Recurrent Hypokalemia Research Articles

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

A case report on Sjogren syndrome with autoimmune liver disorder

Background: Primary Sjogren’s syndrome (pSS) is a chronic systemic and autoimmune disorder characterized by inflammation and dysfunction of exocrine glands. Liver involvement was the first extraglandular manifestations to be reported in patients with pSS. Tubulointerstitial nephritis (TIN) is the main renal involvement associated with pSS and manifest as distal renal tubular acidosis (RTA), and others, of which RTA is the main clinical presentation. RTA has been reported in 4.3 to 9% of pSS patients. In this case, patient experiences RTA. Case Presentation: A 19 year old female patient was presented with complaints of abdominal pain, fatigue for 2 months and loose stools. She had history of autoimmune hepatitis and decompensated liver cirrhosis with portal hypertension (autoimmune), bilateral peroneal axonal neuropathy, grade II hepatic encephalopathy resolved and recurrent pustular lesion for past 2 years which rupture spontaneously and heals with scary. She also presented with recurrent hypokalemia which was corrected. No history of similar complaints among the family members. Conclusion: This case explains the autoimmune liver disorder with newly diagnosed primary sjogren’s syndrome associated with recurrent hypokalemia.

Hypokalemia Induced Partial Nephrogenic Diabetes Insipidus: A Case Report

Diabetes insipidus is a condition characterised by a large volume of diluted urine production andincreased thirst. In this case report, a 49-year-old gentleman presented with 3 months of polyuria andpolydipsia. He had a repeated history of hypokalemia. On the evaluation of polyuria and polydipsia,he was diagnosed with partial nephrogenic diabetes insipidus based on his inability to concentrateurine after a water deprivation test and his less than 50% response to exogenous desmopressin.On the evaluation of recurrent hypokalemia, the investigation reports met biochemical criteria forthe diagnosis of Gitelman syndrome. He was encouraged to increase his fluid intake as required,and potassium chloride supplementation relieved his symptoms. This case report demonstrates thereversibility of nephrogenic diabetes insipidus with a correction of hyperkalemia.

Intensive care management of Gitelman syndrome: A rare case

Gitelman syndrome (GS) is an autosomal-recessive disorder distinguished by hypokalemia, hypomagnesemia, and hypocalciuria. Elderly people and women of childbearing age are highly affected by GC. Not much evidence is known about its effects on maternal and fetal outcomes. GS is caused by mutations in the thiazide-sensitive Na-Cl cotransporter gene. Due to its rarity and lack of knowledge, it is susceptible to misdiagnosis or being overlooked. In our case, the patient suffered from recurrent hypokalemia, hypomagnesemia, hypochloraemia, and hypocalciuria with hypotension. After taking proper medication, the patient recovered slowly, and during counseling, the patient was provided a diet chart by nutritionists to avoid recurrent electrolyte imbalances.

Hypokalemia, how to clarify and treat: a review article

Hypokalemia is a frequent electrolyte disturbance in clinical practice and in hospitalized patients. Potassium disturbances are common and have been associated with increased mortality in several populations. The incidence of hypokalemia often occurs refractory and without a clear cause so very difficult to prevent and can increase risk of recurring conditions and require treatment. Through this overview will discuss what are the underlying causes of hypokalemia and what tests are needed to find out the cause of hypokalemia so that it can remind health worker and to prevent recurrence of emergencies conditions due to hypokalemia. The type of study is used literature review. In addition, the purpose of this study method is to reveal various theories that are relevant to the diagnostic approach to determine the causes of hypokalemia so that it can be used as reference material in daily practice. Hypokalemia is usually a sign of various diseases that can cause emergency conditions. If the cause is not known for certain, it will cause recurrent hypokalemia. It is important for health workers to conduct interviews to find out the patient's medical history, physical examination and comprehensive supporting examinations to determine the cause of hypokalemia. Comprehensive management is needed and must be done immediately so that the condition of hypokalemia does not lead to emergency conditions. In some patients, such as in endocrine related hypokalemia cases, multidisciplinary diagnostic and therapeutic approach is needed.

