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Adrenal insufficiency, chronic [keywords]
- Subcutaneous Hydrocortisone Administration for Emergency Use in Adrenal Insufficiency. [JOURNAL ARTICLE]
- Eur J Endocrinol 2013 May 14.
OBJECTIVE:Evaluation of the pharmacokinetics and safety of subcutaneous hydrocortisone injection for use in adrenal emergency
DESIGN:Single center open label, sequence randomized, cross over study in a tertiary care center.
PATIENTS AND METHODS:Twelve Patients with chronic Addison's disease. Comparison of hydrocortisone pharmacokinetics after subcutaneous (sc) and intramuscular (im) injection (100 mg), and after administration of sodium chloride (0.9%) subcutaneously, respectively, at three different visits. Main Outcome Measure: Maximum serum cortisol (Cmax), time to Cmax (tmax), and time to serum cortisol >36 µg/dl (tSerum-Cortisol >36 µg/dl) after subcutaneous administration compared to intramuscular administration, safety and patient preference.
RESULTS:Serum cortisol increased rapidly and substantially after both im and sc injection (Cmax: 110±29 vs 97±28 µg/dl, p=0.27); tmax 66±51 vs 91±34 min, p=0.17, and tSerum-Cortisol > 36 µg/dl 11±5 vs 22±11min, p=0.004, respectively). Both, im and sc injections were well tolerated. Eleven patients (91.7%) preferred sc injection, whereas one patient did not have any preference.
CONCLUSIONS:Subcutaneous administration of 100 mg hydrocortisone shows excellent pharmacokinetics for emergency use with only a short delay in cortisol increase compared to intramuscular injection. It has a good safety profile and is preferred by patients over intramuscular injection.
- Overtraining, Exercise, and Adrenal Insufficiency. [JOURNAL ARTICLE]
- J Nov Physiother 2013 Feb 16; 3(125)
Running, or any aerobic training in moderation, has a positive effect on health. There is a point of diminishing returns, where chronic stress from overtraining, which is common in runners, may be linked to problems in the adrenal gland. Overtraining Syndrome (OS) has been linked with adrenal insufficiency. There is a direct link between stress and the adrenal glands, and the physical stress of overtraining may cause the hormones produced in these glands to become depleted. Overtraining Syndrome (OS) has been described as chronic fatigue, burnout and staleness, where an imbalance between training/competition, versus recovery occurs. Training alone is seldom the primary cause. In most cases, the total amount of stress on the athlete exceeds their capacity to cope. A triggering stressful event, along with the chronic overtraining, pushes the athlete to start developing symptoms of overtraining syndrome, which is far worse than classic overtraining. Overtraining can be a part of healthy training, if only done for a short period of time. Chronic overtraining is what leads to serious health problems, including adrenal insufficiency. Severe overtraining over an extended period can result in adrenal depletion. An Addison-Type overtraining syndrome, where the adrenal glands are no longer able to maintain proper hormone levels and athletic performance is severely compromised has been described by researchers. The purpose of this review is to describe the relationship between overtraining, chronic fatigue, and adrenal insufficiency and to address the overlap in these conditions, as well as examine critical research on the relationship between the dysfunction of the adrenal axis in over trained and stressed athletes.
- Dynamic output and control of the hypothalamic-pituitary-adrenal axis in critical illness and major surgery. [JOURNAL ARTICLE]
- Br J Anaesth 2013 May 9.
The hypothalamic-pituitary-adrenal (HPA) axis is a neuro-endocrine system that regulates circulating levels of glucocorticoid hormones. These hormones are vital for normal homeostasis and play a pivotal role in the response to stress. Levels of cortisol fluctuate throughout the day in a diurnal rhythm, underlying which is an ultradian rhythm of approximately hourly pulses, and this pulsatility directly affects transcriptional outcomes. Pulsatility is not the result of a 'pulse generator', but is inherent within the system as a result of negative feedback. These patterns of secretion change in both acute and chronic illness as a result of inflammatory mediators, splanchnic nerve output, and central nervous system control. Levels of cortisol in both normal and illness states are highly dynamic and so previously used static assessment tools for diagnosing corticosteroid related critical illness insufficiency (CRCI) are not likely to be useful. Therapeutic regimens have also failed so far, to take secretory patterns into account. In this review we look at the dynamic control and effects of glucocorticoids and frame in this context the current evidence surrounding steroid use in critical care and major surgery.
- Clinical phenotypes of autoimmune polyendocrinopathycandidiasis-ectodermal dystrophy seen in the Northern Ireland paediatric population over the last 30 years. [Journal Article]
- Ulster Med J 2012 Sep; 81(3):118-22.
