Experience with growth hormone therapy in Turner syndrome in a single centre: low total height gain, no further gains after puberty onset and unchanged body proportions.

The experience gained since 1987, through observation of 85 girls with Turner syndrome under growth hormone (GH) treatment, has enabled the analysis of one of the largest cohorts. Our results show that age, karyotype and height reflect the heterogeneity of the patients examined at our growth centre. In 47 girls, followed over 4 years on GH (median dose 0.72 IU/kg/week), the median age was 9.4 years and mean height SDS was -3.55 (Prader) and -0.14 (Turner-specific), while height and other anthropometrical parameters [weight, body mass index, sitting height (SH), leg length (LL) SH/LL, head circumference, arm span] were documented and compared to normative data as well as to Turner-specific references established on the basis of a larger (n = 165) untreated cohort from Tübingen. The latter data are also documented in this article. Although there was a trend towards normalization of these parameters during the observation period, no inherent alterations in the Turner-specific anthropometric pattern occurred. In 42 girls who started GH treatment at a median age of 11.8 years, final height (bone age >15 years) was achieved at 16.7 years. The overall gain in height SDS (Turner) from start to end of GH therapy was 0.7 (+/- 0.8) SD, but 0.9 (+/- 0.6) SD from GH start to onset of puberty (spontaneous 12.2 years, induced 13.9 years) and -0.2 (+/- 0.8) from onset of puberty to end of growth. Height gain did not occur in 12 patients (29%) and a gain of > 5 cm was only observed in 16 patients (38%). Height gain correlated positively with age at puberty onset, duration, and dose of GH, and negatively with height and bone age at the time GH treatment started. Final height correlated positively with height SDS at GH start and negatively with the ratio of SH/LL (SDS). We conclude that, in the future, GH should be given at higher doses, but oestrogen substitution should be done cautiously, owing to its potentially harmful effect on growth. LL appears to determine height variation in Turner syndrome and the potential to treat short stature successfully with GH.

Reference values for height and weight in Prader-Willi syndrome based on 315 patients.

UNLABELLED: The spontaneous growth of 315 patients (109 girls and 208 boys) with Prader-Willi syndrome (PWS) was analysed in a mixed longitudinal and cross-sectional manner. 33 patients were seen in the department between 1970 and 1994; height and weight of 76 patients from Germany were evaluated by means of a questionnaire with detailed measuring instructions, and 206 definite cases were added from the literature. Mean ( SD) length of newborn babies with PWS was 50.2+/-2.8 cm (145 boys) and 48.9 3.3 cm (79 girls). Mean weight at birth was 2945 570 g in boys and 2782+/-594 g in girls. During the 1st year, the children's growth was nearly normal, thereafter short stature was present in approximately 50% of PWS patients. Between 3 and 13 years of age, the 50th percentile for height in PWS is roughly identical with the 3rd percentile in healthy controls. Body weight was normal for all boys and girls during the first 2 years. Thereafter, a rapid weight gain occurred; after an age of 10 years weight-for-height index in nearly all patients exceeded the normal range. The extent of pubertal growth was reduced for the group. Mean adult height was 161.6+/-8.1 cm (23 males) and 150.2+/-5.5 cm (21 females). Head circumference for age was normal for boys and girls. CONCLUSION: Reference data on spontaneous development of growth and weight gain of children with Prader-Willi syndrome are described allowing a better counselling of patients and parents.

Outcome in tall stature. Final height and psychological aspects in 220 patients with and without treatment.

