Epidemiology, pathogenesis, and diagnosis of Addison’s disease in adults

Betterle, Corrado; Presotto, Fabio; Furmaniak, Jadwiga

doi:10.1007/s40618-019-01079-6

Cited by 83 publications

(84 citation statements)

References 200 publications

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“…As AD in APS-1 tends to develop after CMC and/or CH, it would seem appropriate to test for ACA and/or 21-OHAbs in all patients with CMC and/or CH. This strategy would alert physicians to the high probability of progression to clinical AD for patients positive for these autoantibodies and would be helpful in preventing unexpected life-threatening adrenal crisis events [74]. Nearly, half of the females with APS-1 in our cohort developed POF (Fig.…”

Section: Discussionmentioning

confidence: 97%

Autoimmune polyendocrine syndrome type 1: an Italian survey on 158 patients

Garelli

Costa

Sabbadin

et al. 2021

J Endocrinol Invest

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Background Autoimmune Polyglandular Syndrome type 1 (APS-1) is a rare recessive inherited disease, caused by AutoImmune Regulator (AIRE) gene mutations and characterized by three major manifestations: chronic mucocutaneous candidiasis (CMC), chronic hypoparathyroidism (CH) and Addison’s disease (AD). Methods Autoimmune conditions and associated autoantibodies (Abs) were analyzed in 158 Italian patients (103 females and 55 males; F/M 1.9/1) at the onset and during a follow-up of 23.7 ± 15.1 years. AIRE mutations were determined. Results The prevalence of APS-1 was 2.6 cases/million (range 0.5–17 in different regions). At the onset 93% of patients presented with one or more components of the classical triad and 7% with other components. At the end of follow-up, 86.1% had CH, 77.2% AD, 74.7% CMC, 49.5% premature menopause, 29.7% autoimmune intestinal dysfunction, 27.8% autoimmune thyroid diseases, 25.9% autoimmune gastritis/pernicious anemia, 25.3% ectodermal dystrophy, 24% alopecia, 21.5% autoimmune hepatitis, 17% vitiligo, 13.3% cholelithiasis, 5.7% connective diseases, 4.4% asplenia, 2.5% celiac disease and 13.9% cancer. Overall, 991 diseases (6.3 diseases/patient) were found. Interferon-ω Abs (IFNωAbs) were positive in 91.1% of patients. Overall mortality was 14.6%. The AIRE mutation R139X was found in 21.3% of tested alleles, R257X in 11.8%, W78R in 11.4%, C322fsX372 in 8.8%, T16M in 6.2%, R203X in 4%, and A21V in 2.9%. Less frequent mutations were present in 12.9%, very rare in 9.6% while no mutations in 11% of the cases. Conclusions In Italy, APS-1 is a rare disorder presenting with the three major manifestations and associated with different AIRE gene mutations. IFNωAbs are markers of APS-1 and other organ-specific autoantibodies are markers of clinical, subclinical or potential autoimmune conditions.

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Section: Discussionmentioning

confidence: 97%

Autoimmune polyendocrine syndrome type 1: an Italian survey on 158 patients

Garelli

Costa

Sabbadin

et al. 2021

J Endocrinol Invest

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“…Thus, as both AI and AC are rare conditions, the degree of applicability of our model to the general population may be limited. However, as well-known risk factors for AC include a history of AI 12 , adrenal or pituitary surgery 13 , dose reduction or discontinuation of exogenous steroid use 14,15 and immune checkpoint inhibitors 16 or steroid synthase inhibitor use 17,18 , the model can prove useful in the early diagnosis of AC in individuals with these conditions. In fact, AC onset in patients with at least one of the aforementioned risk factors accounts for 73.3% (66/90) of the events.…”

