Activity of the neuroendocrine axes in patients with polymyalgia rheumatica before and after TNF-α blocking etanercept treatment

Frederik Flindt Kreiner, Henrik Galbo, Frederik Flindt Kreiner, Henrik Galbo

Abstract

Introduction: In this study, we evaluated the activity of the neuroendocrine axes in patients with polymyalgia rheumatica (PMR) before and after tumor necrosis factor (TNF)-α-blocking etanercept treatment, which previously has been shown to reduce interleukin 6 (IL-6) and C-reactive protein (CRP) markedly in PMR.

Methods: Plasma samples were collected from 10 glucocorticoid-naïve patients with PMR and 10 matched controls before and after etanercept treatment (25 mg biweekly for 2 weeks). The primary end points were pre- and posttreatment levels of adrenocorticotropic hormone (ACTH), cortisol, adrenaline, thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), prolactin, and insulin-like growth factor 1 (IGF-1).

Results: Before TNF-α-blocking treatment, plasma TNF-α, ACTH, and cortisol levels were higher in patients versus controls (P < 0.05 and P < 0.001, respectively); during TNF-α blockade in patients, levels of both hormones decreased (P < 0.05 and P < 0.01, respectively), whereas levels in controls increased (P < 0.05), abolishing the pretreatment differences. Pretreatment adrenaline levels were more than twice as high in patients than in controls (P < 0.01); after treatment in patients, levels had decreased (P < 0.05) but remained higher versus controls (P < 0.05). Levels of the other hormones never differed significantly between groups (P > 0.05).

Conclusions: In PMR, TNF-α may increase the activities of the hypothalamic-pituitary-adrenal and the hypothalamic-sympthoadrenomedullary axes. Secretion of TSH, FSH, prolactin, and IGF-1 is not clearly changed in PMR.

Trial registration: ClinicalTrials.gov (NCT00524381).

Figures

Figure 1
Figure 1
Plasma levels of adrenocorticotropic hormone (ACTH) and cortisol before (gray bars) and after (white bars) 14 days of TNF-α-blocking treatment with etanercept in glucocorticoid-naïve patients with polymyalgia rheumatica (PMR) and in non-PMR control subjects. Box plots show median values and 25% to 75% interquartile ranges. Symbols connected by full lines represent values for individual subjects. Dashed lines represent tendencies between medians of paired data. *P < 0.05; **P < 0.01; ***P < 0.001.
Figure 2
Figure 2
Ratios between plasma levels of ACTH and cortisol, respectively, and IL-6 or CRP before (gray bars) and after (white bars) 14 days of TNF-α-blocking treatment with etanercept in glucocorticoid-naïve patients with polymyalgia rheumatica (PMR) and in non-PMR control subjects. Box plots show median values and 25% to 75% interquartile ranges. Symbols connected by full lines represent values for individual subjects. Dashed lines represent tendencies between medians of paired data. *P < 0.05; **P < 0.01; ***P < 0.001.
Figure 3
Figure 3
Plasma levels of adrenalin before (gray bars) and after (white bars) 14 days of TNF-α[blocking treatment with etanercept in glucocorticoid-naïve patients with polymyalgia rheumatica (PMR) and in non-PMR control subjects. Box plots show median values and 25% to 75% interquartile ranges. Symbols connected by full lines represent values for individual subjects. Dashed lines represent tendencies between medians of paired data. *P < 0.05; **P < 0.01.
Figure 4
Figure 4
Plasma levels of follicle-stimulating hormone (FSH), prolactin, and thyroid-stimulating hormone (TSH) before (gray bars) and after (white bars) 14 days of TNF-α-blocking treatment with etanercept in glucocorticoid-naïve patients with polymyalgia rheumatica (PMR) and in non-PMR control subjects. Box plots show median values and 25% to 75% interquartile ranges. Symbols connected by full lines represent values for individual subjects. Dashed lines represent tendencies between medians of paired data. *P < 0.05.
Figure 5
Figure 5
Plasma levels of insulin-like growth factor 1 (IGF-1) before (gray bars) and after (white bars) 14 days of TNF-α-blocking treatment with etanercept in glucocorticoid-naïve patients with polymyalgia rheumatica (PMR) and in non-PMR control subjects. Box plots show median values and 25% to 75% interquartile ranges. Symbols connected by full lines represent values for individual subjects. Dashed lines represent tendencies between medians of paired data.

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