Treatment Of Adrenal Insufficiency Research Articles

Treatment of adrenal insufficiency with hydrocortisone dual-release formulation: glycometabolic profile and health-related quality of life

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Increased Cardiovascular Risk in Patients with Adrenal Insufficiency: A Short Review.

Cardiovascular disease (CVD) is the most common cause of death in the world. Recent studies have shown an association between adrenal insufficiency (AI) and increased cardiovascular risk (CVR). Patients with AI receive glucocorticoid (GC) replacement therapy which can lead to varying levels of blood cortisol. It was shown that these imbalances in blood cortisol may lead to a higher prevalence of coronary heart disease, major adverse coronary events, and increased mortality. GC substitution is essential in the treatment of AI without which the disease has been shown to be fatal. The most frequently used GC formula for replacement therapy is hydrocortisone (HC). There is no uniform opinion on hydrocortisone replacement therapy. Alternative GC such as prednisolone is also in use. Overreplacement of GC may lead to adverse effects including obesity, high blood pressure, and hyperglycaemia. Outcome may vary between primary and secondary AI mainly due to differences in the renin-angiotensin-aldosterone system (RAAS). Furthermore, decreased blood levels of cortisol may lead to a compensatory secretion of inflammatory mediators such as Interleukin-1 (IL-1), Interleukin-6 (IL-6), and/or tumor-necrosis factor (TNF). Physicians and patients should be properly educated about the increased risk of CVD in patients with AI.

Adrenal Insufficiency

Adrenal insufficiency means hypo-function of the adrenal cortex, usually glucocorticoid, may be associated with mineralocorticoid and rarely adrenal androgen. It can be categorized into two types: Primary adrenal insufficiency, or Addison’s disease (cortisol low and ACTH high) or secondary/ tertiary adrenal insufficiency due to pituitary or hypothalamic disorders (both cortisol and ACTH are low). Identification of etiology is very important for plan of treatment. The reported incidence of adrenal insufficiency varies greatly depending on the population studied, the test and cut off levels used, and the cause. Many patients may present with adrenal crisis, some of them have subtle symptoms, hyperpigmentation, hypotension, electrolyte imbalance, shock etc. Many of them have iatrogenic adrenal insufficiency with features of Cushing’s syndrome. So, the manifestations of adrenal insufficiency are numerous and nonspecific, and clinicians should have a high index of suspicion and be alert to see important diagnostic clues, such as hyponatremia, hyperkalemia, and hypotension (that are refractory to fluids and vasopressors), diarrhea, weight loss, vomiting, fever etc. without any clear causation. Treatment of adrenal insufficiency is usually life-long, of course based on etiology. Short acting glucocorticoid is better, like hydrocortisone. Patients may be treated with prednisolone. Patients should be provided a “steroid card”. Sometimes it is essential to take patients under “withdrawal protocol”.Birdem Med J 2015; 5(1) Supplement: 43-48

Low Impact of Urinary Cortisol in the Assessment of Hydrocortisone Replacement Therapy.

Hydrocortisone replacement therapy is a cornerstone in the treatment of adrenal insufficiency (AI). While urinary cortisol has been used as a diagnostic tool for AI, it remains unclear whether it is a useful parameter to monitor hydrocortisone replacement therapy. Aim of this study was to evaluate possible differences in cortisol metabolism between adrenal insufficient patients and healthy subjects and to assess the value of urinary cortisol in AI management. In a case-control study, urinary cortisol excretion was determined in 14 patients with primary and secondary AI receiving hydrocortisone infusions from midnight to 8:00 AM. Results were correlated with serum cortisol levels and compared to urinary values obtained from 53 healthy volunteers. Urinary cortisol excretion in healthy subjects was 14.0±7.8 μg/8 h (range: 0.24-35.4), levels did not differ between 3 groups aged 20-34 years, 35-49 years, and ≥50 years. Patients with AI receiving hydrocortisone infusions demonstrated significantly higher rates of urinary cortisol excretion (51.6±37.8 μg/8 h; range 17.1-120.0, p<0.001); the values correlated with serum cortisol levels (r(2)=0.98). Of interest, patients with secondary AI showed significantly higher serum cortisol levels after hydrocortisone infusion than those with primary AI, conceivably due to residual adrenal function. In conclusion, we showed that: (i) there is a wide inter-individual variability in urinary cortisol excretion rates; (ii) cortisol metabolism in adrenal insufficient patients differs when compared to controls; (iii) there is a strong correlation between urinary and serum cortisol levels; and (iv) urinary cortisol levels despite their variability may help to discriminate between secondary and primary adrenal insufficiency.

