Response to nutritional and growth hormone treatment in progeria.

Hutchinson-Gilford progeria syndrome (HGPS) is a rare condition with an unknown molecular defect. Patients with HGP progressively develop failure to thrive (FTT), alopecia, loss of subcutaneous fat, scleroderma, stiffening of various joints, and severe atherosclerosis. The median life span is 13 years, and the main cause of death is cardiovascular complications. There are few reports of endocrine and metabolic studies because of the rarity of this condition, and the response to long-term growth hormone (GH) treatment has not been described. We report the results of endocrine and metabolic studies performed to investigate the etiology of growth failure in five patients with HGP. Additionally, the response to nutritional therapy (NT) and GH treatment in three of these patients is presented. Our results suggest that elevated GH levels are characteristic of this disease and that an elevated basal metabolic rate (BMR) could be the cause of the FTT seen in HGP. Nonaggressive NT slightly improved weight gain and growth velocity (GV). Combined NT and GH treatment in three patients improved the GV, increased the levels of growth factors, and paradoxically resulted in decreased BMRs. However, the response to these therapies decreased over time and did not seem to prevent the progression of atherosclerotic disease.

Alterations in spontaneous growth hormone (GH) secretion and the response to GH-releasing hormone in children with nonorganic nutritional dwarfing.

The effects of suboptimal nutrition on the spontaneous overnight GH secretion (SGHS) and the GH response to GHRH were studied. Sixteen patients with nonorganic nutritional dwarfing (ND) were compared with 25 healthy short children with familial short stature with or without constitutional growth delay (FC). The effects of puberty were also assessed. All patients underwent an overnight study to assess SGHS with serum GH levels sampled every 20 min for 12 h, and a GHRH stimulation test was administered. Pubertal ND children had a blunted SGHS with a mean overnight GH level of 4.9 +/- 1.1 micrograms/L, significantly less than the level of 6.2 +/- 1.8 micrograms/L of the pubertal FC children (P less than 0.05). Also, prepubertal ND patients had an area under the curve in GH secretion after GHRH which was greater than that of the pubertal ND patients (2483 +/- 1581 vs. 1600 +/- 1056, P less than 0.05). The peak GH response to GHRH in the prepubertal ND patients was also higher than that of the pubertal ND patients (51.8 +/- 22.1 micrograms/L vs. 22.5 +/- 15.4 micrograms/L, P less than 0.05). This study shows that the SGHS is attenuated in ND patients during puberty but their GH response to GHRH is increased before adolescence. These abnormalities may represent compensatory mechanisms to energy restriction and may increase our understanding of the poor growth seen in ND patients.