Severe Hypokalemia Research Articles

LAPORAN KASUS: HIPOKALEMIA PERIODIK PARALISIS

Hypokalemic periodic paralysis is one form of rare periodic paralysis that can result in sudden weakness. Comprehensive examination is required to determine the management in such cases. This case report discusses a 26-year-old woman who presented to the hospital with a sudden complaint of weakness in all limbs and no neurological deficits. The patient had a history of being admitted three times in the past year with the same complaint. Laboratory results revealed significantly low potassium levels. Although rare, periodic paralysis must be promptly distinguished from other causes of weakness and paralysis. Immediate and appropriate actions are crucial. After rapid administration of potassium through a central vein, the limb weakness disappeared. The patient had a history of three admissions with severe hypokalemia. Abdominal ultrasound revealed mild right hydronephrosis. In this case, the patient fully recovered after receiving both oral and intravenous potassium supplementation with strict ECG monitoring in the ICU. The patient returned to the ward after 2 days in the ICU and was subsequently referred to a nephrology specialist for the management of the observed hydronephrosis. This is important to identify the underlying cause of recurrent hypokalemic paralysis

High carbohydrate diet induced hypokalemic periodic paralysis: A case report

Hypokalemic periodic paralysis (HypoKPP) is a rare disorder characterised by the sudden onset of muscle weakness associated with low serum potassium levels. A 54-year-old man was admitted to the hospital with an abrupt onset of weakness in his right upper and lower extremities which slowly progressed to involve his left upper and lower extremities. He reported having consumed a carbohydrate-rich meal the day before the episode. Laboratory tests indicated severe hypokalemia with a serum potassium level of 2.3 mEq/L. He was treated with intravenous potassium chloride and his paralysis resolved after correction of hypokalemia. The patient was discharged on potassium supplementation and dietary guidelines were advised.

Multiple electrolytes imbalances in a patient with inflammatory bowel disease associated with vitamin D deficiency: a case report

BackgroundInflammatory bowel disease involves chronic inflammation and ulceration, primarily Crohn’s disease and ulcerative colitis. The prevalence of inflammatory bowel disease is rising in industrialized countries. We describe the case of a patient with inflammatory bowel disease and multiple electrolyte disturbances that emphasize the link between a vitamin D deficiency and electrolyte imbalances.CaseAn 86‐year‐old Japanese man with severe hypocalcemia, hypophosphatemia, hypokalemia, and hypomagnesemia was referred to the gastroenterology and hepatology department our university hospital for severe diarrhea and abdominal pain. Based on clinical symptoms and biochemical and endoscopic findings, Crohn’s disease, intestinal Behçet’s disease, and intestinal tuberculosis were considered as differential diagnoses, but a final diagnosis was not reached. Prednisolone, azathioprine, and metronidazole were administered, and no apparent electrolyte abnormality was observed at the patient’s admission to our hospital. On the 80th hospital day, marked hypocalcemia, hypophosphatemia, hypokalemia, and hypomagnesemia were noted and prolonged, despite daily supplementation with Ca and inorganic P. At his consultation with our department, we observed decreased fractional excretion of Ca, tubular reabsorption of phosphate, fractional excretion of K, and fractional excretion of Mg, suggesting the depletion of vitamin D and extrarenal wasting of K and Mg. The patient’s serum Ca and inorganic P were quickly elevated in response to treatment with an active form of vitamin D, and his serum levels of K and Mg were restored to the normal range by an intravenous administration of K and Mg. A vitamin D deficiency is not rare in inflammatory bowel disease and is caused primarily by the decreased intestinal absorption of vitamin D. In the management of electrolyte imbalances in patients with inflammatory bowel disease, clinicians must consider the possible development of vitamin D deficiency-related disorders.ConclusionVitamin D deficiency in entero-Behçet’s disease leads to severe hypocalcemia and hypophosphatemia, highlighting the importance of awareness in management.

