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PubMed1984

Incidence of anterior pituitary deficiency after radiotherapy at an early age: study in retinoblastoma.

Thirty-one patients treated for retinoblastoma in the first few years (3 months to 3 years and 6 months) of life were studied 2 to 15 years later. Radiotherapy delivered 1 300 to 6 500 rads to the hypothalamo-pituitary area. Growth deficiency was documented in 30% of all cases. Other pituitary deficiencies were the exception. The critical dose for GH insufficiency is between 2 000 and 3 000 rads, as in older children or adults. Our study does not support the hypothesis that the hypothalamo-pituitary area is more sensitive to radiation at an early age. Furthermore, conservative therapy of retinoblastoma leads to double lateral irradiation and will increase the number of GH deficient children after retinoblastoma.

Adolescent↗
PubMed2004

The impact of cancer therapy on the endocrine system in survivors of childhood brain tumours.

Survival rates are improving following cancer therapy for childhood brain tumours. There is therefore a growing cohort of survivors at risk of late effects of cancer therapy. Endocrine problems are very common in these patients. The recognition and prompt management of these are essential to prevent further morbidity and impairment of quality of life. Cranial radiation can damage hypothalamic-pituitary function, most frequently affecting GH status; however, higher radiation doses may cause more widespread hypothalamic-pituitary damage. Early puberty secondary to cranial irradiation is now being managed with gonadotrophin-releasing hormone analogues to improve final height. Prompt diagnosis and management of GH deficiency may improve final height outcome; continued GH therapy beyond final height aids the achievement of adult body composition (lean body mass and bone mass) and GH therapy in adulthood improves quality of life. Both cranial irradiation alone and with spinal irradiation can result in radiation damage to the thyroid resulting in hypothyroidism and thyroid nodules, a high proportion of which are malignant. Gonadal damage secondary to spinal irradiation and adjuvant chemotherapy may have long-term consequences including infertility.

Adult↗
PubMed1984

[Pituitary oncocytoma].

Since the first reports of pituitary oncocytoma by Kovacs and Horvath, and Landolt and Oswald increasing numbers of cases have been reported with the advent of electron microscopy. It has been posturated that more cases were not precisely diagnosed because of lack of electron microscopic study. We reported two cases of pituitary oncocytoma and discussed clinicopathological aspects. Case 1 A 66-year-old woman had a 6 year history of visual impairment. Neurological examination revealed loss of vision on the left and decreased visual acuity (0.3) with temporal hemianopsia on the right. The endocrinological study revealed moderate panhypopituitarism. Plain skull X-ray, computed tomography and cerebral angiography showed the findings of a pituitary tumor with suprasellar extension. Subfrontal removal of the tumor followed by irradiation was performed. Case 2 A 50-year-old man was well until 8 years previously, when he experienced loss of libido. Three years before entry, the left sided exophthalmos and ptosis were noted. Neurological examination showed a severe visual impairment with a bitemporal field defect, bilateral optic atrophy and disturbance of eye movements on the left. Endocrinological study revealed panhypopituitarism. Radiological studies showed a pituitary tumor with a suprasellar extension and an invasion into the left orbital cavity. Transcranial and then transsphenoidal partial removal of the tumor were done followed by irradiation. Histological examination of the tumors revealed a poorly granurated adenoma with very weak affinity to acid dyes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1976

The Jewish Hospital of St. Louis therapeutic grand rounds no. 13. Cushing disease.

Although several effective therapies for Cushing disease have been demonstrated, associated complications, side-effects, and production of adrenal insufficiency indicate the continuing need for a completely satisfactory treatment. Of the surgical approaches to the adrenal gland, total adrenalectomy offers the most predictable amelioration, but is necessitates lifelong replacement and augmentation therapy and can be followed by progressive sella enlargement and hyperpigmentation. Drugs can inhibit adrenal steroid biosynthesis or selectively destroy the zona fasciculata. Inhibitors can be overwhelmed by endogenous ACTH increases, and cause variable electrolyte changes and side-effects. The adrenocorticolytic drug (o,pDDD) is slow in onset, irreversibly destroys adrenocortical reserve, and is poorly tolerated in the gastrointestinal tract. Conventional pituitary irradiation is unpredictably effective in only half of the cases, but is not often followed by the serious neurologic sequelae and hypopitiutarism observed after implantation and heavy particle therapy. Selective hypophysectomy via modern techniques is relatively new, but apparently offers a direct, and possibly, definitive therapeutic option in this disorder.

Adult↗
PubMed2003

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.

Animals↗
PubMed1975

Treatment of chromophobe adenmas with megavoltage tirradiation.