THU017 Severe Hypercortisolemia- A Biological Time Bomb

Abstract Disclosure: U. Munasinghe: None. S. Pittampalli: None. D. Das: None. V. Pattan: None. Cushing's disease, the most common cause of endogenous Cushing syndrome, is usually insidious and has less severe hypercortisolemia than ectopic Cushing's. 73 yr.old female with hypertension, hyperlipidemia, T2DM, and OSA on anticoagulation for recent pulmonary embolism, presented with recurrent hypokalemia and proximal muscle weakness of 3 months duration. She denied visual symptoms and headaches. BP was 158/90 mmHg, HR 92 bpm, and BMI 34.9. She had a round face with ruddy complexion, extensive bruising on her upper extremities and proximal muscle weakness. Laboratory tests showed serum bicarbonate 26 mmol/l (22-29), sodium 140 mmol/L (136-145), potassium 2.0 mom/L (3.4- 5.1), chloride 106 mmol/L (98-107), glucose 164 mg/dl. Hemoglobin A1c 9.6 %, random cortisol 46.2mcg/dL, ACTH 72.4 pg/ml (7.2-63.3), late-night salivary cortisol sample was inadequate to assess, 24-hour urine cortisol 1802 ug/24 hr (6-42). Prolactin level was 14.6 ng/ml(4.7-23.3), IGF-1 62 ng/dl (48-191), GH 0.12 ng/ml (0-3.61), FSH< 0.3 mU/ml (25.8-134.8), TSH 0.193 u/ml (0.27-4.2), Ft4 1.1 ng/dl (0.93-1.7), alpha subunit <0.15 ng/ml (<3.56). She had non-suppressed cortisol of 44.3 mcg/dL and ACTH of 113 pg/mL after overnight 8mg dexamethasone suppression test. CT angiogram chest did not reveal any pathology. MRI pituitary revealed pituitary adenoma measuring 9 x 8 mm. IPSS with desmopressin stimulation showed IPSS to peripheral prolactin ratio was greater than 1.8 verifying successful catheterization. Her central to peripheral ACTH gradient was >2 before stimulation confirming pituitary source. Her ACTH concentration gradient >1.4 between 2 sinuses lateralizing the lesion to the right. The patient was started on Osilodrostat 2mg bid for control of hypercortisolemia and subsequently treated with transsphenoidal resection of the pituitary adenoma. Surgical pathology was consistent with densely granulated corticotrophin adenoma. Initial presentation of recurrent hypokalemia, proximal muscle weakness, pulmonary embolism and severe hypercortisolemia was suspicious for ectopic Cushing’s but after initial chest imaging was negative for ectopic pathology, MRI and subsequent IPSS helped with timely diagnoses and management. Severe hypercortisolemia is an endocrine emergency carrying high mortality. Expedited diagnoses, control of hypercortisolemia, anticoagulation and antibiotic prophylaxis can be life saving before definitive treatment can be done. Presentation: Thursday, June 15, 2023

Recurrent Hypokalemic Paresis–A Possibility of Liddle-Gitelman Overlap

Hypokalemia can occur due to various causes that have diverse manifestations varying from mild asthenias to acute onset paraparesis to life-threatening cardiac arrhythmias. A proper algorithmic evaluation for hypokalemia can help us identify various correctable causes and can be life-saving. Here, we discuss a case of 35-year-old hypertensive female who had presented as a case of acute onset flaccid paraparesis. We have further discussed our approach in reaching her diagnosis and stressed upon importance of algorithmic approach in the evaluation of patients presenting with recurrent hypokalemia. It may help in unmasking a rarer cause.

Mckittrick- Wheelock syndrome (MKWS) - Rare cause of recurrent electrolyte derangements with hypotension and falls in elderly patients

We report a case of an 82-year-old gentleman presenting with recurrent hypokalaemia, renal impairment, postural hypotension and falls. Further investigations revealed large villous recto-sigmoid tumour associated with secretary diarrhoea in the closed bowel loop causing electrolyte depletion leading to hypotension and falls.

GITELMAN SYNDROME PRESENTING AS ACUTE RECURRENT HYPOKALEMIA

Gitelman Syndrome is also referred to as familial hypokalemia hypomagnesemia.It is characterised by Hypokalemic metabolic alkalosis in combination with hypomagnesemia and low urinary calcium excretion.Gitelman syndrome is transferred as an autosomal recessive trait.Most cases are diagnosed during adolescence or adulthood.We presented the case of 23year old male with no co-morbidities who presented to casualty with persistent recurrent hypokalemia. There was no history of drugs taken (even potassium supplements).

