Constitutional delay of growth and puberty: from presentation to final height

This retrospective study evaluated clinical characteristics of patients with constitutional delay of growth and puberty (CDGP) at presentation, during puberty and at final height. The records of 151 children (105 boys, 46 girls) with CDGP were reviewed and the results were evaluated with respect to findings in healthy Turkish schoolchildren. CDGP was twice as frequent in boys as in girls. Height and weight deficit and short sitting height of the children were evident at presentation and continued up to final height. Mean age of onset of puberty was retarded by 2.5 years in girls and by 3 years in boys. The time between onset of puberty and pubertal growth spurt was shorter in both girls and boys than in the controls. Peak growth velocity was compromised in both girls and boys. Forty-one patients (30 boys, 11 girls) reached final height (FH). Mean FH was shorter than both target height and predicted adult height. The Bayley-Pinneau method was found to be a better predictor of FH than either the Tanner-Whitehouse method or target height. FH also showed correlation with the father's height. There was no effect of testosterone treatment on final height. Height deficit at onset of puberty, shorter duration between onset of puberty and pubertal growth spurt, compromised peak growth velocity and short upper segment due to delayed puberty, are findings which may explain the decreased final height of children with CDGP.     

Age at onset and long-term metabolic control affect height in type-1 diabetes mellitus

Reduced height as a consequence of type-I-diabetes mellitus in childhood has been reported in many studies. However, it is still debated whether good metabolic control can normalize the growth rate. A total of 436 children (204 boys, 232 girls, mean age at diagnosis of diabetes 8.2±0.2 years) were followed at our outpatient diabetes centre. Z-scores for height were evaluated in relation to duration of diabetes, age at onset and long-term metabolic control. At diagnosis, height in children with diabetes was significantly above the reference population (+0.43± 0.09). Standardized height decreased during the subsequent course of diabetes. This likely represents a delay of growth, as the final height (chronological age >18 years, n = 144) was +0.27 ± 0.09. Growth reduction was more pronounced in patients diagnosed before the onset of puberty and final height in patients with a prepubertal onset of diabetes was significantly lower (+0.10 ± 0.13) compared to patients with a pubertal/postpubertal onset (+0.52 ± 0.14). Among patients with a prepubertal onset, the subgroup with “poor” metabolic control (long-term median HbA_1c >7%) lost significantly more height compared to patients with “good” metabolic control. Conclusion Despite modern treatment regimens, reduced longitudinal growth can still be demonstrated in type-I diabetes. This parameter therefore provides a valuable endpoint for quality control in paediatric diabetology. Received: 8 December 1997/ Accepted in revised form: 11 March 1998     

Final height, gonadal function and bone mineral density of adolescent males with central precocious puberty after therapy with gonadotropin-releasing hormone analogues

Few data are available on the outcome of boys with central precocious puberty (CPP) treated with gonadotropin-releasing hormone (GnRH) analogues. We report on final height, endocrine and exocrine testicular function, and bone mineral density (BMD) in nine males (age 16.7 ± 1.5 years) treated with GnRH analogues from the age 6.0 ± 1.8 years for a mean period of 5.6 ± 2.4 years. The following parameters were evaluated: final height, serum gonadotropin and gonadal steroid levels, spermarche, semen analysis, area and volumetric BMD. Final height (−0.4 ± 1.1 SDS) was significantly higher than pre-treatment predicted adult height (−2.0 ± 1.2 SDS) and not significantly different than midparental height (−0.1 ± 0.8 SDS). Pubertal response of gonadotropins to GnRH test occurred within 1.5 years (mean 0.7 ± 0.4 years) and spermarche (n=7) from 0.7 to 3 years (1.8 ± 0.9 years) after the discontinuation of GnRH analogue therapy. No alteration in semen analysis was found (n=6, sperm count, 10⁶/ml: 52.0 ± 18.7; normal motility (%): 49.5 ± 18.7; atypical morphology (%): 44.5 ± 11.4). Area and volumetric BMD were not reduced (0.2 ± 1.0 SDS and −0.1 ± 0.9 SDS, respectively). Conclusion Long-term treatment with gonadotropin-releasing hormone analogues improves final height in boys with central precocious puberty. Post-therapy data demonstrating normal endocrine and exocrine testicular function support the safety of gonadotropin-releasing hormone analogues on reproductive function. Long-term pharmacological suppression of testicular function in childhood does not impair bone mineral density in late adolescence. Received: 4 May 1999 / Accepted: 30 November 1999     