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), also known as autoimmune polyendocrinopathy syndrome type 1, is a rare autosomal recessive disorder with a variable and evolving phenotypic course. It is caused by mutations in the autoimmune regulator (AIRE) gene. APECED syndrome is diagnosed clinically by the presence of 2 from 3 major criteria; chronic mucocutaneous candidasis, primary hypoparathyroidism and primary adrenocortical insufficiency. Many of the patients develop all three before the age of 20 years. There is also a wide spectrum of other associated conditions including endocrine and non endocrine manifestations. This paper reviews the clinical phenotypes seen in the paediatric population of Northern Ireland during the last 30 years detailed from a retrospective review of clinical notes. Eight patients were identified with APECED and all patients were found to be homozygous for the c.964dell3 mutation. A wide clinical variation is apparent within APECED syndrome. Paediatricians should be vigilant of the diagnosis when they encounter any of the features described and consider the future development of associated diseases. In confirmed APECED syndrome, clinical and laboratory investigation is essential to initiate early treatment in the patient and other affected members of the family.
- Epidemiology of adrenal insufficiency: a nationwide study of hospitalizations in Taiwan from 1996 to 2008. [Journal Article, Research Support, Non-U.S. Gov't]
- J Chin Med Assoc 2013 Mar; 76(3):140-5.
Adrenal insufficiency (AI) is an uncommon but life-threatening disorder if it progresses to adrenal crisis. The nationwide trend of AI epidemiology in Taiwan has been infrequently reported.Based on complete hospitalization datasets from the National Health Insurance Research Database, the trend of the annual incidence of AI from 1996 to 2008 in Taiwan was retrospectively analyzed. Special attention was paid to age-specific incidence, contributing factors as well as comorbidity at the time of AI diagnosis.Of the existing 35,884,231 hospitalization records, there were 52,660 with AI diagnosis in 32,085 patients (15,914 women and 16,163 men). The annual incidence of AI increased over time from 6.4/10(5) (n = 1280) in 1996 to 15.2/10(5) (n = 3494) in 2008. Nearly four-fifths (77%, n = 24,688) of the patients were aged at least 60 years at the time of their first AI diagnosis. The increase of the annual incidence of AI during the study period was largely attributed to disease prevalence in patients aged 60 years and over, with the most marked increase in the population aged 80 years of age from 51.1/10(5) in 1996 to 179.9/10(5) in 2008. Most patients with newly diagnosed AI were treated at internal medicine wards (81.1%, n = 26,032), at academic medical centers (51.9%, n = 16,648) and in southern Taiwan (54%, n = 17,334). The most common comorbidity was pneumonia (6.4%, n = 2051), followed by urinary tract infection (6.4%, n = 2049), diabetes mellitus (6.2%, n = 1985), electrolyte imbalance (4.8%, n = 1551), and chronic obstructive pulmonary disease (4.5%, n = 1428).The annual incidence of AI in Taiwan had continuously increased in recent years, and elderly patients accounted for the majority of the increase. In the face of an increasingly aging population, Taiwanese physicians should pay more attention to this easily overlooked disease.
- Large mitochondrial DNA deletion in an infant with addison disease. [Journal Article]
- JIMD Rep 2012.:5-9.
Background:Mitochondrial diseases are a group of disorders caused by mutations in nuclear DNA or mitochondrial DNA, usually involving multiple organ systems. Primary adrenal insufficiency due to mitochondrial disease is extremely infrequent and has been reported in association with mitochondrial DNA deletion syndromes such as Kearns-Sayre syndrome.
Aim:To report a 3-year-old boy with Addison disease, congenital glaucoma, chronic pancreatitis, and mitochondrial myopathy due to large mitochondrial DNA deletion. Method: Molecular analysis of mitochondrial DNA samples obtained from peripheral blood, oral mucosa, and muscle tissue.
Results:A novel large mitochondrial DNA deletion of 7,372bp was identified involving almost all genes on the big arch of mtDNA.
Conclusions:This case reaffirms the association of adrenal insufficiency and mitochondrial DNA deletions and presents new evidence that glaucoma is another manifestation of mitochondrial diseases. Due to the genetic and clinical heterogeneity of mitochondrial disorders, molecular analysis is crucial to confirm diagnosis and to allow accurate genetic counseling.
- Impaired release of corticosterone from adrenals contributes to impairment of circadian rhythms of activity in hyperammonemic rats. [JOURNAL ARTICLE]
- Arch Biochem Biophys 2013 Feb 1.
Patients with liver cirrhosis may present impaired sleep-wake and circadian rhythms, relative adrenal insufficiency and altered hypothalamus-pituitary-adrenal gland (HPA) axis. The underlying mechanisms remain unclear. Circadian rhythms are modulated by corticosteroids which secretion is regulated by HPA axis. Hyperammonemia alters circadian rhythms of activity and corticosterone in rats. The aims were: (1) assessing whether corticosterone alterations are responsible for altered circadian rhythm in hyperammonemia: (2) to shed light on the mechanism by which corticosterone circadian rhythm is altered in hyperammonemia. The effects of daily corticosterone injection at ZT10 on circadian rhythms of activity, plasma corticosterone, adreno-corticotropic hormone (ACTH) and hypothalamic corticotropic releasing hormone (CRH) were assessed in control and hyperammonemic rats. ACTH-induced corticosterone release was analyzed in cultured adrenal cells. Corticosterone injection restores the corticosterone peak in hyperammonemic rats and their activity and circadian rhythm. Plasma ACTH and CRH in hypothalamus are increased in hyperammonemic rats. Corticosterone injection normalizes ACTH. Chronic hyperammonemia impairs adrenal function, reduces corticosterone content and ACTH-induced corticosterone release in adrenals, leading to reduced feedback modulation of HPA axis by corticosterone which contributes to impair circadian rhythms of activity. Impaired circadian rhythms and motor activity may be corrected in hyperammonemia and hepatic encephalopathy by corticosterone treatment.
