Acquired modification of sphingosine-1-phosphate lyase activity is not related to adrenal insufficiency
Abstract Background Congenital sphingosine-1-phosphate (S1P) lyase deficiency due to biallelic mutations in SGPL1 gene has recently been described in association with primary adrenal insufficiency and steroid-resistant nephrotic syndrome. S1P lyase, on the other hand, is therapeutically inhibited by...
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doaj-bd219541ea214e42ad4d4ea3ea85a1122020-11-25T01:22:19ZengBMCBMC Neurology1471-23772018-04-011811610.1186/s12883-018-1049-9Acquired modification of sphingosine-1-phosphate lyase activity is not related to adrenal insufficiencyGulin Sunter0Ece Oge Enver1Azad Akbarzade2Serap Turan3Pinar Vatansever4Dilek Ince Gunal5Goncagul Haklar6Abdullah Bereket7Kadriye Agan8Tulay Guran9Department of Neurology, Marmara UniversityDepartment of Paediatric Endocrinology and Diabetes, Marmara UniversityDepartment of Paediatric Endocrinology and Diabetes, Marmara UniversityDepartment of Paediatric Endocrinology and Diabetes, Marmara UniversityDepartment of Biochemistry, Marmara UniversityDepartment of Neurology, Marmara UniversityDepartment of Biochemistry, Marmara UniversityDepartment of Paediatric Endocrinology and Diabetes, Marmara UniversityDepartment of Neurology, Marmara UniversityDepartment of Paediatric Endocrinology and Diabetes, Marmara UniversityAbstract Background Congenital sphingosine-1-phosphate (S1P) lyase deficiency due to biallelic mutations in SGPL1 gene has recently been described in association with primary adrenal insufficiency and steroid-resistant nephrotic syndrome. S1P lyase, on the other hand, is therapeutically inhibited by fingolimod which is an oral drug for relapsing multiple sclerosis (MS). Effects of this treatment on adrenal function has not yet been evaluated. We aimed to test adrenal function of MS patients receiving long-term fingolimod treatment. Methods Nineteen patients (14 women) with MS receiving oral fingolimod (Gilenya®, Novartis) therapy were included. Median age was 34.2 years (range; 21.3–44.6 years). Median duration of fingolimod treatment was 32 months (range; 6–52 months) at a dose of 0.5 mg/day. Basal and ACTH-stimulated adrenal steroid measurements were evaluated simultaneously employing LC-MS/MS based steroid panel. Basal steroid concentrations were also compared to that of sex- and age-matched healthy subjects. Cortisol and 11-deoxycortisol, 11-deoxycorticosterone and dehydroepiandrosterone were used to assess glucocorticoid, mineralocorticoid and sex steroid producing pathways, respectively. Results Basal ACTH concentrations of the patients were 20.8 pg/mL (6.8–37.8 pg/mL) (normal range; 5–65 pg/mL). There was no significant difference in the basal concentrations of cortisol, 11-deoxycortisol, 11-deoxycorticosterone and dehydroepiandrosterone between patients and controls (p = 0.11, 0.058, 0.74, 0.15; respectively). All patients showed adequate cortisol response to 250 mcg IV ACTH stimulation (243 ng/mL, range; 197–362 ng/mL). There was no significant correlation between duration of fingolimod treatment and basal or ACTH-stimulated cortisol or change in cortisol concentrations during ACTH stimulation test (p = 0.57, 0.66 and 0.21, respectively). Conclusion Modification and inhibition of S1P lyase activity by the long-term therapeutic use of fingolimod is not associated with adrenal insufficiency in adult patients with MS. This suggests that S1P lyase has potentially a critical role on adrenal development rather than the function of a fully mature adrenal gland.http://link.springer.com/article/10.1186/s12883-018-1049-9Sphingosine-1-phosphate lyaseFingolimodAdrenalMultiple sclerosis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Gulin Sunter Ece Oge Enver Azad Akbarzade Serap Turan Pinar Vatansever Dilek Ince Gunal Goncagul Haklar Abdullah Bereket Kadriye Agan Tulay Guran |
