Severe Hypokalemia Research Articles

Osmotic demyelination syndrome: revisiting the diagnostic criteria through two fatal cases

BackgroundOsmotic Demyelination Syndrome (ODS) encompasses Central Pontine Myelinolysis and Extrapontine Myelinolysis, both of which are serious neurological conditions linked to the overly rapid correction of hyponatremia. Despite growing evidence, the exact etiology of ODS remains incompletely understood. The present paper describes two case studies, aiming to provide a comprehensive overview of the pathological findings and clinical outcomes associated with ODS.Case presentationCase #1. A 74-year-old woman was admitted to the emergency department following a head trauma caused by a loss of consciousness. Initial laboratory tests revealed severe hyponatremia (sodium level of 101 mmol/L) and hypokalemia (potassium level of 2.9 mmol/L). The patient underwent corrective therapy with saline and potassium chloride. Despite the correction of electrolyte imbalances, the patient developed a hyperintense lesion in the median portion of the pons on T2-fluid-attenuated inversion recovery (FLAIR) MRI sequence 14 days post-treatment, consistent with ODS. The patient’s condition deteriorated, leading to irreversible coma and status epilepticus, culminating in death 32 days after admission. Case #2. An 81-year-old woman with a medical history of hypothyroidism, hypertension, major depression, and stage 3 chronic kidney disease presented with mild gait disturbances. Subsequent testing revealed severe hyponatremia (sodium level of 100 mmol/L). Following an initial clinical improvement due to sodium correction, the patient’s condition worsened, with symptoms progressing to confusion, lethargy, and eventually, ODS. Dermatological manifestations, including blistering lesions and facial edema, appeared as the condition advanced. The patient succumbed to irreversible coma 47 days after admission.ConclusionODS traditionally carried a poor prognosis, with high mortality rates and diagnoses often made postmortem. However, recent advances in understanding the pathophysiology, along with improvements in diagnostic techniques such as MRI and intensive care treatments, have led to earlier identification, treatment, and recognition of milder forms of the syndrome. Despite these advancements, ODS remains a critical condition with significant risks, particularly following the rapid correction of severe hyponatremia.

PARALISIA PERIÓDICA HIPOCALÊMICA TIREOTÓXICA: RELATO DE CASO E REVISÃO BIBLIOGRÁFICA INTEGRATIVA

Thyrotoxic Hypokalemic Periodic Paralysis (THPP) is characterized by episodes of muscle weakness associated with hyperthyroidism and hypokalemia. The following study aims to report a case of Thyrotoxic Hypokalemic Periodic Paralysis, in addition to reviewing this uncommon topic in daily medical practice. The patient was a 38-year-old male patient, previously healthy, who was admitted to the emergency room due to pain syndrome in the lower limbs, concomitant with gradual, ascending and progressive loss of strength in the upper limbs, associated with generalized paresis. Hypokalemic flaccid paralysis was confirmed after gasometric and laboratory evidence of severe hypokalemia concomitant with the condition. Investigation was continued with a thyroid profile, which showed suppressed TSH and elevated free T4. The Burch and Wartofsky index was evaluated, compatible with imminent thyrotoxic crisis, and correction of hypokalemia and specific management with propylthiouracil (PTU), corticosteroid therapy and beta-blocker were instituted, with excellent clinical and laboratory response. Subsequently, the presence of antibodies above the reference values ​​was evidenced, confirming the presence of thyroid autoimmunity. Therefore, the insidious onset and rapid deterioration resulting from PPHT are emphasized, with the need for its early recognition as a differential diagnosis in the face of flaccid paralysis, considering the request for thyroid function tests in acute situations for adequate diagnosis and treatment.

Respiratory failure and rhabdomyolysis caused by severe hypokalemia in a young female with hypertension: a rare critical condition in primary aldosteronism

BackgroundThe two classic manifestations of primary aldosteronism are hypertension and hypokalemia. However, acute respiratory failure due to hypokalemia in primary hyperaldosteronism is rare.Case presentationThe patient was a 27-year-old female who presented with drowsiness and weakness in all extremities. She had been diagnosed with hypertension three years prior, with irregular follow-up, and had a history of preeclampsia one year later. She exhibited high blood pressure and severe hypokalemia (2 mEq/L), leading to respiratory depression and impending respiratory arrest. Consequently, the patient was intubated and transferred to the intensive care unit (ICU). She also developed rhabdomyolysis. Blood pressure tests, including hormonal tests (aldosterone: 13.2 ng/dL, plasma renin activity: 0.32 ng/mL/h), were conducted. Due to the high aldosterone-renin ratio, an abdominopelvic computed tomography (CT) scan was performed. The CT scan revealed a 14 × 12 mm round mass with a washout value above 60%, consistent with an adrenal adenoma, leading to a diagnosis of primary aldosteronism. The patient was discharged after stabilization, and one and a half months after ICU admission, a laparoscopic left adrenalectomy was successfully performed without post-operative complications. Histopathology showed encapsulated hypertrophy of the adrenal cortex with a predominance of large clear cells, confirming the diagnosis of adrenal adenoma. At the most recent follow-up, the patient had normal potassium levels, was normotensive without any medications, and exhibited no alarming signs or symptoms.ConclusionRespiratory depression to the extent of impending respiratory failure and rhabdomyolysis as a result of hypokalemia in primary aldosteronism are extremely rare. In this patient, who developed respiratory depression due to resistant hypokalemia, timely investigation of secondary causes and diagnosis of adrenal adenoma were crucial. The surgery provided definitive treatment for the patient’s blood pressure and prevented the recurrence of life-threatening complications.

