Free cortisol index is better than serum total cortisol in determining hypothalamic-pituitary-adrenal status in

C W le Roux1, G A Chapman, W M Kong

  • 1Department of Metabolic Medicine, Hammersmith Hospitals Trust, London, United Kingdom W12 0NN. cleroux@ic.ac.uk

Serum total cortisol has traditionally been used for the interpretation of tests of the hypothalamic-pituitary-adrenal axis. Approximately 80% of total cortisol is bound to cortisol-binding globulin (CBG), and variation in CBG significantly affects serum total cortisol levels. Reliable assessment of hypothalamic-pituitary-adrenal axis reserve is difficult in severely ill patients, because CBG falls substantially during the acute phase response. The free cortisol index (FCI), defined as the ratio of total cortisol/CBG, correlates well with serum free cortisol. We evaluated the FCI in the context of severe stress and the acute phase response by measuring total cortisol and CBG pre- and postoperatively in 31 patients undergoing major elective surgery. Serum total cortisol increased by 55% from 453 +/- 35.2 (mean +/- SEM) nmol/liter (range, 88-882) to 700 +/- 47.2 (range, 294-1631) nmol/liter. Serum CBG decreased by 30% from 45 +/- 1.7 (range, 26.6-64.1) to 31.4 +/- 1.62 (range, 16.1-51.9) mg/liter, but FCI increased by 130% from 10 +/- 0.8 (range, 2-18) to 23 +/- 1.7 (range, 13-58) nmol/mg. In seven patients (23%), postoperative serum total cortisol was less than 500 nmol/liter, but their postoperative CBG levels were significantly lower than levels in the rest of the group (P < 0.01). However, there was no difference in the FCI between this subgroup and the rest of the group. This study demonstrates the importance of CBG measurement and the calculation of FCI for the interpretation of serum total cortisol in situations where CBG changes significantly.

Related Concept Videos

Cushing Syndrome I: Introduction01:26

Cushing Syndrome I: Introduction

Cushing syndrome refers to the collection of clinical manifestations that arise when tissues are exposed to excessive amounts of cortisol or cortisol-like medications over an extended period. Cortisol, a glucocorticoid produced by the adrenal cortex, regulates metabolism, immune responses, and the body’s adaptation to stress. When its concentration remains chronically elevated, these physiological pathways become dysregulated, resulting in the characteristic features of the syndrome.Exogenous...
Cushing Syndrome II: Pathophysiology01:19

Cushing Syndrome II: Pathophysiology

Cortisol production is normally governed by the hypothalamic–pituitary–adrenal (HPA) axis, which maintains hormonal balance through tightly regulated feedback mechanisms. Disruption of this regulatory system is central to the development of Cushing syndrome, whether the excess cortisol originates from external medications or internal pathology. Persistent cortisol elevation alters metabolism, immune function, and endocrine signaling, producing the characteristic clinical features of the...
Hypoglycemia and Glucagon01:15

Hypoglycemia and Glucagon

Without prolonged fasting, healthy individuals maintain blood glucose levels above 3.5 mM due to a well-adapted neuroendocrine counterregulatory system that effectively prevents acute hypoglycemia, a potentially life-threatening condition. The primary clinical scenarios for hypoglycemia encompass diabetes treatment, inappropriate production of endogenous insulin or insulin-like substances by tumors, and the use of glucose-lowering agents in non-diabetic individuals. Notably, hypoglycemia in the...
Blood Studies for Cardiovascular System II: CRP, Hcy, and Cardiac Natriuretic Peptide Markers01:19

Blood Studies for Cardiovascular System II: CRP, Hcy, and Cardiac Natriuretic Peptide Markers

Cardiac biomarkers are critical in diagnosing, prognosing, and managing cardiovascular diseases. Routine measurement of specific biomarkers such as B-type natriuretic peptide (BNP), C-reactive protein (CRP), and homocysteine (Hcy) is common practice in clinical settings to evaluate heart function and predict cardiovascular events.
These markers indicate stress or strain on the heart muscle:
Natriuretic Peptides (BNP)
Cardiac myocytes produce these hormones in response to ventricular stretching...