Quantitation of corticosteroid-binding globulin in serum is useful in assessing unexpected levels of cortisol in serum.
It is also used in the investigation of corticosteroid-binding globulin deficiency, a condition with subtle signs and symptoms, the most frequent being extreme tiredness (fatigue), especially after physical exertion.
Corticosteroid-binding globulin (CBG) or transcortin is a single-chain glycoprotein of 383 amino acids and a molecular mass of 52 kDa. Approximately 27% of its weight consists of carbohydrates. It is a member of the serine protease inhibitor (Serpin) family of proteins and migrates with α1-globulins on electrophoresis. The CBG molecule contains a single steroid-binding site, which binds cortisol and corticosterone with high affinity and other corticosteroids to a lesser extent.
The importance of CBG is highlighted by its ability to bind 80–90% of cortisol in plasma, leaving only about 4–5% circulating in the free fraction and the remainder bound loosely to albumin. Several naturally occurring CBG variants have been identified that are either not produced appropriately or have steroid-binding defects.
CBG is synthesized in the liver. Interestingly CBG is a ‘negative acute-phase protein’ during an inflammatory response, and its plasma concentration decreases rapidly during sepsis, severe burn, and myocardial infarction, and this likely increases the amounts of free glucocorticoids that can control the inflammatory response, gluconeogenesis, and stress.
Corticosteroid-binding globulin concentrations are increased two- to three-fold in pregnancy and also are raised with estrogen therapy. Elevated levels are also observed in acute hepatitis and in inherited abnormality. Insulin inhibits the synthesis of CBG. The serum level of CBG is lower in hyper-insulinemic status, as in diabetes, πolycystic ovary syndrome, and obesity. Severe liver disease and malnutrition may result in a low level of CBG. CBG is also lower in Cushing's syndrome and in disease states associated with increased protein loss or decreased synthesis.
Corticosteroid-binding globulin deficiency is a condition with subtle signs and symptoms, the most frequent being extreme tiredness (fatigue), especially after physical exertion. Many people with this condition have unusually low blood pressure (hypotension). Some affected individuals have fatty livers or experience chronic pain, particularly in their muscles. These features vary among affected individuals, even those within the same family.
Many people with corticosteroid-binding globulin deficiency have only one or two of these features; others have no signs and symptoms of the disorder and are only diagnosed after a relative is found to be affected. Some people with corticosteroid-binding globulin deficiency also have a condition called chronic fatigue syndrome. The features of chronic fatigue syndrome are prolonged fatigue that interferes with daily activities, as well as general symptoms, such as sore throat or headaches.