Biochemical changes in the aetiology of floppy kid syndrome in goat kids

AbstractIn the herd, 20 of 75 goat kids born became progressively ill. Twelve affected kids, aged 4–9 days, exhibited muscle weakness, pain without fever, diarrhoea and dehydration. Their health deteriorated rapidly, and within a few hours, one kid died. The results of the blood test revealed severe metabolic acidosis, hypokalaemia and changes in urea concentrations. Floppy kid syndrome was diagnosed. Treatment was initiated to correct the acid–base balance, and all affected kids were temporarily separated from their mothers. All the treated kids recovered. Before the onset of clinical signs, elevated urea concentrations and differences in maternal blood potassium levels were observed. This is the first report on changes in potassium concentrations in periparturient dams of goat kids with and without floppy kid syndrome, as well as the first report on changes in urea concentrations in kids before the onset of clinical signs.

Severe hydronephrosis complicated with primary aldosteronism: a case report and review of the literature

BackgroundPrimary aldosteronism is characterized by high plasma aldosterone and low renin. The plasma aldosterone-to-renin ratio is recommended for screening. Severe hydronephrosis leads to renal parenchymal ischemia, resulting in increased renin secretion. Since nonsuppression of renin may cause a negative result in the aldosterone-to-renin ratio test, severe hydronephrosis and primary aldosteronism occurring simultaneously in a patient are challenging to diagnose.Case presentationA 54-year-old Chinese man of Han ethnicity was diagnosed with hypertension and severe hypokalemia (minimum 1.57 mmol/L) 13 years prior, and was also diagnosed with severe hydronephrosis due to congenital ureteral stenosis on the left side. His clinical features suggested primary aldosteronism, but the aldosterone-to-renin ratio result of the patient was negative every time he underwent the primary aldosteronism screening test. No further treatment for primary aldosteronism was performed, which led the patient to suffer from severe hypokalemia, such that he was taking 12–15 g/day potassium chloride orally to keep his blood potassium between 3.0 and 3.5 mmol/L (reference value, 3.5–5.5 mmol/L) for 13 years, and the patient needed to be hospitalized in the intensive care unit for rescue several times. At admission, although the aldosterone-to-renin ratio result of the patient was negative, we still did the saline stress test and captopril inhibition test, and the results showed that the plasma aldosterone level was not lower after the test than before the test. Adrenal enhanced computed tomography suggested an adenoma in the left adrenal gland, and the results of adrenal vein sampling suggested that the left side was the dominant side. Therefore, laparoscopic total resection of the left adrenal gland was performed, and 2 weeks later, the patient developed short-term renal function impairment and hyperkalemia, but his renal function and blood potassium returned to normal after treatment that included fluid rehydration. The patient’s biochemical test results and clinical symptoms were completely normal after 1 year.ConclusionWe suggest that for patients with a high suspicion of primary aldosteronism in the clinic, comprehensive analysis must be performed in combination with clinical characteristic assessments, such as severe hydronephrosis, if renin is within the normal range or if the aldosterone-to-renin ratio result is negative at screening and diagnostic tests, and adrenal vein sampling should be performed if necessary. It can help avoid misdiagnoses and contribute to the treatment of patients with severe hydronephrosis and primary aldosteronism.

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

7533 Mifepristone For Primary Hypercortisolism Contributing To Profound Hypokalemia

Abstract Disclosure: J. Watkins: None. J.G. Melendez-Rivera: None. E. Florin: None. K.B. Rivera: None. Background: Primary hypercortisolism is typically treated surgically, but when adrenalectomy is not pursued, medical therapy can be effective. Adrenal enzyme inhibitors or glucocorticoid antagonists can be used. Mifepristone is the only available glucocorticoid antagonist at this time. Mifepristone is approved specifically for glucose control in Cushing’s syndrome. Because mifepristone blocks cortisol action rather than production, hormone levels may increase and are unhelpful in titrating the mifepristone dose. Rather, titration is based on clinical manifestations of Cushing’s syndrome. Further, the increased hormone levels can lead to increased activation of mineralocorticoid receptor, in addition to the increased activation caused by hypercortisolism, which can cause hypokalemia. Clinical Case: An 82-year-old woman had been following with endocrinology for hypercortisolism found to be secondary to bilateral adrenal adenomas. She preferred medical therapy rather than surgery given her age, and she was started on mifepristone 300 mg/day. Within a few weeks, she developed leg swelling and was started on a low dose of chlorthalidone by her primary care doctor. She then presented to the emergency department after five days of nausea, abdominal pain, palpitations, and reduced oral intake. She was found to have severe hypokalemia (potassium 1.8 mEq/L, normal 3.5 - 5.0 mEq/L), and her creatinine was 0.97 µmol/L (baseline 0.6-0.75 µmol/L). Physical exam was unremarkable. CT abdomen/pelvis revealed three adrenal lesions, similar to a study from one year prior. Her mifepristone was stopped, and she was given potassium supplementation and started on spironolactone with eventual stabilization of her potassium level. She was also started on ketoconazole for management of her hypercortisolism. It was discussed that she might now consider adrenal vein sampling to pursue adrenalectomy. Severe hypokalemia and borderline metabolic alkalosis were most likely multifactorial in etiology. Hypercortisolism predisposed the patient to hypokalemia. She was then started on mifepristone, which inhibits the glucocorticoid receptor thereby increasing activation of the mineralocorticoid receptor, which likely further contributed to hypokalemia. The leg swelling that she developed and saw her primary doctor for may have been a sign of over-activation of the mineralocorticoid receptor due to the mifepristone, and prescription of chlorthalidone at that time would have worsened the hypokalemia that was likely present at that time. Conclusion: It is important to be aware of the possible severity of side effects of medical therapy for hypercortisolism, such as severe hypokalemia. There is a role for increased awareness of routine monitoring of potassium levels, as well as considering spironolactone in many patients even prior to onset of hypokalemia. Presentation: 6/3/2024

