A Phase 1b/2a Open-label Multiple-ascending Dose Exploratory Study of CRN04894 in ACTH-dependent Cushing's Syndrome (Cushing's Disease or Ectopic ACTH Syndrome)

A Phase 1b/2a, first-in-disease, open-label, multiple-ascending dose exploratory study to evaluate safety, tolerability, pharmacokinetics (PK), and pharmacodynamic biomarker responses associated with CRN04894 (an adrenocorticotropic hormone [ACTH] receptor antagonist) in participants with ACTH-dependent Cushing's syndrome (Cushing's disease or Ectopic ACTH Syndrome [EAS])

Start Date12 Oct 2023

Sponsor / Collaborator

Crinetics Pharmaceuticals, Inc.

NCT05307328 / Active, not recruitingPhase 2

SPI-62 as a Treatment for Adrenocorticotropic Hormone-dependent Cushing's Syndrome

This is a randomized, placebo-controlled, study of SPI-62 in subjects with ACTH-dependent Cushing's syndrome caused by a non-adrenal tumor. Subjects will receive each of the following 2 treatments for 24 weeks: SPI-62 and matching placebo with the option of long-term extension.

Start Date01 Sep 2022

Sponsor / Collaborator

Sparrow Pharmaceuticals, Inc.

NCT02780882 / WithdrawnPhase 2IIT

A Proof of Concept and Open-label Study to Test the Efficacy and Safety of Pasireotide in Patients With Ectopic ACTH-producing Tumors

The purpose of this prospective open-label phase II study, is to evaluate the efficacy of pasireotide twice daily subcutaneous injections for normalizing 24 hour urine free cortisol in patients with ectopic ACTH-producing tumors as measured by the proportion of patients achieving normal UFC at the end of the study period.

Start Date01 Dec 2015

Sponsor / Collaborator

Cedars-Sinai Medical Center

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100 Clinical Results associated with Ectopic ACTH Syndrome

100 Translational Medicine associated with Ectopic ACTH Syndrome

0 Patents (Medical) associated with Ectopic ACTH Syndrome

1,438

Literatures (Medical) associated with Ectopic ACTH Syndrome

01 Nov 2024·Clinical Nuclear Medicine

Ectopic Cushing Syndrome Localized by 68Ga-DOTA-LM3 PET/CT

Article

Author: Bastian, Moritz B ; Blickle, Arne ; Bastian, Moritz B. ; Ezziddin, Samer ; Rosar, Florian ; Burgard, Caroline

AbstractA 53-year-old woman presented with signs of Cushing syndrome with challenges in diagnosis and localization. A novel somatostatin receptor (SSTR)–targeted PET/CT with 68Ga-DOTA-LM3, an SSTR antagonist, revealed a suspicious focal finding in the pancreatic head, proven to be ectopic Cushing syndrome after surgical resection. This interesting image clearly shows the potential of PET imaging with SSTR antagonists as 68Ga-DOTA-LM3 in the diagnosis of ectopic Cushing syndrome.

15 Oct 2024·The Journal of Clinical Endocrinology & Metabolism

Personalized Noninvasive Diagnostic Algorithms Based on Urinary Free Cortisol in ACTH-dependant Cushing's Syndrome

Article

Author: Tabarin, Antoine ; Mohammedi, Kamel ; Furnica, Raluca Maria ; Lavoillotte, Julie ; Chanson, Philippe ; Young, Jacques ; Salenave, Sylvie ; Maiter, Dominique

