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Background: Management of sepsis is a time critical procedure; the consequences of improperly managed sepsis and septic shock can cause multiple organ dysfunction and death. The aim of this study was to evaluate of the role of hydrocortisone either alone or with fludrocortisone on the outcome septic shock in adults. This study was conducted on 66 patients who were assigned randomly to 3 groups each containing 22 patients. Control group had received standard therapy for sepsis, and H group had received standard therapy for sepsis plus hydrocortisone. HF group had received standard therapy for sepsis plus hydrocortisone and fludrocortisone. Results: It showed that the use of corticosteroids (the hydrocortisone or the hydrocortisone plus fludrocortisone) in septic patients was associated with significant reduction in the time to wean from vasopressors and length of intensive care unit stay. Meanwhile, there were no significant effect of the mortality rate, Sepsis-Related Organ Failure Assessment (SOFA) score reduction, gastrointestinal bleeding, and superinfection as corticosteroids adverse effects between the three groups. Conclusions: The corticosteroids in septic shock have significant positive impacts on some aspects in treatment of septic shock but it does not affect the mortality rate of the patients. [ABSTRACT FROM AUTHOR]

Chronic urinary tract infections by urease-producing bacteria may increase urine pH and promote thereby the formation of recurrent kidney stones made of highly carbonated calcium phosphate apatite and struvite, a magnesium ammonium phosphate. To date, there is no safe and effective treatment decreasing urine pH on a long term. We hypothesized that fludrocortisone, amineralocorticoid, would decrease urine pH by increasing proton secretion in the kidney collecting tubule. We report three cases of patients with kidney stone suffering from chronic urinary infection by ureaseproducing germs, treated by fludrocortisone on a long term. Urine pH decreased sustainably over severalmonths and tolerance was good. [ABSTRACT FROM AUTHOR]

Background: Confirmatory tests are recommended for diagnosing primary aldosteronism, but the supporting evidence is unclear.Methods: We searched Medline, EMBASE, and the Cochrane Central Register of Controlled Trials. Studies evaluating any guideline-recommended confirmatory test (ie, saline infusion test, salt loading test, fludrocortisone suppression test, and captopril challenge test), compared with a reference standard were included. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to assess the risk of bias. Meta-analyses were conducted using hierarchical summary receiver operating characteristic models.Results: Fifty-five studies were included, comprising 26 studies (3654 participants) for the recumbent saline infusion test, 4 studies (633 participants) for the seated saline infusion test, 2 studies (99 participants) for the salt loading test, 7 studies (386 participants) for the fludrocortisone suppression test, and 25 studies (2585 participants) for the captopril challenge test. Risk of bias was high, affecting more than half of studies, and across all domains. Studies with case-control sampling overestimated accuracy by 7-fold (relative diagnostic odds ratio, 7.26 [95% CI, 2.46-21.43]) and partial verification or use of inconsistent reference standards overestimated accuracy by 5-fold (5.12 [95% CI, 1.48-17.77]). There were large variations in how confirmatory tests were conducted, interpreted, and verified. Under most scenarios, confirmatory testing resulted in an excess of missed cases. The certainty of evidence underlying each test (Grading of Recommendations, Assessment, Development, and Evaluations) was very low.Conclusions: Recommendations for confirmatory testing in patients with abnormal screening tests and high probability features of primary aldosteronism are based on very low-quality evidence and their routine use should be reconsidered. [ABSTRACT FROM AUTHOR]

