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PubMed1983

Ionizing radiation alters beta-endorphin-like immunoreactivity in brain but not blood.

Previous behavioral and pharmacological studies have implicated endorphins in radiation-induced locomotor hyperactivity of the C57BL/6J mouse. However, the endogenous opiate(s) responsible for this behavioral change have not been identified. The present study measured beta-endorphin-like immunoreactivity (beta-END-LI) in brain, blood, and combined brain and pituitary samples from irradiated and sham-irradiated C57BL/6J mice. After radiation exposure, levels of beta-END-LI decreased significantly in the brain. A similar, but not statistically significant, decline was measured in combined brain and pituitary samples. Concentrations of blood beta-END-LI were not changed by irradiation. These radiogenic changes in beta-END-LI are in some ways similar to those observed after other stresses. However, radiation-induced locomotor hyperactivity may be mediated more by alterations of beta-END-LI in the brain than in the periphery. Other endogenous opiate systems may also contribute to this behavioral change in the C57BL/6J mouse.

Animals↗

PubMed1990

[Chiasmal radionecrosis after irradiation of the sella turcica using a conventional dosage. Contribution of magnetic resonance imaging].

A 47 year-old man developed rapid visual loss, visual field defects and memory disturbances after radiotherapy with conventional doses for a pituitary metastasis from a renal carcinoma. CT and MRI did not show recurrent tumour, pituitary apoplexy or empty sella. Eventually, T2-weighted MRI images showed abnormal high signals in the optic chiasm, the left mesial temporal lobe and the right inferior frontal lobe, supporting the diagnosis of delayed radionecrosis. The role of chemotherapy associated with radiotherapy is discussed.

Female↗

PubMed1995

Pituitary function after selective adenomectomy for Cushing's disease.

This retrospective analysis was undertaken to determine whether selective adenomectomy for Cushing's disease can achieve acceptable cure rates while causing minimal pituitary dysfunction. Tumour size, histology and pituitary function were evaluated in 34 consecutive patients (26 F: 8 M, mean age 33.6 years) undergoing transphenoidal adenomectomy for Cushing's disease from 1975 to 1992. Follow-up averaged 5.8 years. Cure was defined as resolution of symptoms and signs and normalization of urinary cortisol excretion. Sixty-three per cent of patients achieved cure after selective adenomectomy, repeat adenomectomy cured an additional four patients. Twenty-eight per cent required bilateral adrenalectomy and/or pituitary irradiation. Postoperative pituitary function remained completely intact in 81%. Secondary hypogonadism occurred in 8%, hypothyroidism in 155 and permanent diabetes insipidus in 4%. There was recurrence in 26% after a mean of 4.6 years (range 1-7). It is concluded that selective adenomectomy can achieve acceptable cure rates with a low prevalence of postoperative hypopituitarism, although an increase of recurrence may be the result of conservative surgery.

Adenoma↗

PubMed1992

Magnetic resonance imaging of the pituitary area in children treated for acute lymphoblastic leukemia with low-dose (18-Gy) cranial irradiation. Relationships to growth and growth hormone secretion.

OBJECTIVE: To determine the effects of 18-Gy cranial irradiation on growth, growth hormone (GH) secretion, and pituitary magnetic resonance imaging in children who underwent previous irradiation for treatment of acute lymphoblastic leukemia. DESIGN: Clinical survey. SETTING: Department of Pediatrics of the University of Bologna (Italy). PATIENTS: Ten boys and 18 girls who were treated for acute lymphoblastic leukemia; median age at diagnosis was 3.1 years and at the end of follow-up was 11.5 years. MEASUREMENTS AND RESULTS: Height was periodically measured from diagnosis until the end of follow-up, when GH secretion study and magnetic resonance imaging were performed. The mean height SD score was significantly lower than at diagnosis only at the end of treatment. Nocturnal mean GH concentration and GH response to pharmacological tests (arginine and levodopa [L-dopa]) were pathological in 22 cases (81.5%) and 18 cases (64.3%), respectively. Sixteen cases (59.2%) had a blunted GH release to the three tests. Mean pituitary anterior lobe height was reduced and seven subjects (25%) showed an empty sella. CONCLUSIONS: Cranial irradiation with 18 Gy does not seem to influence the growth pattern of most children who are treated for acute lymphoblastic leukemia, despite severe impairment of GH secretion and morphological abnormalities of the sellar area. However, a follow-up until final height is necessary.

