TY  - JOUR
A1  - Detomas, Mario
A1  - Altieri, Barbara
A1  - Schlötelburg, Wiebke
A1  - Appenzeller, Silke
A1  - Schlaffer, Sven
A1  - Coras, Roland
A1  - Schirbel, Andreas
A1  - Wild, Vanessa
A1  - Kroiss, Matthias
A1  - Sbiera, Silviu
A1  - Fassnacht, Martin
A1  - Deutschbein, Timo
T1  - Case Report: Consecutive Adrenal Cushing’s Syndrome and Cushing’s Disease in a Patient With Somatic CTNNB1, USP8, and NR3C1 Mutations
JF  - Frontiers in Endocrinology
N2  - 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’s disease (CD). The patient was diagnosed at the age of 50 with ACTH-independent CS and a left-sided adrenal adenoma, in January 2015. After adrenalectomy and histopathological confirmation of a cortisol-producing adrenocortical adenoma, biochemical hypercortisolism and clinical symptoms significantly improved. However, starting from 2018, the patient again developed signs and symptoms of recurrent CS. Subsequent biochemical and radiological workup suggested the presence of ACTH-dependent CS along with a pituitary microadenoma. The patient underwent successful transsphenoidal adenomectomy, and both postoperative adrenal insufficiency and histopathological workup confirmed the diagnosis of CD. Exome sequencing excluded a causative germline mutation but showed somatic mutations of the β-catenin protein gene (CTNNB1) in the adrenal adenoma, and of both the ubiquitin specific peptidase 8 (USP8) and the glucocorticoid receptor (NR3C1) genes in the pituitary adenoma. In conclusion, our case illustrates that both ACTH-independent and ACTH-dependent CS may develop in a single individual even without evidence for a common genetic background.
KW  - Cushing’s syndrome
KW  - Cushing’s disease
KW  - hypercortisolism
KW  - glucocorticoid excess
KW  - USP8
KW  - CTNNB1
KW  - NR3C1
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-244596
SN  - 1664-2392
VL  - 12
ER  - 
TY  - JOUR
A1  - Chifu, Irina
A1  - Heinze, Britta
A1  - Fuss, Carmina T.
A1  - Lang, Katharina
A1  - Kroiss, Matthias
A1  - Kircher, Stefan
A1  - Ronchi, Cristina L.
A1  - Altieri, Barbara
A1  - Schirbel, Andreas
A1  - Fassnacht, Martin
A1  - Hahner, Stefanie
T1  - Impact of the Chemokine Receptors CXCR4 and CXCR7 on Clinical Outcome in Adrenocortical Carcinoma
JF  - Frontiers in Endocrinology
N2  - Chemokine receptors have a negative impact on tumor progression in several human cancers and have therefore been of interest for molecular imaging and targeted therapy. However, their clinical and prognostic significance in adrenocortical carcinoma (ACC) is unknown. The aim of this study was to evaluate the chemokine receptor profile in ACC and to analyse its association with clinicopathological characteristics and clinical outcome. A chemokine receptor profile was initially evaluated by quantitative PCR in 4 normal adrenals, 18 ACC samples and human ACC cell line NCI-H295. High expression of CXCR4 and CXCR7 in both healthy and malignant adrenal tissue and ACC cells was confirmed. In the next step, we analyzed the expression and cellular localization of CXCR4 and CXCR7 in ACC by immunohistochemistry in 187 and 84 samples, respectively. These results were correlated with clinicopathological parameters and survival outcome. We detected strong membrane expression of CXCR4 and CXCR7 in 50% of ACC samples. Strong cytoplasmic CXCR4 staining was more frequent among samples derived from metastases compared to primaries (p=0.01) and local recurrences (p=0.04). CXCR4 membrane staining positively correlated with proliferation index Ki67 (r=0.17, p=0.028). CXCR7 membrane staining negatively correlated with Ki67 (r=−0.254, p=0.03) but positively with tumor size (r=0.3, p=0.02). No differences in progression-free or overall survival were observed between patients with strong and weak staining intensities for CXCR4 or CXCR7. Taken together, high expression of CXCR4 and CXCR7 in both local tumors and metastases suggests that some ACC patients might benefit from CXCR4/CXCR7-targeted therapy.
KW  - chemokine receptor
KW  - prognosis
KW  - adrenocortical carcinoma
KW  - CXCR4
KW  - CXCR7
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-216494
SN  - 1664-2392
VL  - 11
ER  -