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Hypothalamic-pituitary function of children with acute lymphocytic leukemia after three forms of central nervous
Insights
Central nervous system (CNS) prophylaxis for acute lymphocytic leukemia (ALL) in children showed no long-term adverse effects on thyroid-stimulating hormone (TSH) and adrenocorticotropic hormone (ACTH) secretion. While some growth hormone (GH) responses were subnormal, linear growth remained unaffected.
Area of Science:
- Pediatric Endocrinology
- Pediatric Oncology
- Neuroendocrinology
Background:
- Children treated for acute lymphocytic leukemia (ALL) often receive central nervous system (CNS) prophylaxis.
- Long-term effects of different CNS prophylaxis regimens on hypothalamic-pituitary function require evaluation.
Purpose of the Study:
- To retrospectively assess the hypothalamic-pituitary function in children treated with three different CNS prophylaxis regimens for ALL.
- To determine if these treatments impact thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), gonadotropin (FSH/LH), and growth hormone (GH) secretion.
Main Methods:
- Retrospective evaluation of 93 children in continuous complete remission from ALL.
- Analysis of treatment regimens: intrathecal methotrexate (IT MTX), IT MTX plus cranial irradiation, or IT MTX with intravenous intermediate-dose methotrexate.
- Hormone level assessment: serum TSH, T4, plasma cortisol response to insulin hypoglycemia, urinary FSH/LH, and GH response to arginine-insulin stimulation.
Main Results:
- Serum TSH and T4 levels were normal in all groups.
- Adrenocorticotropic hormone (ACTH) secretion was normal, indicated by plasma cortisol responses.
- Urinary FSH and LH were appropriate, with isolated exceptions; GH responses were subnormal in some patients across all groups, but linear growth was unaffected.
Conclusions:
- The evaluated CNS prophylaxis regimens for ALL do not appear to have long-term adverse effects on TSH and ACTH secretion.
- FSH-LH production seems normal, though further follow-up is needed.
- Subnormal GH responses were observed in some children, but did not impact overall linear growth.
Abstract:
The hypothalamic-pituitary function of 93 children, who had received central nervous system (CNS) prophylaxis as part of their therapy for acute lymphocytic leukemia (ALL), and who remained in continuous complete remission, was evaluated retrospectively. Treatment regimens included--Group I: 31 subjects, intrathecal methotrexate (IT MTX); Group II: 31 subjects, IT MTX plus 2400 rad cranial irradiation; and Group III: 31 subjects, IT MTX and intravenous intermediate-dose methotrexate. Serum thyroid-stimulating hormone (TSH) and T4 levels were normal. All participants had normal adrenocorticotropic hormone (ACTH) secretion as assessed by plasma cortisol responses to insulin hypoglycemia. Urinary follicle-stimulating hormone (FSH) and luteinizing hormone (LH) excretion of pubertal and postpubertal patients (N = 37) was appropriate, except for one subject from Group I who had an abnormally high output of gonadotropins, and one from Group II who had abnormally low levels. Growth hormone (GH) responses were subnormal after sequential arginine-insulin stimulation as follows--Group 1: 3 of 31 patients; Group II: 6 of 25 patients; and Group III: 2 of 29 patients. Nevertheless, all children had normal linear growth. It was concluded that the three forms of CNS prophylaxis evaluated had no long-term adverse effect on TSH and ACTH secretion. FSH-LH production appears to be normal, but final judgment must await follow-up studies because 60% of the patients were prepuberteral or still receiving chemotherapy. Eleven patients had subnormal GH responses after pharmacologic stimulation of the pituitary, but long-term linear growth was unaffected.