View clinical trials related to Pituitary ACTH Hypersecretion.
Filter by:Currently, 2-3% of the population of the United Kingdom and United States of America receive glucocorticoid therapy. Significant adverse effects are not confined to chronic use; recurrent short-course administration is associated with increased morbidity and mortality. The adverse metabolic features associated with glucocorticoid use include obesity, skeletal muscle myopathy, hypertension, insulin resistance and diabetes and are collectively termed 'iatrogenic Cushing's syndrome'. The efficacy of glucocorticoid therapy is not in doubt, but there are no interventions to reduce their metabolic consequences. Within metabolic tissues (liver, skeletal muscle, adipose), 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates active glucocorticoid and therefore is able to tightly control the availability of glucocorticoids to activate the glucocorticoid receptor. In preclinical studies, the investigators have shown that 11β-HSD1 is critical in regulating the development of the adverse features associated with circulating glucocorticoid excess, endorsing our observations in a patient with Cushing's disease, who was protected from a classical phenotype due to a functional deficit in 11β-HSD1. This study is the first clinical evaluation of the impact of the selective 11β-HSD1 inhibitor, AZD4017, in healthy volunteers taking exogenous glucocorticoids (prednisolone). The investigators propose that in tissues expressing high levels of 11β-HSD1, prednisolone action will be amplified, driving adverse effects within these tissues and have hypothesized that AZD4017 in humans will reduce the adverse metabolic consequences of Prednisolone administration without compromise to its anti-inflammatory action. Our specific research objectives are: 1. To demonstrate the beneficial effect of the selective 11β-HSD1 inhibitor, AZD4017, upon the prednisolone-induced deterioration in metabolic phenotype, including glucose disposal and endogenous glucose production rates. 2. To determine the impact of AZD4017 on the anti-inflammatory actions of Prednisolone. 3. To identify the tissue-specific (skeletal muscle, adipose) mechanisms underpinning the response to Prednisolone therapy administered in conjunction with AZD4017. The investigators will perform a randomized, double-blind placebo controlled study to determine if co-administration of the selective 11β-HSD1 inhibitor, AZD4017, limits the adverse effects of short-course exogenous glucocorticoid administration. 32 healthy male volunteers will have detailed metabolic investigations including 2-step hyperinsulinaemic euglycaemic clamps (with stable isotope measurements of lipid and carbohydrate metabolism), as well as assessment of skeletal muscle forearm glucose uptake. All volunteers will then be treated with Prednisolone (20mg daily) and randomized to the co-administration of placebo or AZD4017. After 1 week of therapy, all investigations will be repeated. Our hypothesis is that the adverse metabolic effects of Prednisolone will be reduced by co-administration of AZD4017.
Background: Pasireotide treatment is strictly associated with glucose metabolism impairment. The aim of the study was to evaluate the effect of pasireotide on β -cell and adipose function in patients with Cushing's disease (CD). Methods: Clinical and hormonal parameters, insulin secretion, evaluated by homostasis model assessment (HOMA-β) and by the area under the curve (AUC2h) of C-peptide during a mixed meal tolerance test and insulin sensitivity, evaluated by the euglycemic hyperinsulinemic clamp, were evaluated in 12 patients with active CD before and after 12 months of pasireotide. Circulating adipokines were evaluated in patients with CD compared to a matched group of 12 diabetic patients.
The purpose of this study was to confirm efficacy and safety of osilodrostat for the treatment of patients with Cushing's disease who are candidates for medical therapy.
