The natural history of adrenal function in autoimmune patients with adrenal autoantibodies

The antiphospholipid syndrome is characterized by clinical evidence of arterial or venous thrombosis, thrombocytopaenia, recurrent fetal loss and repeated positivity of antiphospholipid autoantibodies. The association of antiphospholipid syndrome with the development of adrenal failure has been reported in more than 40 patients in the last 20 years, mostly due to bilateral cortical haemorrhage or thrombosis of adrenal vessels. The presence of antibodies against adrenal cortex was never documented in these patients. Here we report a case of recurrent thrombophlebitis, acute adrenal failure, and chronic hepatitis occurring in a young man found to have antiphospholipid antibodies and lupus anticoagulant. Autoantibodies against adrenal cortex were detected and abdominal ultrasonography showed morphologically normal adrenals. Mild thrombocytopaenia, Coomb's positive anaemia, increase in alanine-and aspartate-aminotransferases and increase in urinary protein excretion were found. Autoantibodies against liver/kidney microsomes were positive and liver biopsy was compatible with autoimmune hepatitis. The patient was treated with cortisone acetate, fludrocortisone and warfarin. Dilated cardiomyopathy was revealed one year later and coronarography did not document any occlusive coronary disease. Three years later, titres of autoantibodies, including those directed towards the adrenal cortex, were increased and others, previously absent, were detected. Nevertheless, the patient's clinical conditions seemed unchanged. At this time, an abdominal CT scan showed adrenal dysmorphisms with bilateral annular calcifications and central hypodensities suggesting previous bilateral adrenal haematomas. The hypercoagulable state that occurs in antiphospholipid syndrome can induce a localized inflammatory response generated by tissue injury, with a consequent release of intracellular antigens and antibodies production. Consequently, tissue-specific autoantibodies positivity may persist until the cells involved in antigen production are completely destroyed.

Section: European Journal Of Endocrinology (1998) 139mentioning

confidence: 73%

“…ACA are regarded as sensitive markers of the autoimmune form of adrenal failure (6,14). Although their role in the primary pathogenic response is unclear, it is likely that they arise as a consequence of T-cell-mediated tissue damage, which seems to be a major event in the pathogenesis of adrenal failure.…”

Section: European Journal Of Endocrinology (1998) 139mentioning

confidence: 99%

Antiphospholipid syndrome, adrenal failure, dilated cardiomyopathy and chronic hepatitis: an unusual manifestation of multiorgan autoimmune injury?

Tauchmanovà¹,

Rossi²,

Coppola³

et al. 1998

“…ACA were detected by the classical indirect immunofluorescence technique, using thin cryostatic sections of normal human adrenal glands, as previously reported (17). Results of StCA and ACA were reported as positive or negative compared with control sera (i.e.…”

Section: Autoantibodiesmentioning

confidence: 76%

Autoantibodies to steroidogenic enzymes in patients with premature ovarian failure with and without Addison's disease

Prà

Chen²,

Furmaniak³

et al. 2003

Design: Adrenal cortex autoantibodies (ACA), steroid-producing cell autoantibodies (StCA) and autoantibodies (Abs) to steroidogenic enzymes in three groups of patients with premature ovarian failure (POF), 15 with autoimmune Addison's disease (AD), 26 with non-adrenal autoimmune diseases and 31 with isolated POF, have been assessed. Methods: ACA and StCA were measured using an immunofluorescence technique. Abs to 21-hydroxylase (21-OH), to 17a-hydroxylase (17a-OH) and to cytochrome P450 side-chain cleavage (P450scc) were measured using an immunoprecipitation assay. Results: Seventy-three percent of patients with POF and AD were positive for StCA, 93% for 17a-OH and/or P450scc Abs, 93% for ACA and 100% for 21-OH Abs. Among patients with POF and nonadrenal autoimmune diseases, 8% were positive for StCA, 12% for 17a-OH and/or P450scc Abs, and 8% and 12% for ACA and 21-OH Abs respectively. StCA, 17a-OH and/or P450scc Abs were all found in 10% of patients with isolated POF, and 13% had ACA and 21-OH Abs. All StCA-, 17a-OH-and/or P450scc Abs-positive patients were also positive for ACA and 21-OH Abs. Two patients with isolated POF who were ACA and 21-OH Ab positive developed AD 3 and 5 years after the onset of POF. Conclusion: This study has shown that, when POF is associated with AD, StCA, 17a-OH and/or P450scc Abs are present in the majority of patients, while in the other two groups these Abs are detectable in a much lower proportion of patients. Measurement of ACA/21-OH Abs in some patients with POF may be important in identifying patients at risk of developing overt AD.

“…Patients with APS type I and type II were classified using the criteria for APS as described elsewhere (1). Adrenal cortex Abs (ACA) were detected by the classical indirect immunofluorescence technique using thin cryostatic sections of normal human adrenal glands, and steroid-producing cell Abs (StCA) were detected by a complement-fixing indirect immunofluorescence technique using normal human testis as described previously (8,9). Autoantibodies to steroid 21-hydroxylase (21-OH) were measured using a diagnostic kit based on 125 I-labelled recombinant human 21-OH (RSR Ltd, Cardiff, UK) (10).…”

Section: Patientsmentioning

confidence: 99%

Autoantibodies to human tryptophan hydroxylase and aromatic L-amino acid decarboxylase

Prà

Chen

Betterle

et al. 2004

Objective: To assess the prevalence of autoantibodies (Abs) to tryptophan hydroxylase (TPH) and aromatic L-amino acid decarboxylase (AADC) in patients with different autoimmune diseases and to analyse their respective epitopes. Design: TPH and AADC Abs were measured in an immunoprecipitation assay using 35 S-labelled fulllength and fragments of TPH and AADC. Methods: Patients with different autoimmune adrenal diseases (n ¼ 84), non-adrenal autoimmune diseases (n ¼ 37), idiopathic vitiligo (n ¼ 8) and 56 healthy blood donors were studied. Results: Fourteen of twenty-three (61%) of patients with autoimmune polyglandular syndrome (APS) type I and 1/34 (3%) of patients with isolated Addison's disease (AD) were positive for TPH Abs. None of the patients with APS type II (n ¼ 27), coeliac disease (n ¼ 10), autoimmune thyroid disease (AITD) (n ¼ 11), type 1 diabetes mellitus (DM) (n ¼ 16) or idiopathic vitiligo (n ¼ 8) was positive for TPH Abs. AADC Abs were detected in 12/23 (52%) patients with APS type I, in 1/29 (3%) patients with APS type II and 1/34 (3%) patients with isolated AD. None of the patients with coeliac disease, type 1 DM, AITD or idiopathic vitiligo was positive for AADC Abs. TPH Abs were found to interact with the C-terminal amino acids (aa) 308-423, central aa 164 -205 and N-terminal aa 1-105 of the TPH molecule. AADC Ab binding epitopes were within the C-terminal aa 382-483, the central aa 243 -381 and the N-terminal aa 1-167. Conclusions: Our study suggests that TPH Abs and AADC Abs react with several different epitopes and that different epitopes are recognized by different sera. The prevalence of TPH Abs and AADC Abs in patients with APS type I in our study is in agreement with previous reports. TPH Abs and AADC Abs were found very rarely in patients with other forms of autoimmune adrenal disease and were not detected in patients with non-adrenal autoimmune diseases.European Journal of Endocrinology 150 313-321