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PubMed1983

The effect of microwave irradiation on vasopressin in plasma and hypothalamo-neurohypophyseal system.

Radioimmunoreactive vasopressin was measured in plasma, neurohypophysis and hypothalamus of the rats after different procedures of killing: a) microwave irradiation; b) decapitation; c) decapitation following a stress induced by immobilization in a restrainer. Vasopressin content in the neurohypophysis and hypothalamus was much lower in microwave irradiated than in both decapitated and stressed decapitated rats. In addition, the data from microwave technique were inconsistent with a large scatter. Plasma vasopressin concentration was elevated in both the microwave irradiated and stressed decapitated rats, demonstrating that restraining of the animals induced an excessive stress. Microwave irradiation technique including the necessary manipulation of the animal proved to be less suitable than decapitation technique for the measurement of vasopressin. It is likely that vasopressin in the hypothalamus and neurohypophysis is relatively resistant against post-mortem proteolysis.

Animals↗

PubMed1991

[Role of age at the moment of irradiation on the induction of tumors].

The probability that rats develop tumours following a 3 Gy exposure to gamma rays from cobalt 60 was observed to depend on age at exposure. Lifetime excess of neoplasia decreased by a factor of about 10 in 9-month-old rats as compared to animals irradiated in utero. The 3-month age group developed slightly fewer tumours than the group irradiated in utero, and tumour location was different. The higher incidence of tumours observed in the foetal group was mainly due to the high sensitivities of central nervous system and gonads during organogenesis.

Adrenal Gland Neoplasms↗

PubMed2002

Ocular neuromyotonia: a case report.

Ocular neuromyotonia is a rare motility disorder occurring after tumor irradiation near the skull base or as a consequence of vascular abnormalities. Ocular myasthenia, convergence spasm and a cyclic third nerve palsy must be considered as differential diagnoses. The case of a 32-year-old woman suffering from intermittent diplopia six months after radiation therapy of a recurrent pituary gland adenoma is presented.

Adenoma↗

PubMed1976

Hypothalamic-pituitary-testicular system following testicular X-irradiATION.

Testes of adult, male rats were exposed to a total dose of 1500 R of X-irradiation. Testicular weight decreased from day 8 after X-ray treatment. This decrease was, however, preceded by an increment of the testis weight on day 4 following treatment. X-ray treatment of testes was associated with significant increases in serum FSH. Testicular irradiation had, however, no effect on ventral prostate and seminal vesicles weights. Serum testosterone increased only on day 1, 2 and 4 after irradiation, while serum LH levels tended to increase from day 8 post-irradiation. These changes were not significant, however, when compared with non-irradiated controls. At 7, 13 and 20 days following 1500 R of bilateral, testicular X-irradiation, the hypothalamic-pituitary unit was still capable of responding to exogenous gonadotrophin releasing factor. Serum FSH may in male rats by regulated at least partly by circulating steroids of testicular origin and partly by an unknown factor of non-interstitial cell nature.

Animals↗

PubMed1975

The effect of nephrectomy on the incidence of breast carcinoma in irradiated parabiosed rats.

The incidence of carsinoma the breast in parabiosed female NEDH rats is 2.5%. When one member of such a pair is irradiated, the incidence rises to 11% in the irradiated partner and 10% in the nonirradiated partner. If in such a pair of rats one kidney is removed from each partner, the incidence of breast carcinoma rises fivefold in the nonirradiated partner. The factors involved in such an increase probably have to do with alteration in retention, interchange, and feedback of the pituitary and ovarian hormones.

Adenocarcinoma↗

PubMed1999

Proton radiation therapy (PRT) for pediatric optic pathway gliomas: comparison with 3D planned conventional photons and a standard photon technique.