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

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≤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. Received: 18 March 1997 / Accepted in revised form: 20 June 1997     

Effect of central precocious puberty and gonadotropin-releasing hormone analogue treatment on peak bone mass and final height in females

To evaluate the effect of central precocious puberty (CPP) and its treatment with gonadotropin-releasing hormone (GnRH) analogues on final height and peak bone mass (PBM), we measured lumbar bone mineral density (BMD) in 23 girls at final height. Patients were distributed in two groups. Group 1: 14 patients with progressive CPP were treated with GnRH analogues; seven patients received buserelin (1600 μg/daily), subsequently switched to depot triptorelin (60 μg/kg/26–28 days); seven patients were treated with depot triptorelin (60 μg/kg/26–28 days); mean age of treatment was 6.2 years (range 2.7–7.8 years); the treatment was discontinued at the mean age of 10.1 years (range 8.7–11.3 years); final height was reached at the mean age 13.4 years (range 12.0–14.9 years). Group 2: 9 patients (mean age 6.5 years, range 4.8–7.7 years) with a slowly progressing variant of CPP were followed without treatment; final height was reached at the mean␣age␣13.6 years (range 12.5–14.8 years). Lumbar BMD (L₂-L₄ by dual energy X-ray␣absorptiometry) was measured in all patients at final height. In group 1, final height␣(158.9 ± 5.4 cm) was significantly greater than the pre-treatment predicted height (153.5 ± 7.2 cm, P < 0.001), but significantly lower than mid-parental height (163.2 ± 6.2 cm, P < 0.005). Subdividing the girls of group 1 according to the bone age at discontinuation of therapy (i.e. ≤11.5 years, n = 5, or ≥12.0 years, n = 9), the former patients had a final height significantly higher than the latter (163.7 ± 3.9 cm vs 156.5 ± 4.6 cm, P < 0.02). In group 2, final height (161.8 ± 4.6 cm) was similar to the pre-treatment predicted height (163.1 ± 6.2 cm, P = NS) and was not significantly different from mid-parental height (161.0 ± 5.9 cm). BMD values (group 1: 1.11 ± 0.14 g/cm², group 2: 1.22 ± 0.08 g/cm²) were not significantly different from those of a control group (1.18 ± 0.10 g/cm²; n = 20, age 16.3–20.5 years) and the patients' mothers (group 1: 1.16 ± 0.07 g/cm², n = 11, age 32.9–45.1 years; group 2: 1.20 ± 0.08 g/cm², n = 7, age 33.5–46.5 years). In group 1, the girls who stopped therapy at a bone age ≤11.5 years had significantly higher BMD (1.22 ± 0.10 g/cm²) compared to those who discontinued therapy at a bone age ≥12.0 years (1.04 ± 0.12 g/cm², P < 0.05). Conclusion In girls with progressive CPP, long-term treatment with GnRH analogues improves final height. A subset of patients with CPP does not require treatment because good statural outcome (slowly progressing variant). In CPP, the abnormal onset of puberty and the long-term GnRH analogue treatment do not impair the achievement of PBM. In GnRH treated patients, the discontinuation of therapy at an appropriate bone age for pubertal onset may improve both final height and PBM. Received: 5 June 1997 / Accepted in revised form 21 November 1997     

Adult height in children with short stature and idiopathic delayed puberty after different management

