Pitfalls in Cushings disease: report of an ectopic ACTH-producing pituitary adenoma in the sphenoid sinus
M. Ritter1, T. Burkhardt2, S. Schmid3, C. Bernreuther4, B. Winterberg5, H. Lehnert3 & J. Flitsch2
Cushings disease is caused by ACTH-secreting pituitary adenomas. Gold standard therapy is the resection of the adenoma by transsphenoidal surgery with high cure rates even in cases of negative MR imaging. Surgical failure despite clear endocrinological test results is possible and mostly explained by hidden minute adenomas within the gland.
We report on a 50-year-old woman suffering from ACTH-dependent Cushings syndrome. Endocrinological work-up was most compatible with a pituitary origin. Although an MRI showed no pituitary tumor, CRH-stimulated petrosal sinus sampling revealed a clear central-peripheral ACTH gradient. The patient underwent transsphenoidal surgery with negative exploration of the pituitary gland. After intraoperative re-evaluation of the preoperative MRI, a polyp at the bottom of the sphenoid sinus was identified. The intraoperative microscopic aspect as well as instantaneous sections and cytology of a biopsy confirmed an adenoma, which was removed. Histological analysis demonstrated an ACTH-producing pituitary adenoma adjacent to respiratory mucous membrane consisting of ciliated epithelium with submucous connective tissue. Histological evaluation of biopsies from the pituitary gland revealed normal pituitary tissue. Thus, an ACTH secreting adenoma was only detectable in the sphenoid sinus. Postoperatively, ACTH concentrations dropped and after 3-month of follow up, Cushings stigmata were found to regress and a temporary hydrocortisone substitution could be reduced.
The adenohypophysis originates from the floor of the nasopharynx, that is partly located in the precursor of the sphenoid bone. Ectopic pituitary tissue is thought to arise from remnants of Rathkes pouch, and ectopic adenomas are believed to originate from remaining cells resting along the path of the embryological formation of the pituitary gland. Ectopic adenomas growing in the sphenoid sinus have been reported in only 10 cases so far1. Keeping in mind that ectopic pituitary tissue may exist in a patient with Cushing disease can potentially prevent failure of surgery.
1. Suzuki J et al. Endocr J 2004; 51 97103.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.