PURPOSE: Following adequate therapy, excellent long-term survival rates can be achieved for patients with optic pathway gliomas. Therefore, avoidance of treatment-related functional long-term sequelae is of utmost importance. Optimized sparing of normal tissue is of primary concern in the development of new treatment modalities. The present study compares proton radiation therapy (PRT) with a three-dimensional (3D)-planned multiport photon and a lateral beam photon technique for localized and extensive optic pathway tumors. METHODS AND MATERIALS: Between February 1992 and November 1997, seven children with optic pathway gliomas underwent PRT. For this study, we computed proton, 3D photon, and lateral photon plans based on the same CT data sets, and using the same treatment planning software for all plans. Radiation exposure for normal tissue and discrete organs at risk was quantified based on dose-volume histograms. RESULTS: Gross tumor volume (GTV) ranged from 3.9 cm3 to 127.2 cm3. Conformity index (relation of encompassing isodose to GTV volume) was 2.3 for protons, 2.9 for 3D photons, and 7.3 for lateral photons. The relative increase of normal tissue (NT) encompassed at several isodose levels in relation to NT encompassed by the 95% proton isodose volume was computed. Relative NT volume of proton plan isodoses at the 95%, 90%, 80%, 50%, and 25% isodose level increased from 1 to 1.6, 2.8, 6.4, to a maximum of 13.3. Relative volumes for 3D photons were 1.6, 2.4, 3.8, 11.5, and 34.8. Lateral plan relative values were 6, 8.3, 11.5, 19.2, and 26.8. Analysis for small (<20 cm3) and larger (> 80 cm3) tumors showed that protons encompassed the smallest volumes of NT at all isodose levels. Comparable conformity and high-dose gradient were achieved for proton and 3D photon plans in small tumors. However, with increasing tumor volume and complexity, differences became larger. At the 50% isodose level, 3D photons were superior to lateral photons for small tumors; this advantage was equalized for larger tumors. At the lowest isodose level, 3D photons encompassed the highest amount of NT. Analysis of organs at risk showed that PRT reduced doses to the contralateral optic nerve by 47% and 77% compared to 3D photons and lateral photons, respectively. Reductions were also seen for the chiasm (11% and 16%) and pituitary gland (13% and 16%), with differences at clinically relevant tolerance levels. Furthermore, reduced dose exposure of both temporal lobes (sparing 39% and 54%) and frontal lobes was achieved with PRT. CONCLUSION: PRT offered a high degree of conformity to target volumes and steep dose gradients, thus leading to substantial normal tissue sparing in high- and low-dose areas. It is expected that this will result in decreased long-term toxicity in the maturing child. Advantages of proton versus 3D photon plans became increasingly apparent with increasing target size and tumor complexity. Even in small tumors, conformity of 3D photon irradiation came at the expense of a larger amount of NT receiving moderate to low radiation doses. Lateral photons resulted in inferior dose distribution with high radiation exposure of clinically relevant normal tissues.

Child↗

PubMed2000

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.

Adrenocorticotropic Hormone↗

PubMed1996

Late health effects of radiation for eustachian tube dysfunction: previous results and ongoing study in The Netherlands.

To study the late health effects of nasopharyngeal radium irradiation, a nonconcurrent prospective study was conducted in The Netherlands. Exposed subjects (n = 2510) were treated unilaterally with nasopharyngeal radium irradiation at five ear, nose, and throat clinics between 1945 and 1965 and followed up through February 1, 1985. Unexposed subjects (n = 2199) were matched to treated patients according to clinic, year of birth, and first consultation within 5 years. No overall significant increase in cancer mortality was found. A statistically significant difference was noted only for cumulative all-site cancer incidence, with the exposed having twice as many verified cancers as the nonexposed. This excess risk was caused mainly by head and neck tumors and other tumors (lung, digestive tract, and urogenital system). The relative risk for these specific sites, however, was not significantly different from 1.00. These findings corroborate the hypothesis that there is some risk of tumor induction involved with nasopharyngeal radium irradiation at the dose level applied to this population. Because of ongoing interest in this subject, I plan to extend the follow-up of the cohort through December 31, 1995, and I am studying the possibility of expanding the study population.

Brain Neoplasms↗

PubMed2006

Conventional pituitary irradiation is effective in lowering serum growth hormone and insulin-like growth factor-I in patients with acromegaly.