P-24 Intriguing association between type 1 diabetes mellitus, Gitelman syndrome and Cacci Ricci disease: Triad of rare diseases

Abstract Introduction Type 1 diabetes mellitus (T1DM) is known to be associated with other autoimmune diseases. Nevertheless, medical conditions can coexist in unexpected ways. Such is the case of a rare and fascinating occurrence, where a patient was diagnosed with T1DM, Gitelman syndrome and Cacci Ricci disease. Clinical Case A 27-year-old male patient was suspected to have Gitelman syndrome at the age of 3 years in the presence of tetany crisis, abdominal pain and severe hypokalemia at 1,4 mmol/L. The diagnosis was confirmed by genetic testing highlighting a mutation in the SLC12A3 gene that codes for the sodium-chloride cotransporter. Abdominal pain disappeared after potassium and magnesium supplementation and the repercussion of Gitelman's syndrome was growth retardation. Diabetic ketoacidosis decompensation due to T1DM was developed. He had poor glycemic control although intensified insulin protocol. Cacci Ricci's disease was revealed by terminal hematuria. Abdomino-pelvic CT-scan objectified precalicial canalicular ectasia with bilateral nephrocalcinosis and about twenty non obstructing bilateral micro-nephrolithiasis. Serum calcium, phosphorus and PTH levels were in the normal range. Conclusion The coexistence of T1DM, Gitelman syndrome, and Cacci Ricci disease in the same patient remains a fascinating medical mystery. Abnormalities in certain ion channels and transporters could affect multiple systems leading to the manifestation of seemingly unrelated conditions in a single patient. As research continues, healthcare professionals hope to gain a better understanding of the underlying mechanisms and develop more effective treatment strategies for these rare and complex cases.

Primary Sjogren’s syndrome with secondary distal renal tubular acidosis unmasked during pregnancy: A rare presentation

ABSTRACT Renal tubular acidosis (RTA) comprises transport defects in renal reabsorption of bicarbonate, impaired acidification of urine, or both. It is broadly classified into distal, proximal, and hyperkalemic RTA. Distal RTA (dRTA) is characterized by reduced net acid excretion in urine. It can be primary or secondary, and hypokalemia is often a central presenting feature. Hypokalemia may present with flaccid quadriparesis, arrhythmia, and respiratory failure. Hypokalemia also causes nephrogenic diabetes insipidus (NDI) due to the downregulation of vasopressin-responsive aquaporin-2 water channel and inhibition of renal response to vasopressin. Primary Sjogren’s syndrome (pSS) is the most common autoimmune disorder associated with secondary dRTA. Here, we present the case of a 22-year-old critically ill pregnant lady with adverse pregnancy outcomes, diagnosed to be pSS with dRTA, who presented with severe hypokalemia and hypernatremia (due to NDI). Both pSS and chronic acidosis are associated with adverse pregnancy outcomes.

Conn´s syndrome after kidney transplantation.

Conn's syndrome, defined as unilateral aldosterone-producing adenoma, accounts for 35-40% of cases of primary hyperaldosteronism. Primary hyperaldosteronism typically occurs in younger patients with poorly controlled arterial hypertension due to extracellular fluid retention, in whom at least atriple combination of antihypertensives, including adiuretic, is needed to maintain normotension. The clinical picture of arterial hypertension may be complemented by symptoms associated with hypokalaemia, such as weakness, fatigue, palpitations, convulsions, polydipsia, or polyuria. In addition to arterial hypertension and hypokalaemia, the diagnosis of Conn's syndrome relies on examination of serum renin and aldosterone concentrations, plasma renin activity, exercise or furosemide stimulation tests, and imaging studies, preferably computed tomography. The method of treatment of Conn's syndrome is adrenalectomy. In patients with primary hyperaldosteronism with underlying bilateral adrenal cortical hyperplasia or patients contraindicated for surgery, mineralocorticoid receptor antagonists are administered in combination with antihypertensives targeted for optimal blood pressure control.In the group of patients after kidney transplantation, the exact incidence of primary hyperaldosteronism is unknown. Based on across-sectional study performed in 2020, it is estimated to be approximately 15% in the group of patients with unsatisfactorily compensated arterial hypertension; in the cohort of normotensive recipients, the incidence of primary hyperaldosteronism is not documented. Diagnosis of Conn's syndrome in patients in the early period after kidney transplantation is problematic, as the prevalence of arterial hypertension in transplanted patients is high (70-90%) according to the literature. Mineral abnormalities, including hypokalaemia, are also common in the early post-transplant period, mainly due to factors such as duration of cold ischaemia, onset of graft function, donor parameters, post-transplant tubulopathy, and diuretics, the effects of immunosuppressive drugs (especially calcineurin inhibitors and corticosteroids), and possibly potassium-restricted dietary habits that the patient brings from the pre-transplant period, which may mask the effect of hyperaldosteronism on potassium.We present the case of apatient who was diagnosed with Conn's syndrome 7 months after primary kidney transplantation from adeceased donor based on persistent hypokalaemia unresponsive to replacement therapy. At the time of the first manifestation of severe hypokalaemia, the patient was treated with adual combination of antihypertensives (amlodipine at adaily dose of 5 mg and carvedilol at adaily dose of 50 mg), without the need for adiuretics.We consider the case interesting because the spectrum of mineral and acid-base abnormalities in advanced renal failure and in the early post-transplant period, as well as acid-base and mineral imbalances, including hypokalaemia, and the high prevalence of arterial hypertension in the post-transplant period, may mask the picture of Conn's syndrome (Fig. 3, Ref. 19). Text in PDF www.elis.sk Keywords: kidney transplantation, primary hyperaldosteronism, hypokalaemia, metabolic alkalosis, secondary arterial hypertension.

