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PubMed1989

[Endocrine complications caused by cranial irradiation].

Cranial irradiation has become one of the leading causes of growth hormone (GH) deficiency. The risk and time of onset of GH deficiency depend mainly on the dose delivered to the hypothalamo-pituitary region: GH deficiency is infrequent after doses under 20 grays and nearly constant after doses above 45 grays. For a given dose, a younger age at the time of irradiation and administration of the dose over a shorter time period increase the risk of GH deficiency. GH secretion can be adequately evaluated using rapid stimulation tests and is usually well correlated with growth, except in patients with radiation-induced precocious puberty or growth delay due to radiation-induced cartilage lesions.

Adolescent↗

PubMed2001

Focal ischemia in the cerebral cortex has an effect on the neurohypophysis. I. Ultrastructural changes in capillary vessels of the neurohypophysis after focal ischemia of the cerebral cortex.

OBJECTIVES: In our investigations we have reported that photochemical reaction leading to brain ischemia can also be precipitated with visible light from a non-coherent light source. It was revealed that focal cerebral ischemia after photochemical reaction cause the alterations in the capillaries ultrastructure and perivascular spaces of the barrier-competent regions of the brain. The purpose of this study is to first characterize the ultrastructural morphological consequences of photochemically induced ischemia in the cerebral cortex on the capillaries of neurohypophysis as the barrier-free region of the brain. METHOD: We used a model of ischemic brain damage due to obliteration of microvessels following the photochemical reaction. Rats were treated with an intravenous injection of rose bengal and irradiated from a halogen lamp source through an intact cranium to precipitate microvascular damage. Material for electron microscopic studies were sampled from the neurohypophysis 1 and 4 days after irradiation (4 animals in each group) in experimental group and 1 and 4 days after a rose bengal injection in control group. RESULTS: Investigations in transmission electron microscopy revealed platelet aggregation on the endothelium preceded by its early ultrastructural damage. In the capillaries of the neurohypophysis, one and four days after irradiation, numerous microthrombi adhering to the damaged endothelium were present. The capillary vessels contained a continuous, rather than a fenestrated endothelium. The basement membrane was thickened, blurred and locally multiplicated. CONCLUSION: Our results show that experimentally-induced thrombosis of cortical microvessels leads to alterations in the capillaries of neurohypophysis.

Animals↗

PubMed1983

Graded footshock stress elevates pituitary cyclic AMP and plasma beta-endorphin, beta-LPH corticosterone and prolactin.

Male rats were subjected to 15 min of various intensities of footshock current (0.0, 0.2, 0.4, 0.8, 1.6, 2.4, 3.2m A) on a variable interval schedule with an average intershock interval of 30 sec (30 shocks/15 min session). Each shock lasted 5 sec. Animals were sacrificed immediately after being removed from the shock box. Two similar studies were conducted. In the first experiment, rats were sacrificed by microwave irradiation and pituitary cyclic AMP levels were determined. In the second study, rats were decapitated and plasma hormones (prolactin, corticosterone, beta-endorphin, beta-LPH) were measured by radioimmunoassay. Although all biochemical indices of stress measured increased as shock intensity increased, some differences among the substrates measured were observed with respect to threshold intensity, range of proportional response and maximal response.

Animals↗

PubMed2003

Role of pituitary radiosurgery for the management of intractable pain and potential future applications.

RATIONALE: Two or three decades ago, cancer pain was treated by surgical/chemical hypophysectomy. In one report, the control of central pain (thalamic pain syndrome) was also approached with chemical hypophysectomy. Although in most of the patients these treatments resulted in a decrease in severe pain, concomitantly severe adverse effects (panhypopituitarism, diabetes insipidus and visual dysfunction) occurred in most patients. This historical evidence prompted us to perform Gamma Knife surgery (GKS) for this kind of intractable severe pain using a high irradiation dose to the pituitary stalk/gland. In the majority of patients, marked pain relief was achieved, surprisingly without any of the complications mentioned above. MATERIALS AND METHODS: A prospective multicenter study was conducted to evaluate the efficacy and safety in patients treated in Prague, Hong Kong and Tokyo. Indications of this treatment were: (1) failure of other effective treatment approaches prior to GKS, (2) good general patient condition (Karnofsky performance status >40%), (3) response to morphine for pain control (cancer pain), and (4) no previous radiotherapy of brain metastases (GKS/conventional radiotherapy). Eight patients with severe cancer pain due to bone metastasis and 12 patients with post-stroke thalamic pain syndrome were treated with GKS. The target was the border between the pituitary stalk and gland. Maximum dose was 160 Gy for cancer pain and 140 Gy for central pain. Follow-up included 6 patients (>1 month) with cancer pain and 8 patients (> 6 months) with thalamic pain syndrome. RESULTS: All patients (6/6) with cancer pain experienced significant pain reduction, and 87.5% (7/8) of the patients with thalamic pain had initially significant pain reduction. In some patients, pain reduction was delayed for several hours. Pain relief was noted within 7 days (median 2 days). No recurrence was observed in the patients with cancer pain. However, in 71.4% (5/7) of the patients with thalamic pain syndrome, disease recurred during the 6-month follow-up. Up to now, other complications have not been observed. CONCLUSION: Our clinical study protocol is only preliminary. Further clinical results on the management of thalamic pain are required to develop this treatment protocol. However, efficacy and safety have been shown in all our cases. In our opinion, this treatment has a potential to control severe pain, and GKS will play an important role in the management of intractable pain.

