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Cited by 21Pituitary Gland Disorders and TreatmentsAdrenal Hormones and DisordersAdrenal and Paraganglionic Tumors

Improved clinical outcomes during long-term osilodrostat treatment of Cushing disease with normalization of late-night salivary cortisol and urinary free cortisol

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Newell-Price, John, Fleseriu, Maria, Pivonello, Rosario, Feelders, Richard A, Gadelha, Mônica R, Lacroix, André, Witek, Przemysław, Heaney, Anthony P +3 more·2024·Journal of the Endocrine Society
DOI 10.1210/jendso/bvae201PMC PMC11604051
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Abstract

Purpose: To assess whether simultaneous normalization of late-night salivary cortisol (LNSC) and mean urinary free cortisol (mUFC) in patients with Cushing disease treated with osilodrostat is associated with better clinical outcomes than control of mUFC or LNSC alone. Methods: Pooled data from two phase III osilodrostat studies (LINC 3 and LINC 4) were analyzed. Both comprised a 48-week core phase and an optional open-label extension. Changes in cardiovascular/metabolic-related parameters, physical manifestations of hypercortisolism, and quality of life (QoL) were evaluated across the following patient subgroups: both LNSC and mUFC controlled, only mUFC controlled, only LNSC controlled, and neither controlled. Results: Of 160 patients included in the analysis, 85.0% had both LNSC and mUFC uncontrolled at baseline. At week 72, 48.6% of patients had both LNSC and mUFC controlled; these patients generally exhibited greater improvements in cardiovascular/metabolic-related parameters than those with only mUFC controlled or both LNSC and mUFC uncontrolled: systolic/diastolic blood pressure, −7.4%/−4.9%, −6.0%/−5.5%, and 2.3%/0.8%, respectively; fasting plasma glucose, −5.0%, −4.8%, and 1.9%; glycated hemoglobin, −5.1%, −4.8%, and −1.3%. Weight, waist circumference, and body mass index improved with control of LNSC and/or mUFC; physical manifestations of hypercortisolism generally improved regardless of LNSC/mUFC control. Patients with both LNSC and mUFC controlled or only mUFC controlled had the greatest improvement from baseline to week 72 in QoL. Conclusion: In osilodrostat-treated patients with Cushing disease, normalization of LNSC and mUFC led to improvements in long-term outcomes, indicating that treatment should aim for normalization of both parameters for optimal patient outcomes. Clinical trial identifiers: NCT02180217 (LINC 3); NCT02697734 (LINC 4)

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  • Among patients with CS, normalization of cortisol concentrations results in improvements in morbidity, mortality, and quality of life.

    “Among patients with CS, normalization of cortisol concentrations results in improvements in morbidity, mortality, and quality of life (28, 35, 109, 110).”

    From Measuring cortisol in Cushing syndrome: diagnosis, monitoring, and cortisol circadian rhythm improvement. (2026) · cites this paper as [110]

    The Discussion (page not provided) says cortisol normalization is a treatment goal intended to reduce comorbidities and mortality risk. The Results report improved cardiovascular/metabolic measures and quality of life in patients with Cushing disease whose cortisol measures were controlled. The paper does not report improved mortality, and describes mortality reduction as a potential benefit rather than an observed outcome. (LLM, conf=0.88)

    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 [110]

    The Discussion reports that combined LNSC and mUFC control was associated with better clinical measures in patients with Cushing disease and could reduce comorbidities and mortality risk. However, the Methods (Assessments; page unavailable) describe mUFC as a 24-hour urine measure, not a measure of late-night cortisol secretion; only LNSC is sampled late at night. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • A total of 48.6% of patients with CD treated with osilodrostat in 2 Phase 3 studies achieved control of both LNSC and mean UFC.

    “A total of 48.6% of patients had achieved control of both LNSC and mean UFC.”

    From Measuring cortisol in Cushing syndrome: diagnosis, monitoring, and cortisol circadian rhythm improvement. (2026) · cites this paper as [110]

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Cites

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Research works printed but not linked: 29

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Authors
Newell-Price, J., Fleseriu, M., Pivonello, R., Feelders, R. A., Gadelha, M. R., Lacroix, A., Witek, P., Heaney, A. P., Piacentini, A., Pedroncelli, A. M., & Biller, B. M. K.
Affiliations
  • University of Sheffield (GB)
  • Oregon Health & Science University (US)
  • University of Naples Federico II (IT)
  • Erasmus MC (NL)
  • Universidade Federal do Rio de Janeiro (BR)
  • Centre Hospitalier de l’Université de Montréal (CA)
  • Medical University of Warsaw (PL)
  • University of California, Los Angeles (US)
  • Recordati (Italy) (IT)
  • Recordati AG , 4057 Basel ,
  • Massachusetts General Hospital (US)
Corresponding author
Newell-Price, John
ORCID
Venue
Journal of the Endocrine Society
Publisher
The Endocrine Society
Published
2024-11-12
Volume
9
Issue
1
Pages
bvae201-bvae201
ISSN
2472-1972 (ISSN-L)
DOI
10.1210/jendso/bvae201
PMC
PMC11604051
OpenAlex
W4404275769
Cited by
21
References
6
Citations by year
2026: 10 · 2025: 11
FWCI
6.92
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of the Endocrine Society (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, cc-by)
  • White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders
Novartis Pharma
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, osilodrostat, late-night salivary cortisol, urinary free cortisol, hypercortisolism, quality of life, blood pressure, HbA1c, long-term treatment outcomes

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