise unremarkable. Laboratory tests revealed mild hypernatremia of 147, potassium of 4.7, chloride 108, HCO3 18, anion gap 21, BUN 33, elevated creatinine 1.62 and elevated beta-hydroxybutyrate 5.4. EKG revealed sinus rhythm. Patient was admitted for further evaluation of orthostasis and starvation ketosis. Initial management included IV fluids and Midodrine. However, patient continued to have episodes of orthostatic hypotension. Lack of improvement of symptoms led to further workup which revealed low AM cortisol of 1.0 and a low ACTH level <3.0 pg/ml, concerning for secondary adrenal insufficiency. Patient was administered Solu-Medrol 40 mg IV before being transitioned to a daily hydrocortisone regimen with subsequent improvement of symptoms. Pembrolizumab induced AI is a very rare event. It is estimated that the incidence approaches 1% and symptoms can develop at any time throughout treatment. Despite its low incidence, it can be life-threatening if not diagnosed and treated promptly. However, given its very heterogeneous and vague clinical presentation, a prompt diagnosis can be difficult. The clinical course of our patient and subsequent resolution of symptoms after appropriate treatment was started, supports the diagnosis of pembrolizumab induced adrenal insufficiency after a year of initiating treatment. This patient had prior hospitalizations and office visits with symptoms that are usually already present in individuals with underlying malignancy, which resulted in underestimation of his symptoms. This case highlights the importance of always considering AI as a potential adverse effect of immune check-point inhibitors. This will ensure a prompt diagnosis and treatment of an endocrine disorder that could otherwise lead to deleterious outcomes if left untreated.

Presentation: 6/1/2024
8733 Adrenal Crisis In A Patient Diagnosed With Primary Adrenal Insufficiency Following COVID-Vaccination
Authors: Hayat Aamir , Aslam Noreena
Published: October 2024

Disclosure: A. Hayat: None. N. Aslam: None.

Primary adrenal insufficiency, or Addison's disease, is characterized by the inadequate production of cortisol and often requires lifelong hormone replacement therapy. COVID-19 vaccines have demonstrated overall safety, but this report explores a unique case of adrenal crisis post-vaccination in a patient with pre-existing adrenal insufficiency. A 38-year-old female, diagnosed with primary adrenal insufficiency, received her second dose of a COVID-19 vaccine. Within 48 hours after vaccine administration , she presented to the emergency department with severe fatigue, hypotension, nausea, and abdominal pain. Clinical examination and laboratory tests confirmed an adrenal crisis, with markedly decreased cortisol levels, hyponatremia, hyperkalemia, and an elevated ACTH level. The patient was promptly treated with intravenous hydrocortisone and saline fluids. Close monitoring of vital signs and cortisol levels was maintained, with a gradual tapering of hydrocortisone as the patient's symptoms improved. The importance of stress-dose steroids during illness or vaccination in patients with adrenal insufficiency is underscored. This case highlights that the Healthcare providers should be aware of this rare but severe complication and consider appropriate monitoring and stress-dose steroid coverage in susceptible populations.

Presentation: 6/3/2024
7247 Adrenal Insufficiency In Advanced Cirrhosis: A ‘Shocky’ Clinical Dilemma
Authors: Aboishava Lizaveta , Pareek Ashutosh , Mertens Avalon , Erokhin Aleksandr
Published: October 2024

Disclosure: L. Aboishava: None. A. Pareek: None. A. Mertens: None. A. Erokhin: None.

