Refractory Hypokalemia Research Articles

Pseudo-Hyperaldosteronism Arising from Licorice Cough Syrup Self-Ingestion: A Case Report

Background: Licorice (glycyrrhiza glabra) cough syrup intoxication is manifested with refractory hypokalemia, hypertension, and metabolic alkalosis. The transformation of glycyrrhiza glabra metabolic into glycyrrhetic acid after ingestion further inhibits the 11-β-hydroxysteroid dehydrogenase-2 enzyme, impeding the conversion of cortisol into cortisone. The accumulation of cortisol can also stimulate mineralocorticoid receptors, which leads to a pseudo-hyperaldosteronism-like effect. Case Presentation: We report a 60-year-old male patient with licorice intoxication due to the chronic consumption of licorice cough syrup. He exhibited a transient seizure lasting approximately one minute. Initially, hypokalemia (potassium level was 2.0 mmol/L), metabolic alkalosis, and QT interval prolongation with premature ventricular complexes were demonstrated on his electrocardiogram. Despite the administration of both intravenous and oral potassium supplements over two days, there was no significant improvement in hypokalemia. Spironolactone, an aldosterone receptor antagonist, was administered in addition to ongoing potassium supplementation from the 3rd day. This intervention led to a rapid normalization of hypokalemia in one day. The patient was ultimately discharged on the 6th day without any subsequent complications. Conclusions: The licorice-induced chronic intoxication, which led to pseudo-hyperaldosteronism and refractory hypokalemia, was successfully managed with aggressive potassium supplementation and spironolactone treatment.

8411 Ectopic ACTH-dependent Cyclical Cushing’s Syndrome- the Art of Hide-and-seek

Abstract Disclosure: H. Mon: None. A. Kapoor: None. S. Qureshi: None. M. Martineau: None. K. Meeran: None. Case report: A 72-years-old lady was admitted with hypokalaemia, hyperglycaemia with metabolic alkalosis with background hypertension, type2 diabetes, osteoporosis and right-sided breast cancer treated with chemotherapy and radiotherapy 3years ago. She was previously seen in Endocrinology Clinic for similar episode and deemed not having Cushing’s or Conn’s syndrome on workup. During this admission, although there was no obvious Cushingoid appearance, there was refractory hypokalaemia. On further exploration, there were previous admissions with similar episodes in UK and in her home country, within the same year, a few months apart. Therefore, endocrinology workup was conducted for suspected cyclical Cushing’s syndrome. It demonstrated raised 24-hour urinary free cortisol of 5643 nmol/24hour (reference range 0-164 nmol/24hours), unsuppressed low dose dexamethasone suppression test with cortisol level of 800 nmol/L and increased ACTH level of 429 ng/L. MRI (pituitary) showed no pituitary lesion with probable empty sella and CSF filled. However, CT (thorax) showed enlarging lesion (previously from 1cm to 1.6cm) in the left lower lobe, concerning lung metastasis or primary lung malignancy. PET scan showed left lower lobe nodule having low-grade activity with likelihood of indolent malignancy and appearances of physiologic adrenal hyperplasia. Management: Given persistently high cortisol levels during admission with ongoing hyperglycaemia and refractory hypokalaemia, metyrapone was started and titrated accordingly. Her clinical condition including potassium and cortisol levels effectively responded to metyrapone. Gallium scan was booked for detail localization with ongoing lung MDT (multidisciplinary team meeting) and neuroendocrine tumour MDT.However, after starting metyrapone, she had type 1 respiratory failure, not responding to initial antibiotics. After excluding other possible respiratory aetiologies, empirical treatment for Pneumocystosis pneumonia (PCP) was initiated, after which blood test for Beta-D-glucan was found out to be significantly raised, supporting the presumptive diagnosis. Conclusion: Our case highlighted the following interesting points 1. diagnostic challenges, due to the fluctuating nature of cyclical Cushing’s syndrome, presenting with recurrent hypokalaemia. 2. the interesting nature of likely ACTH-dependent cyclical Cushing’s syndrome, progressing into florid Cushing’s syndrome, with efficacy to metyrapone 3. rare and compelling combination of 3 conditions of Cyclical Cushing’s syndrome, being ectopic ACTH-dependent and complicated by Pneumocystosis pneumonia (PCP). Presentation: 6/1/2024

