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Thyroid abnormalities after therapeutic external radiation.

The thyroid gland is the largest pure endocrine gland in the body and one of the organs most likely to produce clinically significant abnormalities after therapeutic external radiation. Radiation doses to the thyroid that exceed approximately 26 Gy frequently produce hypothyroidism, which may be clinically overt or subclinical, as manifested by increased serum thyrotropin and normal serum-free thyroxine concentrations. Pituitary or hypothalamic hypothyroidism may arise when the pituitary region receives doses exceeding 50 Gy with conventional, 1.8-2 Gy fractionation. Direct irradiation of the thyroid may increase the risk of Graves' disease or euthyroid Graves' ophthalmopathy. Silent thyroiditis, cystic degeneration, benign adenoma, and thyroid cancer have been observed after therapeutically relevant doses of external radiation. Direct or incidental thyroid irradiation increases the risk for well-differentiated, papillary, and follicular thyroid cancer from 15- to 53-fold. Thyroid cancer risk is highest following radiation at a young age, decreases with increasing age at treatment, and increases with follow-up duration. The potentially prolonged latent period between radiation exposure and the development of thyroid dysfunction, thyroid nodularity, and thyroid cancer means that individuals who have received neck or pituitary irradiation require careful, periodic clinical and laboratory evaluation to avoid excess morbidity.

Humans↗

Stimulation of guanosine 3',5'-monophosphate accumulation in anterior pituitary glands in vivo by synthetic luteinizing hormone-releasing hormone.

The in vivo effect of an iv injection of synthetic LHRH on cAMP and cGMP concentrations in the anterior pituitary gland of pentobarbital (31.5 mg/kg BW)-injected proestrous rats and ovariectomized estradiol (10 micrograms)-primed rats was studied. At a specific time after an injection of LHRH or saline (as the control), the animals were sacrificed by microwave irradiation to the head. LHRH (100 ng/100 g BW) injection in the proestrous rat caused a significant increase in the cGMP level from 10-20 min associated with an increase in the serum LH level, whereas it exerted no effect on cAMP. No changes were observed in saline-injected animals. In the ovariectomized estradiol-primed rat, LHRH (50 ng/100 g BW) injection performed under ether anesthesia also induced a significant elevation of cGMP level, after 5-10 min, in parallel with an elevation of serum LH level. Saline injection caused no change in cGMP. cAMP concentrations were increased 5-10 min after either LHRH or saline injection. These results suggest the involvement of a guanylate cyclase-cGMP mechanism in the mediation of LHRH action in the pituitary.

Animals↗

Delayed cerebral radiation necrosis.

The clinical features and long-term outcome of seven patients with delayed cerebral radiation necrosis (DCRN) are described. Radiotherapy had been given for pituitary tumour (1), astrocytoma (2), pinealoma (2), craniopharyngioma (1) and parotid carcinoma (1). The mean latency to onset of the first neurological symptoms was 22 months (range 6-40 months), and mean duration of follow-up was 86 months (range 60-126). Three patients died at a mean of 84 months after radiotherapy (range 62-98). A fourth patient probably died from metastatic disease. Three patients remain alive, albeit severely disabled, after 5-10 years. The illness typically ran a stepwise course, with fits and stroke-like episodes occurring against a background of progressive dementia and somnolence. CT and MRI scans showed progressive ventricular dilatation associated with cerebral atrophy and diffuse or focal changes in the white matter. Four patients had had two or more neurosurgical procedures after the radiotherapy. In only one of the seven patients was the diagnosis made at presentation. DCRN produces a distinctive clinical picture, yet remains a poorly recognized complication of cranial irradiation.

Adolescent↗

Effects of whole-body 50-Hz magnetic field exposure on mouse Leydig cells.