By retrospectively collecting data from nine Italian centres of pediatric endocrinology, we assessed the different management and final outcome of children with short stature and idiopathic delayed puberty. Data were obtained in 77 patients (54 males, 23 females) diagnosed and followed-up in the various centres during the last 15 years. Inclusion criteria were short stature at initial observation and idiopathic delayed puberty diagnosed during follow-up. At first observation, age was 13.8 ± 1.0 years and height standard deviation score (SDS) was –2.6 ± 0.6 in males. In females age was 13.1 ± 0.9 years and height SDS –2.6 ± 0.4. Local diagnostic and therapeutic protocols included testing for growth-hormone deficiency (six centres) and treatment in case of deficiency or, in the remaining centres, testosterone or no treatment in males, and no treatment in females. At diagnosis, both in males and in females, the auxological features (height SDS, target height SDS and bone age delay) were similar in the patients treated with growth hormone, testosterone or not treated. Overall 32 patients received growth hormone (25 males, 7 females), 33 no treatment (17 males, 16 females) and 12 testosterone. There was no difference in the adult height of males and females in the different treatment groups. In males there were no differences between adult and target height SDSs (growth hormone-treated 0.31 ± 0.79, untreated 0.10 ± 0.82, testosterone-treated 0.05 ± 0.95), between adult and initial height SDSs (growth hormone-treated 1.70 ± 0.93, untreated 1.55 ± 0.92, testosterone-treated 1.53 ± 1.43) and percentage of subjects with adult height above target height. In females, there were no differences between adult and target height SDSs (growth hormone-treated –0.49 ± 1.13; untreated 0.10 ± 0.97) and between adult and initial height SDSs (growth hormone-treated 1.76 ± 0.92; untreated 1.77 ± 0.98), whereas a significantly higher percentage of patients remained below target height in the growth hormone-treated group (6/7, 85.7% vs 5/11, 31.3%) (P = 0.02). In conclusion, the diagnostic and therapeutic management of the patients with short stature and delayed puberty is different among Italian pediatric endocrinologists. Our data do not support the usefulness of growth-hormone therapy in improving adult height in subjects with short stature and delayed puberty, particularly in the female sex.     

Growth hormone secretion, puberty and adult height after cranial irradiation with 18 Gy for leukaemia

The dose of prophylactic cranial irradiation given to patients for acute lymphoblastic leukaemia has been decreased from 24 to 18 Gy, but the beneficial effect of this decrease on growth is controversial. This study compares the growth hormone (GH) secretion and growth of 35 patients (20 boys) given 18 Gy at 3.7 ± 0.3 (SE) years, and routinely evaluated 5.4 ± 0.4 years after irradiation to define the indications for GH treatment in these patients. Of these, 63% had a low GH peak (<10 μg/l) after one (22 cases) or two (17 cases) stimulation tests. The plasma concentrations of insulin-like growth factor I and its GH-dependent binding protein were normal for age in all but two cases. The height changes between irradiation and evaluation were correlated with the GH peaks (P < 0.03) and were concordant, except in patients with early puberty. This occurred in 16 patients including all 12 girls irradiated before 4 years of age. A significant (P < 0.03) reduction in height (SD) between irradiation and adult height occurred in untreated GH-deficient patients (−1 ± 0.3, n = 6), but not in GH-deficient patients given GH (−0.6 ± 0.3, n = 8) or in those with normal GH peak (−0.4 ± 0.3, n = 7). Conclusion In children irradiated for acute lymphoblastic leukaemia, GH deficiency is frequent after 18 Gy but its impact on adult height is smaller than after higher doses. We suggest that the indications for gonadotropin releasing hormone analogue therapy should be broad in patients with early or rapidly progressing puberty and those for GH therapy in those patients with a below average constitutional height before irradiation. Received: 17 November 1997 / Accepted: 9 February 1998     

Growth, puberty and hypothalamic-pituitary function in children with suprasellar arachnoid cyst