Adolescent↗

PubMed1998

A preliminary experimental in vivo study of the effect of photodynamic therapy on human pituitary adenoma implanted in mice.

As surgery alone may prove inadequate to effect a cure for invasive pituitary adenomas, photodynamic therapy (PDT) was investigated as a possible adjuvant treatment for this group of tumours. Different subtypes of human pituitary adenoma cells were implanted subcutaneously into nude mice to study the in vivo effect of PDT on such lesions. The photosensitizer used in this study was polyhaematoporphyrin at a dose of 10 mg/kg b.w., followed by light irradiation at a wavelength of 630 nm with varying light doses between 10 and 75 J/cm2. Histopathological examination of the treated implants consistently showed tumour vascular changes with acute inflammatory reaction, interstitial haemorrhage, and evidence of cell death at higher doses of light. These changes were absent in the control groups. These findings indicate that the cytotoxic effect of PDT demonstrated in vitro in previous studies, is also present in vivo.

Adenoma↗

PubMed1978

Unilateral adrenalectomy and pituitary irradiation in the treatment of ACTH-dependent Cushing's disease in children and adolescents.

In four juvenile patients with Cushing's disease, the therapeutic approach used was unilateral adrenalectomy followed by irradiation of the pituitary. The follow-up time of these patients has ranged from 1.5 to 10 years. All four are clinically well. Concentrations of adrenal steroids are within normal limits and they require no additional medication. It is felt that this method gives young patients the chance for normal growth and pubertal development as well as a normal social life, so important in the stressful adolescent years, thus avoiding the handicap incurred by bilateral adrenalectomy and the consequent requirement for continuous substitution therapy.

Adolescent↗

PubMed2004

Growth and puberty after treatment for acute lymphoblastic leukemia.

UNLABELLED: Over the last 20 years, after combining treatment of chemotherapy and radiotherapy, there has been an improvement in the survival rate of acute lymphoblastic leukemia patients, with a current cure rate of around 70%. Children with the disease have been enrolled into international treatment protocols designed to improve survival and minimize the serious irreversible late effects. Our oncology unit uses the international protocol: GBTLI LLA-85 and 90, with the drugs methotrexate, cytosine, arabinoside, dexamethasone, and radiotherapy. However, these treatments can cause gonadal damage and growth impairment. PATIENTS AND METHOD: The authors analyzed 20 children off therapy in order to determine the role of the various doses of radiotherapy regarding endocrinological alterations. They were divided into 3 groups according to central nervous system prophylaxis: Group A underwent chemotherapy, group B underwent chemotherapy plus radiotherapy (18 Gy), and group C underwent chemotherapy plus radiotherapy (24 Gy). Serum concentrations of LH, FSH, GH, and testosterone were determined. Imaging studies included bone age, pelvic ultrasound and scrotum, and skull magnetic resonance imaging. RESULTS: Nine of the patients who received radiotherapy had decreased pituitary volume. There was a significant difference in the response to GH and loss of predicted final stature (Bayley-Pinneau) between the 2 irradiated groups and the group that was not irradiated, but there was no difference regarding the radiation doses used (18 or 24 Gy). The final predicted height (Bayley-Pinneau) was significantly less (P = 0.0071) in both groups treated with radiotherapy. Two girls had precocious puberty, and 1 boy with delayed puberty presented calcification of the epididymis. CONCLUSION: Radiotherapy was been responsible for late side effects, especially related to growth and puberty.

Adolescent↗

PubMed1989

The frequency and natural history of diabetes insipidus in children with Langerhans-cell histiocytosis.