6409 Successful Treatment Of Severe Ectopic ACTH-dependent Cushing’s Syndrome With Osilodrostat

Abstract Disclosure: K.A. Lee: None. C. Mendes Pessoa: None. W. Huang: Consulting Fee; Self; WH, Honoraria from Consulting and Speaking received from Recordati Rare Disease. Background: Cushing’s syndrome due to ectopic ACTH secretion is rare and may progress rapidly, making treatment very challenging. Previous case reports have described therapeutic options including adrenal steroidogenesis inhibitors, bilateral adrenalectomy (BAL), and adrenal embolization with success. Clinical Case: A 27-year-old woman with metastatic neuroendocrine tumor presented with sudden onset and rapidly progressing symptoms of fatigue, muscle weakness, acne and weight gain within two weeks. Laboratory findings confirmed severe Cushing’s syndrome due to ectopic ACTH secretion: AM cortisol 173.4 µg/dL (5-25), ACTH 1425 pg/mL (7.2-63.3), 24 hour urine cortisol 29,498 mcg/24hr (4-50), DHEA-Sulfate 1314 µg/dL (65 - 380), and testosterone 133 ng/dL (0-100). She was also found to have severe hypokalemia, hypocalcemia and hyperglycemia (despite an HbA1C of 6.2 at 2 weeks before presentation). CT- scan showed diffuse thickening of the bilateral adrenal glands. Due to widely metastatic disease in the peritoneum, BAL was considered non-feasible. The patient was admitted to hospital and initiated on osilodrostat at 20mg twice daily (after correction of hypokalemia) with close monitoring of her electrolytes, cortisol, EKG and steroid withdrawal symptoms. There was a rapid improvement of cortisol levels in response to osilodrostat. During treatment, she developed steroid withdrawal symptoms for which she was started on medium dose hydrocortisone. Bilateral adrenal arterial embolization was attempted but ultimately needed to be converted to right only adrenal gland embolization due to a hypertensive urgency and difficulty with catheterization. Her symptoms of Cushing’s syndrome significantly improved with the treatment. During her hospitalization, her hypokalemia was managed with spironolactone and potassium supplement, hypocalcemia with calcium supplement, and hyperglycemia with basal and bolus insulins. With significant improvement of cortisol levels, her hypocalcemia and hyperglycemia resolved and required no further treatment. Her potassium levels normalized and spironolactone was stopped. She remains on potassium supplement to keep K level at upper half of normal range to avoid long QTc. After discharge, her morning cortisol levels (before morning dose of hydrocortisone) continued to decrease and her osilodrostat dose was gradually tapered to 5mg once daily at night. Hydrocortisone was continued as part of the block-and-replace regimen. Conclusion: This case described a unique sudden onset and rapid progression of ectopic ACTH dependent Cushing’s syndrome and successful utilization of a block-and-replace approach by using the steroidogenesis inhibitor osilodrostat in prompt control of the hypercortisolism and related comorbidities. We also explored the feasibility of adrenal embolization for definitive management in the context of unfeasible BAL. Presentation: 6/2/2024

12459 Exceptional Response To A Single Dose Of Pembrolizumab As Salvage Therapy In A Patient With Metastatic Adrenocortical Carcinoma (ACC)

