CBG

**1. Corticosteroid-binding globulin (CBG, transcortin, SERPINA6)** - Structure and synthesis: an alpha-globulin glycoprotein made by the liver. It belongs to the serpin family but is non-inhibitory. Cortisol release occurs when neutrophil elastase cleaves it at sites of inflammation. - Function: binds about 80-90% of circulating cortisol with high affinity. Albumin binds about 5-10% with low affinity, and about 5% is free. Only free cortisol is active, can enter cells, and is filtered into urine (urinary free cortisol). - Also binds progesterone, with lower affinity than cortisol, and other glucocorticoids. - Raised CBG: - Estrogen states: pregnancy, oral contraceptives, and hormone therapy. Total serum cortisol is elevated, but free cortisol and urinary free cortisol are normal. The patient is not Cushingoid, and the HPA axis is intact. - Hyperthyroidism and congenital CBG excess. - Lowered CBG: - Cirrhosis, nephrotic syndrome (urinary loss), protein-losing states, critical illness and sepsis, hypothyroidism, and congenital CBG deficiency. - Total cortisol falls, but free cortisol is normal. Do not misdiagnose adrenal insufficiency from a low total cortisol alone. - Testing pearls: - Total serum cortisol is unreliable when binding proteins are altered, as with OCP use or nephrotic syndrome. - Use late-night salivary cortisol, 24-hour urinary free cortisol, or a 1 mg overnight dexamethasone suppression test to screen for Cushing syndrome. - Estrogen-induced CBG elevation can cause a false-positive dexamethasone suppression test, because total cortisol stays high. The way around this is to stop estrogen for about 6 weeks, or to use free-cortisol measurements. - Parallels with other binding proteins: - TBG: estrogen raises total T4, but free T4 and TSH are normal. - SHBG: estrogen raises it, and androgens lower it. - Total hormone changes with normal free hormone and no clinical disease is a classic board theme.

**2. Other meanings (context-dependent)** - Capillary blood glucose: a point-of-care fingerstick glucose, used in inpatient diabetes management and when evaluating altered mental status. - Cannabigerol: a non-psychoactive cannabinoid. This is not a board topic. - CABG (coronary artery bypass graft) is a different, similar-looking abbreviation. It is sometimes mistyped as CBG.

**High-yield takeaway:** a high total cortisol with normal free cortisol and no Cushing features in a woman on OCPs or who is pregnant reflects increased CBG, not hypercortisolism.