8233 Cushing Disease Presenting As Severe Persistent Hypokalemia

Abstract Disclosure: G. Palaguachi: None. A. Randhawa: None. M. Sattar: None. G. Mahajan: None. J. Karam: None. Introduction: The clinical presentation of Cushing Disease represents a wide spectrum of clinical and laboratory findings, including electrolyte derangements such as hypokalemia. In this case report, we describe a patient in whom the admission for severe persistent hypokalemia prompted the diagnosis of Cushing Disease. Clinical Case: A 35-year-old woman with history of type 2 diabetes, hypertension, and hyperlipidemia, presented to the Emergency Department with worsening bilateral lower extremities swelling, impairing her ability to walk, found to have severe hypokalemia with K level of 2.8 (3.4-4.8 mmol/L), in additional to right pubic rami fracture, left breast abscess, oral thrush, and severe hyperglycemia with HbA1C of 15.4%. Additional history was relevant for hirsutism, scalp hair thinning, weight gain, and amenorrhea of few months duration. Physical examination was significant for round face, thin scalp hair, oral thrush, facial hirsutism, central obesity, wide abdominal striae, onychomycosis, thin skin with multiple ecchymoses, bilateral lower extremity edema, and thin extremities. Her hypokalemia was resistant to therapy and K level remained in 3.2-3.5 mmol/L range on the third week of admission despite oral and intravenous potassium replacements and spironolactone high dose therapy at 100mg twice a day. Additional laboratory testing showed Cortisol 25.0 (6.70 - 27.60 ug/dL) and normal Aldosterone and renin levels. Given absence of otherwise clear etiology of hypokalemia, and presence of multiple features of Cushing’s syndrome, further inpatient evaluation included 24-hour Urine Free Cortisol level that came back at 2754 (3.5 - 45.0 mcg/24hour), 1 mg Dexamethasone Suppression Test Cortisol of 24.9 (6.70 - 27.60 ug/dL), ACTH of 151.0 (7.2 - 63.3 pg/mL), and 8 mg Dexamethasone Suppression Test Cortisol of 14.2 (6.70 - 27.60 ug/dL). MRI Pituitary showed a pituitary adenoma (0.7 x 0.3 cm) with cavernous sinus involvement. A diagnosis of Cushing disease was made and the patient underwent transsphenoidal surgery on the fourth week of hospital stay with diffuse ACTH staining of the tumor. Postoperatively, cortisol levels were not suppressed suggesting persistent disease, but hypokalemia resolved while on Spironolactone. Conclusion: This patient had several classical features of hypercortisolemia with associated hyperglycemia, recurrent infections, and bone fractures, however the finding that connected the dots and prompted establishing her diagnosis was her severe refractory hypokalemia. Although not a defining feature of Cushing Disease, and usually more pronounced with ectopic ACTH secretion, severe and/or persistent hypokalemia can be part of the presenting symptoms. This case demonstrates the importance of including Cushing Disease as part of the differential diagnosis of persistent hypokalemia in correlation with other clinical signs and diagnostics. Presentation: 6/2/2024

Non-classical presentation of primary aldosteronism in patient presenting with normotensive refractory hypokalaemia leading to delayed diagnosis

Non-classical presentation of primary aldosteronism in patient presenting with normotensive refractory hypokalaemia leading to delayed diagnosis

Refractory hypokalaemia secondary to an aggressive adrenal cortical carcinoma - a case report

Refractory hypokalaemia secondary to an aggressive adrenal cortical carcinoma - a case report

346 Refractory Hypokalemia in ESRD complicated by Ogilive's syndrome

346 Refractory Hypokalemia in ESRD complicated by Ogilive's syndrome

Respiratory arrest following severe muscle weakness as initial presentation of Sjögren’s syndrome: diagnostic and therapeutic strategies: a case report

Background: SjÖgren’s syndrome refers to an autoimmune disorder defined by chronic inflammation as a consequence of the exocrine gland’s lymphocytic infiltration. Patients may present with heterogeneous clinical symptoms involving impairment in the lungs, kidneys, and nervous system. The most common renal involvement is tubulointerstitial nephritis (TIN) responsible for 20% of renal tubular acidosis. We report a case of respiratory failure resulting from severe hypokalemia in a patient with SjÖgren syndrome. Case presentation: A 46-year-old female who experienced progressive quadriplegia leading to respiratory distress caused by severe hypokalemia. Laboratory findings showed: sodium 128 mmol/L, potassium 1.1 mmol/L, Cloride 93 mmol/L, Calcium 7.3 mg/dL (corrected 7.5 mg/dL), albumin 3.3 g/dL, Magnesium 1.8 mg/dL with amylase 244 U/L, lipase 4168 U/L, The ANA test increased slightly and Ro-52, PM-Scl100 showed strong positive results, finally the patient was diagnosed with SjÖgren's syndrome with renal tubular acidosis (RTA). She was later diagnosed with renal tubular acidosis secondary to SjÖgren’s syndrome and treated using methylprednisolone, potassium, and alkali administration. Later, her potassium levels reached normal, muscle weakness improved, and she was extubated. Conclusion: This case emphasizes the concept of an uncommon form of SjÖgren's syndrome in the form of severe refractory hypokalemia due to renal tubular acidosis accompanied by acute pancreatitis disguised in patients without SICCA complaints. Renal tubular acidosis is a rare case, but SjÖgren's syndrome is a cause that must be considered in all patients who present with paralysis due to refractory hypokalemia so that there is no misinterpretation and management.

