Endocrine Abstracts

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...

Background: Endogenous Cushing’s syndrome (CS) is caused by overproduction of cortisol. Current first-line screening tests for CS can produce false positive results due to medication use and stress, rely heavily on patient adherence to sampling instructions, and only measure short-term cortisol exposure which limits sensitivity. In general multiple tests are required to establish a diagnosis. Hair cortisol concentrations (HCC) offer a minimally invasive way to measure lon...

Introduction: Pancreatic neuroendocrine neoplasm (pNEN) patients often present with locally advanced or metastatic disease. The objective response rate of peptide receptor radionuclide therapy (PRRT) in pNENs is 55%. Therefore, PRRT may be a possibility for patients who are not eligible for upfront curative surgery.Aims: To assess the potency of PRRT to render locally advanced or oligometastatic pNENs resectable and to evaluate the effect of surgery afte...

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...

Background: Adrenocortical carcinoma (ACC) is an uncommon malignancy with a still scantily understood pathogenesis and generally poor prognosis. Surgery, performed at early stages, offers the best chance for cure, but unfortunately, it is often noncurative. Medical treatment produced disappointing responses. mTOR inhibitors, such as sirolimus (S) and temsirolimus (T), are promising antineoplastic drugs in several types of carcinomas.Methods: To evaluate ...

Background: A metastatic mesenteric mass is a hallmark of small intestinal neuroendocrine tumours (SI-NETs). However, little is known about the evolution of a SI-NET-associated mesenteric mass over time.Methods: Retrospectively, 530 patients with proven SI-NET and ≥2 available CT-scans were assessed for clinical characteristics at diagnosis and the presence and growth of a mesenteric mass on every consecutive CT-scan until end of follow-up or resec...

Introduction: Long-acting pasireotide reduced urinary free cortisol (UFC) in most patients with Cushing’s disease (CD) during a large Phase III study (Lacroix et al. Lancet Diabetes Endocrinol 2018). The analyses presented here explored the impact of baseline characteristics on response to long-acting pasireotide.Methods: 150 patients with persistent, recurrent or de novo CD and mean UFC (mUFC; from three 24-hour samples collected ...

ContextGermline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) have been identified in patients with pituitary adenomas, most frequently presenting as somatotropinomas in the setting of familial isolated pituitary adenoma (FIPA). Our current understanding of AIP related tumorigenesis indicates that it leads to isolated pituitary adenomans, while other associated tumors have not typically been considered part of the...

Background: Adrenocortical carcinoma (ACC) is a rare but devastating malignancy (5-year survival 18–57%), with limited treatment options. Currently, mitotane is the first-line medical treatment for metastatic ACC and is used in the adjuvant setting after surgery to prevent recurrence. Mitotane is an adrenolytic drug that is thought to act by disruption of mitochondria with subsequent activation of apoptosis. However, mitotane treatment comes with many drawbacks, such as s...

Introduction: Potent 11β-hydroxylase inhibitor osilodrostat provides cortisol level control in patients with Cushing’s syndrome (CS), as demonstrated by the LINC clinical development programme in Cushing’s disease (CD) patients.1 We report data from year 1 of the prospective observational LINC6 study (NCT05382156), evaluating long-term safety and efficacy of osilodrostat in CS patients during 3 years of routine clinical practice.<p class="abstext"...