Factors influencing the adrenocorticotropin test: role of contemporary cortisol assays, body composition, and oral contraceptive agents

Marianne Klose; Martin Lange; Aase Krogh Rasmussen; Niels Erik Skakkebaek; Linda Hilsted; Egil Haug; Marianne Andersen; Ulla Feldt-Rasmussen

doi:10.1210/jc.2006-1791

Factors influencing the adrenocorticotropin test: role of contemporary cortisol assays, body composition, and oral contraceptive agents

Marianne Klose, Martin Lange, Aase Krogh Rasmussen, Niels Erik Skakkebaek, Linda Hilsted, Egil Haug, Marianne Andersen, Ulla Feldt-Rasmussen

Research output: Contribution to journal › Journal article › Research › peer-review

Abstract

CONTEXT: The normal cortisol response to an ACTH test remains inconsistently defined, possibly caused by various subject- and test- condition-related factors. OBJECTIVE: Our objective was to evaluate the impact of newer automated immunoassays; gender, age, body composition, and endogenous sex-hormone levels; corticosteroid-binding globulin levels; and test conditions (fasting/nonfasting, rest/intermittent exercise). METHODS: A 250-microg ACTH test (0800-1000 h) was performed in 100 unmedicated subjects, 13 women taking oral contraception (OC), and six men with nephrotic syndrome. Tests were performed fasting supine (n=119), nonfasting supine (n=38), and fasting with intermittent exercise (n=45). Serum cortisol was analyzed by three immunoassays. RESULTS: Even with a negligible between-assay mean bias, individual samples from unmedicated subjects differed by as much as 110 nmol/liter. The normative 2.5th percentile for total cortisol ranged from 475-523 nmol/liter when analyzed by the three assays. In multivariate analyses, 30-min total cortisol was predicted by baseline cortisol (men plus women) and central adiposity (men) but not by gender, age, and endogenous sex hormones, corticosteroid-binding globulin, fasting/nonfasting, and exercise. Compared with unmedicated subjects, OC women had 2-fold elevated 30-min cortisol (P<0.001) but lowered calculated free cortisol (P<0.001), whereas nephrotic syndrome patients had lowered 30-min cortisol (P<0.01) in two of three assays, but similar calculated free cortisol (P>0.1). CONCLUSION: The normal response to an ACTH test is assay specific, even with newer methods, and this also applies to calculated free cortisol. Both total cortisol and calculated free cortisol were severely affected by OC, and the test is therefore only reliable if OC has been discontinued. The ACTH test is, however, robust for most of the other evaluated subject- and test-condition-related factors

Original language	English
Journal	The Journal of Clinical Endocrinology & Metabolism
Volume	92
Issue number	4
Pages (from-to)	1326-33
Number of pages	8
ISSN	0021-972X
DOIs	https://doi.org/10.1210/jc.2006-1791
Publication status	Published - 1. Apr 2007

Keywords

Adrenocorticotropic Hormone
Body Composition
Contraceptives, Oral
Female
Humans
Hydrocortisone
Male
Nephrotic Syndrome
Patient Selection
Regression Analysis
Reproducibility of Results

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10.1210/jc.2006-1791

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@article{b1a8f7a0cc2111dc8674000ea68e967b,

title = "Factors influencing the adrenocorticotropin test: role of contemporary cortisol assays, body composition, and oral contraceptive agents",

abstract = "CONTEXT: The normal cortisol response to an ACTH test remains inconsistently defined, possibly caused by various subject- and test- condition-related factors. OBJECTIVE: Our objective was to evaluate the impact of newer automated immunoassays; gender, age, body composition, and endogenous sex-hormone levels; corticosteroid-binding globulin levels; and test conditions (fasting/nonfasting, rest/intermittent exercise). METHODS: A 250-microg ACTH test (0800-1000 h) was performed in 100 unmedicated subjects, 13 women taking oral contraception (OC), and six men with nephrotic syndrome. Tests were performed fasting supine (n=119), nonfasting supine (n=38), and fasting with intermittent exercise (n=45). Serum cortisol was analyzed by three immunoassays. RESULTS: Even with a negligible between-assay mean bias, individual samples from unmedicated subjects differed by as much as 110 nmol/liter. The normative 2.5th percentile for total cortisol ranged from 475-523 nmol/liter when analyzed by the three assays. In multivariate analyses, 30-min total cortisol was predicted by baseline cortisol (men plus women) and central adiposity (men) but not by gender, age, and endogenous sex hormones, corticosteroid-binding globulin, fasting/nonfasting, and exercise. Compared with unmedicated subjects, OC women had 2-fold elevated 30-min cortisol (P<0.001) but lowered calculated free cortisol (P<0.001), whereas nephrotic syndrome patients had lowered 30-min cortisol (P<0.01) in two of three assays, but similar calculated free cortisol (P>0.1). CONCLUSION: The normal response to an ACTH test is assay specific, even with newer methods, and this also applies to calculated free cortisol. Both total cortisol and calculated free cortisol were severely affected by OC, and the test is therefore only reliable if OC has been discontinued. The ACTH test is, however, robust for most of the other evaluated subject- and test-condition-related factors",

keywords = "Adrenocorticotropic Hormone, Body Composition, Contraceptives, Oral, Female, Humans, Hydrocortisone, Male, Nephrotic Syndrome, Patient Selection, Regression Analysis, Reproducibility of Results",

author = "Marianne Klose and Martin Lange and Rasmussen, {Aase Krogh} and Skakkebaek, {Niels Erik} and Linda Hilsted and Egil Haug and Marianne Andersen and Ulla Feldt-Rasmussen",

year = "2007",

month = apr,

day = "1",

doi = "10.1210/jc.2006-1791",

language = "English",

volume = "92",

pages = "1326--33",

journal = "The Journal of Clinical Endocrinology & Metabolism",

issn = "0021-972X",

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Factors influencing the adrenocorticotropin test: role of contemporary cortisol assays, body composition, and oral contraceptive agents. / Klose, Marianne; Lange, Martin; Rasmussen, Aase Krogh et al.
In: The Journal of Clinical Endocrinology & Metabolism, Vol. 92, No. 4, 01.04.2007, p. 1326-33.