TARS2 Variants Cause Combination Oxidative Phosphorylation Deficiency-21: A Case Report and Literature Review.

The aim of the study is to explore the clinical and genetic characteristics of the combined oxidative phosphorylation defect type 21 (COXPD21) caused by the TARS2 compound heterozygous pathogenic variants, and to improve clinicians' awareness of the disease. The proband was a girl of first birth, with repeated refractory hypokalemia, hearing impairment, developmental delay, intellectual disability, developmental retardation after infection, high limb muscle tension, and increased serum lactate as the clinical phenotype. The clinical performance, diagnosis, treatment process, and gene characteristics of COXPD21 caused by TARS2 of the case were analyzed, reviewed, and compared with the literature from the CNKI, Wanfang Data, and biomedical literature database (PubMed) until November 2021. The child was diagnosed with COXPD21 after two heterozygous variants in the TARS2 gene were found via whole exome sequencing. One of the variants was c.1679(exon14) A > C (p.Asp560Ala) missense, derived from the mother, and the other was c.1036(exon10)C > T (p.Arg346Cys) missense, derived from the father. The literature was searched and reviewed with the keywords "mitochondrial encephalomyopathy," "TARS2," and "combination oxidative phosphorylation deficiency type 21." A total of four complete domestic and foreign cases were collected from the literature search. COXPD21 onset by a complex heterozygous variant of TARS2 causes refractory hypokalemia, which is rarely reported in China and abroad.

THU016 Hiding In Plain Sight: Florid Cushing’s Disease Presenting As A Severe Extremity Cellulitis

Abstract Disclosure: C.M. Godar: None. E.B. Noble: None. N.O. Vietor: None. T.S. Knee: None. Background: Cushing’s syndrome may rarely present as an emergency known as Florid Cushing’s Syndrome. Patients can exhibit severe hyperglycemia, hypertension, hypokalemia, infections, and hypercoagulability. Cushing’s syndrome is a rare disease, and the constellation of clinical features can be overlooked if clinicians are not aware of the manifestations of hypercortisolism. We present the case of a patient with Cushing’s syndrome that went unrecognized with life-threatening sequelae. Case presentation: A 52-year-old woman with well-controlled type 2 diabetes and hypertension was admitted to the hospital for severe left lower extremity cellulitis. Prior to hospitalization she had noted rapid weight gain, fatigue, weakness, mental clouding, and moodiness. She was admitted for antibiotics and surgical debridement. The infection persisted despite broad spectrum antibiotics, multiple surgical debridements, and skin grafting. She became bacteremic, and extremity amputation was considered. She additionally developed hypertensive emergency, refractory hypokalemia, and hyperglycemia to 396 mg/dL. Exam was notable for facial plethora, supraclavicular fullness, dorsocervical fat pad, and violaceous abdominal striae. Cushing’s Syndrome was suspected, and labs revealed a significantly elevated random serum cortisol of 60.5mcg/dL (Ref 6.2-19.4), significantly elevated 24H urine cortisol of 2157mcg/24H (Ref 0-50), and ACTH elevated to 81.8pg/mL (Ref 7.2-63.3) that confirmed Cushing’s Disease. MRI sella and octreotide scans did not localize a lesion. Inpatient therapy included multiple antihypertensive agents, insulin drip, aggressive potassium repletion, and initiation of ketoconazole to reduce cortisol levels. Ketoconazole was maximally dosed and she underwent surgical exploration and removal of a small pituitary microadenoma. Following surgery, she developed transient adrenal insufficiency requiring hydrocortisone and she no longer required antihypertensives, insulin, or potassium therapy. Follow up 7 years later has revealed no recurrence of Cushing’s Disease. Discussion: Cushing’s Syndrome may present with a variety of clinical features and rarely may present as a medical emergency. Delay in diagnosis can lead to Florid Cushing’s Syndrome which carries high risk for morbidity and mortality. This case illustrates the need for clinician awareness of the features of Cushing’s Syndrome: hypertension, hyperglycemia, rapid weight gain, cushingoid exam features, hypokalemia, hirsutism, virilization, infection, and/or hypercoagulable state. Severe hypercortisolism was responsible for this patient’s refractory infection, and if not controlled, she likely would have endured a lower extremity amputation. Rapid detection with elevated random serum and/or urine cortisol and treatment with a cortisol-lowering agent is critical and lifesaving. Presentation: Thursday, June 15, 2023

