[Irradiation of intracranial structures in small animals by a narrow beam of high-energy protons].
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Animals↗
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Results for “PITUITARY GLAND IRRADIATION”
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Influence of the age of mice at exposure to radiation on life-shortening and carcinogenesis.
Female B6C3F1 mice were irradiated on day 17 prenatal age, or day 0, 7, 35, 105, 240 or 365 postnatal age with 0.95, 1.9, 2.85, 3.8 or 5.7 Gy of gamma-rays from 137Cs. They were allowed to live out their entire life spans under specific pathogen free conditions. All the mice were given autopsies at death and were examined histologically for neoplastic and non-neoplastic diseases. The mice in the early postnatal period were most sensitive to the life-shortening effect of radiation. The shortening effect of irradiation given during the late fetal period was almost the same as that given during the young adult period. Incidences of lung, liver, pituitary, ovarian and bone tumors and malignant lymphoma of the lymphocytic type increased after irradiation of mice in the late fetal period. Mice in the early postnatal period are more susceptible to the induction of liver and ovarian tumors and malignant lymphoma of the lymphocytic type than are fetal mice. Myeloid leukemia and Harderian gland tumor did not develop in excess when mice were irradiated in fetal or in neonatal period; whereas, these neoplasms were induced by irradiation during the adult period.
Aging↗
Photic threshold for stimulation of testicular growth and pituitary FSH release in male Djungarian hamsters.
While the effects of photoperiod on neuroendocrine-gonadal activity have been extensively studied in a number of species, surprisingly little information concerning the quantitative aspects of light regulating reproductive activity is available. In the present experiment, Djungarian hamsters were exposed to two 10 min pulses of light per day and the light irradiance was systematically varied to determine the threshold for photostimulation by white light. After 10 days testes weight and serum follicle-stimulating hormone (FSH) levels were determined. The data indicate that the irradiance threshold necessary for induction of significant increases of both serum FSH levels and testes weight lies between 0.1 and 0.34 microW/cm2 for 10 min pulses of light. These results demonstrate a strong correlation between the effects of light on serum FSH levels and testes weight and provide the first quantitative assessment of the irradiance threshold for light involved in photoperiodic stimulation of the hypothalamic-pituitary gonadal axis of a mammalian species.
Animals↗
5-Bromodeoxyuridine-induced carcinogenesis and its modification by persistent estrus syndrome, unilateral nephrectomy, and X-irradiation in rats.
We showed earlier that 5-bromodeoxyuridine (BrdUrd), which can substitute for thymidine during DNA synthesis, inducing transition mutations, is incorporated into DNA of various tissues when administered to newborn rats and is not subjected to repair processes. The main purpose of the present experiment is to verify if a direct perturbation of DNA would be sufficient to initiate carcinogenesis. Rats aged 1, 3, 7, and 21 days were given BrdUrd s.c. at a dose of 3.2 mg/animal. At 2 months some of the females were subjected to treatment known to induce persistent estrus; at 1 month a group of males underwent removal of one kidney, and groups of males and females were exposed to a single total-body X-irradiation at a dose of 1.5 Gy (150 rads) per rat. In females, treatment with BrdUrd induced tumors of the ovaries, polyps in the uterus, and tumors of the soft tissues, nervous system, forestomach, glandular stomach, and salivary gland; no such tumor occurred in control females. Induction of persistent estrus increased the incidences of ovarian tumors and of malignant tumors of the uterus. Treatment with BrdUrd also increased the carcinogenic effect of X-rays on the mammary gland. In males, BrdUrd induced tumors of the testis (seminomas) and adenomas of the thyroid gland; solitary tumors of the kidney, nervous system, soft tissues, and bladder were also found. Unilateral nephrectomy reduced the incidences of tumors in the testis and pituitary gland, whereas subsequent treatment with X-rays did not alter the incidences of tumors induced by BrdUrd. These studies demonstrated for the first time that a nucleoside analogue, BrdUrd, has carcinogenic potential. Possible molecular mechanisms for its carcinogenicity and for the effects of the promoting factors are discussed.
Animals↗
Cushing's disease: megadose dexamethasone suppression in a case refractory to medical therapy.