BACKGROUND: There has been recent controversy as to the effectiveness of conventional pituitary irradiation in reducing circulating GH levels to less than 2.5 ng/ml and/or normalization of serum IGF-I. OBJECTIVES: Our objectives were to determine the effects of conventional pituitary irradiation on 1) lowering of serum GH and IGF-I levels, 2) the proportion of patients who achieve a GH level less than 2.5 ng/ml and a normal age-corrected IGF-I and the time taken to achieve this, and 3) the incidence of hypopituitarism and other adverse effects. DESIGN: We conducted retrospective data collection from 14 centers throughout the United Kingdom. PATIENTS: We studied 1840 patients with acromegaly, of whom 884 had received conventional pituitary irradiation. MEASUREMENTS: We assessed circulating GH and IGF-I levels and pituitary function at intervals after irradiation. RESULTS: Mean GH levels declined from 13.5 to 5.3 ng/ml at 2 yr after irradiation, to 2.0 ng/ml by 10 yr, and to 1.1 ng/ml at 20 yr. Twenty-two percent of patients achieved a level less than 2.5 ng/ml by 2 yr, 60% by 10 yr, and 77% by 20 yr. The interval to achieve this depended on the preirradiation GH level. IGF-I levels fell in parallel to those of GH with 63% of patients having a normal level by 10 yr. The proportions of patients with new pituitary hormone deficiencies 10 yr after irradiation were 18% for LH/FSH, 15% for ACTH, and 27% for TSH. No other side effects were noted. CONCLUSIONS: In this, the largest series reported, conventional pituitary irradiation is shown to be an effective and safe means of reducing both serum GH and IGF-I concentrations in patients with acromegaly.

Acromegaly↗

PubMed1983

Gonadotropin releasing-hormone receptors: photoaffinity labeling with an antagonist.

A photoaffinity antagonist of gonadotropin releasing hormone (GnRH), D pGlu-D-Phe-D-Trp-Ser-D-Lys6(N epsilon-azidobenzoyl)-Leu-Arg-Pro-Gly-NH2 (photoaffinity antagonist) was prepared by reacting [D-pGlu1, D-Phe2, D-Trp3, D-Lys6]GnRH with the N-hydroxysuccinimide ester of 4-azidobenzoic acid. The analog appeared homogeneous when analyzed by thin-layer chromatography and its photoreactivity was demonstrated by spectral changes when exposed to light. The photoaffinity antagonist retained high affinity binding to the GnRH receptor of pituitary membrane preparations and exhibited antagonistic activity when assayed in vitro in whole pituitaries. Pituitary membrane preparations were incubated with the radioactive photoaffinity GnRH antagonist and irradiated with light. Sodium dodecyl sulfate gel electrophoresis after solubilization and reduction showed the specific labeling of a single specific protein with an apparent molecular weight of 60,000 daltons. These results indicate that GnRH agonists and antagonists bind to the same receptor.

Affinity Labels↗

PubMed1976

Failure of cyprohepatdine to inhibit vasopressin-stimulated cortisol release in a patient with Cushing's disease.

A case of a 21-year-old woman with Cushing's disease due to a pituitary tumor is described. The patient was treated with cyprohepatadine for 4 weeks immediately following pituitary alpha-particle irradiation. A standard vasopressin test to measure ACTH-mediated cortisol release was performed four times: prior to pituitary irradiation, after irradiation, after 4 weeks of cyproheptadine therapy, and off cyproheptadine for 2 weeks. Cyproheptadine failed to modify vasopressin-stimulated cortisol release in the patient described. This study suggests that cyproheptadine, which has previously been shown to decrease ACTH secretion, probably acts principally at the hypothalamic, rather than at the pituitary level.

Adult↗

PubMedDate not supplied

[The effect of one-time external gamma irradiation at different stages of ontogeny on the thyroid status of rats].

A single external gamma-irradiation (1 Gy) of rats on day 35 of their life causes stable structural and functional disturbances in the thyroid gland leading to the development of hypothyrosis at the remote times following irradiation which is demonstrated by the decrease in the concentration of thyroxine in the blood, increase in the thyrotropic function of the hypophysis and inhibition of the activity of tyrosine-dependent enzyme, alpha-glycerophosphate dehydrogenase, in the liver. Disturbances induced by such exposure in the thyroid gland of adult rats are insignificant and compensatory in time.

Aging↗

PubMed1976

Growth hormone deficiency after treatment of acute leukaemia in children.

