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Billy Gellepis

Lori korsakoff, RN

Vivien Bonert, MD

Lori Korsakoff, RN

Vivian Bonert, MD

The purpose of the study is to determine genetic links among blood-relatives and between spouses of patients with pituitary tumors.

The purpose of the family study is to investigate the genetic basis for the development of pituitary tumors by assessing the prevalence of pituitary tumors in relatives of probands with the disease as compared to the prevalence in unrelated spouses sharing a similar environment.

cell lines are established for future genetic analysis

Prevalence of Pituitary Incidentaloma in Relatives of Patients With Pituitary Adenoma

Cedars-Sinai Medical Center

ACTH-Secreting Pituitary Adenoma

Pituitary ACTH Hypersecretion

ACTH-secreting Pituitary Adenoma

Antineoplastic Agents

All Drugs and Chemicals

Bexarotene

Zachary Bush, MD

Mary Lee Vance, MD

The objective of this pilot study is to establish the safety and tolerability of short-term therapy with bexarotene in patient's with Cushing's disease, and study the clinical, biochemical, and cellular effects of a preoperative five-day course of bexarotene in these patients before undergoing transsphenoidal surgery.

Cushing's disease refers to a condition of glucocorticoid excess caused by an adrenocorticotropic hormone (ACTH) producing pituitary tumor, which account for 10-15% of all pituitary tumors. The majority of corticotroph tumors are microadenomas at the time of diagnosis, and accurate surgical and histologic identification of these tumors can be challenging. ACTH is produced in corticotroph cells within the anterior pituitary via the precursor pro-opiomelanocortin (POMC). In both physiologic and pathologic conditions the promoter for POMC is regulated by multiple transcription factors which include AP-1 and Nurr77. Retinoic acid has been shown to inhibit activation of the POMC promoter in corticotroph tumor cell culture via disruption of Nurr77 transcriptional activity. The expression of the orphan nuclear receptor termed chicken ovalbumin upstream promoter-transcription factor I (COUP-TFI) antagonizes retinoic acid signaling, and has been reported to be present in normal corticotroph cells, but lacking in adenomatous corticotroph cells in tissue culture studies. Through the retrospective analysis of 34 human corticotroph tumors we have demonstrated a consistent lack of COUP-TFI in 100% of the microadenomas that were not visible, or measured less than 5 millimeters by preoperative MRI. In total, 85% of all tumors studied showed absence of COUP-TFI. Based on in vitro data from rat and human corticotroph tumors, cells lacking COUP-TFI are vulnerable to retinoid-induced cell death via Nurr77-mediated apoptosis, an effect that is reversed by COUP-TFI gene transfection. In 2006, Castillo et al. published the results of a six-month trial which randomized 44 dogs with Cushing's disease to an RXR agonist (9-cis retinoic acid), or to ketoconazole. RXR agonist therapy outperformed ketoconazole for all endpoints, resulting in normalization of ACTH and cortisol levels in 100% of subjects that completed the study, and improved morbidity and mortality. All of the dogs treated with the RXR agonist remained in remission for the duration of the 6 to 12 month post-treatment followup.

This pilot study will involve inpatient admission to our General Clinical Research Center for 5 days prior to scheduled transsphenoidal surgery. During the five days of the study each individual will receive the RXR-agonist bexarotene at the FDA approved dose of 300 mg/m2/day. Clinical signs and symptoms of acute adrenal insufficiency will be monitored routinely throughout each 24-hour period. Baseline and twice-daily biochemical analysis for ACTH and cortisol will be performed. 24-hour urine collection for cortisol will be obtained pre-treatment and in the last 24-hours of treatment. Laboratory safety analysis will include serial comprehensive metabolic panels to monitor liver and kidney function, complete blood count to monitor for neutropenia, as well as thyroid function studies to monitor for central hypothyroidism which can develop with therapy.

Preoperative Bexarotene Treatment for Cushing's Disease

University of Virginia

Mary Lee Vance

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Prevalence of Pituitary Incidentaloma in Relatives of Patients With Pituitary Adenoma	NCT00598949	Pituitary Tumor		18 Years -	Cedars-Sinai Medical Center
Prevalence of Pituitary Incidentaloma in Relatives of Patients With Pituitary Adenoma	NCT00598949	Pituitary Tumor		18 Years -	Cedars-Sinai Medical Center
Preoperative Bexarotene Treatment for Cushing's Disease	NCT00845351	Cushing's Disea...	Bexarotene	18 Years - 65 Years	University of Virginia

Spots Global Cancer Trial Database for cushing's

Every month we try and update this database with for cushing's cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for cushing's

Every month we try and update this database with for cushing's cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for cushing's cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.