Diabetes insipidus is a well-recognized complication of Langerhans-cell histiocytosis (histiocytosis X), but its frequency and natural history are not well defined. Of 52 children with histiocytosis whom we studied, 12 (23 percent) had diabetes insipidus. Only two children had diabetes insipidus at presentation with histiocytosis, but the cumulative risk that it would develop during the first four years after the presentation and diagnosis of histiocytosis was found to be 42 percent. Diabetes insipidus occurred most often among children with multisystem disease and those with proptosis. To determine the natural history of diabetes insipidus in children with histiocytosis, we measured the response of urinary arginine vasopressin to water deprivation every six months in 21 children who did not have diabetes insipidus and who had had histiocytosis for less than four years. Five of the 21 children (24 percent) had subnormal responses during the initial test. One subsequently had spontaneous improvement in the functioning of the posterior pituitary, and diabetes insipidus subsequently developed in two, as it did in one of the children who initially had normal function of the posterior pituitary. Two of the children received irradiation to the pituitary within two to four weeks after diabetes insipidus developed, but they had no improvement in pituitary function. However, diabetes insipidus improved transiently during prednisolone therapy in one of these children and improved permanently after etoposide therapy in another child. We conclude that prospective study with the use of a simple water-deprivation test will allow partial defects of posterior-pituitary function to be detected in patients with histiocytosis and will permit a more appropriate evaluation of the effects of therapeutic intervention.

Adolescent↗

PubMed2000

Usefulness of gallium-67 scintigraphy in neurohypophyseal germinoma.

The application of gallium-67 (67Ga) citrate has not been reported for the detection of an intracranial germinoma. The purpose of this report is to further evaluate the effectiveness of 67Ga scintigraphy in neurohypophyseal germinomas. 67Ga studies in five male patients with histologically verified intracranial pure germinomas were evaluated. Two germinomas were located in the neurohypophysis, two in the pineal region, and one in both the neurohypophysis and pineal region. The control group included 36 patients with histologically verified pituitary macro-adenomas. 67Ga study at the time of original diagnosis showed an abnormal accumulation in two neurohypophyseal germinomas, and negative accumulation in the other germinomas. In the two patients with neurohypophyseal germinomas, 67Ga study showed an abnormal accumulation in the intracranial tumour region in accordance with magnetic resonance (MR) findings. After postoperative irradiation or chemoradiotherapy, MR imaging and 67Ga studies revealed the complete disappearance of this tumour and no metastatic spread. In one of these two patients, a whole-body 67Ga study demonstrated multiple bone metastases one year later, and the reduction of these metastatic regions after chemotherapy. 67Ga study disclosed negative accumulation in all 36 pituitary macroadenomas. Although 67Ga uptake by neurohypophyseal germinomas may not be specific for this condition, this approach may provide some clues for diagnosing patients with neurohypophyseal germinomas.

Adolescent↗

PubMed2002

Establishment of the reproductive function and transient fertility of female rats lacking primordial follicle stock after fetal gamma-irradiation.

In mammals, the primordial follicle stock is not renewable, and its size, therefore, limits the reproductive life span of the female. In this study we have investigated the morphological and functional differentiation of dysgenesic ovaries in female rats exposed in utero to 1.5 Gy gamma-irradiation. As a consequence of the severe depletion in oocytes, females evidenced premature ovarian failure from 6 months on. Nevertheless, puberty onset and fertility at the beginning of reproductive life were similar to those of controls. The differentiation and evolution of the entire follicular population were followed during the immature period, using follicle counts, in situ hybridization of follicular maturation markers, and analysis of atresia. Primordial follicles were much more affected by irradiation (1.4-1.9% of controls) than growing follicles (30-45% of controls). As the very low number of primordial follicles remained constant throughout this period, it may be considered that the growing follicle pool plays the role of follicular reserve, permitting the transient normal fertility of irradiated females. Within the neonatal period, primary and secondary follicles, as revealed by proliferating cell nuclear antigen immunostaining, remain quiescent longer in irradiated than in control ovaries. Consequently, the majority of the most mature follicles (i.e. the first follicular wave) characterized by a high expression of aromatase transcripts during the infantile period, are missing in irradiated ovaries. Concomitantly, the 17beta-estradiol plasma peak is absent, and plasma FSH levels are higher than those in control females. In conclusion, these observations emphasize that the female reproductive life span depends not merely on the size of the primordial follicle stock, but also on the entire follicle complement as well as follicular dynamics during the immature period.

Animals↗

PubMed1986

Assessment of radiogenic cancer initiation frequency per clonogenic rat mammary cell in vivo.