Decrease of Consciousness Due to Severe Hypokalemia: A Case Report

Severe electrolyte imbalances can present with a wide range of clinical manifestations, and hypokalemia, or low levels of potassium in the blood, is one such condition that can have profound effects on the human body. Hypokalemia can directly impact the brain’s function, leading to a range of neurological manifestations. This electrolyte imbalance can have severe and life-threatening consequences, including the development of coma. This case report aims to identify whether the decrease of consciousness in patients is related to the condition of severe hypokalemia.

A case of chronic licorice intoxication-induced apparent mineralocorticoid excess syndrome

Licorice is a perennial herb belonging to the legume family that mainly grows in northeastern China, Mongolia, Siberia, and other regions. It is used in traditional medicine in the form of dried roots in the East and the West. The main active component of licorice, glycyrrhizin, is known to produce mineralocorticoid effects when consumed chronically, which can lead to apparent mineralocorticoid excess syndrome. Herein, we present the case of a 72-year-old woman who was admitted to the emergency room with severe generalized weakness and difficulty keeping her neck upright, which had developed after daily consumption of licorice-infused water for the past 2 months. Blood tests revealed metabolic alkalosis and severe hypokalemia, and an electrocardiogram showed ventricular bigeminy. The patient was treated with daily potassium and spironolactone supplements, leading to a significant improvement in muscle strength after a week. One week later, the patient was discharged, showing rare ventricular premature contractions on electrocardiography, but with no specific complaints. Chronic licorice ingestion leading to hypokalemia and muscle weakness can be life-threatening, necessitating the discontinuation of the causative agent, close monitoring, and cautious supplementation of potassium and spironolactone as treatment.

Dexamethasone induced severe paralysis hypokalemia: A case report

Acute weakness related with hypokalemia periodic paralysis (HPP) is a rare clinical condition. The one common etiology of hypokalemia is the shifting of potassium into the cells. The common provoke factors are high-carbohydrate diet, heavy exercise, stress, extreme cold weather, alcohol consumption, and certain medications. We present the case of a 32‐year-old Javanese male with an acute onset of bilateral lower and upper limb weakness with severe hypokalemia following dexamethasone injection. He was diagnosed with HPP. Our systematic review found similar cases, with possible pathophysiology explanation. Steroids should be considered as an unusual precipitating factor while managing patients with HPP.

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.

Thyrotoxic Periodic Paralysis after Surgery: A Case Report and Literature Review

Thyrotoxic periodic paralysis (TPP) is a rare but potentially life-threatening muscle disease in a thyrotoxic patient. Due to the lack of knowledge, the diagnosis is easily missed. Diagnosis of TPP is made by documentation of hypokalemia and hyperthyroidism in acute generalized muscle weakness. Hypokalemia is caused by an intracellular shift of potassium because of an increased Na-K-ATPase pump activity and the inhibition of the inward rectifying potassium (Kir) channels. The initial treatment aims to treat potentially life-threatening cardiac arrhythmias caused by severe hypokalemia. This can be done with potassium substitution and nonselective beta-blockers, being aware of the potential of rebound hyperkaliemia. Definitive treatment consists of avoiding triggers and correcting the hyperthyroid state with antithyroid drugs, radioactive iodine, or thyroidectomy. Once patients are, permanently euthyroid complete remission of the paralytic attacks usually occurs. We present a case of a 37-year-old male with diffuse muscle weakness after surgery. A new diagnosis of thyrotoxic periodic paralysis was made in the emergency department. This review summarizes the epidemiology, clinical manifestations, pathogenesis, diagnostics, and treatment of TPP.

