Body composition during GH treatment in Prader-Labhardt-Willi syndrome.

Prader-Labhardt-Willi syndrome (PLWS) is a model to study GH secretion, body composition and consequences of GH therapy. Twenty-seven patients were studied by dual-energy X-ray absorptiometry (DXA) and were each compared to two age- and sex-matched controls (obese and normal weight). Fat mass (FM) was significantly greater in PLWS than in patients with simple obesity; lean body mass (LM) and bone mineral content (BMC) were significantly lower compared to both controls. The peculiar body composition of PLWS patients seems to be similar to that found in GH deficiency. In six PLWS children treated with GH, LM increased after 6 months (p<0.02) up to 12 months (p<0.03); FM decreased in 5/6 patients. Obese adult PLWS patients treated with GH for 6 months showed a reduction in adiposity; LM increased significantly only in the leg compartment. Abdominal CT scan did not show a significant reduction of intrabdominal fat area. In conclusion, GH therapy might improve final stature and exert a positive influence on body composition in patients with PLWS.

Impairment of growth hormone responsiveness to growth hormone releasing hormone and pyridostigmine in patients affected by Prader-Labhardt-Willi syndrome.

In order to evaluate the impairment of GH response in patients affected by Prader-Labhardt-Willi (PLW) syndrome, in 18 patients we studied GH response to clonidine and to GHRH + pyridostigmine, a cholinergic drug which enhances GHRH induced GH responsiveness in obese patients. After clonidine GH response was abnormal in 14/18 subjects (mean GH peak: 4.1 +/- 1.3 micrograms/l; area under curve: 208.1 +/- 74.2 micrograms/l.h) while all but 5 patients showed an inadequate GH response to GHRH + pyridostigmine (mean GH peak: 13.4 +/- 2.5 micrograms/l; area under curve: 903.4 +/- 171.0 micrograms/l.h). However, in the three patients with low adiposity index, GH response to GHRH + pyridostigmine was significantly higher than that observed in fatter subjects. In addition, GH response to GHRH + pyridostigmine was negatively correlated to age and adiposity index. In conclusion, our data are consistent with the hypothesis of the existence of a complex derangement of GH neuroendocrine regulation in these subjects.

GH secretion in Prader-Labhard-Willi syndrome: somatotrope responsiveness to GHRH is enhanced by arginine but not by pyridostigmine.

Low somatotrope responsiveness to secretagogues has been reported in patients affected by Prader-Labhard-Willi Syndrome (PLWS). In normal subjects, GH response to GHRH is known to be greatly potentiated to the same extent by pyridostigmine (PD) or arginine (ARG) which probably act via inhibition of hypothalamic somatostatin release. To clarify somatotrope responsiveness in 7 PLWS patients, we studied GH response to GHRH alone and to GHRH combined with PD or ARG. Eight normal short children were studied as controls (NC). GH response to GHRH in PLWS was lower than in NC (AUC: 615 +/- 205 micrograms/l.h, vs 1271 +/- 333 micrograms/l.h, p < 0.02). In NC, the GHRH-induced GH rise was potentiated to the same extent by PD or ARG. In contrast, in PLWS PD failed to increase the GH response to GHRH (AUC: 615 +/- 205 micrograms/l.h vs 621 +/- 176 micrograms/l.h, n.s.) which was enhanced by ARG (AUC: 615 +/- 205 micrograms/l.h vs 1633 +/- 425 micrograms/l.h, p < 0.02). However, the GH response to GHRH + ARG in PLWS was lower than in NC. In conclusion, our results demonstrate that in PLWS the low somatotrope responsiveness to GHRH is not enhanced by cholinergic potentiation while it is increased by arginine.