Does Low Cortisol from Adrenal Insufficiency Increase SHBG?
No, low cortisol from adrenal insufficiency does not increase sex hormone-binding globulin (SHBG)—in fact, the opposite relationship exists: higher cortisol reserves and cortisol responses are associated with lower SHBG levels. 1
The Cortisol-SHBG Relationship
Cortisol reserves are inversely related to SHBG levels, with corticotropin-stimulated cortisol responses showing a strong negative association with SHBG (explaining 34% of SHBG variation in healthy men). 1
In a study of 30 men, SHBG was inversely correlated with corticosteroid-binding globulin and negatively associated with ACTH-stimulated cortisol responses (P < 0.001), meaning that individuals with higher cortisol production capacity had lower SHBG levels. 1
Free testosterone was positively related to both basal cortisol (P < 0.01) and free cortisol (P < 0.05), suggesting that higher cortisol states are associated with lower SHBG and consequently higher free testosterone. 1
Clinical Implications for Adrenal Insufficiency
In patients with adrenal insufficiency (characterized by low cortisol production), you would theoretically expect SHBG levels to be normal or possibly elevated rather than suppressed, though this specific relationship has not been extensively studied in the adrenal insufficiency population. 1
Factors That Actually Increase SHBG
According to the European Association of Urology, SHBG is increased by: 2
- Drugs: anticonvulsants, estrogens, thyroid hormone
- Hyperthyroidism
- Hepatic disease
- Aging
- Smoking
- AIDS/HIV
Factors That Decrease SHBG
SHBG is decreased by: 2
- Drugs: growth hormone, glucocorticoids (including exogenous cortisol/hydrocortisone), testosterone, anabolic androgenic steroids
- Hypothyroidism
- Obesity
- Acromegaly
- Cushing's disease (high endogenous cortisol)
- Insulin resistance (metabolic syndrome/type 2 diabetes)
- Nonalcoholic fatty liver disease, nephrotic syndrome
Key Clinical Pitfall
Do not confuse the effect of exogenous glucocorticoid treatment (which lowers SHBG) with the state of untreated adrenal insufficiency (low endogenous cortisol). 2 Patients receiving hydrocortisone replacement therapy for adrenal insufficiency will have suppressed SHBG due to the pharmacologic glucocorticoid effect, not due to the underlying disease. 2