Norio Kanie

Long-term growth hormone responses to nonspecific hypothalamic hormones in acromegalic patients

Nonspecific hypothalamic hormones such as thyrotropin-releasing hormone or luteinizing hormone-releasing hormone, or both, elicited abnormal growth hormone responses in 73 of 108 (67.6%) acromegalic patients. After transsphenoidal adenomectomy, the provocative tests using these hormones were repeated in 26 patients with abnormal preoperative growth hormone responses to study variations in these responses during a 1-8-year observation period (average duration, 4 years). After surgery, 7 of the 26 patients regained normal basal growth hormone levels (less than 5 ng/mL) and manifested normal responses to the hypothalamic hormones. During the postoperative observation period, their basal growth hormone levels remained normal as did their responses to provocation with hypothalamic hormones, confirming that the adenoma had been completely resected. Eight other patients demonstrated normal growth hormone levels after surgery; however, they continued to have abnormal responses to provocation with hypothalamic hormones, suggesting the presence of residual adenomatous tissue in the gland. These patients manifested no marked increase in basal or peak growth hormone levels during the follow-up period (from less than 1 to less than 7.5 years) and they were all in clinical remission without any other treatment. Only one incompletely adenomectomized patient who had received no additional treatment experienced regrowth of the tumor. The main factor affecting the surgical results appears to be the preoperative basal growth hormone level, because abnormal growth hormone secretion ceased in all patients who had manifested preoperative levels below 45 ng/mL. Technical refinements of the operative procedure are another important factor in the postoperative outcome. Peritumoral tissue resection after simple selective adenomectomy is mandatory for better surgical results. Our studies indicate that fairly good results can be obtained without risk of the recurrence of the tumor or regrowth, when postoperative growth hormone levels are below 5 ng/mL and that the results are not affected by the postoperative growth hormone responses to provocation with hypothalamic hormones.

Treatment of Cushing's Disease by Transsphenoidal Microsurgery

Six patients of ACTH dependant Cushings disease were treated by transsphenoidal resection of pituitary adenomas. Preoperative endocrinological results showed that both plasma ACTH and cortisol were maintained at higher levels and their normal diurnal rhythms were lost. Urinary 17-OHCS excretion was partially suppressed by larger doses of dexamethasone (8 mg). These data was suggestive of pituitary dependent Cushings disease, rather than ectopic ACTH-producing tumors. The sella volume was measured by Di Chiros method and in 3 cases it exceeded minimally above the upper limit of the normal value, but the other 3 showed completely normal sella. Localized bulging of the sella floor was found in 2 cases by midline lateral tomography. In the A-P tomogram asymmetry of the sella floor was found in one case and localized bulging in other 2 cases. Minimal suprasellar expansion of the tumor was found only in one case by midline pneumotomography. Magnified cerebral angiography with subtraction method or computed tomography was not diagnostic to verify pituitary microadenomas. The indication of pituitary surgery had to be decided mainly by endocrinological findings. In only one case the adenoma occupied most of the intrasellar space, but in the other 5 they were microadenomas and 3 of them were buried in the normal glands. Complete resection of the adenoma was attempted, but macroscopically normal tissue was tried to be left as much as possible. Typical Crookes hyaline changes were found in the normal adenohypophysis in one case and immunohistochemical studies using anti-ACTH serum revealed that the Crookes cells are still reactive. After surgery most patients showed decreased plasma ACTH and cortisol levels and substitution therapy of adrenocortical hormones was necessary for the first one or two months. Rapid clinical remission of Cushings syndrome was observed in all but one, who might have residual tumor cells due to technical incompleteness. Successive endocrinological reevaluation showed that pituitary-adrenal function has been normal or subnormal in 5 cases. One showed no significant improvement. None had pan-hypopituitarism nor any serious side effects, such as liquorrhea and continuous diabetes insipidus. Overall results suggest that transsphenoidal resection of pituitary adenomas in Cushings disease should be located in the center of the treatment.