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Glucocorticoid replacement therapy prolongs the survival of patients with adrenal insufficiency, but life-threatening adrenal crises still develop in many such patients. This review examines the pathophysiology, epidemiology, and treatment of adrenal crises.

Magnesium is the fourth most abundant cation in the body. It has several functions in the human body including its role as a cofactor for more than 300 enzymatic reactions. Several studies have shown that hypomagnesemia is a common electrolyte derangement in clinical setting especially in patients admitted to intensive care unit where it has been found to be associated with increase mortality and hospital stay. Hypomagnesemia can be caused by a wide range of inherited and acquired diseases. It can also be a side effect of several medications. Many studies have reported that reduced levels of magnesium are associated with a wide range of chronic diseases. Magnesium can play important therapeutic and preventive role in several conditions such as diabetes, osteoporosis, bronchial asthma, preeclampsia, migraine, and cardiovascular diseases. This review is aimed at comprehensively collating the current available published evidence and clinical correlates of magnesium disorders.

Abstract Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders affecting cortisol biosynthesis. Reduced activity of an enzyme required for cortisol production leads to chronic overstimulation of the adrenal cortex and accumulation of precursors proximal to the blocked enzymatic step. The most common form of CAH is caused by steroid 21-hydroxylase deficiency due to mutations in CYP21A2. Since the last publication summarizing CAH in Endocrine Reviews in 2000, there have been numerous new developments. These include more detailed understanding of steroidogenic pathways, refinements in neonatal screening, improved diagnostic measurements utilizing chromatography and mass spectrometry coupled with steroid profiling, and improved genotyping methods. Clinical trials of alternative medications and modes of delivery have been recently completed or are under way. Genetic and cell-based treatments are being explored. A large body of data concerning long-term outcomes in patients affected by CAH, including psychosexual well-being, has been enhanced by the establishment of disease registries. This review provides the reader with current insights in CAH with special attention to these new developments. Graphical Abstract Graphical Abstract

Pheochromocytomas and paragangliomas (PPGLs) are rare neuro-endocrine tumors. The catecholamine surge causes paroxysmal or chronic secondary hypertension. PPGLs may present as hypertensive- or PPGL-crisis with severe life-threatening cardiac and cerebrovascular complications. PPGLs-induced cardiac manifestations have been reported with diagnoses as PPGLs-induced electrocardiogram (ECG) changes “mimicking acute myocardial infarction”, arrhythmias, myocarditis, acute coronary syndrome, dilated cardiomyopathy, and lately as takotsubo syndrome. Critical analysis of these reports reveals that most of these cardiac manifestations have certain features in common. They have a dramatic clinical presentation and are reversible if the disease is treated with appropriate medical therapy and surgical resection of the PPGL tumor. They may have the same repolarization ECG changes irrespective of the clinical cardiac diagnosis, usually associated with mild to moderate elevations of myocardial biomarkers as troponins and normal coronary arteries. The histopathological findings are usually focal or multifocal in the form hypercontracted sarcomeres and contraction band necrosis (myofibrillar degeneration) with subsequent secondary mononuclear cell infiltration. Evidences argue the PPGL caused surge of catecholamines triggers hyperactivation of the sympathetic nervous system with cardiac sympathetic nerve terminal disruption with norepinephrine spillover causing the cardiac complications. A comprehensive review of various reported cardiovascular manifestations and complications of PPGLs are presented.

Abstract Context The characteristics of catecholamine-secreting pheochromocytomas have been well studied. However, less is known about the characteristics, management and outcome in patients with ectopic adrenocorticotropic hormone (ACTH) and/or corticotrophin-releasing hormone (CRH)-secreting pheochromocytomas. Objective To review the characteristics and outcomes of ACTH- and/or CRH-secreting pheochromocytomas. Data Source A systematic search of PubMed/MEDLINE and Web of Science, identifying relevant reports published up to 10 February 2020. Study Selection Original articles, including case reports and case series, reporting individual patient data from patients with ACTH- and/or CRH-secreting pheochromocytomas. Data extraction Information on sex, age, symptoms at presentation, comorbidities, biochemistry, imaging, histopathology, and outcomes was extracted. Data Synthesis We identified 91 articles reporting on 99 cases of ACTH- and/or CRH-secreting pheochromocytomas (CRH-secreting n = 4). Median age at diagnosis was 49 years (interquartile range 38-59.5) with a 2:1 female to male ratio. Most patients presented with clinical Cushing syndrome (n = 79; 81%), hypertension (n = 87; 93%), and/or diabetes (n = 50; 54%). Blood pressure, glucose control, and biochemical parameters improved in the vast majority of patients postoperatively. Infections were the most common complication. Most cases (n = 70, 88%) with reported long-term outcome survived to publication (median follow-up 6 months). Conclusion Ectopic ACTH- and/or CRH-secreting pheochromocytoma should be considered in patients presenting with ACTH-dependent Cushing syndrome and adrenal mass. Despite the challenge in diagnosis, patient outcomes appear favorable.

