Dataset Information

Natural History of Adrenal Steroidogenesis in Autoimmune Addison's Disease Following Diagnosis and Treatment.

ABSTRACT:

Context

The natural history of adrenal function in autoimmune Addison disease once diagnosed and treated has not been systematically studied, but several case reports of recovery from established adrenal failure suggest it may not be uniform.

Objective

To ascertain steroidogenic function in autoimmune Addison disease immediately following diagnosis and during prolonged treatment.

Design

We studied peak serum cortisol in response to ACTH1-24 in 20 newly diagnosed autoimmune Addison disease patients at first presentation and then again within a month. We also studied 37 patients with established Addison disease (for between 7 months and 44 years) in a medication-free state, measuring peak serum cortisol responses to ACTH1-24 and the urine LC-MS steroid metabolome.

Results

Adrenal steroidogenesis declined rapidly after steroid replacement treatment for newly diagnosed Addison disease was started, with a peak serum cortisol falling from 138 ± 19 nmol/L (SEM) at presentation to 63 ± 13 nmol/L over 4 weeks (P < 0.003).Six of 37 participants (16%) with established Addison disease had detectable serum cortisol and urine glucocorticoid and mineralocorticoid metabolites during repeat testing, indicating variable degrees of residual adrenal function.

Conclusion

Autoimmune Addison disease is a heterogeneous condition, showing a rapid decline in adrenal steroidogenesis during the first few weeks following diagnosis, but low-level residual function in a minority of patients, which appears to persist for many years.

SUBMITTER: Napier C

PROVIDER: S-EPMC7250207 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Publications

Natural History of Adrenal Steroidogenesis in Autoimmune Addison's Disease Following Diagnosis and Treatment.

Napier Catherine C Allinson Kathleen K Gan Earn H EH Mitchell Anna L AL Gilligan Lorna C LC Taylor Angela E AE Arlt Wiebke W Pearce Simon H S SHS

The Journal of clinical endocrinology and metabolism 20200701 7

<h4>Context</h4>The natural history of adrenal function in autoimmune Addison disease once diagnosed and treated has not been systematically studied, but several case reports of recovery from established adrenal failure suggest it may not be uniform.<h4>Objective</h4>To ascertain steroidogenic function in autoimmune Addison disease immediately following diagnosis and during prolonged treatment.<h4>Design</h4>We studied peak serum cortisol in response to ACTH1-24 in 20 newly diagnosed autoimmune ...[more]

PMID: 32300791

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Project description: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.

Project description:Objective Patients with adrenal insufficiency (AI) need to adapt their glucocorticoid replacement under stressful conditions to prevent adrenal crisis (AC). Prednisone (PN) suppositories are used for emergency treatment. Pharmacokinetics of 100 mg PN suppositories after vaginal or rectal administration was evaluated. Design Single-center, open-label, sequence-randomized, cross-over, bioequivalence study. Methods Twelve females with primary AI were included. Comparison of pharmacokinetics after vaginal and rectal administration of 100 mg PN suppositories. Main outcome measures: bioequivalence (Cmax: maximum plasma concentration of prednisolone; AUC0 -360: area under the plasma concentration curve of prednisolone from administration to 360 min), adrenocorticotropin (ACTH) levels, safety and tolerability. Comparison of ACTH-suppressive effect with subcutaneous and intramuscular administration of 100 mg hydrocortisone. Results Vaginal administration of PN suppositories was not bioequivalent to rectal administration: Cmax and AUC0-360 were significantly lower after vaginal compared to rectal administration: 22 ng/mL (109%) vs 161 ng/mL (28%), P < 0.001; 4390 ng/mL * min (116%) vs 40,302 ng/mL * min (26%), P < 0.001; (mean (coefficient of variation), respectively). A suppression of ACTH by >50% of baseline values was observed 149 min (32%) after rectal PN administration; after vaginal PN administration, the maximum decrease within 360 min was only 44%. Adverse events were more frequent after vaginal administration and mainly attributable to the glucocorticoid deficit due to inadequate vaginal absorption. The ACTH-suppressive effect was more pronounced after parenteral hydrocortisone compared to rectal or vaginal PN. Conclusion Vaginal administration of PN suppositories in the available form is not useful for prevention of AC. Pharmacokinetics after rectal use of PN show inferiority compared to available data on parenteral glucocorticoids. In adrenal emergencies, hydrocortisone injection should be the first choice.

Project description:BackgroundKnowledge of the effect of kidney transplantation on bone is limited and fragmentary. The aim of this study was to characterize the evolution of bone disease in the first post-transplant year.MethodsWe performed a prospective, observational cohort study in patients referred for kidney transplantation under a steroid-sparing immunosuppressive protocol. Bone phenotyping was done before, or at the time of, kidney transplantation, and repeated at 12 months post-transplant. The phenotyping included bone histomorphometry, bone densitometry by dual-energy x-ray absorptiometry, and biochemical parameters of bone and mineral metabolism.ResultsPaired data were obtained for 97 patients (median age 55 years; 72% male; 21% of patients had diabetes). Bone turnover remained normal or improved in the majority of patients (65%). Bone histomorphometry revealed decreases in bone resorption (eroded perimeter, mean 4.6% pre- to 2.3% post-transplant; P<0.001) and disordered bone formation (fibrosis, 27% pre- versus 2% post-transplant; P<0.001). Whereas bone mineralization was normal in all but one patient pretransplant, delayed mineralization was seen in 15% of patients at 1 year post-transplant. Hypophosphatemia was associated with deterioration in histomorphometric parameters of bone mineralization. Changes in bone mineral density were highly variable, ranging from -18% to +17% per year. Cumulative steroid dose was related to bone loss at the hip, whereas resolution of hyperparathyroidism was related to bone gain at both spine and hip.ConclusionsChanges in bone turnover, mineralization, and volume post-transplant are related both to steroid exposure and ongoing disturbances of mineral metabolism. Optimal control of mineral metabolism may be key to improving bone quality in kidney transplant recipients.Clinical trial registry name and registration numberEvolution of Bone Histomorphometry and Vascular Calcification Before and After Renal Transplantation, NCT01886950.

Dataset Information

Natural History of Adrenal Steroidogenesis in Autoimmune Addison's Disease Following Diagnosis and Treatment.

Context

Objective

Design

Results

Conclusion

Publications

Natural History of Adrenal Steroidogenesis in Autoimmune Addison's Disease Following Diagnosis and Treatment.

Similar Datasets

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