Melatonin Receptor Mel1b- and Mel1c-mediated Green Light Induced the Secretion of Growth Hormone in Anterior Pituitary of Chicks.

Previous studies have found that melatonin was related to the growth and development in avian. Therefore, the newly hatched broilers were exposed to colors of light to establish a model of pinealectomy and explored the mechanism of pineal melatonin promoting growth hormone (GH) secretion. The results showed that green light (GL) promoted the levels of GH, pituitary-specific transcription factor-1 (Pit-1) genes and proteins in pituitary. Moreover, the mRNA and protein levels of melatonin receptor subtypes Mel1b and Mel1c in the pituitary in GL were higher than other monochromatic light groups. After pinealectomy, the expression of Pit-1, GH, Mel1b and Mel1c in pituitary decreased. In vitro, exogenous melatonin promoted the level of Pit-1 mRNA and the secretion of GH in anterior pituitary cells. However, when melatonin was added with exogenous selective Mel1b antagonist (4-phenyl-2-propionamideotetralin) and selective Mel1c antagonist (prazosin), the level of Pit-1 mRNA and the GH secretion decreased. When selective Mel1b and Mel1c antagonists were added simultaneously, the decrease in Pit-1 mRNA and GH secretion was more significant. These results indicated that pineal melatonin promotes the expression of Pit-1 under GL by binding to melatonin receptor subtypes Mel1b and Mel1c in the pituitary, thereby increasing GH secretion and promoting the growth.

Pulsed electromagnetic wave exposure induces ultrastructural damage and upregulated expression of heat shock protein 70 in the rat adenohypophysis.

The aim of the present study was to investigate the ultrastructural damage and the expression of heat shock protein 70 (HSP70) in the rat adenohypophysis following pulsed electromagnetic wave (PEMW) exposure. The rats were randomly divided into four groups: Sham PEMW exposure, 1 x 10(4) pulses of PEMW exposure, 1 x 10(5) pulses of PEMW exposure and 3 x 10(5) pulses of PEMW exposure. Whole body radiation of 1 x 10(4) pulses, 1 x 10(5) pulses and 3 x 10(5) pulses of PEMW were delivered with a field strength of 100 kV/m. The rats in each group (n=6 in each) were sacrificed 12, 24, 48 and 96 h after PEMW exposure. Transmission electron microscopy was then used to detect the ultrastructural changes and immunocytochemistry was used to examine the expression of HSP70. Cellular damage, including mitochondrial vacuolation occurred as early as 12 h after PEMW exposure.More severe cellular damages, including cell degeneration and necrosis, occurred 24 and 48 h after PEMW exposure. The PEMW-induced cellular damage increased as the number of PEMW pulses increased. In addition, the expression of HSP70 significantly increased following PEMW exposure and peaked after 12 h. These findings suggested that PEMW induced ultrastructural damages in the rat adenohypophysis and that HSP70 may have contributed to the PEMW-induced adenohypophyseal damage.

Anterior hypopituitarism in adult survivors of childhood cancers treated with cranial radiotherapy: a report from the St Jude Lifetime Cohort study.

PURPOSE: To estimate the prevalence of and risk factors for growth hormone deficiency (GHD), luteinizing hormone/follicle-stimulating hormone deficiencies (LH/FSHD), thyroid-stimulatin hormone deficiency (TSHD), and adrenocorticotropic hormone deficiency (ACTHD) after cranial radiotherapy (CRT) in childhood cancer survivors (CCS) and assess the impact of untreated deficiencies. PATIENTS AND METHODS: Retrospective study in an established cohort of CCS with 748 participants treated with CRT (394 men; mean age, 34.2 years [range, 19.4 to 59.6 years] observed for a mean of 27.3 years [range, 10.8 to 47.7 years]). Multivariable logistic regression was used to study associations between demographic and treatment-related risk factors and pituitary deficiencies, as well as associations between untreated deficiencies and cardiovascular health, bone mineral density (BMD), and physical fitness. RESULTS: The estimated point prevalence was 46.5% for GHD, 10.8% for LH/FSHD, 7.5% for TSHD, and 4% for ACTHD, and the cumulative incidence increased with follow-up. GHD and LH/FSHD were not treated in 99.7% and 78.5% of affected individuals, respectively. Male sex and obesity were significantly associated with LH/FSHD; white race was significant associated with LH/FSHD and TSHD. Compared with CRT doses less than 22 Gy, doses of 22 to 29.9 Gy were significantly associated with GHD; doses ≥ 22 Gy were associated with LH/FSHD; and doses ≥ 30 Gy were associated with TSHD and ACTHD. Untreated GHD was significantly associated with decreased muscle mass and exercise tolerance; untreated LH/FSHD was associated with hypertension, dyslipidemia, low BMD, and slow walking; and both deficits, independently, were associated with with abdominal obesity, low energy expenditure, and muscle weakness. CONCLUSION: Anterior pituitary deficits are common after CRT. Continued development over time is noted for GHD and LH/FSHD with possible associations between nontreatment of these conditions and poor health outcomes.

