Late onset Cushings disease, occurring years following the diagnosis of a silent corticotroph adenoma (SCA) is rare, with very few previously reported cases. We present a series of 5 subjects with SCA, aggressive tumour recurrences and late onset Cushings disease.
The mean age of subjects at initial presentation was 41 yrs (3552), sex 3:2 (M:F). There were no clinical features of hypercortisolism at diagnosis. Two subjects had hypocortisolim requiring steroid replacement. Three patients had aggressive tumours radiologically and clinically (visual field defects) at presentation. Initially all patients had trans-sphenoidal surgery, and four subjects had post-operative radiotherapy.
Histologically 80% of tumours had predominantly positive ACTH immunostaining, and one subject had a plurihormonal tumour (<1% ACTH, 5% TSH).
On average each subject had 3 recurrences (range 27) requiring surgery or radiotherapy. Mean time to first recurrence was 8.6 yrs (range 216 yrs).
Tumour recurrences had a similar immunophenotype to the original tumour. Mitotic index as measured by Ki-67 at presentation was low (0.32%), and remained low in two subjects. However recurrent tumours in 3 subjects had unusually high rates of mitosis (>10%).
Cushings disease occurred rapidly over a few weeks, and required medical treatment in all subjects. This was confirmed by urinary free cortisol measurements and dexamethasone suppression testing. Cushings disease occurred on average 10.8 yrs (219) following the initial diagnosis of SCA.
Progress: Two subjects died very rapidly, following aggressive tumour recurrence, one of whom had a spinal metastasis (thus a pituitary carcinoma). The 3 remaining subjects continue to have progressive disease.
Conclusion: We report a series of five young subjects with a rare particularly aggressive subset of silent corticotroph adenomas, with multiple recurrences and late-onset Cushings disease occurring up to 19 years following initial diagnosis. This would suggest careful biochemical as well as radiological monitoring of subjects with silent corticotroph adenomas is required.
01 - 05 Apr 2006
European Society of Endocrinology