SAT327 A Curious Case of Immune Checkpoint Inhibitor Induced Hypophysitis with Transient ACTH-dependent Hypercortisolism

Abstract Disclosure: M. Shi: None. F. AlRubaish: None. N. Gupta: None. V. Larouche: None. S. Christopoulos: None. The use of immune checkpoint inhibitors (ICI) has increased exponentially over the last decade as these agents have shown to substantially improve the prognosis in multiple advanced malignancies. Despite these important clinical benefits, ICI are associated with many immune-related adverse events (irAE). Endocrinopathies are the most frequent irAE and include autoimmune thyroid disorders, hypophysitis and primary adrenal insufficiency. These endocrinopathies often require long-term surveillance and hormone supplementation. We report a relatively novel irAE case of transient central hypercortisolism that progressed to hypopituitarism. A 72-year-old woman with metastatic melanoma on combined ICI therapy of nivolumab-ipilimumab developed subclinical hyperthyroidism (TSH <0.02 mU/L [reference range (RR) 0.40-4.50 mU/L]; FT4 20.2 pmol/L [RR 9.0-26.0 pmol/L]) eight weeks following initiation of her immunotherapy. At week 11, she was found to have refractory hypokalemia (initial potassium at presentation 2.3 mmol/L RR 3.5-5.5 mmol/L) and metabolic alkalosis (pH 7.57 [RR 7.35-7.45]; bicarbonate 39 mmol/L [RR 22-31 mmol/L]). Physical exam was unremarkable for Cushingoid features. Subsequent investigations revealed central hypothyroidism (TSH 0.02 mU/L [RR 0.40-4.50 mU/L]; FT4 8.1 pmol/L [RR 9.0-26.0 pmol/L]) and levothyroxine replacement was started. She also had evidence of hypogonadotropic hypogonadism (FSH 4.2 U/L [postmenopausal RR 25.8-143.9 U/L]; LH 1.5 U/L [postmenopausal RR 13.2-45.7U/L]) and central hypercortisolism with a morning cortisol of 1082 nmol/L [RR 172-497 nmol/L] and an ACTH level of 18.3 pmol/L [RR 1.6-13.9 pmol/L]. The low dose dexamethasone suppression test was not suppressed (morning cortisol at 983 nmol/L). She underwent imaging studies of her abdomen and brain which revealed normal adrenal and pituitary glands, respectively. Close pituitary function monitoring during endocrinology follow-up revealed persistent elevation of cortisol and ACTH levels until week 15, then a subsequent decline in both cortisol and ACTH levels for which she started hydrocortisone replacement. Further follow-up blood work revealed morning cortisol levels below 50 nmol/L [RR 172-497 nmol/L] with undetectable ACTH levels from week 16 onwards. The hydrocortisone and levothyroxine replacement were continued, and the patient remained asymptomatic throughout her follow-ups. This case highlights that a transient episode of ACTH dependent hypercortisolism may be an early marker prior to the development of central adrenal insufficiency from ICI-related destructive immune hypophysitis. Furthermore, our report highlights that physicians and other healthcare professionals should remain vigilant in monitoring laboratory progression in these patients, as early recognition facilitated timely management in our patient and prevented complications. Presentation: Saturday, June 17, 2023