Background and Objective: In an experiment designed to explore the mechanisms of fludrocortisone-induced high blood pressure, we serendipitously observed aortic aneurysms in mice infused with fludrocortisone. The purpose of this study was to investigate whether fludrocortisone induces aortic pathologies in both normocholesterolemic and hypercholesterolemic mice. Methods and Results: Male adult C57BL/6J mice were infused with either vehicle (85% polyethylene glycol 400 (PEG-400) and 15% dimethyl sulfoxide (DMSO); n = 5) or fludrocortisone (12 mg/kg/day dissolved in 85% PEG-400 and 15% DMSO; n = 15) for 28 days. Fludrocortisone-infused mice had higher systolic blood pressure, compared to mice infused with vehicle. Fludrocortisone induced aortic pathologies in 4 of 15 mice with 3 having pathologies in the ascending and aortic arch regions and 1 having pathology in both the ascending and descending thoracic aorta. No pathologies were noted in abdominal aortas. Subsequently, we infused either vehicle (n = 5/group) or fludrocortisone (n = 15/group) into male ApoE −/− mice fed a normal laboratory diet or LDL receptor −/− mice fed either normal or Western diet. Fludrocortisone increased systolic blood pressure, irrespective of mouse strain or diet. In ApoE −/− mice infused with fludrocortisone, 2 of 15 mice had ascending aortic pathologies, but no mice had abdominal aortic pathologies. In LDL receptor −/− mice fed normal diet, 5 had ascending/arch pathologies and 1 had pathologies in the ascending, arch, and suprarenal aortic regions. In LDL receptor −/− mice fed Western diet, 2 died of aortic rupture in either the descending thoracic or abdominal region, and 2 of the 13 survived mice had ascending/arch aortic pathologies. Aortic pathologies included hemorrhage, wall thickening or thinning, or dilation. Only ascending aortic diameter in LDLR −/− mice fed Western diet reached statistical significance, compared to their vehicle. Conclusion: Fludrocortisone induces aortic pathologies independent of hypercholesterolemia. As indicated by the findings in mouse studies, people who are taking or have taken fludrocortisone might have an increased risk of aortic pathologies. [ABSTRACT FROM AUTHOR]

Introduction and purpose Addison's syndrome is defined as primary adrenal insufficiency, the symptoms of which result from hormonal deficiencies: glucocorticosteroids, mineralocorticosteroids and androgens. Currently, autoimmunity is considered the most common cause of Addison's Syndrome. Antibodies are most often directed against the enzymes 21-hydroxylase and 17-hydroxylase involved in steroidogenesis. The aim of the study is to present a typical clinical course, diagnostic path and current therapeutic options of Addison's syndrome. Description of the state of knowledge Currently, in developed countries, the number of cases is 100-140 people per million people. Initially, Addison's syndrome runs secretly. The clinical picture is closely correlated with the degree of adrenal cortex destruction. The most common symptoms include hypotonia, weight loss, weakness, salt craving, gastrointestinal disorders, and hyperpigmentation of the skin and mucous membranes. In extreme cases, adrenal crisis may develop, characterized by rapid clinical deterioration with hypotension, fever, vomiting, dehydration, and loss of consciousness. Diagnostics uses the measurement of the concentration of morning cortisol and corticotropin (ACTH) in the blood, and in doubtful situations, additionally a stimulation test using synthetic ACTH. Summary A diagnosis of Addison's syndrome requires end-of-life hormonal substitution. For this purpose, hydrocortisone or prednisone and fludrocortisone are used. In stressful situations, the doses of glucocorticoids should be adequately increased. Patients with adrenal crisis require intensive fluid resuscitation to restore intravascular volume, correct hypoglycemia and electrolyte disturbances, and administer rapidly high doses of hydrocortisone.

Objective: Treatment of classic congenital adrenal hyperplasia (CAH) is necessary to compensate for glucocorticoid/mineralocorticoid deficiencies and to suppress androgen excess. Hydrocortisone (HC) is preferred in growing children with classic CAH but recommendations regarding dosage/administration are inconsistent. The aim of this study was to evaluate HC dosing in children with CAH in relation to chronological age, sex, and phenotype based on a multicenter CAH registry. Design: The CAH registry was initiated in 1997 by the AQUAPE in Germany. On December 31st 2018, data from 1571 patients were included. Methods: A custom-made electronic health record software is used at the participating centers. Pseudonymized data are transferred for central analysis. Parameters were selected based on current guidelines. Descriptive analyses and linear regression models were implemented with SAS 9.4. Results: We identified 1288 patients on exclusive treatment with hydrocortisone three times daily (604 boys; median age 7.2 years; 817 salt-wasting phenotype, 471 simple-virilizing phenotype). The mean (lower-upper quartiles) daily HC dose (mg/m² body surface area) was 19.4 (18.9–19.8) for patients