Radiogenic initiation of mammary cancer is here shown to be a common cellular event. With the aid of a rat mammary clonogen transplant system designed to maximize progression of initiated cells to overt neoplasia, the estimated absolute cancer risk per surviving 7 Gy-irradiated mammary clonogen was [4.1 +/- 1.2 (SE)] X 10(-3), that is (5.8 +/- 1.7) X 10(-4) initiated cells per clonogen-Gy. To maximize neoplastic progression, all clonogen graft recipient rats were glucocorticoid deficient (adrenalectomized with minimal mineralocorticoid replacement) and hyperprolactinemic (implanted intrasplenically with pituitary tissue and an estrone capsule). Each rat was grafted with 4 X 10(6) "morphologically intact" monodispersed mammary cells in the interscapular white fat pad. Group A received cells which had been irradiated 1 day earlier with 7 Gy 137Cs gamma-rays. Groups B and C received unirradiated mammary cells. On day 35 after transplantation, the graft sites of group B were locally exposed to 7 Gy 140 kVp X-rays. Kaplan-Meier estimates (11) of the survivor functions were used to calculate the final tumor incidences corrected for intercurrent animal loss. Estimated mammary carcinoma frequencies so calculated were 65 tumors/131 graft sites in group A, 93/119 in group B, and 13/129 in group C. The relative cancer risks per rat due to the radiation exposure of the grafted cells were 5.0 for group A and 7.8 for group B. These data on neoplasia incidence in grafted mammary clonogens and data on autologous neoplasia in the host rat mammary glands were subjected to statistical analysis. The results indicate that both neoplasm frequency and latency are in large part dependent on initiation target cell number. The high frequency of radiogenic initiation per mammary clonogen observed in this study is in accord with findings with a similar thyroid clonogen transplant system.

Adrenalectomy↗

PubMed1979

Progressive visual failure in acromegaly following external pituitary irradiation.

Four out of twenty-three acromegalic patients selected for treatment with external megavoltage pituitary irradiation between 1961 and 1975 developed progressive visual failure. They had received megavoltage external irradiation through multiple portals from a cobalt-60 unit over a period of 3 weeks. Visual deterioration began 2 months to 6 years after irradiation. In two patients the optic nerves were explored. In both, post-mortem later confirmed radiation damage to the optic nerves and hypothalamus. In one case there was also necrosis of the right frontal lobe with necrosis and inflammation of the bone surrounding the pituitary fossa. In the two other patients, extensive clinical and neuroradiological investigation excluded the presence of a suprasellar mass as a cause for this visual failure and a clinical diagnosis of radiation necrosis was made.

Acromegaly↗

PubMed2006

Cisplatin-based chemotherapy followed by focal, reduced-dose irradiation for pediatric primary central nervous system germinomas.

The objective of this study was to evaluate retrospectively one institution's experience treating pediatric central nervous system (CNS) pure germinomas with platinum-based chemotherapy followed by focal, reduced-dose irradiation. Eight patients were identified with localized, pure CNS germinomas from 1993 to 2004 at the authors' institution. The median age at diagnosis was 13 years (range 7-19). The median follow-up was 40 months (range 8-141). The tumor location was suprasellar in four, the pineal region in three, and the third ventricle in one. Irradiation was started a median of 20 weeks (range 17-22) from diagnosis and consisted of conformal fields to the primary site as determined by the initial diagnostic MR plus a 1.5- to 2-cm margin. Six of the eight patients received a dose of 3,060 cGy; two patients received 3,600 cGy. The 5-year actuarial event free survival was 71% (56-86%, 95% CI). Two patients suffered marginal (at field edge) failures and both were salvaged using reinduction platinum-based chemotherapy followed by cranial spinal irradiation and a boost to the primary tumor. The 5-year actuarial overall survival was 100%. There were no spinal failures. These data suggest that a reduction in both volume and dose (30.6-36 Gy) retains the excellent survival rates for patients with localized, pure germinomas of the CNS. A higher rate of ventricular relapse rate is observed, although salvage of those patients is feasible.

Adolescent↗

PubMed1992

[Changes in hypophyseal-thyroid system function and in the level of atrial natriuretic factor and cyclic nucleotides in the blood of patients with ischemic heart disease exposed to ultrasonic irradiation of the precordial area].

Radiation of the precordial region with ultrasound at 880 kHz, 0.4 W/cm2 for 12 minutes was examined for its impact on blood levels of thyrotropin, tri-iodothyronine, thyroxine, atrial natriuretic factor, cyclic nucleotides (cAMP and cHMP) in 70 patients with Functional Classes II-III exercise-induced angina. The radiation was found to lead to elevated plasma levels of atrial natriuretic factor, cHMP and inhibited plasma cAMP in patients with coronary heart disease as compared to the control group.