THU577 Acth Dependent Cushing Syndrome Identification And Management Challenges

Abstract Disclosure: B.C. Barreto: None. S. Patrick: None. H. Oktaei: None. H.O. Steinberg: None. Endogenous Cushing Syndrome(CS) is rare with an incidence of 0.2-5.0 per million people per year. 70 to 80% of CS is ACTH dependent and subclassified into Cushing Disease, Ectopic ACTH Syndrome and Ectopic CRH Syndrome. Ectopic ACTH secretion(EAS) has a variable clinical presentation. Atypical features like refractory hypokalemia in a patient with a tumoral lesion should raise suspicion. When imaging is inconclusive, differentiating between pituitary or ectopic disease includes invasive and noninvasive methods. We report a case of EAS. Case: A 57-year-old male with history of metastatic small-cell lung-cancer on palliative chemotherapy was admitted for acute coronary syndrome. Endocrinology evaluated the patient’s uncontrolled hypertension, hyperglycemia, and hypokalemia (1.5 mmol/L). He had no suppression with low dose dexamethasone (cortisol>75mcg/dL, ACTH 926pg/mL). Examination was pertinent for an elevated BMI 36.1kg/m2, hyperpigmented anterior thorax but no other stigmata of hypercortisolism. Laboratory analysis showed baseline cortisol 146.1mcg/dL(8.7-22), ACTH 590pg/ml(6-50), 24hr Urine Free Cortisol 736mcg/24h(5-50), which were not suppressed by high dose dexamethasone suppression test(HDDST). Aldosterone and PRA were undetectable. Brain MRI showed an enlarged pituitary gland, but no focal mass. CT abdomen pelvis showed bilateral adrenal hyperplasia, multiple hepatic masses, and bone lesions. Since the patient was a poor surgical candidate, medical therapy was initiated with ketoconazole 200mg TID, aldactone 50mg BID and potassium chloride 40mEq TID. After twelve days cortisol levels decrease to 65.2 mcg/dL, potassium 3.8 mmol/L and glucose 146 mg/dL. Hospitalization was complicated by a small bowel ileus. Medications were held due to poor gastrointestinal absorption and parenteral octreotide 200mcg TID was initiated. Once the ileus resolved, ketoconazole 200mg TID, eplerenone 50mg daily, and dexamethasone 0.5mg daily was started. Despite medical care, the patient eventually expired. Discussion: The HDDST can help distinguish pituitary from an ectopic ACTH overproduction. HDDST with >50% suppression, has been described with sensitivity-specificity of 60 to 100% for pituitary ACTH source. Symptomatic treatment of CS requires rapid normalization of hypercortisolism action. Surgery is the first line approach. When surgery is not an option, medical therapy should be considered. Adrenal steroidogenesis inhibitors, such as ketoconazole, are the first line due to rapid onset of action. Agents such as glucocorticoid receptor antagonists have limited availability in the inpatient setting. Somatostatin analogs and etomidate that inhibit 11-ßhydroxylase are potential options but require close monitoring. Severe hypercortisolism in the critically ill prompts the use of noninvasive evaluation tools and alternative medical approaches. Presentation Date: Thursday, June 15, 2023

FRI226 Ectopic Cushing’s Syndrome Of Unknown Primary Origin With Etomidate Use

Abstract Disclosure: C. Ohammah: None. J. Lloyd: None. T. Abdulwahid: None. R. Tangri: None. C. Musgrove: None. K. Selk: None. Background: Ectopic Cushing's syndrome (ECS) is rare and requires adrenolytic agents to control hypercortisolism until a definitive plan can be made to treat the underlying cause. We present a case of ECS of unknown primary origin causing immunosuppression due to the hypercortisolism that responded with etomidate infusion. Case: A 61-year-old male who presented to the hospital after a few weeks of increasing weakness, dyspnea, and hemoptysis. In the months prior to his admission, he was found to have persistent hypokalemia, COVID pneumonia, and new onset diabetes mellitus. On admission, his examination was remarkable for proximal hip flexor weakness. Labs were significant for metabolic alkalosis, hyperglycemia (A1c 7.7%) and persistent hypokalemia requiring about 300 mEq of potassium daily. CT chest, abdomen and pelvis was remarkable for aspiration pneumonia, vertebral compression fracture, and bilateral adrenal enlargement. Blood cultures grew Staphylococcus Aureus (MSSA) (suspected lung source) and Candida albicans. Treatment with vancomycin and caspofungin was initiated and narrowed to cefazolin after speciation. His MSSA cleared rapidly however, fungemia was persistent after 1.5 weeks of treatment. MRI brain was unremarkable for causative lesion. Further testing revealed elevated morning cortisol (136.2ug/dL) confirmed on repeated testing and elevated ACTH (653pg/mL). Serum metanephrines were normal. A high-dose dexamethasone suppression was unremarkable. In the following days, he developed respiratory failure secondary to a spontaneous hemothorax requiring intubation and ICU admission. He was started on an etomidate infusion given abnormal liver enzymes and unavailability of metyrapone. The infusion was titrated every 6 hours based on cortisol levels. His liver enzymes improved and ketoconazole was added but later discontinued due to development of thrombocytopenia. His cortisol level decreased (21.5ug/dL) and fungemia cleared. Arrangement for bilateral adrenalectomy was made but the patient decompensated and developed shock requiring pressors. After a goals of care discussion, he was transitioned to comfort measures and eventually passed. Conclusion: ECS is rare, and the diagnosis is challenging and often delayed. Ectopic ACTH can result from various malignancies. Medical management with adrenolytic agents should be considered early in the management of ECS until a definitive plan is made. Etomidate, ketoconazole, metyrapone, and mitotane can be used to treat hypercortisolism to achieve medical adrenalectomy. Bilateral adrenalectomy should be considered in patients without adequate response to adrenolytic agents. This case describes the severity of hypercortisolism from an ectopic ACTH production causing refractory hypokalemia and immunosuppression resulting in fatal infections. We highlight the use of etomidate to control hypercortisolism. Presentation: Friday, June 16, 2023

