Searchable abstracts of presentations at key conferences in endocrinology

ea0037ep1125 | Endocrine tumours | ECE2015

Mitotane directly interacts with lipid membranes and alters membrane structure and dynamics

Muller Peter , Theisgen Stephan , Schirbel Andreas , Sbiera Silviu , Haralampiev Ivan , Fassnacht Martin , Huster Daniel , Kroiss Matthias

Context: Mitotane (1,1-dichloro-2-[o-chlorophenyl]-2-[p-chlorophenyl]ethane) is the only drug approved for treatment of adrenocortical carcinoma (ACC). Mitotane counteracts both tumor growth and tumoural steroid hormone production but treatment is severely hampered by unfavorable pharmacokinetics and serious side effects. Mitotane is a lipophilic compound and treatment emergent alterations of lipid metabolism are frequently observed. This raises the question whether mitotane d...

ea0020oc1.3 | Endocrine Tumours | ECE2009

131I-Iodometomidate radiotherapy for metastatic adrenocortical carcinoma: first clinical experience

Hahner Stefanie , Kreissl Michael , Fassnacht Martin , Johanssen Sarah , Haenscheid Heribert , Reiners Christoph , Allolio Bruno , Schirbel Andreas

Subject: Treatment options for adrenocortical carcinoma (ACC) are still unsatisfactory. We could recently demonstrate that several patients with ACC exhibit a high and specific uptake of 123I-Iodometomidate (123I-IMTO). Therefore, we investigated if 131I-IMTO holds potential for radiotherapy in ACC.Methods: Dosimetry with 40 MBq I-131-IMTO was performed over 5 days in 7 patients and calculated activities were administered on a compassionate use basis in ...

ea0016oc4.4 | Bone and adrenal | ECE2008

Comparison of different test systems for the screening of inhibitors of CYP11B enzymes

Stuermer Andrea , Hahner Stafanie , Lang Katharina , Linss Heidi , Zink Martina , Schirbel Andreas , Allolio Bruno

Subject: Inhibitors of CYP11B enzymes, particularly of aldosterone synthase, are currently under development as adrenostatic agents in heart failure or hyperaldosteronism, and for use in adrenal imaging. As CYP11B1 and CYP11B2 show high homology, analysis of specific binding to the respective human enzymes is of key importance.Methods: Y1 cell lines stably expressing hsCYP11B1 or hsCYP11B2 were established. Primary cultures of porcine and human adrenocor...

ea0035p2 | Adrenal cortex | ECE2014

Development of new improved derivatives of iodometomidate for the diagnosis of adrenocortical tumours and radiotherapy of adrenal carcinoma

Heinze Britta , Schirbel Andreas , Michelmann David , Nannen Lukas , Ries Martin , Thomas Elke , Gobel Heike , Allolio Bruno , Hahner Stefanie

Objective: We have developed (123/131I)iodometomidate (IMTO) for specific adrenal imaging and radiotherapy of adrenocortical carcinoma. IMTO binds with high affinity and specificity to the two adrenocortical enzymes aldosterone synthase (CYP11B2) and 11β-hydroxylase (CYP11B1). Metabolic analysis has revealed very rapid metabolization of IMTO both in vitro and in vivo by hepatic esterases. Due to the low metabolic stability of (123/131</su...

ea0014oc3.5 | Endocrine tumors &amp; neoplasia | ECE2007

[123I]Iodometomidate as a radiotracer for adrenal scintigraphy – first clinical experience

Hahner Stefanie , Stuermer Andrea , Fassnacht Martin , Kreissl Michael , Reiners Christoph , Beuschlein Felix , Zink Martina , Zolle Ilse , Schirbel Andreas , Allolio Bruno

Adrenal masses are highly prevalent tumours comprising of a variety of entities. Therefore, therapeutic consequences also vary considerably. The CYP11B-specific PET-tracer [11C]metomidate has been shown to be suitable to characterize adrenal lesions. However, its availability is restricted to PET-centers with an on-site cyclotron. Also imaging is hindered by the short tracer half-life (20 min). Therefore, we have developed [123I]iodometomidate as a tracer...

ea0099ep415 | Adrenal and Cardiovascular Endocrinology | ECE2024

Adrenal specific functional imaging with 123I-IMAZA for non-invasive diagnostic evaluation of TART - a case series

