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PubMed1997

Anti-carcinogenic activity of simvastatin during the promotion phase of radiation-induced mammary tumorigenesis of rats.

Pregnant Wistar-MS rats received whole body irradiation with 2.6 Gy gamma-rays from a 60Co source at day 20 of pregnancy. Control rats were fed a basal diet and were implanted with a diethylstilbestrol (DES) pellet at 30 days after weaning. In the experimental group, rats were fed a diet containing simvastatin immediately after weaning and received a DES pellet at 30 days after weaning. A high incidence of total mammary tumours was observed in the rats fed the control diet and treated with DES for 1 year. The administration of dietary simvastatin together with DES treatment significantly decreased the incidence of mammary tumours. The development of adenocarcinoma in the control rats was significantly higher than that in the rats fed the simvastatin diet. After the administration of simvastatin to the experimental group for 1 year, the serum estradiol-17beta concentration in these rats was markedly reduced, but that of prolactin was not. No significant difference was seen in the development of the mammary glands between rats fed the control diet and those fed the simvastatin diet by whole mount observations. Simvastatin feeding produced an increased development of ER- PgR- tumours and a reduced incidence of ER+ PgR+ tumours. These findings suggest that simvastatin has a potent preventive activity during the DES-dependent promotion/progression phase of radiation-induced mammary tumorigenesis.

Administration, Oral↗

PubMed2001

Fractionated stereotactically guided radiotherapy and radiosurgery in the treatment of functional and nonfunctional adenomas of the pituitary gland.

PURPOSE: We evaluated survival rates and side effects after fractionated stereotactically guided radiotherapy (SCRT) and radiosurgery in patients with pituitary adenoma. METHODS AND MATERIALS: Between 1989 and 1998, 68 patients were treated with FSRT (n = 63) or radiosurgery (n = 5) for pituitary adenomas. Twenty-six had functional and 42 had nonfunctional adenomas. Follow-up included CT/MRI, endocrinologic, and ophthalmologic examinations. Mean follow-up was 38.7 months. Seven patients received radiotherapy as primary treatment and 39 patients received it postoperatively for residual disease. Twenty-two patients were treated for recurrent disease after surgery. Mean total dose was 52.2 Gy for SCRT, and 15 Gy for radiosurgery. RESULTS: Overall local tumor control was 93% (60/65 patients). Forty-three patients had stable disease based on CT/MRI, while 15 had a reduction of tumor volume. After FSRT, 26% with a functional adenoma had a complete remission and 19% had a reduction of hormonal overproduction after 34 months' mean. Two patients with STH-secreting adenomas had an endocrinologic recurrence, one with an ACTH-secreting adenoma radiologic recurrence, within 54 months. Reduction of visual acuity was seen in 4 patients and partial hypopituitarism in 3 patients. None of the patients developed brain radionecrosis or radiation-induced gliomas. CONCLUSION: Stereotactically guided radiotherapy is effective and safe in the treatment of pituitary adenomas to improve local control and reduce hormonal overproduction.

Adenoma↗

PubMed1978

Evaluation of the results of trans-sphenoidal surgery in acromegaly by assessment of the growth hormone response to thyrotrophin-releasing hormone.

Eighteen acromegalic patients GH-responsive to TRH were reinvestigated following trans-sphenoidal surgery and radiotherapy. Basal serum GH decreased below 10 microgram/1 in thirteen cases; nine of them became GH-unresponsive to TRH 1 month after operation, and another one following conventional pituitary irradiation. Four of these ten patients also showed a normal GH response to L-Dopa after treatment, and five responded normally to insulin-induced hypoglycaemia; two patients had a normal GH secretory pattern after both these stimuli. No recurrences were observed over a follow-up period of 15-80 months among the ten patients who became GH-unresponsive to TRH following operation, while one of the three subjects still responsive to TRH in spite of normalized basal serum GH concentration relapsed 10 months after surgery. Three patients with normalized TRH test following operation were repeatedly reinvestigated over a 3-6 years period and always found unresponsive. The present study shows that the 'paradoxical' GH responses to TRH and L-Dopa frequently disappear after surgery, that complete normalization of GH secretory pattern may rarely be attained, and that the disappearance of GH response to TRH probably indicates satisfactory treatment of acromegaly. These data suggest that the 'paradoxical' GH responses frequently found in acromegaly are dependent on the adenoma per se and not on hypothalamic dysfunction.

