Fludrocortisone Research Articles

Challenges in Administration of Corticosteroids for the Treatment of Addison’s Disease: A Case Study of Fludrocortisone Acetate

Fludrocortisone is a known corticosteroid used to control the amount of sodium and fluids in body. Fludrocortisone act by decreasing the amount of sodium that is excreted in your urine. It is indicated to take orally and it is recommended not to stop Fludrocortisone treatment without Physician consent as sudden stoppage leads to several moderate to severe adverse effects. There are several moderate to severe adverse effects reported with treatment of Fludrocortisone including high Blood Pressure (BP), Heart failure, weakness of muscles, changes in mood and low immune system function. Considering this there is need to develop sustained release formulation as microparticles which help to improve patient compliance by reducing dosage frequency which overall help to reduce side effects reported with Fludrocortisone. The aim of this research is to develop different formulations of Fludrocortisone (FLU) by using various polymers (poly(e-caprolactone, PLC), Eudragit® RS and Eudragit® RL) and different processes (oil-in-water (O/W) solvent evaporation methods and suspension-in-oil-in-water (S/O/W) evaporation methods). Small poly(e-caprolactone (PCL)-based microparticles have successfully developed during study which was leading to good efficiency when it was prepared by oil-in-water (O/W) emulsion method with 7.5 mg/ml of FLU.

PRIMARY HYPOADRENOCORTICISM IN A DOG

This report describes the clinical and laboratorial findings as well as the therapeutic protocol performed in a three-year-old mongrel female intact dog, referred to the Veterinary Hospital of FAMEZ/UFMS. The animal had a previous history of recurrent gastrointestinal signs (such as lethargy, vomiting, loss of appetite, melena and abdominal pain), acute crisis episodes, bradycardia, hypotension, hypothermia and increase of capillary refill time, recognized as addisonian crisis due to primary hypoadrenocorticism. Laboratorial findings included anemia, eosinophilia, neutrophilia, lymphocytosis, sodium-potassium ratio of 14,02 mEq/L and prerenal azotemia. Based on that, it was confirmed the diagnosis of primary hypoadrenocorcitism. Thus, it was recommended supplementation therapy with mineralocorticoid (aldosterone) and glucocorticoid (cortisol) corresponding respectively, fludrocortisone acetate of 0.2 mg per kg of BW, by mouth, once daily and prednisone 0.2 mg per kg of BW, by mouth, twice daily until further recommendations. The prognostic was excellent, since the animal significantly improved body condition, andclinical signs disappeared after therapy which lead the sodium-potassium ratio to 35.11 mEq/L. Thus, the clinician must always suspect of primary hypoadrenocorticism in dogs with intermittent nonspecific signs that get better with support therapy. Presumably, hypoarenocorticism must be under diagnosed in veterinary medicine, reinforcing the need to require specific exams in patients that show this wax and wane feature of clinical signs.

Corticosteroid Fludrocortisone Acetate Targets Multiple End Points in Zebrafish (Danio rerio) at Low Concentrations.

Synthetic corticosteroids may pose an environmental risk to fish. Here, we describe multiend point responses of adult zebrafish (8 months old) upon 21-day exposure to a commonly prescribed corticosteroid, fludrocortisone acetate (FLU), at concentrations between 0.006 and 42 μg/L. No remarkable reproductive impacts were observed, while physiological effects, including plasma glucose level and blood leukocyte numbers were significant altered even at 42 ng/L. Ovary parameters and transcriptional analysis of hypothalamic-pituitary-gonadal-liver axis revealed negligible effects. Significant alterations of the circadian rhythm network were observed in the zebrafish brain. Transcripts of several biomarker genes, including per1a and nr1d1, displayed strong transcriptional changes, which occurred at environmental relevant concentrations of 6 and 42 ng/L FLU. Importantly, the development and behavior of F1 embryos were significant changed. Heartbeat, hatching success and swimming behavior of F1 embryos were all increased even at 6 and 42 ng/L. All effects were further confirmed by exposure of eleuthero-embryos. Significant transcriptional changes of biomarker genes involved in gluconeogenesis, immune response and circadian rhythm in eleuthero-embryos confirmed the observations in adult fish. Hatching success, heartbeat, and swimming activity were increased at 81 ng/L and higher, as with F1 embryos. These results provide novel insights into the understanding of potential environmental risks of corticosteroids.

