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Ferdinand Roelfsema Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands

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Diana van Heemst Department of Internal Medicine, Section Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands

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Ali Iranmanesh Endocrine Section, Medical Service, Salem Veterans Affairs Medical Center, Salem, Virginia, USA

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Paul Takahashi Primary Care Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA

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Rebecca Yang Endocrine Research Unit, Mayo Medical and Graduate Schools, Clinical Translational Research Center, Mayo Clinic, Rochester, Minnesota, USA

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Johannes D Veldhuis Endocrine Research Unit, Mayo Medical and Graduate Schools, Clinical Translational Research Center, Mayo Clinic, Rochester, Minnesota, USA

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Context

Studies on 24-h cortisol secretion are rare. The impact of sex, age and adiposity on cortisol levels, often restricted to one or a few samples, are well recognized, but conflicting.

Objective

To investigate cortisol dynamics in 143 healthy men and women, spanning 7 decades and with a 2-fold body mass index (BMI) range with different analytic tools.

Setting

Clinical Research Unit.

Design

Cortisol concentrations in 10-min samples collected for 24 h. Outcomes were mean levels, deconvolution parameters, approximate entropy (ApEn, regularity statistic) and 24-h rhythms.

Results

Total 24-h cortisol secretion rates estimated by deconvolution analysis were sex, age and BMI independent. Mean 24-h cortisol concentrations were lower in premenopausal women than those in men of comparable age (176 ± 8.2 vs 217 ± 9.4 nmol/L, P = 0.02), but not in subjects older than 50 years. This was due to lower daytime levels in women, albeit similar in the quiescent overnight period. Aging increased mean cortisol by 10 nmol/L per decade during the quiescent secretory phase and advanced the acrophase of the diurnal rhythm by 24 min/decade. However, total 24-h cortisol secretion rates estimated by deconvolution analysis were sex, age and BMI independent. ApEn of 24-h profiles was higher (more random) in premenopausal women than those in men (1.048 ± 0.025 vs 0.933 ± 0.023, P = 0.001), but not in subjects older than 50 years. ApEn peaked during the daytime.

Conclusion

Sex and age jointly determine the 24-h cortisol secretory profile. Sex effects are largely restricted to age <50 years, whereas age effects elevate concentrations in the late evening and early night and advance the timing of the peak diurnal rhythm.

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Ferdinand Roelfsema Department of Internal Medicine, Section Endocrinology, Leiden University Medical Center, Leiden, The Netherlands

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Peter Y Liu Department of Medicine, David Geffen School of Medicine at UCLA, Harbor-UCLA Medical Center and Los Angeles Biomedical Research Institute, Los Angeles, California, USA

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Rebecca Yang Endocrine Research Unit, Mayo Clinic College of Medicine, Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota, USA

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Paul Takahashi Primary Care Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA

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Johannes D Veldhuis Endocrine Research Unit, Mayo Clinic College of Medicine, Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota, USA

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Background:

Interleukin-2 (IL-2), one of the proinflammatory cytokines, is used in the treatment of certain malignancies. In some studies, transient increases in cortisol and ACTH secretion occurred. Thus, this agent may be used as an experimental probe of adrenal cortisol secretion.

Objective:

This study quantifies the effects of low and moderate doses of IL-2 on cortisol secretion and assesses the modulation by age, dose and body composition.

Site:

Mayo Clinical Translational Research Unit.

Subjects:

Study comprised 35 healthy men, 17 young and 18 older.

Methods:

Randomized prospective double-blind saline-controlled study of IL-2 administration in two doses with concurrent 10-min blood sampling for 24 h.

Outcome measures:

Deconvolution analysis and approximate entropy of cortisol secretion.

Results:

Low-dose IL-2 administration increased nocturnal pulsatile cortisol secretion from 1460 ± 160 to 2120 ± 220 nmol/L/8 h in young subjects and from 1680 ± 105 to 1960 ± 125 nmol/L/8 h (treatment P < 0.0001, but more in young than older, P = 0.02). Comparable results were obtained for total cortisol secretion (P treatment <0.0001, age effect P = 0.005). The higher IL-2 dose caused a large increase in young (P < 0.0001), but not in older (P = 0.90) subjects. This dose also increased approximate entropy from 0.877 ± 0.041 to 1.024 ± 0.049 (P = 0.008), pointing to reduced secretory orderliness. Incremental cortisol (nocturnal) secretion correlated negatively with visceral fat mass (R = −0.41, P = 0.019).

Conclusion:

In healthy men, IL-2 injection drives pulsatile cortisol secretion in a dose-dependent way in young, but not older, individuals and erodes cortisol secretory orderliness at a higher dose in young subjects. Cortisol responses are diminished with increasing abdominal visceral fat mass.

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