Anterior Pituitary Function in Patients With Newly Diagnosed Rheumatoid Arthritis

Templ, E.; Koeller, M.; Riedl, Michaela; Wagner, O; Graninger, Wolfgang; Luger, Anton

doi:10.1093/rheumatology/35.4.350

Cited by 88 publications

(53 citation statements)

References 20 publications

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“…In patients with MS, the cortisol response to CRF differs depending on the disease status of the individual (Wei & Lightman, 1997). Similarly, in patients with RA, the cortisol response to challenge with releasing hormones is impaired in individuals with established disease (Gudbjornsson et al 1996), but not in newly diagnosed untreated RA patients (Templ et al 1996).…”

Section: Is the Hpa Axis Altered In Patients With Autoimmune Disease?mentioning

confidence: 99%

Neuroendocrine Function and Chronic Inflammatory Stress

Harbuz

2002

Experimental Physiology

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The HPA axis and the response to acute stress The end-point of the activation of the HPA axis is the release of glucocorticoids (cortisol in man, corticosterone in rodents) from the adrenal cortex into the general circulation. The synthesis and release of glucocorticoids are controlled by ACTH released from the anterior pituitary gland. ACTH is synthesised from the precursor proopiomelanocortin (POMC) mRNA. The release of ACTH is regulated by the corticotrophin releasing factors corticotrophin-releasing factor(1-41) (CRF) and arginine vasopressin (AVP), which are released from the median eminence and synthesised in the parvocellular cells of the paraventricular nucleus (PVN). Under normal conditions approximately 50 % of these CRF neurons contain AVP; the remainder contain CRF but no vasopressin. CRF and AVP exert a synergistic action on the release of ACTH. The PVN acts as a co-ordinating centre receiving signals from many brain areas to regulate the response to stress. The glucocorticoids are able to regulate their own synthesis by negative feedback mediated by two corticosteroid receptors, the type II (glucocorticoid) receptor, which is found in the pituitary, PVN and other brain areas such as the hippocampus, and the type I receptor, which is found in the hippocampus. The hippocampus has a tonic inhibitory input to the PVN. In response to acute stress, the HPA axis is activated evoking the release of CRF and AVP into the The factors regulating susceptibility and severity of autoimmune diseases are poorly understood. That neuroendocrine factors are critical modulators in this regard is self-evident. For example, there are major gender differences in susceptibility with women at greater risk than men of, for example, rheumatoid arthritis (RA) and multiple sclerosis (MS). The hypothalamo-pituitary-adrenal (HPA) axis has rightly attracted a considerable amount of attention. Of particular interest has been the hypothesis that susceptibility to autoimmune disease may be related to an impaired responsiveness of the HPA axis; that is, an inability to mount an appropriate cortisol response with which to down-regulate the immune system might allow the immune system to rampage unchecked and attack self. This hypothesis links regulation of the release from the adrenal gland of the potent anti-inflammatory glucocorticoids to the disease process. Endogenous glucocorticoids are crucial for the regulation of the severity of the disease process. The hypothesis proposing a link between a hyporesponsive HPA axis and susceptibility to disease is compelling. However, evidence from a number of sources has suggested that this may not be the entire story and alterations in the activity of the HPA axis have not been consistently observed in patients with RA. This review will concentrate on recent findings concerning the HPA axis in determining susceptibility to, and in regulating the severity of, inflammatory processes in autoimmune disease. These studies have revealed that a single exposure to endotoxin can confer protection to sub...

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Section: Is the Hpa Axis Altered In Patients With Autoimmune Disease?mentioning

confidence: 99%

Neuroendocrine Function and Chronic Inflammatory Stress

Harbuz

2002

Experimental Physiology

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“…A significant decrease in serum concentrations of IGF-I as well as in pituitary GH mRNA content has been described in arthritic rats (5,6), indicating a decrease in pituitary GH secretion. In humans with rheumatoid arthritis, a significant decrease in GH and IGF-I secretion has also been described (7,8). We have recently observed that recombinant human GH (rhGH) administration to arthritic rats can ameliorate the decrease in IGF-I and BW and the increase in circulating IGF-binding proteins (9).…”

Section: Introductionmentioning

confidence: 99%

The decrease in hepatic IGF-I gene expression in arthritic rats is not associated with modifications in hepatic GH receptor mRNA

López-Calderón

Cáceres²,

Soto³

et al. 2001

European Journal of Endocrinology

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Objective: Adjuvant-induced arthritis induces a catabolic response, and a decrease in circulating IGF-I. Hypermetabolism and GH insensitivity have been described in acute inflammation. The aim of this study was to analyze whether impaired IGF-I secretion in arthritic rats can be attributed to hepatic GH resistance. Design and methods: Male Wistar rats were injected with complete Freund's adjuvant, and 14 days afterwards arthritic and control rats were injected daily with recombinant human GH (rhGH) (3 IU/kg) or saline for 8 days. GH receptor (GHR) gene expression in the liver and the effect of rhGH on hepatic IGF-I synthesis in arthritic rats were examined. Results: There was a significant decrease in hepatic concentrations of IGF-I P , 0X01 as well as in the IGF-I gene expression in arthritic but not in pair-fed rats. In contrast, arthritis did not modify GHR mRNA levels in the liver. The 8 day administration of rhGH resulted in an increase in body weight gain in arthritic but not in control rats. There was an increase in hepatic IGF-I synthesis and in GHR mRNA levels after rhGH treatment, both in control and in arthritic rats. Two endotoxin lipopolysaccharide (LPS) (1 mg/kg) injections decreased hepatic concentrations of IGF-I and IGF-I mRNA P , 0X01X Contrary to the results obtained in arthritic rats, mRNA expression of GHR in the liver was lower in LPS-than in saline-treated rats P , 0X01X Conclusion: These data suggest that the decrease in IGF-I synthesis induced by chronic arthritis is not secondary to GH resistance.

