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Cited by 28Pituitary Gland Disorders and TreatmentsAdrenal Hormones and DisordersStress Responses and Cortisol

Apparently complete restoration of normal daily adrenocorticotropin, cortisol, growth hormone, and prolactin secretory dynamics in adults with Cushing's disease after clinically successful transsphenoidal adenomectomy

Veldman, R. G.·2000·Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.85.11.4039
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Abstract

ACTH production in Cushing's disease is characterized by a markedly elevated rate of basal (nonpulsatile) secretion, an increased mass of ACTH released per burst and an unremarkable pulse frequency. In addition, the ACTH secretory process and that of GH and PRL exhibit profoundly disordered patterns. Whether some or all of these disturbances can be reversed or normalized by transsphenoidal microadenomectomy remains unknown. We therefore investigated the detailed dynamics of ACTH, GH, and PRL in eight patients (aged 38.9+/-4.2 yr) with pituitary-dependent Cushing's disease who were in long-term (8.2+/-1.7 yr) clinical remission following transsphenoidal surgery and eight controls matched for age, gender, and body mass index. To this end, blood was sampled at 10-min intervals for 24 h for the later assay of ACTH, cortisol, GH, and PRL. Secretory activity was quantitated by deconvolution methods, and the pattern orderliness (regularity) of hormone release was determined by the approximate entropy (ApEn) statistic. The joint synchrony of ACTH and cortisol secretion was monitored by the cognate bivariate statistic, cross-ApEn. Diurnal properties of the hormonal release were appraised by cosinor analysis. Based on deconvolution analysis, postsurgical patients exhibited a normal frequency, half-life, duration, and mass of ACTH and cortisol secretory bursts. Accordingly, the 24-h production rates of both ACTH (2.5+/-0.7 microg/L in patients vs. 2.9+/-0.7 microg/L in controls; P = 0.755) and cortisol (49+/-11 micromol/L in patients vs. 73+/-15 micromol/L in controls; P = 0.217) were normal also. The acrophase of the diurnal rhythm of ACTH (patients, 0817 h +/- 37 min; controls, 0850 h +/- 38 min; P = 0.629) and cortisol (patients, 1000 h +/- 24 min; controls, 0855 h +/- 30 min; P = 0.175) was also restored by surgery. ApEn values of ACTH (patients, 1.168 +/- 0.090; controls, 0.864+/-0.122; P = 0.133) and cross-ApEn of ACTH-cortisol (patients, 1.396+/-0.087; controls, 1.170+/-0.076; P = 0.140) secretion were both normal in this cohort, denoting restoration of the secretory process regularity. Cortisol ApEn was slightly higher in patients (patients, 1.034+/-0.084; controls, 0.831+/-0.038; P = 0.048). Both GH and PRL time series manifested full reconstitution of pulsatile, 24-h rhythmic, and entropic properties. In summary, clinically successful transsphenoidal microadenomectomy in adults with Cushing's disease can fully normalize virtually all quantitative features of regulated ACTH, cortisol, GH, and PRL secretion. Further studies will be needed to establish the consistency of these findings in larger cohorts of adults with Cushing's disease and in children with this disorder and to delineate the significance, if any, of a residual, minimally detectable disruption of orderly cortisol secretion in this patient population.

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  • Normalization of the cortisol circadian rhythm after most medical therapies has rarely been investigated and is not routinely measured to assess treatment response.

    “Although this can be achieved after successful surgery selectively removing the source of excess ACTH or cortisol, normalization of the cortisol circadian rhythm after most medical therapies has rarely been investigated and is not routinely measured to assess treatment response (39-44).”

    From Measuring cortisol in Cushing syndrome: diagnosis, monitoring, and cortisol circadian rhythm improvement. (2026) · cites this paper as [44]

  • Apparent restoration of the normal cortisol circadian rhythm has been reported following surgical therapy.

    “Apparent restoration of the normal cortisol circadian rhythm has been reported following surgical therapy (44).”

    From Measuring cortisol in Cushing syndrome: diagnosis, monitoring, and cortisol circadian rhythm improvement. (2026) · cites this paper as [44]

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Authors
Veldman, R. G.
Affiliations
Leiden University Medical Center (NL)
Venue
Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2000-11-01
Volume
85
Issue
11
Pages
4039-4046
ISSN
0021-972X (ISSN-L)
DOI
10.1210/jc.85.11.4039
OpenAlex
W2074535071
Cited by
27
References
32
Citations by year
2021: 1 · 2016: 2 · 2014: 2 · 2013: 1 · 2012: 2
FWCI
1.51
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords
Cushing's disease, ACTH secretion, cortisol secretion, growth hormone secretion, prolactin secretion, pulsatile hormone secretion, approximate entropy, deconvolution, diurnal cycle, pituitary adenoma, surgical remission, cosinor analysis, cross-approximate entropy
MeSH terms
Adenoma, Adrenocorticotropic Hormone, Adult, Circadian Rhythm, Cushing Syndrome, Female, Follow-Up Studies, Humans, Hydrocortisone, Male, Middle Aged, Pituitary Neoplasms, Prolactin, Reference Values, Human Growth Hormone, Hormone Replacement Therapy

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