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      Endocrine complications after busulphan and cyclophosphamide based hematopoietic stem cell transplant: A single tertiary care centre experience

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          Abstract

          Introduction:

          Endocrine complications are common after hematopoietic stem cell transplant (HSCT). Although HSCT is performed at various centers in India, no study is available for endocrine dysfunctions among them. This study was carried out with the objective to evaluate endocrine dysfunction among patients undergone HSCT in the past.

          Materials and Methods:

          We carried out a cross-sectional study in a 50 post-HSCT recipients (39 allogenic, 11 autologous). All relevant data were collected from patient's records. Samples for hormonal estimation were collected and stimulation tests for cortisol and growth hormone were interpreted based on peak values achieved during insulin tolerance test.

          Results:

          The mean age of patients was 26.3 ± 16.9 years (range 4-74). Adrenal insufficiency (AI) was present in 60%, hypergonadotropic hypogonadism (HH) in 60%, growth hormone deficiency (GHD) in 54%, hypothyroidism in 4%, hyperprolactinemia in 4%, new onset diabetes after transplant in 4%, and impaired fasting glucose in 6%. Multiple endocrine complications were common. GHD was present in 77% of children ( n = 22) although height standard deviation score was not statistically different compared to those who didn’t have GHD. HH was present in 36% of children. In adults ( n = 28), 36% had GHD, all females had HH, and 89% of males had HH. Germ cell dysfunction with compensated Leydig cell dysfunction was the most common pattern of HH in males. Fifteen patients had graft versus host disease (GVHD). GVHD had no bearing on development of endocrine deficiencies. AI was related to duration after and type of transplant, but was unrelated to steroid intake.

          Conclusions:

          Endocrine manifestations are common after HSCT; they can occur as early or late complications. All HSCT recipients should have endocrine evaluation as per prevailing guidelines.

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          Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp.

          Several methods have been proposed to evaluate insulin sensitivity from the data obtained from the oral glucose tolerance test (OGTT). However, the validity of these indices has not been rigorously evaluated by comparing them with the direct measurement of insulin sensitivity obtained with the euglycemic insulin clamp technique. In this study, we compare various insulin sensitivity indices derived from the OGTT with whole-body insulin sensitivity measured by the euglycemic insulin clamp technique. In this study, 153 subjects (66 men and 87 women, aged 18-71 years, BMI 20-65 kg/m2) with varying degrees of glucose tolerance (62 subjects with normal glucose tolerance, 31 subjects with impaired glucose tolerance, and 60 subjects with type 2 diabetes) were studied. After a 10-h overnight fast, all subjects underwent, in random order, a 75-g OGTT and a euglycemic insulin clamp, which was performed with the infusion of [3-3H]glucose. The indices of insulin sensitivity derived from OGTT data and the euglycemic insulin clamp were compared by correlation analysis. The mean plasma glucose concentration divided by the mean plasma insulin concentration during the OGTT displayed no correlation with the rate of whole-body glucose disposal during the euglycemic insulin clamp (r = -0.02, NS). From the OGTT, we developed an index of whole-body insulin sensitivity (10,000/square root of [fasting glucose x fasting insulin] x [mean glucose x mean insulin during OGTT]), which is highly correlated (r = 0.73, P < 0.0001) with the rate of whole-body glucose disposal during the euglycemic insulin clamp. Previous methods used to derive an index of insulin sensitivity from the OGTT have relied on the ratio of plasma glucose to insulin concentration during the OGTT. Our results demonstrate the limitations of such an approach. We have derived a novel estimate of insulin sensitivity that is simple to calculate and provides a reasonable approximation of whole-body insulin sensitivity from the OGTT.
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            High prevalence of endocrine dysfunction in long-term survivors after allogeneic bone marrow transplantation for hematologic diseases.

