Cranial Irradiation

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The deleterious effects of cranial irradiation on GH secretion are an unfortunate and common morbidity for individuals with a variety of neoplastic and hematologic diseases. The initial studies detailing the hypothalamic-pituitary effects of cranial irradiation exposure were performed with male rhesus monkeys (40 Gray), demonstrating a blunted GH secretory response to insulin hypoglycemia and a decrease in GH pulse frequency and amplitude. Doubling the dose of insulin (0.1-0.2 units/kg) normalized the GH response, suggesting an intact, but altered or "reset" hypothalamic sensitivity for influencing GH secretion (Figs. 1 and 2) (46).

Fig. 1. GH responses to arginine (Arg), insulin (Ins), and L-dopa stimulation 50 wk after cranial irradiation. Primates treated with 2400 rads (open circles, n = 4) and 4000 rads (closed circles, n = 4) showed a normal response to arginine and L-dopa, but a blunted response to insulin (0.1 U/ kg, iv). The shaded area represents the mean ± SEM from 9-13 controls. *,p < 0.001. Reproduced with permission from ref. 46.

Fig. 1. GH responses to arginine (Arg), insulin (Ins), and L-dopa stimulation 50 wk after cranial irradiation. Primates treated with 2400 rads (open circles, n = 4) and 4000 rads (closed circles, n = 4) showed a normal response to arginine and L-dopa, but a blunted response to insulin (0.1 U/ kg, iv). The shaded area represents the mean ± SEM from 9-13 controls. *,p < 0.001. Reproduced with permission from ref. 46.

Subsequently, cranial irradiation at lower doses (24 Gray [Gy]) has been associated with growth retardation and diminished spontaneous GH secretion in subjects with acute lymphoblastic leukemia (ALL) (47). Twenty-four h sampling of spontaneous GH secretion appears to be a more sensitive means of identifying quantitative and qualitative abnormalities in GH secretion, including reductions in GH pulse amplitude and frequency (Fig. 3). A "normal" GH secretory response to provocation in subjects with a history of cranial irradiation associated with an abnormal 24-h GH study suggests the presence of selective defects in neurotransmitter control of GH secretion (47). The term "neurosecretory dysfunction" was coined to describe subjects with growth retardation and neuroregulatory abnormalities of GH secretion.

Fig. 2. GH secretory pattern over 24 h in two primates treated with cranial irradiation (4000 rads; top panel) and two normal controls (bottom panel). The study was performed 1 yr after treatment. There was a decrease in the number (frequency) and amplitude of secretory spikes in the animals that received radiation. The shaded area represents the detection limit of the assay. The dark period was from 1700-0500 h (solid bar). Reproduced with permission from ref. 46.

Fig. 2. GH secretory pattern over 24 h in two primates treated with cranial irradiation (4000 rads; top panel) and two normal controls (bottom panel). The study was performed 1 yr after treatment. There was a decrease in the number (frequency) and amplitude of secretory spikes in the animals that received radiation. The shaded area represents the detection limit of the assay. The dark period was from 1700-0500 h (solid bar). Reproduced with permission from ref. 46.

We also examined 24-h studies of spontaneous GH secretion in a group of children following central nervous system or total body irradiation for acute lymphoblastic leukemia (ALL) and a variety of other central nervous system (CNS) tumors not involving the hypothalamic-pituitary axis. Mean 24-h GH concentrations were significantly reduced (1.8 ± 0.2 vs 3.9 ± 0.3 [ig/L, treatment vs controls; p < 0.001). Blunting of the peak GH response to a variety of provocative stimuli again suggests widespread neuronal damage affecting neurotransmitter regulation of GH secretion including dopaminergic (levodopa); noradrenergic (clonidine, propranolol); GABAergic (valproic acid); and cholinergic (pyridostigmine) neurons. GH response to a serotonin-like compound (l-tryptophan) was not significantly affected (9,48).

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Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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