Background: In patients with advanced cirrhosis, profound hypoproteinemia can complicate the laboratory assessment of the hypothalamic-pituitary-adrenal axis, but a clinical phenotype of persistent hypotension and suboptimal cortisol response to ACTH stimulation raises the question of whether adrenal insufficiency could also be a contributing factor. Clinical Case: A 65-year-old man with a history of cirrhosis complicated by esophageal varices, ascites, encephalopathy and hepatorenal syndrome was admitted to the ICU with worsening fatigue, profound hypotension, and respiratory arrest. He was started on pressors, antibiotics and was also intubated for a short time. A broad workup was negative for cardiac or infectious causes of shock and showed decreased total protein and albumin (1.6 g/dl (3.5-5.2), with normal serum sodium and potassium. The patient had no previous history of adrenal disease or corticosteroid use. Workup for adrenal insufficiency was initiated and showed decreased morning blood serum cortisol (10.6 ug/dl (2.5-19.5)) and ACTH (<5.0 pg/ml (7.2-63)), as well as suboptimal cortisol response on ACTH stimulation testing (12.5 ug/dl initially, 16.7 ug/dl after stimulation). Head CT on admission was negative for intracranial pathology, and lab results showed normal TSH and mildly increased prolactin of 36.2 ng/ml (4.0-15.0). Pt was started on IV hydrocortisone 50 mg TID. Glucocorticoid therapy didn’t improve his state significantly but was continued with a gradual tapering down of the dose. After intense treatment in the ICU the patient’s state was stabilized. Unfortunately, an endoscopy performed for worsening anemia and blood in stools showed gastric cancer. The patient was transferred to comfort care after a discussion of goals of treatment and died within the next 24 hours. Conclusion: The nature of decreased cortisol levels in patients with cirrhosis is most likely multifactorial, due to impaired hepatic synthetic function, dysregulation of hormone-binding protein balance, abnormal ACTH secretion, and other factors. Impaired corticosteroid-binding globulin synthesis might affect the ratio of globulin-bound and free hormone fractions and alter the accuracy of cortisol assays. Whether adrenal insufficiency is truly one of the complications of advanced cirrhosis contributing to persistent hypotension, or a mere laboratory finding is difficult to answer. It is also yet to be determined whether patients with advanced cirrhosis might benefit from screening and treatment of adrenal insufficiency in circumstances of persistent hypotension, and studies are needed to decide on optimal diagnostic tests to recognize the disease and develop treatment algorithms.

Presentation: 6/3/2024
6436 Adrenal Venous Congestion Clinically Mimicking Carcinoma In A Large Degenerated Adrenocortical Adenoma
Authors: Ishiwata Kazuki , Suzuki Sawako , Watanabe Suzuka , Yamazaki Yuto , Sasano Hironobu , Yokote Koutaro
Published: October 2024

Disclosure: K. Ishiwata: None. S. Suzuki: None. S. Watanabe: None. Y. Yamazaki: None. H. Sasano: None. K. Yokote: None.

Introduction: A large heterogenous adrenal tumor is often malignant. Only eight reported cases of adrenal adenoma harboring hemorrhage or venous thrombosis have been reported but their details not. We encountered a case of large degenerated adrenocortical adenoma harboring adrenal venous congestion mimicking adrenocortical carcinoma. Case: Adrenal tumor was incidentally detected in a 71-year-old woman with a history of hypertension, dyslipidemia, and osteoporosis in her regular health check-up. Abdominal CT and MRI demonstrated a heterogenous mass measuring 7.6 cm with peripheral enhancement in the left adrenal gland. [1]3[1]I-adosterol scintigraphy revealed accumulation only in the left tumor margins with no accumulation in [1]8F-FDG-PET scan. Results of endocrinologic evaluation were consistent with subclinical Cushing syndrome. The large size and heterogeneous nature of the mass clinically suggested adrenocortical malignancy, and left laparoscopic adrenalectomy was subsequently performed. The resected left adrenal lesion was encapsulated and measured 6.5 x 6.3 x 5.8 cm appearing almost black and partially yellow on the cut surface. Microscopically, the nodule was composed of SF-1 positive, clear cortical cells with abundant hyaline stroma containing numerous dilated veins with CD31/34-positive endothelial cells, and no foci of necrosis or hemorrhage were detected. The tumor cells above were positive for steroidogenic enzymes including CTP17, HSD3β and CYP11B1 but negative for CYP11B2. Ki-67 labeling index was <2% in the tumor. The criteria of Weiss (0 out of 9) revealed that the tumor was cortisol-producing adrenocortical adenoma. Discussion: In this case, clusters of SF1-positive cortisol producing adrenocortical adenoma cells were present in the hyalinized stroma containing many dilated blood vessels. These findings indicated that those histological features were caused by ischemic degeneration due to intratumoral circulatory disturbance, which clinically simulated adrenocortical carcinoma. Conclusion: We have experienced a very rare case of cortisol-producing adrenocortical adenoma with adrenal venous congestion, resulting in marked enlargement of the lesion.