Prolonged Hypokalemia and Delayed Diagnosis of Primary Aldosteronism: Clinical Course and Risk Factors.

Primary aldosteronism (PA) is a common cause of hypertension (HT). However, diagnosis is often delayed, leading to poorer clinical outcomes. Hypokalemia with HT is characteristic of PA, and is an indication for screening. We evaluated if patients with PA had prolonged hypokalemia before diagnosis, the subsequent biochemical/clinical control, and factors associated with delayed diagnosis. Our study included all PA patients with hypokalemia diagnosed between 2001 and 2022. Delayed diagnosis was defined as duration of hypokalemia of more than 1 year from first occurrence to first evaluation by a PA specialist. Patients were reassessed post adrenalectomy using the Primary Aldosteronism Surgery Outcomes criteria. We performed multivariable analysis to assess for factors associated with delayed diagnosis. Among 240 patients with PA who presented with hypokalemia, 122 (51%) patients had delayed diagnosis, with prolonged hypokalemia of median duration 4.5 years (range, 2.4-7.5 years). Patients with delayed diagnosis were older, had longer duration of HT, higher pill burden, lower renal function, and more prevalent cardiovascular disease. Factors associated with delayed diagnosis included older age, presence of hyperlipidemia, and less severe hypokalemia (serum potassium >3.0 mmol/L). Compared to patients with early diagnosis, a lower proportion of those with delayed diagnosis underwent adrenal vein sampling (73% vs 58%) (P < .05). Sixty of 118 (50.8%) nondelayed, and 39 of 122 (32.0%) patients with delayed diagnosis, underwent surgery. Despite manifestation of hypokalemia, many patients with PA fail to be promptly screened. Greater emphasis in HT guidelines, and efforts to improve awareness of PA among primary care physicians, are urgently needed.

Cushing syndrome in a 55-year-old case of small-cell lung cancer

Lung cancer is one of the most fatal types of cancer and paraneoplastic syndromes are commonly associated with lung cancer. Paraneoplastic Cushing can be associated with different types of tumors, especially small cell lung cancer (SCLC). The aim of this report was to describe the status of a patient presenting with progressive weakness, who did not have a previous medical history. Clinical examination revealed bilateral edema of the lower limbs. Lab results exhibited severe hypokalemia and metabolic alkalosis. physical examination showed elevated blood pressure. Imaging revealed a large mass with necrosis. Bronchoscopy was done and biopsy pathology showed SCLC. The patient underwent chemotherapy with cisplatin and etoposide. Following SCLC, the patient developed a type of paraneoplastic syndrome called Cushing syndrome. He experienced a severe decrease in saturation in the second session of chemotherapy and eventually died. With respect to the fact that most paraneoplastic syndromes are associated with poor response to treatment, high clinical suspicion is essential for the rapid diagnosis of these syndromes to improve outcomes.

Hypokalaemia in pregnancy – Prevalence, underlying causes, and an approach to investigation

Objective To investigate the prevalence and aetiology of hypokalaemia in pregnancy. Methods This was a five-year retrospective audit of women who received care at a tertiary hospital, who developed hypokalaemia during pregnancy and within three weeks postpartum. Serum potassium and magnesium levels cause(s) of hospitalization and investigations for hypokalaemia were obtained from hospital records. Results One hundred and ten women developed hypokalaemia during pregnancy and the immediate postpartum period, representing 0.36% of total births. Ninety-one per cent of patients had mild to moderate hypokalaemia (K 2.6–3.1 mmol/L), while 9% had severe hypokalaemia (K &lt; 2.6 mmol/L). The most common associations of hypokalaemia were infection (38%), vomiting (18%), hypertensive disorders (12%) and postpartum haemorrhage (9%). Twenty-four patients did not have a clear underlying aetiology of hypokalaemia, but only five had further investigations. Conclusions There was inadequate investigation and follow-up of hypokalaemia, particularly in women in whom an obvious cause was not apparent.