Acromegaly↗

PubMed1990

Transplantation analysis of B cell destruction in (NOD x CBA)F1 mouse bone marrow chimeras.

F1 hybrids produced by outcross of non-obese diabetic (NOD) mice with diabetes resistant strains are also diabetes resistant. This resistance is abrogated if F1 hybrids are lethally irradiated and then haematopoietically reconstituted with NOD bone marrow. This model was employed to determine whether T lymphocyte recognition and elimination of pancreatic B cells in NOD mice is restricted by the MHC haplotype of the target B cell. Diabetes resistant (NOD/Lt x CBA/J)F1 hybrids were lethally irradiated and reconstituted with NOD/Lt bone marrow. Following haematopoietic reconstitution, donor matched NOD/Lt or CBA/J pancreatic islet and anterior pituitary grafts were grafted under a renal capsule to determine whether effector cells derived from NOD/Lt marrow progenitors would reject islet grafts in a MHC restricted fashion. The H-2k haplotype expressed by CBA/J mice differs from all known loci of the unique H-2 haplotype of NOD; therefore, if NOD/Lt T lymphocytes eliminate pancreatic B cells in a MHC restricted fashion. NOD islet grafts would be eliminated in these chimeras while CBA islet grafts would be retained. Overt diabetes developed in 80% of the female and 40% of the male F1 hybrids following reconstitution with NOD/Lt marrow, while no hybrids reconstituted with CBA/J marrow became diabetic through a year of age. The retention of CBA/J skin and pituitary grafts in NOD/Lt marrow reconstituted F1 hybrids confirmed that the F1 thymic environment imparted tolerance to CBA/J alloantigens. Nonetheless, responses to a T cell dependent model antigen were restricted to the unique MHC haplotype of NOD. This was associated in the hyperglycaemic chimeras with rejection (8-21 days post-implantation) of both CBA/J and NOD/Lt islet grafts.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

GHRF test in acromegalic patients for the evaluation of therapeutic results.

We studied here the clinical significance of GHRF test in evaluating therapeutic results in patients with acromegaly. Three cases of acromegaly were studied at pre- and posttreatment. Case 1 is a 42 year old woman, and her plasma GH showed slight increases responding to TRH and arginine administration before therapy. Eleven years after the pituitary irradiation, basal plasma GH decreased to low normal ranges and showed no response to the above two agents. Only an insufficient increase in plasma GH was observed after GHRF injection. This case would have pituitary lesions not only in the tumor somatotrophs but also in the normal somatotrophs. Case 2 is a 38 year old man. His plasma GH showed a marked increase after TRH injection. To GHRF administration, however, no clear response was observed. After transsphenoidal adenomectomy, the aberrant responses to TRH was still observed despite the marked GH decrease to the near normal ranges. Interestingly, plasma GH became responsive to GHRF after the operation. It seems that the adenomectomy was inadequate in this case and the normal somatotrophs recovered the responsiveness to GHRF. Case 3 is a 53 year old woman, and she showed aberrant GH responses to TRH and to L-dopa. Her plasma GH clearly increased after GHRF injection. Postoperatively, the abnormal responses of plasma GH disappeared completely, while a normal GH response was observed following GHRF injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗

PubMed1998

Surgery combined with dopamine agonists versus dopamine agonists alone in long-term treatment of macroprolactinoma: a retrospective study.