- Diagnostic complexities of eosinophilia. [Case Reports, Journal Article, Review]
- Arch Pathol Lab Med 2013 Feb; 137(2):259-69.
The advent of molecular tools capable of subclassifying eosinophilia has changed the diagnostic and clinical approach to what was classically called hypereosinophilic syndrome.To review the etiologies of eosinophilia and to describe the current diagnostic approach to this abnormality.Literature review.Eosinophilia is a common, hematologic abnormality with diverse etiologies. The underlying causes can be broadly divided into reactive, clonal, and idiopathic. Classically, many cases of eosinophilia were grouped together into the umbrella category of hypereosinophilic syndrome, a clinical diagnosis of exclusion. In recent years, an improved mechanistic understanding of many eosinophilias has revolutionized the way these disorders are understood, diagnosed, and treated. As a result, specific diagnoses can now be assigned in many cases that were previously defined as hypereosinophilic syndrome. Most notably, chromosomal rearrangements, such as FIP1L1-PDGFRA fusions caused by internal deletions in chromosome 4, are now known to be associated with many chronic eosinophilic leukemias. When present, these specific molecular abnormalities predict response to directed therapies. Although an improved molecular understanding is revolutionizing the treatment of patients with rare causes of eosinophilia, it has also complicated the approach to evaluating and treating eosinophilia. Here, we review causes of eosinophilia and present a framework by which the practicing pathologist may approach this diagnostic dilemma. Finally, we consider recent cases as clinical examples of eosinophilia from a single institution, demonstrating the diversity of etiologies that must be considered.
- [A multi-centre randomized controlled trial of domiciliary non-invasive ventilation vs long-term oxygen therapy in survivors of acute hypercapnic respiratory failure due to COPD. Non-invasive ventilation in obstructive lung disease (NIVOLD) study]. [English Abstract, Journal Article, Multicenter Study, Randomized Controlled Trial]
- Rev Mal Respir 2012 Nov; 29(9):1141-8.
Patients with chronic hypercapnic respiratory failure due to chronic obstructive pulmonary disease (COPD) are very likely to develop acute exacerbations. Non-invasive ventilation is often used to treat acute respiratory failure but little information is available about the benefits of domiciliary non-invasive ventilation in COPD patients with chronic hypercapnic respiratory failure who survive an acute episode. The purpose of this study is to determine whether domiciliary non-invasive ventilation can reduce the incidence of recurrent acute hypercapnic respiratory failure in COPD patients who survived an episode of acute hypercapnic respiratory failure (AHRF).A multi-center randomized controlled trial including patients with COPD who survived an episode of AHRF. Patients will be randomly assigned to receive long-term oxygen therapy (LTOT) (no intervention) or domiciliary non-invasive ventilation (active comparator) in addition to LTOT. In France, three university hospitals: Rouen, Caen and Amiens and three general hospitals: Dieppe, Le Havre and Elbeuf are recruiting.Age above 18 years; patients with COPD who have survived an episode of AHRF; patients weaned from non-invasive or mechanical ventilation for at least seven days following an acute episode; with stable arterial blood gases for at least two days: PaCO(2) greater than 55mmHg and pH greater than 7.35. Exclusion criteria are: age above 85 years, other causes of respiratory failure, obstructive sleep apnoea, adverse psychosocial status, serious co-morbidity. Primary outcome is the frequency of episodes of acute hypercapnic respiratory failure (time frame: up to 102 weeks), secondary outcome is mortality (time frame: 1 month and every 6 months for 2 years).A decreased rate of episodes of acute hypercapnic respiratory failure in the group of patients receiving non-invasive ventilation in addition to long term oxygen therapy.
- The neuropsychiatric aspect of Addison's disease: a case report. [Journal Article]
- Innov Clin Neurosci 2012 Oct; 9(10):34-6.
Chronic adrenal insufficiency, known as Addison's disease, presents with a constellation of symptoms and signs. The neuropsychiatric aspect of this condition is not fully understood and not much has been documented about it in the English literature. This article presents a case of a 41-year old male patient who presented initially with depression after a recent life stressor. After his condition escalated and therapy continued to fail, the medical team revised its diagnosis to Addison's disease. Neuropsychiatric symptoms could be the first presentation of Addison's disease, and thus should be kept in mind whenever such a case presents to the physician.