Abstract Disclosure: L. Branchaud-Croisetière: None. J. Castilloux: None. E. Turcotte: None. A. Bégin: None. M. St-Jean: Advisory Board Member; Self; GlaxoSmithKline, HRA Pharmaceuticals. Research Investigator; Self; AstraZeneca, Novo Nordisk, Spruce Biosciences. Speaker; Self; GlaxoSmithKline, Recordati Rare Diseases. In advanced ACC, limited effective treatment options are available beyond mitotane and cytotoxic chemotherapy. PD-L1 blockade has shown promising results in small numbers of advanced ACC. In ACC, the reported partial response rate to pembrolizumab is around 25%.[1] Only one case of a significant partial response to a single dose of Pembrolizumab as salvage therapy for metastatic ACC was previously published.[1] In April 2023, a 19-year-old woman presented with severe hypertension, hypokalemia and clinical signs of Cushing syndrome (CS). Thoraco-abdominal scan revealed a left-sided cluster of confluent adrenal masses (7.3 x 14.4 x 11.4 cm), a left cortical renal lesion (2.8x2x2.1cm), a right ovarian teratoma (7.9 x 7.8x7.9 cm) and at least 25 pulmonary micronodules. FDG-PET SCAN revealed a significant hypermetabolism of the left adrenal lesions (SUV 18.6), ovarian teratoma (SUV 5.5) and pulmonary micronodules (SUV 1.1-2). Cortisol and androgens secretion was confirmed biochemically. Initially, she was not candidate for a debulking surgery because the tumor was surrounding the aorta, and mesenteric arteries. Hypertension and hypokalemia were treated with spironolactone, amlodipine, amiloride and irbesartan. Cushing syndrome was treated with metyrapone. In April 2023, Etoposide-Doxorubicine-Cisplatin (EDP) was administered in combination with Mitotane (max: 8g/day). After 6 cycles of EDP-M the disease regressed slightly but was considered stable based on RECIST criteria. After 8 cycles, the follow-up imaging showed a progression of the adrenal lesion (9.2x18.2cm) but stable pulmonary micronodules. A biopsy of the adrenal lesion, for therapeutic purpose, revealed microsatellite stability (MSS). The patient refused germinal genetic testing. It was decided in multidisciplinary tumor board to try Pembrolizumab. In December 2023, she received one cycle of Pembrolizumab (140mg), but the treatment was complicated by grade 4 immune-mediated hepatitis. A few weeks following Pembrolizumab she completely normalized her blood pressure and hypokalemia despite cessation of all her anti-hypertensive drugs. Pembrolizumab and Mitotane were stopped and hepatitis completely resolved after two months of Mycophenolate Mofetil and ongoing decreasing dose of prednisone. In March 2024, CT scan showed a 60% regression of the adrenal mass (4.1 x 7.2 cm), stability of the renal lesion and ovarian teratoma and complete resolution of the pulmonary micronodules. We suspect an ongoing effect of immunotherapy and Mitotane, since Mitotane levels were still in the therapeutic range (15.1 mg/L) six weeks following cessation. Mitotane was resumed in March 2024. The patient will potentially have a resection of the left adrenal lesion in the next month. This is second published case of a significant response to Pembrolizumab as second-line therapy for advanced ACC. [1] Raj Net al. J Clin Oncol. 2020 Presentation: 6/1/2024

7342 Thyrotoxic Periodic Paralysis

Abstract Disclosure: G. Arora: None. Case presentation: A 40 year old male with no significant past medical history presented to the emergency department with diffuse body weakness for one day. On the night prior to admission, his thighs started getting sore which in a matter of a few hours, progressed to weakness involving his entire body. He was unable to flex his hips, shoulders, and neck. He was unable to get up or move without assistance. He was found to have an irregular heartbeat two weeks prior to admission and had undergone a thyroid ultrasound which showed inflammation of the thyroid gland. He was not started on any new medications. He endorsed fatigue, palpitations, neck swelling, and 45 lbs unintentional weight loss over 6 months. No fever, chills, vision changes, congestion, chest pain, shortness of breath, cough, tingling, numbness or weakness. He denied alcohol or drug use. Physical examination was notable for blood pressure 151/80 mm Hg, heart rate 120 bpm, enlarged thyroid gland tender to palpation, and muscle weakness (motor strength 3/5 in flexors and extensors of hips and knees). Labs were notable for K 2.3 (3.5 - 5.1 mmol/L), ALP 218 (32 - 91 U/L), TSH <0.010 (0.400 - 4.300 mcIU/mL), Free T4 3.5 (0.6 - 1.6 ng/dL), CK 608 (49 - 397 U/L). Urine toxicology was negative. MRI spine did not show any acute abnormality except for thyromegaly. He received potassium supplementation which led to symptomatic improvement and was admitted to medical floor. Further tests revealed: TSI 39.50 (<=0.54 IU/L), TSH receptor antibody 26 (<=1.75 IU/L), thyroid microsomal antibody 773.3 (0.0 - 9.0 IU/mL), anti-thyroglobulin antibody 4 (<4 IU/mL). Thyroid ultrasound showed an enlarged, heterogenous, hypervascular thyroid without any nodules. He was started on Propranolol and Propylthiouracil, which led to symptom resolution and he was discharged. Discussion: Thyrotoxic periodic paralysis (TPP) is a rare muscle disorder, belonging to the family of diseases called channelopathies. Thyroid hormone increases tissue responsiveness to beta-adrenergic stimulation, which increases Na-K ATPase activity on the skeletal muscle membrane driving potassium into cells. This leads to hyperpolarization of the muscle membrane and relative inexcitability of the muscle fibers, especially in the presence of a trigger such as provocation with exercise, fasting state or a high carbohydrate meal (insulin stimulates Na-K ATPase pump). Furthermore, more than 95% of TPP cases occur in males. This predominance is due to androgen-induced Na-K ATPase sensitization, more pronounced hyperinsulinemia, comparatively higher sympathetic and catecholamine-induced Na-K ATPase activity and higher muscle mass in males. Given the life-threatening association of severe hypokalemia, TPP should be considered in all patients presenting with acute painless muscle weakness. Presentation: 6/3/2024

