Toshichi Nakane

Long Term Results of Transsphenoidal Adenomectomy in Patients with Cushing's Disease

As part of an ongoing series, 100 patients with Cushings disease underwent transsphenoidal operations. Pituitary adenomas were confirmed in 93 patients, and initial remission was achieved in 86 (92%) of them. Hypercortisolemia was not corrected in 7 patients, and in 4 this was due to invasive adenomas. These patients were subjected to irradiation, medical treatment, or both after operation. Only 7 of the 100 patients had no pituitary adenoma found at operation, and they obtained no clinical remission even after partial or subtotal hypophysectomy. Follow-up review, with an emphasis on endocrinological studies, was performed on these patients for a mean period of 38 months. Seventy-eight patients were in long term remission after operation and had restoration of noncorticotropic hormone secretion as well as pituitary-adrenal function. Recurrence was noted in 8 patients after 19 to 82 months in remission. In all of these patients, pituitary adenomas were verified by reoperation and no case of corticotrophic cell hyperplasia was noted. We conclude that late recurrence of Cushings disease may occur after adenoma removal and is due to the regrowth of adenoma cells left behind in the peritumoral tissue at the first operation. In view of the overall remission rate, transsphenoidal adenomectomy is considered a highly effective treatment for Cushings disease.

Early operation for ruptured intracranial aneurysms: comparative study with computed tomography

The relationship between the results of early operation for ruptured intracranial aneurysms (72 cases) and the preoperative computed tomographic (CT) findings was studied. There was a correlation among the surgical results, the development of symptomatic vasospasm, and high density on the preoperative CT scan, particularly the presence of a localized, thick layer in the subarachnoid space. However, no relationship was found between the occurrence of ventricular enlargement and the preoperative CT findings. Cisternal or ventricular drainage might contribute to an uncomplicated postoperative course for patients with severe subarachnoid clot shown on the preoperative CT scan.

Transsphenoidal approach to pituitary adenomas with suprasellar extension

Abstract During the past six years, we have operated upon a total of 59 pituitary adenomas with suprasellar extension. Of 26 patients treated by transsphenoidal operations, 54% (19 of 35 eyes) recovered normal visual acuity; improvement was noted in another 37% (13 of 35 eyes). The visual field was corrected in 84% (41 of 49 eyes). In about 60% (31 of 51 eyes) of the patients who underwent frontal craniotomy, visual improvement occurred. Endocrinologic cure of hypersecreting adenomas with suprasellar extension was difficult, although visual impairment improved. We suggest that in most cases the transsphenoidal approach is the method of choice in pituitary adenomas with suprasellar extension. With this approach there has been excellent visual improvement and fewer operative complications.

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.