From 1956-1972, 62 previously untreated patients with chromophobe adenomas received high-dose (average equivalent dose: 5700rads in 6 weeks) megavoltage (4-4.8 MeV) irradiation at Stanford, 33 postoperatively and 29 as the only intended treatment. Initialtreatment failure rates were 18% and 41%, respectively; however, overall control was 85% and 90%, despite 2 uncontrolled "invasive" adenomas in each group. Nine of the 12 failures in the group treated by irradiation alone had cystic tumors, and 9 of the 12 "failed" in less than 3 months. Despite a considerably greater degree of abnormal vision initially in the postoperative irradiation group, improvement of vision with treatment in that group was 83% (19% returned to normal) compared to 46% (only 8% to normal) in the irradiation alone group. Based upon an evaluation of the extent of findings at diagnosis and our results, we recommend surgical decompression followed by 5000 rads in 5 weeks for patients with any one or more of the following findings: 1)more than minimal depression of peripheral visual fields; 2) corrected visual actuity of less than 20/30 in either eye; or 3)more than 1-cm suprasellar extension of tumor. We recommend irradiation alone, as specified, for smaller adenomas accompanied by less extensive or no visual abnormalities.

Adenoma, Chromophobe↗
PubMed1988

Acromegaly from ectopic growth hormone-releasing hormone secretion by a malignant carcinoid tumor. Successful treatment with long-acting somatostatin analogue SMS 201-995.

A 26-year-old man with acromegaly secondary to ectopic growth hormone-releasing hormone (GHRH) secretion by a metastatic carcinoid tumor is the subject of this study. He previously failed to respond to conventional therapeutic modalities (partial hypophysectomy, pituitary irradiation, high-dose bromocriptine and a combination of streptozotocin and 5-fluorouracil) and was treated with long-acting somatostatin analogue SMS 201-995 (Sandoz, East Hanover, NJ). Growth hormone and somatomedin C concentrations became normal, and GHRH-LI (GHRH-like immunoreactivity) was suppressed by more than 60%. The growth hormone response to exogenous GHRH 1-40 was stopped and growth hormone rise to thyrotropin-releasing hormone (TRH) was significantly attenuated. A significant shrinkage of the pituitary gland was observed. Similarly, the size of the metastatic carcinoid lesions decreased dramatically and was accompanied by a normalization of liver function. After almost 2 years of SMS 201-995 therapy, the patient was well and had no clinical signs of acromegaly. Thus, SMS 201-995 appears to be a remarkably effective agent for treatment of acromegaly secondary to ectopic GHRH secretion.

Acromegaly↗
PubMed1988

Effect of gonadotropin secretion rate on the radiosensitivity of the rat luteinizing hormone-releasing hormone neuron and gonadotroph.

To test the hypothesis that the functional state of hypothalamic LHRH neurons and pituitary gonadotrophs might alter their radiosensitivity, we determined the experimental conditions under which the gonadotropin response to castration could be impaired by a single dose of cranial irradiation. Single doses of cranial irradiation greater than 2000 rads were lethal to unshielded rats. Shielding of the oropharynx and esophagus allowed the animals to survive doses up to 5000 rads. Doses between 2000 and 5000 rads had no effect on basal gonadotropin levels for as long as 3 months after irradiation. Irradiation caused a dose- and time-dependent impairment, however, in the gonadotropin response to castration. Impairment of the gonadotropin levels of castrate animals occurred in animals that were irradiated either before or after castration. However, rats irradiated in the castrate state showed a decreased susceptibility to irradiation damage. Additionally, stimulation of the pituitary by LHRH agonist (LHRHa) 3 h before irradiation significantly reduced the impairment of gonadotropin secretion 12-20 weeks after irradiation (P less than 0.05). Thus, increased functional activity of the rat hypothalamus or pituitary at the time of irradiation, induced by either castration or acute LHRHa administration, was associated with some protection against the gonadotropin-lowering effect of irradiation. Based upon these data, we hypothesize that stimulation of gonadotropin secretion at the time of therapeutic cranial irradiation in humans might protect against subsequent impairment of gonadotropin secretion.

Animals↗
PubMed1983

[The effect of graduated radiation doses on the follicular apparatus of the ovaries and the adenohypophysis in sheep].

