An evaluation of measured and calculated serum free cortisol in a group of patients with known adrenal suppression

Barlow, Nicola; Holme, Jayne; Stockley, Robert A.; Clark, P. M. S.

doi:10.1258/acb.2010.009246

Cited by 11 publications

(7 citation statements)

References 18 publications

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“…While not as accurate as equilibrium dialysis in assessing free serum cortisol, Coolen's equation is an accepted surrogate measure of free cortisol and has been shown to correlate with measured serum free cortisol in a number of studies. [32][33][34][35][36] While Barlow et al 35 found Coolen's equation to underestimate measured free cortisol, Ho et al found close agreement between measured and calculated free cortisol. 36 Discrepancies are amplified once CBG is saturated at cortisol levels of 650 nmol/l.…”

Section: Discussionmentioning

confidence: 99%

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Optimizing glucocorticoid replacement therapy in severely adrenocorticotropin‐deficient hypopituitary male patients

Behan

Rogers

Hannon

et al. 2011

Clinical Endocrinology

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Section: Discussionmentioning

confidence: 99%

“…32-36 While Barlow et al 35 found Coolen's equation to underestimate measured free cortisol, Ho et al found close agreement between measured and calculated free cortisol. 32-36 While Barlow et al 35 found Coolen's equation to underestimate measured free cortisol, Ho et al found close agreement between measured and calculated free cortisol.…”

Section: Discussionmentioning

confidence: 99%

Optimizing glucocorticoid replacement therapy in severely adrenocorticotropin‐deficient hypopituitary male patients

Behan

Rogers

Hannon

et al. 2011

Clinical Endocrinology

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“…However given the study was carried out in normal volunteers, Coolens’ equation [ 25 ] is an accepted surrogate measure of plasma free cortisol, which has been used in a recent study in the assessment of hydrocortisone replacement [ 43 ]. While Barlow et al [ 44 ] found that Coolens’ equation underestimated measured cortisol, Ho et al [ 37 ] reported close agreement between measured and calculated free cortisol. The number of participants was relatively small and did not allow further analysis of other factors which may affect clearance such as body mass index.…”

Section: Discussionmentioning

confidence: 99%

Plasma, salivary and urinary cortisol levels following physiological and stress doses of hydrocortisone in normal volunteers

et al. 2014

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BackgroundGlucocorticoid replacement is essential in patients with primary and secondary adrenal insufficiency, but many patients remain on higher than recommended dose regimens. There is no uniformly accepted method to monitor the dose in individual patients. We have compared cortisol concentrations in plasma, saliva and urine achieved following “physiological” and “stress” doses of hydrocortisone as potential methods for monitoring glucocorticoid replacement.MethodsCortisol profiles were measured in plasma, saliva and urine following “physiological” (20 mg oral) or “stress” (50 mg intravenous) doses of hydrocortisone in dexamethasone-suppressed healthy subjects (8 in each group), compared to endogenous cortisol levels (12 subjects). Total plasma cortisol was measured half-hourly, and salivary cortisol and urinary cortisol:creatinine ratio were measured hourly from time 0 (between 0830 and 0900) to 5 h. Endogenous plasma corticosteroid-binding globulin (CBG) levels were measured at time 0 and 5 h, and hourly from time 0 to 5 h following administration of oral or intravenous hydrocortisone. Plasma free cortisol was calculated using Coolens’ equation.ResultsPlasma, salivary and urine cortisol at 2 h after oral hydrocortisone gave a good indication of peak cortisol concentrations, which were uniformly supraphysiological. Intravenous hydrocortisone administration achieved very high 30 minute cortisol concentrations. Total plasma cortisol correlated significantly with both saliva and urine cortisol after oral and intravenous hydrocortisone (P <0.0001, correlation coefficient between 0.61 and 0.94). There was no difference in CBG levels across the sampling period.ConclusionsAn oral dose of hydrocortisone 20 mg is supraphysiological for routine maintenance, while stress doses above 50 mg 6-hourly would rarely be necessary in managing acute illness. Salivary cortisol and urinary cortisol:creatinine ratio may provide useful alternatives to plasma cortisol measurements to monitor replacement doses in hypoadrenal patients.

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“…A power function model was selected to build the relationship between serum and saliva cortisol in the population approach instead of the published regression approach . This provided not just population estimates but also individual prediction.…”

Section: Discussionmentioning

confidence: 99%

“…As a result, another advantage of testing salivary sampling is that the distribution of cortisol from blood to saliva generally occurs by passive diffusion and different researches have shown that the salivary cortisol concentration correlates well with the serum‐free cortisol concentration throughout the physiological concentration range . Under normal physiological condition without a pharmacological challenge, the relationship between serum and saliva cortisol has already been studied with regression analysis . However, after a challenge of 5‐HTP, the higher range of cortisol in both serum and saliva should further be studied.…”

Section: Introductionmentioning

confidence: 99%

PK/PD modeling of 5‐hydroxytryptophan (5‐HTP) challenge test with cortisol measurement in serum and saliva

Zheng

Jacobs

Pelt³

et al. 2020

Pharmacology Res & Perspec

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This research was planned to build a Pharmacokinetic/Pharmacodynamic (PK/PD) model of 5‐hydroxytryptophan (5‐HTP) challenge study including a circadian rhythm component of cortisol and to predict serum cortisol based on saliva cortisol. Data from three 5‐HTP challenge studies in healthy volunteers were collected. Serum 5‐HTP, saliva, and serum cortisol were sampled as PK and PD marker. The population PK/PD modeling approach was applied. A baseline model of serum cortisol was built to assess the circadian rhythm before a pharmacodynamic model was used to evaluate the drug effect of the 5‐HTP on cortisol. Finally, linear and power function relationships were tested to predict serum cortisol based on saliva cortisol. The PK of 5‐HTP could be described using a one‐compartment model with a transit compartment. The typical value for clearance was 20.40 L h−1 and showed inter‐study variability. A cosine function was chosen and properly described the circadian rhythm of serum cortisol. A linear approximation model was applied to fit the 5‐HTP PD effect on cortisol data with a slope of 4.16 ng mL−1 h. A power function provided a better description than a linear function to relate the saliva and serum cortisol. In conclusion, a circadian rhythm component was built in the PK/PD model of the 5‐HTP challenge test which could better improve the understanding of the stimulating effect on HPA with cortisol change. After the 5‐HTP challenge, saliva cortisol correlated well with serum cortisol and was predictable by a population PK‐PD model.

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An evaluation of measured and calculated serum free cortisol in a group of patients with known adrenal suppression

Cited by 11 publications

References 18 publications

Optimizing glucocorticoid replacement therapy in severely adrenocorticotropin‐deficient hypopituitary male patients

Optimizing glucocorticoid replacement therapy in severely adrenocorticotropin‐deficient hypopituitary male patients

Plasma, salivary and urinary cortisol levels following physiological and stress doses of hydrocortisone in normal volunteers

PK/PD modeling of 5‐hydroxytryptophan (5‐HTP) challenge test with cortisol measurement in serum and saliva

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