Mark Vandeweghe

Short and long‐term effects of growth hormone treatment on bone turnover and bone mineral content in adult growth hormone‐deficient males

OBJECTIVE In view of the fact that GH‐deficient adults present with pronounced osteopaenia and can be considered at risk for osteoporotic fractures, we wanted to investigate the effects of biosynthetic GH replacement therapy (0.25 IU/kg/week) on biochemical indices of bone turnover and on bone mineral content (BMC) in a group of GH‐deficient adult males.

Two years of replacement therapy in adults with growth hormone deficiency

Although several studies have shown beneficial short‐term effects of recombinant human growth hormone (rhGH) therapy in adult GH deficient (GHD) patients, few data are available on large groups of patients treated for more than one year. In addition, the optimal dose of rhGH for each patient and the baseline parameters that predict which patients will benefit most from therapy or will have adverse events are not entirely elucidated.

Final Height in Children with Idiopathic Growth Hormone Deficiency Treated with Recombinant Human Growth Hormone: The Belgian Experience

Background: The growth response to recombinant hGH (rhGH) treatment and final height of 61 Belgian children (32 boys) with idiopathic growth hormone deficiency (GHD) were studied. Patients/Methods: Two patient groups were compared: Group 1 with spontaneous puberty (n = 49), Group 2 with induced puberty (n = 12). The patients were treated with daily subcutaneous injections of rhGH in a dose of 0.5–0.7 IU/kg/week (0.17–0.23 mg/kg/week) from the mean ± SD age of 11.9 ± 3.1 years during 5.1 ± 2.1 years. Results: rhGH treatment induced a doubling of the height velocity during the first year and resulted in a normalisation of height in 53 (87%) patients. Final height was –0.7 ± 1.1 SDS, being 170.4 ± 7.2 cm in boys and 158.0 ± 6.4 cm in girls. Corrected for mid-parental height, final height was 0.0 ± 1.1 SDS. Ninety-two percent of the patients attained an adult height within the genetically determined target height range. Although height gain during puberty was smaller in the patients with induced puberty (boys: 17.1 ± 7.0 cm vs. 27.5 ± 6.6 cm (p < 0.005); girls: 9.6 ± 7.4 cm vs. 22.2 ± 6.1 cm (p < 0.005)), no differences in final height after adjustment for mid-parental height were found between patients with spontaneous or induced puberty. Conclusions: We conclude that patients with idiopathic GHD treated with rhGH administered as daily subcutaneous injections in a dose of 0.5–0.7 IU/kg/week reach their genetic growth potential, resulting in a normalisation of height in the majority of them, irrespective of spontaneous or induced puberty.

Macroprolactinoma associated with Cushing’s disease, successfully treated with cabergoline

Multiple pituitary hormone hypersecretions have already been described, but the co-occurrence of PRL and ACTH excess is very rare. To our knowledge, medical treatment with cabergoline only, avoiding pituitary surgery and radiotherapy in this type of tumor has never been reported before. This case report deals with a 31-yr-old man affected with a macroprolactinoma associated with a florid clinical image of Cushing’s disease. Normalization of the prolactin levels and the disappearance of clinical and biochemical features of Cushing’s disease were obtained after administration of medical treatment only.

Treatment of central precocious puberty with an intranasal analogue of GnRH (Buserelin)

One boy and 13 girls with central precocious puberty were treated for 1 year using Buserelin, a GnRH analogue, given intranasally (0.3 mg, four times a day). After 1, 3 and 12 months of therapy, the gonadotropin responses to GnRH were abolished in all the patients whereas mean basal serum concentrations of luteinizing hormone (LH) remained similar to those of pubertal controls. During Buserelin treatment, genital development in the boy and breast development in the girls showed no further progress or some regression. In the boy, serum testosterone levels returned to prepubertal values. In the girls, serum oestradiol levels were variable and, in four of them, vaginal smears showed the persistence of a slight oestrogenic effect during therapy. Pelvic ultrasonography did not show any significant variation in ovarian and uterine lengths. Among the 14 patients, 3 had some progression of pubic hair development, irrespective of serum dehydroepiandrosterone sulphate (DHEAS) levels. In eight patients previously treated with cyproterone, elevated prolactin levels were observed before and during the first month of Buserelin administration. During treatment, mean height velocity was markedly reduced from 11.6 to 6.1 cm/year and mean bone age velocity (±1 SD) was 0.85±0.38 year/year. After 1 year of treatment, the differences in predicted adult height ranged between −0.74 and +1.04 SDS (standard deviation score). These differences were inversely related (r=−0.72) to the prognosis of adult height calculated before treatment. We conclude that, in central precocious puberty, intranasal administration of Buserelin, 1.2 mg/day, may arrest sexual development and reduce height velocity and bone maturation. Improvement of adult height prognosis may occur, especially when it was markedly impaired before treatment.

Influence of spontaneous or induced puberty on the growth promoting effect of treatment with growth hormone in girls with Turner's syndrome

OBJECTIVE The aim was to evaluate the effect of 3 years treatment with recombinant human growth hormone (rhGH) on height velocity and height in girls with Turners syndrome (TS) and to study to influence of spontaneous or induced puberty on the growth promoting effect of rhGH.

