Masayoshi Takanohashi

Morphofunctional study of pituitary adenomas with acromegaly by immunoperoxidase technique and electron microscopy

In attempting to establish a functional classification of acidophilic adenomas of the pituitary gland, immunoperoxidase staining techniques specific for growth hormone (GH), prolactin (PRL), and luteinizing hormone (LH) were carried out. Surgically removed specimens from 24 acromegalic patients were studied. The pathologic observations were then compared with the basal plasma levels of each of the hormones. The existence of GH was demonstrated in all patients. Immunohistologically, GH‐secreting adenomas could be subdivided into three types: Type I had the highest plasma‐GH level (average 121 ng/ml), while the average plasma‐GH levels of types II and III were 103 ng/ml and 73 ng/ml, respectively. This result suggested that the serum‐GH level may correlate with the GH cell population in a tumor. In 13 of the acromegalic patients, immunoenzyme methods were utilized in order to identify prolactin cells. No clear correlation between serum‐PRL levels and the distribution of PRL cells could be demonstrated. A few immunoreactive LH cells were found in 13 patients. These LH cells may be a mixture of normal cells, based on our clinical finding.

Multiple forms of monoamine oxidase in human brain tumors

Abstract The multiplicity of monoamine oxidase (MAO) in human brain tumors was studied with a criterion of inhibitor sensitivity. All of the human brain tumors of glial origin, irrespective of their malignances, showed similar or lower ratios of type A MAO to type B MAO as compared with the normal cerebral hemispheres. This result is quite different from those of mouse neuroblastoma and rat glioma.

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.

The Correlationship between Basal Prolactin Levels and the Suppressive Effect of CB-154 or L-DOPA on GH Release in Acromegalic Patients

It has been reported that the plasma growth hormone (GH) and prolactin (PRL) levels in acromegalic patients were suppressed after intensive administration of dopaminergic drugs, but we found that the plasma GH levels in some acromegalic patients were not suppressed. Plasma GH and PRL levels after a single oral administration of CB-154 (2.5mg) and L-DOPA (1g) were measured in 18 active acromegalic patients with and without galactorrhea. 1. The mean plasma GH levels after the administration were clearly suppressed in 8 patients with galactorrhea, while they were not suppressed in 10 patients without galactorrhea. These drugs were more effective in suppressing plasma GH levels in acromegalic patients with galactorrhea and hyperprolactinemia. 2. We calculated the responsiveness of the plasma GH level as follows: GH responsiveness (%) = (mean plasma GH level after the administration of CB-154 or L-DOPA)/ (basal GH level) x 100. The basal plasma PRL levels were inversely correlated with GH responsiveness (CB-154: r=-0.690, p less than 0.01. L-DOPA: r=-0.541, p less than 0.05). It was found that the effect of dopaminergic drugs on plasma GH levels was closely correlated with basal PRL levels in acromegalic patients. This implies that the chronic administration of CB-154 may be effective in acromegalic patients with galactorrhea and hyperprolactinemia.