Pasireotide-resistant Refractory Cushing's Disease without Somatostatin Receptor 5 Expression.

Pasireotide, which has a high affinity for somatostatin receptor (SSTR) 5, has attracted attention as a new treatment for refractory Cushing's disease. The patient was a 28-year-old man. He had refractory Cushing's disease and underwent multiple surgeries, radiotherapy, and medication therapy. An examination of the adenoma by immunohistochemistry revealed a low SSTR5 expression. An USP8 mutation was not detected by reverse transcription polymerase chain reaction. Although we administered pasireotide, it was ineffective. While a further investigation is necessary, the analysis of SSTR5 expression may support the prediction of the efficiency of pasireotide for Cushing's disease. We report this case as a useful reference when considering whether or not to use pasireotide for refractory corticotroph adenomas.

Recent advances in understanding corticotroph pituitary tumor initiation and progression.

Cushing's disease is the most frequent form of hypercortisolism and is caused by hypophyseal corticotroph adenomas secreting excessive amounts of adrenocorticotropic hormone. Most of the tumors develop sporadically and only a limited number of corticotroph adenomas have been found to be associated with different neuroendocrine syndromes or with familial isolated pituitary adenomas. The pathogenic mechanisms of corticotroph adenomas are largely unknown, but the discovered aberrant chaperoning activity of heat shock protein 90 on the one hand and the presence of ubiquitin-specific protease 8 mutations on the other hand partially explained the causes of their development. Corticotroph tumors arise initially as benign microadenomas but with time form invasively growing aggressive macroadenomas which can switch to corticotroph carcinomas in extremely rare cases. The mechanisms through which corticotroph tumors escape from glucocorticoid negative feedback are still poorly understood, as are the processes that trigger the progression of benign corticotroph adenomas toward aggressive and malignant phenotypes. This review summarizes recent findings regarding initiation and progression of corticotroph pituitary tumors.