Anethole Alleviates Doxorubicin-Induced Cardiac and Renal Toxicities: Insights from Network Pharmacology and Animal Studies.

Doxorubicin (Dox) is widely used as a chemotherapy drug, while anethole (AN) is primarily known as the main aromatic component in various plant species. This research focused on the impact of AN on the cardiac and renal toxicity induced by Dox and to understand the underlying mechanisms. For cardiac toxicity, Wistar rats were categorized into four groups: a Control group; a Dox group, where rats received 2.5 mg/kg of Dox intraperitoneally every other day; and two Dox + AN groups, where animals were administered Dox (2.5 mg/kg/every other day, IP) along with 125 mg/kg or 250 mg/kg of AN, respectively. The renal toxicity study included similar groups, with the Dox group receiving a single dose of 20 mg/kg of Dox intraperitoneally on the tenth day, and the Dox + AN groups receiving 125 mg/kg and 250 mg/kg of AN for two weeks, alongside the same dose of Dox (20 mg/kg, IP, once on the 10th day). Parameters assessed included ECG, cardiac injury markers (CK, CK-MB, and LDH), and kidney function tests (Cr, BUN, uric acid, LDL, Kim-1, NGAL, and CysC). Antioxidant activity, lipid peroxidation, inflammation, and apoptotic markers were also monitored in heart and renal tissues. Gene expression levels of the TLR4/MyD88/NFκB pathway, along with Bax and Bcl-2, were evaluated. Dox significantly altered ECG, elevated cardiac injury markers, and renal function markers. It also augmented gene expressions of TLR4/MyD88/NFκB, amplified oxidative stress, inflammatory cytokines and apoptotic markers. Conversely, AN reduced cardiac injury markers and kidney function tests, improved ECG, diminished TLR4/MyD88/NFκB gene expression, and alleviated oxidative stress by increasing antioxidant enzyme activities and reducing inflammatory cytokines. AN also enhanced Bcl-2 levels and inhibited Bax and the cleavage of caspase-3 and 9. AN countered the lipid peroxidation, oxidative stress, inflammation, and apoptosis induced by Dox, marking it as a potential preventive strategy against Dox-induced nephrotoxic and cardiotoxic injuries.

ED Revisits Within 72 Hours to a Tertiary Health Care Facility in Dubai: A Descriptive Study.

Unplanned emergency department (ED) revisit is one of the major challenges faced by emergency care facilities and reflects their quality of care. It is an important key performance indicator (KPI) for emergency medical care. Often, inadequate medical care by physicians is claimed to be the main cause of unplanned ED revisits, yet this assumption is not well studied in the literature. Thus, this study aimed to identify the causes of unplanned ED revisits within 72 hours from the initial visit to the emergency department which could help in developing an action plan and improve quality of care and patient safety. A retrospective study was conducted in Rashid Hospital Trauma Center, from December 2019 to January 2020, using electronic medical records reviewed by two independent investigators. The reasons for the ED revisits were categorized into the following four domains: illness, physician, patient, and system related. A total of 584 revisits were found which accounted for 1.9% of ED attendance from December 2019 to January 2020. Majority of them were male patients, and 63% of the population had a mean age of 33 years. Majority of the ED revisits were due to illness (54%), followed by patient related (20%), physician related (18%), and system related (8%) factors. Most of the patients were discharged on the second visit. The two most common reasons for revisits in the ED department that were seen within the 72 hours were illness related and patient related, followed by physician related. The cause is mainly rooted in suboptimal discharge plans.

Effectiveness, safety, and drug sustainability of biologics in elderly patients with inflammatory bowel disease: A retrospective study.