A patient with Cushing's disease failed to show complete suppressibility of adrenal function with conventional "high" doses of dexamethasone (8 mg per day). Higher doses were required to achieve suppression. Pituitary irradiation and medical therapy (cyproheptadine, metyrapone, and aminoglutethimide) failed to control the disease, necessitating bilateral adrenalectomy. The diagnostic and therapeutic implications of megadose dexamethasone suppression have not been clearly addressed in the medical literature. It is possible that adrenal suppression achieved only with unconventionally high doses of steroids may be predictive of refractoriness to nonsurgical therapy.
17-Hydroxycorticosteroids↗
Acceleration of pubertal development following pituitary radiotherapy for Cushing's disease.
A 7-year-old boy with pituitary dependent Cushing's disease was treated with pituitary irradiation following unsuccessful microadenomectomy. This led to normalization of the hypercortisolaemia, but was followed by GH deficiency. Two years after radiotherapy he had the onset of pubertal development with testicular enlargement to 8 ml bilaterally. Pubertal regression was induced using the long-acting GnRH analogue goserelin. Acceleration of skeletal maturation was also arrested, resulting in improvement of final height prediction. Irradiation directly to the hypothalamo-pituitary region, as well as whole brain irradiation, may thus be associated with accelerated pubertal development.
Child↗
Radiation-induced hyperprolactinaemia in a treated acromegalic.
A 31-year-old acromegalic was normoprolactinaemic after partial removal of her pituitary tumour. The post-operative external pituitary irradiation lowered the mean growth hormone (GH) level from 75 mU/1 to less than 1 mU/1 within 2 years. However, at the same time hyperprolactinaemia developed. These changes in the GH and prolactin levels were confirmed 3 and 4 years after irradiation. The cause of the hyperprolactinaemia was radiation-induced hypothalamic damage. Therefore it is suggested that similar damage may occur in patients receiving external pituitary irradiation for 'prolactinomas' and that this mechanism may contribute to the persistent hyperprolactinaemia observed in such patients.
Acromegaly↗
Conventional pituitary irradiation is effective in normalising plasma IGF-I in patients with acromegaly.
OBJECTIVE: For patients in whom acromegaly persists despite pituitary surgery, conventional pituitary irradiation represents an additional treatment option. A 30-60% cure rate is described in the literature, but these studies did not utilise strict rules of remission, such as "safe" GH levels <2.5 microg/l, and age-adjusted normal IGF-I levels. DESIGN AND METHODS: We report the outcome of 41 patients with acromegaly who received pituitary conventional external irradiation. The median follow-up time was 12.8 years (3.7-43.4 years) post-radiotherapy. RESULTS: The median pre-irradiation GH level was 31.0 microg/l (7.0-210 microg/l). Information on IGF-I levels was only available for 6 patients prior to therapy. Utilising strict rules of remission, one-third (14/41) of our patients had normal biochemical parameters, i.e. "safe" GH (0.5 microg/l (range 0.2-1.6 microg/l)) and normal age-adjusted IGF-I levels (multiple of upper limit of normal range (xULN); 0.45 (0.2-1.0)) at the end of the follow-up period. An additional 9 patients achieved normal levels with adjunctive drug therapy. Furthermore, disease activity was reduced in a considerable proportion of the 18 patients who did not achieve normal biochemical levels (GH: 3.6 microg/l (1.9-15.7 microg/l); xULN of IGF-I: 1.6 (0.9-2.6)). In retrospect, remission is unlikely in patients who had a GH level greater than 52 microg/l (mean+2 s.d. of cured patients) prior to radiotherapy. In addition to the 12 patients with pre-irradiation pituitary functional deficiency, another 11 patients developed symptoms of panhypopituitarism during the 3-year period following irradiation. Within a 6-year period, partial pituitary insufficiency was observed in a further 7 patients, thus necessitating hormone substitution treatment. CONCLUSION: Using strict rules of remission, in our cohort we found both a normalisation of IGF-I and safe GH levels in 34% of patients treated for acromegaly with conventional irradiation therapy.
Acromegaly↗
Further studies of adrenal weight-maintaining activity in the plasma of patients with Cushing's disease.
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Adolescent↗
Isolated histiocytosis X of the pituitary stalk.
A case of histiocytosis X granuloma localized in the pituitary stalk is reported. Coronal and sagittal magnetic resonance imaging views were useful to determine the precise size and location of the mass lesion. The diagnosis was established immunohistochemically and the patient was treated with low-dose irradiation therapy. After irradiation, the patient improved well without endocrine replacement treatment. The pituitary stalk recovered its normal size with no evidence of recurrence on MRI at 7-year follow-up. We emphasize the importance of MRI before initiating therapy to evaluate the pituitary mass lesion and the effectiveness of low-dose irradiation for isolated histiocytosis X.