Perioperative Management of Patients on Steroids Requiring Surgery

Patients with chronic lung disease, inflammatory bowel disease, rheumatoid arthritis, and solid-organ transplantations are often on steroid supplementation either intermittently or chronically. Endogenous steroid use results in decreased adrenocorticotropic hormone secretion by the pituitary gland through negative feedback mechanisms. Over several weeks, this can result in adrenal gland atrophy, eventually leading to secondary adrenal insufficiency. Appropriate management of perioperative glucocorticoid replacement therapy can be challenging, but appropriate replacement is essential to optimize patient outcomes. Insufficient dosing of glucocorticoids during the perioperative period can result in hypotension and even death. Excessive treatment with glucocorticoids decreases wound healing, increases the risk of hyperglycemia, and increases susceptibility to infection. This review covers the historical perspective, the hypothalamic-pituitary-adrenal (HPA) axis, when to suspect an impaired HPA axis, an argument against supraphysiologic glucocorticoid treatment in the perioperative period, the rationale for treating patients with impaired renal function, guidelines for dosing glucocorticoids in the perioperative period, and consulting a specialist. Figures show a clinical algorithm for evaluation and treatment of adrenal insufficiency in the perioperative period and the HPA axis. Tables list steroid conversions and perioperative glucocorticoid treatment recommendations. This review contains 2 highly rendered figures, 2 tables, and 22 references.

Pituitary-Adrenal Axis in Prader Willi Syndrome.

Purpose: Prader Willi syndrome (PWS) is a rare genetic condition that has concurrent endocrinological insufficiencies. The presence of growth hormone deficiency has been well documented, but adrenal insufficiency (AI) is not widely reported. A review was conducted to investigate its prevalence and relevance in PWS in both adults and children. Methodology: A literature review was performed with the search terms “Prader-Willi syndrome” and “adrenal insufficiency”. Results: The review found studies disagree on the prevalence and method of investigation of AI in PWS. Case studies demonstrate that patients with PWS are at risk of premature death, often secondary to respiratory infections. The possibility that this may be the result of the inability to mount an effective cortisol response has been studied, with some evidence confirming AI in PWS patients. Most reports agreed AI is present in PWS, however, Farholt et al. showed no HPA axis dysfunction in adults, suggesting that perhaps it is rare in adults, and children should be the focus of further studies. Conclusion: AI is present in some patients with PWS. Further research is required to ensure optimal treatment can be implemented and to prevent premature deaths related to adrenal insufficiency. Clinicians should have a low threshold for testing the adrenal axis and considering treatment for adrenal insufficiency in PWS patients.

An improved micro-method for the measurement of steroid profiles by APPI-LC–MS/MS and its use in assessing diurnal effects on steroid concentrations and optimizing the diagnosis and treatment of adrenal insufficiency and CAH