The main goal of this study was to evaluate the possible effect of whole-body magnetic field (MF) exposure on the steroidogenic capacity of Leydig cells in vitro. In four separate experiments, male CFLP mice were exposed to sinusoidal 50-Hz, 100-microT MF. The duration of exposure was 23.5 h/day over a period of 14 days. At the end of the exposure, interstitial (Leydig) cells were isolated from the testicles of the sham-exposed and exposed animals. The cells were cultured for 48 h in the presence or absence of 1, 10, or 100 mIU/ml human chorionic gonadotropin (hCG). The luteinizing hormone (LH) analog hCG was used to check the testosterone (T) response of the sham-exposed controls and to evaluate the possible effect of the whole-body MF exposure on the steroidogenic capacity of Leydig cells in vitro. Testosterone content of the culture media and blood sera was measured by radioimmunoassay (RIA). In the cultures obtained from MF-exposed animals, the hCG-stimulated T response was significantly higher (p < 0.01) compared with the sham-exposed controls, while the basal T production of cells and the level of serum T remained unaltered. No MF exposure-related histopathological alterations were found in testicles, epididymes, adrenals, prostates, and pituitary glands. The MF exposure did not affect the animal growth rate and the observed hematologic and serum chemical variables. Our results indicate a presumably direct effect of whole-body MF exposure on the hCG-stimulated steroidogenic response of mouse Leydig cells.

Adrenal Glands↗

Successful treatment of recurrent malignant germ cell tumors: report of two cases.

We report two patients with recurrent malignant germ cell tumors who were successfully treated with radiation therapy and cisplatin combination chemotherapy. Patient 1, who had a suprasellar mixed yolk sac tumor, had been free of tumor for 3.5 years after cisplatin/vinblastine/bleomycin combination chemotherapy alone but showed a recurrent tumor in the pineal region. In Patient 2, who had a pineal alpha-fetoprotein-producing tumor, recurrent tumors appeared in the lateral ventricle 3 years after the tumor was controlled by radiation and cisplatin/vinblastine/bleomycin therapy. They were treated successfully again by radiation therapy, followed by cisplatin and etoposide combination therapy, and they have been free of tumor for 5.5 and 7 years after recurrence, respectively. The total dose of cisplatin in both patients exceeded 1,000 mg/m2, which would have contributed to the control of the recurrent tumors. Anterior pituitary dysfunction observed in Patient 1 did not improve, even after tumor disappearance by chemotherapy, suggesting severe damage to the neurohypophysis by direct invasion of the tumor.

Adolescent↗

Growth, growth hormone and final height after BMT. Possible recovery of irradiation-induced growth hormone insufficiency.

The aim of the present study was to assess growth, final height, growth hormone (GH) secretion and growth factors after BMT including TBI in childhood. The median age of the 25 participants was 11.3 years at BMT, and a median of 7.5 years had elapsed since BMT. The median height standard deviation score (SDS) declined significantly from diagnosis until 4 years after BMT (n = 25, P = 0.015), and decreased 1.08 SDS from diagnosis until final height (n = 14, P = 0.030). Sitting height to standing height ratio was impaired, -0.64 SDS, P < 0.05. GH insufficiency was found in 32% at follow-up. Repeated assessments of GH production over the years indicated improvement in GH secretion in nine individuals. Evaluation of spontaneous 24-h GH secretion indicated a secretory pattern similar to controls, although the total amount of GH secreted was lower. Neither insulin-like growth factor-1 (IGF-1) nor IGF binding protein-3 (IGFBP-3) alone could be used as a marker of GH insufficiency. IGF-1 was low: -1.18 SDS; (P < 0.001). In conclusion, our study demonstrated the impact on growth, final height, body proportions, GH secretion and growth factors after BMT including TBI. We hypothesize that children who receive BMT at a younger age are more at risk of loss of final height and abnormal body proportions. Our data indicate that some improvement in GH production may occur over the years.