Innumerable physical stress factors including externally administered catecholamines, and pheochromocytomas and paragangliomas (PPGLs) have been reported to trigger Takotsubo syndrome (TS). A systematic search of PubMed/MEDLINE identified 156 patients with catecholamine‐induced TS up to December 2017. Data were compared within the catecholamine‐induced TS cohort, but some comparisons were also done to a previously published large all‐TS cohort (n = 1750). The mean age was 46.4 ± 16.4 years (72.3% women). The clinical presentation was dramatic with high complication rates in (68.2%, n = 103; multiple complications 34.6%, n = 54). The most common TS ballooning pattern was apical or mid‐apical (45.2%, n = 69), followed by basal pattern (28.8%, n = 45), global pattern (16.0%, n = 25), mid‐ventricular (8.3%, n = 13), focal (0.6%, n = 1), and unidentified pattern (1.9%, n = 3). There was an increase in the prevalence of apical sparing ballooning pattern compared to all‐TS population (37.7% vs 18.3%, P < .00001). Higher complication rates were observed in TS with global ballooning pattern compared to apical ballooning pattern (23/25, 92% vs 38/65, 58.5%; P = .0022). Higher complication rates were observed in patients with age < 50 years than patients >50 years (73/92, 79.3% vs 29/56, 51.8%, P = 0.0009). Recurrence occurred exclusively in patients with PPGL‐induced TS (18/107 patients, 16.8%). PPGL‐induced TS was characterized by more global ballooning's pattern (22/104, 21.2% vs 3/49, 6.1%, P = 0.02), and lower left ventricular ejection fraction (25.54 ± 11.3 vs 31.82 ± 9.93, P = 0.0072) compared to exogenous catecholamine‐induced TS. In conclusion, catecholamine‐induced TS was characterized by a dramatic clinical presentation with extensive left ventricular dysfunction, and high complication rate.

PurposeThiazide diuretics are the most common origin of drug-induced hyponatremia. However, population-based studies on clinical outcomes are lacking. We therefore explored the time course and absolute risk of thiazide-associated hospitalization due to hyponatremia in Sweden.MethodsPopulation-based case-control study including patients hospitalized with a principal diagnosis of hyponatremia (n = 11,213) compared with controls (n = 44,801). Linkage of registers was used to acquire data. Multivariable regression was applied to explore time-dependent associations between thiazide diuretics and hospitalization due to hyponatremia. Attributable risks were calculated assessing the disease burden attributable to thiazides.ResultsIndividuals initiating thiazide treatment were exposed to an immediate increase in risk for hospitalization with adjusted odds ratio (aOR) (95% CI) of 48 (28–89). The associations gradually declined reaching an aOR of 2.9 (2.7–3.1) for individuals treated for longer than 13 weeks. The attributable risk of hyponatremia-associated hospitalization due to thiazides of any treatment length was 27% (3095/11,213). Among 806 patients initiating treatment < 90 days before hospitalization, hyponatremia could be attributed to thiazides in 754. Based on nationwide data, 616,678 individuals were initiated on thiazides during the 8-year study period suggesting an absolute risk of 0.12% (754/661,678) for subsequent hospitalization with a main diagnosis of hyponatremia.ConclusionsThiazide diuretics attributed to more than one in four individuals hospitalized due to hyponatremia. The risk increase was very pronounced during the first month of treatment and then gradually declined, without returning to normal. However, the absolute risk for the development of hyponatremia demanding hospitalization may for most individuals be modest.