THU527 Metastatic Adenocarcinoma Of The Colon Concealing An ACTH Secreting Neuroendocrine Differentiated Cluster: A Lethal Zebra Within A Trojan Horse

Abstract Disclosure: M. Velasquez: None. S. Shekhar: None. R.M. Goyal: None. Background: Ectopic ACTH secreting tumors are responsible for almost 10% of all cases of Cushing Syndrome. Tumors associated with this entity are most commonly small cell lung, thymic, and pancreatic neuroendocrine tumors. Few cases of colon adenocarcinoma with paraneoplastic ACTH secretion have been reported. They are associated with poor outcomes. Clinical case: A 57-year-old previously healthy male presented with shortness of breath and hypertension. CTA of the chest revealed metastatic liver lesions. CT abdomen and pelvis confirmed metastatic liver lesions with an apple core colonic mass consistent with a primary malignancy. Liver biopsy showed well-differentiated neuroendocrine tumor; tumor cells were negative for CK20, chromogranin, and CD56 but positive for CK7 and synaptophysin. The Ki-67 index was 30%. He was not evaluated for paraneoplastic hormonal secretion and the colonic mass wasn’t biopsied at that time. Ga-DOTATATE scan was negative for somatostatin uptake. He was started on carboplatin-etoposide + dexamethasone (three doses of 4mg each). Two months later presented with large bowel obstruction. Colonoscopy was performed and histopathology demonstrated colonic adenocarcinoma with focal neuroendocrine differentiation with positive CDX2 and negative CK7 and CK20. Synaptophysin was diffusely positive with sparse chromogranin positivity. ACTH stain of the colonic biopsy was negative. Chemotherapy was switched to FOLFORINOX and dexamethasone (one dose of 12mg). After two weeks of being on this regimen, he developed refractory hypokalemia and metabolic alkalosis and was sent to the emergency department. Vitals signs were within normal limits except for mildly elevated blood pressure. Physical examination remarkable for redness of his truncal skin. He did have changes in his handwriting, 0/3 three-word recall, and reduced short term memory. Primary team performed a morning cortisol that was elevated, and endocrinology was consulted. Two repeated 8AM cortisol level and a serum ACTH were found to be elevated. An 8mg overnight dexamethasone suppression test revealed an increase in cortisol. MRI brain showed no evidence of intracranial abnormalities. Refractory hypokalemia due to ectopic ACTH-dependent Cushing syndrome was diagnosed warranting treatment with ketoconazole. Unfortunately, he developed septic shock which led to his demise. Conclusion: This case illustrates a paradoxical rise in serum cortisol levels after dexamethasone suppression test suggesting the presence of positive feedback effects of exogenous corticosteroids on tumor’s ACTH release/production. Recognition of this syndrome is critical to avoid unnecessary use of exogenous glucocorticoids since they could trigger paraneoplastic Cushing syndrome in these patients. Presentation: Thursday, June 15, 2023

THU518 Ectopic Cushing Syndrome In A Case Of Ewing Sarcoma

Abstract Disclosure: M. Fasen: None. S.E. Mayson: None. Background: Ewing sarcoma (ES) is a rare and aggressive neoplasm occurring in bone and soft tissue in children to young adults. It is part of a spectrum of neoplastic diseases known as the ES family of tumors that display varying degrees of neuroendocrine features. Ectopic Cushing’s syndrome (ECS) is also a rare but severe condition associated with unregulated ACTH or CRH secretion by neuroendocrine tumors (NETs) that can cause severe hypercortisolism. The most common tumors associated with ECS include small cell lung carcinoma, bronchial carcinoid and medullary carcinoma of the thyroid gland. Sarcomas causing ECS are extremely rare with only a handful of cases reported in the literature, mostly in children. Herein we detail what we believe to be the first reported case of ECS occurring in an adult male patient with ES. Clinical Case: A 23-year-old man with ES metastatic to pancreas, liver and bone was admitted to the hospital with acute on chronic back pain and lower extremity weakness, and subsequently diagnosed with cord compression and neutropenia from chemotherapy. New onset hypertension and refractory hypokalemia were observed prompting endocrinology consultation. Physical examination revealed facial fullness, central obesity and wide violaceous striae on his abdomen and axillae. Biochemical evaluation demonstrated blood glucose consistently over 300 mg/dL, serum potassium 2.5 mmol/L, renin 0.9 ng/ml/hr (0.2-1.6 ng/ml/hr), aldosterone renin ratio < 3.3, morning cortisol 73 ug/dL (4-22 ug/dL), and ACTH 1020 pg/mL (72-63 pg/mL). A 1 mg overnight dexamethasone suppression test yielded a serum cortisol of 90 ug/dL and 24-hour urine free cortisol was 6388 ug/d (<60 ug/d). MRI brain demonstrated a normal pituitary gland, and FDG PET-CT showed new areas of uptake in bone concerning for metastatic progression and new bilateral adrenal enlargement without nodularity. High dose dexamethasone suppression testing was deferred in the context of rapid neuropsychiatric deterioration characterized by somnolence and psychosis. The decision was made to treat immediately with spironolactone and ketoconazole, as well as insulin for hyperglycemia management. His mental status, blood pressure, serum potassium, glucose and cortisol improved following the initiation and titration of medical therapy. He was discharged home with addition of metyrapone and hospice support. Two months later the patient succumbed to his illness. Conclusion: The severity of hypercortisolism is a negative predictor of survival and prompt control should be the main therapeutic goal along with prevention of cortisol-induced complications in patients with ECS. ACTH and CRH immunostaining of the patient’s ES histopathology slides is pending. Presentation: Thursday, June 15, 2023