A suprasellar arachnoid cyst may cause disorders of growth, puberty and hypothalamic-pituitary function, due to the proximity of the cyst to the hypothalamic-pituitary area. A total of 30 patients (17 boys) with cyst diagnosed at 4.3 ± 1 years were routinely evaluated at 5.4 ± 1 years; 24 of them had one or multiple cyst derivations. Some 23 cases had an abnormal height, weight or puberty: short (<−2SD, 5 cases) or tall (>2SD, 10 cases) stature, overweight (body mass index, BMI, >2SD, 6 cases), central precocious puberty (10 cases) and/or no progression of pubertal development (3 cases). The growth hormone (GH) peaks after pharmacological stimulation test were low (<10 μg/l) in 16 patients, confirmed by a second evaluation in 8/11 of them. The plasma free thyroxine was low in five patients, prolactin was high in two and the cortisol and concomitant plasma and urinary osmolalities were normal. BMI was correlated negatively with the GH peaks (r=−0.37, P < 0.01) and positively with the plasma leptin concentrations (r=0.55, P < 0.01). The plasma fasting insulin concentrations were also correlated negatively with the GH peaks (r=−0.55, P < 0.02) and positively with the plasma insulin-like growth factor I concentrations (r=0.64, P < 0.002). The adult height (12 cases) was at 4SD in 1 and <−2SD in 4 patients, two of whom had precocious puberty untreated with gonadotropin releasing hormone (GnRH) analogue, and two had untreated GH deficiency. The adult height of those treated was normal. One girl had primary amenorrhoea and two boys had low plasma testosterone, despite a normal gonadotropin response to a GnRH test. Conclusion Suprasellar arachnoid cysts may cause deficiencies of growth hormone and thyrotropin, stimulation of the hypothalamic-pituitary-gonadal axis, tall stature and/or overweight. These last two disorders may be due to hyperinsulinism, itself due to suprasellar arachnoid cyst. Received: 5 May 1999 / Accepted: 28 October 1999     

The effect of colchicine on physical growth in children wıth familial mediterranean fever

Familial Mediterranean fever (FMF) is an autosomal recessive disease, characterized by recurrent, self-limited attacks of fever with serositis involving the peritoneum, pleura, and joints. There is very scarce information on physical growth of affected children. The aim of this study was to determine whether there is significant improvement in growth parameters in FMF patients after colchicine treatment. Patient files were retrospectively evaluated and patients that used colchicine for more than 1 year were included in the study. Demographic features, clinical findings before and after colchicine therapy, duration and dosage of therapy, weight, height, parentally adjusted height, and body mass index before and after colchicine therapy were noted and transformed into standard deviation scores (SDS). The study group consisted of 50 FMF (25 male and 25 female) patients. Median age at the time of diagnosis was 6.5 years. Median follow-up period was 3.6 (1–12.5) years. Mean height SDS increased from −0.19 ± 1.01 to 0.13 ± 0.99 (p = 0.026), and mean parentally adjusted height increased from −0.18 ± 1.23 to 0.13 ± 1.24 (p = 0.027), and both of them were found to be statistically significant. Mean body mass index SDS increased from −0.61 ± 1.32 to −0.32 ± 1.33, but this improvement was statistically insignificant (p = 0.18). In this study, we found that colchicine significantly improved height development in FMF patients.     

The effect of prolonged administration of an anabolic steroid (oxandrolone) on growth in boys with constitutionally delayed growth and puberty

Short-term oxandrolone treatment is used to stimulate growth in boys with constitutional delay of growth and puberty (CDGP). Oxandrolone stimulates growth, but a beneficial effect on final height has not been established. In our study, we report the effect of long-term treatment (30–57 months) with oxandrolone in 18 boys with CDGP, compared with nine puberty-matched, untreated controls (group 1). The oxandrolone-treated boys were divided into two groups: four boys who received oxandrolone before onset of puberty (group 2), and 14 boys who started oxandrolone therapy during Tanner stage 2 (group 3). Height standard deviation scores for calender age (HSDSCA) between the three groups of patients at Tanner stage 2 (G2) were not different: –2.86 (SD 0.56) in the controls and –2.60 (SD 0.52) in group 2 and –2.81 (SD 0.59) in group 3. Age at G2 was 15.1 (SD 1.4) years (controls), 14.6 (SD 0.5) years (group 2) and 14.0 (SD 0.9) years (group 3). Height velocity in the time span from G2 to G5 was more pronounced in the oxandrolone-treated boys: 7.7 (SD 0.5) cm/year in group 2 and 7.7 (SD 1.4) cm/year in group 3 versus 5.1 (SD 0.9) cm/year in the controls. Height gain was significantly increased in the oxandrolone treated groups: 25.8 (SD 3.8) in group 2 and 25.2 (SD 3.7) in group 3 versus 19.8 (SD 4.9) in the controls (P<0.05). Final height did not differ significantly among the three groups: 168.5 (SD 7.0) cm in the controls and 173.0 (SD 4.0) cm in group 2 and 167.8 (SD 5.3) cm in group 3. HSDSCA increased during puberty in all three groups. At final height, HSDSCA (calculated at age=20 years) was –2.01 (SD 1.05), –1.34 (SD 0.59) and –2.12 (SD 0.79) respectively in groups 1, 2 and 3. An effect of oxandrolone on HSDSCA was not found. Target height was neither reached by the controls nor by the treated groups. Tempo of pubertal development was not different in the three groups, and BA/CA did not alter after start of oxandrolone treatment in groups 2 and 3.Conclusion Boys with CDGP may benefit from oxandrolone treatment in terms of increased height gain. Starting treatment before the onset of puberty may be favourable.     