Factors associated with endocrine deficits after stereotactic radiosurgery of pituitary adenomas.

OBJECTIVE: To analyze the factors associated with anterior pituitary deficits after pituitary adenoma stereotactic radiosurgery (SRS). METHODS: The tumor, pituitary stalk, and pituitary gland were segmented on the dose plans of 82 patients (secreting tumors, n = 53; nonsecreting tumors, n=29) for dose-volume analysis. No patient had undergone prior radiation therapy and all patients had at least 12 months of endocrinological follow-up (median, 63 months; mean, 69 months; range, 13-134). RESULTS: Thirty-four patients (41%) developed new anterior pituitary deficits at a median of 32 months (range, 2-118) after SRS. The risk of developing new anterior pituitary deficits was 16% and 45% at 2 and 5 years, respectively. Multivariate analysis of the entire group showed that poor visualization of the pituitary gland (hazard ratio [HR]=2.63, 95% confidence interval [CI]=1.10-6.25, P=.03) was associated with a higher rate of new anterior pituitary deficits. Dosimetric analysis of 60 patients whose pituitary gland could be clearly identified showed that increasing mean pituitary gland radiation dose correlated with new anterior pituitary deficits (HR=1.11, 95% CI=1.02-1.20, P=.02). New anterior pituitary deficits stratified by mean pituitary gland radiation dose: 19.1 Gy, 83% (5/6). CONCLUSION: New endocrine deficits after pituitary adenoma radiosurgery were correlated with increasing radiation dose to the pituitary gland. Methods that limit the radiation dose to the pituitary gland during SRS may increase the probability of preserving pituitary function.

[Proton irradiation of the pituitary gland for alleviating pain in patients with disseminated prostate cancer].

Central Research Institute of Roentgeno-Radiology; Medical Academy for Further Education, St. Petersburg Stereotactic ablation of the frontal lobe of the pituitary with narrow beams of 1,000 MeV protons was performed in 80 patients to alleviate pain caused by bone metastases. Pain was aborted for a long time so that pain-relieving medication was suspended in 56 (70%) patients. The remaining patients cut down on taking analgetics: peripheral drugs were taken by 11(13.75%), non-narcotic opioids (tramal)--4 (5%), class III opioid narcotics--7 (8.75%), and morphine-type drugs--only 2. No untoward side-effects were reported.

[Heavy particle beams (proton) in oncology (35-year practice of N.N. Blokhin Cancer Research Centre)].

Clinically proved "alternative breast-preserving method" applicable for patients with locally advanced nodal breast cancer. These patients refuse to go in to surgery or have indications for surgery (183 patients--T(1-4)N(0-3)M(0-1)). This method consists of the combination of the traditional method of the whole breast and/or nodal photon irradiation with local highly concentrated proton irradiation in the dosage iso-equivalent to tumor (proton with energy from 130 to 180 MeV, with stop in the target in notice depth). We used the irradiation of the adenohypophysis with narrow proton beams energy 200 MeV. The aim of the first combination of the components is the selectively influence on the target and the channeling to the tumor and its subclinical substances the dosages sufficient for the total irradiation of tumor with sparing surrounding tissues and parts of body. The goal of irradiation of adenohypophysis with protons is the normalization of its hormonal activity and elimination of factors stimulating growth of tumor cells in case of dishormonal cancer. The suggested method didu't only improve the results of the treatment of locally advanced breast cancer, but also contributed to the reducing of the emotional stress. We received high results of the patients with locally advanced nodal breast cancer of criteria: local control rate (96%), long remission (more then 40%) and 5-year actuarial survival rate (83%). The patients examined during 5 and 18 years. It made a good cosmetic effect and high quality life of the patients with breast cancer.

