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  • Author: D. H. MATTHEWS x
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H A Spoudeas, P C Hindmarsh, D R Matthews and C G D Brook


To determine the aetiopathology of post-irradiation growth hormone (GH) deficiency, we performed a mixed longitudinal analysis of 56 24 h serum GH concentration profiles and 45 paired insulin-induced hypoglycaemia tests (ITT) in 35 prepubertal children, aged 1·5–11·8 years, with brain tumours in the posterior fossa (n=25) or cerebral hemispheres (n = 10). Assessments were made before (n = 16), 1 year (n = 25) and 2 to 5 years (n = 15) after a cranial irradiation (DXR) dose of at least 30 Gy. Fourier transforms, occupancy percentage, first-order derivatives (FOD) and mean concentrations were determined from the GH profiles taken after neurosurgery but before radiotherapy (n = 16) and in three treatment groups: Group 1: neurosurgery only without DXR (n = 9); Group 2: ≥30 Gy DXR only (n = 22); Group 3: ≥30 Gy DXR with additional chemotherapy (n = 9). Results were compared with those from 26 short normally growing (SN) children.

Compared with SN children, children with brain tumours had faster GH pulse periodicities (200 min vs 140 min) and attenuated peak GH responses to ITT (24·55 (19·50–30·20) vs 8·32 (4·57–15·14) mU/I) after neurosurgery, before radiotherapy. However, spontaneous GH peaks (19·05 (15·49–23·44) vs 14·13 (9·12–21·38) mU/l), 24 h mean GH (5·01 (4·37–5·62) vs 3·98 (2·63–5·89) mU/l) and FODs (1·43 (1·17–1·69) vs 1·22 (0·88–1·56) mU/l per min) were similar. The abnormalities present before radiotherapy persisted in group 1 children at 1 year when 24 h mean GH (2·45 (1·17– 5·01) mU/l) and FODs (0·73 (0·26–1·20) mU/l per min) were additionally suppressed, although partial recovery was evident by 2 years.

With time from radiotherapy, there was a progressive increase in GH pulse periodicity (Group 2: 200 min at 1 year, 240 min at ≥2 years; Group 3: 140 min at 1 year, 280 min at ≥2 years) and a decrease in 24 h mean GH (Group 2 vs Group 3 at ≥2 years: 2·45 (1·70–3·47) vs 1·86 (1·32–2·69) mU/l) and FODs (Group 2 vs Group 3 at ≥2 years; 0·56 (0·44–0·69) vs 0·44 (0·27–0·61) mU/l per min). Initial discrepancies between measures of spontaneous and stimulated (ITT) GH peaks were lost by 2 or more years (spontaneous vs ITT; Group 2: 7·76 (5·89–9·77) vs 3·80 (0·91–15·84) mU/l; Group 3: 6·03 (4·27–8·32) vs 3·80 (0·31–46·77) mU/l).

After cranial irradiation, a number of changes evolved within the GH axis: faster GH pulse periodicities and discordance between physiological and pharmacological tests of GH secretion before irradiation gave way to a slow GH pulse periodicity, decreased GH pulse amplitude and rate of GH change (FOD) and, with time, eventual concordance between physiological and pharmacological measures. The evolution of these disturbances may well reflect differential pathology affecting hypothalamic GH-releasing hormone and somatostatin.

Journal of Endocrinology (1996) 150, 329–342

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Results in 53 llamas (33 mated animals and 20 controls) showed that ovulation is copulation-induced in this species. Ovulation without copulation occasionally occurred during the height of the recognized breeding season in Bolivia.

The first mating during the luteal phase (12–24 days after the preceding ovulation) resulted in ovulation in four out of ten llamas.

Determination of pituitary luteinizing hormone (LH) content showed the highest level on the day before mating (9·00 μg./mg.) and the lowest level on day 4 (6·25 μg./mg.). LH level on day 8 was significantly higher than on day 4 (7·62 μg./mg.). Corpora lutea (c.l.) were well formed on day 4 after mating (408 mg.), reached a maximum size by day 8 (1920 mg.) and rapidly decreased in size to day 16 (136 mg.). The corpus albicans remained as an entity but decreased in size to 21 mg. on day 120. Similar changes were found in c.l. histology and progesterone content. The combined results indicate that the functional life of the c.l. in a non-pregnant llama is 16 days or less.

Treatment with 25 i.u. human chorionic gonadotrophin was sufficient to cause ovulation in 50% of the animals treated.

A large (150 mg.) dose of norethandrolone did not cause morphological regression of the c.l. when measured 5 days after treatment. Treatment with 5 mg. daily for 14 days caused regression of c.l. as compared with untreated controls and animals treated with oestradiol valerate.

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M. Ryalls, H. A. Spoudeas, P. C. Hindmarsh, D. R. Matthews, D. M. Tait, S. T. Meller and C. G. D. Brook


We studied 24-h hormone profiles and hormonal responses to insulin-induced hypoglycaemia prospectively in 23 children of similar age and pubertal stage, nine of whom had received prior cranial irradiation (group 1) and fourteen of whom had not (group 2), before and 6–12 months after total body irradiation (TBI) for bone marrow transplantation in leukaemia.

Fourier transformation demonstrated that group 1 children had a faster periodicity of GH secretion before TBI than group 2 children (160 vs 200 min) but the amplitude of their GH peaks was similar. There were no differences between the groups in circadian cortisol rhythm, serum concentrations of insulin-like growth factor-I (IGF-I), sex steroids and basal thyroxine (T4). The peak serum GH concentrations observed after insulin-induced hypoglycaemia were similar between the two groups but the majority of patients had blunted responses.

TBI increased the periodicity of GH secretion in both groups (group 1 vs group 2; 140 vs 180 min), but the tendency to attenuation of amplitude was not significant. There were no significant changes in the peak serum GH concentration response to insulin-induced hypoglycaemia which remained blunted. Serum IGF-I, sex steroid, cortisol or T4 concentrations were unchanged.

Low-dose cranial irradiation has an effect on GH secretion affecting predominantly frequency modulation leading to fast frequency, normal amplitude GH pulsatility. This change is accentuated by TBI. In patients with leukemia, there is a marked discordance between the peak serum GH response to insulin-induced hypoglycaemia compared with the release of GH during 24-h studies, irrespective of the therapeutic regimen used. Pharmacological assessment of GH reserve needs to be interpreted with caution in such situations.

Journal of Endocrinology (1993) 136, 331–338