Objective: The development of computed tomography (CT) and magnetic resonance imaging (MRI) has resulted in the discovery of unsuspected endocrinologically silent pituitary masses (pituitary incidentalomas). The aim of this study was to perform a national survey on pituitary incidentalomas in order to establish an appropriate approach to them. Design and methods: Five hundred and six patients with pituitary incidentalomas were obtained by questionnaire from March 1999 to May 2000 under the auspices of the Ministry of Health, Labor and Welfare in Japan. Two hundred and fifty-eight patients underwent surgery (surgical group), while 248 patients were followed up conservatively for a mean period of 26.9 months (range 6-173 months) (non-surgical group). Clinical and biochemical assessment, CT or MRI of the pituitary, and visual field testing by Goldman perimetry were assessed at baseline and 6 months and yearly thereafter. Results: Thirty-three patients with pituitary incidentalomas (13.3%) developed tumor enlargement during the mean follow-up period of 45.5 months. Of 115 estimated non-functioning adenomas, 23 tumors (20.0%) increased during a mean follow-up period of 50.7 months (range 10 -173 months), while 5 of 94 (5.3%) estimated Rathke's cysts increased in size during follow-up. Pituitary apoplexy occurred in one of 248 patients (0.4%). Conclusions: Pituitary incidentalomas usually follow a benign course. We recommend transsphenoidal adenectomy for a solid mass attached to the optic chiasma estimated to be a pituitary adenoma by MRI. Other patients should be followed up by MRI every 6 months for the first 2 years, and then yearly.

Incidental lesions should be considered a cause of false-positive findings (6.1%) when an imaging diagnosis is made of a functioning pituitary microadenoma.

Ghrelin mRNA, in addition to GHSR mRNA, is expressed in various types of pituitary adenoma with different levels of expression in each type. Our findings suggest that ghrelin produced in pituitary adenoma may play some role in the mechanism underlying the development of adenoma cells through autocrine and/or paracrine pathways.

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These results suggest that 1) cavernous sinus sampling without CRH administration can demonstrate hypersecretion of ACTH from the pituitary gland with a high diagnostic accuracy; 2) intercavernous gradients will indicate the correct lateralization in laterally localized microadenomas; and 3) sampling should be performed from the posterior portion of the cavernous sinus.

Transsphenoidal surgery can achieve a good long-term outcome in patients with thyrotropin-secreting pituitary adenomas if surgery is performed before these become larger, invasive tumors. In the authors' experience, thyrotropin-secreting adenomas are fibrous and firm, which makes it difficult to achieve surgical remission. In addition, even satisfactory resection of the tumor sometimes results in recurrence of SITS or hyperthyroid symptoms due to coexistent primary hyperthyroidism. It is emphasized that a careful follow-up review is necessary after surgery, especially in patients with a long preoperative history of hyperthyroidism.

A 53-year-old Japanese woman was diagnosed with Cushing's disease caused by a adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma on the basis of clinical an imaging data. The surgically resected tumor tissue was investigated histopathologically using immunohistochemical analysis of pituitary hormones. Our study revealed that the adenoma expressed not only ACTH but growth hormone (GH) in the tumor cells. Furthermore, immunohistochemical double staining showed that some adenoma cells were positive for both ACTH and GH. In situ hybridization for GH mRNA revealed that the adenoma cells produced GH as opposed to simply storing it. Although many pituitary adenomas produce multiple pituitary hormones, pituitary adenoma producing both ACTH and GH in the same adenoma cells, such as seen in this case, is extremely rare. To elucidate the molecular mechanism involved, we investigated the expression of transcription factors NeuroD1 and Pit-1 and found that both transcription factors were expressed in many tumor cells. This case report describes a very rare case of pituitary adenoma that produced both ACTH and GH. We propose a hitherto undescribed translineage expression of transcription factors as the basic mechanism of this unique functional differentiation.