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PubMed2001

Endocrine complications of pediatric stem cell transplantation.

Abnormalities of endocrine function and growth are common following stem cell transplantation in the pediatric/adolescent population. Impaired linear growth and adult short stature are associated with younger age at transplant, use of TBI and prior cranial irradiation, and development of chronic GvHD. Primary hypothyroidism is the most common abnormality of the thyroid and is observed in 10-28% of cases following fractionated TBI. Autoimmune hyperthyroidism has also been described post-stem cell transplant and most often results from adoptive transfer of abnormal clones of T or B cells from donor to recipient. Gonadal dysfunction is extremely prevalent and includes oligo-azoospermia in the majority of males treated with TBI, and primary ovarian failure in most women treated with TBI or Busulfan/Cyclophosphamide. Leydig cell function, however, is retained in most males treated with standard forms of cytoreduction. Many patients demonstrate reduced bone mineral density and are at risk of developing osteoporosis in the future.

Adolescent↗
PubMed1998

Long-term effects of allogeneic bone marrow transplantation (BMT) on pituitary, gonad, thyroid and adrenal function in adults.

To evaluate the late-effects of allogeneic bone marrow transplantation (BMT) on endocrine function 20 adults (10 females, 10 males) with hematological malignancies were studied after a mean of 3.2 years (range 1.0-10.0) following BMT. The mean age of patients at the time of BMT was 39 years. Dynamic tests of the hypothalamic-pituitary axis included growth hormone releasing hormone (GHRH), gonadotropin releasing hormone (GnRH) and thyrotropin releasing hormone (TRH) stimulations with measurements of serum growth hormone (GH), follicle stimulating hormone (FSH), luteinizing hormone (LH), thyrotropin (TSH) and prolactin (PRL) responses. Adrenal function was assessed with the adrenocorticotropin (ACTH) test. Five patients (25%) had a subnormal GH response to GHRH stimulation, but all had a normal serum insulin-like growth factor I (IGF-I) value. There was an inverse nonlinear relationship between the body mass index (BMI; kg/m2) and GH response but no relation between the GH response and total body irradiation (TBI), intrathecal treatment or occurrence of graft-versus-host disease. In females, serum FSH and LH basal levels and responses to GnRH, in spite of oestrogen substitution therapy in 9/10 patients, indicated ovarian failure and early menopause. Most responses to GnRH were delayed. All males had elevated serum basal FSH levels indicating damage in seminiferous tubulus and infertility. Serum basal LH was elevated only in four males but testosterone values were all within normal limits. However, the mean free androgen index (FAI) was in the low normal range, and two subjects had abnormally low FAI. Serum free thyroxine (fT4) levels were normal in all but one, but an exaggerated TSH response to TRH occurred in seven patients (35%). Four of them had received TBI and one total nodal irradiation suggesting radiation-induced damage to the thyroid gland. In 19 of the 20 patients, adrenal function judged with ACTH test was normal. We conclude that functional impairments of the hypothalamus-pituitary-gonad/thyroid axis are common while disturbances in GH, adrenal and prolactin occur less often in patients after intensive treatment and BMT. Typically, the target organ is more commonly affected than the hypothalamus-pituitary axis. In spite of normal serum testosterone and LH values, serum FAI may reveal androgen deficiency.

Adolescent↗
PubMed1995

Growth in children after bone marrow transplantation for acute leukemia.

We evaluated the growth of children with acute leukemia who received a bone marrow transplant (BMT) after preparation with hyperfractionated total body irradiation (TBI). Seventy-two patients (27 female and 45 male patients) with acute lymphoblastic leukemia (ALL; n = 39) or acute myelogenous leukemia (AML; n = 33) who were less than 14 years of age at BMT were studied. Before BMT all had received multiagent chemotherapy and 31 had received cranial irradiation (RT). Preparation for BMT included total body irradiation (1,375 cGy [n = 37] or 1,500 cGy [n = 35]). Heights, expressed as standard deviation scores (SDS), were studied up to 4 years post-BMT. The estimated height SDS for the entire group at the time of BMT was -0.28 +/- 0.05 and decreased to -1.11 +/- 0.22 at 4 years post-BMT (P < .0001). Using a growth curve model to compare covariate groups over the period of study, we found that the loss in height SDS was most significant in those patients who received cranial RT before BMT (P = .005). The estimated height SDS for patients treated with cranial RT went from -0.52 +/- 0.20 at transplantation to -1.83 +/- 0.23 4 years later. In contrast, patients who did not receive cranial RT before BMT showed a smaller decrease in height SDS over the 4-year observation period, ie, -0.11 +/- 0.20 decreasing to -0.73 +/- 0.21. Similarly, patients with a diagnosis of ALL had a greater loss of height SDS than those with AML (P = .033). Fifteen of 18 patients tested were found to be growth hormone (GH) deficient; 9 patients were treated with GH and all showed an improvement in growth velocity (P < .0001). We conclude that (1) children with acute leukemia who have received cranial RT and subsequently undergo BMT, primarily those with ALL, are at high risk for growth failure and GH deficiency, and (2) that fractionation of TBI may have a relative sparing effect on growth.