BACKGROUND: Biologic therapy resulted in a significant positive impact on the management of inflammatory bowel disease (IBD) however data on the efficacy and side effects of these therapies in the elderly is scant. AIM: To evaluate retrospectively the drug sustainability, effectiveness, and safety of the biologic therapies in the elderly IBD population. METHODS: Consecutive elderly (≥ 60 years old) IBD patients, treated with biologics [infliximab (IFX), adalimumab (ADAL), vedolizumab (VDZ), ustekinumab (UST)] followed at the McGill University Inflammatory Bowel Diseases Center were included between January 2000 and 2020. Efficacy was measured by clinical scores at 3, 6-9 and 12-18 mo after initiation of the biologic therapy. Patients completing induction therapy were included. Adverse events (AEs) or serious AE were collected during and within three months of stopping of the biologic therapy. RESULTS: We identified a total of 147 elderly patients with IBD treated with biologicals during the study period, including 109 with Crohn's disease and 38 with ulcerative colitis. Patients received the following biologicals: IFX (28.5%), ADAL (38.7%), VDZ (15.6%), UST (17%). The mean duration of biologic treatment was 157.5 (SD = 148) wk. Parallel steroid therapy was given in 34% at baseline, 19% at 3 mo, 16.3% at 6-9 mo and 6.5% at 12-18 mo. The remission rates at 3, 6-9 and 12-18 mo were not significantly different among biological therapies. Kaplan-Meyer analysis did not show statistical difference for drug sustainability (P = 0.195), time to adverse event (P = 0.158) or infection rates (P = 0.973) between the four biologics studied. The most common AEs that led to drug discontinuation were loss of response, infusion/injection reaction and infection. CONCLUSION: Current biologics were not different regarding drug sustainability, effectiveness, and safety in the elderly IBD population. Therefore, we are not able to suggest a preferred sequencing order among biologicals.

Exploring Quality Differences in Telemedicine Between Hospital Outpatient Departments and Community Clinics: Cross-sectional Study.

BACKGROUND: Telemedicine is a care delivery modality that has the potential to broaden the reach and flexibility of health care services. In the United Arab Emirates, telemedicine services are mainly delivered through either integrated hospital outpatient department (OPDs) or community clinics. However, it is unknown if patients' perceptions of, and satisfaction with, telemedicine services differ between these two types of health care systems during the COVID-19 pandemic. OBJECTIVE: We aimed to explore the differences in patients' perceptions of, and satisfaction with, telemedicine between hospital OPDs and community clinics during the COVID-19 pandemic. We also aimed to identify patient- or visit-related characteristics contributing to patient satisfaction with telemedicine. METHODS: In this cross-sectional study that was conducted at Abu Dhabi health care centers, we invited outpatients aged 18 years or over, who completed a telemedicine visit during the COVID-19 pandemic, to participate in our study. Patients' perceptions of, and satisfaction with, telemedicine regarding the two system types (ie, hospital OPDs and community clinics) were assessed using an online survey that was sent as a link through the SMS system. Regression models were used to describe the association between patient- and visit-related characteristics, as well as the perception of, and satisfaction with, telemedicine services. RESULTS: A total of 515 patients participated in this survey. Patients' satisfaction with telemedicine services was equally high among the settings, with no statistically significant difference between the two setting types (hospital OPDs: 253/343, 73.8%; community clinics: 114/172, 66.3%; P=.19). Video consultation was significantly associated with increased patient satisfaction (odds ratio [OR] 2.57, 95% CI 1.04-6.33; P=.04) and patients' support of the transition to telemedicine use during and after the pandemic (OR 2.88, 95% CI 1.18-7.07; P=.02). Patients who used video consultations were more likely to report that telemedicine improved access to health care services (OR 3.06, 95% CI 1.71-8.03; P=.02), reduced waiting times and travel costs (OR 4.94, 95% CI 1.15-21.19; P=.03), addressed patients' needs (OR 2.63, 95% CI 1.13-6.11; P=.03), and eased expression of patients' medical concerns during the COVID-19 pandemic (OR 2.19, 95% CI 0.89-5.38; P=.09). Surprisingly, middle-aged patients were two times more likely to be satisfied with telemedicine services (OR 2.12, 95% CI 1.09-4.14; P=.03), as compared to any other age group in this study. CONCLUSIONS: These findings suggest that patient satisfaction was unaffected by the health system setting in which patients received the teleconsultations, whether they were at hospitals or community clinics. Video consultation was associated with increased patient satisfaction with telemedicine services. Efforts should be focused on strategic planning for enhanced telemedicine services, video consultation in particular, for both emergent circumstances, such as the COVID-19 pandemic, and day-to-day health care delivery.

Physicians' Attitudes Toward Telemedicine Consultations During the COVID-19 Pandemic: Cross-sectional Study.

