scholarly journals Hypothalamo-pituitary-adrenal axis dysregulation in patients with rheumatoid arthritis after the dexamethasone/corticotrophin releasing factor test

2003 ◽  
Vol 178 (1) ◽  
pp. 55-60 ◽  
Author(s):  
MS Harbuz ◽  
E Korendowych ◽  
DS Jessop ◽  
AL Crown ◽  
SL Li pdfan ◽  
...  

A defective hypothalamo-pituitary-adrenal axis response to inflammatory cytokines may contribute to the pathophysiology of rheumatoid arthritis (RA). The purpose of this study was to define further the mechanisms responsible for this dysregulation. Six normal individuals and seven patients with active RA were recruited and given an oral dose of dexamethasone at 2300 h the evening before the study. The next day, an i.v. catheter was fitted at 1300 h. Blood samples were collected between 1400 h and 1700 h before and after infusion (at 1500 h) of corticotrophin releasing factor (CRF). Plasma was separated and stored at-20 degrees C before radioimmunoassay for ACTH, cortisol and dihydroepiandrosterone (DHEA). Before the CRF challenge, ACTH and cortisol were significantly increased and DHEA significantly decreased in the patients with RA compared with the controls. Neither ACTH nor DHEA was significantly altered after CRF infusion. Control individuals did not mount a cortisol response to infusion of CRF. Similarly, four of the patients with RA did not respond to CRF. However, in contrast to the controls, three of the patients mounted an immediate and sustained cortisol response after receiving CRF. These data reveal that three of the seven patients with RA were able to escape from dexamethasone suppression and mount a cortisol response to CRF challenge. This suggests that there may be a subpopulation of patients with RA who have impaired glucocorticoid feedback. The implications of this alteration for disease progression remain to be determined.

Endocrinology ◽  
2006 ◽  
Vol 147 (7) ◽  
pp. 3501-3509 ◽  
Author(s):  
A. J. Tilbrook ◽  
A. I. Turner ◽  
M. D. Ibbott ◽  
I. J. Clarke

We investigated the effect of the presence and absence of lambs and suckling by lambs to attenuate activation of the hypothalamo-pituitary-adrenal (HPA) axis to isolation and restraint stress in lactating sheep. In experiment 1, blood samples were collected every 10 min from nonlactating (n = 5) and lactating (n = 5) ewes for 4 h before and during stress. In experiment 2, ewes (n = 6) were allocated to 1) nonlactating, 2) lactating with lambs absent, 3) lactating with lambs present but unable to suckle, and 4) lactating with lambs present and able to suckle. Blood samples were collected over 8 h with no stress (control day) and for 4 h before and 4 h during stress (stress day). In experiment 1, the mean (±sem) cortisol concentrations increased significantly (P < 0.05) in nonlactating ewes during stress but did not change in lactating ewes. In experiment 2, cortisol did not vary on the control day or pretreatment of the stress day but increased (P < 0.05) during stress in all groups except lactating ewes with lambs present and able to suckle. The greatest cortisol response occurred in nonlactating ewes followed by lactating ewes with lambs absent and lactating ewes with lambs present but unable to suckle. During stress, the ACTH concentrations increased (P < 0.05) in nonlactating ewes and lactating ewes with lambs absent but not in lactating ewes with lambs present. We conclude that the activity of the HPA axis during isolation and restraint is reduced in lactating ewes and that the presence of lambs increases this level of attenuation.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jacob M. Maskal ◽  
Luiz F. Brito ◽  
Alan W. Duttlinger ◽  
Kouassi R. Kpodo ◽  
Betty R. McConn ◽  
...  