Gradually increased radiation doses were applied directly to the ovaries of laparotomized ewes. The effect of these doses was studied as exerted on the qualitative and quantitative changes in the follicular apparatus of the ovaries and adenohypophysis of ewes in anoestrus and upon the recovery processes later on after irradiation. The ovaries irradiated with the dose of 4.79 Gy were found to be heavier when examined after some time from irradiation. The 10th and 30th day from irradiation the number of tertiary follicles decreased, the 100th day from irradiation their number increased to a four-fold level, as compared with the 10th day. Adenohypophysis showed a gradual growth of the number of PAS-positive cells. After the irradiation of ovaries with the dose of 9.57 Gy the ovaries showed the lowest rate of damage on the 10th day from irradiation; the 30th and 100th day from irradiation all the present tertiary follicles were in the state of atresia. In comparison with the control group, the amount of gonadotropic cells of adenohypophysis gradually increased, recovering from a rapid drop after irradiation. When the ovaries were irradiated with the dose of 19.14 Gy, all the tertiary follicles were in the state of atresia and the number of PAS-positive cells of adenohypophysis was lower in comparison with the control group.

Anestrus↗
PubMed1980

[Effect of hypophysectomy on neutrophilopoiesis].

The bone marrow of hypophysectomized rats exposed to irradiation with a dose of 400 C/kg or 6-hour immobilization has been studied. It has been found that hypophysectomy itself does not affect neutrophilopoiesis since its insufficiency is revealed only on the body exposure to additional loadings (irradiation or immobilization). This was manifested in the suppression of postradiative regeneration of neutrophilopoiesis and in the lack of granulocytopoiesis activation over a period of 24-48 h after the commencement of 6-hour immobilization.

Animals↗
PubMed2004

[Dosimetric evaluation for three dimensional conformal, conventional, and traditional radiotherapy plans for patients with early nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: Traditional external beam irradiation techniques for nasopharyngeal carcinoma have a lot of shortcomings, and improving external beam techniques have become an endeavor to enhance curative effectiveness. This study was designed to compare the dose distribution of three dimensional conformal radiotherapy (3D CRT) with traditional and conventional radiotherapy plans in the patients with early nasopharyngeal carcinoma using three dimensional treatment planning system. METHODS: Twenty-two patients with early nasopharyngeal carcinoma were selected. Traditional, conventional, and 3D CRT plans were made for each of them and compared with respect to target coverage (V95), normal tissue sparing (D50, D33, and D5, etc), normal tissue complication probability (NTCP). RESULTS: Dosimetric comparison indicated that the V95 of PTVnx60 and PTVnx50 for three different plans were 90.29% and 77.67% (traditional), 98.44% and 98.85% (conventional), 99.98% and 99.63% (3D CRT), respectively; and both conventional and 3D CRT had satisfied dose coverage of target volume especially in subclinical lesion region compared with traditional radiotherapy. With respect to normal tissue sparing, 3D CRT and conventional treatment plans could spare more brainstem, temporal lobe, optic chiasm, and pituitary than traditional plans; and 3D CRT could spare more parotid gland and temporomandibular joint than traditional and conventional treatments. CONCLUSION: Considering the dose distribution of the three treatment plans, both conventional and 3D CRT had satisfied dose coverage of target volume especially in subclinical lesion region compared with traditional radiotherapy, and 3D CRT plans can spare more normal tissues such as parotid gland and temporomandibular joint etc, and decrease their NTCP while it get the same dose distribution in target volume as traditional and conventional plans do in the treatment of early nasopharyngeal carcinoma.

Adult↗
PubMed1979

Liver RNA biosynthesis in adrenalectomized rats: effect of whole-body X-irradiation.

Exposure of rats to a single whole-body dose of X-rays led to an enhanced rate of RNA synthesis in the liver during 4 to 18 hours post-irradiation. This increase in RNA synthesis could not be obliterated by protecting the liver during irradiation. On the other hand, if adrenals were surgically removed prior to whole-body radiation exposure, no elevation either in liver RNA synthesis in vivo or liver chromatin template activity in vitro was apparent. Protection of only the head during irradiation could also prevent the stimulation in liver RNA synthesis in vivo. These results are suggestive of the involvement of neuro-endocrine reactions along the hypothalamus-pituitary-adrenal axes to be the underlying factors in whole-body radiation-evoked activation of the transcription machinery in the liver.

Adrenal Glands↗
PubMed1986

The incidence of late endocrine dysfunction following irradiation for childhood medulloblastoma.

A retrospective analysis of treatment in 20 patients who had received post-operative radiotherapy for medulloblastoma between 1969 and 1977 was completed. The patients were followed for a minimum of 60 months. Eleven patients survived for 5 or more years after treatment. The patients received 3600 cGy to the whole brain. The posterior fossa received 5600 cGY and the spinal axis 3600 cGY. Eight of eleven patients developed growth impairment; 6 of 7 patients had growth hormone deficiency. Since all endocrine gland failures are amenable to therapy, early attention to patients' growth rate and detection of hypothalamic-pituitary failure, would be of benefit to longterm survivors.