Whether the use of fludrocortisone affects outcomes of patients with aneurysmal subarachnoid hemorrhage (aSAH). We conducted a retrospective analysis of 78 consecutive patients with a ruptured aSAH at a single academic center in the United States. The primary outcome was the score on the modified Rankin scale (mRS, range, 0 [no symptoms] to 6 [death]) at 90 days. The primary outcome was adjusted for age, hypertension, aSAH grade, and time from aSAH onset to aneurysm treatment. Secondary outcomes were neurologic and cardiopulmonary dysfunction events. Among 78 patients at a single center, the median age was 58 years [IQR, 49 to 64.5]; 64 % were female, and 41 (53 %) received fludrocortisone. The adjusted common odds ratio, aOR, of a proportional odds regression model of fludrocortisone use with mRS was 0.33 (95 % CI, 0.14-0.80; P = 0.02), with values <1.0 favoring fludrocortisone. Organ-specific dysfunction events were not statistically different: delayed cerebral ischemia (22 % vs. 39 %, P = 0.16); cardiac dysfunction (0 % vs. 11 %; P = 0.10); and pulmonary edema (15 % vs. 8 %; P = 0.59). The risk of disability or death at 90 days was lower with the use of fludrocortisone in aSAH patients. [ABSTRACT FROM AUTHOR]

Background: Autosomal‐recessive renal tubular dysgenesis (AR‐RTD) is a rare genetic disorder caused by defects in the renin‐angiotensin system that manifests as fetal anuria leading to oligohydramnios and Potter sequence. Although the most common outcome is neonatal death from renal failure, pulmonary hypoplasia, and/or refractory arterial hypotension; several cases have been reported that describe survival past the neonatal period. Methods: Herein, we report the first family with biallelic ACE variants and more than one affected child surviving past the neonatal period, as well as provide a review of the previously reported 18 cases with better outcomes. Results: While both siblings with identical compound heterozygous ACE variants have received different treatments, neither required renal replacement therapy. We show that both vasopressin and fludrocortisone in the neonatal period may provide survival advantages, though outcomes may also be dependent on the type of gene variant, as well as other factors. Conclusion: While AR‐RTD is most often a lethal disease in the neonatal period, it is not universally so. A better understanding of the factors affecting survival will help to guide prognostication and medical decision‐making. [ABSTRACT FROM AUTHOR]

For salt-wasting 21-hydroxylase deficiency (21OHD), fludrocortisone (FC) is usually supplemented at 0.05-0.2 mg/d dose. To date, no report has described 21OHD neonates requiring > 0.4 mg/d of FC. Our female 21OHD patient was lethargic and experienced weight loss with hyponatremia (133 mEq/L), hyperkalemia (6.5 mEq/L), and elevated active renin concentration (ARC, 1942.2 pg/mL) at 6 days of life. Hydrocortisone and FC replacement were initiated. FC dose was gradually increased to 0.4 mg/d at 21 days of life, but her hyperkalemia (6.4 mEq/L) and high ARC (372.3 pg/mL) persisted. We increased FC to 0.6 mg/d and used a low-potassium and high-sodium formula. Hyperkalemia subsequently improved. At 33 days of life, the ARC decreased to 0.6 pg/mL and FC dosage was gradually decreased. At 3 months of age, the low-potassium and high-sodium formula was discontinued, but the serum potassium level was normal and ARC remained low at 0.1 mg/d of FC. We speculated that severe mineralocorticoid resistance was the reason why her hyperkalemia persisted even with 0.4 mg/d of FC; however, the pathophysiology of transiently severe resistance to FC in this patient is unknown. In conclusion, 21OHD neonates may show severe salt-wasting that transiently require > 0.4 mg/d of FC. [ABSTRACT FROM AUTHOR]

Abstract Background Autosomal‐recessive renal tubular dysgenesis (AR‐RTD) is a rare genetic disorder caused by defects in the renin‐angiotensin system that manifests as fetal anuria leading to oligohydramnios and Potter sequence. Although the most common outcome is neonatal death from renal failure, pulmonary hypoplasia, and/or refractory arterial hypotension; several cases have been reported that describe survival past the neonatal period. Methods Herein, we report the first family with biallelic ACE variants and more than one affected child surviving past the neonatal period, as well as provide a review of the previously reported 18 cases with better outcomes. Results While both siblings with identical compound heterozygous ACE variants have received different treatments, neither required renal replacement therapy. We show that both vasopressin and fludrocortisone in the neonatal period may provide survival advantages, though outcomes may also be dependent on the type of gene variant, as well as other factors. Conclusion While AR‐RTD is most often a lethal disease in the neonatal period, it is not universally so. A better understanding of the factors affecting survival will help to guide prognostication and medical decision‐making.