Section: Discussionmentioning

confidence: 99%

Development of a simple prediction model for adrenal crisis diagnosis

Katabami

Tsukiyama

Tanabe

et al. 2020

Sci Rep

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to develop a prediction model for adrenal crisis (Ac) diagnosis among individuals with adrenal insufficiency that relies on the values of routinely measured clinical parameters, for application in standard clinical practice. We retrospectively analysed data from five referral centres in Japan. Multivariate binary logistic regression was used to identify independent predictors of Ac, and receiver operating characteristic curve analysis was used to determine their optimal cutoff points. The analysis included data from 54 patients with 90 AC events. Logistic regression revealed that serum sodium and C-reactive protein (CRP) levels were independent predictors of AC. Serum sodium levels < 137 mEq/L had a sensitivity of 71.1% and specificity of 95.6%. CRP levels > 1.3 mg/dL had a sensitivity of 84.4% and specificity of 94.9%. In combination, serum sodium levels < 137 mEq/L or CRP levels > 1.3 mg/ dL for AC diagnosis had sensitivity and specificity values of 97.8% and 94.4%, respectively. The combined use of serum sodium and CRP levels had high sensitivity and specificity, and can be used for Ac screening in standard clinical practice. the model can assist in identifying Ac among high-risk individuals. A larger prospective study is needed to validate these results. In individuals with chronic adrenal insufficiency (AI), adrenal crisis (AC) is a serious and life-threatening event, even among those with steroid replacement therapy 1. The mortality of individuals with chronic AI is higher than that of the general population, with the associated mortality risk shown to be approximately 2.5-fold higher 1,2. Epidemiological studies have shown that the AC incidence among individuals with AI who are receiving standard replacement therapy is 6-8% per year 3,4. Among the important risk factors for AC is a previous episode of AC 5. A prospective study showed that the AC-related mortality value was 0.5 deaths/100 patient-years 6. As no consensual definition of AC exists, a physician must diagnose AC based on the presence of non-specific symptoms, signs, and/or the results of routine laboratory tests. Furthermore, some endocrine tests such as rapid assays for cortisol and adrenocorticotropin (ACTH) are available only in a limited number of medical institutes. AC diagnosis is challenging and there is a need for a rapid, widely available sensitive method for the same. Therefore, the purpose of this study was to develop a prediction model for AC diagnosis that relies on the values of standard biochemical tests and can be applied in standard clinical practice. Results Baseline patient characteristics and precipitating factors for Ac. In total, 90 events in 54 patients with AC were included in the analysis (Table 1). Twenty-one (38.9%) patients experienced more than one AC event during the data collection period (twice, N = 13; three times, N = 4; more than three times, N = 4). The mean age at admission for AC was 62.8 ± 1.7 years (range, 29-91 years) and approximately half of the patients were women. Twenty-four patients were diagnosed ...

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“…Primarily, the physiological pattern of cortisol secretion is difficult to mirror using the conventional oral replacement therapy regimens [immediate-release hydrocortisone (HC), cortisone acetate (CA) or prednisolone] [2]. For this reason, a new formulation of once daily HC, defined as modifiedrelease hydrocortisone (MRHC), has been recently introduced [3,4].…”

Section: Introductionmentioning

confidence: 99%

What factors have impact on glucocorticoid replacement in adrenal insufficiency: a real-life study

Puglisi

Rossini

Tabaro

et al. 2020

J Endocrinol Invest

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Purpose The impact of patient's characteristics on glucocorticoid (GC) replacement therapy in adrenal insufficiency (AI) is poorly evaluated. Aims of this study were to assess the influence of sex and body weight on GC dosing and to describe the choice of GC in AI of different etiologies. Methods We retrospectively evaluated hydrocortisone (HC) equivalent total daily dose (HC-TDD) and per-kg-daily dose (HC-KDD) in 203 patients (104 primary AI [pAI], 99 secondary AI [sAI]) followed up for ≥ 12 months. They were treated with HC, modified-release HC (MRHC) or cortisone acetate (CA) and fludrocortisone acetate (FCA) in pAI. Results At baseline, CA was preferred both in pAI and sAI; at last visit, MRHC was most used in pAI (49%) and CA in sAI (73.7%). Comparing the last visit with baseline, in pAI, HC-TDD and HC-KDD were significantly lower (p = 0.04 and p = 0.006, respectively), while FCA doses increased during follow-up (p = 0.02). The reduction of HC-TDD and HC-KDD was particularly relevant for pAI women (p = 0.04 and p = 0.002, respectively). In sAI patients, no change of HC-KDD and HC-TDD was observed, and we found a correlation between weight and HC-TDD in males (r 0.35, p = 0.02). Conclusions Our real-life study demonstrated the influence of etiology of AI on the type of GC used, a weight-based tailoring in sAI, a likely overdosage of GC treatment in pAI women at the start of treatment and the possibility to successfully increase FCA avoiding GC over-treatment. These observations could inform the usual clinical practice.

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Epidemiology, pathogenesis, and diagnosis of Addison’s disease in adults

Cited by 83 publications

References 200 publications

Autoimmune polyendocrine syndrome type 1: an Italian survey on 158 patients

Autoimmune polyendocrine syndrome type 1: an Italian survey on 158 patients

Development of a simple prediction model for adrenal crisis diagnosis

What factors have impact on glucocorticoid replacement in adrenal insufficiency: a real-life study

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