Aerosolization, Drug Permeation and Cellular Interaction of Dry Powder Pulmonary Formulations of Corticosteroids with Hydroxypropyl-β-Cyclodextrin as a Solubilizer.

The purpose of this study was to assess the feasibility of hydroxypropyl-β-cyclodextrin as a solubilizer for the corticosteroids prednisolone and fludrocortisone acetate in dry powder inhalation formulations. The dry particles were simultaneously produced and coated with nanosized L-leucine crystals using an aerosol flow reactor method. The aerosolization performances of carrier-free powders were studied using Easyhaler® and Twister™ at 2 and 4 kPa pressure drops over the inhalers. Drug permeation properties of the formulations were tested across a Calu-3 cell monolayer. Toxicity and reactive oxygen species induction were tested against Calu-3 and A549 cell lines. The hydroxypropyl-β-cyclodextrin in the powders promoted the dissolution of fludrocortisone the most, followed by that of prednisolone. Fine particle fractions were 52-70% from emitted doses which showed good repeatability with a coefficient variation of 0.9-0.17. In addition, hydroxypropyl-β-cyclodextrin enhanced the permeation of the corticosteroids. The powders showed no statistically significant toxicity nor reactive oxygen species induction in the tested cell lines. This study demonstrated the preparation and function of fine powder formulations which combine improved dissolution of poorly soluble drugs with good aerosolization performance. These results are expected to promote particle engineering as a way to develop new types of therapeutic pulmonary powders.

Factors that affect stabilisation times of canine spontaneous hypoadrenocorticism

The objective of this retrospective study was to examine factors that may have affected the stabilisation times of 50 dogs with spontaneous hypoadrenocorticism that were being treated with fludrocortisone acetate,...

The acute effect of a mineralocorticoid receptor agonist on corticotrope secretion in Addison's disease.

Mineralocorticoid receptors (MR) in the hippocampus display an important role in the control of hypothalamic-pituitary-adrenal (HPA) axis, mediating the ''proactive'' feedback of glucocorticoids (GC). Fludrocortisone (FC), a potent MR agonist, has been shown to decrease HPA activity through a hippocampal mechanism. Since it has been demonstrated that FC shows a significant inhibition of the HPA axis response to hCRH stimulus in normal subjects, also at doses usually administered as replacement therapy in patients with Addison's disease, an FC effect at MRs in human pituitary or a GR-pituitary agonism stronger than believed until now has been postulated. Ten patients affected by autoimmune Addison's disease received: (1) placebo p.o. + placebo i.v., (2) hydrocortisone (H) 10 mg p.o. + placebo i.v., (3) FC 0.1 mg p.o. + placebo i.v., (4) FC 0.1 mg and H 10 mg p.o. + placebo i.v. to verify a possible GR FC-mediated effect that might display a repercussion on the GC-replacement therapy. H reduced ACTH (p < 0.01) and increased cortisol levels (p < 0.01) with respect to the placebo session, while FC did not affect either ACTH or cortisol levels compared to placebo, and higher ACTH and lower cortisol levels (p < 0.03 and p < 0.01) were observed compared with the H session; furthermore the co-administration of FC + H showed ACTH and cortisol profiles similar to that observed during H alone. Our study showed a lack of FC effect on corticotrope secretion in Addison's disease, thus making unlikely the hypothesis of its GR pituitary agonism and the risk of glucocorticoid excess in primary adrenal insufficiency.

Investigation into hippocampal nerve cell damage through the mineralocorticoid receptor in mice.

