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      MANAGEMENT OF ENDOCRINE DISEASE: Residual adrenal function in Addison’s disease

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      Author(s): 1 , 2 , 1 , 2 , 2
      Publication date (Electronic):
      Journal: European Journal of Endocrinology
      Publisher: Bioscientifica Ltd

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          Abstract

          Over the last 10 years, evidence has accumulated that autoimmune Addison’s disease (AAD) is a heterogeneous disease. Residual adrenal function, characterised by persistent secretion of cortisol, other glucocorticoids and mineralocorticoids is present in around 30% of patients with established AAD, and appears commoner in men. This persistent steroidogenesis is present in some patients with AAD for more than 20 years, but it is commoner in people with shorter disease duration. The clinical significance of residual adrenal function is not fully clear at the moment, but as it signifies an intact adrenocortical stem cell population, it opens up the possibility of regeneration of adrenal steroidogenesis and improvement in adrenal failure for some patients.

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          Clinical, immunological, and genetic features of autoimmune primary adrenal insufficiency: observations from a Norwegian registry.

          Martina M. Erichsen, Kristian Løvås, Beate Skinningsrud … (2009)
          Primary adrenal insufficiency [Addison's disease (AD)] is rare, and systematic studies are few, mostly conducted on small patient samples. We aimed to determine the clinical, immunological, and genetic features of a national registry-based cohort. Patients with AD identified through a nationwide search of diagnosis registries were invited to participate in a survey of clinical features, health-related quality of life (HRQoL), autoantibody assays, and human leukocyte antigen (HLA) class II typing. Of 664 registered patients, 64% participated in the study. The prevalence of autoimmune or idiopathic AD in Norway was 144 per million, and the incidence was 0.44 per 100,000 per year (1993-2007). Familial disease was reported by 10% and autoimmune comorbidity by 66%. Thyroid disease was most common (47%), followed by type 1 diabetes (12%), vitiligo (11%), vitamin B12 deficiency (10%), and premature ovarian insufficiency (6.6% of women). The mean daily treatment for AD was 40.5 mg cortisone acetate and 0.1 mg fludrocortisone. The mean Short Form 36 vitality scores were significantly diminished from the norm (51 vs. 60), especially among those with diabetes. Concomitant thyroid autoimmunity did not lower scores. Anti-21-hydroxylase antibodies were found in 86%. Particularly strong susceptibility for AD was found for the DR3-DQ2/ DRB1*0404-DQ8 genotype (odds ratio, 32; P = 4 x 10(-17)), which predicted early onset. AD is almost exclusively autoimmune, with high autoimmune comorbidity. Both anti-21-hydroxylase antibodies and HLA class II can be clinically relevant predictors of AD. HRQoL is reduced, especially among diabetes patients, whereas thyroid disease did not have an impact on HRQoL. Treatment modalities that improve HRQoL are needed.
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            Effect of intensive therapy on residual beta-cell function in patients with type 1 diabetes in the diabetes control and complications trial. A randomized, controlled trial. The Diabetes Control and Complications Trial Research Group.