Bone Neoplasms↗

PubMed1975

Sertoli cell origin of testicular androgen-binding protein (ABP).

In this report it is suggested that the specific adrogen-binding protein (ABP), previously shown to originate in the testis of rat and other species, is produced by the Sertoli cells. This suggestion is based upon the following experimental findings: 1) ABP was found in high concentrations in testicular efferent duct fluid but only in trace amounts in inter-tubular lymph. i) ABP could be recovered from crude preparations of testis tubules, but not from Leydig cells from the same testes. 3) Testes whose germinal epithelium had been severly damaged by gamma irradiation showed no decrease in ABP content. The transport of ABP to epididymis was also preserved as judged from the levels of ABP in caput epididymis. 4) Testes that were completely devoid of germ cells following prenatal gamma irradiation showed high levels of ABP, These high levels approached zero following hypophysectomy, but could be restored by FSH administration to the hypophysectomized animals. ABP has been well characterized and now provides a valuable experimental tool as an indicator of Sertoli cell function.

Animals↗

PubMed2001

Reduction of gamma-aminobutyric acid-ergic neurotransmission as a putative mechanism of radiation induced activation of the gonadotropin releasing-hormone-pulse generator leading to precocious puberty in female rats.

Brain irradiation in prepubertal children with malignomas can cause precocious puberty. A selective cranial cobalt (Co(60))-irradiation technique has been developed in rats. In two experiments early juvenile (13-15 days old) female rats received a single dose of 5 Gy or sham irradiation. At pubertal age (post-natal days 33-34) irradiated rats had higher serum estradiol and luteinizing hormone levels. In experiment 1 irradiated rats had higher gonadotropin releasing-hormone (GnRH) mRNA levels in the preoptic area compared to controls (P<0.05). In experiment 2 the release rates of gamma-aminobutyric acid (GABA) in vitro from preoptic mediobasal hypothalamic areas of irradiated rats were significantly reduced after stimulation with the GABA(A) receptor agonist muscimol (maximum values 4607+/-804 vs. 7399+/-1048 pM in controls, mean+/-SEM, P<0.05). Radiation induced central precocious puberty might be caused by damage to inhibitory GABAergic neurons leading to premature activation of the GnRH-pulse generator.

Animals↗

PubMed1990

Radiation therapy for gliomas of the optic nerve and chiasm.

Thirty-three patients with optic glioma seen over a 30-year period were reviewed. Five patients (15%) had tumor confined to the optic nerve, 8 patients (24%) had optic nerve and chiasmal involvement, and the remaining 20 patients (61%) had invasion of contiguous structures as well as chiasmal involvement. Eleven patients (33%) had a history of neurofibromatosis. Two-thirds of the patients had either a biopsy or a partial resection of the tumor, with the remaining one-third being clinically diagnosed. All patients received irradiation to local fields. The median dose was 5040 cGy in 160 cGy fractions. Of patients alive at last follow-up, the median time of follow-up was 12.3 years. The 5-, 10-, and 15-year overall actuarial survivals were 94, 81, and 74%, respectively. Univariate and multivariate analysis were performed on the following clinical variables: extent of primary tumor, extent of surgery, dose of radiation, gender, race, age, and presence or absence of neurofibromatosis. Extension of the primary lesion to the optic chiasm and age less than or equal to 15 years were the only two variables to have statistically significantly inferior 15-year progression free survivals by multivariate analysis. Eighteen (55%) patients had treatment related complications with most involving the pituitary gland. We conclude that postoperative radiotherapy is beneficial in patients with chiasmal involvement and those with incomplete resections. A minimum tumor dose of 4000 cGy is recommended.