Our goals were to (1) develop an improved micro-method usable for neonates for steroid profile measurements and a method to measure androsterone, a key steroid in the recently described androgen backdoor pathway together, with dehydroepiandrosterone and (2) to assess if dehydroepiandrosterone diurnal concentration fluctuations exist potentially necessitating strict adherence to time of blood sample draw and requirement of separate time-dependent reference intervals. Liquid chromatography–tandem mass spectrometry was performed with an atmospheric pressure photoionization source [1]. For each sample 50μL (100μL for the backdoor pathway) of serum was deproteinized by adding 75μL (150μL for the backdoor pathway) of acetonitrile containing the internal standards. After centrifugation, 75μL (150μL for the backdoor pathway) of supernatant was diluted with 250μL of water and injected onto a Poroshell 120 EC-C8 column (SB-C8 column for the backdoor pathway). Within-run coefficients of variation ranged from 2.4 to 10.4% and between-day coefficients of variation from 2.9 to 11.2%. Comparison studies yielded correlation coefficient between 0.97 and 1.00 with recoveries of 90% or greater. Our methods analyze a 9 steroid profile and an additional 2 steroid profile (backdoor pathway) with minimal sample volume (usable in neonates optimizing early diagnosis of endocrinopathies and genetic diseases). Low limits of quantitation make these methods ideal for steroid measurement in women and prepubertal children. As diurnal variations of dehydroepiandrosterone and other steroids [2] concentrations are clinically significant we recommend that separate reference intervals be developed for 8 am, 8 pm, and midnight sample draws. The use of this approach in improving the diagnosis of patients with adrenal insufficiency and congenital adrenal hyperplasia is discussed.

Relative Adrenal Insufficiency in Pediatric Septic Shock.

Sepsis and septic shock represent important causes of morbidity and mortality in children, and adrenal dysfunction may play a role in the cardiovascular and immunological response. According to existing reports, the incidence of adrenal dysfunction in critically ill children varies significantly between 4 and 52% of patients. This article reviews the concept of adrenal insufficiency and the role it may play in a pediatric septic shock. Also discussed are the diagnosis, prognosis, and treatment of adrenal insufficiency in septic shock in adults and children. Finally, the latest recommendations about steroid use in pediatric septic shock are summarized.

Adrenal Insufficiency in Australia: Is it Possible that the Use of Lower Dose, Short-Acting Glucocorticoids has Increased the Risk of Adrenal Crises?

Morbidity from adrenal insufficiency (AI) in Australia is poorly described. The objective of this study was to evaluate AI morbidity patterns in adults between 1999/2000 and 2011/2012 using national databases. A descriptive study of hospitalisations for AI and adrenal crises (AC) in adults and trends in prescriptions for 2 short-acting glucocorticoids (GC) was designed. The setting was the Australian healthcare system. Main outcome measures are the trends in hospitalisation and prescription rates. There were 7,378 hospital admissions for treatment of AI in adults between 1999/00 and 2011/12. Of these, 29.5% were for an AC. Admission rates for AC increased from 9.5 to 12.4 admissions/10(6)/year (p < 0.05). There was a 5.8% decrease in admission rates for AI (excluding AC), from 27.0 to 25.5/10(6)/year (p = ns). Short-acting GC [hydrocortisone (HCT) and cortisone acetate (CA)] prescription rates increased significantly (p < 0.001) from 3,176.1/10(6) to 3,463.8/10(6). Prescription rates for CA decreased by 22.4% (p < 0.001) but HCT prescription rates increased to 77.1% (p < 0.001). The increase in AC admission rates was positively correlated with the rise in both the total GC prescription rate (r = 0.63, p < 0.05) and the HCT prescription rate (r = 0.74, p< 0.01). Over the 13-year study period, there was a 30.8% increase in hospitalisation rates for ACs and a concomitant 77.1% increase in prescribing of HCT. The association between AC events and HCT use and/or reduced effective GC dose is plausibly causal, but confirmatory studies are required before suggesting any change to GC replacement in AI.

Adrenal Insufficiency in Metastatic Lung Cancer

We report a case of adrenal insufficiency in patient with lung cancer. Although adrenal metastases are common in cancer patients, adrenal insufficiency is a rare occurrence. Diagnosis and treatment of adrenal insufficiency will improve the physical status and the quality of life in those patients.