We retrospectively analysed the long-term treatment results (median 8 years) of 31 patients with macroprolactinoma. 17 patients were treated by pituitary surgery (group 1) followed by long-term dopamine agonist therapy whereas 14 patients received long-term dopamine agonist therapy alone (group 2). 2 patients of group 1 and 1 patient of group 2 had external pituitary irradiation because of progressive disease. The two groups were comparable with respect to age, gender and initial prolactin (PRL) levels. At the end of the observation period dopamine agonist dosage could be reduced by 50% in group 1 and by 39.3% in group 2. Pituitary function did not change substantially during therapy. Complete remissions (no visible tumour in CT or MRI, normal PRL levels under current dopamine agonist medication) were achieved in 23.5% of group 1 vs. 21.4% of group 2, partial remissions (reduction of PRL and tumour size) in 35.3% vs. 64.3%, stable disease in 23.5% vs. 7.1% and progressive disease in 17.7% vs. 7.1% (differences not significant). Visual field defects showed 28.4% remissions (complete and partial) in group 1 versus 50% in group 2. Dopamine agonist therapy could be stopped definitively in only 1 patient of group 2 with an invasive macroprolactinoma. Initial surgical reduction of tumour load followed by medical therapy does not seem to guarantee a better long-term outcome than dopamine agonist therapy alone if the patient responds to and tolerates dopamine agonist therapy. Surgery should be reserved for non-responders, drug-intolerant or non-compliant patients, and for those with acute severe neurological compromise.

Adolescent↗

PubMed1986

In-vitro secretion of inhibin-like activity by Sertoli cells from normal and prenatally irradiated immature rats.

The influence of in-vitro conditions on the production of inhibin by Sertoli cells from 21-day-old normal and prenatally irradiated rat testes was studied by measuring inhibin activity in culture media, using the suppression of the release of FSH from cultured rat pituitary cells. Sertoli cells secreted inhibin-like activity during at least 21 days of culture, and cells cultured at 37 degrees C produced significantly more inhibin than those cultured at 32 degrees C. The presence of fetal calf serum had no significant effect on inhibin production at 32 degrees C, while at 37 degrees C the production was decreased. The presence of ovine FSH stimulated inhibin secretion, while inhibin concentrations in Sertoli cell culture media were decreased after the addition of testosterone. Testosterone, added together with ovine FSH, suppressed inhibin secretion when compared with the levels found in the presence of FSH alone. The presence of spermatogenic cells decreased the release of inhibin. From these results it was concluded that both Sertoli cells isolated from normal immature rat testes and those from testes without spermatogenic cells can secrete inhibin-like activity in culture. A number of discrepancies with in-vivo observations was observed. Therefore, it is likely that the in-vivo situation is too complicated for direct study of the regulation of inhibin production, because of mutual interactions between the testicular compartments.

Animals↗

PubMedDate not supplied

Survival following alpha particle pituitary irradiation for diabetic retinopathy.

The purpose of this study was to evaluate the mortality experience of persons with longstanding diabetes who had received pituitary irradiation for diabetic retinopathy compared to a matched group of persons with diabetes who had not had pituitary ablation. The irradiated cohort consisted of 167 patients treated at the Donner Pavilion (Lawrence Berkeley Laboratory, University of California, Berkeley), and the comparison cohort was the population evaluated in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR). Survival analyses were performed comparing the two cohorts using three different sets of matching criteria, each more restrictive than the previous analyses. The three different strategies were (1) matched only on severity of diabetic retinopathy; (2) matched on severity of retinopathy and age; and (3) matched on severity of retinopathy, age, gender, and hypertension status. Tests of comparison were the log-rank test, the Wilcoxon test, and the likelihood ratio test. For the model matching only on severity of retinopathy, mean survival was 8.3 years for the WESDR group and 9.4 years for the ablated group (p > 0.05 for all three statistical tests). For the model matched on retinopathy and age, mean survival was 8.9 years for the WESDR group and 9.2 years for the ablated group (p=0.05 log-rank test, 0.32 Wilcoxon test, and 0.06 likelihood ratio test). For the model matching on retinopathy, age, gender, and hypertension status, mean survival was 8.9 years for the WESDR group and 11.6 years for the ablated group (p=0.72 log-rank test, 0.08 Wilcoxon test, and 0.82 likelihood ratio test). These data are compatible with the notion that pituitary ablation, and therefore induced pituitary growth hormone deficiency, may not decrease survival in those with severe diabetic retinopathy.

