Effects of total-body irradiation on growth, thyroid and pituitary gland in rhesus monkeys

Bakker, Boudewijn; Massa, Guy; Rijn, Ariadne M van; Mearadji, Amir; Kamp, H.J. van der; Niemer-Tucker, M. M. B.; Hage, M. H. van der; Broerse, J.J.; Wit, Jan M.

doi:10.1016/s0167-8140(99)00059-6

Cited by 13 publications

(6 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These effects on the testis further complete the discovery of problems that may arise at long intervals after TBI. In the same group of monkeys, effects on body fat and thyroid gland [63] as well as gastrointestinal function [64], ophthalmological complications [65], and cardiovascular damage [66] have already been described.…”

Section: Discussionmentioning

confidence: 92%

Long-Term Effects of Irradiation Before Adulthood on Reproductive Function in the Male Rhesus Monkey1

Rooij

Kant

Dol

et al. 2002

Biology of Reproduction

View full text Add to dashboard Cite

Today, many patients, who are often young, undergo total body irradiation (TBI) followed by bone marrow transplantation. This procedure can have serious consequences for fertility, but the long-term intratesticular effects of this treatment in primates have not yet been studied. Testes and epididymides of rhesus monkeys that received doses of 4-8.5 Gy of TBI at 2-4 yr of age were studied 3-8 yr after irradiation. In all irradiated monkeys, at least some seminiferous tubule cross-sections lacked germ cells, indicating extensive stem cell killing that was not completely repaired by enhanced stem cell renewal, even after many years. Testes totally devoid of germ cells were only found in monkeys receiving doses of 8 Gy or higher and in both monkeys that received two fractions of 6 Gy each. By correlating the percentage of repopulated tubules (repopulation index) with testicular weight, it could be deduced that considerable numbers of proliferating immature Sertoli cells were killed by the irradiation. Because of their finite period of proliferation, Sertoli cell numbers did not recover, and potential adult testis size decreased from approximately 23 to 13 g. Most testes showed some dilated seminiferous tubules, indicating obstructed flow of the tubular fluid at some time after irradiation. Also, in 8 of the 29 irradiated monkeys, aberrant, densely packed Sertoli cells were found. The irradiation did not induce stable chromosomal translocations in spermatogonial stem cells. No apparent changes were seen in the epididymides of the irradiated monkeys, and the size of the epididymis adjusted itself to the size of the testis. In the irradiated monkeys, testosterone and estradiol levels were normal, whereas FSH levels were higher and inhibin levels lower when testicular weight and spermatogenic repopulation were low. It is concluded that irradiation before adulthood has considerable long-term effects on the testis. Potential testis size is reduced, repopulation of the seminiferous epithelium is generally not complete, and aberrant Sertoli cells and dilated tubules are formed. The latter two phenomena may have further consequences at still longer intervals after irradiation.

show abstract

Section: Discussionmentioning

confidence: 92%

Long-Term Effects of Irradiation Before Adulthood on Reproductive Function in the Male Rhesus Monkey1

Rooij

Kant

Dol

et al. 2002

Biology of Reproduction

View full text Add to dashboard Cite

show abstract

“…7,21 Although TBI-based preparative regimen has been widely suggested for ALL patients, 22 there are some opposing views regarding the use of TBI-based conditioning regimen, especially in young children, in attempt to avoid radiation-related sequel. 10,11,23,24 However, this regimen is currently being used worldwide for ALL patients. 12,25 Many morbidities of TBI are now well proven.…”

Section: Discussionmentioning

confidence: 99%

“…Endocrinologic disturbances such as decreased fertility, hypogonadism, hypothyroidism, and growth hormone deficiency have been reported. 11,12,23 Secondary malignancies, renal damage, chronic renal dysfunction, early renal damage, interstitial pneumonitis, cataract, and neurocognitive effects are among other adverse consequences. 11,12,20,[26][27][28][29][30] Chemotherapy regimens are developed to minimize the toxicities of irradiation-based regimens.…”