AbstractContextCurrent guidelines for distinguishing Cushing's disease (CD) from ectopic ACTH secretion (EAS) are questionable, as they use pituitary magnetic resonance imaging (MRI) as first-line investigation for all patients. CRH testing is no longer available, and they suggest performing inferior petrosal sinus sampling (BIPPS), an invasive and rarely available investigation, in many patients.ObjectiveTo establish noninvasive personalized diagnostic strategies based on the probability of EAS estimated from simple baseline parameters.DesignRetrospective study.SettingUniversity hospitals.PatientsTwo hundred forty-seven CD and 36 EAS patients evaluated between 2001 and 2023 in 2 French hospitals. A single-center cohort of 105 Belgian patients served as external validation.ResultsTwenty-four-hour urinary free cortisol (UFC) had the highest area under the receiver operating characteristic curve for discrimination of CD from EAS (.96 [95% confidence interval (CI), .92-.99] in the primary study and .99 [95% CI, .98-1.00] in the validation cohort). The addition of clinical, imaging, and biochemical parameters did not improve EAS prediction over UFC alone, with only BIPPS showing a modest improvement (C-statistic index .99 [95% CI, .97-1.00]). Three groups were defined based on baseline UFC: < 3 (group 1), 3-10 (group 2), and > 10 × the upper limit of normal (group 3), and they were associated with 0%, 6.1%, and 66.7% prevalence of EAS, respectively. Diagnostic approaches performed in our cohort support the use of pituitary MRI alone in group 1, MRI first followed by neck-to-pelvis computed tomography scan (npCT) when negative in group 2, and npCT first followed by pituitary MRI when negative in group 3. When not combined with the CRH test, the desmopressin test has limited diagnostic value.ConclusionUFC accurately predicts EAS and can serve to define personalized and noninvasive diagnostic algorithms.

15 Oct 2024·The Journal of Clinical Endocrinology & Metabolism

Mesenchymal Stem Cells Induce an Immunosuppressive Microenvironment in Pituitary Tumors

Article

Author: Vela-Patiño, Sandra ; Hinojosa-Alvarez, Silvia ; Hernandez-Perez, Jesus ; Chavez-Santoscoy, Alejandra ; Fajardo-Orduña, Guadalupe R ; Taniguchi-Ponciano, Keiko ; Cano-Zaragoza, Amayrani ; Marrero-Rodriguez, Daniel ; Gomez-Apo, Erick ; Montesinos, Juan Jose ; Martinez-Mendoza, Florencia ; Kerbel-Suton, Jacobo ; Cortes-Morales, Victor A ; Mercado, Moises

AbstractContextThe tumor microenvironment (TME) includes diverse cellular components such as mesenchymal stem cells (MSCs) and immune cells, among others. MSC have been isolated from different tumors and they favor tumor cell growth; however, their role in pituitary tumors (PTs) remains unknown.ObjectiveHerein we report the presence of MSCs in 2 adrenocorticotropin (ACTH)-secreting PTs causing Cushing disease (MCU), 2 nonfunctioning adenomas of gonadotrope differentiation (MNF), and 2 nontumoral pituitary glands (MS).MethodsWe have analyzed the transcriptomic profiles by RNA sequencing and compared MSCs in terms of their immunosuppressive effects against lymphoid T-cell and macrophage populations by means of cocultures and flow cytometry.ResultsOur transcriptomic analysis revealed molecular differences between MSCs derived from nontumoral pituitaries and MSCs derived from PTs. Two distinct subpopulations of MSC emerged: one displaying immunosuppressive properties and the other with increased proproliferative capabilities, regardless of their origin. MSCs derived from ACTH- and nonfunctioning PTs, but not those derived from nontumoral glands, significantly inhibited the proliferation of activated T cells, favored the generation of regulatory T cells, and promoted M2 macrophage polarization. Such immunosuppressive effects were correlated with an upregulation of programmed death ligand 1 and intracellular expression of macrophage colony-stimulating factor (M-CSF) and interleukin-10. Importantly, MSC derived from ACTH-PTs showed a higher immunosuppressive potential than MSC isolated from nonfunctioning tumors.ConclusionThis study demonstrates the presence of at least 2 MSC subpopulations in the pituitary gland and suggests that immunosuppressive effects of MSCs may have important implications in PT growth.

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