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Residual endogenous corticosteroid production in patients with adrenal insufficiency

Artikel i vetenskaplig tidskrift
Författare A. Vulto
Ragnhildur Bergthorsdottir
M. van Faassen
I. P. Kema
Gudmundur Johannsson
A. P. van Beek
Publicerad i Clinical Endocrinology
Volym 91
Nummer/häfte 3
Sidor 383-390
ISSN 0300-0664
Publiceringsår 2019
Publicerad vid Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition
Sidor 383-390
Språk en
Länkar dx.doi.org/10.1111/cen.14006
Ämnesord 11-deoxycortisol, adrenal insufficiency, aldosterone, corticosterone, cortisol, hydrocortisone, tandem mass-spectrometry, liquid-chromatography, addisons-disease, cortisol, recovery, ms/ms, hydrocortisone, Endocrinology & Metabolism
Ämneskategorier Endokrinologi och diabetes

Sammanfattning

Objective This study aimed at comparing precursors of endogenous corticosteroid production in patients with primary adrenal insufficiency and in secondary adrenal insufficiency. Design Twenty patients with primary adrenal insufficiency and matched controls and 19 patients with secondary adrenal insufficiency participated in this ancillary analysis of two different studies. Patients and measurements Patients with primary adrenal insufficiency were on stable hydrocortisone and fludrocortisone therapy. Patients with secondary adrenal insufficiency received two different doses of hydrocortisone in a randomized crossover study. Main outcome measures were concentrations of precursors of cortisol and aldosterone measured by LC-MS/MS Results Compared to controls, progressively lower concentrations of the glucocorticoid precursors 11-deoxycortisol, 11-deoxycorticosterone and corticosterone concentrations were found in patients with secondary adrenal insufficiency on lower hydrocortisone dose, secondary adrenal insufficiency on higher hydrocortisone dose and primary adrenal insufficiency, respectively. Half of the primary adrenal insufficient patients showed evidence of residual endogenous cortisol or aldosterone synthesis, as determined by quantifiable 11-deoxycortisol, 11-deoxycorticosterone and corticosterone conce ntrations. In secondary adrenal insufficient patients with higher endogenous cortisol production, as indicated by 11-deoxycortisol concentrations above the median, no increased cortisol exposure was observed both by plasma pharmacokinetic parameters and 24-hour free cortisol excretion in urine. Conclusions Adrenal corticosteroid production is likely to continue during treatment in a considerable percentage of patients with both primary and secondary adrenal insufficiency. In patients with secondary adrenal insufficiency, this synthesis appears to be sensitive to the dose of hydrocortisone. However, the residual corticosteroid concentrations were quantitatively low and its clinical significance remains therefore to be determined.

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