Non-functioning pituitary carcinoma.

Null-cell carcinomas of the pituitary are extremely rare. We describe a 41-year-old woman with a large adenohypophyseal neoplasm presenting as a primary nonfunctioning tumor without pituitary insufficiency. Signs of mass effect with progressive unilateral ocular motility disorders and anterior pituitary failure developed rapidly. Histopathological examination of the trans-sphenoidally removed tumor showed a primary pituitary null cell tumor with high mitotic index. Pituitary carcinoma was suspected because of rapid relapse of ocular motility disorders and of intra-sellar tumor growth after surgery. Radiotherapy of the sellar and parasellar area with a total dose of 59.4 Gy was performed, achieving marked tumor reduction and a significant improvement of ocular motility disorders. However, 6.5 months after presentation the patient rapidly declined and died of carcinomatous meningitis. Less than 100 pituitary carcinomas have been published so far, most of them as single-case reports, and endocrine, immunohistochemical, and ultrastructural data have not been described in the majority of cases. At presentation, there are no specific symptoms that allow to distinguish benign from malignant tumor. Prognosis is poor, since no curative treatment has been established, but aggressive surgery and radiotherapy has been recommended. Our case highlights the poor prognosis of nonfunctioning pituitary carcinomas.

Effect of therapeutic doses of ionising radiation on the somatomammotroph pituitary cell line, GH3.

Ionising radiation is used for the treatment of pituitary tumours as fractionated radiotherapy, where the total dose reaching the tumour area is in the range of 40-50 Gy, or during stereotactic radiosurgery, where the total dose reaching the tumour area during one session is in the range of 20-90 Gy. In this study, we investigated the effect of ionising radiation of (60)Co (dose rate of 3 Gy/min, similar to that used during gamma knife procedure) on the mode of cell death of the somatomammotroph pituitary cell line, GH3, an immortalized cell line derived from a rat pituitary adenoma. We found that the basic mechanism of cell death induced by irradiation of this GH3 cell line by gamma-rays was programmed cell death-apoptosis. Doses of 20-50 Gy were shown to inhibit proliferation in these cells. 24 hours after irradiation with a dose of 20 and 50 Gy, cells were shown to accumulate in the G(2)/M phase of cell cycle. This cell cycle arrest lasted for at least ten days. Apoptosis was detected 72 hours towards until the end of the study (10 days). However, a significant number of cells were still alive ten days following irradiation. We conclude that ionising radiation doses of 20 and 50 Gy induce pituitary GH3 cell apoptosis following cell cycle arrest in the G(2)/M phase.

Heterogeneous regulation of individual lactotroph cells by photoperiod in the Syrian hamster (Mesocricetus auratus).

In many mammals, changes in daylength (photoperiod) regulate multiple aspects of physiology, including the synthesis and secretion of the anterior pituitary hormone prolactin. Here, we tested the hypothesis that individual lactotroph cells exhibit a heterogeneous response to changes in photoperiod, by exploiting a recently developed assay for prolactin gene expression in single pars distalis (PD) cells. Male Syrian hamsters were exposed to either long (LD; 16 h light: 8 h dark) or short (SD; 8 h light: 16 h dark) photoperiods for 12 weeks. Response of the lactotrophic axis to photoperiod was confirmed by the significantly (P<0.01) lower plasma prolactin concentrations in SD than LD hamsters. Analysis of freshly dispersed PD cells by in situ hybridisation demonstrated that photoperiod has no effect (P>0.05) on the proportion of PD cells (approximately 25%) that expressed prolactin mRNA. Heterogeneity of prolactin mRNA expression was observed in both LD and SD. A similar proportion of cells expressed low levels of prolactin mRNA in both photoperiods, suggesting that they may be unresponsive to photoperiod change. In contrast, the remaining PD cells that expressed prolactin mRNA exhibited markedly increased gene expression in LD, consistent with the selective recruitment of a lactotroph subpopulation to a more transcriptionally active state in this photoperiod.

Differential radiosensitivity of hypothalamo-pituitary function in the young adult rat.