Growth hormone (GH) secretion was studied in 15 children at various times after treatment for acute lymphatic leukaemia. Impaired GH responses both to hypoglycaemia and to Bovril were found in 4 children. 13 of the children had been given prophylactic cranial irradiation of either 2500 rads in 10 fractions or 2400 rads in 20 fractions. The reduction in GH responses in those given the former dose was highly significant compared with the reduction in those given the latter dose. However, other differences between the two groups included the length of time since cranial irradiation and the chemotherapy used. The main cause of the GH deficiency is not yet clear, but we conclude that it may occur in children treated successfully for acute lymphatic leukaemia.

Antineoplastic Agents↗

PubMed1999

Diagnosis and management of Cushing's syndrome: results of an Italian multicentre study. Study Group of the Italian Society of Endocrinology on the Pathophysiology of the Hypothalamic-Pituitary-Adrenal Axis.

The past 45 yr' experience with Cushing's syndrome (CS) has led to the awareness of its complex nature and, by the same token, brought about an increase in the diagnostic and therapeutic dilemmas. We carried out a retrospective multicentre study on the diagnostic work-up and treatment in 426 patients with CS, subdivided as follows: 288 with Cushing's disease (CD), 80 with an adrenal adenoma, 24 with an adrenal carcinoma, 25 with ectopic ACTH and/or CRH secretion, and 9 with ACTH-independent nodular adrenal hyperplasia. Normal urinary free cortisol (UFC) values among multiple collections were recorded in about 10% of patients with CS. In 28% of patients with ACTH-independent CS, basal ACTH concentrations were within the normal range but did not respond to CRH stimulation. Measurement of ACTH levels by immunoradiometric assay, rather than by RIA, offered a greater chance of recognizing patients with ACTH-independent CS or ectopic secretion. A 50% increase in ACTH or cortisol levels after CRH yielded a diagnostic accuracy of 86% and 61%, respectively, in the differential diagnosis of ACTH-dependent CS. An 80% decrease in cortisol levels after 8 mg dexamethasone overnight, or in UFC values after the classical 2-day administration, excluded an ectopic secretion but carried a low negative predictive value given the high number of nonsuppressors among patients with CD. Pituitary imaging identified an adenoma in 61% of patients with CD. At inferior petrosal sinus sampling, an ACTH centre: periphery gradient after CRH less than 3, correctly classified all patients with ectopic secretion but misdiagnosed 15% of 76 patients with CD. Transsphenoidal pituitary surgery, the standard therapy for CD, resulted in complete remission (appearance of clinical signs of adrenal insufficiency associated with low/normal UFC excretion and, when available, low/normal morning plasma ACTH and cortisol levels) in 69% of patients. The overall relapse rate after pituitary surgery was 17%. The probability of relapse-free survival, as assessed by Kaplan-Meier analysis, was 95% at 12 months, 84% at 2 yr, and 80% at 3 yr. Risk of relapse was significantly correlated with postoperative baseline plasma ACTH and cortisol peak after CRH. No relapses were observed among patients who did not respond to CRH. Other therapeutic approaches for CD, such as pituitary irradiation and medical therapy, resulted in normalization of cortisol secretion in about half of treated cases. In summary, an accurate selection of the available diagnostic tools leads to the correct diagnosis in the majority of patients with CS. The therapeutic options for CD, adrenal carcinoma, and ectopic secretion are, as yet, not fully satisfactory. The high incidence of relapse after pituitary surgery calls for a prolonged follow-up.

Adenoma↗

PubMedDate not supplied

[FSH, LH, prolactin and testosterone levels in peripheral blood and urinary excretion of 17-ketosteroids and 17-hydroxycorticosteroids in patients after removal of chromophobe adenoma of the pituitary gland].

The aim of the study was clinical evaluation of a new marker of pituitary tumours--the alpha subunit of glycoprotein hormones. The studies were performed in 152 patients with manifestations of intersellar tumours; an elevated serum alpha subunit concentration was found in 49 of these cases. The determinations of alpha subunit were performed by double antibody radioimmunoassay. Iodination of alpha subunit was made by chloramine T technique with subsequent purification of Ultrogel AcA54 column. The remaining pituitary hormones were also determined by radioimmunoassay. The incidence of pituitary tumours of alphoma type was 30 percent. Tumours occurred frequently in association with an increased serum growth hormone and manifestations of acromegaly, less frequently with hyperprolactinemia and signs of prolactinoma. Following neurosurgery of 60Co pituitary irradiation hypopituitarism was of high occurrence.