UNLABELLED: In 135 women and 85 men who initially presented for tall stature, the outcome in treated (56 women and 33 men; cases) and untreated (controls) was investigated. At the time of height prediction, cases were significantly taller (P < or = 0.03) than the controls, they had higher target heights (P < 0.001) and adult height predictions (P < 0.001) (according to Bailey and Pinneau) compared to the controls. Bone age (according to Greulich and Pyle) and chronological age were well matched in both groups. Final height was measured after cessation of growth at a mean age above 21.5 years. The final height prediction according to Bailey and Pinneau (BP method) overestimated the final height in controls. The mean error of estimation was -0.14 cm (+/- 3.10) in women, and -1.86 cm (+/- 4.37) in men. Age at the time of prediction did not significantly correlate with the degree of the prediction error. Sex hormone therapy comprised a daily oral dose of 7.5 mg conjugated oestrogens in girls (plus 5 mg dydrogesterone for 10 days a month), while boys received 500 mg testosterone enantate, intramuscularly, every 2 weeks. Therapy was well tolerated. The mean corrected effect of height reducing therapy was 3.6 cm (range: 11.9 cm to -3.3 cm) in women and 4.4 cm (range: 14.2 cm to -5.2 cm) in men. Therapy was significantly more effective when started at an earlier chronological (P < 0.01) and bone age (P < 0.01). The residual mean growth, after therapy was stopped, was 1.8 (+/- 1.6) cm in women and 3.1 (+/- 2.3) cm in men. In men, post-treatment growth was inversely correlated to chronological age (P < 0.01) and bone age (P < 0.05) at the end of treatment, while these correlations were not significant in women. Both groups had a higher educational level than the normal population. Treated tall women reported teasing because of tallness more frequently than controls. In tall men, practical issues such as clothing size predominated. Maximum tolerated height in males was 200 cm and in females 180 cm, thus being nearly analogous to the actual professional criteria for treatment recommendation. A positive attitude to treatment was documented in over 90% of treated individuals. CONCLUSIONS: Our results show that the BP method gives acceptable adult height predictions in girls, but less accurate predictions in boys. The treatment with high doses of sex hormones was low effective in both sexes and showed a wide range of response. For success, treatment must be initiated in early puberty and terminated late. The answers to a questionnaire revealed no major psychological or social maladjustment of treated individuals compared to those untreated.

Spontaneous adult height in idiopathic short stature.

Two hundred and thirty-six patients with idiopathic short stature (ISS) (184 m, 52 f) who presented at a mean age of 12.2 (range 2.8-17.5) years, a mean height of -2.16 standard deviation score (SDS), a mean target height (THT) of -0.27 SDS (m = f), were reinvestigated at a mean age of 20.5 (range 18-24) years. 182(142 m, 37 f) (67%) had reached normal adult height (AHT) while 54 (39 m, 15 f) (23%) had not. However, only 23 (17 m, 6 f) did not reach a height within their familial target. Patients were subdivided into 2 groups according to deviation from familial height target: 60(44 m, 16 f) were considered adequate for their families (group 1), while 176 (140 m, 39 f) were smaller (group 2). Children in group 1 were younger and bone age (BA) was less retarded. Patients in group 1 reached their THT, this was not the case in group 2. Young age, low THT and low predicted adult height (PAH) at presentation were the factors associated with poor stratural outcome, but AHT could not be predicted in individuals. In boys, PAH (Bayley-Pinneau) (0.0 SDS) exceeded AHT (-0.7 SDS), in girls, both were almost identical (-0.79, -0.77 SDS). Since most children with ISS reach an AHT within the normal range, attempts to improve AHT by means of growth-promoting therapies appear to be justified only in a minority of selected patients with ISS. Methods to improve the accuracy of individual height prognoses are needed.

Adult height in Turner syndrome: results of a multinational survey 1993.

Under the auspices of ESPE/LWPES, a survey on spontaneous adult height in patients with Turner syndrome was conducted in 12 European countries. A total of 661 patients (45,X = 51%) with a median age of 23.6 years (range: 16-63) who had never received any growth-promoting treatment until the age of 14 had reached a mean height of 144.3 +/- 6.7 cm. There was no height difference between those (n = 220) who had received oxandrolone and/or estrogen after the age of 14 years and those (n = 441) who never received any treatment until the age of 20. On average, there was no major gain in height after an age of 16 years. The height achieved was positively associated with the height of normal women in the underlying population. There was a high positive correlation (r = 0.436; p < 0.0001) between adult height and target height in adults never treated. A positive correlation of these parameters was present irrespective of karyotype (45,X vs. 'others') or treatment with oxandrolone/estrogen. The findings strengthen the observations on height development from national studies.