Adult↗

PubMed1992

[Medulloblastoma: analysis of 14 cases treated at the J. Bordet Institute and literature review].

Between 1966 and 1986, 14 patients with histologically verified cerebellar medulloblastomas were seen at J. Bordet Institute after total (4 cases) or partial (10 cases) tumor removal. Twelve received postoperative irradiation after some courses of chemotherapy (Vincristine, Procarbazine, Methotrexate) for 5. In 10 cases the X ray treatment was given to the whole cerebrospinal axis with approximately 50 Gy delivered to the primary tumor site, 25-35 Gy to the remaining brain and spinal cord. As in other series of the literature the long term prognosis is not too good, with approximately 50% of the patients surviving more than 5 years. Failure at the primary site happened in 4 cases. As a consequence of the small number of patients treated, no conclusion can be drawn from risk factor analysis. Yet it appears that younger patients fared better than older ones. A detailed description of the side effects of the treatment is therefore given for the five children treated at prepubertal age: some growth impairment seems to be the rule, a consequence of GH deficiency--if not compensated--and of the direct effect of ionizing radiation on the vertebral bodies. While discussing the progress of neurosurgery and radiotherapy for the treatment of medulloblastoma, the authors emphasize the need of more efficient adjuvant chemotherapy regimens and the interest of multicenter trial for evaluating them.

Adolescent↗

PubMed1994

Radiotherapy for nasopharyngeal carcinoma: shielding the pituitary may improve therapeutic ratio.

PURPOSE: Nasopharyngeal carcinoma (NPC) is well known for its invasiveness and erosion of the base of the skull is not uncommon. Before the advent of computed tomography, the evaluation of the base of the skull was by plain radiography. Because of the low sensitivity of these investigations, traditional teaching has included the sphenoid sinus in the volume of irradiation. Increase in longevity of patients allows the manifestation and documentation of the long-term sequelae of irradiating the hypothalamic-pituitary axis and the temporal lobes. This study is an attempt to evaluate whether the hypothalamic-pituitary axis can be shielded from the target volume in a proportion of NPC patients. METHODS AND MATERIALS: One hundred fifty-two NPC patients with no evidence of erosion of the base of the skull and sphenoid, nor extension to the nasal fossa and ethmoid sinuses were randomized to receive standard radiotherapy covering the whole sphenoid sinus or radiotherapy using a modified technique that shields the pituitary and the anterior part of the hypothalamus. This modified technique also shields a large part of the lower temporal lobes that are otherwise covered by standard treatment portals. The characteristics and treatment of the two subgroups of patients were otherwise comparable. RESULTS: At a median follow-up of 31.5 months, the tumor control between the two subgroups of patients were comparable (p = 0.3928). However, 8 of the 71 patients in the unshielded group had developed symptomatic neuroendocrine complications, while none of the other group did (p = 0.0061). Two patients developed secondary hypothyroidism, one patient developed oligomenorrhoea associated with raised prolactin, and five patients developed temporal lobe necrosis. CONCLUSIONS: The protective effect on neuroendocrine complication of this shield was demonstrated at median follow-up of 31.5 months, and the local control was not jeopardized. Modification of treatment technique as presently described, which is applicable to one-third of NPC patients to improve the therapeutic ratio, is recommended for general use.

Adult↗

PubMed2005

Function of the hypothalamic-pituitary-gonadal axis in long-term survivors of hematopoietic stem cell transplantation for hematological diseases.

