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Is the Prevalence of Addison’s Disease Underestimated?

Department of Internal Medicine and Endocrine & Metabolic Sciences University of Perugia Perugia, Italy I-06126

The clinical spectrum of Addison’s disease has changed dramatically over the last 30 years, and autoimmunity is now the most common cause of primary adrenal insufficiency in Western countries (1). Using an original flowchart of immune and biochemical markers, we have shown that adrenal autoantibodies are present in 70% of Addison patients (2). Furthermore, approximately 1% of patients with endocrine autoimmune disorders have clinical or subclinical signs of adrenal insufficiency (3). In spite of the availability of accurate biochemical and immune markers of Addison’s disease, its prevalence in the general population has not been widely investigated. In initial studies (4, 5), the prevalence of Addison’s disease in Western countries was calculated at 35–60 per million. However, the results of a recent study (6) suggest that this disease could be more common than previously reported.

To accurately evaluate the prevalence of Addison’s disease in the general population, we selected a geographically delimited region of central Italy, Umbria, and we determined the total number of subjects suffering from Addison’s disease, during the period January 1–December 31, 1996 in this region. According to the Italian Institute of Statistics (ISTAT), the population resident in Umbria is 811,887 (394,211 males and 417,676 females). We used the clinical records of the patients attending the endocrine unit of our department as the primary data source. Because cortisone acetate is the only treatment for Addison’s disease available in Italy, given the unavailability of oral preparations of hydrocortisone, we used the regional computerized file of the prescriptions of cortisone acetate as a secondary and independent source. Diagnosis of Addison’s disease was confirmed by interviewing the treating physicians and by following standard criteria (1).

The primary source identified 59 Addison patients and the secondary source 234 subjects in treatment with cortisone acetate. Of these latter 234 subjects, 91 had Addison’s disease, and 55 of them had already been identified by the primary source. The remaining 143 subjects identified by the secondary source had either secondary adrenal insufficiency or a neoplasm impairing adrenal function. Overall, the two data sources identified a total of 95 (42 males and 53 females) Addison patients, and the combined case ascertainment was 97% as calculated by capture-recapture analysis. The resulting prevalence of Addison’s disease in the general population was 117 per million (95% confidence interval: 95–143). Prevalence among males and females was 106 per million (95% confidence interval: 77–144) and 127 per million (95% confidence interval: 95–166), respectively.

The frequency of Addison’s disease in our study represents the highest prevalence reported so far, and it is 2- to 3-fold higher than those previously reported in other studies (4, 5). Our results indicate that the prevalence of Addison’s disease has so far been underestimated. Given the increase in frequency of adrenal autoimmunity in Addison patients observed over the last 20 years, we hypothesize that the incidence and prevalence of autoimmune adrenal insufficiency is rising. Additional population-based studies are needed to monitor the yearly incidence of this disease and to test this latter specific hypothesis.

Footnotes

Address correspondence to: Alberto Falorni, M.D., Ph.D., Department of Internal Medicine and Endocrine & Metabolic Sciences, Università degli Studi di Perugia, Via E. dal Pozzo, Perugia, Italy I-06126.

Received December 11, 1998.

References

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3. Laureti S, De Bellis AM, Muccitelli VI, et al. 1998 Levels of adrenocortical autoantibodies correlate with the degree of adrenal dysfunction in subjects with preclinical Addison’s disease. J Clin Endocrinol Metab. 83:3507–3511.[Abstract/Free Full Text]
4. Mason AS, Meade TW, Lee JAH, Morris JN. 1968 Epidemiological and clinical picture of Addison’s disease. Lancet. II:744–747.
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