Abstract Management of congenital adrenal hyperplasia (CAH) requires both glucocorticoid replacement and suppression of adrenal androgen synthesis. It is recommended that children with CAH be treated with hydrocortisone, but the appropriate glucocorticoid regimen in adults is uncertain. In order to review the outcomes of different glucocorticoid regimens in the management of CAH, a systematic search of PubMed/MEDLINE and Web of Science was conducted, including reports published up to 25 February 2019. Studies that compared at least two types of glucocorticoid preparation were included. The following information was extracted from each study: first author, year of publication, number and characteristics of patients and control subjects, types and doses of glucocorticoid regimen used, study design and outcomes [e.g., biochemical tests, weight, height, body mass index (BMI), bone mineral density (BMD)]. A total of 23 studies were included in the qualitative synthesis, with 19 included in the quantitative synthesis. Dexamethasone was associated with the greatest degree of adrenal suppression; there was no significant difference in 17-hydroxyprogesterone (17OHP) and androstenedione levels between patients treated with hydrocortisone or prednisolone. Patients treated with dexamethasone had the lowest BMD and the highest BMI. Although dexamethasone therapy is associated with significantly lower 17OHP and androstenedione levels, it is also associated with more adverse effects. There do not appear to be significant differences between hydrocortisone and prednisolone therapy, and the choice of agent should be based on individual patient factors.

Background Diabetic foot ulcers (DFU) are a common problem in longstanding diabetes. However, mortality outcomes in Australian patients with DFU are still unclear. Methods All patients with DFU presenting for the first time to the Multi-Disciplinary Foot Clinic (MDFC) at Royal Darwin Hospital, Northern Territory Australia, between January 2003 and June 2015 were included in this study. These patients were followed until 2017, or death. Individual patient data was extracted from hospital and primary care information systems. Kaplan-Meier survival curves were developed. The association between various risk factors and mortality was analysed using Cox regression. Results In total 666 subjects were screened, and 513 were included in the final analysis. Of these subjects, 247 were Indigenous and 266 were non-Indigenous. The median follow-up period was 5.8 years (IQR, 3.1–9.8). The mean age at inclusion was 59.9 ± 12.3 years and 62.8% were males. The majority (93.6%) had type 2 diabetes and the median diabetes duration was 7 years (IQR, 3–12). There were 199 deaths, with a 5-year-mortality rate of 24.6%, and a 10-year-mortality rate of 45.4%. The mean age at death was 64.6 ± 11.8 years. In a multivariate analysis, the following variables were associated with mortality (adjusted HR, 95% CI): age 1.04 (1.02–1.05, P  < 0.001); chronic kidney disease 1.22 (1.11–1.33, P  < 0.001), and plasma albumin 0.96 (0.94–0.99, P  < 0.05). The most common causes of death were chronic kidney disease (24.6%), cardiovascular events (19.6%), sepsis (15.6%), respiratory failure (10.0%), malignancy (9.5%) and multi-organ failure (5.0%). Conclusion Patients with DFU have high mortality. Age, chronic kidney disease, and low albumin levels increase the risk of mortality. Strategies should focus on ulcer prevention and aggressive risk factor reduction.

Background Abscess in the thyroid gland is a rare but severe infectious disease. The condition can have anatomic or iatrogenic underlying causes. If untreated it could be fatal. Pathogens vary considerably. Treatment is intravenous antibiotics, drainage, and sometimes surgery. Methods The electronic medical records of all adult patients with acute thyroiditis 2003–2017 treated at the Karolinska University Hospital (catchment area 2 million) in Sweden were systematically reviewed. Results Five patients were found in the catchment area. One patient from another region but known to us was also included. Thus, six patients (aged 28–73 years) were included in the study. Median length of hospital stay was 7.5 days (4–79 days). All were treated with antibiotics (intravenous n  = 5, oral n  = 1). Total antibiotic treatment duration was 13.5 days (10–41 days). Blood cultures were positive in three ( streptococcus pneumonia , streptococci sanguineous, pepto streptococci ), deep tissue culture in three ( Escherichia coli , Candida , Hemophilic influenza ) and no positive culture at all in two. Drainage was used in three patients. All patients recovered without recurrences. Surgery was performed twice in the acute phase in one. There was no recurrence during 7 years (3–12) of follow-up, but one patient died after three years (severe heart failure and pneumonia). Conclusion Thyroid abscess in adults is extremely rare nowadays in the developed world. With prompt antibiotic therapy, drainage and in some cases thyroidectomy the prognosis seems favourable.