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PubMed1989

Effect of cranial irradiation on hypothalamus and pituitary functions.

Hypopituitarism can occur after cranial irradiation for tumors distant from the pituitary gland. Recent studies have suggested that this is hypothalamic in origin. Hypothalamic and pituitary functions were studied in 11 patients, 4 men and 7 women, 4.5 years or more after radiotherapy for nasopharyngeal carcinomas. The estimated average total dose was 5000 cGys for the hypothalamus and pituitary gland. Except for 2 women with amenorrhea and 4 men with impotency, the patients did not have evident endocrine deficiency. Baseline hormone profiles revealed normal T4, T3 and cortisol levels, 6 with elevated prolactin, 3 with reduced testosterone and 3 with slightly elevated basal TSH. The four menopausal women had impaired gonadotropin response to LHRH (100 micrograms, i.v.). Four (1 menstruating, 1 amenorrheic, 2 menopausal) women did not reach peak FSH response 4 hours after LHRH injection. The other amenorrheic woman had minimal FSH and LH response to LHRH which persisted even after 8 days of pulsatile infusion of LHRH (1 microgram/90min). TSH response to TRH (400 micrograms, i.v.) was delayed in 7 patients. GH response to human GRH (1 microgram/kg, i.v.) was impaired in 6 patients (maximal GH less than 5 mU/l). ACTH response to ovine CRH (1 microgram/kg, i.v.) was impaired in 3 patients (less than 50% elevation from baseline). Three patients who had normal GRH tests had impaired GH response to insulin hypoglycemia. Six patients had an empty sella on CT scan. From this study the following conclusions are drawn: (1) Among the four axes, GH is the most vulnerable. (2) The insulin tolerance test is still the best single test for evaluation of hypothalamic function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2003

Immunohistochemical proliferation markers may overestimate the growth potential after ionizing radiation: in vivo study in the rat anterior pituitary gland.

The effect of ionizing radiation on the expression of immunohistochemical proliferation markers was examined in the rat pituitary gland. Rats were irradiated in the pituitary region with a dose of 40 Gy, or were sham-irradiated as controls. Bromodeoxyuridine (BrdU) was given to the rats after one week, either one hour (Br-1 group) or 17 hours (Br-17 group) before perfusion fixation. Immunohistochemical staining for BrdU, topoisomerase II-alpha (TopoII), Ki-67 (MIB-5), p21WAF1/Cip1 (p21), and p27Kip1 (p27) was performed. Apoptotic cells were detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling method. The mean BrdU labeling index (LI) and MIB-5 LI were significantly higher in the irradiated rats than in the sham rats in the Br-1 group. TopoII LI was higher in the irradiated rats than in the sham rats, although not significantly. p27-positive cells decreased in irradiated rats, but p21-positive cells increased more than in the sham rats. The number of apoptotic cells increased significantly after radiation. BrdU LIs were lower in the irradiated rats than in the sham rats in the Br-17 group. A few small BrdU-positive fragments with apoptotic features were phagocytosed in the anterior lobe cells. These results indicate that some "immunohistochemically proliferating cells" subsequently undergo apoptosis in the irradiated pituitary gland. The values of proliferative indices should be cautiously interpreted after irradiation of tissue.

Animals↗
PubMed1987

Early effects of cranial irradiation on hypothalamic-pituitary function.

Hypothalamic-pituitary function was studied in 31 patients before and after cranial irradiation for nasopharyngeal carcinoma. The estimated radiotherapy (RT) doses to the hypothalamus and pituitary were 3979 +/- 78 (+/- SD) and 6167 +/- 122 centiGrays, respectively. All patients had normal pituitary function before RT. One year after RT, there was a significant decrease in the integrated serum GH response to insulin-induced hypoglycemia. In the male patients, basal serum FSH significantly increased, while basal serum LH and testosterone did not change. Moreover, in response to LHRH, the integrated FSH response was increased while that of LH was decreased. Such discordant changes in FSH and LH may be explained by a defect in LHRH pulsatile release involving predominantly a decrease in pulse frequency. The peak serum TSH response to TRH became delayed in 28 patients, suggesting a defect in TRH release. Twenty-one patients were reassessed 2 yr after RT. Their mean basal serum T4 and plasma cortisol levels had significantly decreased. Hyperprolactinemia associated with oligomenorrhoea was found in 3 women. Further impairment in the secretion of GH, FSH, LH, TSH, and ACTH had occurred, and 4 patients had hypopituitarism. Thus, progressive impairment in hypothalamic-pituitary function occurs after cranial irradiation and can be demonstrated as early as 1 yr after RT.

Adult↗
PubMed1988

Results of surgery and irradiation or irradiation alone for pituitary adenomas.