Adult↗
Effect of dexamethasone on pituitary-adrenocortical response to acute irradiation stress in rats.
After the irradiation with a lethal dose of 387 mC kg-1 (1500 R) an increase of plasma and adrenal corticosterone concentration was found in male rats (about 250 g body weight) during first 24 h as compared to sham-irradiated animals, the maximum increase being observed at 60 min after irradiation. A second period of corticosterone increase was found at 48 and 72 h. At the same time the adrenal weight increased and severe lesions of gastrointestinal tract were found. In a second experiment dexamethasone (50 mg kg-1) was injected 3 h before irradiation and this prevented the increase of plasma and adrenal corticosterone level at 60 min after irradiation. It was suggested that the degradation of corticosterone might be slowed down during the first period after irradiation, while at the same time the feed-back regulatory mechanism of ACTH release from the pituitary apparently remained intact. The second period of corticosterone increase was apparently due to severe gastrointestinal lesions.
Adrenal Cortex↗
Evidence of oncogenic cofactors in radiation-induced tumors in mice.
Five groups of 587 inbred female mice (WHC) were studied to determine the incidence of tumors as affected by irradiation of different areas. A dose of 400 rad of 60Co was given to all the groups. One group of 166 mice was total body irradiated, another group of 90 mice was irradiated in the upper-third portion of the body, another group of 93 mice was irradiated in the lower two-thirds of the body, and another group of 90 mice was half body irradiated on the right side. As control, a group of 148 nonirradiated mice was followed. The results showed a different incidence of cancer in mice, depending not only on the irradiated areas but also on the shielded ones. This suggested that other factors besides irradiation affect carcinogenesis.
Animals↗
Hypothalamic-pituitary function following successful treatment of intracranial tumours.
Hypothalamic-pituitary function was examined in seventeen patients treated in the past for extrasellar intracranial tumours. All patients had received a course of external cranial irradiation. Biochemical abnormalities of endocrine function were present in almost all of the patients. In particular, the growth hormone response to insulin induced hypoglycaemic stress was impaired in eleven out of fifteen patients. Preliminary data from a group of seven patients with intracranial tumours prior to radiotherapy are also presented. The possibility that cranial irradiation causes hypothalamic-pituitary dysfunction is discussed. The results suggest that endocrine assessment should be considered in patients who have been treated for intracranial tumours, even in the absence of direct pituitary involvement.
17-Hydroxycorticosteroids↗
Phase II evaluation of interferon-alpha-2a for progressive or recurrent craniopharyngiomas.
OBJECT: Craniopharyngiomas originate from the same cells as squamous cell skin carcinoma, which can be treated successfully with interferon-alpha (IFNalpha)-2a. The authors evaluated the activity and toxicity of systemic IFN in young patients with craniopharyngiomas. METHODS: Fifteen patients between the ages of 4.2 and 19.8 years who had progressive or recurrent craniopharyngiomas were enrolled in this study. Nine of these patients had never received external-beam radiation therapy. Therapy consisted of 8,000,000 U/m2 IFNalpha-2a administered daily for 16 weeks (induction phase) followed by the same dose three times per week for an additional 32 weeks (maintenance phase). Of the 12 patients who could be evaluated, radiological studies demonstrated a response to treatment in three with predominantly cystic tumors (one minor response, one partial response, and one complete response); one of these patients also showed improvement in visual fields. The size of the cystic component of the tumors often increased temporarily during the first several months of therapy. Three patients met the criteria for progressive disease during therapy. The median time to progression was 25 months. The need for radiation therapy in patients treated with IFN was delayed for 18 to 35 months (median 25 months) in six patients. All patients developed transient flulike symptoms shortly after receiving the first dose of IFN. Other toxicities (predominantly hepatic, neurological, and cutaneous) were seen in nine (60%) of the 15 patients during the first 8 weeks of treatment but resolved after temporary discontinuation and/or dose reduction. CONCLUSIONS: Interferon-alpha-2a is active against some childhood craniopharyngiomas; its toxicity precludes administration of high daily doses, and the optimum dose level and schedule remain to be defined.