9388 Unusual Case Of Ectopic Adrenocorticotropic Hormone Syndrome Secondary To Non-small Cell Lung Cancer

Abstract Disclosure: A. TakallooBakhtiari: None. G.L. Nunlee-Bland: None. V. Ganta: None. A. Zenebe: None. H. Abdalla: None. A. Elobeid: None. W.A. Odonkor: None. Introduction: Ectopic adrenocorticotropic hormone syndrome (EAS) is a rare condition due to adrenocorticotropic hormone (ACTH) release from non-pituitary tumors. It increases the mortality of affected patients thus finding and removal of the ACTH-producing source allows for curing or reduction of symptoms and serum cortisol levels. The most common cause of EAS is lung cancer. Cushing syndrome (CS) due to EAS is an uncommon paraneoplastic phenomenon in non-small cell lung cancer. Clinical case: The patient is an 80-year-old man with a past medical history of hypertension, dementia, stroke, schizophrenia, and recently diagnosed lung adenocarcinoma. He presented with a few weeks history of dysuria and generalized fatigue. There was no family history for any endocrine disorders. He has a 40 pack-year history of tobacco use. He denied alcohol or illicit drug use. Upon initial evaluation, VS: BP 155/95 mmHg, HR 82 beats/min, Ht 77 inches, Wt 125 lb with a BMI 14.7 Kg/m2. He had no typical symptoms of CS. A physical exam showed a cachectic man with no other remarkable findings. Laboratory tests on admission showed severe hypokalemia of 1.8 mEq/L (3.5-5 mEq/L) with hypochloremic metabolic alkalosis. (bicarbonate 45 mEq/L (22-28 mEq/L) and chloride 79 mEq/L (96-106 mEq/L)). Patient was normoglycemic with HbA1c of 5.0%. Random morning cortisol was 55 μg/dL (13-24 μg/dL). Supine renin and aldosterone levels were 0.45 ng/ml/h (0.25-5.8 ng/ml/h) and 1.0 ng/dL (3-16 ng/dL), respectively, excluding hyperaldosteronism. Beside urinary tract infection, other biochemical workup revealed elevated 24-h urinary free cortisol level 5233 mcg/24h (4.0-50.0 mcg/24h) with creatinine 0.7 g/24h (0.5-2.15 g/24h). Failure to suppress cortisol with low dose dexamethasone suppression test (LDDST) was evident: morning cortisol >60.0 g/dL , with concurrent serum dexamethasone 299 ng/dL (180-550 ng/dL). Plasma ACTH level was elevated 327 pg/ml (6-50 pg/ml), favoring ACTH-dependent CS. A magnetic resonance imaging (MRI) of the sella and computed tomography (CT) of the abdomen did not show pituitary or adrenal masses. Therefore, a diagnosis of ectopic CS due to lung cancer was established. Pathology of the lung mass showed tumor cells were negative for synaptophysin, chromogranin, and CD52. The immunohistochemically findings support primary adenocarcinoma of the lung. Patient refused surgical or medical treatment and was discharged to a hospice facility. Conclusion: The clinical presentation of EAS ranges from the abrupt onset of the signs and symptoms of severe hypercortisolism, including hypertension, hypokalaemia, metabolic alkalosis as in our patient to the gradual and slow onset of the classical signs and symptoms of CS. Though EAS with adenocarcinoma of the lung is rare, it is important to consider it within the differential diagnosis of any adenocarcinoma of the lung presenting with the relevant symptoms. Presentation: 6/3/2024

7743 A Case Study of Ectopic Adrenocorticotropic Hormone Secretion from Pancreatic Neuroendocrine Tumor

Abstract Disclosure: K.S. Wei: None. J. Huang: None. Introduction: Pancreatic neuroendocrine tumors (PanNETs) are uncommon cancers that account for less than 2% of pancreatic malignancies. Even rarer are ACTH-producing NETs which may only become symptomatic until after metastasis. This case study examines the distinct presentation and diagnostic complexities associated with ectopic adrenocorticotropic hormone (ACTH) secretion from a PanNET. Clinical Case:A 42 year-old male with hypertension and type 2 diabetes initially presented to the hospital with increased abdominal girth for one month, bilateral lower extremity edema for two weeks, and generalized abdominal pain. He had unremarkable surgical, family, and social histories. Patient was afebrile, normotensive, saturating well on room air, with exam notable for a distended abdomen and 2+ bilateral pitting edema. Admission labs were notable for potassium of 2.4 (ref: 3.5-5.1 mmol/L). MRI abdomen showed hepatomegaly with numerous heterogeneously enhancing masses and an ill-defined pancreatic tail mass with involvement of the spleen. Liver biopsy showed well-differentiated neuroendocrine tumor, grade 2. He was started on octreotide 20mg q4weeks and capecitabine/temozolomide q4weeks. Two months later, the patient was readmitted after presenting with back pain for two days, found to have acute compression fractures of T9-L1 without spinal PET activity. At follow-up visit with endocrinology, he endorsed easy bruising and muscle weakness and had hypertension (161/96 mmHg) with hypokalemia. Random cortisol was 43.7 (ref: 2.5-11.9 mcg/dL). ACTH was 124 (ref: 6-50 pg/mL) despite receiving chemotherapy. 24-hour urine cortisol was 3,049 (ref: 4-50 mcg/24 hrs). He was diagnosed with ectopic Cushing’s disease from ACTH-producing PanNET leading to osteoporosis and fracture of the vertebral bodies. For the ectopic Cushing’s disease, he was started on ketoconazole 200mg BID with plan to start osilodrostat once approved. For the fracture, he is scheduled for Zometa infusion and IR kyphoplasty. Conclusion: This case offers several important clinical insights. In patients with PanNET with Cushingoid exam findings, ACTH-producing PanNET should be high on the differential. Most ACTH NETs are aggressive often with liver metastases, whereby metastatic disease will have already occurred by the time the Cushingoid features develop. The initial severe hypokalemia and hypertension should have prompted investigation for mineralocorticoid excess from hypercortisolism, which may have led to an earlier diagnosis of ectopic ACTH Cushing’s disease, thereby decreasing the possibility of developing vertebral fractures, uncontrolled diabetes and hypertension. Ketoconazole or osilodrostat may be used to treat Cushing’s disease from ACTH NETs. Presentation: 6/1/2024

