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Cited by 39Pituitary Gland Disorders and TreatmentsAdrenal Hormones and DisordersAdrenal and Paraganglionic Tumors

Cortisol diurnal rhythm and quality of life after successful medical treatment of Cushing's disease

van der Pas, R., de Bruin, C., Pereira, A. M., Romijn, J. A., Netea-Maier, R. T., Hermus, A. R., Zelissen, P. M., de Jong, F. H. +6 more·2013·Pituitary
DOI 10.1007/s11102-012-0452-2
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Abstract

Cushing's disease (CD) is associated with severely impaired quality of life (QoL). Moreover, the physiological cortisol diurnal rhythm (CDR) is disturbed in CD. QoL can improve after successful surgery, the primary treatment for CD. We evaluated the effects of medical treatment on QoL and CDR. In 17 patients, stepwise medical treatment was applied with the somatostatin analog pasireotide, the dopamine agonist cabergoline and the adrenal-blocking agent ketoconazole. After 80 days, 15/17 (88%) patients had reached normal urinary free cortisol excretion (UFC). Subsequently, patients continued medical therapy or underwent surgery. UFC, plasma and salivary CDR and QoL-related parameters (assessed using 5 questionnaires: Nottingham Health Profile, Hospital Anxiety and Depression Scale, Multidimensional Fatigue Index-20, RAND-36, CushingQoL) were measured. At baseline, 5/17 patients had preserved CDR. In 6/12 patients with disturbed baseline CDR, recovery was observed, but without any correlation with QoL. QoL was significantly impaired according to 18/20 subscales in CD patients compared to literature-derived controls. According to the RAND-36 questionnaire, patients reported more pain at day 80 (p < 0.05), which might reflect steroid-withdrawal. Generally, QoL did not improve or deteriorate after 80 days. CushingQoL scores seemed to improve after 1 year of remission in three patients that continued medical therapy (p = 0.11). CDR can recover during successful pituitary- and adrenal-targeted medical therapy. Patients with CD have impaired QoL compared to controls. Despite the occurrence of side-effects, QoL does not deteriorate after short-term biochemical remission induced by medical therapy, but might improve after sustained control of hypercortisolism.

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  • Evidence suggests that restoring cortisol circadian rhythm may improve disease control and alleviate symptoms.

    “However, evidence suggests that restoring cortisol circadian rhythm may improve disease control and alleviate symptoms (39-43).”

    From Measuring cortisol in Cushing syndrome: diagnosis, monitoring, and cortisol circadian rhythm improvement. (2026) · cites this paper as [39]

  • 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 [39]

  • Recovery of cortisol diurnal rhythm, measured by midnight serum and salivary cortisol levels, was achieved in 50% of patients treated with pasireotide alone or in combination with cabergoline and/or ketoconazole.

    “Recovery of cortisol diurnal rhythm, measured by midnight serum and salivary cortisol levels, was achieved in 50% of patients treated with pasireotide alone or in combination with cabergoline and/or ketoconazole.”

    From Measuring cortisol in Cushing syndrome: diagnosis, monitoring, and cortisol circadian rhythm improvement. (2026) · cites this paper as [39]

  • Medical therapy for CS may restore cortisol circadian rhythm.

    “This study suggests that medical therapy for CS may restore cortisol circadian rhythm, but further research is required to delineate the effectiveness of each medication in normalizing cortisol rhythms.”

    From Measuring cortisol in Cushing syndrome: diagnosis, monitoring, and cortisol circadian rhythm improvement. (2026) · cites this paper as [39]

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Authors
van der Pas, R., de Bruin, C., Pereira, A. M., Romijn, J. A., Netea-Maier, R. T., Hermus, A. R., Zelissen, P. M., de Jong, F. H., van der Lely, A. J., de Herder, W. W., Webb, S. M., Lamberts, S. W. J., Hofland, L. J., & Feelders, R. A.
Affiliations
  • Leiden University Medical Center (NL)
  • Radboud University Nijmegen (NL)
  • Utrecht University (NL)
  • Universitat Autònoma de Barcelona (ES)
  • Erasmus MC (NL)
ORCID
Venue
Pituitary
Publisher
Springer Science and Business Media LLC
Published
2012-12-08
Volume
16
Issue
4
Pages
536-544
ISSN
  • 1386-341X (ISSN-L)
  • 1573-7403
DOI
10.1007/s11102-012-0452-2
OpenAlex
W1974653576
Cited by
39
References
40
Citations by year
2026: 3 · 2025: 3 · 2024: 3 · 2023: 2 · 2021: 3 · 2020: 4 · 2018: 2 · 2017: 3 · 2016: 7 · 2015: 4 · 2014: 4 · 2013: 1
FWCI
2.19
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Pituitary (publishedVersion)
  • PubMed (publishedVersion)
  • Pure Amsterdam UMC (publishedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
  • Leiden Repository (Leiden University) (submittedVersion)
  • Radboud Repository (Radboud University) (submittedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
Keywords
Cushing's disease, diurnal cortisol rhythm, quality of life, medical treatment, pasireotide, cabergoline, ketoconazole, somatostatin analogues, dopamine agonists, urinary free cortisol, hypercortisolism, corticosteroid withdrawal, fatigue, anxiety and depression, pituitary surgery
MeSH terms
Cabergoline, Adult, Aged, Circadian Rhythm, Ergolines, Female, Humans, Hydrocortisone, Ketoconazole, Male, Middle Aged, Quality of Life, Surveys and Questionnaires, Somatostatin, Dopamine Agonists, Pituitary ACTH Hypersecretion, Young Adult

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