The article focuses on a Japanese girl with aldosterone synthase deficiency (ASD), a rare autosomal recessive disorder causing severe dehydration, salt wasting, and failure to thrive in infancy due to CYP11B2 gene variants. Topics discussed include the patient's clinical presentation, genetic analysis revealing compound heterozygous variants, successful fludrocortisone therapy, and the overall good prognosis of ASD with decreasing treatment needs in adulthood.

Orthostatic hypotension is a frequent cause of falls and syncope, impairing quality of life. It is an independent risk factor of mortality and a common cause of hospitalizations, which exponentially increases in the geriatric population. We present a management plan based on a systematic literature review and understanding of the underlying pathophysiology and relevant clinical pharmacology. Initial treatment measures include removing offending medications and avoiding large meals. Clinical assessment of the patients' residual sympathetic tone can aid in the selection of initial therapy between norepinephrine "enhancers" or "replacers." Role of splanchnic venous pooling is overlooked, and applying abdominal binders to improve venous return may be effective. The treatment goal is not normalizing upright blood pressure but increasing it above the cerebral autoregulation threshold required to improve symptoms. Hypertension is the most common associated comorbidity, and confining patients to bed while using pressor agents only increases supine blood pressure, leading to worsening pressure diuresis and orthostatic hypotension. Avoiding bedrest deconditioning and using pressors as part of an orthostatic rehab program are crucial in reducing hospital stay. [ABSTRACT FROM AUTHOR]

Background: Cardiogenic shock (CS) is a life-threatening condition characterized by circulatory insufficiency caused by an acute dysfunction of the heart pump. The pathophysiological approach to CS has recently been enriched by the tissue consequences of low flow, including inflammation, endothelial dysfunction, and alteration of the hypothalamic-pituitary-adrenal axis. The aim of the present trial is to evaluate the impact of early low-dose corticosteroid therapy on shock reversal in adults with CS.Method/design: This is a multicentered randomized, double-blind, placebo-controlled trial with two parallel arms in adult patients with CS recruited from medical, cardiac, and polyvalent intensive care units (ICU) in France. Patients will be randomly allocated into the treatment or control group (1:1 ratio), and we will recruit 380 patients (190 per group). For the treatment group, hydrocortisone (50 mg intravenous bolus every 6 h) and fludrocortisone (50 μg once a day enterally) will be administered for 7 days or until discharge from the ICU. The primary endpoint is catecholamine-free days at day 7. Secondary endpoints include morbidity and all-cause mortality at 28 and 90 days post-randomization. Pre-defined subgroups analyses are planned, including: postcardiotomy, myocardial infarction, etomidate use, vasopressor use, and adrenal profiles according the short corticotropin stimulation test. Each patient will be followed for 90 days. All analyses will be conducted on an intention-to-treat basis.Discussion: This trial will provide valuable evidence about the effectiveness of low dose of corticosteroid therapy for CS. If effective, this therapy might improve outcome and become a therapeutic adjunct for patients with CS.Trial Registration: ClinicalTrials.gov , NCT03773822 . Registered on 12 December 2018. [ABSTRACT FROM AUTHOR]

ObjectivesTo determine whether administration of intravenous hydrocortisone is a safe and effective alternative treatment in comparison to the traditional treatment with prednisolone/dexamethasone in dogs presenting with Addisonian crisis; and to assess if there is any advantage of the former over the latter in normalisation of electrolyte imbalances and in hospitalisation length in these dogs.MethodsMedical records of client-owned dogs with hypoadrenocorticism were retrospectively reviewed. Time until normalisation of sodium and potassium concentration, intravenous fluid needs over the first 24 h and hospitalisation length were compared between hydrocortisone and prednisolone/dexamethasone treated dogs.ResultsTwenty-five dogs met the inclusion criteria; 13 received hydrocortisone and 12 prednisolone/dexamethasone. Intravenous hydrocortisone was well-tolerated but failed to prove superiority in terms of time to normalisation of sodium and potassium concentration. Interestingly, potassium normalised in all dogs prior to discharge, but sodium did not in 1/11 hydrocortisone and 5/9 prednisolone/dexamethasone treated dogs with initial hyponatraemia (p = 0.05). Hydrocortisone treated dogs, however, had more electrolyte re-checks [hydrocortisone treated dogs, median (range): 4 (2–16); prednisolone/dexamethasone treated dogs: 2 (0–6); p = 0.001]. There was no difference in intravenous fluid needs over the first 24 h but hydrocortisone treated dogs had longer hospitalisation [hydrocortisone: 81 (45–309) h; prednisolone/dexamethasone: 52 (22–138) h; p = 0.01].Clinical SignificanceIntravenous hydrocortisone is well-tolerated and safe, but no clear additional benefit over traditional glucocorticoid replacement could be identified. Also, it might result in longer hospitalisation time and more intensive monitoring.

