Naoki Kageyama

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.

Immunoreactive β-Endorphin and Adrenocorticotropin in Human Cerebrospinal Fluid

: To elucidate the significance of beta-endorphin in human cerebrospinal fluid (CSF), CSF levels of beta-endorphin-like immunoreactivity (beta-EP-LI) in various diseases were determined by a specific radioimmunoassay and compared with simultaneously determined ACTH-like immunoreactivity (ACTH-LI) levels in CSF. CSF beta-EP-LI and ACTH-LI in the control group, consisting of 5 normal subjects and 19 patients with nonendocrine diseases, were 22.2+/-1.3 and 14.6+/-0.4 fmol/ml, respectively. CSF levels of these peptides in patients with schizophrenia (n = 19) and acromegaly (n = 10) were not significantly different from those in the control group. Patients with Cushings disease (n = 7) had significantly lower CSF beta-EP-LI and ACTH-LI levels than those in the control group. Four of them showed a parallel increase in CSF beta-EP-LI and CSF ACTH-LI levels after the complete removal of pituitary microadenomas (P < 0.05). Gel chromatography of CSF beta-EP-LI from a normal volunteer, a control patient, and one patient each with catatonia, Nelsons syndrome, Cushings syndrome (adrenal adenoma), and acromegaly gave similar patterns consisting of three peaks with the elution positions comparable to those of authentic beta-endorphin, beta-lipotropin, and possibly their precursor molecule. Gel chromatographic patterns of CSF beta-EP-LI and ACTH-LI were compared in a normal volunteer. The first peaks of beta-EP-LI and ACTH-LI eluted at the same position and the second peak of ACTH-LI coincided with the elution position of authentic ACTH.CSF beta-EP-LI and ACTH-LI levels determined every 5 min over a period of 80 min in three normal volunteers did not show moment-to-moment variability.A significant correlation (r = 0.75, P < 0.001) was seen between CSF beta-EP-LI and ACTH-LI levels in normal subjects and patients studied (n = 73). This suggests that beta-endorphin and ACTH in human CSF share the common regulatory mechanism in normal and pathologic conditions.

Pineal Tumors: clinical diagnosis, with special emphasis on the significance of pineal calcification.

The clinical presentations, findings of neuroradiological examinations, laboratory findings, pathological diagnoses, methods of treatment, and results of follow-up of 43 cases of pineal tumor collected at the Nagoya University Hospital from 1958 to 1979 are reviewed. The definitions of calcification of the pineal body and of pineal tumor are given. There is a significant difference in the incidence of calcification of the pineal body between pineal teratomas and pineal germinomas. Although there is a 100% rate of calcification of the pineal body in cases of pineal germinoma, the rate is very low in cases of pineal teratoma; calcification appears in only a small percentage of the cases of teratoma mixed with germinoma or embryonal carcinoma, or both. In male patients with suprasellar germinoma, there is a high frequency of an associated pineal calcification. No pineal calcification is seen in cases of basal ganglia germinoma. The computed tomographic (CT) findings of pineal teratoma and germinoma are characteristic. CT scanning is superior for early diagnosis of suprasellar and basal ganglia germinomas.

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.

Brain metastasis of choriocarcinoma

Twenty-four patients with histologically verified brain metastasis of choriocarcinoma were analyzed regarding autopsy and operative findings, signs and symptoms, diagnosis, method of treatment, and prognosis. The autopsy incidence of brain metastasis was 66.7% in patients with choriocarcinoma, and the predominance of single brain lesions was confirmed. Most of the metastatic lesions were hemorrhagic. The hemorrhages were intratumoral, peritumoral, and/or subarachnoid. These findings were well correlated with the findings on computed tomographic (CT) scans and the acute onset with rapid progression of symptoms. The history of molar pregnancy, measurements of urinary chorionic gonadotropin, and findings on CT scans were diagnostic. Surgical removal of the lesion followed by chemotherapy combined with irradiation is the treatment of choice in patients with progressive neurological deterioration in whom chemotherapy alone is ineffective.

Effect of Estrogen on Prolactin mRNA in the Rat Pituitary

The effect of estrogen on prolactin (PRL) synthesis at a single-cell level was studied by in situ hybridization and immunohistochemistry. Long-term estrogen treatment increased PRL-containing cells from 10-20% of total cell population to 80-90%, as revealed by immunohistochemistry. PRL mRNA containing cells also increased in a similar fashion. Moreover, cytoplasmic PRL mRNA expressed as the number of silver grains per cell increased 4- to 5-fold by estrogen. These results suggest that long-term estrogen treatment causes not only PRL cell proliferation but also an increase in PRL mRNA in a single cell.

Long-term follow-up of patients with optic glioma

Patients with optic glioma were classified into two types: infant type and childhood. The infant type was usually immature astrocytomas that had an aggressive course and had a poor prognosis. On the other hand, the childhood type was usually mature astrocytomas with a rather benign, self-limiting course, even when the tumor had been left untreated. To make a long-term assessment, 11 patients with optic glioma were studied and 6 long-term survivors with chiasmal tumor invasion, in whom total removal of the tumor had not been feasible, were followed up for 8–12 years. Most of them had a stable course both clinically and radiologically.

Radioreceptor assay of methionine-enkephalin-like substance in human cerebrospinal fluid

&NA; A sensitive and simple radioreceptor assay system for measuring methionine(met)‐enkephalin‐like substance in human cerebrospinal fluid (CSF) was developed using a particulate fraction of rat brain as a receptor preparation and [3H]dihydromorphine as a radiolabeled ligand in the presence of 1 mM ethylenediamine tetraacetate (EDTA) and 2 mM magnesium acetate. Metenkephalin‐like substance was purified from CSF by the combination of Sephadex G‐10 and SP‐Sephadex (H+) column chromatographies to be free of sodium and large molecular weight substance such as &bgr;‐endorphin. The assays were carried out on samples obtained from normal subjects and patients with the disease of the brain or pituitary by lumbar or ventricular puncture. Mean level in samples obtained from normal subjects by lumbar puncture was 2.6 ± 1.0 pmoles/ml.

Thermal Analysis on the State of Free and Bound Water in Normal and Edematous Brains

Analysis of the state of tissue water in brain parenchyma is essential for studying the pathogenesis of brain edema. However, due to technological problems the state of water in tissue remains difficult to assess. Ambo1 attempted in 1951 to measure bound water by the cobalt chloride method applied to formalin-fixed brain. Utilizing NMR, Go and Edzes5 studied in 1975 the state of protons of fresh brain tissue and found an increase in relaxation time of edematous brain tissue compared to controls. An increase of relaxation time is considered to result from an increase of free water. However, absolute values of free and bound water have not been determined yet.

Sensitivity to 1‐(4‐amino‐2‐methyl‐5‐pyrimidinyl)methyl‐3‐(2‐chloroethyl)‐3‐nitrosourea hydrochloride (ACNU) of glioma cells in vivo and in vitro

A new water‐soluble nitrosourea (ACNU) was tested for its antitumor activity against four glioma cell lines. Four factors were studied to determine its antitumor activity: inhibition of cell growth, morphologic observation, analysis of DNA histogram with flow microfluorometry, and sensitivity testing with microtest plate. Growth inhibition in response to ACNU was seen in two cell lines (EA285, U251‐MG), whereas two cell lines (YE2‐2, T98) were resistant to ACNU. The results of the present sensitivity test concur with those of other examinations that this test is useful in selecting a drug and determining the effective dose.