Recurrent Hypokalaemia Due to Gittleman Syndrome: A Case Report

Gittleman syndrome (GS) is autosomal recessive renal tubulopathy caused by mutation of genes encoding protein for sodium chloride cotransporter and magnesium channel in the distal convoluted tubule.1 We present the case of a-20-years old female patient admitted in our Internal Medicine Department for recurrent hypokalaemia. She presented with recurrent quadriparesis. There was no history of taking inhaled salbutamol, insulin, steroid, diuretics and vomiting or diarrhoea. Investigations revealed hypokalaemia. Hypomagnesaemia, normal urinary excretion of sodium and potassium and hypercalcaemia. Her Serum albumin was within normal limit and renal function was normal. Diagnosis of Gittleman syndrome was established and was given potassium chloride and magnesium sulphate. Subsequently, the patient improved clinically and biochemically. Bangladesh Med J. 2021 Sept; 50(3): 49-51

Thyrotoxic Periodic Paralysis in the Post-COVID Era: A Case Report with Literature Review

Thyrotoxic Periodic Paralysis (TPP) is an acute potentially lethal emergency in patients with hyperthyroidism who present with sudden muscle weakness and hypokalemia. It is commonly precipitated by high carbohydrate or high salt content meals, strenuous exercise, stress, trauma, glucocorticoids, epinephrine, alcohol, or respiratory infections. COVID-19 infection or vaccination may represent a novel trigger for TPP. Furthermore, COVID-19 infection or vaccination may incite inflammatory processes leading to thyrotoxicosis, which can manifest as TPP. While COVID-19 causing subacute thyroiditis, euthyroid sick syndrome, Hashimoto’s disease, or Graves’ disease have been well documented in the literature; there have only been six case reports of post-COVID-19 TPP. Notably, all cases thus far have been restricted to male patients, and there is paucity of literature from North America. The purpose of this paper is to outline the first case of post-COVID-19 TPP in a female patient, who presented to the emergency department with acute paralysis and severe hypokalemia (2.2 mmol/L) three months after COVID-19 infection. Investigations in the emergency department showed thyrotoxicosis. She was treated with potassium replacement, which improved her paralysis. Subsequent investigations revealed severe hyperthyroidism from Graves’ disease, which is currently managed with metoprolol and methimazole. Her hyperthyroidism improved without recurrent hypokalemia or paralysis. In addition, we outline the epidemiology, pathophysiology, precipitants, and management of TPP, with a particular focus on COVID-19 infection or vaccination precipitating TPP. We discuss post-COVID-19 TPP cases thus far described in the literature. Knowing that North American COVID-19 infection waves lagged Asia, we could anticipate additional future TPP cases.

Recurrent Hypokalemia and Adrenal Steroids in Patients With APECED.

ContextHypokalemia is a common finding in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) but its exact cause often remains unknown.ObjectiveTo explore the prevalence and etiology of hypokalemia and the role of adrenal steroids therein in a cohort of patients with APECED.MethodsWe performed a cross-sectional assessment and retrospective data collection on 44 Finnish patients with APECED to identify subjects with episodes of hypokalemia. Also 68 healthy matched controls attended the cross-sectional evaluation. Factors associating with a tendency for hypokalemia were analyzed by reviewing medical records during 1960-2021 and performing a cross-sectional analysis of serum adrenal steroids.ResultsIn total 14 of the 44 APECED patients (32%) had episodes of hypokalemia; 2 presented with hypokalemia at cross-sectional evaluation and 12 had a history of hypokalemia before the cross-sectional evaluation. Hypokalemic episodes started at the median age of 14.1 years; 12/14 (86%) had primary adrenal insufficiency (PAI). The median number of hypokalemic periods per year was 0.3 (range 0.04-2.2); the frequency correlated positively with the number of clinical APECED manifestations at the time of cross-sectional evaluation (r=0.811, p<0.001). Etiologies of hypokalemia varied but episodes often occurred when new clinical manifestations developed and during hospitalizations. Three patients had kidney defects, also associated with electrolyte imbalances. Severity of hypokalemia varied (range 2.2-3.2 mmol/L), but no severe complications were observed. At cross-sectional evaluation, patients with PAI (n = 30) had significantly lower median plasma potassium and higher sodium concentration than controls, suggesting that fludrocortisone treatment contributed to hypokalemia. Detailed analysis of adrenal steroids provided no conclusive differences between patients with and without episodes of hypokalemia.ConclusionsIn APECED, hypokalemia is common and varies in terms of frequency, etiology, and severity. PAI and kidney disease predispose to hypokalemia. In addition, hypokalemic periods seem to be more common in patients with more severe phenotype of APECED.

