The dominant role of increased intrasellar pressure in the pathogenesis ofhypopituitarism, hyperprolactinemia, and headaches in patients with pituitary adenomas

Mild hyperprolactinemia frequently accompanies the hypopituitarism seen in patients with pituitary macroadenomas that do not secrete PRL. Recent data suggested that the hypopituitarism and mild hyperprolactinemia in this sett ing are largely due to compression of pituitary stalk and portal vessels. H eadaches (HAs) are frequently seen in patients with large adenomas and at t imes in those with microadenomas. Because the walls of the sella turcica ar e relatively rigid, we postulate that tumor growth within the sella increas es intrasellar pressure (ISP), which in turn impairs portal blood flow, res ulting in mild hyperprolactinemia and hypopituitarism. We also postulate th at increased mean ISP (MISP) contributes to the development of HAs. Normal MISP is not known but is unlikely to exceed normal intracranial pressure of less than 10-15 mm Hg. We determined MISP in 49 patients who had transsphenoidal surgery for pitui tary adenomas. MISP was measured using a commonly available intracranial mo nitoring kit where a fiberoptic transducer was inserted through a 2-mm dura l incision at the time of adenomectomy. Patients with deficient FSH, LH, AC TH, or TSH secretion were considered hypopituitary. Data on serum PRL level s were included for analysis only in patients whose adenomas had negative i mmunostaining for the hormone. MISP measurements ranged from 7-56 mm Hg, with a mean (+/-SD) of 28.8 +/- 1 3.5 and a median of 26 mm Hg. The pressure measurements were higher in pati ents with hypopituitarism than in those with normal pituitary function (P = 4.6013 x 10(-6)). Patients presenting with HAs had higher MISP than those who did not (P = 5.44 x 10(-7)), regardless of their pituitary function or tumor sizes. PRL levels correlated positively with MISP values (r = 0.715, P < 0.0001). Tumor size did not correlate with MISP or PRL levels. The findings of increased MISP in hypopituitary patients and the documented correlation with PRL levels, suggest that ISP is a major mechanism involve d in the pathogenesis of hypopituitarism and hyperprolactinemia. Similarly, the increased MISP in patients with HAs, irrespective of tumor size or pit uitary function, suggest that increased ISP is a major mechanism involved i n the pathogenesis of this symptom. The data support the hypothesis that in patients with pituitary adenomas increased ISP is a major mechanism contri buting to the development of hyperprolactinemia, hypopituitarism, and HAs. Increased ISP in these patients leads to compression of the portal vessels and the associated interruption of the delivery of hypothalamic hormones to the anterior pituitary. This would explain the reversibility of pituitary function observed in most patients after adenomectomy. However, increased I SP may also lead to decreased blood supply, resulting in ischemic necrosis in some regions of the pituitary. The latter could limit potential recovery of pituitary function after adenomectomy.