BACKGROUND: To mitigate the effect of the COVID-19 pandemic, health care systems worldwide have implemented telemedicine technologies to respond to the growing need for health care services during these unprecedented times. In the United Arab Emirates, video and audio consultations have been implemented to deliver health services during the pandemic. OBJECTIVE: This study aimed to evaluate whether differences exist in physicians' attitudes and perceptions of video and audio consultations when delivering telemedicine services during the COVID-19 pandemic. METHODS: This survey was conducted on a cohort of 880 physicians from outpatient facilities in Abu Dhabi, which delivered telemedicine services during the COVID-19 pandemic between November and December 2020. In total, 623 physicians responded (response rate=70.8%). The survey included a 5-point Likert scale to measure physician's attitudes and perceptions of video and audio consultations with reference to the quality of the clinical consultation and the professional productivity. Descriptive statistics were used to describe physicians' sociodemographic characteristics (age, sex, designation, clinical specialty, duration of practice, and previous experience with telemedicine) and telemedicine modality (video vs audio consultations). Regression models were used to assess the association between telemedicine modality and physicians' characteristics with the perceived outcomes of the web-based consultation. RESULTS: Compared to audio consultations, video consultations were significantly associated with physicians' confidence toward managing acute consultations (odds ratio [OR] 1.62, 95% CI 1.2-2.21; P=.002) and an increased ability to provide patient education during the web-based consultation (OR 2.21, 95% CI 1.04-4.33; P=.04). There was no significant difference in physicians' confidence toward managing long-term and follow-up consultations through video or audio consultations (OR 1.35, 95% CI 0.88-2.08; P=.17). Video consultations were less likely to be associated with a reduced overall consultation time (OR 0.69, 95% CI 0.51-0.93; P=.02) and reduced time for patient note-taking compared to face-to-face visits (OR 0.48, 95% CI 0.36-0.65; P<.001). Previous experience with telemedicine was significantly associated with a lower perceived risk of misdiagnosis (OR 0.46, 95% CI 0.3-0.71; P<.001) and an enhanced physician-patient rapport (OR 2.49, 95% CI 1.26-4.9; P=.008). CONCLUSIONS: These results indicate that video consultations should be adopted frequently in the new remote clinical consultations. Previous experience with telemedicine was associated with a 2-fold confidence in treating acute conditions, less than a half of the perceived risk of misdiagnosis, and an increased ability to provide patients with health education and enhance the physician-patient rapport. Additionally, these results show that audio consultations are equivalent to video consultations in providing remote follow-up care to patients with chronic conditions. These findings may be beneficial to policymakers of e-health programs in low- and middle-income countries, where audio consultations may significantly increase access to geographically remote health services.

ACUTE ABDOMEN systemic sonographic approach to acute abdomen in emergency department: a case series.

BACKGROUND: Acute abdomen is a medical emergency with a wide spectrum of etiologies. Point-of-care ultrasound (POCUS) can help in early identification and management of the causes. The ACUTE-ABDOMEN protocol was created by the authors to aid in the evaluation of acute abdominal pain using a systematic sonographic approach, integrating the same core ultrasound techniques already in use-into one mnemonic. This mnemonic ACUTE means: A: abdominal aortic aneurysm; C: collapsed inferior vena cava; U: ulcer (perforated viscus); T: trauma (free fluid); E: ectopic pregnancy, followed by ABDOMEN which stands: A: appendicitis; B: biliary tract; D: distended bowel loop; O: obstructive uropathy; Men: testicular torsion/Women: ovarian torsion. The article discusses two cases of abdominal pain the diagnosis and management of which were directed and expedited as a result of using the ACUTE-ABDOMEN protocol. The first case was of a 33-year-old male, who presented with a 3-day history of abdominal pain, vomiting and constipation. Physical exam revealed a soft abdomen with generalized tenderness and normal bowel sounds. Laboratory tests were normal. A bedside ultrasound done using the ACUTE-ABDOMEN protocol showed signs of intussusception. This was confirmed by CT-abdomen. The second case was of a 70-year-old female, a known case of diabetes and hypertension, who presented with a 3-hour history of abdominal pain, vomiting and diarrhea. She had a normal physical exam and laboratory studies. Her symptoms mimicking simple gastroenteritis had improved. However, bedside ultrasound, using the ACUTE-ABDOMEN protocol showed localized free fluid with dilated small bowel loop in right lower quadrant with absent peristalsis. A CT abdomen confirmed a diagnosis of intestinal obstruction. These two cases demonstrate that the usefulness of applying POCUS in a systematic method-like the "ACUTE-ABDOMEN" approach-can aid in patient diagnosis and management. CASE PRESENTATION: We are presenting two cases of undifferentiated acute abdomen pain, where ACUTE ABDOMEN sonographic approach was applied and facilitated the accurate patient management and disposition. CONCLUSION: ACUTE ABDOMEN sonographic approach in acute abdomen can play an important role in ruling out critical diagnosis, and can guide emergency physician or any critical care physician in patient management.

