Endocrine Abstracts

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...

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 ...

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...

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...

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...

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...

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...

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...

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 ...

Context: The 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&apos;s disease (CD).Case Description: A 50-year-old female was diagnosed with ACTH-independent CS and a left-sided adrenal adenoma in January 2015. After adrenalectomy and histopathological co...