Abstract Background Adrenal patients have a lifelong dependency on steroid replacement therapy and are vulnerable to sudden death from undertreated adrenal crisis. Urgent treatment with parenteral steroids is needed, often with IV saline for volume repletion. Episodes of adrenal crisis are, for most patients, relatively infrequent and they may not be well prepared to respond. This study explores how patients recall previous episodes of adrenal crisis and their satisfaction with UK emergency medical treatment. Methods We invited members of the main UK support groups representing steroid-dependent adrenal patients to complete an online questionnaire identifying the number, causes and location of previous adrenal crises (episodes needing injected steroids and/or IV fluids). Respondents were asked to rate the adequacy of their medical treatment in 2 successive questionnaires, conducted 2013 and 2017–18. Results Vomiting was the major factor identified as a cause of adrenal crisis, indicated by 80% of respondents. The most common location, at 70%, was the home. Of the 30% away from home, 1 in 3 were overseas or travelling long-distance. Self-treatment played an increasing role in emergency response: in the 5 year interval between questionnaires an increasing number of patients self-injected. By the time of the 2017–18 survey self-injection was the most common method of initial treatment, with less than two-thirds travelling to hospital for follow-up medical treatment. This finding help to explain the higher rate of adrenal crisis identified in patient surveys than in hospital records. Satisfaction with medical care received stayed constant between the 2 surveys despite growing resourcing pressures across the NHS. Two-thirds were happy with the quality of the medical treatment they received for their most recent adrenal emergency; timeliness was the main factor influencing satisfaction. Conclusions Around one-third of adrenal patients report sub-optimal treatment at emergency medical departments. Medical staff have a low probability of encountering adrenal crisis and may be unfamiliar with either the urgency of adrenal crisis or the specific treatment response it requires. Comprehensive protocols for emergency medical staff with detailed patient education and training are needed in how to respond to this infrequently encountered – but acutely life-threatening – scenario.

Background: Hyperkalemia is a frequent and potentially lethal complication of chronic kidney disease (CKD). We retrospectively examined the potassium-lowering effect of oral fludrocortisone and its adverse effects in hyperkalemic CKD patients not yet on dialysis., Methods: Thirty-three patients (23 men and 10 women, ages 69±14 years) were included. To control hyperkalemia at the outpatient clinic, twenty-one patients (Group 1) received fludrocortisone (0.05-0.1 mg/day) without changes in angiotensin II receptor blockers (ARBs) and calcium polystyrene sulfonate (CPS), while twelve patients (Group 2) were treated with fludrocortisone in addition to stopping ARBs and/or adding low-dose CPS., Results: Fludrocortisone was administered for a median of 169 days (interquartile range, 47-445). At the first follow-up after fludrocortisone administration, serum potassium dropped from 6.14±0.32 mEq/L to 4.52±1.06 mEq/L (p<0.001) in Group 1 and from 6.37±0.35 mEq/L to 4.08±0.74 mEq/L (p<0.01) in Group 2. Ten patients in Group 1 and five patients in Group 2 measured serum potassium levels at four outpatient visits before and after fludrocortisone administration, respectively. The frequency of serum potassium ≥6.0 mEq/L decreased from 19/40 (48%) to 2/40 (5%) (p<0.001) in Group 1 and from 11/20 (55%) to 0/20 (0%) (p<0.001) in Group 2. Eleven patients experienced sodium retention-related problems after fludrocortisone administration: 7 with worsening leg edema, 2 with pleural effusions, and 2 with pulmonary edema., Conclusion: In pre-dialysis CKD patients, fludrocortisone at low doses effectively reduced serum potassium levels; however, sodium retention was a common adverse effect., Competing Interests: Conflict of Interest: The authors have no conflicts of interest to declare., (Copyright © 2024 Korean Society for Electrolyte and Blood Pressure Research.)

