Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The prognosis of patients with metastatic adrenal cortical carcinoma is poor, and their disabling symptoms are usually unresponsive to conventional therapy. A patient with Cushing's syndrome secondary to a secretory adrenal cortical carcinoma was treated with octreotide, endocrine therapy and chemotherapy having failed. Treatment led to a dramatic relief of her symptoms with a fall in corticosteroid secretion. Somatostatin analogue therapy for this tumour should be encouraged in view of the lack of alternative palliative treatment.
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PMID:Secretory symptoms from metastatic adrenal cortical carcinoma responding to octreotide. 754 Mar

Functional metastatic adrenocortical carcinoma is an uncommon cause of Cushing's syndrome, which rarely responds to conventional treatment. A patient presenting with Cushing's syndrome secondary to adrenocortical carcinoma underwent surgical resection. Postoperatively, she developed metastatic disease resistant to conventional chemotherapy. Octreotide, a somatostatin analogue which is effective in the treatment of several types of neuroendocrine tumour, was tried to ameliorate her secretory symptoms, but without any therapeutic effect.
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PMID:Lack of response to octreotide in Cushing's syndrome due to metastatic adrenocortical carcinoma. 1044 70

Cushing's syndrome is a complex endocrine condition with potential serious complications if untreated or inadequately treated. Transsphenoidal surgery with resection of a pituitary adenoma is successful in 75 - 80% of patients, but approximately 20 - 25% show persistence of Cushing's, and a similar proportion may experience recurrence within 2 - 4 years post-op. When surgery fails, medical treatment can temporarily suppress excessive cortisol production and ameliorate its clinical manifestations while more definitive therapy becomes effective. We describe pharmacological approaches to the treatment of Cushing's syndrome. Drugs used to suppress cortisol secretion are mostly inhibitors of steroidogenesis. Ketoconazole, fluconazole aminoglutethimide, metyrapone, mitotane and etomidate are in that category. Ketoconazole is in current use while other drugs, although mostly available in the past, continue to have a potential role either alone or in combination. Drugs that suppress adrenocorticotropic hormone (ACTH) secretion are less popular as standard treatment and include cyproheptadine, valproic acid, cabergoline, somatostatin analogs, PPAR-gamma agonists, vasopressin antagonists. Some of these drugs have been tested in limited clinical trials but there is potential therapeutic benefit in analogs with better specificity for the class of receptors present in ACTH-secreting tumors. A third category of drugs is glucocorticoid receptor antagonists. Mifepristone is currently being tested in clinical trials in patients with persistent or recurrent Cushing's disease and in patients with metastatic adrenal cortical carcinoma or ectopic ACTH syndrome not amenable to surgery. We also review replacement therapy after surgery and non-specific drugs to treat complications in patients with severe hypercortisol. The review provides a complete survey of the drugs used in the medical treatment of Cushing's, and new advances in the development of pituitary-active drugs as well as receptor blockers of glucocorticoid action. It also provides avenues for exploration of new drugs active on somatostatin, dopamine and vasopressin receptors. There are effective pharmacological agents capable of chronically reversing biochemical and clinical manifestations of hypercortisolemia in Cushing's syndrome but new drugs are needed with action at the pituitary level.
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PMID:Drugs in the medical treatment of Cushing's syndrome. 1993 10

Positron emission tomography (PET) has seen an increasing clinical utilization in the last decade, such that it is now a standard oncology imaging modality. Its success is based on the detection of altered fluorine-18 fluorodeoxyglucose (18F-FDG) biodistribution, reflecting glucose transport/metabolism in malignant tumor tissues. Integrated PET/computed tomography cameras combine functional and anatomical information in a synergistic manner that improves diagnostic interpretation, and newer positron-emitting radiopharmaceuticals have been developed to expand the application of non-FDG PET imaging. The increasing use of cross-sectional imaging procedures has led to a more frequent detection of incidental adrenal masses. Although conventional imaging modalities such as computed tomography and MRI can characterize the majority of these lesions, 18F-FDG PET has been reported as a useful tool to distinguish benign from malignant etiologies in indeterminate adrenal masses. Although 18F-FDG PET has enjoyed success in staging a wide range of cancers, including detection of adrenal metastases and evaluation of adrenocortical carcinoma, it has had limited impact for the evaluation of neuroendocrine tumors. Positron-emitting amine precursor and somatostatin analogs have been validated in research settings to provide accurate imaging of enterochromaffin and chromaffin neuroendocrine tumors and medullary thyroid cancer. The aim of this review article is to provide an overview of the role of 18F-FDG and newer positron-emitting radiopharmaceuticals in the evaluation of adrenal and neuroendocrine tumors.
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PMID:Role of positron emission tomography/computed tomography in adrenal and neuroendocrine tumors: fluorodeoxyglucose and nonfluorodeoxyglucose tracers. 2179 67

New therapies for advanced adrenocortical carcinoma (ACC) are urgently needed, as the majority of the patients experience a rapid and inexorable progression despite surgery and adjuvant mitotane. In vitro data suggest that somatostatin receptors (SSTRs) and mTOR pathway might represent reasonable targets for novel therapies, being involved in functionality and growth of ACC cells. However, in vitro analysis of combination treatments targeting both mTOR and SSTR as compared to mitotane are poorly explored in ACC. This study aimed to investigate in vitro the effects on cell growth of pasireotide, everolimus, and mitotane, alone or combined, in the two ACC cell lines H295R and SW13 (mitotane sensitive and resistant, respectively). Moreover, the tissue expression of mTOR pathway molecules and SSTR (types 1-5) was assessed in 58 ACCs. In both cell lines, only everolimus induced a significant inhibition of cell growth. Conversely, the combinations among mitotane, pasireotide, and everolimus produced antagonistic effects on mitotane-induced growth inhibition on H295R cell line. A heterogeneous profile of mTOR-related molecules and SSTR expression was observed in ACC samples, being the mTOR pathway found activated in approximately 30% of cases. In conclusion, our data suggest caution in designing combinations of mitotane with other drugs potentially active in ACC, such as mTOR inhibitors or somatostatin analogs.
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PMID:Tissue Expression and Pharmacological In Vitro Analyses of mTOR and SSTR Pathways in Adrenocortical Carcinoma. 2827 81

Advanced adrenocortical carcinoma (ACC) is an aggressive disease with poor prognosis, and the current therapeutic options, such as mitotane or platinum-based chemotherapy regimens, often offer limited efficacy. Here, we present the first report, to the author's knowledge, of metastatic ACC with positive octreoscan scintigraphy that was successfully treated with octreotide long-acting release (LAR). A patient with metastatic ACC who showed poor tolerance to mitotane received octreotide LAR because of positive octreoscan scintigraphy. She obtained major partial response to the somatostatin analog. Interestingly, the expression of somatostatin receptor 2 from the previous local recurrence lesion was negative. The next-generation sequencing-based circulating tumor DNA analysis in the patient was performed and failed to identify any alterations. These findings suggest that octreotide LAR may be a good option for the treatment of metastatic ACC in selected patients.
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PMID:Metastatic Adrenal Cortical Carcinoma Responding to Octreotide: A Case Report. 3107 23