We report a unique patient with a germline USP8 mutation who presented with CD and a constellation of other findings that constitute an intriguing genetic syndrome.
In human patients, somatic mutations in USP8 were identified as the underlying cause of adrenocorticotropic hormone (ACTH) releasing pituitary adenomas causing Cushing's disease (CD).
The USP8 mutational status could predict remission in patients with CD, so our objective was to correlate the presence of somatic USP8 mutations with the rate of recurrence after transsphenoidal surgery (TSS) retrospectively.
The pathogenesis of Cushing's disease is poorly understood; two recent reports identifying somatic mutations in USP8 in pituitary corticotroph tumors provide exciting advances in this field.
Further prospective studies using a systematic protocol will provide more consistent information about the influence of the corticotropinomas with USP8-mutated alleles on the phenotype, responses to treatment and outcome of patients with CD.
Mutations in USP8 have been identified in 35-62 % of functional sporadic corticotroph adenomas causing Cushing's disease, but not in any other type of pituitary tumor.
We characterized SCAs based on clinical, hormonal and molecular data, and compared the characteristics of these tumours with those of macro (MCA)- and micro (mCA)-ACTH adenomas with Cushing's disease.
OBJECT Functional corticotroph pituitary adenomas (PAs) secrete adrenocorticotropic hormone (ACTH) and are the cause of Cushing's disease, which accounts for 70% of all cases of Cushing's syndrome.
The primary treatment of Cushing disease (hypercortisolism due to ACTH-producing adenomas, which is the cause in approximately 65% of the cases of hypercortisolism) is adenoma resection and medical therapies including ketoconazole, mifepristone, and pasireotide.
Age of patients ranged from 52 to 72, five females and one male, four with Cushing's disease and two with ectopic ACTH production, one from a pancreatic neuroendocrine tumor and one from medullary carcinoma of the thyroid.
We present an unusual case of Turner syndrome (TS) and Cushing disease (CD) in a young woman, admitted to our department seven years after a successful surgical removal of ACTH-secreting pituitary tumor.