Introduction: Congenital adrenal hyperplasia (CAH) is a condition resulting from a deficiency in enzymes involved in the biosynthesis of steroid hormones in the adrenal cortex. Most cases of CAH are due to impaired 21- hydroxylase production, leading to insufficient cortisol and aldosterone synthesis. The classic form of CAH is subdivided into two types: salt-wasting and simple-virilizing. Case Report: A 2-year-old girl consulted the endocrinology department for reevaluation presenting ambiguous external genitalia. She was first diagnosed at 6 months with salt-wasting 21-hydroxylase-deficiency and was under treatment with hydrocortisone, fludrocortisone, and an additional salt intake of 1g/day. Upon clinical examination the patient had virilization (Prader stage II), increased 17- hydroxyprogesterone (91.3 ng/ml), androstenedione (1.77 ng/ml), and plasma renin (373.3 uUI/ml). She had also developed hypertension (130/90 mmHg). For this reason, the decision to cease fludrocortisone administration was made. The evolution of the patient was good, the hypertension subsided after discontinuing fludrocortisone treatment (105/65 mmHg), the laboratory results showed good control of 17-hydroxyprogesterone and ACTH, as well as normal levels of electrolytes, corticoid, and mineralocorticoid hormones. The diagnosis was revised, and the enzyme deficiency was described as simple-virilizing. On further follow-ups at 3, 4 and 5 years of age, the patient's hormonal levels were well controlled and the blood pressure stayed within the normal range. Discussions : Our case highlights the fact that treatment for this particular genetic disease should be closely monitored and adjusted in accordance to the evolution of the disease to avoid unwanted side effects. The disease was at first identified and treated as a salt-wasting form and although the administration of mineralocorticoids is crucial in preventing adrenal crisis in infants with salt loss, prolonged administration of fludrocortisone was the likely cause of hypertension. This aligns with current literature which suggests that the classification of 21- hydroxylase deficiency as salt-wasting and simple-virilizing is slowly falling out of use as CAH shows a high variability of clinical phenotypes. Moreover, although one mutation in the CYP21A2 gene was detected (P30L mutation), a second mutation could not be detected by the available test. Sequencing to find a possible rare mutation could have explained the unique phenotype of the disease because generally, the P30L mutation is associated with less severe forms of CAH. Conclusions: This case emphasizes the importance of monitoring infants with CAH and shows that the current classification of this disease is not always in accordance with its evolution, thus incorrect treatment can result in iatrogenic adverse effects. [ABSTRACT FROM AUTHOR]

This study aims to gather knowledge about the use of deoxycorticosterone pivalate (DOCP) byWestern European Veterinarians (WEV) in dogs with typical hypoadrenocorticism. An observational cross-sectional study was conducted using an online survey, translated into four languages and disseminated to veterinary affiliates and mailing lists in six countries of Western Continental Europe. Respondents were tasked to share their therapeutic approach to hypoadrenocorticism, whether they preferred DOCP or fludrocortisone and the specific practical use of DOCP. One-hundred and eighty-four responses were included. Of these, 79.9% indicated that they preferred prescribing DOCP over fludrocortisone as a first-line treatment for mineralocorticoid supplementation. A total of 154 respondents had used DOCP at least once. Eighty percent of those who reported their initial dosage prescribed 2.2 mg/kg. After starting DOCP, 68.2% of the respondents assess electrolytes 10 and 25 days after administration following manufacturer instructions. In stable dogs, electrolytes are monitored quarterly, monthly, semi-annually, and annually by 44.2%, 34.4%, 16.9%, and 4.6% of respondents respectively. When treatment adjustment is required, 53% prefer to reduce dosage while 47% increase the interval between doses. Overall, DOCP is the preferred mineralocorticoid supplementation among WEV. Reported variability underlies the need to investigate the best strategies for DOCP use and therapeutic adjustments. [ABSTRACT FROM AUTHOR]

The present work was aimed at the development of an analytical method with high sensitivity, selectivity, and rapidity for pharmacokinetic studies. The new method for quantitative determination of fludrocortisone in human blood plasma employs HPLC and mass spectrometric detection with electrospray ionization (ESI). The deuterium-labeled analog of fludrocortisone (fludrocortisone-D5) was used as the internal standard. The lower limit of quantitation (LLOQ) was 10 pg/mL. The calibration curve was linear in the range 10 – 1000 pg/mL. The coefficient of reliability was at least 0.99. Liquid extraction was used for sample preparation. The proposed technique was tested by studying the bioequivalence of a generic drug in a single administration to healthy volunteers at a dose of 0.1 mg. [ABSTRACT FROM AUTHOR]

