Growth hormone therapy in achondroplasia

A pilot study was carried out to examine the safety and efficacy of recombinant human growth hormone for growth-promoting therapy of achondroplasia. The data suggest that the agent in doses used to treat non-GH-deficient forms of short stature (0.3 mg/kg/wk) modestly increases overall height velocity in some children with achondroplasia. The effect was seen mainly in children with the lowest growth velocities prior to treatment. No untoward effects were noted. Several questions were raised that require further study.     

Growth and growth hormone therapy in children with achondroplasia: A two-year experience

The efficacy and safety of recombinant human growth hormone (hGH) administration was studied in children with achondroplasia. Fifteen children with achondroplasia, seven boys (4.8–12.2 years of age) and 12 girls (5.7–2.2 years of age), were treated daily with hGH at a dosage of 1 IU/kg/week. Auxological assessments were performed 6 months before, at initiation of, and at 6, 12, and 24 months following initiation of growth hormone (GH) therapy. Before initiating GH therapy, hypothalamic-pituitary and thyroid functions were evaluated. Levels of serum insulin-like growth factor (IGF)-I and IGF binding protein (BP)-3 (IGFBP-3) were assessed, as was GH response to provocative stimuli. GH responses in two stimulation tests were normal for all but three children. During the first semester of GH treatment, a significant increase in height velocity (HV), from 3.2 to 8.3 cm/year, was observed in all children. However, during the second semester, a relative decrease in growth rate was observed. By the end of the first year, HV had increased from 3.2 to 6.9 cm/year (mean, 3.7 cm/year; range, 1.1–8 cm/year) in 13 children and remained unchanged in two children. HV declined progressively during the next 12 months and, by the end of the second year of treatment, had increased in seven of the nine children who had completed 2 years of therapy (mean increase, 3.1 cm/year); two children did not respond to GH therapy, as shown by the lack of increase in HV. Sitting-height (SH) to standing-height ratio % (SH%) remained unchanged throughout GH therapy, and no significant change in skeletal maturation was observed. In conclusion, hGH treatment resulted in an increased growth rate in some children with achondroplasia; however, this increase waned during the second year of treatment. Children with the lowest pretreatment HVs seemed to benefit most from GH therapy. Nonetheless, the usefulness of GH treatment in achondroplasia will be known only when a study of final height is completed. Am. J. Med. Genet. 72:71–76, 1997. © 1997 Wiley-Liss, Inc.     

Growth hormone therapy

Growth hormone therapy with rhGH (recombinant human growth hormone) has been recommended for treatment of GH deficient short stature in children, repeated hypoglycemias in infancy and early childhood due to GH deficiency, short stature accompanying chronic renal failure prior to renal transplantation and Turner's syndrome. It is now increasingly recommended to adults with GH deficiency following pituitary tumour surgery or irradiation or idiopathic hypopituitarism. There are other indications for its use where evidence for protein catabolism is very strong such as burns injury. The end points of GH therapy in children include achievement of desirable adult height or a growth rate velocity of < 2.5 cm/year. In adults GH deficiency, GH therapy is intended for improvement of general well being, body composition and metabolic markers of GH function.     

Growth hormone deficiency and growth hormone therapy in Ullrich-Turner-Syndrome

Summary In a girl with Ullrich-Turner-Syndrome (gonadal dysgenesis 45, XO) and growth hormone deficiency, 10 U of human growth hormone/m² body surface area/week increased the growth rate from 2.0 to 4.1 cm/year. Doses of up to 36 U/m²/week did not improve the growth rate in 4 girls with Ullrich-Turner-Syndrome who had normal plasma growth hormone concentration and incretion. We conclude that growth hormone therapy is unsuccessful in dwarfism in Ullrich-Turner-Syndrome and should be reserved for patients with proven growth hormone deficiency.Supported by Deutsche Forschungsgemeinschaft, SFB 51/C10     

Growth of the foramen magnum in achondroplasia

Foramen magnum growth curves in achondroplasia and in the general population are presented. The achondroplastic foramen magnum is small at birth, and during the first year it has a severely impaired rate of growth especially in the transverse dimension. This markedly diminished growth results not only from abnormal endochondral bone growth but also because of abnormal placement and premature fusion of the synchondroses. Evaluation of the foramen magnum in achondroplasia should address absolute size of the transverse and sagittal dimensions, shape, and growth centers to determine growth potential of this area.     