Adolescent↗

PubMed1978

Clinical course and outcome of pregnancies in amenorrhoeic women with hyperprolactinaemia and pituitary tumors.

Seventeen term pregnancies occurred in 14 amenorrhoeic women with hyperprolactinaemia and radiological evidence of pituitary tumour. The abortion rate was high (32%). All but one of the term pregnancies occurred after ovulation-inducing treatment with human gonadotrophins and bromocriptine (four and 12 pregnancies respectively). Two of the 14 women had visual complications during pregnancy, but neither had serious residual visual impairment. Two patients had possible pituitary enlargement during pregnancy.Bromocriptine may be the most suitable primary treatment for many infertile women with prolactin-secreting tumours. Tumour complications during pregnancy are a definite risk, but most pregnancies went uneventfully to term. Patients with pituitary tumour should be carefully evaluated before starting ovulation-inducing treatment with bromocriptine alone, and they should be told of the possible risks and of the advantages and disadvantages of pretreatment with irradiation or surgery. Patients should be carefully monitored during pregnancy and have their visual fields checked frequently. If visual complications due to tumour enlargement occur during a pregnancy, reinstituting bromocriptine may be the treatment of choice. If this fails, other forms of treatment such as induction of labour, high-dose corticosteroid treatment, pituitary implantation of yttrium-90, or surgery may be effective.

Abortion, Spontaneous↗

PubMed1996

Epidemiologic issues related to nasopharyngeal radium exposures.

A number of topics are discussed related to the potential for and pitfalls in undertaking epidemiologic studies of the late effects of nasopharyngeal radium irradiation. The available evidence indicates that linear extrapolation of risk estimates from high-dose studies is a reasonable basis for estimating risk from radium exposure or other situations in which the radiation exposures were fairly low and fractionated. Epidemiologic study of populations given nasopharyngeal radium irradiation is worthwhile scientifically if several criteria can be met. It is very important that any such study has adequate statistical power, which is a function of the doses to the organs of interest and the radiation risk coefficients for those organs, as well as the available sample size. If the organ doses are low, a prohibitively large sample size would be required. Other problems with low-dose studies include the likelihood of false-positive results when a number of health end points are evaluated and the impact of dose uncertainties, small biases, and confounding factors that make the interpretation uncertain. Cluster studies or studies of self-selected cohorts of irradiated patients are not recommended because of the potential for severe bias with such study designs. The ability to define subgroups of the population who have heightened genetic susceptibility may become a reality in the next few years as genes conferring susceptibility to brain cancers or other head and neck tumors are identified; this scientific advance would have the potential to alter greatly the prospects and approaches of epidemiologic studies.

Humans↗

PubMed1990

Effect of lithium on tachykinins, calcitonin gene-related peptide, and neuropeptide Y in rat brain.

The effects of lithium on brain regional concentrations of substance P (SP)-, neurokinin A (NKA)-, calcitonin gene-related peptide (CGRP)- and neuropeptide Y (NPY)-like immunoreactivities (-LI) were studied in rat. In the pilot study, rats were divided into three groups that were administered vehicle, or 1 or 4 mEq/kg lithium sulphate, respectively, intraperitoneally once/day for 9 days. In the second experiment, rats were divided into three groups receiving vehicle, or 1 or 2 mEq/kg lithium sulphate, respectively, intraperitoneally twice/day for 9 days. After sacrifice by focused microwave irradiation, brains were dissected, weighed, and frozen. Peptides were extracted and measured in extract aliquots by specific radioimmunoassays. Marked regional differences (P less than .001) were found for each of the peptides measured. In the pilot study the higher lithium dose, 4 mEq/kg, significantly raised neuropeptide levels. However, animals receiving this dose also showed signs of toxicity. In the second experiment, lithium increased SP-LI concentrations in striatum and hypothalamus (72 and 29%, P's less than .001 and .05). NKA-LI was also elevated in striatum (44%, P less than .01). CGRP-LI, in parallel to SP-LI, was increased in striatum and hypothalamus (58 and 78%, P's less than .05 and .01). In contrast, lithium decreased CGRP-LI in the pituitary gland (56%, P less than .01). NPY-LI was increased in striatum, and frontal and occipital cortex (30, 66, and 60%, respectively; P's less than .01, .01, and .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Persistent or recurrent acromegaly. Long-term endocrinologic efficacy and neurologic safety of postsurgical radiation therapy.