17-Hydroxycorticosteroids↗

PubMed1985

Long-term results of transsphenoidal pituitary microsurgery in 60 acromegalic patients.

Sixty patients with clinically and biochemically active acromegaly were treated by transsphenoidal surgery. All patients underwent a full assessment of pituitary function both preoperatively and postoperatively; these studies were repeated 6 months after surgery and every year, when possible. The mean follow-up period was 3.3 years (range 0.5-7 years). The GH level normalized in 62% of patients after surgery. A paradoxical reaction of GH to TRH was present in 35 patients before surgery and had normalized in 17 after surgery. Large tumours were associated with higher GH levels than smaller tumours. A prognostic factor in terms of normalization of both the GH level and an eventual paradoxical reaction to TRH or a glucose challenge was a low preoperative GH level. Three out of seven patients with either a positive postoperative TRH test but a normal GH level, or a slightly elevated GH level suffered a biochemical and clinical recurrence and two of them underwent reoperation. In contrast, when the TRH test had normalized (always in association with normal GH levels) no recurrence was found. The impact of surgery on the other pituitary functions was generally slight and the numbers of patients with preoperative and postoperative impairment were about equal. Postsurgical radiation therapy was administered to patients with an elevated GH level, a non-normalized TRH test irrespective of whether the GH level had normalized, or local invasion of the tumour. In 11 out of 17 patients with elevated GH levels after surgery, normalization was achieved by radiation therapy after a mean period of 2.7 years. The incidence of pituitary failure after irradiation appeared to be high; gonadal function in men and the GH reserve function were especially vulnerable. From this study we conclude that in many cases the adenoma can be removed effectively, without compromising the other pituitary functions. However, a substantial number of the patients require additional radiation therapy, leading to an inevitable loss of other pituitary functions.

Acromegaly↗

PubMed1984

Malignant evolution of an ACTH-producing pituitary tumor treated with intrasellar implantation of 90Y. Case report and review of the literature.

A case of pituitary carcinoma is here presented, together with a review of the 25 cases so far reported in the literature. After a long-standing history of Cushing's disease, treated with interstitial pituitary irradiation and total adrenalectomy, Nelson's syndrome developed due to a pituitary neoplasm that finally spread through the subarachnoidal space, bringing the patient to death. The possible long-term role of surgery and radiotherapy in switching an aggressive behavior is also discussed.

Adrenalectomy↗

PubMed2004

Poor responses to a test dose of subcutaneous octreotide predict the need for adjuvant therapy to achieve 'safe' growth hormone levels.

OBJECTIVE: Somatostatin analogues are an established treatment in acromegaly. This study was designed to evaluate whether the acute serum growth hormone (GH) response to a test dose of octreotide in acromegaly predicts longer-term response to the drug at 3 years. DESIGN AND METHODS: In 23 patients, GH responses across 8 h to a subcutaneous test dose (50 microg) of octreotide were compared with GH levels after 3 years of therapy. The majority had pituitary surgery as primary therapy and at 3 years were receiving at least 600 microg octreotide daily subcutaneously or 20 mg LAR monthly intramuscularly. RESULTS: Seven had a test day GH Nadir of 5 mU/l or less of whom 4 achieved GH < 5 mU/l at 3 years. Sixteen had a test day nadir GH of 10 mU/l or less and of these 8 achieved GH < 5 mU/l at 3 years. Seven of the 23 had a GH Nadir >10 mU/l and of these 3 had achieved GH <5 mU/l at 3 years. However all of these 3 had received external pituitary irradiation within 4 years of the 3 year assessment, as compared with 3 of the <5 mU/l nadir group and 5 of the <10 mU/l nadir group. CONCLUSIONS: In patients on optimal long-term doses of octreotide for acromegaly, absence of a nadir GH <10 mU/l in the 8 h after a test dose was associated with failure to achieve GH levels associated with a normal life expectancy (5 mU/l or less) unless adjunctive external pituitary irradiation was given. As well as testing tolerability a test dose of octreotide may help in determining which patients should be offered early external pituitary irradiation or therapy with a GH receptor antagonist if surgery has failed to achieve 'safe' GH levels.

Acromegaly↗