Endocrine Abstracts

Background: True cyclical Cushing's syndrome is rare and usually due to an ACTH-secreting corticotrophinoma. We describe a man with cyclical Cushing's syndrome of 15 years duration who had unexpected pituitary immunohistopathology.
Clinical details: A 22-year-old man presented in 1986 with clinical features of Cushing's syndrome & urinary free cortisols up to 1800 nmol/24h, but normal low-dose DXM suppression, & normal pituitary and adrenals on CT. He was then lost to follow-up. In 1995, he was investigated for secondary hypothyroidism; on examination he was a short, plethoric, hirsute man with truncal obesity. Investigations revealed elevated cortisol levels which remained easily suppressible with DXM. Imaging showed a pituitary macroadenoma 1.6 x 1.5 x 2 cm with suprasellar extension. Transsphenoidal debulking achieved a good initial result but follow-up showed persistent symptoms and an enlarging tumour remnant. External pituitary XRT produced rapid control of his cyclical Cushing's and he remains in remission.
Pathology: Immunocytochemistry showed an adenoma strongly positive for FSH-beta but negative for ACTH, CRH & IL-6. In contrast, the surrounding normal pituitary tissue was strongly positive for ACTH. MIB-1 monoclonal antibody immunostaining, which recognises Ki-67, the gold-standard marker of cell proliferation, was positive in 50% of adenoma cells (most pituitary adenomas have mean staining scores <4%). Tumour tissue was also positive for p53 and p21.
Conclusion: We postulate that his cyclical Cushing's was due to episodic secretion of an ACTH-secretagogue by the pituitary adenoma: however, CRH and IL-6 immunostaining of the tumour were negative. His clinical and biochemical responses suggest the adenoma has proved very radiosensitive despite unusually aggressive histological appearances.