TY  - JOUR
A1  - Nowotny, Hanna
A1  - Ahmed, S. Faisal
A1  - Bensing, Sophie
A1  - Beun, Johan G.
A1  - Brösamle, Manuela
A1  - Chifu, Irina
A1  - Claahsen van der Grinten, Hedi
A1  - Clemente, Maria
A1  - Falhammar, Henrik
A1  - Hahner, Stefanie
A1  - Husebye, Eystein
A1  - Kristensen, Jette
A1  - Loli, Paola
A1  - Lajic, Svetlana
A1  - Reisch, Nicole
T1  - Therapy options for adrenal insufficiency and recommendations for the management of adrenal crisis
JF  - Endocrine
N2  - Adrenal insufficiency (AI) is a life-threatening condition requiring life-long glucocorticoid (GC) substitution therapy, as well as stress adaptation to prevent adrenal crises. The number of individuals with primary and secondary adrenal insufficiency in Europe is estimated to be 20–50/100.000. A growing number of AI cases are due to side effects of GC treatment used in different treatment strategies for cancer and to immunotherapy in cancer treatment. The benefit of hormone replacement therapy is evident but long-term adverse effects may arise due to the non-physiological GC doses and treatment regimens used. Given multiple GC replacement formulations available comprising short-acting, intermediate, long-acting and novel modified-release hydrocortisone as well as subcutaneous formulations, this review offers a concise summary on the latest therapeutic improvements for treatment of AI and prevention of adrenal crises. As availability of various glucocorticoid formulations and access to expert centers across Europe varies widely, European Reference Networks on rare endocrine conditions aim at harmonizing treatment and ensure access to specialized patient care for individual case-by-case treatment decisions. To improve the availability across Europe to cost effective oral and parenteral formulations of hydrocortisone will save lives.
KW  - adrenal insufficiency
KW  - congenital adrenal hyperplasia
KW  - adrenal crisis
KW  - glucocorticoid replacement
KW  - hydrocortisone
KW  - stress instructions
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-308769
SN  - 1355-008X
SN  - 1559-0100
VL  - 71
IS  - 3
ER  - 
TY  - JOUR
A1  - Mitchell, Anna L.
A1  - Macarthur, Katie D. R.
A1  - Gan, Earn H.
A1  - Baggott, Lucy E.
A1  - Wolff, Anette S. B.
A1  - Skinningsrud, Beate
A1  - Platt, Hazel
A1  - Short, Andrea
A1  - Lobell, Anna
A1  - Kampe, Olle
A1  - Bensing, Sophie
A1  - Betterle, Corrado
A1  - Kasperlik-Zaluska, Anna
A1  - Zurawek, Magdalena
A1  - Fichna, Marta
A1  - Kockum, Ingrid
A1  - Eriksson, Gabriel Nordling
A1  - Ekwall, Olov
A1  - Wahlberg, Jeanette
A1  - Dahlqvist, Per
A1  - Hulting, Anna-Lena
A1  - Penna-Martinez, Marissa
A1  - Meyer, Gesine
A1  - Kahles, Heinrich
A1  - Badenhoop, Klaus
A1  - Hahner, Stephanie
A1  - Quinkler, Marcus
A1  - Falorni, Alberto
A1  - Phipps-Green, Amanda
A1  - Merriman, Tony R.
A1  - Ollier, William
A1  - Cordell, Heather J.
A1  - Undlien, Dag
A1  - Czarnocka, Barbara
A1  - Husebye, Eystein
A1  - Pearce, Simon H. S.
T1  - Association of Autoimmune Addison's Disease with Alleles of STAT4 and GATA3 in European Cohorts
JF  - PLOS ONE
N2  - Background: Gene variants known to contribute to Autoimmune Addison's disease (AAD) susceptibility include those at the MHC, MICA, CIITA, CTLA4, PTPN22, CYP27B1, NLRP-1 and CD274 loci. The majority of the genetic component to disease susceptibility has yet to be accounted for. 
Aim: To investigate the role of 19 candidate genes in AAD susceptibility in six European case-control cohorts. 
Methods: A sequential association study design was employed with genotyping using Sequenom iPlex technology. In phase one, 85 SNPs in 19 genes were genotyped in UK and Norwegian AAD cohorts (691 AAD, 715 controls). In phase two, 21 SNPs in 11 genes were genotyped in German, Swedish, Italian and Polish cohorts (1264 AAD, 1221 controls). In phase three, to explore association of GATA3 polymorphisms with AAD and to determine if this association extended to other autoimmune conditions, 15 SNPs in GATA3 were studied in UK and Norwegian AAD cohorts, 1195 type 1 diabetes patients from Norway, 650 rheumatoid arthritis patients from New Zealand and in 283 UK Graves' disease patients. Meta-analysis was used to compare genotype frequencies between the participating centres, allowing for heterogeneity. 
Results: We report significant association with alleles of two STAT4 markers in AAD cohorts (rs4274624: P = 0.00016; rs10931481: P = 0.0007). In addition, nominal association of AAD with alleles at GATA3 was found in 3 patient cohorts and supported by meta-analysis. Association of AAD with CYP27B1 alleles was also confirmed, which replicates previous published data. Finally, nominal association was found at SNPs in both the NF-kappa B1 and IL23A genes in the UK and Italian cohorts respectively. 
Conclusions: Variants in the STAT4 gene, previously associated with other autoimmune conditions, confer susceptibility to AAD. Additionally, we report association of GATA3 variants with AAD: this adds to the recent report of association of GATA3 variants with rheumatoid arthritis.
KW  - Graves disease
KW  - identical twins
KW  - hashimotos-thyroiditis
KW  - population
KW  - gene
KW  - polymorphism
KW  - susceptibility
KW  - prevalence
KW  - haplotype
KW  - rheumatoid arthritis
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117105
VL  - 9
IS  - 3
ER  -