Cerebral salt wasting syndrome (CSWS) is an important cause of persistent hyponatremia in children admitted to the intensive care unit. It needs to be promptly differentiated from the syndrome of inappropriate antidiuretic hormone (SIADH) secretion as a cause of hyponatremia in pediatric neurological patients. These two entities often have similar presenting symptoms however the treatment of both can be drastically different, which makes the distinction critical. We present a 6-month-old male child with hydrocephalus secondary to aqueductal stenosis, a blocked VP shunt, meningitis, and hyponatremia. A diagnosis of CSWS was considered and fludrocortisone was started. The patient improved gradually with a reduction in urine output and a gradual increase in serum sodium levels. A diagnosis of CSWS should be strongly considered in hyponatremic pediatric patients with significant natriuresis and suitable treatment should be initiated promptly to prevent long-term neurologic sequelae. [ABSTRACT FROM AUTHOR]

Background: The cornerstone of the treatment of vasovagal syncope (VVS) is lifestyle modifications; however, some patients incur life-disturbing attacks despite compliance with these treatments which underscores the importance of pharmacological interventions.Methods: In this open-label multi-center randomized controlled trial, we are going to randomize 1375 patients with VVS who had ≥2 syncopal episodes in the last year into three parallel arms with a 2:2:1 ratio to receive midodrine, fludrocortisone, or no medication. All patients will be recommended to drink 2 to 3 liters of fluids per day, consume 10 grams of NaCl per day, and practice counter-pressure maneuvers. In medication arms, patients will start on 5 mg of midodrine TDS or 0.05 mg of fludrocortisone BD. After one week the dosage will be up-titrated to midodrine 30 mg/day and fludrocortisone 0.2 mg/day. Patient tolerance will be the principal guide to dosage adjustments. We will follow-up the patients on 3, 6, 9, and 12 months after randomization. The primary outcome is the time to first syncopal episode. Secondary outcomes include the recurrence rate of VVS, time interval between first and second episodes, changes in quality of life (QoL), and major and minor adverse drug reactions. QoL will be examined by the 36-Item Short Form Survey questionnaire at enrollment and 12 months after randomization.Conclusion: The COMFORTS trial is the first study that aims to make a head-to-head comparison between midodrine and fludrocortisone, against a background of lifestyle modifications for preventing recurrences of VVS and improving QoL in patients with VVS. [ABSTRACT FROM AUTHOR]

Initiation of desmopressin acetate (DDAVP) for untreated diabetes insipidus (DI) in Wolfram syndrome (WS) causes abrupt volume expansion resulting in particularly high secretion of Atrial Natriuretic Peptide (ANP) and/or Brain Natriuretic Peptide (BNP), which in turn blocks all stimulators of zona glomerulosa steroidogenesis, resulting in secondary mineralocorticoid deficiency and acute hyponatremia, causing renal salt wasting (RSW). Two sisters, a 19-y-old girl (A) and a 7-y-old girl (B) with WS, presented with severe polyuria-polydipsia due to never treated DI. Both had neurogenic bladder and "B" had severe hydronephrosis secondary to untreated grade III bilateral vesicoureteral reflux. They initiated therapy with oral melt DDAVP which resulted in RSW. ANP was found ×50 and BNP ×2-4 fold elevated. Fludrocortisone 100-200 × 2 μg/d controlled natriuresis and restored electrolytes to normal within 48 h. Fludrocortisone treatment rescues otherwise potentially life-threatening hyponatremia due to RSW and the secondary mineralocorticoid deficiency driven by elevated ANP and/or BNP, caused by sudden volume expansion following DDAVP initiation. [ABSTRACT FROM AUTHOR]