Stress-associated neuropsychiatric disease is associated with glucocorticoid levels; however, the behavior of mineralocorticoid receptors (MR) under conditions of stress remain to be elucidated. Steroid receptors in the brain are classified into glucocorticoid receptors (GR) and/or MR, exhibiting a difference in affinity for corticosteroids. The hippocampus is one of the most stress-susceptible regions in the brain. In the present study, it was investigated whether the two steroid receptors affect hippocampal neuron damage. The effect of fludrocortisones (FD) on hippocampal neurons caused by FD-containing cholesterol pellets subcutaneously embedded in the backs of mice (FD pellet group, 80 mg cholesterol and 20 mg FD) was investigated. A significant extension of the tail length by ~2.22 fold was observed in the FD pellet group compared with that in the control group as elucidated via the comet assay. Cytotoxicity (pyknosis and degranulation) and DNA fragmentation due to the death of nerve cells were observed using Kluver-Barrera staining and terminal deoxynucleotidyl transferase dUTP nick end labeling. Compared with the sham group mice, hippocampal neuron damage was observed in the adrenalectomized mice and the damage was suppressed by the combinatorial use of spironolactone, which suggested MR-induced hippocampal neuron damage. In conclusion, the present study clearly indicated a regional difference in vulnerability and/or sensitivity to corticosteroids. MR sensitivity to corticosteroids was high in the CA3 region and pyramidal cells of the hippocampus, which may therefore be vulnerable to corticosteroids. Thus, it is clearly suggested that MR function is important in the stress response.

Effects of fludrocortisone on water and sodium intake of C57BL/6 mice

Little is known about steroidal control of thirst- and salt-appetite behaviors of mice. The current study investigates effects of fludrocortisone acetate (FCA), a steroid with potent glucocorticoid and mineralocorticoid effects, on thirst- and salt-appetite responses of C57BL/6 mice. Treatment with FCA produced dose-dependent (5, 10, and 25 mg/kg) increases in both magnitude and duration of water and sodium intake. Chronic elevation of water and saline intake was achieved with daily injections of FCA. Daily injection of FCA, when only 0.9% saline was available, produced a remarkably rapid increase in saline intake. A single injection of FCA stimulated brisk diuresis and natriuresis in fluid-restricted animals. This work is the first to demonstrate copious water drinking by mice in response to FCA. The results are discussed in terms of the possibility that the renal effects of FCA promote increases in water and sodium turnover and thereby, increases in water and sodium ingestion.

Modern Hydrocortisone Replacement Regimens in Adrenal Insufficiency Patients and the Risk of Adrenal Crisis.

The aim of this study was to examine the incidence of adrenal crises (AC) and the prescription of short-acting glucocorticoids (GC) in different geographic areas. To do this we conducted a descriptive study of AC hospitalisations and prescriptions for two GCs (hydrocortisone (HC) and cortisone acetate (CA)), and fludrocortisone acetate (FA), in different geographic areas of Australia between 1999/2000 and 2011/2012, using government databases.There were 2,584 hospital admissions for AC in Australia between 1999/00 and 2011/12 and the corresponding admission rates increased significantly from 7.4 to 11.1/10(6)/year (p<0.001). AC admission rates increased in 5 out of 6 geographic areas. Prescription rates for the combined GCs (HC/CA) increased at an annual rate of between 0.2-2.0% in all areas. All areas had significant (p<0.01) increases in HC prescription rates (4.5% to 13.7% annually) and CA prescription rates decreased in 5 out of the 6 regions (3.5% annual decrease to a 0.5% annual increase). When the geographic areas were combined, there was a significant correlation between the AC admission rates and HC/CA prescription rates (r=0.30, p<0.01). Admissions for AC and GC prescriptions increased significantly in Australia after 1999 and these varied significantly by geographic area. These results suggest that modern recommendations for lower dose, short-acting GC replacement may be of concern and further investigation is warranted.

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Autoimmune autonomic ganglionopathy manifesting as acute-onset orthostatic hypotension in a patient undergoing peritoneal dialysis.

Orthostatic hypotension is an important complication in the management of patients receiving dialysis therapy. As for the orthostatic hypotension caused by decreased peripheral artery resistance, diabetic neuropathy and amyloidosis are the two main causes of hypotension in dialysis patients. However, some patients develop orthostatic hypotension that is caused by dysfunction of the autonomic nervous system, not by diabetic or amyloidosis-related neuropathy. We herein present a case of a 56-year-old man with a 17-year history of peritoneal dialysis therapy, who developed acute-onset orthostatic hypotension accompanied by hypohidrosis and erectile dysfunction. Because serum autoantibodies to ganglionic nicotinic acetylcholine receptor were detected, he was diagnosed with autoimmune autonomic ganglionopathy (AAG). He was treated with high-dose immunoglobulin therapy (0.6g per kg of body weight per day) for 5 consecutive days, which resulted in a gradual improvement in dizziness. Two months after the onset of AAG, he could discontinue vasopressors (fludrocortisone acetate and midodrine hydrochloride) and continued maintenance dialysis therapy without the use of vasopressors. This case indicates that physicians should consider autonomic neuropathy including AAG as a differential diagnosis when they encounter dialysis patients with orthostatic hypotension.

