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Cited by 60Pituitary Gland Disorders and TreatmentsAdrenal Hormones and DisordersAdrenal and Paraganglionic Tumors

Use of late-night salivary cortisol to monitor response to medical treatment in Cushing's disease

Open access
Newell-Price, John, Pivonello, Rosario, Tabarin, Antoine, Fleseriu, Maria, Witek, Przemysław, Gadelha, Mônica R, Petersenn, Stephan, Tauchmanova, Libuse +4 more·2020·European Journal of Endocrinology
DOI 10.1530/eje-19-0695PMC PMC7003692
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Abstract

Objective: Monitoring of patients with Cushing’s disease on cortisol-lowering drugs is usually performed with urinary free cortisol (UFC). Late-night salivary cortisol (LNSC) has an established role in screening for hypercortisolism and can help to detect the loss of cortisol circadian rhythm. Less evidence exists regarding the usefulness of LNSC in monitoring pharmacological response in Cushing’s disease. Design: Exploratory analysis evaluating LNSC during a Phase III study of long-acting pasireotide in Cushing’s disease (clinicaltrials.gov: NCT01374906). Methods: Mean LNSC (mLNSC) was calculated from two samples, collected on the same days as the first two of three 24-h urine samples (used to calculate mean UFC [mUFC]). Clinical signs of hypercortisolism were evaluated over time. Results: At baseline, 137 patients had evaluable mLNSC measurements; 91.2% had mLNSC exceeding the upper limit of normal (ULN; 3.2 nmol/L). Of patients with evaluable assessments at month 12 (n = 92), 17.4% had both mLNSC ≤ULN and mUFC ≤ULN; 22.8% had mLNSC ≤ULN, and 45.7% had mUFC ≤ULN. There was high variability in LNSC (intra-patient coefficient of variation (CV): 49.4%) and UFC (intra-patient CV: 39.2%). mLNSC levels decreased over 12 months of treatment and paralleled changes in mUFC. Moderate correlation was seen between mLNSC and mUFC (Spearman’s correlation: ρ = 0.50 [all time points pooled]). Greater improvements in systolic/diastolic blood pressure and weight were seen in patients with both mLNSC ≤ULN and mUFC ≤ULN. Conclusion: mUFC and mLNSC are complementary measurements for monitoring treatment response in Cushing’s disease, with better clinical outcomes seen for patients in whom both mUFC and mLNSC are controlled.

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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 [42]

    The Discussion (page unavailable) suggests that controlling both daily cortisol secretion and late-night cortisol is an important treatment goal. The Results report greater blood-pressure improvements in patients with both measures controlled. However, the paper says it did not collect the additional within-day samples needed to confirm restoration of circadian rhythm, so it cannot establish that restoring the rhythm itself alleviates symptoms. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Improved regulation of late-night cortisol secretion, as measured by UFC and LNSC, has the potential to further reduce morbidity and mortality associated with hypercortisolemia.

    “Data from these analyses support that improved regulation of late-night cortisol secretion, a key component of circadian cortisol control, as measured by UFC and LNSC, has the potential to further reduce morbidity and mortality associated with hypercortisolemia.”

    From Measuring cortisol in Cushing syndrome: diagnosis, monitoring, and cortisol circadian rhythm improvement. (2026) · cites this paper as [42]

    The Discussion (page unavailable) identifies simultaneous control of UFC and late-night cortisol as a likely treatment goal and reports greater blood-pressure improvement when both were controlled. The Introduction (page unavailable) says effective treatment is needed to reduce morbidity and mortality in Cushing’s disease, but this analysis does not establish that improved late-night cortisol control reduces mortality. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • 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 [42]

  • Improvements in systolic and diastolic blood pressure and weight were greatest among patients who achieved normalization of both LNSC and UFC levels.

    “Improvements in systolic and diastolic blood pressure and weight were the greatest among patients who achieved normalization of both LNSC and UFC levels.”

    From Measuring cortisol in Cushing syndrome: diagnosis, monitoring, and cortisol circadian rhythm improvement. (2026) · cites this paper as [42]

  • Reductions in LNSC levels corresponded to changes in mean UFC over a 12-month treatment period in patients with CD treated with long-acting pasireotide.

    “Over the 12-month treatment period, reductions in LNSC levels corresponded to changes in mean UFC.”

    From Measuring cortisol in Cushing syndrome: diagnosis, monitoring, and cortisol circadian rhythm improvement. (2026) · cites this paper as [42]

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Research works printed but not linked: 21

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Authors
Newell-Price, J., Pivonello, R., Tabarin, A., Fleseriu, M., Witek, P., Gadelha, M. R., Petersenn, S., Tauchmanova, L., Ravichandran, S., Gupta, P., Lacroix, A., & Biller, B. M. K.
Affiliations
  • University of Sheffield (GB)
  • University of Naples Federico II (IT)
  • Centre Hospitalier Universitaire de Bordeaux (FR)
  • Oregon Health & Science University (US)
  • Medical University of Warsaw (PL)
  • Universidade Federal do Rio de Janeiro (BR)
  • 7ENDOC Center for Endocrine Tumors, Hamburg, Germany
  • 8Novartis Pharma AG, Basel, Switzerland
  • Novartis (United States) (US)
  • Novartis (India) (IN)
  • Centre Hospitalier de l’Université de Montréal (CA)
  • Massachusetts General Hospital (US)
Corresponding author
Newell-Price, John
ORCID
Venue
European Journal of Endocrinology
Publisher
Oxford University Press (OUP)
Published
2020-02
Volume
182
Issue
2
Pages
207-217
ISSN
  • 0804-4643 (ISSN-L)
  • 1479-683X
DOI
10.1530/eje-19-0695
PMC
PMC7003692
OpenAlex
W2992631679
Cited by
60
References
8
Citations by year
2026: 4 · 2025: 16 · 2024: 9 · 2023: 9 · 2022: 11 · 2021: 8 · 2020: 3
FWCI
5.84
Type
journal article
Language
en
Open access
Licence
Locations
  • European Journal of Endocrinology (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
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, late-night salivary cortisol, urinary free cortisol, pasireotide, treatment response monitoring, hypercortisolism, diurnal cortisol rhythm, blood pressure, weight loss
MeSH terms
Adult, Circadian Rhythm, Female, Hormones, Humans, Hydrocortisone, Male, Middle Aged, Pituitary Neoplasms, Saliva, Somatostatin, Treatment Outcome, Pituitary ACTH Hypersecretion, ACTH-Secreting Pituitary Adenoma

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