A Valuable Improvement of Adult Height Prediction Methods in Short Normal Children

OBJECTIVES The potential benefit of growth hormone (GH) administration to increase adult height of normal children of short stature might be blurred by the accuracy and the precision of the prediction methods used to estimate final height before onset of therapy. The aim of the present study was to evaluate three prediction methods: Bayley-Pinneau (BP), Roche-Wainer-Thissen (RWT) and Tanner-Whitehouse Mark II (TW2) and to improve their accuracy and precision by exploring their correlation with various parameters obtained in peripubertal children with poor predicted adult height. STUDY DESIGN Accuracy and precision of the prediction methods were evaluated retrospectively by comparing predicted adult heights estimated in 62 boys at 13.7 +/- 0.9 years and in 28 girls at 12.1 +/- 0.9 years of age, with their adult heights measured respectively at 20.7 +/- 2.6 years and 18.8 +/- 2.8 years. RESULTS At the time of prediction, the height for chronological age was -2.07 +/- 0.68 standard deviation scores for boys and -2.15 +/- 0.6 years for girls. Measured adult heights were significantly lower than target heights (165.1 +/- 5.1 vs. 169.4 +/- 4.8 cm for boys; p < 0.001 and 153.1 +/- 3.9 vs. 156.3 +/- 5.0 cm for girls; p = 0.001). For boys, the BP method was the most accurate and also the most convenient with a predicted adult height of 164.7 +/- 5.0 cm and a small underestimation of 0.4 +/- 3.5 cm. For girls, the TW2 method was the most accurate with a predicted height of 152.4 +/- 3.7 cm with a little underestimation of 0.7 +/- 3.5 cm. There were no important differences between the precision of these methods. The use of a correction factor derived from the bone age delay at the time of prediction in boys and from the chronological age at the time of prediction in girls improved the accuracy of the predicted adult height. CONCLUSIONS The use of a factor correcting the accuracy of the BP method in boys and of the TW2 method in girls should be valuable in assessing the potential benefit of GH therapy to increase adult height in short normal children.

Growth hormone treatment of Turner syndrome patients with insufficient growth hormone response to pharmacological stimulation tests

Growth before and during treatment with biosynthetic human growth hormone (hGH) was studied in 13 patients with Turner syndrome (TS) and a growth hormone (GH) response of less than 10 μg/l to two standard provocative tests. During 1 year of treatment with hGH (0.15 IU/kg per day) height velocity (mean±SD) increased significantly (P<0.001) from 3.7±1.8 cm/year to 7.6±1.5 cm/year. The auxological data in these girls before and during treatment with hGH were similar to those observed in TS patients with a normal response of GH to pharmacological stimuli. It is concluded that in girls with Turner syndrome GH testing should only be performed when height velocity is below the Turner norm. In TS patients with residual growth potential a clinically significant growth acceleration can be obtained with a higher-than-replacement dose of hGH, i.e. 0.15 IU/kg per day, regardless of GH testing.

Effect of Growth Hormone Administration on the Fatty Acid Composition of Adipose Tissue in Growth-Hormone-Deficient Men

In adult patients with growth hormone deficiency, the fatty acid composition of abdominal and gluteal fat tissues was determined prior to and at several time points after administration of recombinant human growth hormone. Values obtained before growth hormone treatment were not different from those seen in a normal population. However, as in healthy individuals, significant differences were found in the composition of the fat sampled at the different sites. Administration of growth hormone had no effect on the composition. It is concluded that a change in fatty acid composition of fat tissue is unlikely to be a factor contributing to the reported increased cardiovascular mortality in hypopituitarism and that treatment with recombinant human growth hormone has no effect on that potential cardiovascular risk factor.

GROWTH PROMOTING EFFECT OF GROWTH HORMONE AND LOW DOSE ETHINYL ESTRADIOL IN GIRLS WITH TURNER SYNDROME: FINAL HEIGHT RESULTS

In 1987 a multicenter trial was started to evaluate the effect of daily s.c. rhGH treatment (0.15 IU/kg/day Genotonorm, Kabi Pharmacia, Sweden) in 40 girls with Turner syndrome (TS) (mean±SD age: 11.3±2.6 yrs). Twenty randomly selected girls received in addition 25 ng/kg/day ethinylestradiol (EE2) orally. From the 3rd year of treatment puberty was induced with 100 ng/kg/day EE2 in the girls with a bone age older than 11 years. Thirty-six patients have been followed for 5 years. Except early breast budding in 9 out of 20 girls treated with rhGH and 25 ng/kg/day EE2, no differences were found between the patients treated with rhGH alone and those also treated with low dose EE2. In 28 patients with a bone age above 13 yrs, height attained 5 years after the start of rhGH treatment is 150.5±4.4 cm. This is higher (P<0.001) than the adult height of 144.8±5.8 cm of 43 untreated TS girls. In these 28 girls, the difference in height attained after 5 years of treatment and corrected mid parental height is 10.8±4.8 cm, which is less (P<0.001) than in untreated adult TS patients (16.2±4.8 cm). These results provide further evidence that treatment with rhGH increases final height in TS girls.