Irregular and frequent cortisol secretory episodes with preserved diurnal rhythmicity in primary adrenal Cushing's syndrome
Open accessAbstract
To evaluate the pathophysiology of altered cortisol secretion in patients with primary adrenal hypercortisolism, cortisol secretion was investigated in 12 patients, seven with a unilateral adenoma and five with ACTH-independent macronodular adrenal hyperplasia compared with age- and gender-matched controls and with patients with pituitary-dependent hypercortisolism. Pulsatile secretion was increased 2-fold (P = 0.04), attributable to increased event frequency (P = 0.002). All patients showed a significant diurnal rhythm with a delay in phase shift of 3 h (P = 0.01). Approximate entropy ratio, a feedback-sensitive measure, was increased compared with controls (P = 0.00003) but similar to that of pituitary-dependent hypercortisolism (P = 0.77), denoting loss of autoregulation. Cortisol burst-mass tended to be smaller in patients with ACTH-independent macronodular adrenal hyperplasia than in unilateral adenoma (P = 0.06). In conclusion, increased cortisol secretion in patients with primary adrenal Cushing's syndrome is caused by amplified pulsatile secretion via event frequency modulation. We speculate that partial preservation of secretory regularity and diurnal rhythmicity point to incomplete autonomy of these tumors.
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High frequency sampling in humans shows that hypercortisolism is associated with a reduction in the ultradian period of CORT oscillations.
“Evidence from high frequency sampling in humans shows hypercortisolism is associated with a reduction in the ultradian period of CORT oscillations (Van Aken et al., 2005).”
From Dynamic Hormone Control of Stress and Fertility (2020) · cites this paper as Van Aken et al., 2005
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- Authors
- van Aken, M. O., Pereira, A. M., van Thiel, S. W., van den Berg, G., Frölich, M., Veldhuis, J. D., Romijn, J. A., & Roelfsema, F.
- Affiliations
- Department of Endocrinology and Metabolic Diseases (M.O.v.A., A.M.P., S.W.v.T., G.v.d.B., M.F., J.A.R., F.R.), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
- Leiden University Medical Center (NL)
- Mayo Clinic (US)
- Corresponding author
- Roelfsema, F.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2005-03-01
- Volume
- 90
- Issue
- 3
- Pages
- 1570-1577
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC1237022
- OpenAlex
- W2095865455
- Cited by
- 31
- References
- 51
- Citations by year
- 2025: 3 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 4 · 2017: 1 · 2016: 3 · 2015: 2 · 2014: 1 · 2013: 2 · 2012: 2
- FWCI
- 0.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Funders
- Universiteit Leiden
- Leids Universitair Medisch Centrum
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK060717)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Keywords
- cortisol secretion, pulsatile secretion, diurnal cycle, approximate entropy, ACTH-independent macronodular adrenal hyperplasia, adrenal adenoma, pituitary-dependent hypercortisolism, event frequency
- MeSH terms
- Adenoma, Adrenal Gland Neoplasms, Adrenal Glands, Adult, Aged, Circadian Rhythm, Cushing Syndrome, Female, Humans, Hydrocortisone, Male, Middle Aged, Entropy
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