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Corticosteroid-binding globulin deficiency
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Condition

Corticosteroid-binding globulin deficiency

Corticosteroid-binding globulin deficiency is a rare condition that may cause fatigue, low blood pressure, and chronic pain due to the body's inability to properly transport the hormone cortisol.

Overview

Corticosteroid-binding globulin deficiency is characterized by subtle symptoms, most notably extreme fatigue following physical exertion. Many individuals also experience low blood pressure (hypotension), fatty liver, or chronic muscle pain. Some affected individuals may have no symptoms at all and are only identified after a relative is diagnosed.

Symptoms

  • Extreme tiredness (fatigue)
  • Unusually low blood pressure (hypotension)
  • Chronic pain, particularly in the muscles
  • Fatty liver
  • Some individuals may also have myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

Causes

The disorder is caused by mutations in the SERPINA6 gene, which provides instructions for making the protein corticosteroid-binding globulin (CBG). CBG is produced in the liver and binds to the hormone cortisol, regulating its availability in the body.

SERPINA6 mutations often decrease the ability of CBG to bind to cortisol. While this leads to increased levels of unbound (active) cortisol, the body often compensates by reducing total cortisol production. Researchers believe the symptoms may arise because CBG is unable to effectively transport cortisol to the specific tissues that require it, or because of the resulting reduction in total cortisol levels.

Inheritance

This condition is reported to have an autosomal recessive pattern of inheritance. However, the presentation can be variable; some individuals with only one mutated gene may experience symptoms like fatigue or pain, while others with two mutations may remain asymptomatic.

Frequently Asked Questions

In some patients, low‑dose glucocorticoid therapy (e.g., hydrocortisone 5‑10 mg in the morning) can raise total cortisol levels and alleviate fatigue and hypotension. Treatment must be individualized and monitored with repeat cortisol and blood pressure checks to avoid overtreatment.
dopting a Mediterranean‑style diet low in saturated fat, maintaining a healthy weight, and limiting alcohol can reduce hepatic steatosis. Gentle, regular aerobic exercise (e.g., walking, swimming) improves muscle perfusion without overtaxing fatigued muscles; physical therapy may also help manage chronic myalgia.
Diagnosis usually starts with a blood panel that measures total cortisol, free (unbound) cortisol, and CBG concentration. Low CBG with an inappropriately low total cortisol but normal or elevated free cortisol suggests the disorder. Definitive confirmation is done by sequencing the SERPINA6 gene to identify pathogenic mutations.
Because the condition follows an autosomal‑recessive pattern, each sibling has a 25 % chance of being affected and a 50 % chance of being a carrier. Genetic counseling is recommended, and carrier testing or targeted SERPINA6 sequencing can clarify risk, even in asymptomatic relatives.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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