A case of Sjogren’s syndrome presenting with recurrent hypokalemia

We report a case of a 26-year old lady who presented with a history of several episodes of limb weakness requiring repeated hospitalization over the last 12 years and about 6 years back, she also developed features of sicca complex. Further investigations revealed hypokalemia, distal renal tubular acidosis and bilateral extensive nephrocalcinosis. Finally, a diagnosis of Sjogren’s syndrome was made. Hypokalemia may be the presenting feature of Sjogren’s syndrome. Sjogren’s syndrome may be suspected in patients with recurrent hypokalemia and renal tubular acidosis. IMC J Med Sci 2022; 16(2): 004. DOI: https://doi.org/10.55010/imcjms.16.014 *Correspondence: Shapur Ikhtaire, Department of Internal Medicine, Bangabandhu Sheikh Mujib Medical University, Shahbag, Dhaka 1000, Bangladesh. Email: shapur17@gmail.com

Malaria and channelopathy- recurrent hypokalaemia - A case report

Malaria is associated with various forms of neurological complications. Weakness like paraparesis and quadriparesis is being described in malaria, the pathologies being polyneuropathy, hypokalaemia, hyperkalaemia, myelitis etc. Recurrent hypokalaemic paralysis has not been described to the best of my knowledge in malaria. I hereby describe a young patient with recurrent episodes of weakness due to hypokalaemia who on investigation was found to be because of malaria. The case report is being described because of it is being novel or not described earlier.

Abstract 135: A case of acquired Gitelman syndrome presenting as hypokalemic paralysis and AKI

Introduction: Gitelman syndrome is usually an inherited disorder, it is induced by defect in the thiazide sensitive Na –Cl co-transporter in distal tubules. Case reports on hypokalemia, AKI secondary to GS has been discussed in present case report.Clinical Case: A 18 year old female referred from department of General Medicine as a case of AKI having recurrent hypokalemia. She gave history of hypokalemic paralysis. There was no potential cause of dehydration such as diarrhoea, vomiting, nephrotoxic agent intake or contrast exposure. Family history was negative. During current hospitalization, she was normotensive with normal renal function test. Other electrolyte levels including calcium and routine laboratory parameters were determined to be normal. Kidney dimensions and echogenicity were determined to be normal without hydronephrosis in the urinary system as oer USG finding. Further workup for hypokalemia revealed urine potassium creatinine ratio (17 mmol/g), ABG (pH 7.44, bicarbonate 26.5 mmol/l), urine chloride (111.3 mmol/l) and urine calcium creatinine ratio (0.05 mmol/mmol) respectively with serum Mg (1.7 mg/dl) on lower range. Based on above findings, a diagnosis of Gitelman syndrome has been made. Autoimmune etiology were ruled out. These finding suggested that patient had AKI secondary to hypokalemia. She was started on oral potassium supplementation and magnesium supplementation.Conclusion: GS is a rare tubulopathy transmitted as an autosomal recessive trait. It is caused by mutation in thiazide sensitive Na Cl co-transporter coding gene, SLC12A3. Patients may be referred with hypokalemia, hypomagnesemia and metabolic alkalosis associated muscular weakness and cramping. By contrast, worsening hypokalemia and profound volume depletion as the predisposing factors for ischemic AKI appears to coexist.

A 48-year adult male with convulsion, collapses and generalized weakness – a rare presentation of Gitelman’s Syndrome