spellingShingle |
Gulin Sunter Ece Oge Enver Azad Akbarzade Serap Turan Pinar Vatansever Dilek Ince Gunal Goncagul Haklar Abdullah Bereket Kadriye Agan Tulay Guran Acquired modification of sphingosine-1-phosphate lyase activity is not related to adrenal insufficiency BMC Neurology Sphingosine-1-phosphate lyase Fingolimod Adrenal Multiple sclerosis |
author_facet |
Gulin Sunter Ece Oge Enver Azad Akbarzade Serap Turan Pinar Vatansever Dilek Ince Gunal Goncagul Haklar Abdullah Bereket Kadriye Agan Tulay Guran |
author_sort |
Gulin Sunter |
title |
Acquired modification of sphingosine-1-phosphate lyase activity is not related to adrenal insufficiency |
title_short |
Acquired modification of sphingosine-1-phosphate lyase activity is not related to adrenal insufficiency |
title_full |
Acquired modification of sphingosine-1-phosphate lyase activity is not related to adrenal insufficiency |
title_fullStr |
Acquired modification of sphingosine-1-phosphate lyase activity is not related to adrenal insufficiency |
title_full_unstemmed |
Acquired modification of sphingosine-1-phosphate lyase activity is not related to adrenal insufficiency |
title_sort |
acquired modification of sphingosine-1-phosphate lyase activity is not related to adrenal insufficiency |
publisher |
BMC |
series |
BMC Neurology |
issn |
1471-2377 |
publishDate |
2018-04-01 |
description |
Abstract Background Congenital sphingosine-1-phosphate (S1P) lyase deficiency due to biallelic mutations in SGPL1 gene has recently been described in association with primary adrenal insufficiency and steroid-resistant nephrotic syndrome. S1P lyase, on the other hand, is therapeutically inhibited by fingolimod which is an oral drug for relapsing multiple sclerosis (MS). Effects of this treatment on adrenal function has not yet been evaluated. We aimed to test adrenal function of MS patients receiving long-term fingolimod treatment. Methods Nineteen patients (14 women) with MS receiving oral fingolimod (Gilenya®, Novartis) therapy were included. Median age was 34.2 years (range; 21.3–44.6 years). Median duration of fingolimod treatment was 32 months (range; 6–52 months) at a dose of 0.5 mg/day. Basal and ACTH-stimulated adrenal steroid measurements were evaluated simultaneously employing LC-MS/MS based steroid panel. Basal steroid concentrations were also compared to that of sex- and age-matched healthy subjects. Cortisol and 11-deoxycortisol, 11-deoxycorticosterone and dehydroepiandrosterone were used to assess glucocorticoid, mineralocorticoid and sex steroid producing pathways, respectively. Results Basal ACTH concentrations of the patients were 20.8 pg/mL (6.8–37.8 pg/mL) (normal range; 5–65 pg/mL). There was no significant difference in the basal concentrations of cortisol, 11-deoxycortisol, 11-deoxycorticosterone and dehydroepiandrosterone between patients and controls (p = 0.11, 0.058, 0.74, 0.15; respectively). All patients showed adequate cortisol response to 250 mcg IV ACTH stimulation (243 ng/mL, range; 197–362 ng/mL). There was no significant correlation between duration of fingolimod treatment and basal or ACTH-stimulated cortisol or change in cortisol concentrations during ACTH stimulation test (p = 0.57, 0.66 and 0.21, respectively). Conclusion Modification and inhibition of S1P lyase activity by the long-term therapeutic use of fingolimod is not associated with adrenal insufficiency in adult patients with MS. This suggests that S1P lyase has potentially a critical role on adrenal development rather than the function of a fully mature adrenal gland. |
topic |
Sphingosine-1-phosphate lyase Fingolimod Adrenal Multiple sclerosis |
url |
http://link.springer.com/article/10.1186/s12883-018-1049-9 |
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