Malignant lymphoma associated with Addison's disease

A 62-year-old man was admitted to our hospital in Oct. 1986, because of easy fatigability, generalized pigmentation and lymph node swelling. Radiological examination showed massive adrenal tumor and two lung tumors. Endocrinological findings showed cortisol 8.3 micrograms/dl, aldosterone 35.3 ng/dl, ACTH 348 pg/ml, and non reacting pattern was observed in ACTH-overloading test, suggesting a presence of Addison's disease. A diagnosis of malignant lymphoma (Non-Hodgkin's lymphoma, diffuse large cell type) was made by lymph node biopsy, and radiotherapy to bulky bilateral adrenal tumors and cervical lymph nodes was performed with some response. Then, treatment with VEPA and PEP-VP regimens were carried out, and adrenal tumor became remarkably small in size. However, adrenal function did not recover. He relapsed in Jan. 1987 and died of multiple organ failure.     

Reversible cardiomyopathy associated with Addison's disease

Myocardial involvement in Addison's disease has been described previously. A 36-year-old man presented with cardiomyopathy and was found to have Addison's disease. The patient's myocardial function improved after steroid therapy for Addison's disease. This is the only case report of reversible cardiomyopathy associated with Addison's disease in an adult patient.     

Subclinical vascular disease in patients with diabetes is associated with insulin resistance

Patients with diabetes experience increased cardiovascular risk that is not fully explained by deficient glycemic control or traditional cardiovascular risk factors such as smoking and hypercholesterolemia. Asymptomatic patients with diabetes show structural and functional vascular damage that includes impaired vasodilation, arterial stiffness, increased intima-media thickness and calcification of the arterial wall. Subclinical vascular injury associated with diabetes predicts subsequent manifestations of cardiovascular disease, such as ischemic heart disease, peripheral artery disease and stroke. Noninvasive detection of subclinical vascular disease is commonly used to estimate cardiovascular risk associated to diabetes. Longitudinal studies in normotensive subjects show that arterial stiffness at baseline is associated with a greater risk for future hypertension independently of established risk factors. In patients with type 2 diabetes, vascular disease begins to develop during the latent phase of insulin resistance, long before the clinical diagnosis of diabetes. In contrast, patients with type 1 diabetes do not manifest vascular injury when they are first diagnosed due to insulin deficiency, as they lack the preceding period of insulin resistance. These findings suggest that insulin resistance plays an important role in the development of early vascular disease associated with diabetes. Cross-sectional and prospective studies confirm that insulin resistance is associated with subclinical vascular injury in patients with diabetes, independently of standard cardiovascular risk factors. Asymptomatic vascular disease associated with diabetes begins to occur early in life having been documented in children and adolescents. Insulin resistance should be considered a therapeutic target in order to prevent the vascular complications associated with diabetes.     

Erythrocyte insulin receptors and insulin sensitivity in adrenocortical insufficiency. Report of a case of diabetes mellitus type I with superimposed Addison's disease

Studies on erythrocyte insulin receptors were performed in a boy with type I diabetes mellitus and superimposed adrenocortical insufficiency before and during treatment with hydrocortisone and 9-alpha-fluorohydrocortisone. The development of the adrenal insufficiency was associated with a progressively increased sensitivity to insulin which reverted after therapy. The maximum specific insulin binding of the erythrocytes was low during threatening addisonian crisis (6.9%) but normalized during hydrocortisone treatment (12.0%). These findings suggest that the increased insulin sensitivity characteristic for adrenocortical insufficiency is not an effect of an increased insulin receptor concentration and that hypocortisolaemia is associated with a down-regulation of the insulin receptors.     

Vitamin D receptor genotype is associated with Addison's disease

OBJECTIVE: Autoimmune Addison's disease is a rare disorder which results from the T cell-mediated destruction of adrenocortical cells. A number of genetic susceptibility markers are shared by Addison's disease, type 1 diabetes, Graves' disease and Hashimoto's thyroiditis. The vitamin D endocrine system has been shown to influence immune regulation. Variants of the nuclear vitamin D receptor (VDR) gene were found to be associated with type 1 diabetes and thyroid autoimmunity amongst others. We therefore investigated the role of VDR polymorphisms in Addison's disease. DESIGN AND METHODS: Patients (n=95) and controls (n=220) were genotyped for VDR polymorphisms FokI, BsmI, ApaI and TaqI. RESULTS: The 'ff' (13.7% vs 5.5%; P=0.0243; odds ratio = 2.75) and the 'tt' (28.4% vs 14.1%; P=0.0043; odds ratio = 2.42) genotypes were significantly more frequent in patients than in controls. Furthermore, the BsmI genotype distribution differed significantly between patients and controls (chi(2)=6.5016 (2 d.f.) P=0.0387). CONCLUSIONS: These data suggest that the VDR genotype is associated with Addison's disease. The mechanisms by which distinct receptor variants might confer disease susceptibility remain to be elucidated.     

Microcytosis in Hodgkin disease associated with unbalanced globin chain synthesis

A review of 162 patients with Hodgkin disease disclosed 36 with microcytic anemia (mean corpuscular hemoglobin values [MCV] less than 80 fl). Three patients had iron deficiency, and one had beta-thalassemia. Of the remaining 32 patients, 24 had microcytic anemia at the time of diagnosis of Hodgkin disease, and ten, including two patients with this finding initially, developed microcytic anemia in association with recurrence of Hodgkin disease. Seven patients with Hodgkin disease and normal MCV had normal alpha-to-beta-globin chain ratios (1.0 +/- 0.14). Seven patients with Hodgkin disease and MCV less than 80 fl had significantly lower alpha-to-beta chain ratios (0.66 +/- 0.05). Twelve normal controls and four with iron-deficiency anemia and MCV less than 80 fl had normal ratios. Anemia was corrected, and MCV returned to normal in all patients who responded to therapy for Hodgkin disease. In the two patients studied sequentially, abnormal alpha-to-beta-chain ratio was corrected along with the anemia.     

Screening for associated autoimmune disorders in Polish patients with Addison's disease

Autoimmune Addison's disease (AAD) is the main reason of primary adrenal failure. More than a half of patients display additional autoimmune conditions, which represent a considerable clinical concern. This study aimed to investigate the prevalence of concomitant autoimmune disorders in 85 Polish AAD patients (61 females, 24 males). Mean age at AAD onset was 34.6 ± 12.6 years, significantly earlier in males (P < 0.001). Sixty-nine patients presented positive serum antibodies to 21-hydroxylase and shorter AAD duration than those with negative results (P = 0.027). Seventy-three subjects suffered from coexisting autoimmune disorders. Serum autoantibodies against thyreoperoxidase, thyroglobulin, TSH receptor, glutamic acid decarboxylase, insulin, tyrosine phosphatase-like protein IA2, parietal cell H(+)/K(+)-ATPase, intrinsic factor and tissue transglutaminase were detectable in 71.8, 41.2, 4.7, 21.0, 4.9, 2.5, 49.4, 12.0 and 3.5% of patients, respectively. Antinuclear antibodies were found in 12.5%. Thyroid autoimmunity was most common (46 subjects with lymphocytic thyroiditis, 19 with Graves' disease), followed by atrophic gastritis (29.4%), pernicious anaemia (11.8%), hypergonadotropic hypogonadism (8.2%), vitiligo (8.2%), type 1 diabetes (7.1%), celiac disease (3.5%) and alopecia (2.4%). Gender differences were observed only for thyroid autoimmunity. Current study confirms particular tendency of AAD patients to develop other autoimmune disorders. Active search for concomitant conditions is warranted to prevent serious complications.