The molecular mechanisms leading to increased cellular proliferation rates and, thus, tumor formation in the anterior pituitary gland are poorly understood. The cyclin-dependent kinase inhibitor p27Kip1 is a key molecule regulating the G1 phase of the cell cycle in many cell types. Furthermore, it was shown that p27 knock-out mice develop pro-opiomelanocortin-positive pituitary tumors. In an effort to clarify the role of p27 in the normal and tumorous human pituitary, we studied the expression of p27 by immunohistochemistry, using a highly specific mouse monoclonal anti-human p27 antibody. Normal pituitaries and 54 pituitary adenomas (twelve somatotrope adenomas, nine prolactinomas, twelve corticotrope adenomas, three TSH-producing tumors, six gonadotrope adenomas, six null cell adenomas, and six oncocytomas) were analyzed. p27 expression was determined semiquantitatively with regard to both the percentage of positive cells and the intensity of the staining. Normal human pituitaries showed strong expression of p27 in most nuclei. In contrast, the levels of p27 were reduced in the majority of the tumors analyzed. Twenty-two tumors (six somatotrope adenomas, five prolactinomas, four corticotrope adenomas, two TSH-producing tumors, two gonadotrope adenomas, and three null cell adenomas) were completely p27-negative. In 18 tumors, p27 expression was found in Յ10% of the cells. In the other ten tumors, 11-80% of the cells were p27-positive. In summary, we were able to demonstrate reduced expression levels of the cell-cycle inhibitor p27 in tumors derived from all pituitary cell types. Our data indicate that p27 may be an important regulator of cellular proliferation in the anterior pituitary, the underexpression of which could play a role in pituitary tumorigenesis.

In 17 primary transnasal operations on Nelson tumours long-term results are assessed measuring ACTH plasma levels and performing regular neuroradiological controls. In small intrasellar adenomas only one recurrent ACTH elevation near to pretreatment levels without symptoms from tumour growth was observed after 10 years. ACTH normalization was rarely achieved in large tumours, but only in one patient was a relapse visible in CT scan after three years. Thus selective tumour removal seems to be advisable at an early stage when sellar enlargement occurs. Interpretation of ACTH plasma levels has to include completeness of adrenalectomy, cystic tumour necrosis, and corticoid replacement which reduces ACTH levels. Elevation of ACTH plasma levels over 5,000 pg/ml has been regularly accompanied by extrasellar tumour extension. In large adenomas with definitely elevated ACTH levels, additional radiation therapy should be considered.

SummaryThe authors describe a microsurgical pressure-irrigation-suction system (MPIS) which allows a rapid adjustment of suction and irrigation to the operative situation by one-hand manipulation. This system is especially suitable for transsphenoidal microsurgery of pituitary disorders and has proved its usefulness in 60 such operations.

A patient with a ganglioglioma of the neurohypophysis developed the syndrome of inappropriate antidiuretic hormone secretion (SIADH). We present the case and describe its microscopic and ultrastructural features. Malignant neoplasms were thought to be the main cause of ectopic production of vasopressin. Head trauma, infection, or drugs, however, can also induce hypersecretion of vasopressin. Mechanical compression of the pituitary stalk can lead to an excessive antidiuretic hormone (ADH) release by affecting the inhibitory system. Primary neuroendocrine tumors of the hypothalamic-neurohypophyseal system are extremely rare. We demonstrate the presence of vasopressin in the tumor cells by immunocytochemistry. This represents the first case of SIADH caused by a tumor of the neurohypophysis.