Right Ventricular Diastolic Function After Repair of Tetralogy of Fallot

The objective of this study was quantitate diastolic dysfunction in the postoperative phase of tetralogy of Fallot (TOF) and to correlate it with the type of surgical procedure and clinical parameters. Fifty consecutive patients (mean age, 5.0 years; mean weight, 13.5 kg), operated for TOF during the period November 2004 to May 2005, were prospectively studied [infundibular resection, 23; infundibular resection and transannular patch (TAP), 19; right ventricle→pulmonary artery conduit, 8). Detailed echocardiography was done on postoperative days 3 and 9 with a focus on Doppler indices of right ventricular (RV) function, Antegrade late diastolic flow in the right ventricular outflow tract (RVOT) was taken as the marker of restrictive RV physiology. The previous parameters were correlated to the type of surgery and clinical indices of RV dysfunction. There was no mortality. Twenty-four patients showed restrictive RV physiology. This finding correlated with lower values of E/A ratio (0.98 ± 0.17 vs 1.33 ± 0.49, p < 0.002), tricuspid valve E-wave deceleration time (86.9 ± 21.7 vs 151.4 ± 152 msec, p < 0.05), index of myocardial performance (0.15 ± 0.06 vs 0.26 ± 0.09, p < 0.001), isovolumic relaxation time (19.4 ± 17 vs 39±30 msec, p < 0.009), and a higher central venous pressure (15.1 ± 1.5 vs 12.7 ± 1.9, p < 0.001). Restrictive RV physiology correlated with prolonged intensive case unit (ICU) stay (5.1 ± 3.7 vs 2.8 ± 2 days, p < 0.015), longer duration of inotropic support (108.3 ± 56.2 vs 55.5 ± 28.3 hours, p < 0.02), and higher dosage of diuretics. RV diastolic dysfunction is demonstrable by Doppler echocardiography in the first week following surgery for TOF and tends to be worse with TAP. Restrictive physiology demonstrated by RVOT pulse Doppler predicts longer duration of inotropic support, prolonged ICU stay, and higher dosage of diuretics.     

Talla final en diabéticos tipo 1 diagnosticados en la edad pediátrica

ObjectiveTo describe the final height and height-gain in relation to target height, in children with type 1 diabetes mellitus, and analyse their relationship to different variables.Patients and methodsRetrospective analysis of the growth data of 52 children (27 girls) diagnosed with type 1 diabetes mellitus before 14 years old, and followed up until their final height was attained. Main variables: final height, target height, illness duration, glycated haemoglobin (HbA1c), insulin dose, BMI, and other autoimmune diseases.ResultsThe height SDS (standard deviation scale) at diagnosis was slightly higher (0.734 in boys and 0.563 in girls). During the development of the disease, a growth reduction was seen, which was significantly higher in boys of prepubertal age (p=0.016). The mean final height attained was 173.14±5.28 cm in boys and 161.9±6.97 cm in girls. Height gain was 1.56±3.66 in boys (SDS=?0.034) and 2.26±6.13 in girls (SDS=0.385). The only variable significantly related to height gain was mean glycated-haemoglobin (growth reduction of 2 cm for every increment of 1% in mean glycated-haemoglobin).ConclusionsAt onset, diabetic children were slightly taller than the general population. A growth reduction was shown as the disease developed, significantly higher in boys of prepubertal age. The final height in boys was slightly lower than the mean, but in girls was similar to the general population. Both sexes attained their target height, although the height gain was less in boys. Poorer metabolic control was associated with reduced height gain.     