Mutation analysis of steroid acute regulatory protein gene in a patient affected with congenital lipoid adrenal hyperplasia

Objective To analyze the clinical characteristic s of an infant with congenital lipoid adrenal hyperplasia (CLAH),and to sequence the acute regulatory protein (steroid acute regulatory,StAR) gene of the infant patient and her pedigree.Methods Physical examination,laboratory tests,and imaging examination of the 11-month-old patient with CLAH were collected.DNA was extracted from blood samples of the patient and her parents.The 7 exons of StAR gene were amplified by PCR and then sequenced.Results Dark skin,girl vulva,and one each 1.0 cm×1.0 cm palpable lump in inguinal area bilaterally were observed.The adrenocorticotropic hormone (ACTH) was 253 pg/ml,cortisol was 27.6 nmol/L at 8 am,17-hydroxyprogesterone was 3 nmol/L.Uhrasound showed that sign of testicular ultrasonography existed in bilateral inguinal regions.Karyotype analysis showed 46,XY.Sequencing of PCR amplified fragments showed that there were two heterozygous mutations c.229C ＞ T,p (Gln77X) and C.659A＞G,p (His220Arg) of StAR gene in this patient.By rectifying the disturbance of electrolyte,and treating with hydrocortisone and 9α fludrocortisone,etc,the patient has been stable so far.Conclusion The patient presents typical clinical manifestations.Two heterozygous mutations including c.229C ＞T,p (Gln77X) from maternal and C.659A＞G,p (His220Arg) from paternal of StAR gene were detected.Wherein the c.659A＞G,p.(His220Arg) as a novel point mutation of StAR gene,has not been reported so far. Key words: Congenital lipoid adrenal hyperplasia; Steroid acute regulatory protein; Sequence analysis

Effect of fludrocortisone acetate on chronic unexplained nausea and abdominal pain in children with orthostatic intolerance.

We hypothesized that orthostatic intolerance (OI) is associated with gastric dysrhythmias, nausea, and abdominal pain, which improves using fludrocortisone to treat OI. Patients (n=16, girls) with OI completed questionnaires before and after fludrocortisone treatment (age 14.8 ± 2.8 years). Ten patients underwent electrogastrograms (EGGs) before fludrocortisone. All EGGs showed gastric dysrhythmias. Fludrocortisone reduced mean scores as follows: nausea, 3.1 ± 0.8 to 2.1 ± 1.1 (P=0.016); dizziness, 3.0 ± 1.0 to 2.2 ± 1.1 (P=0.0371); abdominal pain, 2.8 ± 1.3 to 1.9 ± 1.4 (P=0.0063); flushing, 2.3 ± 1.2 to 1.5 ± 1.4 (P=0.0476); and missing school, 2.2 ± 1.5 to 1.2 ± 1.5 (P=0.0078). Chronic nausea and abdominal pain accompany OI and improve with OI treatment.

Blood pressure, fludrocortisone dose and plasma renin activity in children with classic congenital adrenal hyperplasia due to 21‐hydroxylase deficiency followed from birth to 4 years of age