Quantum-First: Safety By Treatment Phase and By Age in Newly Diagnosed (nd) Patients (pts) with FMS-like Tyrosine Kinase 3-Internal Tandem Duplication ( FLT3-ITD) Positive Acute Myeloid Leukemia (AML)

Background Results from the phase 3 QuANTUM-First study (NCT02668653) showed that in nd FLT3-ITD+ AML pts, the addition of the oral, highly potent, selective, type 2 FLT3 inhibitor quizartinib (Quiz) to standard chemotherapy ± allogeneic hematopoietic cell transplantation (allo-HCT), followed by Quiz monotherapy for up to 36 cycles (3 years [yrs]), decreased the relative risk of death by 22.4% vs placebo (PBO), with a generally manageable safety profile (PMID: 37116523). We describe safety by treatment phase (Induction [IND], Consolidation [CONS], Continuation [CONT]) and by age group (&amp;lt;60, 60-64, ≥65 yrs). Methods Eligible pts (18-75 yrs) with nd FLT3-ITD+ AML were randomized 1:1 to Quiz (40 mg/d) or PBO + standard IND chemotherapy. Pts in complete remission (CR) or CR with incomplete neutrophil or platelet recovery received standard CONS chemotherapy + Quiz (40 mg/d) or PBO and/or allo-HCT (Quiz/PBO not given with allo-HCT), followed by CONT of single-agent Quiz (30-60 mg/d) or PBO for up to 36 cycles. Safety was evaluated in pts treated with ≥1 dose of Quiz or PBO. Treatment-emergent adverse events (TEAEs) were coded by MedDRA v24.0, severity by NCI-CTCAE v4.03. Results In both arms, median treatment durations were 2 weeks in IND, 4 weeks in CONS, and 1.3 yrs in CONT. Rates of TEAEs and grade ≥3 TEAEs were similar in both arms in IND &amp; CONS, although grade ≥3 TEAEs were more common with Quiz vs PBO in CONT (Table 1). In IND &amp; CONS, the most common TEAEs were gastrointestinal (GI) AEs (diarrhea, nausea, vomiting), infections (pneumonia, sepsis), hypokalemia, pyrexia, febrile neutropenia, and rash. In IND &amp; CONS, myelosuppression occurred in most pts in the Quiz and PBO arms, with a median blood count recovery time &amp;lt;4 weeks from the time of onset. In CONT, most common TEAEs were upper respiratory tract infections, GI AEs, cytopenias, and ALT increase. In CONT, more pts with Quiz had myelosuppression, with trends toward earlier onset and delayed recovery with Quiz. ECG QT prolonged was more common with Quiz vs PBO in all phases, QTcF &amp;gt;500 ms was low (2.3%) and observed in IND &amp; CONS only. Ventricular arrythmias were few with Quiz (2 pts [0.8%] had cardiac arrest/ventricular fibrillation with severe hypokalemia). Infections were the most common serious TEAEs (TESAEs), with febrile neutropenia, pneumonia, and sepsis in IND &amp; CONS and pneumonia and viral infections in CONT. TEAEs leading to death were numerically higher with Quiz vs PBO in IND &amp; CONS, mainly due to infections in older pts, but numerically lower with Quiz vs PBO in CONT. In IND &amp; CONS, TEAEs leading to dose interruptions or dose reductions were similar in both arms, whereas TEAEs leading to discontinuation (disc) were higher with Quiz vs PBO. TEAEs leading to dose interruptions, dose reductions, or disc in CONT were higher with Quiz vs PBO. TEAE leading to disc of Quiz were mostly infections in IND &amp; CONS and cytopenias in CONT. Cytopenias and QT prolonged were the most common AEs leading to dose modifications and were more common with Quiz. There was no evidence of increasing toxicity with long-term Quiz therapy for up to 36 cycles in CONT, and no new AEs were observed in pts receiving &amp;gt;12 cycles. Rates of TEAEs and grade ≥3 TEAEs were similar in both arms across age groups (Table 2). TESAEs, TEAEs leading to death, and TEAEs leading to disc were more common in older pts (≥65 yrs [n=134]) vs younger pts (&amp;lt;60 and 60-64 yrs [n=399]) in both arms. Infections in the elderly were most commonly severe, serious, and fatal AEs and a main cause of more early deaths (&amp;lt;60 days of Quiz start). TEAEs leading to dose modifications were higher with Quiz vs PBO across age groups. In the Quiz arm, cytopenias, headache, rash, cough, ALT increase, hypomagnesemia, oropharyngeal pain, and back pain were more common in younger vs older pts; ECG QT prolonged was highest in the 60-64 yrs group. GI AEs and were more common in older pts with Quiz. QTcF &amp;gt;500 ms occurred mainly in pts 60-64 yrs with Quiz. Conclusions In QuANTUM-First, infections and cytopenias associated with Quiz were observed across phases. Fatal infections were more common with Quiz in IND &amp; CONS but not in CONT. Rates of prolonged QTcF &amp;gt;500 ms were low overall, occurring mostly in IND &amp; CONS, not in CONT. Pts ≥65 yrs had higher TESAEs, TEAEs leading to death (including early death), and TEAEs leading to disc (mainly infections) vs younger pts in both arms. Quiz safety profile in different treatment phases and age subgroups supports an overall positive benefit/risk.