Guía para el diagnóstico y tratamiento de la insuficiencia suprarrenal en el adulto

Adrenal insufficiency (AI) is a disease characterized by a deficient production or action of glucocorticoids, with or without deficiency in mineralcorticoids and/or adrenal androgens. It can result from disease intrinsic to the adrenal cortex (primary AI), from pituitary diseases that hamper the release of corticotropin (secondary AI) or from hypothalamic disorders that impair the secretion of the corticotropin-releasing hormone (tertiary AI).It is a disease with a low prevalence but its impact on the affected individual is very high as it can be life-threathening if not treated or lead to health problems if inadequately treated. However, currently there are no specific guidelines for the management of this disease. Therefore, at the proposal of the Spanish Society of Endocrinology and Nutrition (SEEN) board, a task-force under the Neuroendocrinology Knowledge Area of the SEEN was established, with the mandate of updating the diagnosis and treatment of AI. In fulfilment of this mandate the task-force has elaborated the present guide that, based on a comprehensive review of literature, is intended to provide an answer to questions related to the management of this disease. It is, therefore, an essentially practical document, mainly aimed at guiding the health professionals involved in the care of IA patients.

Guidelines for diagnosis and treatment of adrenal insufficiency in adults

Abstract Adrenal insufficiency (AI) is a disease characterized by a deficient production or action of glucocorticoids, with or without deficiency in mineralcorticoids and/or adrenal androgens. It can result from disease intrinsic to the adrenal cortex (primary AI), from pituitary diseases that hamper the release of corticotropin (secondary AI) or from hypothalamic disorders that impair the secretion of the corticotropin releasing hormone (tertiary AI). It is a disease with a low prevalence but its impact on the affected individual is very high as it can be life threathening if not treated or lead to health problems if inadequately treated. However, currently there are no specific guidelines for the management of this disease. Therefore, at the proposal of the Spanish Society of Endocrinology and Nutrition (SEEN) board, a task force under the Neuroendocrinology Knowledge Area of the SEEN was established, with the mandate of updating the diagnosis and treatment of AI. In fulfilment of this mandate the task force has elaborated the present guide, that, based on a comprehensive review of literature, is intended to provide an answer to questions related to the management of this disease. It is, therefore, an essentially practical document, mainly aimed at guiding the health professionals involved in the care of IA patients.

Endocrine diseases: progress in diagnosis and treatments. Topics: V. Adrenal cortex; 1. Early diagnosis and treatment of adrenal insufficiency

Endocrine diseases: progress in diagnosis and treatments. Topics: V. Adrenal cortex; 1. Early diagnosis and treatment of adrenal insufficiency

Delay in Diagnosis of Adrenal Insufficiency Is a Frequent Cause of Adrenal Crisis

Delay of diagnosis of primary adrenal insufficiency (PAI) leads to adrenal crisis which is potentially lethal complication. The objective of our work was an assessment whether the establishment of diagnosis of adrenocortical insufficiency in Poland is so much delayed as assessed in the past. We have analysed data from 60 patients with diagnosis of PAI established in our department during the past 12 years and who are still under our care. We found that the time to diagnosis of primary adrenal insufficiency in Poland exceeds 3 months in every patient and 6 months in patients admitted with symptoms of adrenal crisis. Forty-four percent of patients were diagnosed only just after the hospitalisation due to crisis, despite the evident signs and symptoms of PAI. Lack of appetite and loss of body weight occurred in all patients and for that reason a diagnosis of chronic gastric and duodenal ulcer disease was the most often incorrect diagnosis. After the proper diagnosis and treatment, in the course of 1–11 years of observation, there was only 6 imminent adrenal crises in 5 patients. Our results indicated that training of primary care physicians in the field of recognising and treatment of adrenal insufficiency is still essential.

