Loss of serum transcortin in human shock associated with severe infection by candida albicans

Abstract

The cortisol binding ability of transcortin (corticosteroid binding globulin or CBG) was found to be virtually absent from the sera of patients in a state of shock associated with high levels of antibodies to candida albicans.At the same time the serum proteins of the patients in shock displayed a number of the classical responses seen in acute inflammation: increased haptoglobin (28 \m=+-\10 vs 10.8 \m=+-\7.7 \g=m\m in normals), reduced prealbumin (1.7 \m=+-\ 0.6 vs 3.6 \m=+-\0.1 \g=m\m in normals) and albumin (485 \m=+-\78 vs 600 \ m=+-\200 \ g=m\ m in normals).The shock sera also showed increases in levels of endogenous cortisol (610 \ m=+-\ 260 vs 395 \ m=+-\ 192 nM in normals) and progesterone (2.40 \ m=+-\ 0.7 vs 1.4 \ m=+-\ 1.2 nM in normals) similar to those seen in inflammatory conditions.In sera from patients with superficial chronic candidiasis no significant variation of cortisol binding was observed. Haptoglobin was increased (26.4 \ m=+-\8.2 \g=m\m) and prealbumin decreased (2 \m=+-\0.8 \g=m\m), while the other serum indices tested retained essentially normal levels.Compared with previous studies from this laboratory which demonstrate a fall of CBG in septic shock of bacterial origin and lack of this response in acute inflammation, these results suggest that the loss of serum CBG acitivity is a specific marker for shock of fungal or bacterial aetiology. Possible endocrine or immune implications and clinical applications of our findings are discussed.Uow transcortin (CBG) values have been described in a few cases of liver, adrenal or renal disease (Brien 1981) or as a result of surgery (Hamanaka et al. 1970). Until recently, however, no consistent decrease of this corticosteroid binding activity has been reported in human disease states.Studies from this laboratory have shown that a severe and highly reproducible fall of CBG activity occurs in the rat as a result of turpentine-induced inflammation (Savu et al. 1980) and in man during the early phase of septic shock of bacterial aetiology (Savu et al. 1981). In man, this response resulted in virtual disappearence of the glucocorticoid binding activity of the serum ; this seemed specific for septic shock, since sera from patients with shock or acute inflammation displayed similar responses of their classical acute phase reactants (APRs), and endo¬ genous cortisol or progesterone levels, whereas the CBG fall was only seen in the shock sera.We have now extended our observations to shock associated with severe acute infection by the fungus candida albicans and shown that this dis¬ order brings about an almost complete loss of CBG activities similar to that caused by bacterial septic shock.In addition, to further delineate the specificity of the CBG fall in various shock and inflammatory conditions, we have examined the serum levels of typical APRs, steroids, and thyroid hormones, in patients with severe or superficial candidiasis.The physiological and practical implications of our findings are discussed.

A solid-phase radioimmunoassay for human corticosteroid binding globulin

“…septic shock (Zouaghi, Savu, Delorme et al 1983), where the CBG cortisol binding capacity appears to be very low. Serum concentrations of CBG generally increase in women taking various forms of oral contraceptives, almost to the same extent as observed during preg¬ nancy, and this is thought to be due to the induction of hepatic CBG synthesis by oestrogens.…”

The Functions of Corticosteroid-Binding Globulin and Sex Hormone-Binding Globulin: Recent Advances*

“…However, whereas a high carbohydrate diet causes a 35-40% increase in plasma SHBG, plasma CBG falls by about 20% under the same conditions (40). As already mentioned plasma CBG decreases drastically in septic shock (12,13). Doe et al (41) made the interesting observation that CBG was depressed in pernicious anemia, but not folate deficiency, and that treatment of the disease with vitamin B 12 reversed the change within 2 weeks.…”

“…Although there is little direct evidence to support this sequence of events in stress, neither is there a convincing counterexample. Indeed, in certain types of stress, CBG rapidly disappears from plasma (12,13); although that observation can be interpreted in a number of ways, it is compatible with CBG freeing all of its bound hormone and making it rapidly available. A probable mechanism for the rapid disappearance of CBG has been published (14) and lends support to this view of the biology (see below).…”

Corticosteroid-Binding Globulin during Inflammation and Burn Injury: Nutritional Modulation and Clinical Implications

“…In the first study concerning this question, subcutaneous turpentine injections to 2-monthold rats were shown to induce a 3-fold decrease in serum corticosterone binding [36]. Subsequent investigations by the same group found that serum CBG binding capacity was lower during severe infection [37] and septic shock [38]. Recently, this latter finding was confirmed by ra dioimmunoassay of CBG [39].…”