Infants with congenital adrenal hyperplasia (CAH) require higher doses of fludrocortisone (FC) due to physiological mineralocorticoid resistance. The adequacy of mineralocorticoid replacement should be closely monitored to avoid hypertension. To evaluate blood pressure (BP) in infants with CAH due to 21-hydroxylase deficiency. Thirty-three patients (18f/15m) diagnosed by newborn screening were followed until the age of 4years. Mean start of HC and FC treatment was day 9·8±9·2 postnatally. Mean daily HC dose ranged from 8·6 to 12·3mg/m(2) /day. During the first year of life prevalence of systolic hypertension was up to 45·5%. At 12 and at 18months, BP was highest. Prevalence of systolic hypertension was up to 57·6% at 18months of age. After 24months BP levels were lower and at 48months prevalence of hypertension decreased to 15·2%. Systolic and diastolic BP correlated significantly with the administered fludrocortisone dose (r=0·3, P=0·005), but not with body mass index. Hypertensive children received significantly higher FC doses and had significantly lower plasma renin activity during the study period. High prevalence of transient, most likely FC induced hypertension was found in young children with classic CAH diagnosed by newborn screening. The changing mineralocorticoid sensitivity in infants is a risk factor for the development of hypertension in patients with CAH, who are treated with FC. Therefore suppressed plasma renin activity should be avoided to prevent arterial hypertension.

Posterior subcapsular cataract in association with fludrocortisone acetate therapy

Clinical & Experimental OphthalmologyVolume 42, Issue 8 p. 799-800 Letter to the Editor Posterior subcapsular cataract in association with fludrocortisone acetate therapy Ian M Whyte FRACP, Ian M Whyte FRACP Department of Clinical Toxicology and Pharmacology, Calvary Mater Newcastle, Newcastle, New South Wales, Australia Hunter Drug Information Service, Calvary Mater Newcastle, Newcastle, New South Wales, AustraliaSearch for more papers by this authorFelicity H Prior GradDipEpi(Pharmaco) MSHP, Felicity H Prior GradDipEpi(Pharmaco) MSHP Hunter Drug Information Service, Calvary Mater Newcastle, Newcastle, New South Wales, AustraliaSearch for more papers by this authorIan K Emslie BOptom, Ian K Emslie BOptom Shop 22, Warners Bay Plaza, Newcastle, New South Wales, AustraliaSearch for more papers by this authorPeter EJ Davies MPH FRANZCO, Peter EJ Davies MPH FRANZCO Newcastle Eye Hospital, Newcastle, New South Wales, AustraliaSearch for more papers by this authorJohn Cosgrove FRANZCP, John Cosgrove FRANZCP St Leonards Mood Disorders Clinic, Sydney, New South Wales, AustraliaSearch for more papers by this author Ian M Whyte FRACP, Ian M Whyte FRACP Department of Clinical Toxicology and Pharmacology, Calvary Mater Newcastle, Newcastle, New South Wales, Australia Hunter Drug Information Service, Calvary Mater Newcastle, Newcastle, New South Wales, AustraliaSearch for more papers by this authorFelicity H Prior GradDipEpi(Pharmaco) MSHP, Felicity H Prior GradDipEpi(Pharmaco) MSHP Hunter Drug Information Service, Calvary Mater Newcastle, Newcastle, New South Wales, AustraliaSearch for more papers by this authorIan K Emslie BOptom, Ian K Emslie BOptom Shop 22, Warners Bay Plaza, Newcastle, New South Wales, AustraliaSearch for more papers by this authorPeter EJ Davies MPH FRANZCO, Peter EJ Davies MPH FRANZCO Newcastle Eye Hospital, Newcastle, New South Wales, AustraliaSearch for more papers by this authorJohn Cosgrove FRANZCP, John Cosgrove FRANZCP St Leonards Mood Disorders Clinic, Sydney, New South Wales, AustraliaSearch for more papers by this author First published: 19 March 2014 https://doi.org/10.1111/ceo.12326Citations: 2 Competing/conflicts of interest: No stated conflict of interest. Funding sources: No stated funding sources. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume42, Issue8November 2014Pages 799-800 RelatedInformation

Solid-state NMR study of fluorinated steroids

Solid-state {1H}13C cross-polarization/magic angle spinning (CP/MAS) NMR spectroscopy was performed to analyze two fluorinated steroids, i.e., betamethasone (BMS) and fludrocortisone acetate (FCA), that have fluorine attached to C9, as well as two non-fluorinated analogs, i.e., prednisolone (PRD) and hydrocortisone 21-acetate (HCA). The 13C signals of BMS revealed multiplet patterns with splittings of 16–215Hz, indicating multiple ring conformations, whereas the 13C signals of FCA, HCA, and PRD exhibited only singlet patterns, implying a unique conformation. In addition, BMS and FCA exhibited substantial deviation (>3.5ppm) in approximately half of the 13C signals and significant deviation (>45ppm) in the 13C9 signal compared to PRD and HCA, respectively. In this study, we demonstrate that fluorinated steroids, such as BMS and FCA, have steroidal ring conformation(s) that are distinct from non-fluorinated analogs, such as PRD and HCA.