THU505 Severe Acute Hypercortisolism From Stable Pre-existing Lung Nodule

Abstract Disclosure: N. Raza: None. S. Wagle: None. R.N. Kiani: None. K. Kaput: None. A 63-year-old male with uncontrolled hypertension and Rheumatoid arthritis was admitted for acute psychosis, progressive asthenia, and severe refractory hypokalemia. He was afebrile on admission and blood pressure was 151/99 mmHg. Physical examination lacked typical Cushingoid appearance of moon facies, central obesity, or purple striae. Labs showed a potassium of 1.8 (ref: 3.3-5 mmol/L), HbA1c 6.0% (ref<=5.6 %), 24-hour urinary free cortisol of 9438 (ref<=60.0 ug/d) and random ACTH level of 229 (ref:7.7-63.3pg/ml). The presentation was felt to be consistent with ectopic ACTH dependent Cushing's syndrome. He was treated with ketoconazole 400 mg BID, Deep veinous thrombosis prophylaxis and trimethoprim-sulfamethoxazole daily for PJP prophylaxis. CT chest/abdomen/pelvis was performed and showed a 1.9 cm right middle lobe pulmonary nodule. Past records were reviewed and showed a stable lung nodule from 2020 (2.5 years earlier). Elective lung biopsy was discussed, and the patient was discharged home with plan for outpatient biopsy. Prior to his biopsy, he was readmitted with worsening agitation, hypertension, and extremity edema. After extensive discussion with CT surgery, a decision was made to perform robotic-assisted thoracoscopic resection of the right middle lobe with mediastinal lymph node dissection. Post-surgery his BP improved, agitation resolved, and cortisol level declined to 3.4 (ref: 6.0 - 18.4 ug/dL). Final pathology showed a well differentiated neuroendocrine tumor, low grade. Lymphovascular invasion was present, and one lymph node was positive for tumor. ACTH immunostaining was performed and was also positive. Ectopic ACTH dependent Cushing syndrome represents a rare condition, contributing to 5-20% of Cushing’s cases. Lung carcinoid tumor is one of the major causes of ectopic ACTH syndrome and typically resolves with surgery. Unusual in our case is the stability of the lung lesion prior to his acute decompensation and lymph node positivity. To date, we have not identified a reason for the indolent nature of his tumor. He is currently on a hydrocortisone taper and is actively undergoing treatment planning with our multidisciplinary peer review process. Essential to his management is the coordination of multiple providers, which includes complex medical decision making and treatment decisions. In the future, lung carcinoid should be considered in the differential for persons with difficult to control hypertension and a stable pulmonary nodule Presentation: Thursday, June 15, 2023

Late Presentation of Bartter Syndrome as Refractory Hypokalemia

Bartter syndrome is a rare salt-wasting nephropathy characterized by sporadic or inherited genetic defects in transporters and channels in the thick ascending limb of the loop of Henle and distal tubule of Nephron leads to renal potassium wasting with hypokalemia, metabolic alkalosis, increased renin-angiotensin-aldosterone system, normal blood pressure. Most of the cases have been noted in the pediatric age group and adult-onset cases are very rare. Here we report an unusual case report of Bartter's syndrome in a 52 years old male patient.