6568 A Novel Case of Liddle Syndrome in Siblings: Insights into a Rare Genetic Mutation

Abstract Disclosure: A.B. Humrickhouse: None. M. Peltsverger: None. Introduction: Liddle syndrome (LS) is an inherited form of hypertension caused by a mutation in the epithelialsodium channel (ENaC). This condition is characterized by hypertension (HTN), hypokalemia,hyporeninemia, and metabolic alkalosis, although clinical presentation can vary. Asymptomaticearly-onset HTN is common, and if left undiagnosed, it can lead to advanced renal disease,cardiovascular complications, stroke, and even sudden death. Treatment typically involves theadministration of ENaC blockers such as amiloride and triamterene. We present a novel case ofLS in two siblings resulting from a missense mutation in the SCNN1B gene. Case Presentation: The patient is a 24-year-old Hispanic female who presented for evaluation of poorly controlledHTN and severe hypokalemia of 2.9 mmol/L during the first trimester of pregnancy. She wasdiagnosed with HTN at age eighteen. The family history was notable for resistant HTN in herfather and younger brother. Biochemical evaluation revealed normal plasma-free metanephrinesand 24-hour urine-free cortisol. Low plasma renin activity (0.530 ng/mL/hr) and aldosterone(<1.0 ng/dL) were detected on multiple tests. The urine-free cortisol-to-cortisone ratio was <0.5,excluding the diagnosis of apparent mineralocorticoid excess syndrome. The diagnosis of LS wasconfirmed by genetic analysis, which identified a novel heterozygous mutation, c.1859 A>G(Tyr620Cys), in the SCNN1B gene, which had not been reported in the literature to date. Thesame mutation was identified in her brother. The patient was treated with a high dose ofamiloride (15 mg daily), which controlled her HTN and hypokalemia throughout her pregnancy. Discussion: LS is an autosomal dominant disorder with genetic heterogeneity. It is characterized by HTN,low plasma aldosterone and renin activity, and increased potassium excretion. This leads tohypokalemia and metabolic alkalosis. LS is caused by germline mutations found in theSCNN1A, SCNN1B, and SCNN1G genes, which encode the alpha, beta, and gamma subunits ofthe ENaC channel. These mutations lead to enhanced sodium reabsorption in the kidneys,independent of aldosterone. Our patient was diagnosed with hypertension at the age of 18.However, the diagnosis of LS was not made until six years later when she presented during herfirst trimester of pregnancy. Treatment with amiloride effectively controlled her hypertension andhypokalemia, which allowed her to deliver a healthy child. Amiloride was also prescribed for thepatient's brother. A combination of biochemical analysis and genetic testing enables a betterunderstanding of the various clinical presentations, ensuring appropriate treatment andprevention of end-organ damage. Genetic counseling is essential for families affected by LS. Presentation: 6/1/2024