Hypokalaemia is a common clinical condition, very often the cause of which can be determined by the patient’s clinical history. Gitelman’s syndrome is an inherited renal tubular disorder that must be considered in some cases of hypokalaemia. We present this case of a 48-year-old male patient admitted in our nephrology department for recurrent hypokalaemia. The patient had generalized seizure followed by unconsciousness, generalized weakness, fatigue, palpitation, orthostatic hypotension and polyuria for one month. Patient was on treatment for systemic hypertension with amlodipine and olmesartan. On blood gas analysis, he had a metabolic alkalosis (pH 7.53; pCO2 40 mm Hg; HCO3 34.1mmol/l). Biochemical analysis revealed hyponatremia (105.8mmol/l), hypokalemia (2.07mmol/l), hypochloraemia (74.0mmol/l), hypomagnesaemia (1.10mmol/l) and hypocalcaemia (7.2 mg/dl). Serum creatinine (1.9 mg/dl) and blood urea (6.3mmol/l) were normal. Further investigations revealed hypocalciuria (0.5mmol/l; NR 2.5–7.5) and increased urinary excretion of sodium (210.0 mmol/l; NR 20–110), Potassium (35mmol/l) and chloride (220mmol/l; NR 55–125). Renal ultra-sonogram was normal. A diagnosis of Gitelman’s syndrome was established. We started treatment with sodium chloride, potassium chloride and magnesium sulfate supplementation. Serum potassium was stabilized around 3mmol/l and the patient had significant clinical improvement. The aim of our article is to remind Gitelman’s syndrome in the differential diagnosis of persistent hypokalemia and to highlight the need for further investigations in patients with recurrent hypokalaemic episodes. This rare, inherited, autosomal recessive renal tubulopathy is associated with several genetic mutations in the thiazide-sensitive sodium chloride co-transporter and magnesium channels in the distal convoluted tubule. Patients with Gitelman’s syndrome present during adolescence or adulthood as an inherited autosomal recessive traits with a wide range of clinical presentations from being asymptomatic to predominant muscular symptoms such as fatigue, weakness in association with hypocalciuria, hypomagnesemia with hypermagnesuria and normal prostaglandin production. Clinical suspicion should be raised in those with recurrent hypokalaemic paralysis with metabolic alkalosis associated with hypomagnesaemia. Treatment of Gitelman’s syndrome consists of long-term potassium and magnesium salt supplementation. In general, the long-term prognosis and life expectancy is excellent. CBMJ 2021 January: vol. 10 no. 01 P: 54-58

Sensorineural hearing loss in Bartter syndrome

ABSTRACTBackground: Bartter syndrome is a rare inherited case characterized by autosomal recessive and has few different types. Diagnosis is established by laboratory findings, namely hypokalemic metabolic alkalosis, and normotensive. Hearing loss indicates Bartter syndrome type IV. Purpose: To report a case of Bartter syndrome with delayed speech. Case report: A seven years old girl with delayed speech and recurrent hypokalemia was referred to the Otolaryngology Head and Neck Surgery Department, Dr. Cipto Mangunkusumo Hospital, in order to evaluate the hearing level and treatment needed. Based on the Otoacoustic Emission (OAE), Brainstem Evoked Response Audiometry (BERA), and Auditory State Steady Response (ASSR), the diagnosis was profound bilateral sensorineural hearing loss and proceeded with hearing aid and also speech occupational therapy. Clinical question: Is there a relationship between Bartter’s syndrome and the incidence of hearing loss? Review method: Literature review through PubMed, Cochrane, and EBSCO, using keywords such as the impacts of Bartter syndrome on hearing loss, and sensorineural hearing loss in Bartter syndrome case. Result: Following screening of double publication and based on clinical questions over the past five years, only one relevant literature was found. Conclusion: Audiological assessment should be done in all Bartter syndrome’s cases. Early intervention and timely audiological rehabilitation could improve the quality of life in of such children.

Hypokalemic paralysis and renal tubular acidosis: Initial presentation of Sjogren’s syndrome

Sjogren’s syndrome is a rare autoimmune disease affecting multiple systems with varying clinical features.We report a case of 37 year old woman who presented with recurrent episodes of quadriparesis which was attributable to hypokalemia and initially labelled as hypokalemic periodic paralysis. Later on she was found to have metabolic acidosis rather than alkalosis which pointed towards the diagnosis of renal tubular acidosis (RTA) in the absence of apparent gastrointestinal tract loss. Once the diagnosis of RTA was established, an attempt to search the aetiology revealed that she was having primary Sjogren’s syndrome (pSS) though she did not have any symptom at the time of diagnosis. She was found positive for anti-SSA. Lip biopsy revealed lymphocytic infiltration in periductal as well as parenchymal region. Schirmer test confirmed presence of severe dry eye. A concomitant existence of autoimmune hypothyroidism was a noteworthy association. She responded well with potassium supplementation and symptomatic treatment. Presentation of this case reminds the importance of vigilance while managing a case of recurrent hypokalemia which might be a rare presenting feature of pSS.&#x0D; Bangladesh J Medicine July 2021; 32(2) : 145-148