Gonadal dysfunction in adult long-term survivors of hematopoietic stem cell transplantation (HSCT) is an adverse effect of conditioning regimens consisting of chemotherapy and total body irradiation (TBI). The impact of conditioning regimens consisting of chemotherapy alone on the function of the hypothalamic-pituitary-gonadal (HPG) axis was evaluated in a series of 41 female and 31 male patients who had undergone either autologous or allogeneic bone marrow/peripheral blood stem cell transplantation; mean age at transplantation was 32.6 years and mean time interval from transplantation was 1.5 years (range 0.2-9.8 years). Provocative testing of the HPG axis by administration of luteinizing hormone-releasing hormone was included in the first endocrinological evaluation. The follow-up period extended to three consecutive years. Gonadal dysfunction was not reported by any of the patients prior to their underlying illness. Hypergonadotrophic hypogonadism was observed in 97% of female and 19% of male patients. Leydig cell strain (normal testosterone, high luteinizing hormone levels) was evident in 32% and spermatogenesis damage (high follicle-stimulating hormone levels) in 68% of the male population. At the conclusion of the study four women (10%) had regained spontaneous menses and all hypogonadal men had resumed normal testosterone levels. Our results indicate a high incidence of gonadal dysfunction due to target organ failure in HSCT recipients not treated by TBI.

Adult↗

PubMed2004

Exocytosis sensitivity to growth hormone-releasing hormone in subsets of GH cells in rats under different corticosterone conditions. Ultrastructural study using microwave irradiation for fixation and immunocytochemistry.

Growth hormone (GH) cells in the rat anterior pituitary have been morphologically classified into three subtypes: type I (mature) containing large secretory granules about 350 nm in diameter, type II (intermediate) containing a mixture of large and small granules, and type III (immature) containing small granules about 150 nm in diameter. However, the functional implications of morphological heterogeneity, especially the different sensitivities to growth hormone-releasing hormone (GRH) under different corticosteroid conditions have not been elucidated to date. In the present study, by application of microwave irradiation (MWI) for fixation and immunocytochemistry, new findings of the exocytotic response have been revealed among the subsets of GH cells following adrenalectomy (ADX), corticosterone treatment and/or GRH treatment. The MWI gave effective results for fixation, especially for the permeability of the fixative, and showed good results for immunoelectron microscopy using the protein-A gold method. Moreover, the use of MWI greatly shortened the fixation, processing and immunolabeling times without compromising the quality of ultrastructural preservation and the specificity of labeling. The number of exocytotic figures was low in all subtypes of GH cells in the sham-operated control rats. GRH treatment induced a significant increase in exocytosis in each subtype of GH cells, particularly in type I (mature) and type II (intermediate) GH cells in the control rats. GRH injection to rats for 4 days after ADX also showed an increase in exocytosis, but the degree was significantly less in comparison with the GRH injection in the control group. Corticosterone replacement given to ADX rats induced a clear recovery of the exocytotic response to GRH to the control level. Serum GH content measured by radioimmunoassay correlated with these morphological results. These results suggest that the secretion of GH stimulated by GRH is closely related to corticosteroids, and that the sensitivity to GRH differs among the three subtypes of GH cells.

Animals↗

PubMed1989

Androgen-dependent somatotroph function in a hypogonadal adolescent male: evidence for control of exogenous androgens on growth hormone release.

A 14(10/12)-year-old white male with primary gonadal failure following testicular irradiation for acute lymphocytic leukemia was evaluated for poor growth. He had received 2400 rad of prophylactic cranial irradiation. The growth velocity had decelerated from 7 to 3.2 cm/yr over 3 years. His bone age was 12(0/12) years (by TW2-RUS), and his peak growth hormone (GH) response to provocative stimuli was 1.4 ng/mL. The 24-hour GH secretion was studied by drawing blood every 20 minutes for 24 hours. The resulting GH profile was analyzed by a computerized pulse detection algorithm, CLUSTER. Timed serum GH samples were also obtained after a 1 microgram/kg IV bolus injection of the GH releasing factor (GRH). The studies showed a flat 24-hour profile and a peak GH response to GRH of 3.9 ng/ml. Testosterone enanthate treatment was started, 100 mg IM every 4 weeks. Ten months after the initiation of therapy the calculated growth rate was 8.6 cm/yr. The 24-hour GH study and GRH responses were repeated at the time, showing a remarkably normal 24-hour GH secretory pattern and a peak GH response to GRH of 14.4 ng/mL. Testosterone therapy was discontinued, and 4 months later similar studies were repeated. A marked decrease in the mean 24-hour GH secretion and mean peak height occurred, but with maintenance of the GH pulse frequency. The GH response to GRH was intermediate, with a peak of 8 ng/mL. There was no further growth during those 4 months despite open epiphyses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1981

Pituitary function in prolactinoma. Effect of surgery and postoperative bromocriptine therapy.