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“…Previous literature data have shown that, in comparison with controls, RA patients have, almost signi®cantly, reduced plasma IGF-I levels and clearly reduced plasma IGF-II and insulin-like growth factor-binding protein-3 levels which, however, are increased in synovial¯uid (28). Previous literature data have shown a blunted GH response after growth hormone-releasing hormone in RA patients when compared with controls, and this ®nding might be due to the increased IL-1 levels found in these patients which is known to stimulate somatostatin synthesis and release in rat hypothalamus (29). The reduced IGF-I levels found in our RA patients might not therefore be merely secondary to a chronic illness such as RA, but might be due to multiple factors such as a reduced activity of the GH±IGF-I axis and a passage of the peptide from the circulation to the synovial space (28).…”

Section: Journal Of Endocrinology (1998) 138mentioning

confidence: 73%

Desmopressin and low-dose ACTH test in rheumatoid arthritis

Foppiani

Cutolo²,

Sessarego³

et al. 1998

European Journal of Endocrinology

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Objective: To ascertain whether a different regulation and sensitivity of the hypothalamic±pituitary± adrenal axis exists and whether a type of cortisol resistance is present in rheumatoid arthritis (RA) patients, a chronic disease in whose pathogenesis modi®cations of the steroid milieu are involved. Design: We studied the basal and dynamic response of ACTH and adrenal steroids to various stimuli acting on the hypophysis or directly on the adrenal gland. Methods: We studied ten RA patients (39.8 6 7.4 (S.D.) years), de®ned according to the American Rheumatism Association, and seven healthy control patients (34.1 6 9.6 (S.D.) years). All subjects underwent testing, in random order, with placebo, desmopressin (DDAVP) (10 mg i.v.), ovine corticotropin-releasing hormone (oCRH) (1 mg/kg body weight) and low-dose ACTH (5 mg i.v.), during the follicular phase of two different menstrual cycles. Blood samples were collected at different times for ACTH and adrenal steroids assay. Baseline estradiol (E2), testosterone and IGF-I levels were also evaluated. All subjects collected urine specimens for 24 h urine free cortisol (UFC). Results: No difference in E2, testosterone or UFC was found between RA patients and controls. IGF-I levels were signi®cantly (P < 0.01) lower in RA patients (110.6 6 6.4 mg/l) than in controls (207.0 6 37.9 mg/l). Mean baseline dehydroepiandrosterone (DHEA) and D4-androstenedione levels of the four tests were signi®cantly (P < 0.05) lower in RA patients than in controls. In RA, a negative correlation was found between mean DHEA levels, class of disease (r À 0.67, P < 0.05) and erythrocyte sedimentation rate (r À 0.63, P < 0.05). After placebo no difference in ACTH and cortisol area under curves (AUCs) was found between RA patients and controls. After DDAVP no cortisol or ACTH response was found in RA patients, while a signi®cant (P < 0.05) ACTH release was found in controls. Only in RA patients was DDAVP able to induce a signi®cant (P < 0.01) DHEA increase. After oCRH a similar signi®cant response in ACTH (P < 0.05), cortisol (P < 0.01), and DHEA (P < 0.01) was found in both groups. After low-dose ACTH, a similar signi®cant (P < 0.01) cortisol response was found in both RA patients and controls; indeed in RA patients DHEA AUC (2196.0 6 321.8 nmol/l per 90 min) was signi®cantly lower (P < 0.01) than DHEA AUC (4280.8 6 749.0 nmol/l per 90 min) in controls. A similar signi®cant (P < 0.01), though not abnormal, 17-hydroxyprogesterone response to ACTH was found in both groups. Conclusions: Our study underlines reduced adrenal steroid and IGF-I levels, but not the previously described cortisol resistance in RA patients; it shows that baseline and dynamic cortisol levels arè normal' but inadequate in the setting of a sustained in¯ammatory disease like RA. The reduced basal and low-dose ACTH-induced DHEA levels could re¯ect both a reduced sensitivity of the adrenal gland to exogenous corticotropin and a decreased steroid synthesis due to a partial adrenal enzymatic defect (P450 17,20 lyase). Europ...

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Anterior Pituitary Function in Patients With Newly Diagnosed Rheumatoid Arthritis

Cited by 88 publications

References 20 publications

Neuroendocrine Function and Chronic Inflammatory Stress

Neuroendocrine Function and Chronic Inflammatory Stress

The decrease in hepatic IGF-I gene expression in arthritic rats is not associated with modifications in hepatic GH receptor mRNA

Desmopressin and low-dose ACTH test in rheumatoid arthritis

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