When Manual Analysis of 12-Lead ECG Holter Plays a Critical Role in Discovering Unknown Patterns of Increased Arrhythmogenic Risk: A Case Report of a Patient Treated with Tamoxifen and Subsequent Pneumonia in COVID-19

Several medicines, including cancer therapies, are known to alter the electrophysiological function of ventricular myocytes resulting in abnormal prolongation and dispersion of ventricular repolarization (quantified by multi-lead QTc measurement). This effect could be amplified by other concomitant factors (e.g., combination with other drugs affecting the QT, and/or electrolyte abnormalities, such as especially hypokalemia, hypomagnesaemia, and hypocalcemia). Usually, this condition results in higher risk of torsade de point and other life-threatening arrhythmias, related to unrecognized unpaired cardiac ventricular repolarization reserve (VRR). Being VRR a dynamic phenomenon, QT prolongation might often not be identified during the 10-s standard 12-lead ECG recording at rest, leaving the patient at increased risk for life-threatening event. We report the case of a 49-year woman, undergoing tamoxifen therapy for breast cancer, which alteration of ventricular repolarization reserve, persisting also after correction of concomitant recurrent hypokalemia, was evidenced only after manual measurements of the corrected QT (QTc) interval from selected intervals of the 12-lead ECG Holter monitoring. This otherwise missed finding was fundamental to drive the discontinuation of tamoxifen, shifting to another “safer” therapeutic option, and to avoid the use of potentially arrhythmogenic antibiotics when treating a bilateral pneumonia in recent COVID-19.

Concurrent Pseudohyperaldosteronism and Primary Glucocorticoid Deficiency From Posaconazole

Abstract Background: Posaconazole can cause pseudohyperaldosteronism via inhibition of 11-beta hydroxylase and 11-beta-hydroxysteroid dehydrogenase type 2 (1). The accumulation of 11-deoxycorticosterone and increased cortisol-to-cortisone ratio in the kidney causes apparent mineralocorticoid excess. The effect of posaconazole on the glucocorticoid axis is less established. Clinical Case: A 56-year-old Hispanic man with a history of chronic septic arthritis of the left ankle from Coccidioides presented with 3 months of malaise, nausea, weight loss of 30 pounds, and recurrent hypokalemia. He was recently switched from long-term fluconazole therapy to posaconazole around the time his symptoms began. His initial labs at our hospital were notable for low potassium (2.9 mmol/L, nl 3.5–5.5 mmol/L) and a random cortisol of 5.8 mcg/dL (nl ≥2.0 mcg/dL). A Cosyntropin stimulation test revealed elevated ACTH (168 pg/mL, nl 7.2–63.3 pg/mL) with minimal rise of cortisol from 4.6 to 7.2 mcg/dL at 1 hour after Cosyntropin administration (nl ≥18 mcg/dL at 1-hour post-Cosyntropin). His plasma renin activity was below detection (&amp;lt;0.6 ng/ml/h, nl 0.6–3.0 ng/mL/h), consistent with renin suppression from apparent mineralocorticoid excess. Hydrocortisone for glucocorticoid deficiency was started. A posaconazole determination indicated elevation (5240 ng/mL, usual therapeutic range ≥1000 ng/mL). His posaconazole was stopped, and he was switched back to fluconazole. Three months later, his symptoms were improved with regain of lost weight. Repeat Cosyntropin stimulation test showed ongoing primary glucocorticoid deficiency (ACTH 123 pg/mL, cortisol 4.1 mcg/dL at 1-hour post-Cosyntropin) but normal levels of plasma renin activity (1.2 ng/mL/h), aldosterone (8.6 ng/dL, nl ≤21 ng/dL), and potassium. Quantiferon TB and 21-hydroxylase antibody tests were negative. Hydrocortisone has been continued with plans to repeat Cosyntropin testing in 3 months to reassess. Conclusion: Pseudohyperaldosteronism with glucocorticoid deficiency requiring hydrocortisone treatment has thus far not been reported with posaconazole. Our case shows that posaconazole may lead to true primary glucocorticoid deficiency that can persist after discontinuation of posaconazole and reversal of pseudohyperaldosteronism. Reference: (1) Sanchez-Niño MD, Ortiz A. Unravelling drug-induced hypertension: Molecular mechanisms of aldosterone-independent mineralocorticoid receptor activation by posaconazole. Clin Kidney J 2018;11(5):688–90.