Endocrine Abstracts

Introduction: Adrenocortical carcinoma (ACC) is a rare, but highly malignant endocrine tumor. Surgery is the primary choice of treatment. In case of inoperable disease or tumor recurrence, therapy with the adrenolytic drug mitotane is usually applied. Plasma mitotane concentrations of >14 mg/l (50 μM) seem required for an effect on tumor mass. Despite its clinical use, the effects of mitotane on cell proliferation and hormone production have been poorly investigated <...

Background: The response to first-generation long-acting somatostatin analogues (LA-SSA) treatment in acromegaly depends on the expression of the somatostatin receptor (SSTR) subtypes. In contrast to octreotide and lanreotide which preferentially bind to SSTR2, pasireotide targets multiple SSTRs, with the highest binding affinity for SSTR5. It has previously been suggested that SSTR5 expression could predict the response to pasireotide LAR (PAS-LAR) treatment in acromegaly.</p...

Background: Temozolomide (TMZ) has been suggested as a treatment option for patients with pancreatic neuroendocrine tumours (PNETs). The tumour response to TMZ has been linked to expression levels of O6-methylguanine-DNA methyltransferase (MGMT) and components of the mismatch repair (MMR) system. However, there is no in vitro data on TMZ sensitivity and the expression of MGMT and MMR components in PNETs. Moreover, the effect of TMZ exposure on chemosensitivity and exp...

Background: Neuroendocrine tumors (NET) are malignant neoplasms that can be associated with specific hormonal syndromes. We describe a novel syndrome of postmenopausal vaginal bleeding and ovarian estradiol overproduction due to ovarian NET localizations.Methods: A clinical workup was performed for 2 index patients with ovarian metastases of small bowel neuroendocrine tumors and symptoms of postmenopausal vaginal bleeding. Ovarian tissue was collected af...

Background: Previous studies indicate that PAS-LAR can achieve control of insulin-like growth factor I (IGF-I) levels and may reduce tumor size, however a subset of acromegaly patients responds poorly. T2-signal intensity, somatostatin receptor (SST) subtype 2 and 5 expression, and the response to first-generation somatostatin receptor ligands (SRLs) are recognized predictors of therapy response. Valid prediction of the response to PAS-LAR can alter treatment stratification.</...

Background: Prolactinomas are the most frequent secreting pituitary adenomas encountered in the clinical setting. Cabergoline is considered the mainstay medical treatment and transsphenoidal surgery (TSS) is recommended for patients that are medically resistant to dopamine agonist therapy. Resistance to dopamine agonists is commonly defined as failure to normalize prolactin and less than 50% decrease in tumor diameter at a maximal labeled dose of 2.0 mg/week. Pasireotide LAR (...

Introduction: The steroidogenesis inhibitors ketoconazole and metyrapone are frequently used for treatment of Cushing’s syndrome, but can cause side effects. LCI699 is a known 11β-hydroxylase inhibitor, but effects on other steroidogenic enzymes are unknown. We aimed to compare effects of LCI699, ketoconazole, and metyrapone in vitro.Methods: HAC-15 cells, with or without 10 nM ACTH, and three primary human adrenocortical adenoma cultu...

Adrenocortical cancer (ACC) is a rare cancer with poor prognosis and scant treatment options. Mitotane alone, or in combination with cytotoxic chemotherapy, represents the referral current treatment for patients with unresectable ACC. Recent studies have shown that mTOR inhibitors suppress growth of ACC cells. This study aimed at evaluating the effects of mitotane in combination with mTOR inhibitors. In H295 and SW13 cells we tested the effects of a 6 day treatment with increa...

The mTOR and IGF/insulin pathways are frequently dysregulated in HCC. Antitumoral activity of mTOR inhibitors (mTORi) has been demonstrated in experimental models but in early clinical studies mTORi alone have shown modest antitumoral activity. IGF/insulin-dependent Akt activation, via IGF1R and IR, has been suggested as potential mechanism for mTORi resistance. This study aimed at evaluating the expression of mTOR and IGF/insulin pathway components and the effects of mTORi al...

Introduction: Ketoconazole is an antifungal agent that, in a high dose, suppresses adrenocortical steroidogenesis by inhibition of cytochrome P-450 dependent enzymes. Currently, ketoconazole is used to decrease cortisol production in patients with Cushing’s syndrome. However, ketoconazole often causes gastrointestinal side effects and hepatotoxicity. Fluconazole may also inhibit steroidogenesis and has the advantage over ketoconazole that it has less side effects. Therefo...