Abiraterone, a rare cause of severe perioperative hypokalemia with unusual presentation as aphonia and quadriparesis: a case report

BackgroundOral Abiraterone acetate is a novel antineoplastic agent approved by the FDA for the treatment of metastatic prostate cancer. Abiraterone is an irreversible inhibitor of the 17α-hydroxylase (CYP17) enzyme complex resulting in a reduction of androgens and corticosteroids. It may cause mineralocorticoid excess syndrome; hence, it is prescribed with steroids. Here we describe a case of postoperative severe hypokalemia with unusual presentation in a patient after spine surgery in which abiraterone with prednisolone was continued preoperatively. Anesthetic concerns about the perioperative administration of abiraterone have not been reported in the literature.Case presentationAn 80-year-old male with a known case of metastatic prostate cancer was posted for spine surgery under general anesthesia. Surgery was uneventful and the patient was extubated after ensuring adequate muscle power and respiratory parameters. Postoperatively, the patient developed aphonia, quadriparesis, and respiratory distress leading to reintubation. After evaluation, severe grade 4 hypokalemia was found to be the causative factor. The patient recovered well after potassium and steroid supplementation. Low potassium and cortisol levels indicate a diagnosis of abiraterone-induced hypokalemia.ConclusionPatients on abiraterone require more stringent and vigilant monitoring of potassium and cortisol levels. In such circumstances, it might be advantageous to add additional steroids or substitute alternative steroids.

Unilateral adrenalectomy for a drug-resistant bilateral primary aldosteronism with heart failure: pathophysiology and surgical indication

BackgroundPatients with bilateral primary aldosteronism (PA) generally are treated with antihypertensive drugs, but optimal treatment for patients with complications due to refractory hypertension has not been established. In this report, we present a case with bilateral PA who presented with persistent hypertension, despite treatment with 6 drugs, and left-dominant heart failure, which was improved after unilateral adrenalectomy.Case presentationA 61-year-old man was admitted to our hospital because of severe left-dominant heart failure. His heart rhythm was atrial fibrillation and the left ventricle was diffusely hypertrophic and hypokinetic. Coronary arteries were normal on coronary arteriogram. Primary aldosteronism was suspected based on severe hypokalemia (2.5 mEq/L) and plasma aldosterone concentration (PAC; 1,410 pg/mL). Although computed tomography (CT) showed a single left cortical nodule, adrenal vein sampling (AVS) indicated bilateral PA. Early in the case, heart failure and hyperkalemia in this patient were improved by treatment with a combination of 6 antihypertensive drugs (spironolactone 25 mg/day, eplerenone 100 mg/day, azosemide 60 mg/day, tolvaptan 7.5 mg/day, enalapril 5 mg/day, and bisoprolol fumarate 10 mg/day); however, heart failure relapsed after four months of treatment. We hypothesized that hypertension caused by excess aldosterone was inducing the patient’s heart failure. In order to reduce aldosterone secretory tissue, a laparoscopic adrenalectomy was performed for the left adrenal gland, given the higher level of aldosterone from the left gland compared to the right. Following surgery, the patient’s heart failure was successfully controlled despite the persistence of high PAC. Treatment with anti-hypertensive medications was reduced to two drugs (eplerenone 100 mg/day and bisoprolol fumarate 10 mg/day). In order to elucidate the mechanism of drug resistance, immunohistochemistry (IHC) and real time-polymerase chain reaction (RT-PCR) assays were performed to assess the expression of steroidogenic factor 1 (SF-1), a regulator of steroid synthesis in adrenal tissue. IHC and RT-PCR demonstrated that the expression of SF-1 in this patient (at both the protein and mRNA levels) was higher than that observed in unilateral PA cases that showed good responsivity to drug treatment.ConclusionsUnilateral adrenalectomy to reduce aldosterone secretory tissue may be useful for patients with drug-refractory, bilateral PA. Elevated expression of SF-1 may be involved in drug resistance in PA.

