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PubMed1994

Addison's disease in Japan: characteristics and changes revealed in a nationwide survey.

Patients with Addison's disease, newly diagnosed in the last five years were surveyed nationwide in conjunction with two past surveys. The decreasing incidence, i.e., 168 patients from 1977 to 1981 (survey 1), 108 from 1982 to 1986 (survey 2), and 74 from 1987 to 1991 (the present survey), reflects a decrease in the incidence (n = 28) of tuberculous Addison's disease, but not that (n = 36) of idiopathic Addison's, making the idiopathic form predominant for the first time in the history of the disease in Japan. Because the interval between the preceding tuberculosis and the onset of Addison's averages 32 +/- 15 years, tuberculous Addison's has a relatively late onset. Pigmentation is the most frequent symptom (90%). Other symptoms, abnormal laboratory data, and positive adrenal antibodies are observed less frequently in Japan than in North America or Europe. The types of associated disorders are also distributed differently. Adrenal CT and MRI scans have been the most useful means in differentiating between the two major types of the disease. This report focuses on features distinguishing Japanese sufferers from their western counterparts.

Addison Disease↗
PubMed1988

Adrenal magnetic resonance imaging in Addison's disease.

Magnetic resonance imaging of the adrenal glands was performed in 9 patients with Addison's disease to evaluate the role of magnetic resonance (MR) in this entity. All patients had bilateral adrenal masses demonstrated by computed tomography (CT); etiologies included adrenal hemorrhage (2 patients), granulomatous disease (1 patient), adrenal lymphoma (3 patients), and adrenal metastases (3 patients). Spin-echo axial images were obtained at repetition times (TR) 0.5, 2.0 s and TE 28, 56 ms, using a Diasonics superconducting magnet operating at 0.35 T. In the patients with lymphoma, metastases, and granulomatous disease, the adrenal masses appeared hypointense or isointense with liver on the T1-weighted images (TR 0.5 s, TE 28 ms). In cases of adrenal hemorrhage, areas of hyperintensity were seen on TR 0.5, TE 56 ms sequences, due to shortening of T1 values. In both groups of patients the masses were hyperintense on T2 weighted sequences. Mean calculated T1 of the hemorrhagic glands was 449 ms, compared with a mean of 782 ms for metastases and lymphoma. While MR is not capable of distinguishing between acute inflammatory and metastatic diseases of the adrenal glands, it may be equally efficacious as CT in suggesting the diagnosis of adrenal hemorrhage in patients with Addison's disease.

Addison Disease↗
PubMed2002

Additional association of intra-MHC genes, MICA and D6S273, with Addison's disease.

Intra-MHC sequences including MHC class I chain-related genes (MICAs), D6S273 and D6S2223 are associated with autoimmune diseases in addition to HLA class II. In the current study, we ascertained the haplotypes of 57 Caucasian patients with Addison's disease composed of these genetic markers and compared them either with 72 general population controls or with 105 child controls carrying Addison's disease high-risk DR3-DQ2/DR4-DQ8 genotypes. The MICA-A5.1/A5.1 genotype as well as HLA DR3/4 especially with DRB1*0404 were the main susceptibility markers. The homozygous MICA-A5.1/A5.1 genotype was significantly more frequent in the patients with Addison's disease (61%) than in the healthy controls (6%). The MICA-A5.1 allele was increased on both the DR3 and DR4 haplotypes, independent of DQ and DRB1 subtyping, in the patients with Addison's disease compared with the controls. Furthermore, the D6S273*140 allele on the DR3 haplotype and the D6S273*134 allele on the DR4 haplotype in the DR3/4 heterozygotes influenced susceptibility relative to the DR3/4 controls. The risk for Addison's disease was increased for the DR3-D6S273*140-MICA-A5.1/DRB1*0404-D6S273*134-MICA-A5.1 genotypes compared with that conferred by the DR3/4 controls. Susceptibility to Addison's disease is influenced by the genes around MICA and D6S273 for both the HLA DR3-DQ2 and DR4-DQ8 haplotypes.

Addison Disease↗
PubMed1995

High diagnostic accuracy for idiopathic Addison's disease with a sensitive radiobinding assay for autoantibodies against recombinant human 21-hydroxylase.

Autoantibodies against 21-hydroxylase (P450c21) are common in idiopathic autoimmune Addison's disease. In the present work, we have developed a sensitive radiobinding assay using in vitro translated recombinant human 35S-P450c21. Levels of P450c21 antibodies (P450c21-Ab) were expressed as a relative index (P450c21 index) using a P450c21-Ab positive Addisonian serum and two antibody-negative healthy sera as positive and negative standards in healthy individuals. The upper level of normal was the mean + 3 SD. Positivity for P450c21-Ab was confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis of immunoprecipitated 35S-P450c21. In 38 Addisonian patients, P450c21-Ab were found in 24/28 (86%) idiopathic, 0/5 post-tuberculosis, 0/3 adrenoleukodystrophy, and 0/2 post-adrenalectomy sera. Among healthy individuals, 1/70 (1.4%) were positive. The P450c21 index, as an estimate of P450c21-Ab levels, correlated inversely with the duration of idiopathic Addison's disease (r = -0.527; P = 0.007): 16/16 (100%) positive in patients with less than 20 yr and 8/12 (67%) positive in patients with more than 20 yr disease duration. The availability of this simple and sensitive radiobinding assay to evaluate levels of P450c21-Ab will permit large clinical studies as well as screening subjects at risk. In addition, the general population can now be screened to evaluate the predictive value of P450c21-Ab for Addison's disease.

Acute Disease↗
PubMed2003

Adrenoleukodystrophy initially diagnosed as idiopathic Addison's disease in two patients: the importance of early testing.

Childhood cerebral X-linked adrenoleukodystrophy (X-ALD) is a rare neurodegenerative disease typically presenting from age 4 to 8 years in males. We report 2 cases of X-ALD in boys. The diagnosis of Addison's disease was made before the development of neurological symptoms in both cases. The first patient had hyperpigmentation of the lips and an adrenocorticotropic hormone (ACTH) level higher than 1250 pg/mL when he was 7 years 3 months old. The initial diagnosis was Addison's disease, but X-ALD was diagnosed at age 8 years 8 months, when his motor and mental function deteriorated. The second boy had hypoglycemia, skin pigmentation, and an ACTH level of 1086 pg/mL when he was 4 years 6 months old, but the diagnosis was changed from Addison's disease to X-ALD owing to deterioration in speech at age 7 years. Since both bone marrow transplantation and Lorenzo's oil are beneficial only at the early stage of disease and idiopathic Addison's disease is very rare in children, it is important to test for very-long-chain fatty acids in boys suspected of having Addison's disease.

Addison Disease↗