Adult↗

PubMed1984

Prolactin and aging: X-irradiated and estrogen-induced rat mammary tumorigenesis.

Both sexes of inbred WF rats at either 8 or 28-60 weeks of age were exposed to 200 rad whole-body radiation, 2.5 or 5.0 mg 17 beta-estradiol (E2), or both agents The female rats treated with E2 alone or with both X-rays and E2 at 8 weeks of age showed a high incidence of mammary carcinomas (MCA), a large increase in pituitary weight, and a rise in serum prolactin (PRL) levels. However, the same treatments to males did not induce MCA despite a moderate increase in both pituitary weight and serum PRL. Ovariectomy prior to E2 treatment failed to modify the occurrence of MCA or pituitary tumors. When X-rays and E2 were given to female rats at 28-60 weeks of age, pituitary weight, serum PRL levels, and the incidence of MCA were unaffected. When the E2 pellet was kept for the first 24 weeks and withdrawn during the last 12 weeks, the incidence of MCA, pituitary weight, and serum PRL was low. It was concluded that: 1) the pituitary glands of young female rats were susceptible to E2 treatment but were insensitive in older females, and 2) the occurrence of MCA in female rats appeared to be promoted by elevated PRL levels secreted by E2-induced pituitary tumors. Mammary tissue of male rats was less sensitive to PRL levels in the development of MCA.

Aging↗

PubMed1990

The role of adrenalectomy in Cushing's syndrome.

Forty-four patients with Cushing's syndrome were treated by adrenalectomy between 1975 and 1989. Twenty patients had adrenal adenomas: 13 with obvious Cushing's syndrome and 7 whose disease was subclinical, detected after evaluation of an incidentally discovered adrenal mass (es). Twelve patients underwent bilateral adrenalectomies for Cushing's disease after failed transsphenoidal explorations and pituitary irradiation. Six patients had primary adrenal hyperplasia, five as manifestations of Carney's complex. Two others underwent bilateral adrenalectomies for ectopic adrenocorticotropic hormone from carcinoid tumors. Four patients had adrenocortical carcinoma treated with transabdominal adrenalectomy. Three are alive from 8 years to 5 months. There was one postoperative death (2.3%) caused by coagulopathy and multiple organ failure and three (7%) minor postoperative complications. Follow-up showed good to excellent results in 95% of patients. It is concluded that adrenalectomy provides prompt relief from the severe morbidity of Cushing's syndrome regardless of the cause. It is the treatment of choice for adrenal adenomas, carcinomas, primary hyperplasia, and selected patients with Cushing's disease.

Adenoma↗

PubMed2006

[Effects of irradiation therapy and inhibiting drugs on the pituitary and its adenomas].

Radiation therapies of pituitary adenomas induce an increase in fibroses and nuclear pleomorphism. Most growth hormone (GH) secreting pituitary adenomas react to somatostatin analogues by a distinct decrease of GH secretion. In two thirds, levels of IGF-1 can be normalized. Some cases show a shrinkage of adenomas that correlates with fibrosis of the tumor. With these drugs, thyroid stimulating hormone secreting adenomas can also be treated. Prolactin secreting adenomas are mostly treated primarily with dopamine agonists. Up to 90% of cases show a strong decrease in hormone secretion and a distinct shrinkage of the adenomas based on strong decrease in adenoma cell volume. Long-term medication with high doses of glucocorticoids induces Crooke's cells in the anterior pituitary. These are suppressed ACTH cells and characterized by increased numbers of large lysosomes and dense bundles of cytofilaments.

Antineoplastic Agents↗

PubMed1983

The effect of single-dose radiation on cell survival and growth hormone secretion by rat anterior pituitary cells.

Cranial irradiation has been shown to impair growth hormone secretion in children. In this study a cell culture of dispersed rat anterior pituitary cells was exposed to single doses of radiation in the range of 100-1500 rad: Survival curves were obtained for the different anterior pituitary cell lines, and growth hormone secretion was measured in the tissue culture medium. Both survival and growth hormone secretion curves showed an initial shoulder in the range of 0-300 rad, followed by a decline between 300-750 rad. It is concluded that growth hormone secreting acidophilic pituicytes are sensitive to radiation at single doses greater than 300 rad.

Animals↗