AbstractIn utero heat stress alters postnatal physiological and behavioral stress responses in pigs. However, the mechanisms underlying these alterations have not been determined. The study objective was to characterize the postnatal hypothalamic–pituitary–adrenal axis response of in utero heat-stressed pigs. Pigs were subjected to a dexamethasone suppression test followed by a corticotrophin releasing hormone challenge at 10 and 15 weeks of age. Following the challenge, hypothalamic, pituitary, and adrenal tissues were collected from all pigs for mRNA abundance analyses. At 10 weeks of age, in utero heat-stressed pigs had a reduced (P < 0.05) cortisol response to the corticotrophin releasing hormone challenge versus controls. Additionally, the cortisol response tended to be greater overall (P < 0.10) in 15 versus 10-week-old pigs in response to the dexamethasone suppression test. The cortisol response tended to be reduced overall (P < 0.10) in 15 versus 10-week-old pigs in response to the corticotrophin releasing hormone challenge. Hypothalamic corticotropin releasing hormone mRNA abundance tended to be greater (P < 0.10) in in utero heat-stressed versus control pigs at 15-weeks of age. In summary, in utero heat stress altered some aspects of the hypothalamic–pituitary–adrenal axis related to corticotropin releasing hormone signaling, and age influenced this response.


1976 ◽  
Vol 4 (5) ◽  
pp. 326-337 ◽  
Author(s):  
Eduardo Ortega ◽  
Consuelo Rodriguez ◽  
L James Strand ◽  
Eugene Segre

The effects of cloprednol and other synthetic corticosteroids on hypothalamic-pituitary-adrenal (HPA) function were studied in healthy subjects after administration of a single oral dose of corticosteroid at 6 a.m. or 6 p.m., and after daily 6 a.m. administration of corticosteroids at various doses for seven days. The degree of HPA suppression was assessed by metyrapone tests (METP), insulin hypoglycaemia tests (IHT) and 6 a.m. fasting plasma Cortisol concentrations. Regardless of the corticosteroid tested, 6 p.m. dosing was at least four-fold more suppressive of METP response than 6 a.m. administration. At therapeutically equivalent doses, single doses of triamcinolone and dexamethasone were more suppressive of HPA-axis function than cloprednol, hydrocortisone or prednisolone. After 6 a.m. administration for seven days, 12·5 mg of cloprednol did not impair the Cortisol response to IHT or interfere with the METP response. The clinically equivalent dose of prednisolone (25 mg) resulted in slightly greater HPA-axis suppression. All doses of dexamethasone (0·5, 3·75 and 6·0 mg) and of betamethasone (2·0, 4·0 and 6·5 mg) were more suppressive of HPA-axis function than either cloprednol or prednisolone. These results suggest that at equipotent anti-inflammatory doses, cloprednol is slightly less suppressive of HPA-axis function than prednisolone, and both cloprednol and prednisolone are much less suppressive than dexamethasone or betamethasone.


2009 ◽  
Vol 2009 ◽  
pp. 1-6 ◽  
Author(s):  
Eman A. Hasan ◽  
David S. Jessop ◽  
Lynsey L. Power ◽  
Paul T. Monk ◽  
John R. Kirwan

Objectives. Hypothalamic-Pituitary-Adrenal axis function may be abnormal in rheumatoid arthritis (RA). A pilot study in 7 patients suggested impaired glucocorticoid feedback in some patients after the dexamethasone-corticotrophin releasing hormone (CRH) test. This study aimed to investigate the dexamethasone-corticotrophin releasing factor test in a larger group of patients and relate the results to characteristics of the disease.Methods. Outpatients with active RA (≥3 swollen and tender joints and C-reactive protein > 10 mg/L) took dexamethasone (1.5 mg) at 23:00 hour in the evening. Next day, baseline saliva and plasma samples were collected, CRH was infused at 11:00 hour, and 4 serial blood and saliva samples were collected. Plasma samples were stored at−80∘Cand a radioimmunoassay performed for saliva and plasma cortisol.Results. All 20 participants showed normal dexamethasone suppression and mounted no response to the CRH challenge. In samples with measurable cortisol, there was a strong correlation between saliva and plasma values (r= 0.876,n= 26,P<.01).Conclusion. No abnormalities were found in the Dexamethasone-CRH test in RA patients in contrast to a previous pilot study. Salivary cortisol measurement may offer an alternative noninvasive technique to plasma cortisol in RA patients in future studies.


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