Treatment with a gonadotropin-releasing-hormone analog and attainment of full height potential in a male monozygotic twin with gonadotropin-releasing hormone-dependent precocious puberty

We report on a pair of male monozygotic twins, one unaffected and the other affected with gonadotropin-releasing hormone (GnRH)-dependent precocious puberty, and discuss the role of treatment with a GnRH analog in the attainment of full height potential in GnRH-dependent precocious puberty. At 1.6 years of age, the affected twin was studied for tall stature (+3.8 SD), and was diagnosed as having GnRH-dependent precocious puberty due to a hypothalamic hamartoma of the tuber cinereum. He was treated with oral cyproterone acetate (110–170 mg/m² daily) from 1.8 through 5.0 years of age, with oral cyproterone acetate and intranasal buserelin acetate (700–900 μg/m² daily) from 5.0 through 7.5 years, and with intranasal buserelin acetate alone (1100– 1400 μg/m² daily) from 7.5 through 12.6 years. He attained a final height of 171.0 cm at 14.9 years of age (+0.10 SD) and his twin 170.0 cm at 15.3 years of age (−0.10 SD), with their target height being 174.5 ± 9.0 cm. Conclusion This study indicates that GnRH analog treatment may preserve near full height potential in some patients with GnRH-dependent precocious puberty. Received: 30 March 1999 / Accepted: 31 May 1999     

Longitudinal growth in HIV-negative boys with haemophilia

It has been shown that HIV-positive haemophilic children develop growth retardation. As not only the HIV infection but also other disease-related factors might compromise growth in these children, growth data were analysed in a longitudinal cross-sectional manner in 84 HIV-negative haemophilic patients from two university clinics. A total of 2–24 height and weight measurements (median 6) were recorded in each patient resulting in 683 single values collected between 1977–1995. Height SDS of all haemophilic boys was −0.31 ± 2.13 (mean ± SD, NS versus 0) and body mass index SDS was 0.21 ± 3.49 (mean SD, NS versus 0) at first measurement and remained unchanged throughout the observation period. Neither height nor body mass index differed with respect to the severity of haemophilia (mild/moderate/severe) or the study centre (Vienna/Prague). Conclusion Growth in HIV-negative patients with haemophilia is not affected in spite of the immunological abnormalities attributed to the substitution therapy or the bleeding episodes in the joints with the potential effect on the growth plate. Received: 5 January 1999 / Accepted: 16 December 1999     

Short-term, high-dose testosterone treatment fails to reduce adult height in boys with constitutional tall stature

Height predictions based on three different methods (Bayley-Pinneau [BP], Tanner-Whitehouse Mark II [TW II], Roche-Wainer-Thissen [RWT]) were compared to adult heights in 19 males with constitutional tall stature previously treated with high-dose testosterone oenanthate for 6 months (group A) and 25 untreated tall males (group B). Their chronological ages (CA) at the initial evaluation of tall stature ranged from 12.1 to 16.6 years in group A and from 10.4 to 15.7 years in group B; at the time of assessment of adult height ages ranged from 18.0 to 26.5 years and from 18.4 to 25.1 years, respectively. Height measurements and predicted adult heights were expressed as height standard deviation scores (height SDS) for chronological age using the tables of Reinken and van Oost [14]. Height SDS in group A were 2.8 (range = 1.8–5.4) before testosterone treatment, 3.0 (range = 2.0–4.8) thereafter and finally 3.0 (range = 2.1–4.2) (P=NS) and in group B 2.7 (range = 0.5–4.3) and 2.4 (range = 1.3–3.5) (P=NS). A significant difference between adult height SDS and predicted height SDS according to BP was detected both in group A (3.0; range = 2.1–4.2 vs 3.6; range = 2.4–5.0; P≤0.004) and group B (2.4; range = 1.3–3.5 vs 3.0; range = 2.0–4.9; P≤0.0002), whereas no significant difference between adult height SDS and predicted height SDS according to TW II and RWT was found in either group. These data indicate that BP height predictions overestimated adult height in our patient group of treated and untreated males with constitutional tall stature. In contrast, the TW II and RWT methods were more accurate in predicting adult height in these patients, but also failed to demonstrate that testosterone therapy in boys with constitutional tall stature can be limited to a 6-month period in order to reduce adult height. Conclusion The widely used height prediction method of BP is inaccurate in boys with constitutional tall stature. High dose testosterone treatment fails to reduce adult height in these individuals when discontinued before complete closure of the epiphyses. Received: 30 January 1997 / Accepted: 20 June 1997     

