Is Diagnosis and Subclassification of Adrenal Insufficiency as Easy as It Looks?

The diagnosis of adrenal insufficiency (AI) is a challenge. Most signs and symptoms are nonspecific and vary considerably depending upon the underlying cause and degree of AI. Identification of AI is crucial because the disease may be life-threatening if left unrecognized. The diagnostic evaluation consists of three steps. The first step is establishing the presence of hypocortisolism. The second step is establishing the level of hypothalamus-pituitary-adrenal axis dysfunction. The third and final step is searching for the exact cause of AI by additional laboratory and imaging techniques. Each diagnostic step can have its own uncertainties. The optimal test in case of intermediate basal cortisol measurements is still a matter of debate. Furthermore, interpretation of the results of the tests is complicated by arbitrary definitions of normal cutoff responses, variability in the analytical accuracy of the cortisol assays used and factors influencing cortisol-binding globulin. This chapter aims to provide a concise stepwise approach for the diagnostic evaluation of AI, taking into account the possible pitfalls associated with the different tests.

Decreased physical activity, reduced QoL and presence of debilitating fatigue in patients with Addison's disease.

BACKGROUND: Health-related quality of life in patients with Addison's disease has been assessed in various European countries, indicating a reduced quality of life. However, no studies have addressed the impact of Addison's disease on physical activity. OBJECTIVE: The aim of this study was to investigate the quality of life in Dutch patients with Addison's disease particularly regarding the presence of fatigue and the ability to be physically active. METHODS: In this cross-sectional study, a postal survey was performed among Dutch patients with Addison's disease on stable glucocorticoid replacement therapy with hydrocortisone or cortisone acetate. For quality of life and physical activity assessment, patients completed general and health-related quality of life and physical activity questionnaires, and scores were compared to Dutch controls. RESULTS: A total of 328 patients with Addison's disease were studied. In patients with Addison's disease, only 45·7% met the standard of physical activity (Combinorm) compared to 67·8% of Dutch controls (P < 0·01). Forty-eight per cent of patients showed abnormal fatigue, while 61% had severe fatigue. The CIS fatigue scores were significantly higher compared to controls (P < 0·01). We found reduced general subjective health-related QoL scores in both male and female patients, especially in younger patients <65 years of age. CONCLUSION: Physical activity is decreased in patients with Addison's disease, combined with a reduced subjective health-related QoL and increased fatigue.

Adrenal Crisis: Still a Deadly Event in the 21st Century.

Adrenal crisis is a life-threatening medical emergency, associated with a high mortality unless it is appropriately recognized and early treatment is rendered. Despite it being a treatable condition for almost 70 years, failure of adequate preventive measures or delayed treatment has often led to unnecessary deaths. Gastrointestinal illness is the most common precipitant for an adrenal crisis. Although most patients are educated about "sick day rules," patients, and physicians too, are often reluctant to increase their glucocorticoid doses or switch to parenteral injections, and thereby fail to avert the rapid deterioration of the patients' condition. Therefore, more can be done to prevent an adrenal crisis, as well as to ensure that adequate acute medical care is instituted after a crisis has occurred. There is generally a paucity of studies on adrenal crisis. Hence, we will review the current literature, while also focusing on the incidence, presentation, treatment, prevention strategies, and latest recommendations in terms of steroid dosing in stress situations.

Incidence of adrenal crisis in patients with adrenal insufficiency.

BACKGROUND: An adrenal crisis (AC) is a potential life-threatening event in patients with adrenal insufficiency (AI). This study aims to determine the incidence, causes, and risk factors of AC in AI. METHODS: Patients with AI diagnosed and treated at the University Medical Center Utrecht for the past 30 years were identified, and all medical records were assessed by two independent investigators. The observed frequency of AC was determined as incidence rate, calculated as the number of AC divided by person-years (PY). In addition, precipitating factors and risk factors were assessed. RESULTS: We observed an incidence rate of 5·2 AC (95% CI 4·3-6·3) per 100 PY in primary adrenal insufficiency (PAI, a total of 111 patients), and 3·6 AC (95% CI 3·1-4·1) per 100 PY in secondary adrenal insufficiency (SAI a total of 319 patients). Patients with an established diagnosis of tertiary (glucocorticoid-induced) adrenal insufficiency (a total of 28 patients) had 15·1 AC (95% CI 11·0-19·9) per 100 PY. The most important risk factor was the existence of comorbidity. Gastro-enteritis and other infections were the most common precipitating factors for AC. CONCLUSION: AC still occurs relatively frequent in patients with AI, mostly precipitated by infections and particularly in patients with high comorbidity. This should be taken into account in the education and follow-up of patients with AI.