As in other clinics, pituitary surgery was definitive treatment in less than 50% of cases of acromegaly treated at one institution over several decades. From 1965 to 1989, 24 acromegalic patients who had noncurative pituitary surgery received radiation therapy at the National Institutes of Health, with a basal human growth hormone level of greater than 5 ng/ml as the criterion for active disease. Using megavoltage irradiation, more than 60% of these patients stabilized at a normal hormonal range, and the overwhelming majority had decreasing growth hormone levels with time. No major side effects of irradiation were encountered except panhypopituitarism of varying degrees. The authors evolved a policy of surgery as the first option, followed by irradiation for patients with postoperative growth hormone levels more than 5 ng/ml.

Acromegaly↗

PubMed1981

Mitogens for glial cells: a comparison of the response of cultured astrocytes, oligodendrocytes and Schwann cells.

We have identified two growth factors for cultured rat astrocytes: fibroblast growth factor, a peptide derived from either whole bovine brain, or pituitaries, and a growth factor in extracts of bovine pituitary which was previously identified as a Schwann cell mitogen. Oligodendrocytes in primary cultures derived from neonatal rat central nervous system divide only rarely if at all. These growth factors did not stimulate primary oligodendrocytes to divide. Occasionally cells found in suspension in long-term cultures of the central nervous system were enriched for cells which were identified as oligodendrocytes by the presence of galactocerebroside on their surface and myelin basic protein in their cytoplasm. When provided with a monolayer of irradiated 3T3 cells, these oligodendrocytes were able to spread out and extend elaborate branched processes typical of oligodendrocytes in the primary cultures. Unlike their counterparts in the primary cultures, these suspension-derived oligodendrocytes are capable of cell division as demonstrated by the uptake of [3H]thymidine and autoradiography.

Animals↗

PubMed1991

Craniopharyngioma in children.

Craniopharyngioma of childhood is a different entity than the tumor found in adulthood. Microscopically adamantinomata tissue is found in children whereas a squamous epithelial origin is more predominant in adults. Partial resection is of little benefit in children because adamantinomous tumors grow at a fast rate. Confidence in a prebiopsy diagnosis of craniopharyngioma provided by modern diagnostic imaging allows the surgeon to choose either radical surgical resection or limited surgery combined with radiotherapy. As aggressive surgery followed by radiotherapy compounds the deleterious effects of the two treatments without any added benefit, this course of action should be avoided when possible. The neurosurgeon should be clear in making a recommendation and plan of action to patients and families. Radical surgery is recommended by the vast majority of pediatric neurosurgeons at academic centers. The long-term survival achieved following radical surgery performed by a highly experienced surgeon may approach the results achieved by limited resection and radiotherapy, but the quality of life issue is left unresolved. Unfortunately the children in series reporting the results of aggressive surgery have not had the benefit of detailed psychologic, IQ, and endocrinologic testing. The major question regarding quality of life with limited resection plus radiotherapy regards the delayed effects of irradiation. Are the complications cumulative with time? The only series with long-term follow-up reporting both treatments overwhelmingly favors limited resection followed by irradiation. This polarization of opinion by the experts needs to be resolved. A true multi-institutional, cooperative study is needed. Unfortunately the bias of potential participants prohibits a randomized study at this time. It is hoped that a prospective, natural history study with detailed psychologic and physiologic testing will give a clearer evaluation of the outcome and standard of care in this country.

Child↗

PubMed1986

Cranial irradiation for cerebral and nasopharyngeal tumours in children: evidence for the production of a hypothalamic defect in growth hormone release.

A synthetic 29-amino acid analogue of human pancreatic GH-releasing hormone (GHRH(1-29)NH2) has recently been shown to stimulate the release of GH in normal subjects. We have studied the GH response to GHRH(1-29)NH2 in nine children irradiated for brain and nasopharyngeal tumours, who were not growing and were deficient in GH as assessed by insulin-induced hypoglycaemia. Serum GH rose in response to GHRH(1-29)NH2 in all the children, and in five the peak serum GH response was greater than 20 mu./l. The data suggest that when hypothalamo-pituitary irradiation results in GH deficiency, this is due to a failure of the synthesis or delivery of endogenous GHRH from the hypothalamus to the pituitary cells. It also suggests that it may be possible to treat such children using synthetic GHRH in place of exogenous GH.

Body Height↗

PubMed1998

Effect of surgery and radiotherapy on visual and endocrine function in nonfunctioning pituitary adenomas.

