Reproductive effects of low-to-moderate medical radiation exposure.

Medical radiation from x-rays and nuclear medicine is the largest man-made source of radiation exposure in Western countries, accounting for a mean effective dose of 3.0 mSv per capita per year, comparable to the radiologic risk of 150 chest x-rays, and in many cases gonads fall in the imaging field, with > 20 millions examinations per year in US being abdominal and pelvic CT, and > 0.5 million barium enema. Of the over 7 million workers exposed to medical radiation, special attention has been paid to those working in the interventional cardiology and radiology labs, with high and increasing professional exposures, two-to three times higher than diagnostic radiologists. Thus, adverse effects of radiation exposure are well worth of the scientific community's interest. Aims of this review are: 1) to assess gonad dose to patients undergoing diagnostic testing or interventional fluoroscopy therapy and in professionally exposed interventional fluoroscopists; and 2) to evaluate the evidence linking radiation exposure in the low-to-moderate range (besides the radiotherapy high dose range) to adverse reproductive effects. In patients, the gonad radiation exposure can reach 5 mSv for a lower limb angiography, 20 mSv for a CT pelvis and hips, and 36 (in females) to 90 mSv (for males) for a lower gastrointestinal series. For interventional cardiologists, the gonad dose (below lead apron) is in the same order of magnitude of the shielded thyroid dose, with a median of 50 to 100 microSievert per cine-angiography procedure. The dose can be ten-fold higher for a complex interventional procedure. This leads to a cumulative exposure in the 0.5-1 Sv range over a professional lifetime of 30 years. At present, the epidemiological approach provided inconclusive results, inadequate for a robust evidence-based advice to exposed subjects, since large groups followed-up for decades would be required to detect a small increase in risk. A molecular epidemiology approach and/or the use of integrated biomarkers of reproductive health (e.h., reproductive hormone balance, sperm quality, sperm DNA damage) might be more fruitful in future research focused in the low-to-moderate dose range (< 1000 mSv) of greatest interest for diagnostic and professional exposures.

Ultrastructural effects on gill, muscle, and gonadal tissues induced in zebrafish (Danio rerio) by a waterborne uranium exposure.

Experiments on adult zebrafish (Danio rerio) were conducted to assess histopathological effects induced on gill, muscle, and gonadal tissues after waterborne uranium exposure. Although histopathology is often employed as a tool for the detection and assessment of xenobiotic-mediated effects in aquatic organisms, few studies have been dedicated to the investigation of histopathological consequences of uranium exposure in fish. Results showed that gill tissue architecture was markedly disrupted. Major symptoms were alterations of the secondary lamellae epithelium (from extensive oedema to desquamation), hyperplasia of chloride cells, and breakdown of the pillar cell system. Muscle histology was also affected. Degeneration and disorganization of myofibrillar sarcomeric pattern as well as abnormal localization of mitochondria within muscle and altered endomysial sheaths were observed. Morphological alterations of spermatozoa within the gonadal tissue were also noticed. This study demonstrated that uranium exposure induced a variety of histological impairments in fish, supporting environmental concerns when uranium contaminates aquatic systems.

Bone and bone turnover.

Children with cancer are exposed to multiple influences that may adversely affect bone health. Some treatments have direct deleterious effects on bone whilst others may have indirect effects mediated through various endocrine abnormalities. Most clinical outcome studies have concentrated on survivors of acute lymphoblastic leukaemia (ALL). There is now good evidence that earlier treatment protocols that included cranial irradiation with doses of 24 Gy or greater may result in growth hormone deficiency and low bone mineral density (BMD) in the lumbar spine and femoral neck. Under current protocols, BMD decreases during intensive chemotherapy and fracture risk increases. Although total body BMD may eventually return to normal after completion of chemotherapy, lumbar spine trabecular BMD may remain low for many years. The implications for long-term fracture risk are unknown. Risk factors for low BMD include high dose methotrexate, higher cumulative doses of glucocorticoids, male gender and low physical activity. BMD outcome in non-ALL childhood cancers has been less well studied but there is evidence that survivors of childhood brain or bone tumours, and survivors of bone marrow transplants for childhood malignancy, all have a high risk of long-term osteopenia. Long-term follow-up is required, with appropriate treatment of any endocrine abnormalities identified.

[Late sequelae of comprehensive antineoplastic therapy in children and adolescents with solid extracranial tumors. Effect on growth, pubertal development and gonadal function]. / Pozdní následky komplexní protinádorové lécby u detí a mladistvých s extrakraniálními solidními nádory. Vliv na rust, pubertální vývoj a funkci gonád.