Pediatric falls from windows and balconies: incidents and risk factors as reported by newspapers in the United Arab Emirates.

BACKGROUND: Falls of children from heights (balconies and windows) usually result in severe injuries and death. Details on child falls from heights in the United Arab Emirates (UAE) are not easily accessible. Our aim was to assess the incidents, personal, and environmental risk factors for pediatric falls from windows/balconies using newspaper clippings. METHODS: We used a retrospective study design to electronically assess all major UAE national Arabic and English newspapers for reports of unintentional child falls from windows and balconies during 2005-2016. A structured data collection form was developed to collect information. Data were entered into an Excel sheet and descriptive analysis was performed. RESULTS: Newspaper clippings documented 96 fall incidents. After cleaning the data and excluding duplicate cases and intentional injuries, 81 cases were included into the final analysis. Fifty-three percent (n = 42) were boys. The mean (range) age was 4.9 years (1-15). Thirty-eight (47%) children fell from windows and 36 (44%) from balconies. Twenty-two (27%) children climbed on the furniture placed on a balcony or close to a window. Twenty-five (31%) children were not alone in the apartment when they fell. Twenty-nine children fell from less than 5 floors (37%), 33 from 5 to 10 floors (42%) and 16 from more than 10 floors (21%). Fifteen children (19%) were hospitalized and survived the fall incident, while 66 died (81%). CONCLUSIONS: Newspapers proved to be useful to study pediatric falls from heights. It is necessary to improve window safety by installing window guards and raising awareness.

Clinical responses to a mega-dose of vitamin D3 in infants and toddlers with vitamin D deficiency rickets.

OBJECTIVES: Was to investigate the effect of treatment with an IM injection, a mega dose of vitamin D3 (10,000 IU/kg) on the clinical, biochemical and radiological parameters of 40 rachitic children with vitamin D deficiency (VDD) over a period of 3 months. DESIGN: In this prospective study we evaluated the clinical, biochemical and radiological responses of an IM injection of cholecalciferol (10,000 IU/kg) for 3 months. RESULTS: At presentation, the most frequent manifestations were enlarged wrist joints, hypotonia, irritability, cranial bossing, wide anterior fontanel, bow legs, delayed teething and walking and Harrison's sulcus with chest rosaries. Short stature (length SDS < -2) was recorded in 30% of patients. Craniotabes and hypocalcemic tetany were the least common presentations. In VDD children the most frequent biochemical abnormality was high alkaline phosphatase (ALP) (100%), followed by low phosphate (PO(4)) (75%) and low calcium (Ca) (12.5%). One month after treatment, serum Ca, PO(4) and 25(OH)D concentrations were normal. Three months after the injection, serum level of ALP and parathormone (PTH) decreased to normal. The majority of patients (87.5%) had serum 25(OH)D level >or= 20 ng/ml, but some (12.5%) had level <20 ng/ml. Hypercalcemia was not recorded in any patient during the 3-month-period. Significant cure of all symptoms and signs related to vitamin D deficiency had been achieved in all children. Leg bowing showed significant improvement in all patients but was still evident in one third. Complete healing of the radiological evidence of rickets was achieved in 95% of all children. CONCLUSION: An IM injection of a mega dose of cholecalciferol is a safe and effective therapy for treatment of VDD rickets in infants and toddlers with normalization of all the biochemical parameters and healing of radiological manifestations. Measurement of serum 25(OH)D level is highly recommended in all short children with a clear need for a general vitamin D supplementation for all infants and young children in Qatar.

Neonatal and late-onset diabetes mellitus caused by failure of pancreatic development: report of 4 more cases and a review of the literature.

