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

1988 ◽  
Vol 117 (3) ◽  
pp. 467-475 ◽  
Author(s):  
C. Betterle ◽  
C. Scalici ◽  
F. Presotto ◽  
B. Pedini ◽  
L. Moro ◽  
...  
Keyword(s):  
Addison’S Disease ◽  
Plasma Renin ◽  
Autoimmune Disorder ◽  
Adrenal Function ◽  
Adrenocortical Function ◽  
Diabetic Patients ◽  
Addison's Disease ◽  
Gonadal Dysfunction ◽  
Insulin Dependent Diabetic ◽  
Low Cortisol

ABSTRACT Adrenal autoantibodies (AA) were found in 23 of 2571 (0·9%) patients with organ-specific autoimmune diseases, in one of 632 first-degree relatives of insulin-dependent diabetic patients, and in none of 375 normal controls. In AA-positive subjects the prevalence of human leucocyte antigens (HLA)-A1, -B8 and -DR3 was significantly higher with respect to the general population. Two groups were followed (15 subjects persistently positive for AA and 51 negative subjects) for a mean period of 3·2 years. Yearly tests were made for AA and adrenal function. Of the 15 subjects persistently positive for AA, six developed Addison's disease after a period varying from 6 months to 10 years. Of the 51 subjects initially negative, two became positive during follow-up, and one of these developed Addison's disease 16 months later. In contrast, all the remaining 49 persistently negative subjects maintained normal adrenal function tests. Overall, of the 17 positive subjects, seven (41%) developed Addison's disease, three (18%) showed various degrees of subclinical adrenocortical failure and the remaining seven maintained normal glandular function. In the positive patients the yearly incidence of detriment in adrenal function was 19%. Patients who developed Addison's disease showed significant association with HLA-B8 phenotype. The development from normal adrenocortical function to overt Addison's disease seemed to progress through four distinct stages of functional impairment: increased plasma renin activity with normal/low aldosterone (stage 1), low cortisol response after i.v. administration of ACTH (stage 2), increased ACTH (stage 3), and low basal cortisol (stage 4). Thus, idiopathic Addison's disease appears to be a chronic autoimmune disorder with a genetic predisposition and a long preclinical period marked by the presence of AA. Steroid-producing cell antibodies were also evaluated but they were not found to be markers of gonadal dysfunction. J. Endocr. (1988) 117, 467–475

Residual adrenocortical function in autoimmune addison's disease: interim results of a cross-sectional study

2019 ◽  
Author(s):  
AEse Bjorvatn Saevik ◽  
Anna-Karin AEkermann ◽  
Paal Methlie ◽  
Nedrebo Bjorn Gunnar ◽  
Anne Lise Dahle ◽  
...  
Keyword(s):  
Addison’S Disease ◽  
Cross Sectional Study ◽  
Adrenocortical Function ◽  
Addison's Disease ◽  
Sectional Study ◽  
Cross Sectional

scholarly journals Residual Adrenal Function in Autoimmune Addison’s Disease—Effect of Dual Therapy With Rituximab and Depot Tetracosactide

2019 ◽  
Vol 105 (4) ◽  
pp. e1250-e1259 ◽  
Author(s):  
Catherine Napier ◽  
Earn H Gan ◽  
Anna L Mitchell ◽  
Lorna C Gilligan ◽  
D Aled Rees ◽  
...  
Keyword(s):  
B Lymphocyte ◽  
Outcome Measure ◽  
Combined Treatment ◽  
Addison’S Disease ◽  
Dual Therapy ◽  
Adrenal Function ◽  
Gas Chromatography Mass Spectrometry ◽  
Addison's Disease ◽  
Open Label ◽  
Main Outcome Measure