Influence of drug content, type of semi-solid vehicle and rheological properties on the skin penetration of the model drug fludrocortisone acetate

Throughout Europe, topical creams containing corticosteroids are diluted with various neutral cream bases to meet the specific needs of patients. Even though this practice has been common for years, its effect has not been thoroughly investigated and so the effectiveness of the diluted topical steroidal creams is difficult to predict. In the present study, the model drug fludrocortisone acetate was incorporated into three cream bases of different hydrophilicity that are commonly used in Austria. Different final drug concentrations were chosen for comparative studies. Additionally, a semi-solid preparation developed by our group was investigated for comparison. These formulations were tested in diffusion and tape stripping experiments. Diffusion cell studies showed that changes in drug concentration do not necessarily change the skin permeation behaviour in vitro. The tape stripping protocol was successfully optimised for investigation of semi-solid preparations to provide reproducible and accurate results despite the challenges of investigating semi-solid formulations. The results showed that tape stripping experiments are more suitable to elucidate subtle differences between formulations. The composition of the cream bases exhibited stronger effects on the skin penetration of the steroidal drug irrespective of its concentration than the rheological properties. No correlation between formulation viscosity and skin penetration was found.

Early Inhibition of Natriuresis Suppresses Symptomatic Cerebral Vasospasm in Patients with Aneurysmal Subarachnoid Hemorrhage

Background: Hyponatremia is a common complication occurring in one third of patients after subarachnoid hemorrhage (SAH). One mechanism that likely mediates the development of hyponatremia in SAH is cerebral salt wasting syndrome (CSWS), which induces natriuresis and reduces total blood volume, resulting in a risk of symptomatic vasospasm (SVS). The mineral corticoid fludrocortisone acetate enhances sodium reabsorption in the renal distal tubules and may help prevent post-SAH hyponatremia. However, management with fludrocortisone acetate is ineffective if hyponatremia is advanced, because CSWS and subsequent SVS develop rapidly. Therefore, an additional earlier marker is required to predict the development of hyponatremia for the initiation of immediate treatment in select patients. However, no conclusive evidence exists showing that hyponatremia influences the risk of SVS, and no standard treatment protocol exists for treating hyponatremia in patients with SAH. This study was undertaken to evaluate whether selective early treatment of hyponatremia prevents SVS in patients with increased urinary sodium excretion in the early phase following SAH. Methods: A total of 103 patients with aneurysmal SAH were managed for a postoperative electrolyte disorder after aneurysmal clipping or coil embolization. Between 2004 and 2007 (period 1), 54 patients started treatment to correct the electrolyte disorder after hyponatremia had occurred. Between 2007 and 2011 (period 2), 49 patients were prospectively subjected to sodium replacement treatment according to their daily sodium balance, and inhibition of natriuresis with fludrocortisone acetate was initiated just after an increase in urinary sodium excretion >300 mEq/day. The occurrence of hyponatremia, SVS, and outcomes were compared between the two periods. Results: Hyponatremia was observed in 14 patients (26%) in period 1 and 7 patients (14%) in period 2. The incidence of fludrocortisone acetate administration was significantly higher, and initiation of electrolyte correction was significantly earlier, in period 2 patients. We observed a significant difference in the frequency of SVS, which occurred in 10 patients (18.5%) in period 1 and 3 patients (6.1%) in period 2. Both urinary sodium excretion and urine volume at day 7 were significantly different between the two periods. However, no significant difference was observed in overall outcome between the two periods. Conclusions: Early inhibition of natriuresis with fludrocortisone acetate before the occurrence of hyponatremia prevented SVS after aneurysmal SAH. Increased urinary sodium excretion in the early phase of SAH is a good indicator for the initiation of electrolyte correction with fludrocortisone acetate.