Innovative treatment for adrenal insufficiency

Innovative treatment for adrenal insufficiency

Poster 108 Functional Outcomes after Treatment of Adrenal Insufficiency in Medical Rehabilitation Patients: A Case Report

Poster 108 Functional Outcomes after Treatment of Adrenal Insufficiency in Medical Rehabilitation Patients: A Case Report

Adrenal insufficiency

AbstractAdrenocortical insufficiency may arise through primary failure of the adrenal glands or due to lack of ACTH stimulation as a result of pituitary or hypothalamic dysfunction. Prolonged administration of exogenous steroids will suppress the hypothalamic–pituitary‐adrenal axis, and hence cortisol secretion. We review briefly the causes, investigation, and treatment of adrenal insufficiency, and highlight aspects of particular relevance to patients with adrenal tumors. J. Surg. Oncol. 2012; 106:595–599. © 2012 Wiley Periodicals, Inc.

Plasma poltergeists: A negative cortisol interference leading to a false diagnosis of adrenal insufficiency

IntroductionAdrenal insufficiency is a rare life threatening condition with non-specific clinical signs and symptoms. This necessitates a high level of reliance on laboratory results for making the diagnosis. MethodsWe report a case involving an interference in cortisol measurement leading to spuriously low-cortisol measurements and the incorrect diagnosis and treatment of adrenal insufficiency. We also discuss the testing used to confirm the presence and nature of the interferent. ResultsInterference with an IgG antibody was demonstrated, and the patient was found to have a normally functioning adrenal axis. ConclusionInterference in immunoassay is well described but often difficult to detect in clinical practice. Negative interference in cortisol measurement can occur and may lead to inappropriate diagnosis and treatment.

Diagnosis and Treatment of Adrenal Insufficiency

Adrenal insufficiency is caused by either primary adrenal failure or by hypothalamic-pitu itary impairment of the corticotropic axis which is predominantly due to long-term glucocorticoid treatment or by pituitary disease. Primary adrenal failure is a rare disease that is life-threatening when overlooked whle adrenal failure secondary to hypothalamo-pituitary disease is a common clinical problem that has serious impact on the quality of life. Recent data suggests that the health-related quality of life in many patients with adrenal insufficiency is more severely impaired than previously thought and that current hormone replacement strategies are insufficient to prevent increased morbidity and mortality due to the disease. Therefore, the optimization and careful monitoring of glucocorticoid and mineralocorticoid replacement therapy remains one of the most challenging tasks in endocrinology. Leaving treatment aside, diagnosis of adrenal insufficiency is also challeng ing, because the main presenting symptoms such as fatigue, anorexia, and weight loss are non-specifically associated with many other common ailments, delaying a correct diagno sis. Some pitfalls in diagnostic work-up, particularly in the identification of secondary adre nal insufficiency, make the diagnosis even more difficult. Despite the difficulties, the com plications associated with adrenal insufficiency make the rapid diagnosis and proper ma nagement of adrenal failure are important tasks for all physicians. We review here current standards for clinical assessment, diagnosis and treatment of adrenal insufficiency in light of recent research findings.

A Single-Center Review of Prescribing Trends and Outcomes of Corticosteroid Replacement Therapy in Critically Ill Children with Septic Shock~!2010-06-18~!2010-08-06~!2010-09-06~!

Recently published consensus treatment guidelines for pediatric sepsis recommend initiating corticosteroid replacement therapy (CRT) for those critically ill children with adrenal insufficiency and refractory shock. The data to support this recommendation is limited, and multiple studies have demonstrated significant variation in both the diagnosis and treatment of adrenal insufficiency and refractory shock in children. In order to better define the variation in practice at our institution, we retrospectively reviewed the experience with CRT in critically ill children with refractory septic shock over a 1-year-period. In addition, as a secondary aim we compared outcomes in critically ill children treated with CRT for variable lengths of time. We found that the initiation of CRT at our center is relatively consistent. However, we noted significant variation in the duration of CRT and whether CRT was gradually tapered or stopped abruptly. The majority of the patients in our cohort received less than the currently recommended duration of 7 days of CRT. There were a higher number of treatment failures in those patients who received CRT for greater than 7 days, suggesting that CRT should be tapered gradually in these patients. There is significant variation in prescribing trends for CRT at our institution, which are likely to be compounded in any multi-center cohort study of CRT in critically ill children with septic shock. Practice variation in CRT should be standardized to address the impact of CRT in this population.