Human growth hormone treatment in prepubertal children with achondroplasia

We studied the effects of recombinant human growth hormone (GH) treatment in 6 prepubertal children with achondroplasia. The patients' age ranged from 2 11/12 to 8 5/12 years and the GH dose was of 0.1 IU/kg/day subcutaneously. Auxological assessments and bone age determinations were performed 6 months before, at the beginning, and after 6 and 12 months of therapy. The growth velocity increase during the whole year of treatment ranged from 1.1 to 2.6 cm/year in 3 patients while in the others no variation was detected. No side effects were observed during the trial apart from a slight advancement of bone age in two patients. MRI at the cervicomedullary junction and CT scan of the base of the skull did not show any variation of the dimensions of the foramen magnum at the end of the trial compared to baseline. Our study shows that r-hGH can safely increase short-term growth velocity in some but not all prepubertal children with achondroplasia. Our data confirm the individual variability in the response to the GH treatment. © 1996 Wiley-Liss, Inc.     

Growth hormone replacement therapy in adults with growth hormone deficiency; thrice weekly low dose administration.

Recent reports on growth hormone (GH) therapy have shown that GH has various beneficial effects in GH deficient adults. In most of these studies, GH was administered daily. Because GH is still expensive and has to be delivered by subcutaneous injection, we studied the 6-month therapeutic effects of thrice weekly GH injection therapy and compared it with daily therapy. Twenty eight adult patients with GH deficiency were randomly assigned into group 1 (ten cases, thrice weekly injections of GH), group 2 (nine cases, daily injections), and group 3 (nine cases, placebo injections). Lean body mass, serum basal GH levels, and insulin-like growth factor 1 levels significantly increased after six months of GH therapy in both groups 1 and 2. According to computed tomography, the mean mid-thigh muscle mass significantly increased in group 1, while the visceral fat mass significantly decreased in group 2. GH levels significantly increased exercise rate-pressure product and hand grip strength only in group 1. These results suggest that thrice weekly injections of GH are as effective as daily injections in GH deficient adults.     

Growth hormone therapy and scoliosis in patients with Prader-Willi syndrome

Growth hormone (GH) therapy for short stature in patients with Prader-Willi syndrome (PWS) has started worldwide, and various favorable effects have been reported. However, the possibility of progression of scoliosis arises as a new problem of the GH therapy. In this study, we analyzed whether 72 patients who have been followed up in our hospital have such a problem. They included 46 males and 26 females (41 patients with the GH therapy and 31 without it) aged from one to 49 years. Consequently, 33 (45.8%) of 72 patients had scoliosis with the Cobb angle of >10 degrees. Twenty (48.8%) of forty-one patients who received a GH therapy and 13 (41.9%) of 31 patients without the therapy had scoliosis, the frequency of scoliosis between the two groups showing no statistical difference (P = 0.56). Height velocity of scoliotic and non-scoliotic patients during the first year of the therapy was 8.59 +/- 1.92 and 10.70 +/- 2.54 cm, respectively, showing a significant difference (P < 0.001). This shows that accelerated height velocity may not induce scoliosis. Comparison of starting age of a GH treatment revealed that non-scoliotic patients received the therapy earlier than scoliotic patients (P = 0.021). Among 20 scoliotic patients who received the GH therapy, the degree of scoliosis progressed during the therapy in six patients, improved in three and fluctuated in one. Many patients showed progression of scoliosis with age irrespective of the use of GH, and some patients improved their scoliosis during the GH therapy. These findings showed that a GH therapy increases height velocity of PWS patients but does not necessarily develop scoliosis, and early start of the therapy may not be an exacerbating factor of scoliosis.     

Obesity in achondroplasia

Obesity is a significant and potentially serious health problem in achondroplasia. Body mass indices, weight-to-square of the height ratio (W/H2), and triceps skinfold measurements show that obesity is common. It begins in early childhood and is prevalent at all ages. We recommend that weight be monitored closely in all persons with achondroplasia and that dietary intervention be instituted whenever the body mass indices, W/H2, and triceps skinfold measurements exceed the 95th centile for the general population.     

Obesity in achondroplasia

Obesity is a significant and potentially serious health problem in achondroplasia. Body mass indices, weight-to-square of the height ratio (W/H²), and triceps skinfold measurements show that obesity is common. It begins in early childhood and is prevalent at all ages. We recommend that weight be monitored closely in all persons with achondroplasia and that dietary intervention be instituted whenever the body mass indices, W/H², and triceps skinfold measurements exceed the 95th centile for the general population.     

Women's knowledge of hormone therapy.

The aim of this study was to assess women's knowledge of hormone therapy. Two hundred and seven women were interviewed by telephone. The median score to 24 questions concerning the benefits, risks and side effects of therapy was 54.2%. Almost three-quarters of women knew that hormone therapy may decrease the risk of osteoporosis, but half were unaware that it should be taken for at least 10 years for maximum protection against bone loss. While many women knew that hormone therapy may increase the risk of breast cancer, 13.5% believed that it would decrease their risk. Many women overestimated the potential reduction in lifetime risk of hip fracture and the potential increase in lifetime risk of breast cancer with hormone therapy. Women may have insufficient knowledge to make informed choices about hormone therapy. This has implications for physicians who wish to ensure that women are able to participate in informed decision-making.