Forty-five women and fifteen men with prolactinomas have been treated surgically. Patients with large tumours received pituitary irradiation and postoperative hyperprolactinaemia was treated with bromocriptine. The patients have been followed-up for 6-36 months following the operation. The tumours were larger and the levels of production higher in men as compared with women. All women had amenorrhoea. Galactorrhoea was present in forty-three women but not in the men. After surgery serum prolactin levels fell significantly in all women but remained above normal in thirty-six; prolactin remained high in twelve men. Bromocriptine effectively decreased the postoperative hyperprolactinaemia. The surgical complications were oculomotor nerve paresis in one woman and one man. After surgery six (23%) women developed impaired GH secretion, six (15%) impaired thyroid function, eight (18%) impaired cortisol secretion and five (17%) impaired LH secretion in isolation or combination which had not been present preoperatively. Three patients relapsed. Fifteen women menstruated after surgery and ten began to do so during the subsequent bromocriptine treatment. Thus, menstruation was restored in all six women with microadenomas in sixteen of twenty patients with intrasellar macroadenomas and three of nineteen patients with suprasellar adenomas. The preoperative LH-reserve proved to be an important prognostic indicator. Nine patients, i.e. 50% of patients desiring fertility became pregnant. In the men gonadal function deteriorated in four patients and did not improve in any without testosterone treatment.

Adenoma↗

PubMed2000

Three-dimensional intensity-modulated radiotherapy in the treatment of nasopharyngeal carcinoma: the University of California-San Francisco experience.

PURPOSE: To review our experience with three-dimensional intensity-modulated radiotherapy (IMRT) in the treatment of nasopharyngeal carcinoma. METHODS AND MATERIALS: We reviewed the records of 35 patients who underwent 3D IMRT for nasopharyngeal carcinoma at the University of California-San Francisco between April 1995 and March 1998. According to the 1997 American Joint Committee on Cancer staging classification, 4 (12%) patients had Stage I disease, 6 (17%) had Stage II, 11 (32%) had Stage III, and 14 (40%) had Stage IV disease. IMRT of the primary tumor was delivered using one of the following three techniques: (1) manually cut partial transmission blocks, (2) computer-controlled autosequencing static multileaf collimator (MLC), and (3) Peacock system using a dynamic multivane intensity-modulating collimator (MIMiC). A forward 3D treatment-planning system was used for the first two methods, and an inverse treatment planning system was used for the third method. The neck was irradiated with a conventional technique using lateral opposed fields to the upper neck and an anterior field to the lower neck and supraclavicular fossae. The prescribed dose was 65-70 Gy to the gross tumor volume (GTV) and positive neck nodes, 60 Gy to the clinical target volume (CTV), and 50-60 Gy to the clinically negative neck. Eleven (32%) patients had fractionated high-dose-rate intracavitary brachytherapy boost to the primary tumor 1-2 weeks following external beam radiotherapy. Thirty-two (91%) patients also received cisplatin during, and cisplatin and 5-fluorouracil after, radiotherapy. Acute and late normal tissue effects were graded according to the Radiation Therapy Oncology Group (RTOG) radiation morbidity scoring criteria. Local-regional progression-free, distant metastasis-free survival and overall survival were estimated using the Kaplan-Meier method. RESULTS: With a median follow-up of 21.8 months (range, 5-49 months), the local-regional progression-free rate was 100%. The 4-year overall survival was 94%, and the distant metastasis-free rate was 57%. The worst acute toxicity was Grade 2 in 16 (46%) patients, Grade 3 in 18 (51%) patients and Grade 4 in 1 (3%) patient. The worst late toxicity was Grade 1 in 15 (43%), Grade 2 in 13 (37%), and Grade 3 in 5 (14%) patients. Only 1 patient had a transient Grade 4 soft-tissue necrosis. At 24 months after treatment, 50% of the evaluated patients had Grade 0, 50% had Grade 1, and none had Grade 2 xerostomia. Analysis of the dose-volume histograms (DVHs) showed that the average maximum, mean, and minimum dose delivered were 79.5 Gy, 75.8 Gy, and 56.5 Gy to the GTV, and 78.9 Gy, 71.2 Gy, and 45.4 Gy to the CTV, respectively. An average of only 3% of the GTV and 2% of the CTV received less than 95% of the prescribed dose. The average dose to 5% of the brain stem, optic chiasm, and right and left optic nerves was 48.3 Gy, 23.9 Gy, 15.0 Gy, and 14.9 Gy, respectively. The average dose to 1 cc of the cervical spinal cord was 41.7 Gy. The doses delivered were within the tolerance of these critical normal structures. The average dose to 50% of the right and left parotids, pituitary, right and left T-M joints, and ears was 43. 2 Gy, 41.0 Gy, 46.3 Gy, 60.5 Gy, 58.3 Gy, 52.0 Gy, and 52.2 Gy, respectively. CONCLUSION: 3D intensity-modulated radiotherapy provided improved target volume coverage and increased dose to the gross tumor with significant sparing of the salivary glands and other critical normal structures. Local-regional control rate with combined IMRT and chemotherapy was excellent, although distant metastasis remained unabated.