            The progressively increasing number of long-term survivors after allogeneic bone marrow transplantation (allo-BMT) led researchers to focus on the early and late complications of this procedure. Endocrine dysfunction occurred mostly in patients who had undergone total body irradiation (TBI) as part of pretransplantation treatment. The extent to which chemotherapy and immune system derangement affect endocrine function in allo-BMT recipients is still unclear. Forty consecutive patients (21 women, 19 men) with hematologic diseases surviving 12 or more months after allo-BMT from HLA-identical siblings were studied. Patients' age at transplantation ranged from 13 to 45 years and their post-BMT follow-up lasted 12-62 months. The conditioning regimen BUCY2 was employed. Graft versus host disease (GVHD) was observed in the acute form in 13 patients and in the chronic form in 26. The function of hypothalamic-pituitary-gonad, thyroid, somatotrophic, and adrenal axes was assessed. The most common endocrine dysfunction was ovarian insufficiency (95% of women), followed by an increase in follicle-stimulating hormone in 47% of men, indicating spermatogenesis damage. Hormone replacement therapy was contraindicated in three women because of chronic liver GVHD and it was ineffective partially in four others because of reduced intestinal or cutaneous absorption. Thyroid dysfunction occurred in 47.5% of patients and included low T3 syndrome, chronic thyroiditis, and transient subclinical hyperthyroidism and subclinical hypothyroidism. Adrenal function was abnormal in 10%, mostly related to the prolonged corticosteroid treatment. IGF-I was lower than age-reference values in 27% of all patients and in 38% of those with chronic GVHD. Thyroid, adrenal, and IGF-I impairments were more frequent in patients with chronic GVHD than in patients without this disease (P = 0.048). A high prevalence of endocrine dysfunction was detected in a cohort of allo-BMT recipients not treated by TBI. Although gonadal failure was likely related to intensive myeloablative treatments, thyroid, adrenal, and IGF-I impairments were late events, suggesting that immunosuppressive treatment and immune system derangement may play a role in the development of endocrine dysfunction after allografting. Copyright 2002 American Cancer Society.
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              Semen analysis following allogeneic bone marrow transplantation. Additional data for evidence-based counselling.

              Knowledge of the impact of different conditioning regimens used in bone marrow transplantation on spermatogenesis is important in pre-BMT counselling for three reasons: (1) Most young patients who have not had children are concerned with their subsequent fertility; (2) For a number of diseases there are competing therapeutic options that may affect spermatogenesis more or less seriously; (3) Since spontaneous recovery of spermatogenesis is rare, it would be necessary to offer cryopreservation as soon as possible after diagnosis and prior to any treatment. This retrospective study evaluates 99 semen samples obtained in 64 patients who underwent BMT between 1982 and 1996. Recovery of spermatogenesis was observed in 90% of patients conditioned with cyclophosphamide (CY), in 50% of patients with CY plus busulphan (BU) or thiotepa and in 17% of patients with CY plus total body irradiation (TBI) or thoracoabdominal irradiation (TAI). Sperm quality following CY was within the normal range (WHO) in the majority of patients, whereas it was consistently severely impaired in patients who received irradiation or two alkylating agents. Following CY, spermatogenesis recovery was observed in 60% of patients tested 1 year post transplant and it was accomplished within the third year in 80% of cases. Following CY + TBI/TAI recovery of spermatogenesis never occurred before the 4th year post transplant and was demonstrated as late as 9 years in one patient who was azoospermic 1 year earlier. No statistical correlation between age and recovery of spermatogenesis could be demonstrated. The overall high incidence of azoospermia (70.3%) supports the indication for semen cryopreservation in young patients undergoing BMT. These results have implications for semen sample timing before and after BMT and underline a need to collect further data through prospective multi-center studies.
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                Author and article information

                Journal
                Indian J Endocrinol Metab
                Indian J Endocrinol Metab
                IJEM
                Indian Journal of Endocrinology and Metabolism
                Medknow Publications & Media Pvt Ltd (India )
                2230-8210
                2230-9500
                Sep-Oct 2013
                : 17
                : 5
                : 855-863
                Affiliations
                [1] Department of Endocrinology, Army Hospital (Research and Referral), Delhi Cantt, New Delhi, India
                [1 ] Department of Haematology, Army Hospital (Research and Referral), Delhi Cantt, New Delhi, India
                Author notes
                Corresponding Author: Col. (Prof.) M. K. Garg, Department of Endocrinology, Command Hospital (Southern Command), Pune, Maharashtra, India. E-mail: mkgargs@ 123456gmail.com
                Article
                IJEM-17-855
                10.4103/2230-8210.117248
                3784869
                24083167
                d38b932f-3fb9-44bd-84a6-28165710f481
                Copyright: © Indian Journal of Endocrinology and Metabolism

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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                Categories
                Original Article

                Endocrinology & Diabetes
                adrenal insufficiency,diabetes,growth hormone deficiency,hematopoietic stem cell transplant,hypogonadism,hypothyroidism

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