Presentation: 6/3/2024
7805 Adrenocortical Carcinoma - A Tertiary Center's Recent ∼10-Year Experience
Authors: Osher E , Tordjman K M , Sofer Y , Stern N , Klausner J , Lahat G , Lubezky N , Goykhman Y , Sagie B , Ravit G , Asaf A , Rivka K , Ido W , Greenman Y
Published: October 2024

Disclosure: E. Osher: None. K.M. Tordjman: None. Y. Sofer: None. N. Stern: None. J. Klausner: None. G. Lahat: None. N. Lubezky: None. Y. Goykhman: None. B. Sagie: None. G. Ravit: None. A. Asaf: None. K. Rivka: None. W. Ido: None. Y. Greenman: None.

Background: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a poor prognosis. Prospective randomized controlled studies to evaluate the optimal treatment modalities are limited. Therefore, retrospective studies are needed. The aim of the study is to describe and summarize additional data and knowledge on treatment modalities in a tertiary medical center treating patients with ACC by a multidisciplinary expert team. Methods: A retrospective study. Results: The study cohort included 42 subjects (57% females), followed for a median of 26 (range 0.3-237) months. The mean age at diagnosis was 54±17 years; 60% of tumors were functioning, 57 % were cortisol-secreting, 41% were androgen-secreting, 12% aldosterone-secreting, and 45% were co-secreting. ENSAT stage at diagnosis was stage 1 in 19%, stage 2 in 26%, stage 3 in 24% and stage 4 in 29%. Eighty-eight % of patients underwent surgery; residual disease was in 21% post surgery. Treatment with mitotane was initiated in 62% of patients, reaching a mean maximal dose of 3.1 ±2 grams/day. Oncologic pharmacological treatment (Chemotherapy, TKI, Immunotherapy) and/or radiation were given in 50 % and 21%, respectively. In 14 /42 patients, genetic evaluation was done, in most cases, no target for treatment was found. 52% of patients died during follow-up; all cohort median time to death was 31(range 0.3-237) months. Time to death longer than 31 months was also seen in advanced disease stage 3- 3/9(33%) and stage 4-4/11(36%). Except association between mitotane and prolonged time to death (p=0.013), no other factors (age, gender, surgery, radiation, residual disease functional status), were associated with prolonged survival. Conclusions: ACC remains a rare disease with a poor prognosis. However, it is a heterogeneous disease, with some patients with advanced disease achieving more prolonged survival. Further characterization of these patients may improve our understanding of the biology and treatment of this rare disease.

Presentation: 6/2/2024
8627 Viral Hormones: The Role Of Viral Insulin/IGF-1 Like Peptides In Host-Pathogen Interactions
Authors: Chuard A , Nesarajah K , Danazumi K , Reiners K , Zhang F , DiMarchi R , Altindis E
Published: October 2024

Disclosure: A. Chuard: None.

Viruses, encode proteins that are similar to host proteins to manipulate the host. Until our recent discovery of viral hormones, examples of viral mimicry were limited to immunomodulatory proteins and growth factors. We recently showed that six viruses in Iridoviridae family encode genes mimicking human insulin and IGF-1. We previously chemically synthesizing these viral insulin/IGF-1 like peptides (VILPs) and showed that VILPs can bind to human insulin and IGF-1 receptor and further stimulate post-receptor signaling. VILPs also stimulate glucose uptake and proliferation in mammalian cells and lower the blood glucose in mice. Originally, VILP-carrying viruses were isolated from fish; however, the role of VILPs in viral pathogenesis is not studied in depth. Here, we examined the effects of Grouper Iridovirus (GIV, one of the VILP carrying viruses) infection and GIV-VILP on host insulin/IGF signaling system using fish cells.To this end, we chemically synthesized GIV-VILP in its single chain (sc, IGF-1 like) and double chain (dc, insulin-like) forms. Stimulation of grouper kidney (GK) and AB9 zebrafish cells with these peptides, insulin and IGF-1, showed that IGF-1 was the most potent ligand in these cells indicating an abundance of IGF-1 receptor (IGF1R). Further, both forms of the VILPs were as potent as insulin in its activity on receptor phosphorylation and post-receptor signaling. Examining the viral kinetics, we also showed that GIV32 gene (encoding GIV VILP) is an early viral gene in both cell types. Virion analysis through mass spectrometry indicated that VILPs are not viral structural proteins. On the other hand, analysis of the supernatant from infected cells indicated that VILPs are secreted peptides during the viral cycle. Our results with supernatant transfer experiments from infected cells to uninfected cells support the same conclusion that VILPs are secreted. The secreted VILPs initiate autophosphorylation of IGF1R and/or insulin receptor (IR), consequently triggering downstream cellular signaling and metabolism. Through the use of specific inhibitors for each receptor, we illustrated that IR signaling is crucial for GIV viral replication. Surprisingly, inhibition of IGF1R increased viral replication and we are currently examining potential inhibitory effects of GIV VILP. Furthermore, VILPs appear to exert a biased effect on the AKT pathway compared to the Erk pathway. Furthermore, the inhibition of the AKT pathway significantly reduces GIV viral replication. In summary, our findings reveal that GIV-VILP is actively produced during infection and contributes to the viral replication. To our knowledge, VILPs are the first hormone-mimics characterized in viral replication. Elucidating the role of VILPs in host-pathogen interactions, we propose a novel viral pathogenesis mechanism where viruses mimic host hormones to manipulate the host's endocrine system.