Section: Discussionmentioning

confidence: 99%

The Outcome of Allogeneic Hematopoietic Stem Cell Transplants Without Total Body Irradiation in Pediatric Patients With Acute Lymphoblastic Leukemia

Hamidieh

Kargar

Jahani

et al. 2012

Journal of Pediatric Hematology/Oncology

View full text Add to dashboard Cite

The most widely accepted conditioning regimen to allogeneic hematopoietic stem cell transplantation consists of total body irradiation, especially in patients affected by acute lymphoblastic leukemia (ALL). In this retrospective study, we report our experience on hematopoietic stem cell transplantation in 44 pediatric patients with acute lymphoblastic leukemia using a non-radiation-based conditioning regimen (busulfan/cyclophosphamide). Median age at transplantation was 12.5 years (range, 4 to 14 y). 39 out of 44 patients received transplants in complete remission. At a median follow-up of 390 days, the probabilities of 3-year disease-free survival and overall survival were 50% and 68%, respectively. Disease status of hematopoietic stem cell transplantation was the only significant variable affecting the overall survival. Acute and chronic graft-versus-host disease occurred in 23 (64%) and 12(18%) patients, respectively. Relapse was significantly higher among patients transplanted in advanced disease status. The results of the study indicate that non-radiation-based preparative regimens can be used in pediatric patients with ALL. However, well-designed comparative trials are needed to better clarify the difference between radiation and non-radiation-based conditioning regimens in pediatric ALL.

show abstract

“…Total body irradiation, often coupled with chemotherapy as myeloablative conditioning treatment, dramatically reduces BMD by suppressing bone formation, enhancing bone resorption, and disrupting the inorganic components of the bone matrix ( 121 – 125 ). Moreover, irradiation has been associated with hypogonadism, hypopituitarism and growth hormone deficiency, thus leading to a decrease in trophic factors important for bone formation ( 105 , 126 , 127 ).…”

Section: Hsct-derived Endocrine Sequelae Pathophysiologymentioning

confidence: 99%

Endocrine sequelae of hematopoietic stem cell transplantation: Effects on mineral homeostasis and bone metabolism

et al. 2023

View full text Add to dashboard Cite

Hematopoietic stem cell transplantation (HSCT) is an established therapeutic strategy for the treatment of malignant (leukemia and lymphoma) and non-malignant (thalassemia, anemia, and immunodeficiency) hematopoietic diseases. Thanks to the improvement in patient care and the development of more tolerable conditioning treatments, which has extended the applicability of therapy to the elderly, a growing number of patients have successfully benefited from HSCT therapy and, more importantly, HSCT transplant-related mortality has consistently reduced in recent years. However, concomitantly to long term patient survival, a growing incidence of late HSCT-related sequelae has been reported, being variably associated with negative effects on quality of life of patients and having a non-negligible impact on healthcare systems. The most predominantly observed HSCT-caused complications are chronic alterations of the endocrine system and metabolism, which endanger post-operative quality of life and increase morbidity and mortality of transplanted patients. Here, we specifically review the current knowledge on HSCT-derived side-effects on the perturbation of mineral metabolism; in particular, the homeostasis of calcium, focusing on current reports regarding osteoporosis and recurrent renal dysfunctions that have been observed in a percentage of HSC-transplanted patients. Possible secondary implications of conditioning treatments for HSCT on the physiology of the parathyroid glands and calcium homeostasis, alone or in association with HSCT-caused renal and bone defects, are critically discussed as well.

show abstract

Effects of total-body irradiation on growth, thyroid and pituitary gland in rhesus monkeys

Cited by 13 publications

References 23 publications

Long-Term Effects of Irradiation Before Adulthood on Reproductive Function in the Male Rhesus Monkey1

Long-Term Effects of Irradiation Before Adulthood on Reproductive Function in the Male Rhesus Monkey1

The Outcome of Allogeneic Hematopoietic Stem Cell Transplants Without Total Body Irradiation in Pediatric Patients With Acute Lymphoblastic Leukemia

Endocrine sequelae of hematopoietic stem cell transplantation: Effects on mineral homeostasis and bone metabolism

Contact Info

Product

Resources

About