Pubertal growth in chronic renal failure

We evaluated the growth records of 15 boys and 14 girls who developed end-stage renal failure before or during puberty and who were regularly followed from the onset to the end of their pubertal growth spurt. Height data were smoothed by using the kernel estimation method. Mean values for age, height, and height velocity at defined points of the pubertal growth period were compared with those of normal children entering puberty both at an average and late age. The start of the pubertal growth spurt was delayed by 2.5 y in both sexes. Its duration and intensity were significantly reduced. Mean pubertal height gain was 17.3 cm in boys and 13.9 cm in girls, i.e. 58 and 48% of that observed in the late maturing control group. Mean height at the onset of the pubertal spurt in the patients was the same as that in the late maturing healthy girls and 1.0 SD below that of corresponding boys. During the pubertal growth spurt, mean height declined to -2.9 SD in boys and -2.3 SD in girls. Although skeletal maturation was increasingly retarded, we did not observe accelerated growth velocity during late puberty. Our data indicate that most patients reaching end-stage renal failure before or during puberty irreversibly lose growth potential during this period. Renal transplantation did not consistently improve pubertal growth.     

Adult height in advanced puberty with or without gonadotropin hormone releasing hormone analog treatment

Advanced puberty is defined as the onset of puberty in girls at 8-10 years of age and in boys at 9-11 years. This study analyzes adult height in 57 children with advanced puberty to evaluate the results of treating children (9 girls and 8 boys) with gonadotropin hormone releasing hormone (GnRH) analog and the impact of advanced puberty on adult height in untreated children (31 girls and 9 boys). For treated girls, adult height predicted at the onset of treatment (151.9+/-1.7 cm) was similar to the final adult height (155.3+/-1.4 cm), but lower than target height (157.2+/-1.6 cm, p = 0.04). For untreated girls, adult height predicted at the initial evaluation (156.7+/-1 cm) was also similar to adult height (157+/-1 cm), but lower than the target height (157.6+/-1 cm, p = 0.03). The adult heights of both treated and untreated girls were similar to their target heights. For treated boys, adult height predicted at the onset of treatment (173.2+/-3.1 cm) was greater than the final adult height (164.1+/-2.1 cm, p = 0.01), which was lower than target height (170.4+/-1.2 cm, p = 0.01). For untreated boys, adult height predicted at the initial evaluation (170.8+/-2.7 cm) was similar to both the adult height (169.1+/-1.9 cm) and target height (170.2+/-1.2 cm). Height gains between the onset of puberty and adult height were similar in treated (29.9+/-2.3 cm in girls and 29.8+/-1.7 cm in boys) and untreated (28.6+/-1 and 33.1+/-2 cm) children. When expressed as SD, the adult height was significantly shorter than that at 4 years in treated girls (difference 1 SD, p = 0.03), in untreated girls (difference 0.9 SD, p = 0.0002) and in treated boys (difference 0.9 SD, p = 0.02), but it was similar to that in untreated boys. Adult height was below target height by >5 cm in seven girls (two of them treated) and five boys (four of them treated). In conclusion, treating advanced puberty did not change the adult height reached by girls, and was associated with reduced growth potential in boys. The adult heights of untreated children were similar to those predicted at the initial evaluation and to target heights, but in girls they were 1 SD lower than the height at 4 years. These data suggest that advanced puberty decreases the growth potential by about 5 cm, and that GnRH analog treatment does not prevent this.     