Adolescent↗
Effect of light irradiance and wavelength on the Syrian hamster reproductive system.
The purpose of this study was to examine how the physical characteristics of light influence the short photoperiod-induced atrophy of the reproductive system. In the first experiment, groups of Syrian hamsters were exposed to a 14-h light, 10-h dark (14:10) photoperiod, a 11:13 photoperiod or a 11:13 photoperiod extended by 3 h of light at an irradiance of 20, 2, 0.2, or 0.002 microW/cm2. Animals in the 11:13 photoperiod and the 11:13 photoperiod extended by 0.02 and 0.002 microW/cm2 underwent reproductive regression, as evidenced by decreased testicular and accessory sex organ weight and pituitary PRL levels. In the second study, groups of hamsters were exposed to a 14:10, 11:13, or 11:13 photoperiod extended by 3 h of red, yellow, green, blue, or near-UV light at 0.2 microW/cm2. Animals in the 11:13 and the 11:13 photoperiod extended by red or yellow light underwent reproductive atrophy. These results demonstrate that light irradiance and wavelength are important determinants of the photoperiodic regulation of the Syrian hamster reproductive system.
Animals↗
The effect of neonatal head-irradiation and subsequent fasting on the mechanisms of catch-up growth.
The heads of 2 day old male and female rats were X-irradiated with 600 rad. Non-irradiated littermates served as controls. At 40 days of age groups of irradiated and non-irradiated rats were subjected to a 48 hour fast. Non-fasted groups of irradiated and non-irradiated rats were fed ad lib. and were used for comparative studies. Growth of body weight and tail length was recorded at intervals through 70 days of age. At sacrifice, pituitary weight, tibial length, and tibial epiphyseal width were also determined. The results confirm earlier findings that whole head irradiation produces reduced growth of body weight and of tail length which remains uncompensated by catch-up growth. After fasting and then refeeding normal catch-up growth acceleration occurred in both male and female irradiated and nonirradiated animals. The fasted non-irradiated animals caught up to the non-irradiated control rat size for both body weight and tail length. Similarly, the fasted irradiated rats caught up to the irradiated, non-fasted rat size, but did not catch up to the size of the non-irradiated controls. Pituitary weight and tibial length were significantly reduced in irradiated males and females. At sacrifice, no significant difference existed between the fasted and non-fasted subgroups. The tibial epiphyseal growth plate was not narrowed in irradiated rats; fasted rats had increased epiphyseal width during recovery in only one group. We conclude that the catch-up growth control is intact in the head-irradiated stunted rat. The findings suggest that the mechanism which recognizes normal body size (set-point for body size) and which determines the limit of catch-up growth acceleration is reset for a smaller body size by the head-irradiation.
Animals↗
Serologic estimation of thymine dimers in the deoxyribonucleic acid of bacterial and mammalian cells following irradiation with ultraviolet light and postirradiation repair.
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Animals↗
Clonogenic cells and rat mammary cancer: effects of hormones, X rays, and fission neutrons.
On Day 0, young adult female F344 rats were adrenalectomized and intrasplenically implanted with a pituitary gland and capsule containing estrone. All were thereafter given 2.5 mg deoxycorticosterone per week and the choice of saline or tap water. This treatment yields high prolactin levels and glucocorticoid deficiency (Prl+/Glc-). On Day +48, total recoverable mammary DNA was increased by more than sevenfold, tritiated thymidine uptake by nearly fourfold, and total mammary clonogens by about fivefold. Irradiation with 4, 40, and 80 cGy X rays on Day +48 increased total mammary carcinomas per rat day at risk linearly with dose, and 40 and 80 cGy significantly decreased first carcinoma latency. A dose of 40 cGy X rays on Day -1 yielded tumor latencies and frequencies insignificantly different from unirradiated controls and significantly different from the dose on Day +48. Total carcinomas per rat day at risk were better fit by a function of dose to the power 0.4 than by a linear function after exposure to 1, 10, and 20 cGy fission neutrons, and 10 and 20 cGy significantly shortened the time to appearance of the first cancer. In contrast to results with X rays, 10 cGy neutrons on Day -1 yielded tumor frequencies and latencies insignificantly different from 10 cGy neutrons on Day +48. The carcinogenic action of X rays was thus influenced by total clonogen numbers and/or proliferation rates; that of neutrons was not.
Animals↗