Cranial irradiation in children and adults often results in irreversible hypopituitarism. The earliest and most common endocrine abnormality is GH deficiency, often followed by other pituitary hormone deficits. We investigated whether a similar pattern of progressive hypopituitarism could be reproduced in an animal model. Different doses of cranial irradiation were delivered to the hypothalamo-pituitary region of normal adult male rats, and the effects on their subsequent growth, pituitary weight and hormone contents were studied. Animals received cranial irradiation with 300 kV X-rays at doses of 0, 20, 22 or 24 Gy (n=15 per group) and five animals from each group were killed at 8, 14 or 20 weeks after irradiation. Their anterior pituitary glands were weighed and assayed for GH, LH, TSH, ACTH and prolactin (PRL) content. All three doses of irradiation reduced body weight compared with that in non-irradiated controls and compromised growth between 8 and 20 weeks. Pituitary weight increased between 8 and 20 weeks in control rats, whereas it decreased significantly in the irradiated animals. Irradiation induced time- and dose-dependent changes in pituitary hormone contents. GH and PRL were most sensitive and decreased by more than 90% after irradiation; TSH contents were unaffected 8 weeks after the lowest dose of irradiation, but were reduced at 14 and 20 weeks. LH and ACTH were the slowest to be affected, and only at the greater doses of radiation. Thus progressive multiple pituitary endocrine deficits can be induced differentially in rats by increasing doses of cranial irradiation. This model should prove useful for defining the sites and mechanisms by which cranial irradiation induces neuroendocrine dysfunction.

[Experimental-morphological and clinical results of laser destruction of adenohypophysis]. / Eksperimental'no-morfologicheskie i klinicheskie rezul'taty lazernoi destruktsii adenogipofiza.

Feasibility of focal adenohypophysis destruction by Nd:YAG laser is experimentally proven. The destruction is not followed by considerable damage of other structures of the hypothalamus-hypophysis region. It is established that the focus of coagulation necrosis produced by laser radiation is replaced by scar tissue. A surgical treatment of hypophysis adenoma surgical treatment is proposed. Its effectiveness, safety and low traumatism were confirmed at its clinical trial.

Responsiveness of irradiated rat anterior pituitary cells to hypothalamic releasing hormones is restored by treatment with growth hormone.

Hypopituitarism is a common sequela of irradiation in cancer patients. Here we report that recombinant human growth hormone (r-hGH) prevents cell death and restores secretory capacity of irradiated rat pituitary cells in vitro. Dispersed rat pituitary cells from male Sprague-Dawley rats, irradiated with a 9-Gy sublethal dose, were incubated with r-hGH before, after, or before and after irradiation. Treatment with GH resulted in increased cell survival, which reached its maximum at the concentration of 5 nM, with an EC(50) of 3.5 nM. Protective effects of GH on pituitary cells were more pronounced in cultures treated before and after irradiation. Similarly, beneficial effects of GH were observed on the secretory capacity of surviving cells. In fact, irradiated pituitary cells treated with GH secreted substantial amounts of GH, luteinizing hormone, follicle-stimulating hormone, prolactin, thyroid-stimulating hormone and adrenocorticotropic hormone in response to specific releasing hormones. Such effects of GH were prevented in the presence of the specific GH receptor antagonists B2036 and G120K. Our results show that r-hGH exerts a specific protective effect on irradiated rat pituitary cells and suggest possible use of GH as an adjuvant agent for prevention of postirradiation hypopituitarism.

Experimental and clinical aspects of laser destruction of adenohypophysis.

Focal destruction of the adenohypophysis by Nd:YAG laser does not destroy other structures of the hypothalamo-pituitary region. During reparative regeneration, the focus of coagulation necrosis after laser destruction of the adenohypophysis is replaced by cicatricial tissue. A method for surgical treatment of pituitary adenomas was developed. The efficiency, safety, and low traumatism of this method were confirmed in 87 patients.

GSM radiocellular telephones do not disturb the secretion of antepituitary hormones in humans.