A Severe Case of Hypokalemic Metabolic Alkalosis: A Quiz

A Severe Case of Hypokalemic Metabolic Alkalosis: A Quiz

A Case of Unusual Oral Theophylline Toxicity

Theophylline is a methylxanthine medicine used for treatment of bronchospasm in asthma and COPD. This reports illustrates a case where a patient was taking oral theophylline for COPD, was admitted to hospital with confirmed COVID-19 and subsequently developed a combination of vague signs, symptoms and biochemistry results, such as confusion, sinus tachycardia, compensated metabolic acidosis, hypomagnesaemia and refractory hypokalaemia. These non-specific signs and symptoms were initially attributed to other causes such as infection; however subsequent review of the patient’s medication suggested that theophylline toxicity could be the cause. These non-specific signs and symptoms were present despite normal plasma aminophylline level and resolved once treatment with oral theophylline was ceased.

PS-R03-10: CASE REPORT: CUSHING SYNDROME IN A YOUNG MALE

A 27-year-old male without any significant past medical history was advised to visit a hospital for elevated blood pressure, elevated liver enzymes, and dyslipidemia in a workplace health checkup. His body weight had increased by more than 10 kg in the last two years. He presented to our department and underwent laboratory work-up. He had bilateral lower limb pitting edema, hypokalemia, and elevation of low-density lipoprotein. No sign of dysthyroidism, renin-angiotensin-aldosterone system disorder, or increased catecholamine secretion was found. Diet and exercise therapy and calcium channel blocker did not improve his hypertension, and he suffered from lumber vertebral fracture, refractory hypokalemia, and lower leg cellulitis. He was admitted to our department for detailed examination of worsening lower limb edema. On admission, he had striae on his abdomen and legs as well as edema of both lower extremities. The endocrinological data showed high levels of adrenocorticotropic hormone (ACTH) and cortisol. Overnight 1 mg dexamethasone suppression test resulted in a non-suppression response, and his circadian rhythm of cortisol was absent. Urine cortisol level was high. These findings confirmed the diagnosis of ACTH-dependent Cushing syndrome. A contrasted magnetic resonance imaging (MRI) scan demonstrated enlargement of the pituitary gland more than 1 cm in length. Taking into account drug-resistant hypokalemia and vulnerability to infection, he was administered with metyrapone 500 mg per day until he underwent transsphenoidal hypophysectomy. The pathological findings were consistent with that of a pituitary adenoma. Postoperative MRI scan showed remnant lesions which stretch to the bilateral cavernous sinuses and the right middle cranial fossa. Although a decrease in urine cortisol was observed, the absence of a circadian rhythm of cortisol, hypertension, and hypokalemia persisted. He is now treated with somatostatin analog and craniotomy followed by gamma knife surgery is planned. Cushing syndrome should be suspected in cases of early-onset hypertension with symptoms including weight gain, hypokalemia, and bone fracture.

224: ALTERNATIVE MANAGEMENT OF DIABETIC KETOACIDOSIS DUE TO REFRACTORY HYPOKALEMIA

Introduction: In a hypoglycemic state, potassium levels are falsely elevated due to potassium shifting extracellularly. Once insulin is initiated, potassium will reverse, returning intracellularly, and leading to a lower potassium level. It is this reason that the standard protocol of diabetic ketoacidosis (DKA) treatment is to not begin insulin until potassium is replenished above a designated level. Below we present a patient with DKA that required treatment outside of standard protocol due to refractory hypokalemia. Description: The patient is a 25-year-old male that presented to the emergency department (ED) with elevated glucose for the past few weeks. He is a type-2 diabetic, controlled with diet and exercise for the last year. Prior to which, he had been on insulin. The only exacerbating factor he can think of is receiving the J&J vaccine around the same time. Other associated symptoms are difficulty breathing, abdominal pain, mild nausea, but no vomiting. In the ED, he was found to be in DKA with labs significant for severe acidosis and critical hypokalemia of 1.6 mmol/L. A central line was placed and potassium repletion began prior to initiating insulin drip, with plan to start insulin once potassium corrected. Following aggressive potassium repletion with up to 40 mEq per hour, it persistently remained below 3 mmol/L. Thus, it was decided to start the patient on the lowest rate of the insulin drip at 0.02 units/kg/hr until his potassium rose above 3.3 mmol/L as per our protocol. While being on the insulin drip, he was also receiving 20 mEq potassium hourly via IV, 40 mEq orally every four hours, with frequent basic metabolic profiles every two hours. The patient remained on the insulin drip for three days until he was finally able to be transitioned to long-acting insulin, 73-hours after admission. Discussion: The treatment of refractory hypokalemia in the setting of DKA is intricate. Insulin, while imperative for the treatment of DKA, can worsen hypokalemia, therefore sequence of medication administration is important in treatment. It is important for providers to recognize and identify the side effects of these treatments. In this case, multidisciplinary rounds were crucial in both monitoring and replacing potassium while on an insulin drip.