Management of endocrino-metabolic dysfunctions after allogeneic hematopoietic stem cell transplantation

Abstract

Allogeneic hematopoietic stem cell transplantation is mainly indicated in bone marrow dysfunction related to blood diseases, but also in some rare diseases (adrenoleucodystrophy, mitochondrial neurogastrointestinal encephalomyopathy or MNGIE…). After decades, this treatment has proven to be efficient at the cost of numerous early and delayed side effects such as infection, graft-versus-host disease, cardiovascular complications and secondary malignancies. These complications are mainly related to the conditioning, which requires a powerful chemotherapy associated to total body irradiation (myelo-ablation) or immunosuppression (non myelo-ablation). Among side effects, the endocrine complications may be classified as 1) hormonal endocrine deficiencies (particularly gonado- and somatotropic) related to delayed consequences of chemo- and above all radiotherapy, with their consequences on growth, puberty, bone and fertility); 2) auto-immune diseases, particularly dysthyroidism; 3) secondary tumors involving either endocrine glands (thyroid carcinoma) or dependent on hormonal status (breast cancer, meningioma), favored by immune dysregulation and radiotherapy; 4) metabolic complications, especially steroid-induced diabetes and dyslipidemia with their increased cardio-vascular risk. These complications are intricate. Moreover, hormone replacement therapy can modulate the cardio-vascular or the tumoral risk of patients, already increased by radiotherapy and chemotherapy, especially steroids and anthracyclins… Therefore, patients and families should be informed of these side effects and of the importance of a long-term follow-up requiring a multidisciplinary approach.

Endocrine dysfunctions in adults post hematopoietic stem cell transplantation

“…Gonadal failure in adult patients post-HSCT was found at a frequency of 40.2% but according to other studies, it can reach 92% in males and 99% in females on long-term follow-up [8] when transplanted children were included. As previously described by others authors [5,[7][8][9][10][11][12][13][14][15][16], in our study risk factors for the development of hypogonadism were age at the transplant, type of conditioning and the treatments for the underlying disease (chemotherapy and ERT). A revision by Brennan, et al [6] showed that gonadal failure was associated with age at transplant, conditioning and underlying disease therapy.…”

“…The use of glucocorticoids for a long-term in a high dose can temporarily change the hypothalamus-pituitary-adrenal axis, as confirmed by Majhail, et al [20] and Vantyghem, et al [9], and could impair the assessment of adrenal function. Some of our patients were using glucocorticoids at the first visit to endocrine service, but during the follow-up we can distinguish them.…”

“…Recover thyroid function was not common (less than 3%). The damage was transitory in these cases, maybe because a transient hypothyroidism related to autoimmune thyroiditis post ERT as Majhaih, et al [20] and Vantyghem, et al [9] saw.…”

“…These patients require hormone replacement therapy for prolonged periods due to the young age they developed hypogonadism (median 29 years old). One study [9] show that when gonadal recovery occurs, there are candidates for early menopause and high-risk pregnancies. We did not assessed this outcome.…”

Dyslipidemia and Metabolic Syndrome in Children and Teenagers After the Allogeneic Hematopoietic Stem Cell Transplantation

“…Для будущих исследований перспективным явля-ется более пристальное внимание к проблеме рацио-нального применения сахароснижающих препаратов для кардио-и вазопротекции у пациентов после алло-ТГСК с метаболическими расстройствами [19]. заключение Эндокринные дисфункции, дислипидемия и мета-болические расстройства являются актуальной пробле-мой у реципиентов после алло-ТГСК.…”