Research output: Contribution to journal › Journal article › Research › peer-review

TY - JOUR

T1 - Factors influencing the adrenocorticotropin test: role of contemporary cortisol assays, body composition, and oral contraceptive agents

AU - Klose, Marianne

AU - Lange, Martin

AU - Rasmussen, Aase Krogh

AU - Skakkebaek, Niels Erik

AU - Hilsted, Linda

AU - Haug, Egil

AU - Andersen, Marianne

AU - Feldt-Rasmussen, Ulla

PY - 2007/4/1

Y1 - 2007/4/1

N2 - CONTEXT: The normal cortisol response to an ACTH test remains inconsistently defined, possibly caused by various subject- and test- condition-related factors. OBJECTIVE: Our objective was to evaluate the impact of newer automated immunoassays; gender, age, body composition, and endogenous sex-hormone levels; corticosteroid-binding globulin levels; and test conditions (fasting/nonfasting, rest/intermittent exercise). METHODS: A 250-microg ACTH test (0800-1000 h) was performed in 100 unmedicated subjects, 13 women taking oral contraception (OC), and six men with nephrotic syndrome. Tests were performed fasting supine (n=119), nonfasting supine (n=38), and fasting with intermittent exercise (n=45). Serum cortisol was analyzed by three immunoassays. RESULTS: Even with a negligible between-assay mean bias, individual samples from unmedicated subjects differed by as much as 110 nmol/liter. The normative 2.5th percentile for total cortisol ranged from 475-523 nmol/liter when analyzed by the three assays. In multivariate analyses, 30-min total cortisol was predicted by baseline cortisol (men plus women) and central adiposity (men) but not by gender, age, and endogenous sex hormones, corticosteroid-binding globulin, fasting/nonfasting, and exercise. Compared with unmedicated subjects, OC women had 2-fold elevated 30-min cortisol (P<0.001) but lowered calculated free cortisol (P<0.001), whereas nephrotic syndrome patients had lowered 30-min cortisol (P<0.01) in two of three assays, but similar calculated free cortisol (P>0.1). CONCLUSION: The normal response to an ACTH test is assay specific, even with newer methods, and this also applies to calculated free cortisol. Both total cortisol and calculated free cortisol were severely affected by OC, and the test is therefore only reliable if OC has been discontinued. The ACTH test is, however, robust for most of the other evaluated subject- and test-condition-related factors

AB - CONTEXT: The normal cortisol response to an ACTH test remains inconsistently defined, possibly caused by various subject- and test- condition-related factors. OBJECTIVE: Our objective was to evaluate the impact of newer automated immunoassays; gender, age, body composition, and endogenous sex-hormone levels; corticosteroid-binding globulin levels; and test conditions (fasting/nonfasting, rest/intermittent exercise). METHODS: A 250-microg ACTH test (0800-1000 h) was performed in 100 unmedicated subjects, 13 women taking oral contraception (OC), and six men with nephrotic syndrome. Tests were performed fasting supine (n=119), nonfasting supine (n=38), and fasting with intermittent exercise (n=45). Serum cortisol was analyzed by three immunoassays. RESULTS: Even with a negligible between-assay mean bias, individual samples from unmedicated subjects differed by as much as 110 nmol/liter. The normative 2.5th percentile for total cortisol ranged from 475-523 nmol/liter when analyzed by the three assays. In multivariate analyses, 30-min total cortisol was predicted by baseline cortisol (men plus women) and central adiposity (men) but not by gender, age, and endogenous sex hormones, corticosteroid-binding globulin, fasting/nonfasting, and exercise. Compared with unmedicated subjects, OC women had 2-fold elevated 30-min cortisol (P<0.001) but lowered calculated free cortisol (P<0.001), whereas nephrotic syndrome patients had lowered 30-min cortisol (P<0.01) in two of three assays, but similar calculated free cortisol (P>0.1). CONCLUSION: The normal response to an ACTH test is assay specific, even with newer methods, and this also applies to calculated free cortisol. Both total cortisol and calculated free cortisol were severely affected by OC, and the test is therefore only reliable if OC has been discontinued. The ACTH test is, however, robust for most of the other evaluated subject- and test-condition-related factors

KW - Adrenocorticotropic Hormone

KW - Body Composition

KW - Contraceptives, Oral

KW - Female

KW - Humans

KW - Hydrocortisone

KW - Male

KW - Nephrotic Syndrome

KW - Patient Selection

KW - Regression Analysis

KW - Reproducibility of Results

U2 - 10.1210/jc.2006-1791

DO - 10.1210/jc.2006-1791

M3 - Journal article

C2 - 17244781

SN - 0021-972X

VL - 92

SP - 1326

EP - 1333

JO - The Journal of Clinical Endocrinology & Metabolism

JF - The Journal of Clinical Endocrinology & Metabolism

IS - 4

ER -

Factors influencing the adrenocorticotropin test: role of contemporary cortisol assays, body composition, and oral contraceptive agents

Abstract

Keywords

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