Adolescent↗

PubMed1995

External radiotherapy of pituitary adenomas.

PURPOSE: To evaluate therapeutic outcome and side effects of radiotherapy in pituitary adenomas as sole or combined treatment. METHODS AND MATERIALS: Retrospective analysis of 138 patients (74 male, 64 female) irradiated for pituitary adenoma from 1972 to 1991 was performed. Mean age was 49.7 years (15-80 years). Regular follow-up (in the mean 6.53 +/- 3.99 years) included radiodiagnostical [computed tomography (CT), magnetic resonance imaging (MRI), x-ray], endocrinological, and ophthalmological examinations. Seventy patients suffered from nonfunctional pituitary adenoma, 50 patients suffered from growth-hormone producing adenomas, 11 had prolactinomas, and 7 patients had adrenocorticotropic hormone (ACTH) producing pituitary adenomas. In 99 patients surgery was followed by radiotherapy in case of suspected remaining tumor (invasive growth of the adenoma, assessment of the surgeon, pathologic CT after surgery, persisting hormonal overproduction). Twenty-three patients were treated for recurrence of disease after surgery and 16 patients received radiation as primary treatment. Total doses from 40-60 Gy (mean: 45.5 Gy) were given with single doses of 2 Gy 4 to five times a week. RESULTS: Tumor control was achieved in 131 patients (94.9%). In seven patients, recurrence of disease was diagnosed in the mean 2.9 years (9-98 months) after radiotherapy and salvaged by surgery. A statistically significant dose-response relationship was found in favor of doses > or = 45 Gy. Ninety percent of the patients with hormonally active pituitary adenomas had a benefit from radiotherapy in means of complete termination (38%) or at least reduction (52%) of hormonal overproduction. Partial or complete hypopituitarism after radiotherapy developed, depending on hormonal axis, in 12 (prolactin) to 27% (follicle-stimulating hormone FSH) of patients who had not already had hypopituitarism prior to radiation. Two out of 138 patients suffered reduction of visual acuity, which was, in part, related to radiotherapy. Both therapeutic effects and side effects occurred after a latency period of 3 months up to 9 years. CONCLUSION: We conclude that radiotherapy of pituitary adenomas, using modern treatment planning techniques, is effective and safe. To achieve optimal tumor control, doses of 45-48 Gy (conventionally fractionated) should be applied.

Adenoma↗

PubMed1989

Megavoltage pituitary irradiation in the management of Cushing's disease and Nelson's syndrome: long-term follow-up.