Cushing's disease is a state of chronic endogenous glucocorticoid excess. Cushing's disease is responsible for increased morbidity and mortality. Recent studies have pinpointed the frequency of somatic sequelas and persistent alteration in quality of life despite the cure of the disease. More specifically, a few studies have described persistent psychopathology, maladaptive personality and cognitive impairments in patients with a history of Cushing's disease. Among these, hippocampal memory deficits have been found in the majority of studies, a finding that is consistent with the alterations described in hippocampal neurons during chronic exposure to glucocorticoids. However, the tools currently available to assess hippocampal-dependent memory are multiple, sometimes difficult to perform by clinicians and to analyze or may lack of diagnostic sensitivity. The investigators have recently developed an original tool, the virtual radial task in 3D, which has shown to be reliable to detect subtle alterations in hippocampal-dependent memory in several human diseases. The primary aim of the study is the evaluation of persistent cognitive impairments (hippocampal memory) in patients cured of Cushing's disease for at least one year using the virtual radial task in 3D and to compare it with that obtained with classical cognitive tests.
This study aims at investigating the complications of Cushing's disease in "de novo" patients. A series of investigations will assay before treatment and every year thereafter during a 3 years follow-up period the various complications of the disease. These investigations will determine the presence and severity of cardiovascular, metabolic, and bone complications as well as the Quality of Life. Outcome of these complications after treatment, especially after pituitary surgery will be monitored, as well as cortisol levels.
The USP8 gene and its downstream target, epidermal growth factor receptor (EGFR), is a potential therapeutic target of Cushing disease. The EGFR inhibitor, Gefitinib, has been shown to reduce the production of ACTH both in vitro and in vivo, especially in USP8-mutated corticotrophin adenomas. The investigators hypothesize that Gefitinib will suppress pituitary corticotroph tumor ACTH production and normalize urinary free cortisol levels in patients with USP8-mutated Cushing's disease. Gefitinib is an FDA approved drug used to treat non-small cell lung cancer. However, in this study, the drug will be used to treat corticotrophin adenoma.
The purpose of this study is to study since 1987 all patients diagnosed with CD in Sweden and determine their outcomes including mortality. A secondary objective is to focus on patients in remission and identify determinants of their different outcomes.
This is a non-interventional, multinational, multi-center post-marketing study, to further document the safety and efficacy of pasireotide s.c. administered in routine clinical practice in patients with Cushing's disease. Patients with Cushing's disease and treated with pasireotide s.c. alone and in combination with other therapies will be monitored. For this study, each enrolled patient will be followed up for 3 years after enrollment. Patients who permanently discontinue pasireotide s.c. prior to completing the 3-year observation period will be followed up for 3 months after the last dose of pasireotide s.c.
Cushing syndrome refers the manifestations induced by chronic glucocorticoid excess and may arise from various causes. Iatrogenic Cushing syndrome accounts for most patients, when they are given exogenous glucocorticoid treatment. In contrast, spontaneous Cushing syndrome results from endogenous glucocorticoid over-secretion. Although Cushing disease is rare, it is the most common cause of spontaneous Cushing syndrome. The patient with Cushing disease has a pituitary corticotroph adenoma, which overproduces adrenocorticotropic hormone (ACTH). ACTH then stimulates adrenal gland to over-secret glucocorticoid. Patients with untreated Cushing disease were shown to have poor prognosis, estimated a 5-year survival rate of 50%. The first line treatment is tumor resection. Other managements include radiotherapy, medication and bilateral adrenalectomy. The initial remission rate is high (66-90%). However, some patients encounter with disease recurrence during follow-up. The aim of this study is to clarify the factors associated with the recurrence after treatment. In this study, we will review the patients with Cushing disease thoroughly and analyze associated predisposing factors. These risk factors can remind the clinical physician to early detect the recurrent disease in these patients, and further prevent morbidity and mortality in their later lives.
The study aimed to confirm long-term efficacy and safety of LCI699 for the treatment of patients with Cushing's disease. It was a pivotal trial which supported the registration of LCI699 for the treatment of patients with Cushing's disease in the US and the EU. This is a phase lll, multi-center, double-blind, randomized withdrawal study of LCI699 following a 24 week, single-arm, open-label dose titration and treatment period which evaluated the safety and efficacy of LCI699 for the treatment of patients with Cushing's disease.