Adolescent↗

Three-dimensional dosimetric evaluation of a conventional radiotherapy technique for treatment of nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: The aim of this study is to evaluate and delineate the deficiencies in conventional two-dimensional (2-D) radiotherapy planning of nasopharyngeal carcinoma (NPC) treatment and to explore the means for improvement of the existing treatment technique aiming at enhancing local tumor control and reducing treatment complications. METHODS AND MATERIALS: Ten patients with NPC sparing the skull base and without intracranial extension or cranial nerve(s) palsy were chosen in the present study. Two sets of CT images for Phases I and II of the radiotherapy treatment were taken with patient immobilized in the flexed-head and the extended-head positions, respectively. Based on the CT images and endoscopic findings, the gross tumor volume (GTV) was defined. The clinical target volume (CTV) circumscribing the GTV was defined according to Ho's (Halnan, K.E. (ed.) Treatment of Cancer. London: Chapman and Hall, 1982. pp. 249-268) description of the organs at risk of tumor infiltration. The planning target volume (PTV) was defined by adding a margin to the CTV which catered for geometrical inaccuracies. The field borders and shields were set at standard distances from certain bony landmarks and were drawn on the simulator radiograph. Data on the beams and shield arrangements were then transferred to the planning computer via a digitizer. By applying 3-D volumetric dose calculation using a commercial three-dimensional (3D) treatment planning computer, the dose-volume-histograms (DVHs) of GTV, CTV, PTV and critical normal organs were generated for both phases of Ho's treatment technique. The same patients were re-planned using a modified Ho's technique which used 3-D beams-eye-view (BEV) in placing the shielding blocks and the same set of DVHs were generated and compared with those obtained from Ho's technique. RESULTS: The median volumes of GTV, CTV and PTV covered by the 95% isodose in Ho's phase I treatment were around 60%. The dose coverage was unsatisfactory in the superior and inferior and the posterolateral regions. In phase II treatment, the median volume of GTV, CTV and PTV covered by the 95% isodose were 99, 96 and 72%, respectively. Even though the dose coverage of the PTV in both phases of treatment were unsatisfactory, radiotherapy with the original Ho's technique had consistently produced good local control for NPC. However, there is potential room for enhancing the local control further because after modifying Ho's technique by using 3-D BEV customization of the treatment portals, the median volume of the target covered by the 95% isodose was defined as V(95). The V(95) of the PTV during the Phase II treatment was improved by 13%. The 90% of the volume of temporo-mandibular joints and parotid glands were both irradiated to 53 Gy and 43.6 Gy of the total prescribed dose of 66 Gy, respectively, in phase I and II treatments. With the addition of a hypothalamus-pituitary shield to Ho's technique, 50% of the volume of optic chiasma and temporal lobes received, respectively, 19.3 Gy and 4.5 Gy. However, small volume of the temporal lobes received a maximum dose (D(max)) of 62.8 Gy (95.2% of 66Gy). Most of the brainstem was shielded from the lateral portals but 5% of its volume received a dose ranging from 25.4 to 50.4Gy. The spinal cord (at C1/C2 level) received a D(max) of 40.8 Gy in phase I and of 4.8 Gy in phase II. After modifying Ho's technique by 3-D BEV customization of the treatment portals, the D(max) to the brainstem, the optic chiasma and the temporal lobes could be reduced by 8, 12 and 5%, respectively. CONCLUSIONS: Our study indicated that the dose-coverage of the PTV in Ho's radiotherapy technique for the early T-stage NPC was less than satisfactory in the superior and inferior and the posterolateral regions. However, in view of the excellent historical local tumor control with Ho's technique, we have to postulate that the present definition of CTV (and hence the PTV after adding margins to the CTV) lacks clinical significance and can be improved. It appears that the inclusion of the entire sphenoid sinus floor and both medial and lateral pterygoid muscles in the CTV is not necessary for maximal tumor control in the absence of clinical/radiological evidence of tumor infiltration of these organs. Ho's technique can be improved by using 3-D BEV to customize the treatment portals with multileaf collimators or blocks.

Brain Stem↗