Background: The role of the combination of glucocorticosteroids and mineralocorticosteroids in treating septic shock is not well-defined. The aim of this study was to perform a systematic review and meta-analysis of the randomized controlled trials and observational studies assessing the effect of low-dose hydrocortisone and fludrocortisone on patients with septic shock. Materials and Methods: MEDLINE, Scopus, and Cochrane databases were reviewed. A random effect model meta-analysis was used and I-square was used to assess the heterogeneity. Short-term mortality was chosen as our primary end point. A subgroup analysis was performed including only the randomized controlled trials. Results: A total of 10,550 patients were included in this meta-analysis. Administration of the steroid combination was associated with improved short-term mortality (odds ratio, 0.78, confidence interval, 0.64–0.96), intensive care unit mortality, and shock reversal, without increase in steroid-related side effects, such as secondary infection or gastrointestinal hemorrhage. Conclusion: This systematic review and meta-analysis showed that use of the combination of glucocorticosteroids and mineralocorticosteroids has a beneficial impact on short-term mortality, intensive care unit mortality, and shock reversal, without increasing the incidence of gastrointestinal hemorrhage or superinfection in patients with septic shock, when used as an adjunct treatment to the established standard of care.

Neurogenic orthostatic hypotension is a common disorder often seen in elderly patients affected with neurodegenerative disorders and peripheral neuropathies. Defective baroreflex-mediated sympathetic activation in response to standing results in neurogenic orthostatic hypotension. Lightheadedness, dizziness, blurring of vision, palpitations, and/or recurrent syncope in response to sudden postural change or prolonged standing are the characteristic symptoms presented by patients with orthostatic hypotension. Orthostatic symptoms may be further aggravated by certain medications, fluid depletion, food intake, increased temperature, or physical deconditioning. Bedside orthostatic test, head-up tilt table test, and 24-h ambulatory blood pressure monitoring are the important tests to diagnose orthostatic hypotension. Discontinuation of medications that cause or exacerbate orthostatic hypotension and non-pharmacological approaches should be initially tried to treat neurogenic orthostatic hypotension. If the patient does not have significant improvement, add-on pharmacotherapy should be administered. Midodrine, droxidopa, and fludrocortisone are the commonly administered medications for treating neurogenic orthostatic hypotension. Systematic reviews have shown that there is moderate level of evidence that droxidopa and midodrine improve orthostatic hypotension in the short term. Fludrocortisone is included in the treatment guidelines based on expert opinion, despite having low level of evidence. However, there is no much evidence for the long-term efficacy of any pharmacological agent used to treat orthostatic hypotension. Treatment of neurogenic orthostatic hypotension should be periodically assessed. Predominantly, it involves measuring symptomatic benefit including impact on activities of daily living as well as blood pressure monitoring.

Background and Objective: In an experiment designed to explore the mechanisms of fludrocortisone-induced high blood pressure, we serendipitously observed aortic aneurysms in mice infused with fludrocortisone. The purpose of this study was to investigate whether fludrocortisone induces aortic pathologies in both normocholesterolemic and hypercholesterolemic mice. Methods and Results: Male adult C57BL/6J mice were infused with either vehicle (85% polyethylene glycol 400 (PEG-400) and 15% dimethyl sulfoxide (DMSO); n = 5) or fludrocortisone (12 mg/kg/day dissolved in 85% PEG-400 and 15% DMSO; n = 15) for 28 days. Fludrocortisone-infused mice had higher systolic blood pressure, compared to mice infused with vehicle. Fludrocortisone induced aortic pathologies in 4 of 15 mice with 3 having pathologies in the ascending and aortic arch regions and 1 having pathology in both the ascending and descending thoracic aorta. No pathologies were noted in abdominal aortas. Subsequently, we infused either vehicle (n = 5/group) or fludrocortisone (n = 15/group) into male ApoE −/− mice fed a normal laboratory diet or LDL receptor −/− mice fed either normal or Western diet. Fludrocortisone increased systolic blood pressure, irrespective of mouse strain or diet. In ApoE −/− mice infused with fludrocortisone, 2 of 15 mice had ascending aortic pathologies, but no mice had abdominal aortic pathologies. In LDL receptor −/− mice fed normal diet, 5 had ascending/arch pathologies and 1 had pathologies in the ascending, arch, and suprarenal aortic regions. In LDL receptor −/− mice fed Western diet, 2 died of aortic rupture in either the descending thoracic or abdominal region, and 2 of the 13 survived mice had ascending/arch aortic pathologies. Aortic pathologies included hemorrhage, wall thickening or thinning, or dilation. Only ascending aortic diameter in LDLR −/− mice fed Western diet reached statistical significance, compared to their vehicle. Conclusion: Fludrocortisone induces aortic pathologies independent of hypercholesterolemia. As indicated by the findings in mouse studies, people who are taking or have taken fludrocortisone might have an increased risk of aortic pathologies.