Risk of hyperkalaemia in patients with type 2 diabetes mellitus prescribed with SGLT2 versus DPP-4 inhibitors.

To investigate the risk of hyperkalaemia in new users of sodium-glucose cotransporter 2 (SGLT2) inhibitors vs. dipeptidyl peptidase-4 (DPP-4) inhibitors among patients with type 2 diabetes mellitus (T2DM). Patients with T2DM who commenced treatment with an SGLT2 or a DPP-4 inhibitor between 2015 and 2019 were collected. A multivariable Cox proportional hazards analysis was applied to compare the risk of central laboratory-determined severe hyperkalaemia, hyperkalaemia, hypokalaemia (serum potassium ≥6.0, ≥5.5, and <3.5mmol/L, respectively), and initiation of a potassium binder in patients newly prescribed an SGLT2 or a DPP-4 inhibitor. A total of 28599 patients (mean age 60±11 years, 60.9% male) were included after 1:2 propensity score matching, of whom 10586 were new users of SGLT2 inhibitors and 18013 of DPP-4 inhibitors. During a 2-year follow-up, severe hyperkalaemia developed in 122 SGLT2 inhibitor users and 325 DPP-4 inhibitor users. Use of SGLT2 inhibitors was associated with a 29% reduction in incident severe hyperkalaemia [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.58-0.88] compared with DPP-4 inhibitors. Risk of hyperkalaemia (HR 0.81, 95% CI 0.71-0.92) and prescription of a potassium binder (HR 0.74, 95% CI 0.67-0.82) were likewise decreased with SGLT2 inhibitors compared with DPP-4 inhibitors. Occurrence of incident hypokalaemia was nonetheless similar between those prescribed an SGLT2 inhibitor and those prescribed a DPP-4 inhibitor (HR 0.90, 95% CI 0.81-1.01). Our study provides real-world evidence that compared with DPP-4 inhibitors, SGLT2 inhibitors were associated with lower risk of hyperkalaemia and did not increase the incidence of hypokalaemia in patients with T2DM.

FRI355 Hypokalemia-induced Nephrogenic Diabetes Insipidus In A Patient With Medullary Thyroid Carcinoma And Paraneoplastic Cushing’s Syndrome