BACKGROUND: Modern treatment of oncological diseases increases markedly the chance of long-term survival and permanent recovery. Due to frequently highly aggressive treatment it is however associated with the risk of late sequelae in the surviving patients. Comprehensive care of patients includes therefore not only control of the neoplastic disease but also efforts of maximal improvement of the quality of life of the patients. In young subjects, in view of their long-term perspective, this problem is particularly important. METHODS AND RESULTS: In 32 patients (25 boys and 7 girls) with extracranial solid tumours without primary endocrinological symptomatology (m. Hodgkin, neuroblastoma, ganglioneuroblastoma, nephroblastoma, Ewings sarcoma and others) a single examination was made assessing height, body weight, grade of sexual maturation according to Tanner, in boys testicular volume by means of a orchidometer and 20 other anthropometric dimensions. The mean age at the time of examination was 16.5 +/- 4.1 years, the mean age at the onset of treatment 6.1 +/- 4.8 years. The patients height, -0.4 +/- 0.9 SD, differs from the Czech national standard (p = 0.025). Impaired growth was recorded in 12.5% patients and had heterogenous causes. The authors proved a negative effect of radiotherapy on the growth of the spine, most markedly in children subjected to irradiation of the abdomen and chest and a highly significant reduction of the testicular volume in boys after cytostatic treatment of m. Hodgkin. CONCLUSIONS: The results are consistent with studies made abroad and indicate the necessity of comprehensive long-term follow-up of somatic growth and development of the gonads in oncological child patients.

Hypothalamic-pituitary dysfunction after radiation for brain tumors.

BACKGROUND: Patients with brain tumors who are treated with radiation frequently have growth hormone deficiency, but other neuroendocrine abnormalities are presumed to be uncommon. METHODS: We studied endocrine function in 32 patients (age, 6 to 65 years) 2 to 13 years after they had received cranial radiotherapy for brain tumors. The doses of radiation to the hypothalamic-pituitary region ranged from 3960 to 7020 rad (39.6 to 70.2 Gy). Nine patients also received 1800 to 3960 rad (18.0 to 39.6 Gy) to the craniospinal axis. Serum concentrations of thyroid, gonadal, and pituitary hormones were measured at base line and after stimulation. RESULTS: Nine patients (28 percent) had symptoms of thyroid deficiency, and 20 patients (62 percent) had low serum total or free thyroxine or total triiodothyronine concentrations. Of the 23 patients treated only with cranial radiation, 15 (65 percent) had hypothalamic or pituitary hypothyroidism. Of the nine patients who also received spinal (and thus direct thyroid) radiation, three (33 percent) had evidence of primary thyroid injury. Seven of the 10 postpubertal, premenopausal women (70 percent) had oligomenorrhea, and 5 (50 percent) had low serum estradiol concentrations. Three of the 10 men (30 percent) had low serum testosterone concentrations. Overall, 14 of the 23 postpubertal patients (61 percent) had evidence of hypogonadism. Mild hyperprolactinemia was present in 50 percent of the patients. Responses to stimulation with corticotropin-releasing hormone and corticotropin were normal in all patients except one, who had panhypothalamic dysfunction. However, serum 11-deoxycortisol responses to the administration of metyrapone were low in 11 of the 31 patients (35 percent) tested. Three of the 32 patients, (9 percent) had no endocrine abnormalities, 9 (28 percent) had an abnormal result on tests of thyroid, gonadal, prolactin, or adrenal function, 8 (25 percent) had abnormalities in two axes, 8 (25 percent) in three axes, and 4 (12 percent) in all four axes. CONCLUSIONS: Cranial radiotherapy in children and adults with brain tumors frequently causes abnormal hypothalamic-pituitary function. The most frequent changes are hypothyroidism and gonadal dysfunction, although subtle abnormalities in adrenal function may also be present.

[Certain characteristics of the perinatal development of children whose parents were exposed to the action of uranium fission products]. / Nekotorye kharakteristiki perinatal'nogo razvitiia detei, roditeli kotorykh podverglis' deistviiu produktov deleniia urana.

Analysis was made of the character of the perinatal development of 238 children. In 65 of these, the parents were exposed to the action of uranium fission products in the basin of the river Techa in the Chelyabinsk region. The parents were radiated approximately 5 years before the children's birth. The mean equivalent dose for endocrine glands (including gonads) of the parents amounted to about 12 centiSievert U. As compared to the control group, the basic one manifested a higher incidence of placenta and umbilical cord pathology. In the group of the radiated persons' progeny, the number of small-weight children appeared greater; a larger physiological reduction of the body weight was recorded as were later times of funic residue falling off.