8356 Total Hypophysectomy in Cushing’s Disease: Results from a Terciary Center

Abstract Disclosure: M.V. Lopes: None. M.D. Severino: None. J. Rocha: None. C.R. Peixe: None. M.I. Alexandre: None. A. Gomes: None. M.J. Bugalho: None. Introduction: Transsphenoidal surgery (TSS) is the first line treatment for Cushing’s disease (CD), leading to remission in 70-80% of cases. Though selective adenomectomy is the preferred approach, total hypophysectomy may be needed. Objective: To describe 3 CD patients in which total hypophysectomy was performed. Clinical cases 1. A 58-year-old man with a history of type 2 diabetes (T2D) and obesity, was referred to the Endocrinology Clinic due to abdominal purple striae and facial plethora. Laboratory tests suggested ACTH dependent hypercortisolism, with normal serum ACTH, high 24h urinary cortisol and no cortisol suppression in the overnight 1mg dexamethasone suppression test (DST). The CRH test was suggestive of CD but no adenoma was found on pituitary MRI. Inferior petrosal sinus sampling (IPSS) was compatible with CD with right-sided lateralization. Right hypophysectomy was performed but no CD remission was achieved, so the patient underwent total hypophysectomy. Corticotroph hyperplasia was identified in histology. After 9 months of follow-up, he mantains CD remission. 2.A 37-year-old woman was diagnosed with ACTH dependent hypercortisolism after referral to the Endocrinology Clinic for alopecia, amenorrhea, hypertension and hirsutism. Laboratory tests showed severe hypokalemia, high plasma ACTH and 24h urinary cortisol and the MRI showed a right-sided macroadenoma. Nonetheless, considering the clinical severity, an IPSS was performed and definitely excluded an ectopic Cushing’s syndrome (CS) thus confirming the diagnosis of CD with right-sided lateralization. The patient underwent selective TSS, however, for lack of CD remission, total hypophysectomy was performed. Histology revealed an adenocorticotrophic adenoma. Yet, a year later, she maintains persistence of CD, although less severe, and is under treatment with metyrapone. 3.A 58-year-old woman with a history of T2D and class 3 obesity, was evaluated in our Endocrinology Clinic due to obesity. Her physical examination suggested CS, so this hypothesis was investigated. Laboratory tests suggested ACTH dependent hypercortisolism, with normal serum ACTH, elevated 24h urinary cortisol and no cortisol suppression in the overnight 1mg DST. The high dose DST was suggestive of CD but the pituitary MRI didn’t show an adenoma. IPSS was compatible with CD but it was not possible to determine lateralization. So, total hypophysectomy was performed. An adenocorticotrophic adenoma was identified in histology. Postoperative CD remission was achieved and persists 3 months later. Conclusions: These 3 cases highlight the challenge of treating CD and suggest that in certain cases total hypophysectomy may be the treatment of choice to cure or at least improve CD. Although it is associated with more complications than selective TSS, our patients had no complications, only developed panhypopituitarism and diabetes insipidus. Presentation: 6/1/2024

Characterization of a novel variant in KCNJ16, encoding Kir5.1 channel.

The essential role of the inwardly rectifying potassium channel Kir5.1 (KCNJ16) in controlling electrolyte homeostasis and blood pressure has been demonstrated in human and animal studies. Previous studies have identified several bi-allelic mutations of KCNJ16 in humans, causing severe hypokalemia, renal salt wasting, and disturbed acid-base homeostasis. Here, we identified a novel homozygous variant of KCNJ16, I26T, in an Amish patient affected with polydipsia, developmental delay, and chronic metabolic acidosis with low serum bicarbonate concentration. Subsequently, we generated the rat model with I26T mutation using Dahl salt-sensitive rat (I26T rat) to characterize this variant. The male mutant rats displayed similar blood pressure and electrolyte homeostasis under baseline and with a high salt (4% NaCl) challenge. Blood pH, HCO3 - and renal damage also remained similar between WT and I26T rats after high salt challenge. Additionally, single-channel patch clamp analysis revealed similar channel activity in CHO cells overexpressed with WT and I26T mutant Kir4.1/5.1 channels. In summary, this study reported a novel variant in KCNJ16, namely I26T, which is likely a benign variant and not associated with pathologic phenotype in either human or Dahl salt-sensitive rats, indicating that the type/location of variant should be considered when diagnosing and treating patients with KCNJ16 mutations.

Assessment of the renal function of patients with anorexia nervosa

BackgroundA decreased glomerular filtration rate (GFR), estimated using creatinine (Cr– eGFR), is often found at the initial presentation of anorexia nervosa (AN). Its pathophysiology has been explained mainly by dehydration, and chronic hypokalemia is also thought to be a cause. However, because we have often experienced cases of AN with decreased Cr-eGFR without these conditions, we must consider different etiologies. The focus of this paper is on low free triiodothyronine (FT3) syndrome. We also discuss the utility of eGFR, estimated using cystatin-C (CysC-eGFR), for these patients.MethodsThe data of 39 patients diagnosed with AN between January 2005 and December 2023 was available for study. The characteristics of patients at the lowest and highest body mass index standard deviation score (BMI-SDS) were examined. Data on the parameters Cr-eGFR, CysC-eGFR, dehydration markers, potassium (K), and hormonal data and BMI-SDS were assessed during the treatment course to evaluate the correlations in these parameters. Blood hematocrit, uric acid (UA), blood urine nitrogen (BUN) level, and urine specific gravity were adopted as dehydration markers; FT3, free thyroxine, thyroid stimulating hormone, and insulin-like growth factor were adopted as hormonal data. Cr-eGFR and simultaneously evaluated dehydration markers, K, or hormonal data were extracted and correlations associated with the changes in BMI-SDS were examined. Furthermore, Cr-eGFR and simultaneously assessed CysC-eGFR were compared.ResultsWhen the BMI-SDS was at the lowest value, low-FT3 syndrome was shown. Severe hypokalemia was not found in our study. A linear relation was not found between Cr-eGFR and BMI-SDS. A statistically significant correlation was found between Cr-eGFR and FT3 (p = 0.0025). Among the dehydration markers, statistically significant correlations were found between Cr-eGFR and BUN or UA. The difference between Cr-eGFR and CysC-eGFR was prominent, and CysC-eGFR showed much higher values.ConclusionsOur data indicates that low-FT3 syndrome and dehydration were related to the renal function of our patients with AN. Furthermore, our data suggest that caution is needed in the interpretation of kidney function evaluation when using CysC-eGFR in cases of AN.