Growth and sexual maturation in children after kidney transplantation

Linear growth and sexual maturation were assessed in 68 long-term pediatric renal allograft recipients (43 boys) receiving daily or alternate-day prednisone therapy. Growth was analyzed both during the prepubertal period and during puberty. Height at transplantation was greater than 2 SD below the mean in 34.2% of prepubertal children. After the first posttransplant year, 59.2% of the prepubertal children had a normal height increment (greater than 4.8 cm/yr). Onset of puberty was recorded at a chronologic age of 14.6 +/- 1.9 years in boys and 13.3 +/- 1.9 years in girls. Height at onset of puberty related to chronologic age was -2.4 +/- 1.3 SD. Height velocity during puberty was within normal limits in 62.5% of the children. No significant difference in pubertal growth was detected in patients who had received transplants before and after the onset of puberty. Duration of pubertal development was within normal limits. In girls, menarche was achieved at a mean chronologic age of 15.9 years and bone age 12.9 years. Adult height was attained at an average age of 20.3 years in boys and 18.7 years in girls. Overall, one third of the children attained an adult height greater than 2 SD below the mean. Our data indicate that although poor growth before kidney transplantation has a great influence on adult height, the loss of growth potential during pubertal development seems even more important.     

Recovery of the Chronically Hypoxic Young Rabbit Heart Reperfused Following No-Flow Ischemia

The objective of this study was to test whether chronically hypoxic immature hearts exhibit greater tolerance to no-flow ischemia than normoxic hearts. Rabbits (N = 36) were raised from birth to 5 weeks of age in either hypoxic (10% O₂/90% N₂) or normoxic (room air) environment. Isolated, isovolumically beating hearts, with a fluid-filled balloon catheter in the left ventricular chamber, were perfused with a well-oxygenated buffer and studied during baseline [30 minutes; perfusion pressure, 60 mmHg; end diastolic pressure (EDP), 5 mmHg], no-flow ischemia (until onset of contracture or for 30 minutes), and Reperfusion (30 minutes; perfusion pressure, 60 mmHg). Time for onset of contracture (TOC) was defined by an increase in balloon pressure of 5 mmHg. The results were as follows: hypoxic vs normoxic: Hct, 56.4 ± 2.5* vs 36.3 ± 0.4%, (right ventricle/left ventricle) weight (dry) ratio, 0.50 ± 0.04* vs 0.28 ± 0.02. Baseline: developed pressure (ΔP), 96 ± 4 vs 93 ± 5 mmHg; coronary flow, 90 ± 10* vs 62 ± 4 ml/min/g_dry. No-flow ischemia: TOC, 12 ± 1* vs 24 ± 2 minutes. All hypoxic (no normoxic) hearts reached peak contracture. Reperfusion: Just after onset of contracture, ΔP, 80 ± 3* vs 67 ± 4 mmHg; EDP, 5 ± 1* vs 13 ± 2 mmHg; after 30 minutes of no-flow ischemia, ΔP, 58 ± 5 vs 46 ± 4 mmHg; EDP, 13 ± 1* vs 24 ± 3 mmHg; lactate release (LR), 0.15 ± 0.01 vs 0.17 ± 0.01 mmol/g_dry, creatine kinase release (CKR), 46 ± 8* vs 242 ± 28 U/g_dry. For hypoxic hearts reperfused after onset of contracture, LR was 0.11 ± 0.03 mmol/g_dry, comparable to that following 30 minutes of no-flow ischemia (*p < 0.05). Rabbit hearts subjected to hypoxia from birth developed ischemic contracture earlier and reached peak contracture, showed no significant increase in LR after onset of contracture, exhibited better recovery of EDP, and had markedly reduced CKR compared to normoxic controls.     

Growth in childhood thyrotoxicosis

Childhood thyrotoxicosis is an uncommon condition. To investigate the effect of thyrotoxicosis on the growth of children and to detect possible influence of the disease on their final height, 105 Chinese children (90 girls; 15 boys) with thyrotoxicosis were studied longitudinally from diagnosis. At presentation their mean age was 11.57 years. Their height and weight measurements were converted to standard deviation scores (SDS) using normal height and weight-for-height reference standards for Chinese children established in Hong Kong. Their mean height SDS at diagnosis was +0.73. Bone age assessment at diagnosis was done in 48 girls and 8 boys and their mean ± S.D. bone development quotient was 1.16 ± 0.11. A total of 53 girls have reached adult height and their mean height was 161.3 cm, corresponding to a SDS of +0.63. Their final heights significantly exceeded their target heights. Conclusion This study demonstrates that children with thyrotoxicosis were tall for age and their bone ages were advanced at presentation. They continued to be tall for age after starting treatment and they achieved final heights exceeding their target height. Received: 4 January 1999 / Accepted in revised form: 23 March 1999