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 <...

Objective: To evaluate the results of the early postoperative low-dose (1 μg) ACTH (adrenocorticotropin) stimulation test in patients with Cushing’s disease (CD) in order to predict long-term outcome of transsphenoidal surgery.Methods: We reviewed the serum cortisol response to 1 μg synthetic ACTH (1–24) in the second week after pituitary surgery in 40 patients with Cushing’s disease. Median follow-up was 48.5 months (range 6&#15...

Background: Testosterone (T) in a hydroalcoholic gel is commonly prescribed as androgen replacement therapy and may not be accompanied by peaks and troughs of serum T levels as seen in T-injectables. We assessed in 17 subjects the differences in serum testosterone (sT) and free T (fT) levels during four different application periods.Methods: Patients where on daily 50 mg Androgel®, for 7 consecutive days in each cycle, on day 8 serum was ...

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: Osilodrostat (potent oral 11β-hydroxylase inhibitor) provided rapid normalisation of mean urinary free cortisol (mUFC) in Cushing’s disease (CD) patients during the 48-week (W) core period of LINC 4 (NCT02697734) and was well tolerated. We report long-term efficacy and safety results from the LINC 4 core and extension phases.Methods: 73 adults with CD and mUFC >1.3 upper limit of normal (ULN) were enrolled. LINC 4 comprised a 12...

Background: Cushing’s disease (CD) is associated with hypercortisolism-induced cardiovascular morbidity and mortality and impaired patient quality of life (QoL). We report long-term effects of osilodrostat (potent 11β-hydroxylase inhibitor) on cardiovascular/metabolic-related risk factors, physical features of hypercortisolism and QoL in CD patients following the core and extension phases of the LINC 4 study (NCT02697734).Methods: LINC 4 compri...

Introduction: In two Phase III studies (LINC3, NCT02180217; LINC4, NCT02697734), osilodrostat, (potent oral 11β-hydroxylase inhibitor), provided rapid, sustained reductions in mean urinary free cortisol (mUFC) and late-night salivary cortisol (LNSC), alongside improvements in clinical signs of hypercortisolism and health-related quality of life (HRQoL), in Cushing’s disease (CD) patients. mUFC and LNSC are recommended for monitoring treatment response. We assessed wh...

Introduction: Phase II (LINC2, NCT01331239) and Phase III (LINC3, NCT02180217; LINC4, NCT02697734) studies showed that osilodrostat, a potent oral 11β-hydroxylase inhibitor, was an effective long-term treatment for Cushing’s disease patients. In this LINC programme pooled analysis, we examined how dose uptitration and adjustments during long-term maintenance can provide rapid, sustained mean urinary free cortisol (mUFC) control, and minimise AEs.<p class="abstext...

Background: Cushing’s syndrome (CS) has numerous comorbidities, including diabetes mellitus (DM). Levoketoconazole is a ketoconazole stereoisomer in clinical trials for treatment of CS.Methods: SONICS is a prospective, open-label, phase 3 maintenance-of-benefit study in adults with confirmed CS and mean urinary free cortisol (mUFC) of ≥1.5x upper limit of normal (ULN). Repeated hospitalization due to hyperglycemia or any complication related t...

Background: Pasireotide is a multireceptor-targeted somatostatin analogue that predominantly binds to somatostatin receptor subtype 5 (SSTR5) and provides sustained control of urinary free cortisol (UFC) levels in some patients with Cushing’s disease (CD). Cabergoline is a dopamine D2 receptor agonist with efficacy in some patients with CD. Most corticotropinomas co-express SSTR5 and D2, providing rationale for combination treatment with pasireotide and cabergoline. Resul...