Life-Threatening Hypokalemic Paralysis and Prevention of Severe Rebound Hyperkalemia in a Female with Barium Poisoning: A Rare Case Report

Hypokalemic paralysis is a clinical syndrome characterized by acute flaccid paralysis with concomitant hypokalemia. Complications, such as acute respiratory failure and cardiac arrhythmias, can be fatal. If treated appropriately, the patient can recover without any sequelae. We present a rare case of life-threatening hypokalemic paralysis following the ingestion of an unknown substance. At presentation, her serum potassium concentration was 1.9 mmol/L. A review of the patient’s history confirmed the ingestion of barium chloride. She was diagnosed with acute barium poisoning characterized by high serum and urine barium levels. Aggressive potassium repletion was administered intravenously and orally. Her serum potassium concentration dropped to 1.5 mmol/L and peaked at 5.4 mmol/L following treatment. The patient achieved a complete recovery and was discharged without sequelae. Barium can competitively block the potassium inward rectifier channels and interfere with the efflux of intracellular potassium, leading to severe hypokalemia. Our report illustrates a rare presentation of acute barium intoxication and a differential diagnosis indicating hypokalemic paralysis. We also discuss the pathophysiological features and compare the clinical findings with cases of rebound hyperkalemia.

Primary aldosteronism with hypokalemic rhabdomyolysis: a case report and review of the literature

BackgroundHypokalemic rhabdomyolysis is a rare clinical manifestation of primary aldosteronism, making its diagnosis challenging, particularly when it becomes the primary presenting symptom. Herein, we present a case of primary aldosteronism with hypokalemic rhabdomyolysis and conduct a related literature review.Case presentationWe report the case of a 54-year-old Chinese male patient who presented with intermittent weakness over the past year and was admitted with sudden limb paralysis for 2 days. The final diagnosis was primary aldosteronism accompanied by hypokalemic rhabdomyolysis syndrome. By reviewing the related Chinese and English literature, we noticed that only a few cases were published since 1978. After excluding irrelevant literatures, we summarized and analyzed 43 patients of with primary aldosteronism accompanied by hypokalemic rhabdomyolysis syndrome. All patients showed good recovery, with normalized blood potassium levels, and a majority achieved normalized blood pressure. Some patients still required medication for blood pressure control.ConclusionsPrimary aldosteronism rarely causes rhabdomyolysis; the occurrence of severe hypokalemia and rhabdomyolysis should prompt consideration of primary aldosteronism in the differential diagnosis. Early detection and treatment are crucial for determining patient prognosis.

Failure to Thrive, Metabolic Acidosis, and Diarrhea in a 7-Week-Old Infant.

A 7-week-old infant presented to the emergency department with fussiness, decreased oral intake, loose stool, and respiratory distress for 2 days. The patient was born full-term with an uncomplicated birth history but had a history of slow weight gain. He was alert, but toxic-appearing at presentation, hypothermic with signs of dehydration, and with respiratory failure. He was found to have severe anion gap metabolic acidosis, hypokalemia, elevated lactate, and hyperammonemia. He responded well to initial resuscitation and was admitted to the ICU for intravenous electrolyte replacement, bowel rest, and respiratory support. A workup was pursued for failure to thrive with severe malnutrition, hyperammonemia, hyperlactatemia, anemia, vitamin D deficiency, and electrolyte abnormalities. After stabilization, he was restarted on enteral feeds and had a recurrence of loose stool and severe electrolyte abnormalities, which were refractory to enteral supplementations and required readmission to the ICU. His hospital course extended several weeks, included several subspecialty consultations, and ended with a surprising diagnosis of exclusion based on his clinical response to therapy.

A case of community-acquired Clostridioides difficile infection causing intussusception, severe pneumonia, and severe hypokalemia

BackgroundClostridioides difficile infection is associated with antibiotic use and manifests as diarrhea; however, emerging cases of fulminant diarrhea caused by binary toxin-producing C. difficile unrelated to prior antibiotic exposure have been reported. Although fulminant colitis caused by C. difficile has been documented, instances of intussusception remain scarce. Here, we present a case of adult intussusception with severe hypokalemia and pneumonia resulting from a community-acquired C. difficile infection in Japan.Case presentationAn 82-year-old male presented with dizziness, progressive weakness, and diarrhea. Initial vital signs indicated severe respiratory and circulatory distress, and laboratory findings revealed hypokalemia, pneumonia, and septic shock. Imaging confirmed intussusception of the ascending colon. Although colonoscopy suggested a potential tumor, no malignancy was found. The C. difficile rapid test result was positive, indicating community-acquired C. difficile infection. Treatment with vancomycin was initiated; however, intussusception relapsed. Surgical intervention was successful and led to clinical improvement.The patient's complex pathophysiology involved community-acquired C. difficile-induced severe diarrhea, hypokalemia, hypermetabolic alkalosis, and subsequent intussusception. Although adult intussusception is uncommon, this case was uniquely linked to binary toxin-producing C. difficile. The identified strain, SUH1, belonged to a novel sequence type (ST1105) and clade 3, suggesting a highly virulent clone. Resistome analysis aligned with phenotypic susceptibility to metronidazole and vancomycin, confirming their treatment efficacy.ConclusionThis case report highlights a binary toxin-producing C. difficile that caused intussusception. The consideration of community-acquired C. difficile in the differential diagnosis of severe enteritis is necessary, even in Japan.