Presentation: 6/3/2024
12389 Viral Insulin/IGF-1-like Peptides: A New Dimension In Understanding The Insulin/IGF System
Authors: Chrudinova M , Chuard A , Zhang F , Dogru Y D , De Meyts P , Kim J K , Kirk N , Jiracek J , DiMarchi R D , Altindis E
Published: October 2024

Disclosure: M. Chrudinova: None. A. Chuard: None. F. Zhang: None. Y.D. Dogru: None. P. De Meyts: None. J.K. Kim: None. N. Kirk: None. J. Jiracek: None. R.D. DiMarchi: None. E. Altindis: None.

Viral Insulin/IGF-1-Like Peptides: A New Dimension in Understanding the Insulin/IGF System Martina Chrudinova, Aurelien Chuard, Dogus Dogru, Nicholas Kirk, Pierre De Meyts, Jason Kim, Richard Di Marchi, Jiri Jiracek, Emrah AltindisMammals have separate insulin and IGF-1 receptors, and in most species, one insulin and two IGFs interact with them. The mammalian Insulin receptor (IR) primarily controls metabolism, while the insulin-like growth factor-1 (IGF-1) receptor (IGF1R) regulates cell apoptosis, growth, and prenatal and postnatal differentiation. Despite their distinct functions, due to high structural similarity, insulin and IGF-1 can bind to each other's receptors with different potencies. However, the presence of viral insulin/IGF-1-like peptides (VILPs) and their effects on mammalian cells were unknown until our recent discovery.For the first time, we demonstrated that viruses possess active gene products that mimic human insulin and IGF-1. These VILPs are approximately 30-50% identical to human insulin and IGF-1 and exhibit atypical effects on the insulin/IGF system. Our initial studies provided insights into VILPs and this complex signaling system: •Introducing the novel concept of a system of viral hormones and viral insulins. •Identifying VILPs in six different Iridoviridae viruses and discovering sequences of these viruses in human samples. •Providing evidence that all VILPs bind to human IR and IGF-1 receptors and that agonist VILPs can stimulate downstream signaling. •Demonstrating that agonist VILPs can increase glucose uptake in vitro and in vivo and have tissue-specific and long-lasting effects. •Showing the expression of VILPs during viral infection and their stimulation of insulin/IGF signaling. •Identifying Mandarin fish ranavirus (MFRV) and Lymphocystis disease virus-1 (LCDV-1) VILPs as potent inhibitors of human IGF1R. To the best of our knowledge, these are the first peptide inhibitors of the IGF1R. •CryoEM studies revealed that two LCDV-1 VILPs bind to IGF1R and lock it. •Unlike the evolution of host insulin/IGFs, these unique characteristics of the VILPs are most likely acquired as a result of distinct co-evolution in viral genomes to facilitate viral pathogenesis in the host.In conclusion, VILPs, as active members of the insulin/IGF superfamily, possess unique characteristics. Our findings on the characterization of the VILPs and their distinct functions open new avenues for a deeper understanding of the insulin/IGF-1 signaling system. Furthermore, VILP research will guide us in designing specific and potent agonists and antagonists of the IR/IGF1R system, with the potential to lead to new therapeutic strategies for a wide range of human diseases.

Presentation: 6/2/2024