OBJECTIVE: Permanent neonatal diabetes mellitus caused by developmental failure of the pancreas is rare. Thus far, only a few genetic causes have been reported. We now report the clinical and genetic aspects of 4 more cases of permanent neonatal diabetes mellitus caused by pancreatic agenesis or hypoplasia. PATIENTS AND METHODS: All 4 of the patients were from consanguineous kinships, and all presented with diabetes mellitus and pancreatic exocrine insufficiency. Three patients had pancreatic agenesis, and 1 had pancreatic hypoplasia on computed tomography scan. DNA was extracted from blood samples of patients and unaffected family members. Specific genes were amplified by polymerase chain reaction and characterized by DNA sequencing. RESULTS: Several genes that encode transcription factors that have known roles in pancreas development were characterized in the affected children and unaffected family members. These genes include Pdx1, the master regulator of pancreas development and beta-cell differentiation, and other transcription factors that are expressed early in pancreas development, namely, Ptf1a, Sox9, Sox17, Hnf6, and HlxB9. Several novel polymorphisms were found in our patients. However, these were also present in unaffected individuals. No disease-causing mutations were found in any of these genes. CONCLUSIONS: These findings add to the 4 cases already in the literature in which the Pdx1 structural gene has been found to be normal in patients with pancreatic agenesis or hypoplasia. The analysis here has been extended to include the screening of 4 other candidate genes in addition to promoter elements upstream of the Pdx1. Two of the cases occurred in a sibling pair, and 2 were isolated, so there may be more than 1 etiology in the cases reported here.

Linear growth in relation to the circulating concentrations of insulin-like growth factor I, parathyroid hormone, and 25-hydroxy vitamin D in children with nutritional rickets before and after treatment: endocrine adaptation to vitamin D deficiency.

The objective of the study was to determine the degree of linear growth retardation of patients with vitamin D deficiency rickets at presentation and the magnitude of catch-up growth in relation to their calcium (Ca) homeostasis and hormones affecting it before and after treatment. This prospective study recorded the anthropometric data and measured the circulating 25-hydroxy vitamin D (25-OH-D), insulin-like growth factor I (IGF-I), parathyroid hormone, Ca, phosphate, and alkaline phosphatase concentrations in 46 infants and children with nutritional (vitamin D deficiency) rickets before and 6 months or more after treatment with one intramuscular injection of vitamin D3 megadose (300000 IU). Forty normal age- and sex-matched children were included as controls for the auxological data. At presentation, patients' mean age = 13.1 +/- 1.1 months, length standard deviation scores (LSDS) = -1.5 +/- 0.2, and body mass index = 16.3 +/- 0.85. They were significantly shorter and had markedly lower growth velocity standard deviation scores (GVSDS) compared with normal controls (LSDS = 0.25 +/- 0.18 and 0.31 +/- 0.22, respectively). Six months after treatment, the LSDS increased significantly in patients to -0.45 +/- 0.13, with a significantly increased GVSDS (2.76 +/- 0.45) and body mass index (16.9 +/- 0.65). They were still shorter but with significantly higher GVSDS compared with normal controls. Serum Ca and phosphate concentrations increased from 2.07 +/- 0.25 and 1.23 +/- 0.24 mmol/L, respectively, before treatment to 2.44 +/- 0.2 and 1.94 +/- 0.2 mmol/L, respectively, after treatment. Serum alkaline phosphatase and parathyroid hormone concentrations decreased from 1183 +/- 219 U/L and 294 +/- 87 pg/mL, respectively, before treatment to 334 +/- 75 U/L and 35.2 +/- 15.2 pg/mL, respectively, after treatment. The 25-OH-D level increased from 4.5 +/- 0.56 ng/mL before treatment to 44.5 +/- 3.7 ng/mL after treatment. Circulating concentrations of IGF-I increased significantly after treatment (52.2 +/- 18.9 ng/mL) vs before treatment (26.6 +/- 12.8 ng/mL). The 25-OH-D concentrations were correlated significantly with the IGF-I levels before and after treatment (r = 0.603 and r = 0.59, respectively; P < .001). The GVSDS after treatment was correlated with the increase of IGF-I and 25-OH-D levels (r = 0.325 and r= 0.314, respectively; P < .01). These data denote that the accelerated linear growth after treatment of nutritional vitamin D deficiency is mediated through activation of the growth hormone/IGF-I system and suggests an important role of vitamin D as a link between the proliferating cartilage cells of the growth plate and growth hormone/IGF-I secretion. Three different sequential stages of vitamin D deficiency can be recognized according to the clinical/radiological, biochemical, and hormonal data of patients at presentation.