Adolescent↗
PubMed1976

Nelson's syndrome: frequency, prognosis, and effect of prior pituitary irradiation.

Previous reports differ regarding the frequency and course of pituitary tumors occurring after adrenalectomy for bilateral adrenal hyperplasia (Nelson's syndrome). In this report, 120 patients who were adrenalectomized for bilateral adrenal hyperplasia were followed for 2 to 20 years. Nine of the 120 developed Nelson's syndrome (8%), the tumors appearing 6 months to 16 years after adrenalectomy. In the majority of cases, the course was benign; seven patients are living an average of 9.7 years after discovery of their tumors. Finally, contrary to previous reports, pituitary irradiation before adrenalectomy did not prevent Nelson's syndrome. Twenty of 120 patients had pituitary irradiation as the initial treatment for bilateral adrenal hyperplasia and two subsequently developed pituitary tumors. Thus, after adrenalectomy for bilateral adrenal hyperplasia, all patients, regardless of previous pituitary irradiation, should be followed indefinitely with periodic X rays of the sella turcica for the possible occurrence of Nelson's syndrome.

Adolescent↗
PubMed1997

Pituitary adenomas: current methods of diagnosis and treatment.

Pituitary adenomas are benign neoplasms that can be effectively managed by a variety of therapeutic options. The clinician's goal in managing patients with these tumors should be to minimize the morbidity of each intervention used in diagnosis and treatment. Standard diagnostic interventions include MRI, hormonal assessment, and tissue diagnosis. Therapies include transsphenoidal surgery, external-beam radiotherapy, newer stereotactic irradiation techniques, and medical management. Appropriate treatment selection requires detailed knowledge of the expected outcomes and side effects of each option. Newer and perhaps less toxic treatment techniques are evolving and require further evaluation.

Adenoma↗
PubMed1988

Behavioral changes and structural defects in rats irradiated in utero.

Pregnant rats were irradiated with whole-body doses (0.25-1.25 Gy) of Cs-137 gamma-rays on gestational day 15, or with 1.0 Gy on gestational days 11, 13, 15, or 17. Postnatal growth (body weight) and several preweaning behaviors (righting reflex, negative geotaxis, reflex suspension, modified open field activity, spatial maze exploration, continuous corridor activity, and gait) of the offspring were monitored prior to sacrifice on post-parturition day 28. Brain (sensorimotor cortex) and pituitary tissues were processed for histological evaluation and morphometric analysis. For most behavioral endpoints, there were dose-dependent changes produced by irradiation on gestational day 15, with one endpoint (continuous corridor activity) demonstrating changes after 0.25 Gy that were significantly different from control values. The data indicate that the most sensitive organ showing radiation-induced alterations changes from the pituitary at gestational day 11 to the primitive cortex of the brain at days 13 to 17 with a peak of sensitivity at day 15. These results demonstrate that a spectrum of related functional and morphological deficits can be produced by even low-dose in utero irradiation, with the specific endpoint showing the greatest change being determined by the specific day of gestation on which irradiation occurs. Extrapolating from these experimental data with rats to the human situation, it is recommended that care be taken, when possible, to avoid exposure of the fetus, even after the early stages of organogenesis.

Animals↗
PubMed1986

Gonadotropin-secreting pituitary adenoma with concomitant hypersecretion of testosterone and elevated sperm count. Treatment with LRH agonist.

Hypersecretion of both FSH and LH was demonstrated in a man with pituitary macroadenoma, who also presented elevated levels of blood testosterone and an increased sperm count. The patient underwent transsphenoidal surgery followed immediately by cranial irradiation. Immunocytochemical analysis of the tumour revealed the presence of FSH, LH, TSH and the alpha-subunit. Gel chromatography of the serum on Sephadex G-100 revealed immunoactive FSH, LH and the alpha-subunit which coeluted with the labelled standards of corresponding hormones. Blood levels of both gonadotropins and testosterone remained persistently elevated up to one year following surgical decompression of the tumour and radiotherapy. It was decided to treat this patient with sc administration of 100 micrograms D-Trp6-LRH biweekly. After 20 weeks, LRH-analogue treatment resulted in the reduction of serum FSH and LH levels and a diminishing in tumour size as assessed by computed tomography scan of the pituitary. This report shows that in a patient with clinically and biochemically documented gonadotropin-secreting adenoma, inducing a state of persistent gonadal hyperfunction, pituitary surgery and cranial irradiation failed to normalize the biochemical abnormality; however, therapy with D-Trp6-LRH agonist induced clinical, biochemical and radiologic improvement.

Adenoma↗