Hahner Stefanie , Andreas Schirbel , Wiebke Schlotelburg , Teresa Fuss Carmina , Welp Ann-Christin , Auer Matthias , Lottspeich Christian , Heinze Britta , Reisch Nicole

Background: Distinction of benign testicular adrenal rest tumours (TART) and potentially malign Leydig cell tumors (LCT) is challenging but important to prevent unnecessary surgery of TART. Ultrasound or magnetic resonance imaging can reliably detect but not distinguish between both tumour entities.Methods: Functional imaging results using the specific CYP11B1/2-inhibitor 123I-IMAZA were investigated in seven adult male patients with classic c...

ea0037oc1.3 | Adrenal 1 | ECE2015

[123/131I] azetidinylamide a novel radiotracer for diagnosis and treatment of adrenocortical tumours -- from bench to bedside

Hahner Stefanie , Heinze Britta , Herrmann Ken , Buck Andreas K , Blumel Christina , Hanscheid Heribert , Brumberg Joachim , Michelmann David , Nannen Lukas , Ries Martin , Fassnacht Martin , Allolio Bruno , Schirbel Andreas

Background: We have recently introduced [123/131I]iodometomidate (IMTO) which selectively binds to the adrenocortical enzymes aldosterone synthase and 11ß-hydroxylase as SPECT tracer. IMTO has been proven to be useful for molecular adrenal imaging and radiotherapy in adrenal cancer (ACC). As IMTO is rapidly inactivated by endogenous esterases which may impair target tissue to background activity and therapeutic efficacy, >50 new IMTO derivatives have been d...

ea0035oc5.3 | Adrenal &amp; Thyroid | ECE2014

Mitotane induces endoplasmic reticulum stress triggering apoptosis and decrease of steroid hormone synthesis

Sbiera Silviu , Wiemer Laura , Leich Ellen , Gehl Annemarie , Gardill Felix , Ronchi Cristina L. , Bala Margarita , Schirbel Andreas , Rosenwald Andreas , Allolio Bruno , Fassnacht Martin , Kroisz Matthias

Background: Mitotane is the only drug approved for treatment of adrenocortical carcinoma (ACC). Molecular events leading to cell death in adrenocortical cells are unknown preventing the development of drugs with improved efficacy-toxicity ratio.Methods: We employed the ACC model cell line NCI-H295 to investigate the effects of mitotane on genome-wide mRNA expression using microarray analysis. Several algorithms were used to delineate signaling pathways t...

ea0016s30.3 | Clinical highlights | ECE2008

[123I]Iodometomidate as a radiotracer for diagnosis of adrenal tumours and adrenocortical carcinoma

Hahner Stefanie , Schirbel Andreas , Kreissl Michael , Fassnacht Martin , Johanssen Sarah , Beuschlein Felix , Quinkler Marcus , Reincke Martin , Stuermer Andrea , Reiners Christoph , Allolio Bruno

Subject: Adrenal tumours (AT) are often detected incidentally and represent a variety of differential diagnoses with variable therapeutic consequences. We have recently developed [123I]Iodometomidate ([123I]IMTO), that specifically binds to adrenal CYP11B enzymes as a SPECT tracer for adrenal scintigraphy. This radiotracer is now evaluated in patients with adrenal tumours in an ongoing clinical trial. The study was approved by the ethical committee and pa...

ea0073aep838 | Late Breaking | ECE2021

Consecutive development of adrenal Cushing´s syndrome and Cushing´s disease in a female patient with somatic CTNNB1, USP8, and NR3C1 mutations

Detomas Mario , Altieri Barbara , Schlötelburg Wiebke , Appenzeller Silke , Sven-Martin Schlaffer , Roland Coras , Andreas Schirbel , Wild Vanessa , Kroiss Matthias , Sbiera Silviu , Fassnacht Martin , Deutschbein Timo

ContextThe occurrence of different subtypes of endogenous Cushing’s syndrome (CS) in single individuals is extremely rare. We here present the case of a female patient who was successfully cured from adrenal CS 4 years before being diagnosed with Cushing’s disease (CD).Case DescriptionA 50-year-old female was diagnosed with ACTH-independent CS and a left-sided adrenal adenoma in January 2015. After ...