Abstract Disclosure: S. Jhawar: None. S. Jumani: None. Y. Sterrett: None. H. Elenius: None. P. Veeraraghavan: None. C. Ryan: None. J. Del Rivero: None. S.M. Sadowski: None. N. Nilubol: None. J.G. Verbalis: None. L.K. Nieman: None. E. Globa: None. M.S. Zemskova: None. J. Klubo-Gwiezdzinska: None. S. Gubbi: None. Introduction: Nephrogenic diabetes insipidus (NDI) is commonly associated with the use of medications such as lithium, antibiotics, and chemotherapeutic agents or with renal disorders. Rarely, NDI can be a manifestation of paraneoplastic conditions. We describe a case of NDI caused by severe hypokalemia in a patient with metastatic medullary thyroid cancer (MTC) and paraneoplastic Cushing’s syndrome (CS). Clinical Case: A 47-year-old male with sporadic, metastatic MTC (RET M918T pathogenic variant) was referred to our institution for further management. The patient had florid metastases to the liver, lungs, and skeleton, with a calcitonin of 158,535 pg/mL [normal (NL): &amp;lt;14.3], and a CEA of 3,634 pg/mL (NL: 0.8-3.4), but surprisingly, without an intrathyroidal primary tumor. Vandetanib and octreotide were previously trialed but discontinued due to financial constraints. The patient had diarrhea, but no other symptoms. Physical exam revealed cervical lymphadenopathy, facial plethora, dorsocervical fat pad, and a single purple stria on the chest. Further work up revealed markedly elevated 24-hr urine free cortisol (12,460 mcg/24hr; NL: 35-45), ACTH 116 pg/mL (normal 5.0-46.0), and an undetectable serum aldosterone and plasma renin activity, raising suspicion for paraneoplastic ectopic-CS. Immunostaining of the MTC biopsy specimen showed ACTH positivity. During the inpatient admission, polyuria of &amp;gt;3L/day was noted on two consecutive 24-hour urine measurements. Laboratory investigations revealed hypernatremia (serum sodium: 147 mmol/L; NL: 136-145), elevated serum osmolality (303 mOsm/Kg; NL: 278-298), and a low urine osmolality (215 mOsm/kg; NL: 300-900), thus establishing the diagnosis of DI. A simultaneous, elevated plasma copeptin (36.3 pmol/L; NL: &amp;lt;13.1) further suggested NDI. Also noted was severe hypokalemia (serum potassium: 1.7 mmol/L; NL: 3.5-5.1), with normal serum magnesium and calcium. A thorough review of patient’s medication list did not reveal any culprit drug for hypokalemia or NDI. Hypokalemia was managed with aggressive oral and intravenous potassium repletion. A bilateral adrenalectomy was performed to treat the ectopic-CS, which improved the hypokalemia and resolved the NDI. Three months later, the patient unfortunately died due to progression of MTC. Conclusion: Severe hypokalemia causes autophagic degradation of aquaporin-2 channels in the renal tubules and is an under-recognized cause of NDI. Profound hypercortisolism in ectopic-CS may result in cortisol-mediated overactivation of mineralocorticoid receptors that can cause renal potassium loss leading to NDI. Only 0.6% of MTCs are associated with ectopic-CS (PMID: 16029131). Our report highlights hypokalemia-induced NDI as a manifestation of paraneoplastic CS resulting from MTC. Presentation: Friday, June 16, 2023

FRI124 Insights From The Incidence Of Primary Aldosteronism In Patients With Hypokalemia (IPAHK+) - Study

Abstract Disclosure: S. Gruber: None. E. Stasi: None. A. Boan Pion: None. R. Steiner: None. I. Sudano: None. F. Beuschlein: None. Background: Hypokalemia plays an important role in the diagnosis and management of primary aldosteronism (PA). The hypokalemic variant of the disease accounts for about one third of all cases. However, little is known about the incidence of PA in a hypokalemic population. Design: The IPAHK+ study is an epidemiological, monocentric, cross-sectional trial to provide evidence on the incidence of PA in a hypokalemic outpatient population. Methods: Recruitment of outpatients with hypokalemia ≤3 mmol/l is carried out on a continuous referral-basis through an automated data delivery system at the University Hospital Zurich (USZ). Todate, 69 patients underwent the study protocol, which includes guideline-compliant workup for PA. Results: The mean age of the participants was 52.5±1.5 years with a sex ratio of 35:34 women to men, a mean potassium value of 2.77±0.03 mmol/l [1.8; 3.0] and a prevalence of arterial hypertension of71%. PA was diagnosed in 45.9% of all participants, all of whom had a history of hypertension. The incidence of PA increased continuously with decreasing potassium level with proportions of 26.7%,45.8% and 59.1% in the subgroups of 3.0 mmol/l (n=15), 2.8-2.9 (n=24) and ≤2.7 mmol/l (n=22),respectively. In the subgroup of hypertensives the incidence of PA was as high as 65.1%. Prior testing,60.9% of all patients presented at least with one plausible other cause for their hypokalemia with potential drug triggers accounting for the largest portion (33.3%). Among participants on diuretics the incidence of PA was 57.9%. Conclusions: The incidence of PA in the investigated outpatient population was more than 4 out of 10and inversely correlated with baseline potassium levels. Moderate or severe hypokalemia, regardless of its cause, should therefore prompt evaluation for PA in hypertensive individuals. Normotensive PA was not observed in our cohort. The significance of the study is limited by the still low number of enrolled patients with a potential selection bias. Presentation: Friday, June 16, 2023