Calcium homeostasis in 40 adolescents with beta-thalassemia major: a case-control study of the effects of intramuscular injection of a megadose of cholecalciferol.

UNLABELLED: The prevalence of disturbed calcium homeostasis in adolescents with beta thalassemia major (T) varies among different populations. Moreover, the cholecalciferol uptake required to achieve or maintain any given serum 25-hydroxycholecalciferol level is not well known, particularly within ranges of the probable physiologic supply of the vitamin. OBJECTIVES: The objectives of the study were to estimate the prevalence of abnormal calcium homeostasis in 40 adolescent thalassemic patients, and to investigate the effect of an IM injection of a mega dose of vitamin D3 on serum 25-hydroxycholecalciferol (25-OH D) concentration and other calcium homeostasis parameters in vitamin D deficient (VDD) thalassemic adolescents, and to compare these results with those for non-thalassemic adolescents with VDD. DESIGN: In this prospective study we measured parameters of calcium homeostasis in 40 adolescents with T and 40 matched non-thalassemic (NT) controls. An IM dose (10,000 IU/kg, max 600,000 IU) of cholecalciferol was injected in those with VDD (38 adolescents with thalassemia and 26 non-thalassemic adolescents). Parameters of calcium homeostasis were measured at intervals of 3 months during the course of the study. RESULTS: Of the 40 adolescents with T, 2 had hypoparathyroidism and low 25-OH D, and 2 had hypocalcemia with hypophosphatemia, high alkaline phosphatase (ALP), high PTH and serum 25-OH D below ng/ml. The rest of the patients (n=36) had low circulating 25-OH D concentrations with normal serum Ca and PO4 concentrations. Of the 40 non-thalassemic adolescents, 26 had 25-OH D levels below 20 ng/ml (65%). Patients with T and VDD had lower circulating PTH and ALP concentrations compared to non-thalassemic patients with VDD. Significant improvement of symptoms related to vitamin D deficiency was reported in 18 out of 26 of symptomatic T and 12 out of 16 of NT adolescents at 1 to 3 months after the injection. Three months after injecting vitamin D the mean serum 25-OH D concentration was lower in the T group as compared to the NT group but the majority of patients had 25-OH D levels equal to or greater than 20 ng/ml. CONCLUSION: Vitamin D deficiency was detected in 100 % of our thalassemic adolescents. An IM injection of a mega dose of cholecalciferol is an effective therapy for treatment of hypovitaminosis D in thalassemic and non-thalassemic adolescents for 3 months but its effects do not persist for 6 months.

Severe loss-of-function mutations in the adrenocorticotropin receptor (ACTHR, MC2R) can be found in patients diagnosed with salt-losing adrenal hypoplasia.

OBJECTIVE: Familial glucocorticoid deficiency type I (FGD1) is a rare form of primary adrenal insufficiency resulting from recessive mutations in the ACTH receptor (MC2R, MC2R). Individuals with this condition typically present in infancy or childhood with signs and symptoms of cortisol insufficiency, but disturbances in the renin-angiotensin system, aldosterone synthesis or sodium homeostasis are not a well-documented association of FGD1. As ACTH stimulation has been shown to stimulate aldosterone release in normal controls, and other causes of hyponatraemia can occur in children with cortisol deficiency, we investigated whether MC2R changes might be identified in children with primary adrenal failure who were being treated for mineralocorticoid insufficiency. DESIGN: Mutational analysis of MC2R by direct sequencing. PATIENTS: Children (n = 22) who had been diagnosed with salt-losing forms of adrenal hypoplasia (19 isolated cases, 3 familial), and who were negative for mutations in DAX1 (NR0B1) and SF1 (NR5A1). RESULTS: MC2R mutations were found in three individuals or kindred (I: homozygous S74I; II: novel compound heterozygous R146H/560delT; III: novel homozygous 579-581delTGT). These changes represent severely disruptive loss-of-function mutations in this G-protein coupled receptor, including the first reported homozygous frameshift mutation. The apparent disturbances in sodium homeostasis were mild, manifest at times of stress (e.g. infection, salt-restriction, heat), and likely resolved with time. CONCLUSIONS: MC2R mutations should be considered in children who have primary adrenal failure with apparent mild disturbances in renin-sodium homeostasis. These children may have been misdiagnosed as having salt-losing adrenal hypoplasia. Making this diagnosis has important implications for treatment, counselling and long-term prognosis.