Hypothalamic-pituitary-adrenal axis function and prolactin secretion in systemic lupus erythematosus

Abstract

The objective was to study the response of cortisol and of prolactin (PRL) to specific stimuli in systemic lupus erythematosus (SLE). We measured the response of cortisol to insulin-induced hypoglycemia and of PRL to thyrotropin releasing hormone (TRH) in seven patients with active untreated SLE and in ten paired control subjects. All were women with regular menstrual cycles. With the exception of two patients, they had never received corticosteroids before the study. The basal serum levels of cortisol (12.5+/-2.4 microg/dl) and PRL (10.7+/-1.0 ng/ml) in the SLE group were not significantly different from those of the control group (12.3+/-1.1 microg/dl and 13.7+/-2.4 ng/ml, respectively). The cortisol response after hypoglycemia was significantly lower in SLE patients compared to the control group at 45 min (P=0.01), at 60 min (P = 0.009), and at 90 min (P = 0.001). The integrated cortisol response to hypoglycemia expressed as area under the response curve (AUC) did not differ significantly in either group (1447+/-187 vs 1828+/-84, P = 0.06). Although the peak of PRL after TRH did not differ significantly in both groups (68.0+/-7.4 ng/ml in SLE vs 66.3+/-77 ng/ml in controls) and the AUC of PRL response after TRH was comparable in both groups (4672+/-537 vs 4128+/-541, P = 0.32), the interval-specific 'delta' response was significantly higher in SLE than the control group at 0-60 min (P=0.02) and 0-90 min (P = 0.01) after TRH injection. These findings suggest that active SLE is associated with some degree of dysfunction of the hypothalamic-pituitary-glucocorticoid axis and PRL secretion.

Brain-immune interactions and disease susceptibility

“…25 A blunted HPA axis has been associated with susceptibility to autoimmune and inflammatory disease in chickens (a model for autoimmune thyroiditis), 143 certain mouse lupus models, 144,145 and in the inbred rat strains 146,147 ( Table 1). The association between blunted HPA axis and autoimmune, inflammatory and allergic diseases has been reported in human illness including RA, [148][149][150][151][152][153] Sjogren's syndrome, 154 systemic lupus erythematosus, 155 multiple sclerosis, 156,157 allergic asthma and atopic skin disease. [158][159][160] (Table 1).…”

Sex hormones and systemic lupus erythematosus: Review and meta‐analysis

“…Estradiol stimulates prolactin secretion, and prolactin suppresses gonadal steroid synthesis (69,70). As shown in Table 4 and Figure 4, several studies have examined the relationship of prolactin and SLE in adults, comparing either the mean concentrations in patients with those of controls or normal and abnormal prolactin concentrations (hyperprolactinemia), with or without a control population (71)(72)(73)(74)(75)(76)(77)(78)(79)(80)(81)(82)(83)(84)(85)(86)(87). Seven of 10 female-only and 2 of 4 male-only SLE studies showed significantly increased serum prolactin concentrations in adult lupus patients compared with controls.…”

“…Other possibilities include cytokine-stimulated pituitary prolactin release (54,55), production of immunoreactive prolactin peripherally (98,99), or aberrant pituitary prolactin secretion in lupus patients (74,75). Some of these explanations are, however, superficially not compatible with the other steroid hormone abnormalities seen in female SLE patients.…”

Neuroendocrine regulation of autoimmune/inflammatory disease

“…The association between a blunted HPA axis and autoimmune, inflammatory and allergic diseases is also relevant to humans with illnesses including rheumatoid arthritis (Neeck et al 1990, Cash et al 1992, Chikanza et al 1992, Cutolo et al 1999, Gutierrez et al 1999, systemic lupus erythematosus (Gutierrez et al 1998), Sjogren's syndrome (Johnson et al 1998), allergic asthma and atopic skin disease (Buske- Kirschbaum et al 1997), fibromyalgia (Crofford et al 1994 and chronic fatigue syndrome (Demitrack et al 1991). However, it may not be necessary for the HPA axis defect to occur centrally, at the level of the hypothalamus or pituitary, to predispose to enhanced susceptibility to autoimmune/inflammatory disease.…”