            DS Group (1998)
            Although insulin secretion is severely decreased in most patients with type 1 diabetes, levels of residual insulin secretion often vary early in the disease. The significance of residual insulin secretion with regard to metabolic control and to long-term complications and ways to preserve such secretion are not well understood. To compare the effects of intensive and conventional therapy on residual insulin secretion in Diabetes Control and Complications Trial (DCCT) participants. Multicenter, randomized, controlled clinical trial. 29 DCCT clinical centers. 855 of the 1441 DCCT participants had had type 1 diabetes for 1 to 5 years at baseline. Of these 855 patients, 303 were C-peptide responders (C-peptide level, 0.20 to 0.50 pmol/mL after ingestion of a standardized, mixed meal); 138 of these patients were randomly assigned to intensive therapy, and 165 were assigned to conventional therapy. Five hundred fifty-two patients were nonresponders (stimulated C-peptide level < 0.2 pmol/mL); 274 of these patients were assigned to intensive therapy, and 278 were assigned to conventional therapy. 1) Intensive therapy with 3 or more insulin injections daily or continuous subcutaneous infusion of insulin, guided by 4 or more glucose tests per day or 2) conventional therapy with 1 or 2 insulin injections daily. Stimulated C-peptide level was measured annually in responders. Development of retinopathy and microalbuminuria was assessed annually, hemoglobin A1c levels were measured quarterly, and episodes of hypoglycemia were ascertained quarterly. Responders receiving intensive therapy maintained a higher stimulated C-peptide level and a lower likelihood of becoming nonresponders than did responders receiving conventional therapy (risk reduction, 57% [95% CI, 39% to 71%]; P < 0.001). As in the entire DCCT cohort, intensively treated responders had a reduced risk for retinopathy progression and development of microalbuminuria and a higher risk for severe hypoglycemia compared with conventionally treated responders. Among intensively treated patients, responders had a lower hemoglobin A1c value (P < 0.01), a 50% (95% CI, 12% to 72%) reduced risk for retinopathy progression, and a lower risk for severe hypoglycemia (risk reduction, 65% [CI, 53% to 74%]; P < 0.001) compared with nonresponders. Intensive therapy for type 1 diabetes helps sustain endogenous insulin secretion, which, in turn, is associated with better metabolic control and lower risk for hypoglycemia and chronic complications. These observations underscore the importance of initiating intensive diabetic management as early as safely possible after type 1 diabetes is diagnosed.
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              Impact of C-Peptide Preservation on Metabolic and Clinical Outcomes in the Diabetes Control and Complications Trial

              John M. Lachin, Paula Friedenberg McGee, Jerry P. Palmer … (2014)
              The Diabetes Control and Complications Trial established that a stimulated C-peptide concentration ≥0.2 nmol/L at study entry among subjects with up to a 5-year diabetes duration is associated with favorable metabolic and clinical outcomes over the subsequent 7 years of follow-up. Herein we further examine the association of both fasting and stimulated C-peptide numerical values with outcomes. In the intensive treatment group, for a 50% higher stimulated C-peptide on entry, such as from 0.10 to 0.15 nmol/L, HbA1c decreased by 0.07% (0.8 mmol/mol; P = 0.0003), insulin dose decreased by 0.0276 units/kg/day (P < 0.0001), hypoglycemia risk decreased by 8.2% (P < 0.0001), and the risk of sustained retinopathy was reduced by 25% (P = 0.0010), all in unadjusted analyses. Other than HbA1c, these effects remained significant after adjusting for the HbA1c on entry. While C-peptide was not significantly associated with the incidence of nephropathy, it was strongly associated with the albumin excretion rate. The fasting C-peptide had weaker associations with outcomes. As C-peptide decreased to nonmeasurable concentrations, the outcomes changed in a nearly linear manner, with no threshold or breakpoint. While preservation of stimulated C-peptide at ≥0.2 nmol/L has clinically beneficial outcomes, so also does an increase in the concentration of C-peptide across the range of values.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Eur J Endocrinol
                Journal ID (iso-abbrev): Eur J Endocrinol
                Journal ID (hwp): EJE
                Title: European Journal of Endocrinology
                Publisher: Bioscientifica Ltd (Bristol )
                ISSN (Print): 0804-4643
                ISSN (Electronic): 1479-683X
                Publication date Collection: February 2021
                Publication date (Electronic): 08 December 2020
                Volume: 184
                Issue: 2
                Pages: R61-R67
                Affiliations
                [1 ]Translational and Clinical Research Institute , Newcastle University, Newcastle, UK
                [2 ]Endocrine Unit , Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK
                Author notes
                Correspondence should be addressed to S H S Pearce; Email: simon.pearce@ 123456ncl.ac.uk
                Author information
                http://orcid.org/0000-0001-8384-8063
                Article
                Publisher ID: EJE-20-0894
                DOI: 10.1530/EJE-20-0894
                PMC ID: 7849375
                PubMed ID: 33306039
                SO-VID: f5a3f3c9-4d9c-4de6-8db8-2885aca8412a
                Copyright © © 2021 The authors
                License:

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                Date received : 06 August 2020
                Date accepted : 08 December 2020
                Categories
                Subject: Review

                ScienceOpen disciplines: Endocrinology & Diabetes
                Data availability:
                ScienceOpen disciplines: Endocrinology & Diabetes

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