Acute Disease↗
PubMed1985

The hormonal effects of pituitary surgery and irradiation: a review of 59 cases.

The endocrine function of 59 patients with pituitary tumours who were treated in our unit between 1962 and 1982 is reviewed. There were 20 patients with growth hormone (GH) secreting adenomas, 17 with prolactinomas (1 tumour secreted both GH and prolactin), 14 corticotrophin (ACTH) secreting adenomas and nine non-functioning pituitary adenomas. Patients were treated with pituitary surgery and/or irradiation, with and without the addition of drugs. Patients treated with drugs alone were not included. Following combined surgery, radiotherapy and bromocriptine therapy only two acromegalic patients had persistently raised growth hormone levels and five continued to be hyperprolactinaemic. Pituitary irradiation alone was associated with the development of hypothyroidism in three of eight patients. A delayed but significant fall in free thyroxine index (p less than 0.01) was noted in patients receiving 4500 cGy radiotherapy and surgery. Four patients also developed delayed ACTH deficiency at times varying from one to six years after treatment. It is concluded that patients who have received pituitary surgery or irradiation require regular long-term endocrine assessment.

Adenoma↗
PubMed1994

Germ cell failure and Leydig cell insufficiency in post-pubertal males after autologous bone marrow transplantation with BEAM for lymphoma.

Thirteen post-pubertal male patients aged 17-25 years were assessed for pituitary-gonadal function 0-3 months prior to and 2-3 months post-bone marrow transplantation for haematological malignancy. All patients had multiagent cytotoxic treatment prior to transplantation and 30% were found to have germ cell dysfunction with abnormal semen parameters before high-dose therapy indicating damage to the germinal epithelium. They also had evidence of reduced Leydig cell reserve even before transplantation. During transplantation all patients sustained sustained gonadal injury, the effect on their germ cells being more pronounced than on the Leydig cells. Fifty per cent had reduction in testicular volume and all had azoospermia 2-3 months post-transplantation. Our results indicate that short-term chemoradiotherapy causes profound damage to the germ cell compartment of the testis, with less severe damage to the Leydig cells, but no overt injury to the anterior pituitary gland. The changes appeared to be identical in patients conditioned with total body irradiation-based protocols and those who received only high-dose chemotherapy prior to bone marrow transplantation.

Adolescent↗
PubMed2002

Cancer incidence after nasopharyngeal radium irradiation.

BACKGROUND: From 1940 until 1970, nasopharyngeal radium irradiation was used to treat children and military personnel suffering from Eustachian tube failure attributable to local lymphoid hyperplasia. METHODS: We studied cancer incidence in a cohort of 4339 Dutch patients treated with nasopharyngeal radium irradiation, mostly in childhood, and 4104 frequency-matched nonexposed subjects. Average doses to the nasopharynx, pituitary gland, brain, and thyroid gland were 275, 10.9, 1.8, and 1.5 cGy, respectively. We assessed cancer incidence from cancer registry linkage (1989-1996), self-report including medical verification (1945-1988), and death certificates (1945-1996). RESULTS: During 18-50 years of follow-up, four thyroid malignancies (standardized incidence ratio [SIR] = 2.8; 95% confidence interval [CI] = 0.8-7.2) and five malignant brain tumors (SIR = 1.3; CI = 0.4-3.1) were observed. Increased risks were observed for malignancies of lymphoproliferative and hematopoietic origin (SIR = 1.9; CI = 1.2-2.8) and breast cancer (SIR = 1.5; CI = 1.1-2.1). Strong dose-response trends could not be demonstrated for any cancer outcome, although relative risk estimates were elevated in the highest-dose category for head and neck cancer and breast cancer. CONCLUSIONS: These data provide little evidence for a high excess risk of cancer associated with nasopharyngeal radium irradiation treatment as applied in the Netherlands. Inconsistent findings across studies and public concern warrant the continuing follow-up of available cohorts.

Adolescent↗
PubMedDate not supplied

In vitro assessment of MR relaxation properties of pituitary adenomas.

Proton magnetic relaxation times (T1 and T2) and bound water content were measured in vitro in pituitary adenomas from 15 patients using 90 MHz radiofrequency excitation. These data were compared with those measured in normal pituitary glands obtained from four cats and seven fresh human cadavers. The T1 and T2 measured at 24 degrees C in the tumors (mean +/- SD: 1,170 +/- 80 and 123 +/- 35 ms, respectively) were significantly higher than those of cadaver pituitary (830 +/- 200 and 76 +/- 12 ms) and cat pituitary gland (790 +/- 120 and 69 +/- 10 ms). Although the absolute values were lower, similar differences were present in T1 measured at 4 degrees C. Two-dimensional T2 versus T1 plot was particularly helpful in distinguishing tumor from the normal gland. When tumors were grouped according to density on CT, histology or previous treatment (e.g., irradiation or bromocriptine), there were no significant differences in T1 values between the groups. Bound water content was not found to correlate with T1 or T2 values. We concluded that pituitary adenomas can be distinguished from normal pituitary glands by their different relaxation properties when measured at high frequency in vitro MR.

Adenoma↗