Abstract Context In autoimmune Addison’s disease (AAD), exogenous glucocorticoid (GC) therapy is an imperfect substitute for physiological GC secretion. Patients on long-term steroid replacement have increased morbidity, reduced life expectancy, and poorer quality of life. Objective The objective of this article is to restore adrenocortical steroidogenic function in recent-onset AAD. Design An open-label, multicenter trial of immunotherapy and trophic stimulation in new-onset AAD was conducted. Serial measurement of serum and urine corticosteroids at baseline and throughout a 72-week follow-up period was performed. Setting This study was conducted at the endocrine departments and clinical research facilities at 5 UK tertiary centers. Patients Thirteen participants (9 female, 4 male; age 19-64 years) were included with AAD confirmed by high adrenocorticotropin, low circulating cortisol (basal < 100 nmol/L or post-tetracosactide < 300 nmol/L), and positive serum 21-hydroxylase antibodies. Intervention All participants received dual therapy with B-lymphocyte–depleting immunotherapy (rituximab 1 g given twice) and repeated depot tetracosactide (1 mg on alternate days for 12 weeks). Main Outcome Measure Restoration of normal GC secretion (stimulated cortisol > 550 nmol/L) at week 48 was the main outcome measure. Results Ten of 13 (77%) participants had detectable stimulated serum cortisol (26-265 nmol/L) at trial entry. Following intervention, 7 of 13 (54%) had an increase in stimulated cortisol measurement, with a peak response of 325 nmol/L at week 18 in 1 participant. Increased steroid metabolites, assayed by urine gas chromatography–mass spectrometry at week 12 and week 48, was detected in 8 of 13 (62%) individuals, reflecting an increase in endogenous steroidogenesis. Four of 13 had residual adrenal function at 72 weeks. Conclusion Combined treatment with rituximab and depot tetracosactide did not restore normal adrenal function. Nevertheless, adrenocortical plasticity is demonstrated in some patients, and this has the potential to be exploited to improve adrenal function.

scholarly journals Addison’s Disease Presenting with Cerebral Edema

1996 ◽  
Vol 23 (2) ◽  
pp. 141-144 ◽  
Author(s):  
Caroline Geenen ◽  
Ingrid Tein ◽  
Robert M. Ehrlich
Keyword(s):  
Cerebral Edema ◽  
Addison’S Disease ◽  
Plasma Renin ◽  
Urine Osmolality ◽  
Early Morning ◽  
Unknown Etiology ◽  
Addison's Disease ◽  
Acth Stimulation ◽  
Serum Acth

ABSTRACT:Background: Increased intracranial pressure with encephalopathy has rarely been reported in Addison’s disease. Method: Case Study. Results: A 16-year-old female who presented with cerebral edema of unknown etiology was eventually diagnosed as having Addison’s disease. She had early morning headaches, fatiguability, diarrhea and deterioration in school performance. She was hyponatremic with a serum sodium of 128 mmol/L and hyperkalemic with a serum potassium of 5.9 mmol/L. She had a low serum osmolality (264 mosm), high urine osmolality (533 mosm) and high urine sodium (87 mosm). She had a postural drop in blood pressure and diffuse hyperpigmentation. An ACTH stimulation test revealed a low baseline Cortisol and no response to ACTH. Plasma renin activity was increased. Serum ACTH was elevated. She responded well to intravenous fluids and solu-cortef and was discharged on hydrocortisone and florinef. She remains well 18 months after the acute episode with no neurologic complaints or findings. Conclusion: Addison’s Disease should be considered in the differential diagnosis of symptomatic cerebral edema and idiopathic intracranial hypertension.

scholarly journals Residual Adrenal Function in Autoimmune Addison's Disease: Improvement After Tetracosactide (ACTH1–24) Treatment

2014 ◽  
Vol 99 (1) ◽  
pp. 111-118 ◽  
Author(s):  
Earn H. Gan ◽  
Katie MacArthur ◽  
Anna L. Mitchell ◽  
Beverly A. Hughes ◽  
Petros Perros ◽  
...  
Keyword(s):  
Addison’S Disease ◽  
Adrenal Function ◽  
Addison's Disease

scholarly journals Estimated Risk for Developing Autoimmune Addison’s Disease in Patients with Adrenal Cortex Autoantibodies

2006 ◽  
Vol 91 (5) ◽  
pp. 1637-1645 ◽  
Author(s):  
Graziella Coco ◽  
Chiara Dal Pra ◽  
Fabio Presotto ◽  
Maria Paola Albergoni ◽  
Cristina Canova ◽  
...  
Keyword(s):  
Adrenal Cortex ◽  
Cox Model ◽  
Cumulative Risk ◽  
Human Leukocyte ◽  
Addison’S Disease ◽  
Adrenal Function ◽  
Addison's Disease ◽  
Risk Algorithm ◽  
Functional Factors ◽  
Estimated Risk