It is known that the endocrine system of experimental animals is susceptible to perturbation by radiofrequency (RF) radiation. Because of the recent interest in health and safety issues of cellular telephones, an experiment was designed to evaluate the effect of a 900 MHz RF radiation emitted by a Global System for Mobile radiotelephone (217 Hz impulses, one-eighth duty cycle, 2 W peak power) on human endocrine functions. Twenty healthy male volunteers aged from 19 to 40 were inducted in the present experiment. Each subject was exposed to RF radiation through the use of a cellular phone 2 h/day, 5 days/wk, for 1 month. Subjects were their own control. End points were serum adrenocorticotropin, thyrotropin, growth hormone, prolactin, luteinizing hormone, and follicle stimulating hormone concentrations. These end points were determined in nine weekly blood samples obtained starting 3 weeks before the commencement of the exposure and ending 2 weeks after exposures. All but one blood sample was drawn 48 h after each weekly session. The seventh drawing was performed the morning after the last weekly exposure. Within each individual, the preexposure hormone concentration was used as a control. Results indicated that all hormone concentrations remained within normal physiologic ranges. A difference was not noted among the nine weekly samples in five of six hormones studied. There was a significant change only in thyrotropin concentration, showing a 21% decrease on the seventh sampling. Because this change recovered fully during the postexposure period, it is concluded that 1 month of intermittent exposures to RF radiation from a cellular telephone does not induce a long-lasting or cumulative effect on the hormone secretion rate of the anterior pituitary gland in humans.

Pituitary corticotroph macrotumors. Diagnosis and treatment.

Pituitary corticotroph macrotumors occur in 10% to 50% of dogs with PDH. Clinical signs may be only those of hypercortisolism or may include neurologic signs such as stupor, inappetance, circling, or pacing. Currently, CT and MRI are the only tests that can confirm the presence of a pituitary macrotumor in these patients. Results of endocrine testing are not significantly different from those of dogs with a microtumor. When a macroscopic pituitary tumor is identified in a dog with neurologic signs, or if a larger tumor is found in a dog even in the absence of neurologic signs, radiation therapy is currently the treatment of choice. Unfortunately, success rates with treatment are variable. A better response may be seen if the tumor is smaller and neurologic signs are minimal or absent at the time of treatment.

Melatonin receptors in the suprachiasmatic nuclei and pars tuberalis of testosterone induced photoresponsive rats.

The sexual axis of rats can be rendered photoresponsive by testosterone implants. We have studied in these conditions whether rat pars tuberalis (PT) melatonin receptor density would be decreased after exposure to short photoperiod (SP) like as observed in long day seasonal breeders. The answer is no, but we observed that testosterone induced a photoperiod independent decrease in PT melatonin receptor density. These results show that testosterone-induced photosensitivity in rat is not linked to an SP-induced decrease in PT melatonin receptor density. However, testosterone regulates PT melatonin receptors independently of the photoperiod.

Growth, growth hormone and final height after BMT. Possible recovery of irradiation-induced growth hormone insufficiency.

The aim of the present study was to assess growth, final height, growth hormone (GH) secretion and growth factors after BMT including TBI in childhood. The median age of the 25 participants was 11.3 years at BMT, and a median of 7.5 years had elapsed since BMT. The median height standard deviation score (SDS) declined significantly from diagnosis until 4 years after BMT (n = 25, P = 0.015), and decreased 1.08 SDS from diagnosis until final height (n = 14, P = 0.030). Sitting height to standing height ratio was impaired, -0.64 SDS, P < 0.05. GH insufficiency was found in 32% at follow-up. Repeated assessments of GH production over the years indicated improvement in GH secretion in nine individuals. Evaluation of spontaneous 24-h GH secretion indicated a secretory pattern similar to controls, although the total amount of GH secreted was lower. Neither insulin-like growth factor-1 (IGF-1) nor IGF binding protein-3 (IGFBP-3) alone could be used as a marker of GH insufficiency. IGF-1 was low: -1.18 SDS; (P < 0.001). In conclusion, our study demonstrated the impact on growth, final height, body proportions, GH secretion and growth factors after BMT including TBI. We hypothesize that children who receive BMT at a younger age are more at risk of loss of final height and abnormal body proportions. Our data indicate that some improvement in GH production may occur over the years.

Role of busulfan and total body irradiation on growth of prepubertal children receiving bone marrow transplantation and results of treatment with recombinant human growth hormone.