High Incidence of Abnormal Circadian Blood Pressure Profiles in Patients on Steroid Replacement Therapy due to Secondary Adrenal Insufficiency and Congenital Adrenal Hyperplasia without Overt Hypertension - Initial Results

Patients on steroid replacement therapy are at an increased risk of cardiovascular complications owing to the fact that disruptions in the cortisol diurnal rhythm may affect the blood pressure (BP) profile. Aim: To evaluate the circadian BP profiles of patients with secondary adrenal insufficiency (SAI) and congenital adrenal hyperplasia (CAH) on steroid replacement therapy and to compare BP profiles of patients receiving hydrocortisone (HC) in different dosing schedules. Methods: The study included 33 patients: 15 SAI and 18 CAH (mean age 13.2 years 95CI 11.3-15.1). There were no patients with previously diagnosed overt hypertension. Patients with SAI received a mean of 7.39 mg/m2 of HC in 3 daily doses (in the morning (M) 50%, in the afternoon (A) 25%, in the evening (E) 25%), CAH patients 17.9 mg/m2 of HC in the following dosing schedules: 5 patients in 3 equal doses, 7 patients received M: 40% A: 40% E: 20%, the remaining 6 patients had the same dosing schedule as patients with SAI. Fludrocortisone (FC) was given to 13 patients with CAH in 2 equal daily doses. The total dose of HC/FC as well as the dosing schedule of HC was adjusted individually based on clinical and biochemical outcomes. Standard 24-hour BP monitoring (ABPM) was performed using an Ambulatory BP Monitor (Space labs 90217, USA). Results: The majority of the patients (almost 70% SAI, 80% CAH) presented with an abnormal 24-hour BP profile. There were no significant differences in ABPM results between SAI and CAH patients, and no differences between CAH patients treated with and without FC. There was no correlation between HC and FC doses [mg/m2] and ABPM results except that mean night SBP values increased with greater HC doses (r=0.51, p<0.05). Among the CAH group the highest percentage of abnormal ABPM results was observed in patients who received HC in doses: M: 50% A: 25% and E: 25%, the most favorable BP profile was observed in patients with dosing schedule: M: 40%, A: 40%, E: 20%.However there were no significant differences between patients with different treatment protocols, the results suggest that observed disruptions of the BP profile could be related to the HC dosing schedule. Conclusions: The incidence of abnormal BP profiles in patients on steroid replacement therapy due to SAI and CAH without overt hypertension is high. The disruptions of the BP profiles are not associated with the dose of HC or FC. The abnormal BP profiles in patients with SAI or CAH may be related to the HC dosing schedule. 24-hour ABPM seems to be a useful, non-invasive and safe method for the monitoring of HC and FC replacement therapy in patients with adrenal insufficiency. Further investigations in the larger groups of patients are needed.

A Rare Combination: Congenital Adrenal Hyperplasia Due To 21 Hydroxylase Deficiency and Turner Syndrome

A combination of Turner syndrome (TS) and classical congenital adrenal hyperplasia (CAH) is rare. A one-day-old newborn was referred to our hospital with ambiguous genitalia. The parents were third-degree relatives. The infant’s weight was 3350g (50-75p), and the head circumference was 34.5cm (50p). The gonads were nonpalpable. Presence of a 3 cm phallus, one urogenital opening into the perineum, and incomplete labial fusion were identified. Laboratory tests revealed a classical type of CAH due to 21-hydroxylase deficiency. Karyotyping revealed a 45X0(35)/46XX(22) pattern with negative sex-determining region Y (SRY) on gene analysis. At the most recent follow-up visit, the patient appeared to be in good health - her height was 70.4 cm [-1.5 standard deviation (SD)] and her weight was 9.8 kg (0.3 SD). She was receiving hydrocortisone in a dose of 10 mg/m2/day, fludrocortisone acetate in a dose of 0.075 mg/day, and oral salt of 1 g/day. System examinations were normal. The patient’s electrolyte levels were found to be normal and she was in good metabolic control. The findings of this patient demonstrate that routine karyotyping during investigation of patients with sexual differentiation disorders can reveal TS. Additionally, signs of virilism should always be investigated at diagnosis or during physical examinations for follow-up of TS cases. [i][/i]SRY analysis should be performed primarily when signs of virilism are observed. CAH should also be considered in patients with negative [i]SRY[/i].Conflict of interest:None declared.