A retrospective analysis was performed on the clinical course of all patients with pituitary adenomas treated at the Radiation Oncology Center, Mallinckrodt Institute of Radiology, Washington University Medical Center, St. Louis, Missouri. Of 212 patients treated from April 1954 through December 1982, 70 were treated with radiotherapy alone (XRT), 121 began immediate post-operative XRT (2-6 weeks) and 20 received XRT following surgical failure. Several sub-groups of adenomas were identified and analyzed, including secreting versus non-secreting adenomas (33.0% secreting) and by clinical syndrome; 27% with amenorrhea/galactorrhea, 18.4% acromegalic, Cushing's disease in 6.1% and 3.3% with Nelson's syndrome. The median follow-up time from the data of diagnosis for those patients alive at the time of last follow-up was 11.9 years (range 3.0 to 30.0 years). Actuarial overall and disease-free survival was analyzed up to 25 years. The 10-year overall and disease-free survival was 77.8 and 75.3% for those patients treated with XRT alone, 86.4 and 87.2% for those treated with immediate post-operative XRT and 100.0 and 87.5% for those who were irradiated after surgical failure. Complications related directly to XRT occurred in only five patients. One patient had documented central nervous system radionecrosis, two had visual complications, and tumor necrosis with hemorrhage occurred in the other two patients. In conclusion, overall survival for all patients did not significantly differ from an age, sex and race matched population. Control of local disease was greater for those patients receiving surgery and post-operative XRT than for those receiving XRT only. XRT salvage of surgical failures was possible. Treatment with XRT results in a low complication rate.

Adenoma↗
PubMed1996

Ocular neuromyotonia.

AIMS/BACKGROUND: Ocular neuromyotonia is characterised by spontaneous spasm of extraocular muscles and has been described in only 14 patients. Three further cases, two with unique features, are described, and the underlying mechanism reviewed in the light of recent experimental evidence implicating extracellular potassium concentration in causing spontaneous firing in normal and demyelinated axons. METHODS: Two patients had third nerve neuromyotonia, one due to compression by an internal carotid artery aneurysm, which has not been reported previously, while the other followed irradiation of a pituitary tumour, a common association in the published reports. Selective activation occurred in both, where neuromyotonic activity was triggered by prolonged voluntary activation of specific extraocular muscles with or without spread of activity to other third nerve muscles. The other patient had fourth nerve involvement, where spasms of the superior oblique muscle were induced only by alcohol, a phenomenon which has not been described. RESULTS: The two patients with third nerve involvement responded to carbamazepine and in one, an improvement in a chronic partial third nerve paresis occurred. The other has not required treatment and remains asymptomatic by refraining from alcohol. CONCLUSIONS: A careful examination, including the effects of prolonged voluntary muscle action is required to initiate episodes and to demonstrate selective activation. Imaging is mandatory to exclude compressive intracranial lesions, particularly where there is no history of pituitary fossa irradiation. A trial of anticonvulsants should be considered in all patients. Extracellular potassium may play a role in spontaneous firing and ephatic transmission in ocular neuromyotonia.

Adult↗
PubMedDate not supplied

Hormone production in pituitary adenomas following external irradiation: an experimental study in rats.

INTRODUCTION: The aim of this study was to investigate the hormone production in pituitary gland tumors following fractionated external irradiation in rats. MATERIALS AND METHODS: Sixty female Wistar rats 3 to 4 month of age at the beginning of the experiments, were subjected to fractionated roentgen-rays exposure, 2 Grays (Gy) daily, either up to 20, 40 or 60 Gy. The animals were sacrificed either 6 month or 1 year after completion of the randomly assigned irradiation protocol. RESULTS: We found 9 pituitary tumors in 60 irradiated rats (15%). All tumors proved to be adenomas. Immunohistochemical analysis of hormone production in remnants of the normal adenohypophysis revealed immunoreactivity for growth hormone (GH), adrenocorticotropic hormone (ACTH), prolactin (PRL), thyroid-stimulating hormone (TSH), and follicle-stimulating hormone (FSH). In adenomas, 4 cases were immunoreactive for TSH, 4 for GH, 2 for PRL, and 2 for FSH. The tumors were not reactive with anti-ACTH and anti-LH (luteinizing hormone). DISCUSSION: We concluded that irradiation accelerates the development of pituitary gland adenomas. In our series these tumors were predominantly incidental findings at necropsies after pre-termed follow-up, with a variety of hormone producing tumor cells. However, 4 of 9 tumors in our study were not producing hormones.

Animals↗
PubMed1984

Changes in intracranial pressure associated with delayed cerebral radionecrosis.

Continuous recording of intracranial pressure (ICP) from one lateral ventricle in a case of histologically proven delayed temporal radionecrosis due to previous irradiation of the pituitary gland for the treatment of an adiposity of the Cushing type has revealed the occurrence of B-waves and ramplike waves despite the absence of raised intracranial pressure. Ventriculo-atrial shunting failed to relieve the severe psychic symptomatology, which was due to direct tissue damage. These observations indicate that B-waves may have a neurogenic origin.

Brain↗
PubMed1979

Treatment of Cushing's disease by O,p'DDD. Survey of 62 cases.

In a study of nonsurgical therapy of Cushing's disease, 62 patients received O,p'-dichlorodiphenyldichloroethane (O,p'DDD), 16 of whom also received cobalt irradiation of the pituitary. After an initial treatment period averaging eight months, a remission of the disease was obtained in 38 of the 46 patients given O,p'DDD alone and in all patients who received drug combined with radiation. Although 60 per cent of these patients subsequently relapsed, additional courses of drug or radiation therapy were usually effective, and 63 per cent of the entire group of patients have so far been kept under control without adrenalectomy. (Forty patients have been followed for at least two years after the initial course of treatment.). O,p'DDD produced little gastrointestinal discomfort; an increased serum cholesterol was the main side effect. This drug allows long-term medical management of Cushings disease in most cases. Whether the combination of O'p'DDD with pituitary radiation is the best therapy has not been established.

17-Hydroxycorticosteroids↗