CBG Full Form
CBG stands for Corticosteroid-Binding Globulin, the principal plasma transport protein for glucocorticoids, particularly cortisol. 1, 2
What CBG Does
CBG is a glycoprotein that binds approximately 80-90% of circulating cortisol with high affinity, leaving only about 5% unbound and biologically active. 2 This protein belongs to the SERPIN (serine proteinase inhibitor) superfamily but has evolved to function primarily as a hormone transport agent rather than as a proteinase inhibitor. 3, 4
Clinical Significance
Normal Physiology
- CBG regulates the bioavailability and delivery of cortisol to target tissues throughout the body 2, 5
- The protein modulates access of glucocorticoids to cells by controlling the free (unbound) fraction of cortisol 1, 2
- At sites of inflammation, proteolytic cleavage of CBG triggers cortisol release, allowing targeted hormone delivery 3, 5
When CBG Levels Matter Clinically
CBG levels directly affect total cortisol measurements, which is why conditions altering CBG can cause falsely elevated or decreased total cortisol values despite normal free cortisol. 1
Key situations where CBG affects cortisol interpretation:
- Oral contraceptives and estrogen therapy increase CBG production, dramatically raising total cortisol measurements while free cortisol remains normal 6, 7
- Pregnancy increases CBG levels, leading to elevated total cortisol that does not reflect true hypercortisolism 6, 8
- Chronic active hepatitis can increase CBG production, falsely elevating total cortisol 6
- Critical illness often causes CBG levels to fall, which may heighten stress responses 1, 5
- Hypoalbuminemia in critically ill patients reduces protein binding, affecting cortisol distribution 1
Genetic CBG Variants
Three documented genetic mutations affect CBG function 9, 5:
- CBG-Leuven mutation: reduces cortisol binding affinity 3-fold 5
- CBG-Lyon mutation (Asp367→Asn): reduces cortisol binding affinity 4-fold, resulting in low total cortisol but normal free cortisol levels 9, 5
- CBG null mutation: causes 50% reduction in heterozygotes or complete absence in homozygotes, potentially associated with hypotension and fatigue 5
Practical Clinical Implications
When interpreting low total cortisol levels, always inquire about oral contraceptives, estrogen therapy, pregnancy, and critical illness status before pursuing extensive workup for adrenal insufficiency. 6 The most important clinical pitfall is interpreting elevated total cortisol as pathologic without considering CBG status. 6
In critically ill patients with low CBG and hypoalbuminemia, measuring free cortisol may provide more accurate assessment than total cortisol, though this remains controversial and is not routinely recommended. 1