The effect of surgery alone or followed by radiotherapy in recovering visual abnormalities, debulking tumor mass and restoring hormone impairments was evaluated in 84 patients with clinical nonfunctioning pituitary adenomas (NFPA) subjected to 1-10 yr follow-up. All patients underwent surgery via transsphenoidal (in 69) or transcranic-pterional approach (in 15). Radiotherapy was performed after surgery in 59 of 72 patients with incomplete tumor removal. The assessment of pituitary function was performed in all patients before and every 1-2 yr after surgery and/or radiotherapy. Radiological and ophthalmologic assessment was performed before and 3, 6 and 12 months after surgery, then yearly. At diagnosis, headache and visual disturbances occurred in 63 and 58 patients, respectively, while deficiency of GH, TSH, ACTH, FSH, LH and ADH was documented in 55, 7, 19 47 and 6 patients, respectively. After surgery, gonadal function recovered in 12 women, visual disturbances improved in 43 patients (15 regained normal vision), pituitary function improved in 8 of 62 patients, worsened in 34 patients. At MRI, complete tumor removal was documented in 12 of 84 patients. After surgery alone, tumor regrowth was observed in 7 patients between 3-7 yr. After radiotherapy, vision improved in 9, remained unchanged in 49 and worsened in 1 of 59 patients. After radiotherapy, tumor regrowth was documented in 9 patients between 2-12 yr and the prevalence of hypopituitarism raised from 28.8% to 92% after 1 and 10 yr. In conclusion, surgery alone is effective only in a minority of patients (14.3%) and radiotherapy causes hypopituitarism in rather the totality of patients after 10 yr. The prevalence of tumor regrowth was similar in irradiated ones (15%) and non irradiated patients (28%; chi(2), p = 0.4). Therefore, a careful radiological followup is suggested after surgery so that radiotherapy can be performed promptly on the basis of clinical data, tumor regrowth and/or invasiveness documented at histology.

Adenoma↗

PubMed1980

[Pituitary function and growth in children under treatment for leukemia (author's transl)].

The effect of cranial irradiation with doses of 2,400 and 4,800 rad on the pituitary function of children with acute lymphoblastic leukaemia was studied. The plasma growth hormone level after arginine simulations was normal in 13 out of 15 children. The rise of TSH after TRH stimulation and the metyrapone test were also normal. The growth of 40 children during an observation period of 3 or more years was also normal.

Adolescent↗

PubMed1983

[The sympathetic-adrenal and hypophyseal-adrenal systems in the preoperative irradiation of patients with cancer of the esophagus and cardia].

A study was made of 74 patients with esophageal and cardiac cancer, Stages II and IV. The excretion of catecholamines, corticosteroids and their precursors was studied, tests with adrenalin before and after preoperative irradiation at a summary dose of 30 Gy were done. It has been shown that before the start of radiation therapy the excretion of catecholamines and corticosteroids is lowered, the reaction to adrenalin administration is negative in most patients, the phase syndrome of cardiac hypodynamics associated with disturbed function of the sympathoadrenal system was revealed. After irradiation DOPA and dopamine excretion gets still lower whereas adrenalin excretion remains at the initial reduced level, the level of noradrenalin increases but does not achieve the normal level, i. e. a predominant decrease of catecholamine synthesis is observed. Adrenalin tests after irradiation revealed the depletion of the reaction of the cardiovascular system interrelated, to a great extent, with the activity of the sympathoadrenal system. Preoperative irradiation in patients with esophageal and cardiac cancer results in an increased excretion of 17-ketosteroids (17-KS) and 17-ketogenic steroids, however 17-KS excretion does not reach the normal level. For better tolerance of irradiation and for a radiosensitization effect testenate is administered to patients before and during radiation therapy. The administration of testenate 7-10 days before the start and during radiotherapy proved to be effective which was confirmed by noticeable necrobiotic and necrotic changes of cancer cells.

17-Ketosteroids↗

PubMed1980

The treatment of acromegaly by transsphenoidal surgery.

Pituitary tumors were removed transsphenoidally in 32 patients with acromegaly. Ten patients had high prolactin (PL) levels as well as elevated growth hormone (GH) levels. In 24 patients, GH levels were lowered to 5 ng/mL or less and remained low. The PL level was reduced to normal in eight patients. Of three patients with postoperative GH levels of 6 to 10 ng/mL, one patient remains in this range but two have relapsed. Five patients showed only a partial lowering in GH level. Pituitary irradiation lowered the level further. Hypopituitarism developed in four patients. Permanent diabetes insipidus occurred in one patient and meningitis developed in another. They subsequently recovered. There were no deaths. Abnormal GH responses to hyperglycemia, hypoglycemia, and levodopa returned to normal following surgery. Transsphenoidal tumor removal appears to be an effective treatment for acromegaly.

Acromegaly↗