Increased use of antimicrobial agents and hospital admission for infections in patients with primary adrenal insufficiency: a cohort study.

BACKGROUND: Previous studies have suggested that infections are an important cause of death in patients with Addison's disease, but epidemiological studies on the frequency of infections in this population are lacking. OBJECTIVE: To assess and compare the incidence risk of infections in patients with primary adrenal insufficiency with controls. DESIGN AND SETTING: We conducted a cohort study, using data from the Dutch PHARMO record linkage system, that links patients' demographics and medication histories to hospital admissions. PATIENTS: From a cohort of oral glucocorticoid users, 390 patients with primary adrenal insufficiency were identified by assessing concurrent use of glucocorticoids and mineralocorticoids using pharmacy dispensing records. A reference cohort (n=1933) with the same age and sex distribution was sampled from patients not using glucocorticoids. OUTCOME MEASURE: Incidence rates and incidence rate ratios (IRR) were calculated of infections, defined by use of antimicrobial agents, as well as hospital admissions for infection. RESULTS: The incidence of infectious episodes, defined by usage of antimicrobial agents, among patients with primary adrenal insufficiency (incidence rate 59.2/100 person-years) was 1.5 times higher compared with controls, yielding a crude IRR OF 1.61 (95% CI 1.51-1.72). The IRR decreased slightly to 1.58 (95% CI 1.47-1.70) After adjustment for co-medication and co-morbidity also associated with infection risk. Also with respect to hospital admissions for infection, the incidence rates observed for patients with primary adrenal insufficiency was higher compared with controls (3.8/100 vs 0.8/100 person-years): crude IRR 5.02 (3.66-6.87) and adjusted IRR 4.34 (95% CI 3.04-6.22). CONCLUSION: Patients with primary adrenal insufficiency had an increased use of antimicrobial agents and hospital admissions related to infection.

[Thomas Addison and the adrenal gland]. / Thomas Addison en de bijnier.

The famous and beautifully illustrated monograph "On the Constitutional and Local Effects of Disease of the Suprarenal Capsules" was published by Thomas Addison in 1855. This was the first description of the disease that now bears his name. Thomas Addison provided the first real contribution to the knowledge of adrenal function after three centuries of non-productive speculation and is one of the founders of modern endocrinology.

Does recovery of adrenal function occur in patients with autoimmune Addison's disease?

OBJECTIVE: We earlier discovered partial recovery in a patient with autoimmune Addison's disease. The aim of this study was to assess the occurrence of adrenocortical recovery in patients with autoimmune adrenalitis. DESIGN: Cross-sectional study. PATIENTS: Twenty-seven adult patients with autoimmune Addison's disease on stable glucocorticoid and mineralocorticoid replacement therapy (RT) attending the Department of Endocrinology of a university teaching hospital were included in this study. METHODS: Adrenocortical function was assessed by performing an adrenocorticotrophic hormone (ACTH) (250 µg Synacthen) stimulation test (SST) after interruption of current glucocorticoid and mineralocorticoid RT. A normal adrenal response was defined as a serum cortisol concentration ≥500 nm 30 or 60 min after stimulation. Partial recovery was defined as a cortisol concentration ≥100 and ≤500 nm after stimulation. RESULTS: In 17 patients (63%), serum cortisol concentrations remained undetectable 30 and 60 min after the administration of ACTH. None of the remaining 10 participants had a normal response. Only one patient reached a cortisol concentration of 100 nm after 60 min, but this could not be confirmed during a second SST. CONCLUSIONS: In this cross-sectional study among 27 patients with autoimmune adrenalitis, no new cases of adrenocortical recovery were found.