Context: Patients with adrenal cortex autoantibodies (ACA) without overt autoimmune Addison’s disease (AAD) are at risk of adrenal failure. Design: To assess the contribution of different clinical, immunological, genetic, and functional factors in the progression to AAD, we followed up 100 ACA-positive and 63 ACA-negative patients without AAD for a maximum of 21 yr (mean 6.0 yr, median 4.8). ACA were measured by immunofluorescence and 21-OH autoantibodies (Abs) by RIA. Adrenal function was assessed by measuring basal levels of cortisol, aldosterone, ACTH, renin activity, and cortisol response to ACTH. The risk of developing AAD was calculated using survival and multivariate analyses. Results: AAD developed in 31 ACA-positive patients and one ACA-negative patient. The cumulative risk of disease in ACA-positive patients was 48.5% [95% confidence interval (CI) 40.8–56.1]. The cumulative risk was higher in children than adults (100 vs. 31.9%; P < 0.0001), males than females (68.6 vs. 42.7%; P = 0.006), patients with subclinical rather than normal adrenal function at entry (87.4 vs. 30.1%; P < 0.0001), patients with hypoparathyroidism and/or candidiasis than patients with other autoimmune or nonautoimmune diseases (100 vs. 29.7%; P < 0.0001), and patients with high rather than low-medium ACA titers (62.8 vs. 41.2%; P = 0.12). The presence of human leukocyte antigen (HLA)-DRB1 did not appear to contribute to the prediction of AAD. Adjusted hazard ratios by Cox model for the development of AAD were 3.37 for males (CI 1.38–8.24), 5.23 for hypoparathyroidism and/or candidiasis (CI 1.53–17.92), 3.33 for high antibody titers (CI 1.43–7.78), and 6.15 for impaired adrenal function at entry (CI 2.79–13.57). Conclusions: These results were used to construct a risk algorithm for estimating the probability of developing AAD from the combination of gender, age, adrenal function, antibody titer, and associated autoimmune disorders at entry. The values of estimated risk could be used to decide appropriate follow-up intervals and future immunointervention strategies.

The natural history of autoimmune Addison’s disease with a non-classical presentation: a case report and review of literature

2018 ◽  
Vol 56 (6) ◽  
pp. 896-900 ◽  
Author(s):  
Jacopo Manso ◽  
Raffaele Pezzani ◽  
Riccardo Scarpa ◽  
Nicoletta Gallo ◽  
Corrado Betterle
Keyword(s):  
Natural History ◽  
Adrenal Cortex ◽  
Clinical Manifestations ◽  
Addison’S Disease ◽  
Plasma Renin ◽  
Dehydroepiandrosterone Sulfate ◽  
Addison's Disease ◽  
Acth Stimulation ◽  
Basal Cortisol ◽  
History Of

Abstract Autoimmune Addison’s disease (AAD) is the most frequent cause of adrenocortical insufficiency. The natural history of AAD usually comprises five consecutive stages with the first stage characterized by the increase of plasma renin consistent with the impairment of pars glomerulosa, which is usually the first affected layer of the adrenal cortex. We describe a 19-year-old female with Hashimoto’s thyroiditis (HT) who underwent an autoantibody screening due to having the personal and family history of other autoimmune diseases in the absence of relevant clinical manifestations. She was positive for adrenal cortex autoantibodies (ACA) and steroid 21-hydroxylase autoantibodies (21-OH Ab) at high titers. She had increased basal levels of ACTH with normal basal cortisol not responding to ACTH stimulation, reduced levels of dehydroepiandrosterone-sulfate but normal levels of orthostatic renin and aldosterone. This scenario was consistent with a subclinical AAD presenting with first impairments in pars fasciculata and reticularis and conserved pars glomerulosa function. Only subsequently, progressive deficiency in pars glomerulosa function has become evident. Review of the literature showed that there was only one case, reported to date, with a similar atypical natural history of AAD. The strategies for screening for ACA/21-OH Ab in patients with HT are discussed.

Postnatal adrenocortical function of the infant born to a mother with treated Addison's disease

1984 ◽  
Vol 104 (4_Supplb) ◽  
pp. S116-S117
Author(s):  
I. HENRICHS ◽  
J. HOMOKI ◽  
M. KÖLLE-FRICK
Keyword(s):  
Addison’S Disease ◽  
Adrenocortical Function ◽  
Addison's Disease
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