We report the long-term follow-up of the clinical and biochemical effects of megavoltage pituitary irradiation (radiotherapy; RT), administered as primary or secondary therapy, for pituitary Cushing's disease and Nelson's syndrome in 52 patients. Irradiation was administered, from a 4-15 MeV linear accelerator, via a three-field technique (two lateral, one frontal), to a total dose of 4500 cGy (rad) in 25 fractions over 35 days. Twenty-one patients received RT as primary ablative therapy for Cushing's disease and were under follow-up 5.8 to 15.5 years later (median 9.5 years). All were initially treated with metyrapone to induce normal mean plasma cortisol levels, and all achieved clinical remission on this therapy. At latest follow-up, 12 (57%) are off all therapy, in clinical remission, with a normal mean cortisol through the day; however, only two show completely normal plasma cortisol responses to dynamic testing; four remain on medical therapy with metyrapone or op'DDD and all have required a steady dose reduction accompanied by falling plasma ACTH levels; five have required alternative therapy with bilateral adrenalectomy and/or transsphenoidal hypophysectomy. Fifteen patients received RT for Nelson's syndrome, developing after bilateral adrenalectomy, and have been followed up for 1.5 to 17.3 years (median 9.6 years). Fourteen patients showed progressive depigmentation, shrinkage of the pituitary adenoma and fall in plasma ACTH levels to 1-72% (median 16%) of the pre-RT basal value. In the remaining patient an initial fall in plasma ACTH was followed by tumour enlargement at 6 years, leading to death at 11 years after RT. Of the remaining patients, results are assessed in nine who received RT after unsuccessful transsphenoidal surgery, three after transfrontal surgery for aggressive macroadenomas, and four prophylactically after bilateral adrenalectomy. Radiotherapy remains a valuable second-line therapy for Cushing's disease and its complications.

Adolescent↗

PubMed2001

Development of growth hormone and adrenocorticotropic hormone deficiencies in patients with prenatal or perinatal-onset hypothalamic hypopituitarism having invisible or thin pituitary stalk on magnetic resonance imaging.

A gradual loss of anterior pituitary hormones is suspected in patients treated with irradiation due to brain tumors. Development of growth hormone deficiency (GHD) with age has been documented in patients with idiopathic GHD. A gradual loss of adrenocorticotropic hormone (ACTH) secretion has been also shown in a patient with severe GHD and an invisible pituitary stalk on magnetic resonance imaging (MRI). The purpose of this longitudinal and cross-sectional study was to evaluate the gradual loss of growth hormone (GH) and ACTH in a homogeneous group of patients with hypopituitarism. Twenty-eight patients (23 males, 5 females) from four hospitals were diagnosed as having prenatal or perinatal-onset hypothalamic hypopituitarism. They had an abnormal pituitary stalk on MRI (invisible in 18 patients, thin in 10 patients) without any other organic disease of the brain. Each patient had GHD upon initial evaluation. Height (n=20) was analyzed as standard deviation score (SDS). Longitudinal (n=8) and cross-sectional (n=28) GH secretion capacity was evaluated by GH peaks, in response to insulin tolerance test (ITT) and growth hormone releasing factor test (GRF test). Longitudinal (n=10) and cross-sectional (n=28) ACTH secretion capacity was evaluated by cortisol peaks in response to ITT. Height SDS decreased each year in all the untreated patients after birth. GH peaks decreased gradually with age. Longitudinal data showed decreased GH peaks with age in seven out of eight patients using ITT and in all four patients using GRF tests. Cortisol peaks also decreased gradually together with signs and symptoms for adrenal deficiency such as general fatigue. Cortisol peaks of less than 414 nmol/L (15 microg/dl) in response to ITT were seen in 24% of the tests before age 10 and 56% before age 25. In conclusion, GHD and ACTH deficiency developed gradually in patients with prenatal or perinatal-onset hypothalamic hypopituitarism who had invisible or thin pituitary stalks examined by MRI.

Adolescent↗