Seventy-six prepubertal children receiving autologous or allogeneic bone marrow transplantation (BMT) were enrolled in a prospective study on the impact of different pretransplant preparative regimens on growth. Patients were divided into three groups: group I, consisting of 37 children who had received total body irradiation (TBI) and cytotoxic drugs as preparative regimen; group II, including 17 children receiving prophylactic cranial irradiation before being conditioned with TBI and cytotoxic drugs; and group III, composed of 22 patients transplanted after a busulfan (BU)-containing myeloablative therapy. All patients have a minimum follow-up of 2 years, whereas 48 and 34 patients have been studied until 3 and 4 years after transplant, respectively. Height and growth rate were expressed as standard deviation score (SDS). Growth hormone (GH) secretion in response to pharmacologic stimuli was evaluated after documented growth failure. Patients with GH deficiency were treated with recombinant human GH, and response to therapy was evaluated. The main impairment of growth rate in patients belonging to group II was observed in the first year after TBI (growth rate SDS changing from -0.12 +/- 0.23 to -1.23 +/- 0.25, P < .005), with only a slight loss in the following years, whereas in group I children growth failure occurred in the third year after TBI (-1.36 +/- 0.28 SDS in comparison to a pre-BMT SDS of 0.10 +/- 0.15, P < .005). Therefore, growth velocity between these two groups differed significantly in the first 2 years (P < .01) but subsequently equalized. On the contrary, all BU-treated children but 2 grew normally. GH deficiency was shown in the vast majority of children with growth impairment. Twenty-three children treated with recombinant human GH are evaluable; a successful response was observed in all but 1, with the mean growth rate increasing from -2.29 +/- 0.27 before treatment to 0.86 +/- 0.38 and to 1.66 +/- 0.56 SDS at 1 and 2 years after treatment, respectively (P < .001). In conclusion, growth rate impairment was common in patients receiving TBI, with the speed of onset of both decreased growth velocity and GH deficiency depending mainly on the total dose of radiation. On the contrary, patients receiving BU did not experience significant problems in terms of growth velocity. The timely start of appropriate hormonal replacement therapy may ameliorate the final growth of children undergoing BMT.

Growth in children after bone marrow transplantation for acute leukemia.

We evaluated the growth of children with acute leukemia who received a bone marrow transplant (BMT) after preparation with hyperfractionated total body irradiation (TBI). Seventy-two patients (27 female and 45 male patients) with acute lymphoblastic leukemia (ALL; n = 39) or acute myelogenous leukemia (AML; n = 33) who were less than 14 years of age at BMT were studied. Before BMT all had received multiagent chemotherapy and 31 had received cranial irradiation (RT). Preparation for BMT included total body irradiation (1,375 cGy [n = 37] or 1,500 cGy [n = 35]). Heights, expressed as standard deviation scores (SDS), were studied up to 4 years post-BMT. The estimated height SDS for the entire group at the time of BMT was -0.28 +/- 0.05 and decreased to -1.11 +/- 0.22 at 4 years post-BMT (P < .0001). Using a growth curve model to compare covariate groups over the period of study, we found that the loss in height SDS was most significant in those patients who received cranial RT before BMT (P = .005). The estimated height SDS for patients treated with cranial RT went from -0.52 +/- 0.20 at transplantation to -1.83 +/- 0.23 4 years later. In contrast, patients who did not receive cranial RT before BMT showed a smaller decrease in height SDS over the 4-year observation period, ie, -0.11 +/- 0.20 decreasing to -0.73 +/- 0.21. Similarly, patients with a diagnosis of ALL had a greater loss of height SDS than those with AML (P = .033). Fifteen of 18 patients tested were found to be growth hormone (GH) deficient; 9 patients were treated with GH and all showed an improvement in growth velocity (P < .0001). We conclude that (1) children with acute leukemia who have received cranial RT and subsequently undergo BMT, primarily those with ALL, are at high risk for growth failure and GH deficiency, and (2) that fractionation of TBI may have a relative sparing effect on growth.

Effects of therapy on anterior pituitary functions in patients with primary intracranial germ cell tumor.

Intracranial germ cell tumors are known to be frequently associated with anterior pituitary hypofunction and diabetes insipidus. In general, these manifestations are not ameliorated even after successful radiotherapy. Since platinum based chemotherapy is introduced as a therapeutic approach to these tumors, its effectiveness is compared with the outcome obtained by radiotherapy in terms of tumor regression and endocrine functions. In this study, six patients received conventional radiotherapy and one received chemotherapy as an initial treatment. In all patients, complete remission was achieved irrespective of the therapeutic method. Their diabetes insipidus was not improved. Many patients treated with radiotherapy did not show the complete improvement of pre-existing hypofunction of the anterior pituitaries. In contrast, chemotherapy achieved almost complete hormonal remission. These clinical observations suggest that chemotherapy is quite effective in oncological as well as endocrinological aspects in treating intracranial germ cell tumors.